<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03234465</url>
  </required_header>
  <id_info>
    <org_study_id>AG013-ODOM-201</org_study_id>
    <nct_id>NCT03234465</nct_id>
  </id_info>
  <brief_title>Efficacy, Safety and Tolerability of AG013 in Oral Mucositis Compared to Placebo When Administered Three Times Per Day</brief_title>
  <official_title>A Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety and Efficacy of Topically-applied AG013 for the Attenuation of Oral Mucositis in Subjects With Cancers of the Head and Neck Receiving Concomitant Chemoradiation Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oragenics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Oragenics, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to evaluate the efficacy, safety and tolerability of topically&#xD;
      administered AG013 compared to placebo for reducing Oral Mucositis (OM) in patients&#xD;
      undergoing chemoradiation for the treatment of head and neck cancer, as measured by the&#xD;
      duration, time to development, and overall incidence of OM during the active treatment phase,&#xD;
      beginning from the start of chemoradiation therapy (CRT) until 2 weeks following its&#xD;
      completion.&#xD;
&#xD;
      The effect of AG013 on patient-reported symptoms and analgesic use during the active&#xD;
      treatment phase, and on the cumulative radiation dose administered before the onset of OM&#xD;
      will also be evaluated, as will biomarkers and, in a subset of subjects, the PK&#xD;
      (pharmacokinetic) profile of AG013.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 2, double-blind, placebo-controlled, 2-arm, multi-center trial in which&#xD;
      subjects will be randomized in a 1:1 ratio to receive either placebo or AG013. AG013 is a&#xD;
      mouth rinse formulation of Lactococcus lactis strain sAGX0085, deficient in the gene coding&#xD;
      for thymidylate synthase and producing human TFF1 (Trefoil Factor 1).&#xD;
&#xD;
      Approximately 200 subjects will be enrolled in the study. To protect subjects from&#xD;
      unanticipated safety risks, enrollment and treatment in the double-blind study will continue&#xD;
      until 10 subjects on AG013 have been recruited. The Data Safety Monitoring Board (DSMB) will&#xD;
      review safety data after these 10 subjects on AG013 have completed study treatment. If there&#xD;
      are no safety signals identified, the study will continue to recruit the planned number of&#xD;
      subjects.&#xD;
&#xD;
      There are 4 study periods as described below: screening, active treatment, short term&#xD;
      follow-up and long term follow-up. The screening phase will be no longer than 4 weeks. The&#xD;
      active treatment phase will be between 7 and 9 weeks depending on the subject's prescribed&#xD;
      CRT (chemoradiation therapy) plan. The short term follow-up phase will be 4 weeks in&#xD;
      duration. The long term follow-up will continue until 12 months post CRT. Oral mucositis (OM)&#xD;
      assessments will begin at the start of CRT and continue until the subject has completed short&#xD;
      term follow-up or until the OM resolves (as defined by a WHO (World Health Organization)&#xD;
      score of ≤ 1), whichever comes first. Long term follow-up will continue for 12 months to&#xD;
      assure that AG013 does not adversely impact the tumor response to anti-neoplastic therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    No efficacy could be demonstrated, sponsor decided to prematurely end the study.&#xD;
  </why_stopped>
  <start_date type="Actual">July 18, 2017</start_date>
  <completion_date type="Actual">July 13, 2020</completion_date>
  <primary_completion_date type="Actual">March 31, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Efficacy of AG013 Compared to Placebo for Reducing OM as Measured by Duration (in Days) of Severe Oral Mucositis (WHO Grades 3 or 4)</measure>
    <time_frame>From the start of radiation therapy (RT) until 2 weeks following its completion, 7 to 9 weeks depending on the duration of CRT.</time_frame>
    <description>Duration (in Days) of Severe Oral Mucositis (WHO Grades 3 or 4)</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">200</enrollment>
  <condition>Oral Mucositis</condition>
  <arm_group>
    <arm_group_label>AG013: three mouth rinses/day</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will rinse three times per day with AG013 mouth rinse beginning from the start of radiotherapy until 2 weeks following its completion. The active treatment phase lasts for 7 to 9 weeks, depending on the duration of radiotherapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo: three mouth rinses/day</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will rinse three times per day with placebo mouth rinse beginning from the start of radiotherapy until 2 weeks following its completion. The active treatment phase lasts for 7 to 9 weeks, depending on the duration of radiotherapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>AG013</intervention_name>
    <description>AG013 is made up of genetically modified (GM) bacteria called Lactococcus lactis (L. lactis). Wild type L. lactis are commonly used to produce dairy products including cheeses and milk. To make AG013, the DNA of L. lactis has been changed in the laboratory to secrete a protein called human Trefoil Factor 1 (hTFF1). hTFF1 is normally secreted in saliva and intestines. Trefoil factors have been shown to be important in protecting and healing mucosal tissues, such as the tissue in the mouth, when these tissues are damaged by cancer therapies such as chemotherapy and radiation therapy.</description>
    <arm_group_label>AG013: three mouth rinses/day</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Subjects assigned to the placebo group will receive appearance- and taste-matched placebo powder.</description>
    <arm_group_label>Placebo: three mouth rinses/day</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Willing and able to understand and sign the study specific Informed Consent Form&#xD;
&#xD;
          2. Pathologically-confirmed squamous cell carcinoma of the oral cavity, oropharynx,&#xD;
             nasopharynx or hypopharynx or HPV-positive unknown primaries presumed to be of&#xD;
             oropharyngeal, nasopharyngeal or hypopharyngeal origin&#xD;
&#xD;
          3. Tumor HPV status established&#xD;
&#xD;
          4. Planned to receive either primary or post-operative CRT&#xD;
&#xD;
          5. Planned IMRT (Intensity-Modulated Radiotherapy)&#xD;
&#xD;
          6. Planned administration of cisplatin administered weekly or tri-weekly during RT&#xD;
&#xD;
          7. Males or females 21 years or older&#xD;
&#xD;
          8. Karnofsky performance score (KPS) ≥ 70%&#xD;
&#xD;
          9. Screening laboratory assessments:&#xD;
&#xD;
               -  Hemoglobin ≥ 10g/dl&#xD;
&#xD;
               -  White blood count ≥ 3500 cells/mm3&#xD;
&#xD;
               -  Absolute neutrophil counts ≥ 1500 cells/ mm3&#xD;
&#xD;
               -  Serum AST (aspartate aminotransferase) and ALT (alanine aminotransferase) ≤ 3 x&#xD;
                  ULN&#xD;
&#xD;
               -  Calculated Creatinine Clearance ≥ 50 ml/min&#xD;
&#xD;
               -  Negative pregnancy test (serum or urine) for females of childbearing potential&#xD;
                  performed 7 days before IMP (Investigational Medicinal Product) administration.&#xD;
&#xD;
         10. Subjects of childbearing potential must confirm to use an effective method of birth&#xD;
             control during study participation and for 30 days following the last treatment with&#xD;
             IMP. Male subjects, when having hetero-sexual intercourse with a female of&#xD;
             childbearing potential must use a condom during study participation and 90 days&#xD;
             following the last treatment with IMP and their partner should use an effective method&#xD;
             of birth control during that period as well.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior radiation to the head and neck&#xD;
&#xD;
          2. Increased risk of developing infectious endocarditis&#xD;
&#xD;
          3. Prior gene therapy&#xD;
&#xD;
          4. Presence of active infectious oral disease&#xD;
&#xD;
          5. Presence of any oral lesions that may confound the ability to assess oral mucositis&#xD;
             grade&#xD;
&#xD;
          6. Current use of antibiotic rinses or troches&#xD;
&#xD;
          7. Herbal, alternative remedies, and alcohol containing over-the-counter mouthwashes are&#xD;
             excluded during the course of the study&#xD;
&#xD;
          8. Current alcohol abuse syndrome&#xD;
&#xD;
          9. Chronic immunosuppression&#xD;
&#xD;
         10. Known seropositive for HIV&#xD;
&#xD;
         11. Use of investigational agent within 30 days of signing informed consent&#xD;
&#xD;
         12. Tooth extraction prior to radiation in which the extraction site is not epithelialized&#xD;
&#xD;
         13. Signs and symptoms of active dental disease&#xD;
&#xD;
         14. Female subjects who are pregnant or nursing&#xD;
&#xD;
         15. Known allergy to excipients of the IMP&#xD;
&#xD;
         16. Inability to give informed consent or comply with study requirements&#xD;
&#xD;
         17. Unwilling or unable to complete subject diary&#xD;
&#xD;
         18. Any other clinical condition, psychiatric condition or prior therapy that, in the&#xD;
             opinion of the Investigator, would make the subject unsuitable for the study or unable&#xD;
             or to comply with follow-up visits&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alan Joslyn, Ph.D.</last_name>
    <role>Study Director</role>
    <affiliation>Sponsor GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Connecticut Health Center</name>
      <address>
        <city>Farmington</city>
        <state>Connecticut</state>
        <zip>06030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helen F. Graham Cancer Center</name>
      <address>
        <city>Newark</city>
        <state>Delaware</state>
        <zip>19713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UF Health Cancer Center</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbus Regional Research Institute</name>
      <address>
        <city>Columbus</city>
        <state>Georgia</state>
        <zip>31904</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Decatur Memorial Hospital</name>
      <address>
        <city>Decatur</city>
        <state>Illinois</state>
        <zip>62526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Vincent Anderson Regional, Cancer Center</name>
      <address>
        <city>Anderson</city>
        <state>Indiana</state>
        <zip>46016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norton Cancer Institute, Multicisciplinary Clinic</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ochsner Clinic Foundation</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Willis-Knighton Cancer Center</name>
      <address>
        <city>Shreveport</city>
        <state>Louisiana</state>
        <zip>71103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109-5008</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Centers of Nevada-Henderson</name>
      <address>
        <city>Henderson</city>
        <state>Nevada</state>
        <zip>89052</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Renown Regional Medical Center</name>
      <address>
        <city>Reno</city>
        <state>Nevada</state>
        <zip>89502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore Medical Center, Albert Einstein College of Medicine, Department of Radiation Oncology</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwell Health Cancer Institute / Center for Novel Cancer Therapeutics</name>
      <address>
        <city>Lake Success</city>
        <state>New York</state>
        <zip>11042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Rochester Medical Center</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Caromont Regional Medical Center</name>
      <address>
        <city>Gastonia</city>
        <state>North Carolina</state>
        <zip>28054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>East Carolina Univ School of Dental Medicine</name>
      <address>
        <city>Greenville</city>
        <state>North Carolina</state>
        <zip>27834-4354</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Medical Center</name>
      <address>
        <city>Canton</city>
        <state>Ohio</state>
        <zip>44708</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University Comprehensive Cancer Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Temple University Hospital, Radiation Oncology</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19140</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Shadyside Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huntsman Cancer Hospital</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radiation Oncology Moser</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PeaceHealth St. Joseph Medical Center</name>
      <address>
        <city>Bellingham</city>
        <state>Washington</state>
        <zip>98225</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Multicare Health Center</name>
      <address>
        <city>Gig Harbor</city>
        <state>Washington</state>
        <zip>98405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Care NW</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jules Bordet Institute</name>
      <address>
        <city>Brussels</city>
        <zip>1000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Brussels</name>
      <address>
        <city>Brussels</city>
        <zip>1090</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Antwerp</name>
      <address>
        <city>Edegem</city>
        <zip>2650</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Leuven</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Maarten General Hospital</name>
      <address>
        <city>Mechelen</city>
        <zip>2800</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Aachen</name>
      <address>
        <city>Aachen</city>
        <zip>52074</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Amper Hospital</name>
      <address>
        <city>Dachau</city>
        <zip>85221</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Freiburg</name>
      <address>
        <city>Freiburg</city>
        <zip>79106</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Giessen and Marburg</name>
      <address>
        <city>Gießen</city>
        <zip>35392</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Kassel</name>
      <address>
        <city>Kassel</city>
        <zip>34125</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Schleswig-Holstein</name>
      <address>
        <city>Kiel</city>
        <zip>24105</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helios Hospital Krefeld</name>
      <address>
        <city>Krefeld</city>
        <zip>47805</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Johannes Gutenberg - University of Mainz</name>
      <address>
        <city>Mainz</city>
        <zip>55131</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Mannheim</name>
      <address>
        <city>Mannheim</city>
        <zip>68167</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ludwig Maximilians University Hospital</name>
      <address>
        <city>Munich</city>
        <zip>81377</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinics Maria Hilf - Hospital St. Franziskus</name>
      <address>
        <city>Mönchengladbach</city>
        <zip>41063</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Regensburg</name>
      <address>
        <city>Regensburg</city>
        <zip>93053</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Caritas Klinikum</name>
      <address>
        <city>Saarbrücken</city>
        <zip>85221</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Derriford Hospital</name>
      <address>
        <city>Plymouth</city>
        <state>Devon</state>
        <zip>PL6 8DH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beatson West of Scotland Cancer Center</name>
      <address>
        <city>Glasgow</city>
        <zip>G12 0YN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guy's Hospital</name>
      <address>
        <city>London</city>
        <zip>SE1 9RT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Christie NHS Foundation Trust</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Cornwall Hospital</name>
      <address>
        <city>Truro</city>
        <zip>TR1 3LJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Germany</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Limaye SA, Haddad RI, Cilli F, Sonis ST, Colevas AD, Brennan MT, Hu KS, Murphy BA. Phase 1b, multicenter, single blinded, placebo-controlled, sequential dose escalation study to assess the safety and tolerability of topically applied AG013 in subjects with locally advanced head and neck cancer receiving induction chemotherapy. Cancer. 2013 Dec 15;119(24):4268-76. doi: 10.1002/cncr.28365. Epub 2013 Sep 24.</citation>
    <PMID>24114811</PMID>
  </results_reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>July 21, 2017</study_first_submitted>
  <study_first_submitted_qc>July 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2017</study_first_posted>
  <results_first_submitted>October 22, 2020</results_first_submitted>
  <results_first_submitted_qc>November 20, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">November 23, 2020</results_first_posted>
  <last_update_submitted>November 20, 2020</last_update_submitted>
  <last_update_submitted_qc>November 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mucositis</mesh_term>
    <mesh_term>Stomatitis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 12, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT03234465/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 19, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT03234465/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>3 patients were randomized but never received study drug and are excluded from the safety analysis set.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>AG013</title>
          <description>Three rinses per day with AG013 mouth rinse beginning from the start of radiotherapy until 2 weeks following its completion for 7 to 9 weeks, depending on the duration of radiotherapy.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Three rinses per day with placebo mouth rinse beginning from the start of radiotherapy until 2 weeks following its completion for 7 to 9 weeks, depending on the duration of radiotherapy.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="100"/>
                <participants group_id="P2" count="100"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="67"/>
                <participants group_id="P2" count="60"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="33"/>
                <participants group_id="P2" count="40"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="27"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Symptomatic deterioration</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-compliance</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>AG013</title>
          <description>Three rinses per day with AG013 mouth rinse beginning from the start of radiotherapy until 2 weeks following its completion for 7 to 9 weeks, depending on the duration of radiotherapy.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Three rinses per day with placebo mouth rinse beginning from the start of radiotherapy until 2 weeks following its completion for 7 to 9 weeks, depending on the duration of radiotherapy.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="100"/>
            <count group_id="B2" value="100"/>
            <count group_id="B3" value="200"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="60.4" spread="9.98"/>
                    <measurement group_id="B2" value="60.4" spread="9.10"/>
                    <measurement group_id="B3" value="60.4" spread="9.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="81"/>
                    <measurement group_id="B2" value="84"/>
                    <measurement group_id="B3" value="165"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="91"/>
                    <measurement group_id="B2" value="81"/>
                    <measurement group_id="B3" value="172"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="93"/>
                    <measurement group_id="B2" value="92"/>
                    <measurement group_id="B3" value="185"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="65"/>
                    <measurement group_id="B2" value="65"/>
                    <measurement group_id="B3" value="130"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Europe</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Efficacy of AG013 Compared to Placebo for Reducing OM as Measured by Duration (in Days) of Severe Oral Mucositis (WHO Grades 3 or 4)</title>
        <description>Duration (in Days) of Severe Oral Mucositis (WHO Grades 3 or 4)</description>
        <time_frame>From the start of radiation therapy (RT) until 2 weeks following its completion, 7 to 9 weeks depending on the duration of CRT.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>AG013</title>
            <description>Three rinses per day with AG013 mouth rinse beginning from the start of radiotherapy until 2 weeks following its completion for 7 to 9 weeks, depending on the duration of radiotherapy.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Three rinses per day with placebo mouth rinse beginning from the start of radiotherapy until 2 weeks following its completion for 7 to 9 weeks, depending on the duration of radiotherapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy of AG013 Compared to Placebo for Reducing OM as Measured by Duration (in Days) of Severe Oral Mucositis (WHO Grades 3 or 4)</title>
          <description>Duration (in Days) of Severe Oral Mucositis (WHO Grades 3 or 4)</description>
          <units>Days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>US</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.6" spread="25.00"/>
                    <measurement group_id="O2" value="20.6" spread="25.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Europe</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.2" spread="22.67"/>
                    <measurement group_id="O2" value="15.3" spread="22.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the time of screening and up to a total of 15 to 17 weeks, depending on the duration of CRT.</time_frame>
      <desc>Safety analyses were performed on the Safety Population which is comprised of all patients randomized to treatment and who received at least one dose of study drug.&#xD;
3 patients were randomized but never received study drug and are excluded from these analyses.</desc>
      <group_list>
        <group group_id="E1">
          <title>AG013</title>
          <description>Three rinses per day with AG013 mouth rinse beginning from the start of radiotherapy until 2 weeks following its completion for 7 to 9 weeks, depending on the duration of radiotherapy.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Three rinses per day with placebo mouth rinse beginning from the start of radiotherapy until 2 weeks following its completion for 7 to 9 weeks, depending on the duration of radiotherapy.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="43" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="25" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Pancytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Cardio-respiratory arrest</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Gastric haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Neutropenic colitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Odynophagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>General physical health deterioriation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Administration site extravasation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Catheter site pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Candida infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Clostridium difficile colitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Tracheobronchitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Tracheostomy infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal anastomotic leak</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Radiation skin injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Troponin increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Failure to thrive</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Hypophagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Malnutrition</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Hairy cell leukaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Epilepsy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Suicidal ideation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Psychiatric decompensation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Oropharynggeal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Acute pulmonary oedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiratoin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Circulatory collapse</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="98" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="95" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="33" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="67" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="69" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="54" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="41" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="39" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="42" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="38" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="38" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="33" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="39" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="43" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Odynophagia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Saliva altered</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="56" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="58" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Secretion discharge</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Localised oedema</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Candida infection</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Mucosal infection</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Radiation skin injury</sub_title>
                <counts group_id="E1" subjects_affected="32" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="45" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Gastrostomy tube site complication</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="29" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Blood urea increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="25" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Malnutrition</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="43" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="49" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="40" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Alan Jolyn</name_or_title>
      <organization>Oragenics, Inc.</organization>
      <phone>+ 1 813-286-7900</phone>
      <email>info@oragenics.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03234465
org study id: AG013-ODOM-201
nct id: NCT03234465
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of the study is to evaluate the efficacy, safety and tolerability of topically
      administered AG013 compared to placebo for reducing Oral Mucositis (OM) in patients
      undergoing chemoradiation for the treatment of head and neck cancer, as measured by the
      duration, time to development, and overall incidence of OM during the active treatment phase,
      beginning from the start of chemoradiation therapy (CRT) until 2 weeks following its
      completion.

      The effect of AG013 on patient-reported symptoms and analgesic use during the active
      treatment phase, and on the cumulative radiation dose administered before the onset of OM
      will also be evaluated, as will biomarkers and, in a subset of subjects, the PK
      (pharmacokinetic) profile of AG013.
This is a Phase 2, double-blind, placebo-controlled, 2-arm, multi-center trial in which
      subjects will be randomized in a 1:1 ratio to receive either placebo or AG013. AG013 is a
      mouth rinse formulation of Lactococcus lactis strain sAGX0085, deficient in the gene coding
      for thymidylate synthase and producing human TFF1 (Trefoil Factor 1).

      Approximately 200 subjects will be enrolled in the study. To protect subjects from
      unanticipated safety risks, enrollment and treatment in the double-blind study will continue
      until 10 subjects on AG013 have been recruited. The Data Safety Monitoring Board (DSMB) will
      review safety data after these 10 subjects on AG013 have completed study treatment. If there
      are no safety signals identified, the study will continue to recruit the planned number of
      subjects.

      There are 4 study periods as described below: screening, active treatment, short term
      follow-up and long term follow-up. The screening phase will be no longer than 4 weeks. The
      active treatment phase will be between 7 and 9 weeks depending on the subject's prescribed
      CRT (chemoradiation therapy) plan. The short term follow-up phase will be 4 weeks in
      duration. The long term follow-up will continue until 12 months post CRT. Oral mucositis (OM)
      assessments will begin at the start of CRT and continue until the subject has completed short
      term follow-up or until the OM resolves (as defined by a WHO (World Health Organization)
      score of ≤ 1), whichever comes first. Long term follow-up will continue for 12 months to
      assure that AG013 does not adversely impact the tumor response to anti-neoplastic therapy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Efficacy of AG013 Compared to Placebo for Reducing OM as Measured by Duration (in Days) of Severe Oral Mucositis (WHO Grades 3 or 4)
time frame: From the start of radiation therapy (RT) until 2 weeks following its completion, 7 to 9 weeks depending on the duration of CRT.
description: Duration (in Days) of Severe Oral Mucositis (WHO Grades 3 or 4)
arm group label: AG013: three mouth rinses/day
arm group type: Experimental
description: Subjects will rinse three times per day with AG013 mouth rinse beginning from the start of radiotherapy until 2 weeks following its completion. The active treatment phase lasts for 7 to 9 weeks, depending on the duration of radiotherapy.
arm group label: Placebo: three mouth rinses/day
arm group type: Placebo Comparator
description: Subjects will rinse three times per day with placebo mouth rinse beginning from the start of radiotherapy until 2 weeks following its completion. The active treatment phase lasts for 7 to 9 weeks, depending on the duration of radiotherapy.
intervention type: Biological
intervention name: AG013
description: AG013 is made up of genetically modified (GM) bacteria called Lactococcus lactis (L. lactis). Wild type L. lactis are commonly used to produce dairy products including cheeses and milk. To make AG013, the DNA of L. lactis has been changed in the laboratory to secrete a protein called human Trefoil Factor 1 (hTFF1). hTFF1 is normally secreted in saliva and intestines. Trefoil factors have been shown to be important in protecting and healing mucosal tissues, such as the tissue in the mouth, when these tissues are damaged by cancer therapies such as chemotherapy and radiation therapy.
arm group label: AG013: three mouth rinses/day
intervention type: Other
intervention name: Placebo
description: Subjects assigned to the placebo group will receive appearance- and taste-matched placebo powder.
arm group label: Placebo: three mouth rinses/day
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Alan Joslyn, Ph.D.
role: Study Director
affiliation: Sponsor GmbH
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belgium
country: Germany
country: United Kingdom
country: United States
citation: Limaye SA, Haddad RI, Cilli F, Sonis ST, Colevas AD, Brennan MT, Hu KS, Murphy BA. Phase 1b, multicenter, single blinded, placebo-controlled, sequential dose escalation study to assess the safety and tolerability of topically applied AG013 in subjects with locally advanced head and neck cancer receiving induction chemotherapy. Cancer. 2013 Dec 15;119(24):4268-76. doi: 10.1002/cncr.28365. Epub 2013 Sep 24.
PMID: 24114811
responsible party type: Sponsor
mesh term: Mucositis
mesh term: Stomatitis
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 