<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/NCT03009396</url>
  </required_header>
  <id_info>
    <org_study_id>RHB-104-04</org_study_id>
    <nct_id>NCT03009396</nct_id>
  </id_info>
  <brief_title>Open Label Efficacy and Safety of Anti-MAP (Mycobacterium Avium Ssp. Paratuberculosis) Therapy in Adult Crohn's Disease</brief_title>
  <acronym>MAPUS2</acronym>
  <official_title>An Open Label Study to Assess the Efficacy and Safety of Fixed-Dose Combination RHB-104 in Subjects With Active Crohn's Disease Despite 26 Weeks of Participation in the MAP US RHB-104-01 Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>RedHill Biopharma Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>RedHill Biopharma Limited</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>
      An open label extension to the RHB-104-01 Study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      An Open Label Phase III Study to Assess the Efficacy and Safety of Fixed-Dose Combination&#xD;
      RHB-104 in Subjects with Active Crohn's Disease Despite 26 Weeks of Participation in the MAP&#xD;
      US RHB-104-01 Study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 18, 2017</start_date>
  <completion_date type="Actual">August 19, 2019</completion_date>
  <primary_completion_date type="Actual">November 13, 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Active</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Patients in Remission at Week 16</measure>
    <time_frame>Week 16</time_frame>
    <description>The number of patients who achieved a reduction of the total Crohn's Disease Activity Index (CDAI) score to less than 150 points.&#xD;
Lower CDAI scores indicate a better outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response at Week 16</measure>
    <time_frame>Week 16</time_frame>
    <description>Reduction of the total Crohn's Disease Activity Index (CDAI) score by a minimum of 100 points Lower CDAI scores indicate a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Number of Weeks for Patients to Achieve Remission</measure>
    <time_frame>Baseline through week 52</time_frame>
    <description>[Date of first observed remission (CDAI less than 150) - date of first dose, or date of randomization if not dosed, plus 1] / 7 days. Subject who never experience remission during the study are censored at the time of their last CDAI assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Weeks the Patients Are in Remission</measure>
    <time_frame>Baseline through week 52</time_frame>
    <description>Duration of remission is defined as the number of weeks the subject is in remission (CDAI score &lt; 150). It is calculated as the first date following remission at which CDAI is ≥150 minus the date of first remission, plus 1 day, divided by 7. Subjects who experienced remission and continued to be in remission at the time of their last CDAI assessment are censored at the date of their last CDAI assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Weeks to Achieve Response</measure>
    <time_frame>Baseline through week 52</time_frame>
    <description>[Date of first observed response (a reduction from baseline of ≥ 100 in CDAI score) - Date of first dose or date of randomization if not dosed + 1] / 7 Days. Subjects who never experienced response during the study are censored at the date of their last CDAI assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Weeks the Patients Are in Response.</measure>
    <time_frame>Baseline through week 52</time_frame>
    <description>Duration of response is defined as the number of weeks the subject is in a state of response (a reduction from baseline of ≥ 100 in CDAI score). It is calculated as the first date following response at which the reduction from baseline in CDAI is &lt;100 minus the date of first response, plus 1 day, divided by 7. Subjects who experienced response and continued to be in response at the time of their last CDAI assessment are censored at the date of their last CDAI assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Durable Remission Week 16 Through Week 52</measure>
    <time_frame>Week 16 through week 52</time_frame>
    <description>When a subject is in remission with a maximum CDAI score of 149 at every visit from week 16 through and including week 52.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Increase in Milliseconds (ms) QT Wave</measure>
    <time_frame>week 52</time_frame>
    <description>The increase in the number of milliseconds change-from-baseline to week 52 in QTcF (Fridericia's Correction Formula of QT wave interval) (based on cardiac safety report).</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>Crohn Disease</condition>
  <arm_group>
    <arm_group_label>RHB-104 - patients on ACTIVE therapy in RHB-104-01 study</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects who were on the active therapy arm in the RHB-104-01 clinical study will continue to receive RHB-104 at 5 capsules twice a day in addition to the standard of care they received in the RHB-104-01 clinical study</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RHB-104 - patients on PLACEBO therapy in RHB-104-01 study</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects who were on the active therapy arm in the RHB-104-01 clinical study will receive RHB-104 at 5 capsules twice a day in addition to the standard of care they received in the RHB-104-01 clinical study. The RHB-104 will be ramped up beginning at 1 capsule twice per day in week 1 increasing to 2 capsules twice per day in week 2, 3 capsules twice per day in week 3, 4 capsules per day in week 4 and achieving 5 capsules per day for the remainder of the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RHB-104 (fixed-dose combination: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine)</intervention_name>
    <description>For patients on ACTIVE or PLACEBO in the parent study (RHB-104-01), who were not in remission after 26 weeks</description>
    <arm_group_label>RHB-104 - patients on ACTIVE therapy in RHB-104-01 study</arm_group_label>
    <arm_group_label>RHB-104 - patients on PLACEBO therapy in RHB-104-01 study</arm_group_label>
    <other_name>RHB-104</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed fully informed consent (ICF) provided as per this protocol.&#xD;
&#xD;
          -  Participation in RHB-104-01 for 26 weeks, and a Crohn's Disease Activity Index (CDAI)&#xD;
             score of ≥ 150 at Visit Week 26.&#xD;
&#xD;
        OR&#xD;
&#xD;
          -  More than 26 weeks, with a CDAI ≥150 at Visit Week 26 and all subsequent visits, and&#xD;
             subject is between Week 26 and 52 within 4 weeks (28 days) of site activation (e.g.&#xD;
             Subject with CDAI = 249 at week 26 and who is at week 38 at the time of site's&#xD;
             activation for RHB-104-04 has a 4-week window to be enrolled in the open label study&#xD;
             via the Optional Screening Visit)&#xD;
&#xD;
          -  Current treatment with at least one of the following therapies which may be&#xD;
             discontinued by the investigator as clinically indicated after 8 weeks of open label&#xD;
             RHB-104 treatment:&#xD;
&#xD;
               -  Oral 5-acetyl salicylic acid (5-ASA) compounds&#xD;
&#xD;
               -  Azathioprine or 6-mercaptopurine (6-MP) or methotrexate&#xD;
&#xD;
               -  Infliximab or adalimumab OR Current treatment with corticosteroid therapy which&#xD;
                  must begin tapering after 4 weeks of treatment with open label RHB-104 (Refer to&#xD;
                  Appendix 13)&#xD;
&#xD;
          -  White blood cell count ≥ 3.5x109 at screening (RHB-104-01 Visit Week 26 visit or&#xD;
             Optional Screening visit)&#xD;
&#xD;
          -  Subject agrees to use the following effective contraceptive methods&#xD;
&#xD;
               -  diaphragm, cervical cap, contraceptive sponge or condom) with spermicidal&#xD;
                  foam/gel/cream/suppository&#xD;
&#xD;
               -  IUD (intrauterine device) /IUS (intrauterine system)&#xD;
&#xD;
               -  progestogen injection (Depo-Provera®) throughout the study and for at least 6&#xD;
                  weeks after last study drug administration, unless subject or partner of subject&#xD;
                  is post-menopausal or otherwise incapable of becoming pregnant by reason of&#xD;
                  surgery or tubal ligation, or has had a vasectomy. Post-menopausal is defined as&#xD;
                  having experienced 12 consecutive months without menstruation.&#xD;
&#xD;
        In regions where local regulatory contraceptive requirements differ, the ICF (Informed&#xD;
        Consent Form) will reflect local policies.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Positive stool results for C. difficile.&#xD;
&#xD;
          2. Currently diagnosed or history of uveitis confirmed by either an ophthalmologist or&#xD;
             optometrist.&#xD;
&#xD;
          3. Treatment with any medication that causes QT prolongation or Torsades de Pointes,&#xD;
             including but not limited to: amiodarone, amitriptyline, astemizole, cisapride,&#xD;
             citalopram dose greater than 20 mg/day, dihydroergotamine, disopyramide, dofetilide,&#xD;
             dronedarone, ergotamine, ibutilide, ondansetron or other 5-HT3 (5-hydroxytryptamine&#xD;
             three) receptor antagonists, pimozide, procainamide, quinidine, quinine, quinolones,&#xD;
             ranolazine, risperidone, sotalol, terfenadine and tolterodine. QT prolonging drugs may&#xD;
             be referenced at the CredibleMeds® web site:&#xD;
             https://crediblemeds.org/index.php/drugsearch/&#xD;
&#xD;
          4. Treatment with the following CYP3A4 interactive medications: alfentanyl, alprazolam,&#xD;
             amlodipine, anti-retroviral agents, apixaban, aprepitant, aripiprazole, atorvastatin,&#xD;
             boceprevir, buspirone, carbamazepine, carvedilol, colchicine, cyclosporine, digoxin,&#xD;
             diltiazem, estrogens, felodipine, fluconazole, fluvoxamine, grapefruit juice,&#xD;
             haloperidol, ketoconazole, lovastatin, lurasidone, metoprolol, nefazodone, nifedipine,&#xD;
             nisoldipine, nitrendipine, propranol, roflumilast, simvastatin, St. John's wort, and&#xD;
             voriconazole.&#xD;
&#xD;
          5. Any evidence of any newly diagnosed significant hematological, hepatic, renal,&#xD;
             cardiac, pulmonary, metabolic, neurological, psychiatric or other disease (e.g.&#xD;
             porphyria) that might interfere with subject's ability to safely enter and or complete&#xD;
             the study requirements.&#xD;
&#xD;
          6. Females who have a positive pregnancy test or are lactating.&#xD;
&#xD;
          7. Refusal to sign the study informed consent form.&#xD;
&#xD;
          8. Inability to be able to adequately communicate with the investigator or their&#xD;
             respective designee and/or comply with the requirements of the entire study.&#xD;
&#xD;
          9. Clinically significant abnormalities of hematology or biochemistry as confirmed by&#xD;
             repeat testing based on investigator's discretion, including but not limited to,&#xD;
             elevations greater than 2 times the upper limit of normal of Aspartate&#xD;
             Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) or&#xD;
             creatinine clearance less than 60 ml/min at screening via estimated Cockcroft-Gault&#xD;
             formula:&#xD;
&#xD;
             Creatinine Clearance = [140 - age in years] * weight (kg) / 72 * Serum Creatinine&#xD;
             (mg/dl) [multiply estimated rate by 0.85 for women], using actual body weight.&#xD;
&#xD;
         10. QTcF (shortening of the QT interval in the heart rate) &gt;450ms in males and QTcF&gt;460ms&#xD;
             in females, bundle branch block, or major ST or T wave abnormalities that make the&#xD;
             assessment of the QT impossible.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>76 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ira N Kalfus, MD</last_name>
    <role>Study Director</role>
    <affiliation>RedHill Biopharma Limited</affiliation>
  </overall_official>
  <overall_official>
    <last_name>David Y Graham, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Medicine / Gastroenterology, Baylor College of Medicine, Houston</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Digestive Care Associates, Inc., 1000 Laurel Street</name>
      <address>
        <city>San Carlos</city>
        <state>California</state>
        <zip>94070</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gastrointestinal Specialists of Georgia PC 711 Canton Rd. #300</name>
      <address>
        <city>Marietta</city>
        <state>Georgia</state>
        <zip>30060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cotton-O'Neil Clinical Research Center, 720 SW Lane St.</name>
      <address>
        <city>Topeka</city>
        <state>Kansas</state>
        <zip>66606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chevy Chase Clinical Research, 5550 Friendship Blvd.</name>
      <address>
        <city>Chevy Chase</city>
        <state>Maryland</state>
        <zip>20815</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Commonwealth Clinical Studies, 189 Quincy St.</name>
      <address>
        <city>Brockton</city>
        <state>Massachusetts</state>
        <zip>02302-2926</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ClinSearch 6035 Shallowford Road Suite 109</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37421</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Discovery Clinical Services Ltd., 601 A Discovery St.</name>
      <address>
        <city>Victoria</city>
        <state>British Columbia</state>
        <zip>V8T 5G4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gastroenterologie s.r.o. Manesova 646</name>
      <address>
        <city>Hradec Kralove</city>
        <zip>500 02</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hepato-Gastroenterologie HK, s.r.o., Hradecka poliklinika III Trida Edvarda Benese 1549/34</name>
      <address>
        <city>Hradec Králové</city>
        <zip>500 12</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ha'Emek Medical Center, Institute of Gastroenterology and Liver diseases, 21 Yitshak Rabin Boulevard</name>
      <address>
        <city>Afula</city>
        <zip>1834111</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gastroenterology Institute, Division of Medicine, Hadassah - Hebrew University Medical Center POB 12000</name>
      <address>
        <city>Jerusalem</city>
        <zip>91120</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Meir Medial Center, 59 Tchemacovsky St.</name>
      <address>
        <city>Kfar-Saba</city>
        <zip>44281</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christchurch Hospital, 2 Riccarton Rd.</name>
      <address>
        <city>Christchurch</city>
        <state>Canterbury</state>
        <zip>80011</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Waikato Hospital, Department of Gastroenterology, Level B1, Menzies Building, Pembroke Street</name>
      <address>
        <city>Hamilton</city>
        <state>Waikato</state>
        <zip>3240</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NZOZ Specjalistyczne Centrum Gastrologii GASTROMED, Wiejska 81</name>
      <address>
        <city>Białystok</city>
        <zip>15-351</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samodzielny Publiczny Zakład Opieki Zdrowotnej MSW W Gdańsku Oddział Gastroenterologiczny, Ul. Kartuska 4/6</name>
      <address>
        <city>Gdansk</city>
        <zip>80-104</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UNICARDIA Specjalistyczne Centrum Leczenia Chorob Serca i Naczyn &amp; UNIMEDICA. Specjalistyczne Centrum Medyczne Sp. z o.o., Kluczborska 15</name>
      <address>
        <city>Kraków</city>
        <zip>31-271</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wojewodzki Szpital Kliniczny w Olsztynie Oddzial Gastroenterologiczny, Zolnierska 18</name>
      <address>
        <city>Olsztyn</city>
        <zip>10-561</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>EuroMedis sp. z.o.o., Al. Powstancow Wielkopolskich 33a</name>
      <address>
        <city>Szczecin</city>
        <zip>70-111</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centralny Szpital Kliniczny MSW w Warszawie. Klinika Chorob Wewnetrznych i Gastroenterologii, Woloska 137,</name>
      <address>
        <city>Warsaw</city>
        <zip>02-507</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ARS MEDICA s.c., Powstancow Slaskich 56A/2</name>
      <address>
        <city>Wroclaw</city>
        <zip>53-333</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Department of Gastroenterology and Hepatology Clinic for Internal Diseases Clinical Hospital Center Zvezdara Dimitrija Tucovica 161</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Gastroenterology and Hepatology, Clinical Hospital Center Zemun, Vukova 9</name>
      <address>
        <city>Belgrade</city>
        <zip>11080</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center for Gastroenterohepatology, Clinic for Internal Medicine, Clinical Center Kragujevac, Zmaj Jovina 30</name>
      <address>
        <city>Kragujevac</city>
        <zip>34000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Czechia</country>
    <country>Israel</country>
    <country>New Zealand</country>
    <country>Poland</country>
    <country>Serbia</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.redhillbio.com</url>
    <description>RedHill home page</description>
  </link>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>December 26, 2016</study_first_submitted>
  <study_first_submitted_qc>December 30, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 4, 2017</study_first_posted>
  <results_first_submitted>September 27, 2020</results_first_submitted>
  <results_first_submitted_qc>February 7, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">February 24, 2021</results_first_posted>
  <last_update_submitted>February 7, 2021</last_update_submitted>
  <last_update_submitted_qc>February 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 24, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Crohn's Disease,</keyword>
  <keyword>moderate to severe</keyword>
  <keyword>remission</keyword>
  <keyword>Mycobacterium avium paratuberculosis</keyword>
  <keyword>antibiotic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paratuberculosis</mesh_term>
    <mesh_term>Crohn Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clarithromycin</mesh_term>
    <mesh_term>Rifabutin</mesh_term>
    <mesh_term>Clofazimine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <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>December 23, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/96/NCT03009396/SAP_000.pdf</document_url>
    </provided_document>
    <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>December 16, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/96/NCT03009396/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>RHB-104 From RHB-104</title>
          <description>RHB-104 (fixed-dose combination 95 mg clarithromycin, 45 mg rifabutin, 10 mg clofazimine): For patients who were in the RHB-104 arm but are not in remission after 26 weeks in the RHB-104-01 study.</description>
        </group>
        <group group_id="P2">
          <title>RHB-104 From Placebo</title>
          <description>RHB-104 (fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, 10 mg clofazimine): For patients who were in the placebo arm but are not in remission after 26 weeks in the RHB-104-01 study.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="38"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="17"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Total Study</population>
      <group_list>
        <group group_id="B1">
          <title>RHB-104</title>
          <description>RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, 10 mg clofazimine.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="54"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <description>Age measured in years at Baseline</description>
          <population>16 subjects who transferred to the RHB-104-04 study were on RHB-104 in the RHB-104-01 (parent) study while 38 subjects were on placebo.</population>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>RHB-104 from RHB-104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="48.6" spread="9.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RHB-104 from placebo</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40.0" spread="13.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <population>16 subjects who transferred to the RHB-104-04 study were on RHB-104 in the RHB-104-01 (parent) study while 38 subjects were on placebo.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>RHB-104 from RHB-104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RHB-104 from placebo</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <population>16 subjects who transferred to the RHB-104-04 study were on RHB-104 in the RHB-104-01 (parent) study while 38 subjects were on placebo.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>RHB-104 from RHB-104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RHB-104 from placebo</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline Crohn's Disease Activity Index (CDAI) score</title>
          <description>Generally, CDAI score can range from 0-approx. 600. (in this protocol up to 450) CDAI scores of 150-219 describe mildly active disease, while scores of 220-450 describe moderately active disease and score above 450 describe severe disease.</description>
          <population>16 subjects who transferred to the RHB-104-04 study were on RHB-104 in the RHB-104-01 (parent) study while 38 subjects were on placebo.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>RHB-104 from RHB-104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="295.42" spread="82.865"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RHB-104 from placebo</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="271.67" spread="58.379"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Patients in Remission at Week 16</title>
        <description>The number of patients who achieved a reduction of the total Crohn's Disease Activity Index (CDAI) score to less than 150 points.&#xD;
Lower CDAI scores indicate a better outcome.</description>
        <time_frame>Week 16</time_frame>
        <group_list>
          <group group_id="O1">
            <title>RHB-104 From ACTIVE Arm of RHB-104-01</title>
            <description>RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, 10 mg clofazimine: For patients who were in the RHB-104 arm, but were not in remission after 26 weeks in the RHB-104-01 study.</description>
          </group>
          <group group_id="O2">
            <title>RHB-104 From PLACEBO Arm of RHB-104-01</title>
            <description>RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, 10 mg clofazimine: For patients who were in the placebo arm, but were not in remission after 26 weeks in the RHB-104-01 study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients in Remission at Week 16</title>
          <description>The number of patients who achieved a reduction of the total Crohn's Disease Activity Index (CDAI) score to less than 150 points.&#xD;
Lower CDAI scores indicate a better outcome.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Response at Week 16</title>
        <description>Reduction of the total Crohn's Disease Activity Index (CDAI) score by a minimum of 100 points Lower CDAI scores indicate a better outcome.</description>
        <time_frame>Week 16</time_frame>
        <population>Number of subjects achieved response</population>
        <group_list>
          <group group_id="O1">
            <title>RHB-104 From ACTIVE Arm of RHB-104-01</title>
            <description>RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, 10 mg clofazimine: For patients who were in the RHB-104 arm, but were not in remission after 26 weeks in the RHB-104-01 study.</description>
          </group>
          <group group_id="O2">
            <title>RHB-104 From PLACEBO Arm of RHB-104-01</title>
            <description>RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, 10 mg clofazimine: For patients who were in the placebo arm, but were not in remission after 26 weeks in the RHB-104-01 study.</description>
          </group>
        </group_list>
        <measure>
          <title>Response at Week 16</title>
          <description>Reduction of the total Crohn's Disease Activity Index (CDAI) score by a minimum of 100 points Lower CDAI scores indicate a better outcome.</description>
          <population>Number of subjects achieved response</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Number of Weeks for Patients to Achieve Remission</title>
        <description>[Date of first observed remission (CDAI less than 150) - date of first dose, or date of randomization if not dosed, plus 1] / 7 days. Subject who never experience remission during the study are censored at the time of their last CDAI assessment.</description>
        <time_frame>Baseline through week 52</time_frame>
        <population>Number of subjects achieved remission, n (%) RHB-104 from RHB-104: 6 (37.5); RHB-104 from Placebo: 20 (52.6).&#xD;
Number of patients censored due to never achieving remission, n (%) RHB-104 from RHB-104: 10 (62.5); RHB-104 from Placebo: 18 (47.4)</population>
        <group_list>
          <group group_id="O1">
            <title>RHB-104 From ACTIVE Arm of RHB-104-01</title>
            <description>RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, 10 mg clofazimine: For patients who were in the RHB-104 arm, but were not in remission after 26 weeks in the RHB-104-01 study.</description>
          </group>
          <group group_id="O2">
            <title>RHB-104 From PLACEBO Arm of RHB-104-01</title>
            <description>RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, 10 mg clofazimine: For patients who were in the placebo arm, but were not in remission after 26 weeks in the RHB-104-01 study.</description>
          </group>
        </group_list>
        <measure>
          <title>The Number of Weeks for Patients to Achieve Remission</title>
          <description>[Date of first observed remission (CDAI less than 150) - date of first dose, or date of randomization if not dosed, plus 1] / 7 days. Subject who never experience remission during the study are censored at the time of their last CDAI assessment.</description>
          <population>Number of subjects achieved remission, n (%) RHB-104 from RHB-104: 6 (37.5); RHB-104 from Placebo: 20 (52.6).&#xD;
Number of patients censored due to never achieving remission, n (%) RHB-104 from RHB-104: 10 (62.5); RHB-104 from Placebo: 18 (47.4)</population>
          <units>weeks</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">The value is not estimable. A 95% CI limit cannot be estimated based on Kaplan Meier methods used.</measurement>
                    <measurement group_id="O2" value="25.1" lower_limit="16.00" upper_limit="56.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.2112</p_value>
            <method>Log Rank</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Weeks the Patients Are in Remission</title>
        <description>Duration of remission is defined as the number of weeks the subject is in remission (CDAI score &lt; 150). It is calculated as the first date following remission at which CDAI is ≥150 minus the date of first remission, plus 1 day, divided by 7. Subjects who experienced remission and continued to be in remission at the time of their last CDAI assessment are censored at the date of their last CDAI assessment.</description>
        <time_frame>Baseline through week 52</time_frame>
        <population>Reached duration of remission (dropped out of remission during the study), n (%): RHB-104 from RHB-104 5 (83.3); RHB-104 from Placebo: 8 (40.0). Number of patients censored due to remaining in remission during the study, n (%): RHB-104 from RHB-104 1 (16.7); RHB-104 from Placebo: 12 (60.0)</population>
        <group_list>
          <group group_id="O1">
            <title>RHB-104 From ACTIVE Arm of RHB-104-01</title>
            <description>RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, 10 mg clofazimine: For patients who were in the RHB-104 arm, but were not in remission after 26 weeks in the RHB-104-01 study.</description>
          </group>
          <group group_id="O2">
            <title>RHB-104 From PLACEBO Arm of RHB-104-01</title>
            <description>RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, 10 mg clofazimine: For patients who were in the placebo arm but are not in remission after 26 weeks in the RHB-104-01 study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Weeks the Patients Are in Remission</title>
          <description>Duration of remission is defined as the number of weeks the subject is in remission (CDAI score &lt; 150). It is calculated as the first date following remission at which CDAI is ≥150 minus the date of first remission, plus 1 day, divided by 7. Subjects who experienced remission and continued to be in remission at the time of their last CDAI assessment are censored at the date of their last CDAI assessment.</description>
          <population>Reached duration of remission (dropped out of remission during the study), n (%): RHB-104 from RHB-104 5 (83.3); RHB-104 from Placebo: 8 (40.0). Number of patients censored due to remaining in remission during the study, n (%): RHB-104 from RHB-104 1 (16.7); RHB-104 from Placebo: 12 (60.0)</population>
          <units>weeks</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.7" lower_limit="NA" upper_limit="NA">The value is not estimable. A 95% CI limit cannot be estimated based on Kaplan Meier methods used</measurement>
                    <measurement group_id="O2" value="45.0" lower_limit="23.00" upper_limit="NA">The value is not estimable. A 95% CI limit cannot be estimated based on Kaplan Meier methods used.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0356</p_value>
            <method>Log Rank</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Weeks to Achieve Response</title>
        <description>[Date of first observed response (a reduction from baseline of ≥ 100 in CDAI score) - Date of first dose or date of randomization if not dosed + 1] / 7 Days. Subjects who never experienced response during the study are censored at the date of their last CDAI assessment.</description>
        <time_frame>Baseline through week 52</time_frame>
        <population>Number of subjects achieved response, n (%): RHB-104 from RHB-104 5 (31.3); RHB-104 from Placebo 21 (55.3). Number of patients censored due to never achieving response, n (%): RHB-104 from RHB-104 11 (68.8); RHB-104 from Placebo 17 (44.7)</population>
        <group_list>
          <group group_id="O1">
            <title>RHB-104 From ACTIVE Arm of RHB-104-01</title>
            <description>RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, 10 mg clofazimine: For patients who were in the RHB-104 arm, but were not in remission after 26 weeks in the RHB-104-01 study.</description>
          </group>
          <group group_id="O2">
            <title>RHB-104 From PLACEBO Arm of RHB-104-01</title>
            <description>RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, 10 mg clofazimine: For patients who were in the placebo arm, but were not in remission after 26 weeks in the RHB-104-01 study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Weeks to Achieve Response</title>
          <description>[Date of first observed response (a reduction from baseline of ≥ 100 in CDAI score) - Date of first dose or date of randomization if not dosed + 1] / 7 Days. Subjects who never experienced response during the study are censored at the date of their last CDAI assessment.</description>
          <population>Number of subjects achieved response, n (%): RHB-104 from RHB-104 5 (31.3); RHB-104 from Placebo 21 (55.3). Number of patients censored due to never achieving response, n (%): RHB-104 from RHB-104 11 (68.8); RHB-104 from Placebo 17 (44.7)</population>
          <units>Weeks</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="16.14" upper_limit="NA">The value is not estimable. A 95% CI limit cannot be estimated based on Kaplan Meier methods used.</measurement>
                    <measurement group_id="O2" value="26.1" lower_limit="9.14" upper_limit="56.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0514</p_value>
            <method>Log Rank</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Weeks the Patients Are in Response.</title>
        <description>Duration of response is defined as the number of weeks the subject is in a state of response (a reduction from baseline of ≥ 100 in CDAI score). It is calculated as the first date following response at which the reduction from baseline in CDAI is &lt;100 minus the date of first response, plus 1 day, divided by 7. Subjects who experienced response and continued to be in response at the time of their last CDAI assessment are censored at the date of their last CDAI assessment.</description>
        <time_frame>Baseline through week 52</time_frame>
        <population>Reached duration of response (dropped out of response during the study), n (%): RHB-104 from RHB-104 3 (60.0); RHB-104 from placebo 7 (33.3). Number of patients censored due to remaining in response during the study, n (%): RHB-104 from RHB-104 2 (40.0); RHB-104 from placebo 14 (66.7)</population>
        <group_list>
          <group group_id="O1">
            <title>RHB-104 From ACTIVE Arm of RHB-104-01</title>
            <description>RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, 10 mg clofazimine: For patients who were in the RHB-104 arm, but were not in remission after 26 weeks in the RHB-104-01 study.</description>
          </group>
          <group group_id="O2">
            <title>RHB-104 From PLACEBO Arm of RHB-104-01</title>
            <description>RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, 10 mg clofazimine: For patients who were in the placebo arm but are not in remission after 26 weeks in the RHB-104-01 study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Weeks the Patients Are in Response.</title>
          <description>Duration of response is defined as the number of weeks the subject is in a state of response (a reduction from baseline of ≥ 100 in CDAI score). It is calculated as the first date following response at which the reduction from baseline in CDAI is &lt;100 minus the date of first response, plus 1 day, divided by 7. Subjects who experienced response and continued to be in response at the time of their last CDAI assessment are censored at the date of their last CDAI assessment.</description>
          <population>Reached duration of response (dropped out of response during the study), n (%): RHB-104 from RHB-104 3 (60.0); RHB-104 from placebo 7 (33.3). Number of patients censored due to remaining in response during the study, n (%): RHB-104 from RHB-104 2 (40.0); RHB-104 from placebo 14 (66.7)</population>
          <units>Weeks</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.4" lower_limit="10.86" upper_limit="NA">The value is not estimable. A 95% CI limit cannot be estimated based on Kaplan Meier methods used.</measurement>
                    <measurement group_id="O2" value="45.0" lower_limit="26.14" upper_limit="NA">The value is not estimable. A 95% CI limit cannot be estimated based on Kaplan Meier methods used.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1259</p_value>
            <method>Log Rank</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Durable Remission Week 16 Through Week 52</title>
        <description>When a subject is in remission with a maximum CDAI score of 149 at every visit from week 16 through and including week 52.</description>
        <time_frame>Week 16 through week 52</time_frame>
        <group_list>
          <group group_id="O1">
            <title>RHB-104 From ACTIVE Arm of RHB-104-01</title>
            <description>RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, 10 mg clofazimine: For patients who were in the RHB-104 arm, but were not in remission after 26 weeks in the RHB-104-01 study.</description>
          </group>
          <group group_id="O2">
            <title>RHB-104 From PLACEBO Arm of RHB-104-01</title>
            <description>RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, 10 mg clofazimine: For patients who were in the placebo arm, but were not in remission after 26 weeks in the RHB-104-01 study.</description>
          </group>
        </group_list>
        <measure>
          <title>Durable Remission Week 16 Through Week 52</title>
          <description>When a subject is in remission with a maximum CDAI score of 149 at every visit from week 16 through and including week 52.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4114</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Increase in Milliseconds (ms) QT Wave</title>
        <description>The increase in the number of milliseconds change-from-baseline to week 52 in QTcF (Fridericia's Correction Formula of QT wave interval) (based on cardiac safety report).</description>
        <time_frame>week 52</time_frame>
        <group_list>
          <group group_id="O1">
            <title>RHB-104 From ACTIVE Arm of RHB-104-01</title>
            <description>RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, 10 mg clofazimine: For patients who were in the RHB-104 arm, but were not in remission after 26 weeks in the RHB-104-01 study.</description>
          </group>
          <group group_id="O2">
            <title>RHB-104 From PLACEBO Arm of RHB-104-01</title>
            <description>RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, 10 mg clofazimine: For patients who were in the placebo arm, but were not in remission after 26 weeks in the RHB-104-01 study.</description>
          </group>
        </group_list>
        <measure>
          <title>Increase in Milliseconds (ms) QT Wave</title>
          <description>The increase in the number of milliseconds change-from-baseline to week 52 in QTcF (Fridericia's Correction Formula of QT wave interval) (based on cardiac safety report).</description>
          <units>ms</units>
          <param>Least Squares Mean</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.9" lower_limit="17.77" upper_limit="30.02"/>
                    <measurement group_id="O2" value="27.6" lower_limit="23.66" upper_limit="31.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline through 30 days after last dose of study drug, or up to 13 months.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>RHB-104 From RHB-104</title>
          <description>RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, 10 mg clofazimine: For patients who were in the RHB-104 arm but are not in remission after 26 weeks in the RHB-104-01 study.</description>
        </group>
        <group group_id="E2">
          <title>RHB-104 From Placebo</title>
          <description>RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, 10 mg clofazimine: For patients who were in the placebo arm but are not in remission after 26 weeks in the RHB-104-01 study.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (17.1)</default_vocab>
        <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="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Crohn's disease</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Peripheral Arterial Occlusive Disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (17.1)</default_vocab>
        <default_assessment>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="14" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>Porokeratosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Crohn's Disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Dental caries</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Anal fistula</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Frequent bowel movements</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Gingival discolouration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Lip dry</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Siliva discolouration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Pirexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Gastroenteritis norovirus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Inflective scleritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Electrocardiogram abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Blood creatine phosphokinase abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Transaminases</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </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="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Chromaturia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </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="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Pain of skin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Pruritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </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>Reza Fathi, Sn. VP Research and Development</name_or_title>
      <organization>Redhill Biopharma</organization>
      <phone>972-(0)3-541-3131</phone>
      <email>reza@redhillbio.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/NCT03009396
org study id: RHB-104-04
nct id: NCT03009396
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
An open label extension to the RHB-104-01 Study.
An Open Label Phase III Study to Assess the Efficacy and Safety of Fixed-Dose Combination
      RHB-104 in Subjects with Active Crohn's Disease Despite 26 Weeks of Participation in the MAP
      US RHB-104-01 Study.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Active
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Patients in Remission at Week 16
time frame: Week 16
description: The number of patients who achieved a reduction of the total Crohn's Disease Activity Index (CDAI) score to less than 150 points.
Lower CDAI scores indicate a better outcome.
measure: Response at Week 16
time frame: Week 16
description: Reduction of the total Crohn's Disease Activity Index (CDAI) score by a minimum of 100 points Lower CDAI scores indicate a better outcome.
measure: The Number of Weeks for Patients to Achieve Remission
time frame: Baseline through week 52
description: [Date of first observed remission (CDAI less than 150) - date of first dose, or date of randomization if not dosed, plus 1] / 7 days. Subject who never experience remission during the study are censored at the time of their last CDAI assessment.
measure: Number of Weeks the Patients Are in Remission
time frame: Baseline through week 52
description: Duration of remission is defined as the number of weeks the subject is in remission (CDAI score < 150). It is calculated as the first date following remission at which CDAI is ≥150 minus the date of first remission, plus 1 day, divided by 7. Subjects who experienced remission and continued to be in remission at the time of their last CDAI assessment are censored at the date of their last CDAI assessment.
measure: Number of Weeks to Achieve Response
time frame: Baseline through week 52
description: [Date of first observed response (a reduction from baseline of ≥ 100 in CDAI score) - Date of first dose or date of randomization if not dosed + 1] / 7 Days. Subjects who never experienced response during the study are censored at the date of their last CDAI assessment.
measure: Number of Weeks the Patients Are in Response.
time frame: Baseline through week 52
description: Duration of response is defined as the number of weeks the subject is in a state of response (a reduction from baseline of ≥ 100 in CDAI score). It is calculated as the first date following response at which the reduction from baseline in CDAI is <100 minus the date of first response, plus 1 day, divided by 7. Subjects who experienced response and continued to be in response at the time of their last CDAI assessment are censored at the date of their last CDAI assessment.
measure: Durable Remission Week 16 Through Week 52
time frame: Week 16 through week 52
description: When a subject is in remission with a maximum CDAI score of 149 at every visit from week 16 through and including week 52.
measure: Increase in Milliseconds (ms) QT Wave
time frame: week 52
description: The increase in the number of milliseconds change-from-baseline to week 52 in QTcF (Fridericia's Correction Formula of QT wave interval) (based on cardiac safety report).
arm group label: RHB-104 - patients on ACTIVE therapy in RHB-104-01 study
arm group type: Experimental
description: Subjects who were on the active therapy arm in the RHB-104-01 clinical study will continue to receive RHB-104 at 5 capsules twice a day in addition to the standard of care they received in the RHB-104-01 clinical study
arm group label: RHB-104 - patients on PLACEBO therapy in RHB-104-01 study
arm group type: Experimental
description: Subjects who were on the active therapy arm in the RHB-104-01 clinical study will receive RHB-104 at 5 capsules twice a day in addition to the standard of care they received in the RHB-104-01 clinical study. The RHB-104 will be ramped up beginning at 1 capsule twice per day in week 1 increasing to 2 capsules twice per day in week 2, 3 capsules twice per day in week 3, 4 capsules per day in week 4 and achieving 5 capsules per day for the remainder of the study.
intervention type: Drug
intervention name: RHB-104 (fixed-dose combination: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine)
description: For patients on ACTIVE or PLACEBO in the parent study (RHB-104-01), who were not in remission after 26 weeks
arm group label: RHB-104 - patients on ACTIVE therapy in RHB-104-01 study
arm group label: RHB-104 - patients on PLACEBO therapy in RHB-104-01 study
other name: RHB-104
criteria: 
gender: All
minimum age: 18 Years
maximum age: 76 Years
healthy volunteers: No
last name: Ira N Kalfus, MD
role: Study Director
affiliation: RedHill Biopharma Limited
last name: David Y Graham, MD
role: Principal Investigator
affiliation: Department of Medicine / Gastroenterology, Baylor College of Medicine, Houston
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country: Canada
country: Czechia
country: Israel
country: New Zealand
country: Poland
country: Serbia
country: United States
url: http://www.redhillbio.com
description: RedHill home page
responsible party type: Sponsor
mesh term: Paratuberculosis
mesh term: Crohn Disease
mesh term: Clarithromycin
mesh term: Rifabutin
mesh term: Clofazimine
sharing ipd: No
provided document: 
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participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 