<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/NCT02200445</url>
  </required_header>
  <id_info>
    <org_study_id>IRB-P00009599</org_study_id>
    <secondary_id>2015P000016</secondary_id>
    <nct_id>NCT02200445</nct_id>
  </id_info>
  <brief_title>Low Dose IL-2 for Ulcerative Colitis</brief_title>
  <official_title>A Phase I Study of Low Dose Subcutaneous Interleukin-2 (IL-2) For The Treatment of Ulcerative Colitis.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Scott B. Snapper, MD PHD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boston Children's Hospital</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 this study is to determine the safety and maximum effective dose (MED) of&#xD;
      Interleukin-2 in subjects with moderate-to-severe ulcerative colitis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Interleukin-2 (IL-2) is a T cell growth factor. IL-2 is currently licensed for the treatment&#xD;
      of metastatic renal cell carcinoma and metastatic melanoma, where it promotes the expansion&#xD;
      of anti-cancer cytotoxic T cells and natural killer (NK) cells. However at low doses&#xD;
      (100-times lower than those used in cancer therapy), IL-2 promotes the selective expansion of&#xD;
      regulatory T cells (Tregs): an immune modulating subset of CD4+ lymphocytes.&#xD;
&#xD;
      A recent phase 1 clinical trial from our collaborators at the Dana Farber Cancer Institute&#xD;
      showed that low-dose IL-2 selectively expands Tregs in patients with treatment-resistant&#xD;
      Graft vs. Host Disease (GvHD), and that low-dose IL-2 is safe in this condition. A detailed&#xD;
      immunological analysis of samples from this study showed that low-dose IL-2 treatment was&#xD;
      associated with increased Treg proliferation, increased de novo thymic generation of Tregs,&#xD;
      and a resolution of defects in intracellular signalling and apoptosis seen in Tregs in&#xD;
      chronic GvHD. A recent phase 1 study from another group showed that low-dose IL-2 is safe in&#xD;
      the treatment of HCV-associated vasculitis. Low-dose IL-2 has also been shown to be&#xD;
      well-tolerated in subjects with HIV.&#xD;
&#xD;
      Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. Evidence from&#xD;
      pre-clinical models of intestinal inflammation, and also from patients with monogenetic&#xD;
      defects in Treg function, suggests that Tregs play a role in the prevention of inflammation&#xD;
      in the intestine.&#xD;
&#xD;
      The treatment (or intervention) in this study is a once-daily, subcutaneous injection of&#xD;
      IL-2, for a total of 8 weeks. The first 2 doses of the study drug will be administered by&#xD;
      research nurses at Boston Children's Hospital. Further doses will be self-administered, at&#xD;
      home. Training will be provided for correct self-administration.&#xD;
&#xD;
      This is a 3+3 dose escalation study of IL-2 in moderate-to-severe UC. This study design is&#xD;
      powered to identify the MED of low-dose IL-2 in UC. Once the MED is identified, a further 10&#xD;
      subjects will receive IL-2 at that dose. Recruitment of between 2 and 28 patients is planned.&#xD;
      The maximum tolerated dose (MED) is the highest tolerated dose level at which a minimum of 6&#xD;
      subjects have been evaluated, with fewer than 2 evaluable subjects in 6 experiencing a dose&#xD;
      limiting toxicity (DLT); i.e. DLT in &gt;1/6 evaluable subjects. In addition to the above at&#xD;
      least 1 patient should meet the criteria for response or remission for it to be considered&#xD;
      the MED.&#xD;
&#xD;
      Dose levels are based on the experience of our collaborators in GvHD. In addition to&#xD;
      determining the MED, this study will determine if low-dose IL-2 is safe and well-tolerated in&#xD;
      patients with moderate-to-severe ulcerative colitis. A detailed immunological analysis of&#xD;
      samples obtained from this study will determine if low-dose IL-2 expands Tregs in vivo, in&#xD;
      patients with moderate-to-severe UC. Immunological changes will then be correlated with&#xD;
      clinical response.&#xD;
&#xD;
      The study will take place at Boston Children's Hospital. The study will involve 10 study&#xD;
      visits. Most of the study visits involve blood tests. A flexible sigmoidoscopy or colonoscopy&#xD;
      will be performed as part of the screening process. A flexible sigmoidoscopy will also be&#xD;
      performed on completion of therapy, to determine clinical response.&#xD;
&#xD;
      The first two subjects to receive the study drug will be admitted overnight following the&#xD;
      first dose. Subsequent doses will be administered on an out-patient basis. All other subjects&#xD;
      will receive IL-2 on an out-patient basis.&#xD;
&#xD;
      Responders (with an acceptable side-effect profile) will be allowed to continue the study&#xD;
      drug for at least 1 year. Compensation will be provided for participants.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2015</start_date>
  <completion_date type="Actual">March 2021</completion_date>
  <primary_completion_date type="Actual">October 1, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Subjects With Serious and Non-serious Adverse Events.</measure>
    <time_frame>8 weeks</time_frame>
    <description>Enumeration of the serious and non-serious adverse events seen in the study. Enumeration of any dose limiting toxicity seen in the study.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinical Response</measure>
    <time_frame>8 weeks.</time_frame>
    <description>A decrease from baseline in the total Mayo score of at least 3 points and at least 30% , with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore for rectal bleeding of 0 or 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinical Remission</measure>
    <time_frame>8 Weeks</time_frame>
    <description>A total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Ulcerative Colitis</condition>
  <arm_group>
    <arm_group_label>Interleukin-2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Study drug: Interleukin-2 (aldesleukin, Proleukin, IL-2).&#xD;
Each subject will receive an 8-week course of once-daily, subcutaneously administered IL-2. There will be three dose cohorts. Each subject will be recruited into a single dose cohort and receive a single dose level of IL-2 throughout the study.&#xD;
The dose levels will be as follows:&#xD;
Cohort 1: 0.3x10^6 IU/m^2/day.&#xD;
Cohort 2: 1.0x10^6 IU/m^2/day.&#xD;
Cohort 3: 1.5x10^6 IU/m^2/day.&#xD;
Up to 6 subjects will be recruited to each dose cohort.&#xD;
Once the maximum effective dose has been identified, a further 10 subjects will receive IL-2 at the maximum effective dose.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Interleukin-2 (aldesleukin).</intervention_name>
    <description>Description of intervention is covered in &quot;Arm&quot;, above.</description>
    <arm_group_label>Interleukin-2</arm_group_label>
    <other_name>Proleukin.</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18-70 years.&#xD;
&#xD;
          -  A diagnosis of UC made by standard clinical, radiological, endoscopic and histological&#xD;
             criteria.&#xD;
&#xD;
          -  Moderate to severe UC with a Mayo score of 6-12.&#xD;
&#xD;
          -  Failure to tolerate or failure to respond to at least one conventional therapy with&#xD;
             the intention of inducing or maintaining remission (examples include oral&#xD;
             corticosteroids, oral 5-aminosalicylates, azathioprine and/or 6-mercaptopurine, or a&#xD;
             tumor necrosis factor (TNF) antagonist). Corticosteroid dependency (inability to taper&#xD;
             oral corticosteroids without a recurrence of disease activity) is also included in&#xD;
             this category.&#xD;
&#xD;
          -  Stable doses of concomitant medications.&#xD;
&#xD;
          -  A negative pregnancy test in the 2 weeks prior to anticipated commencement of the&#xD;
             study drug, in female subjects of child-bearing age. Men and women of reproductive&#xD;
             potential must agree to use an acceptable method of birth control during treatment and&#xD;
             for six months after completion of treatment.&#xD;
&#xD;
          -  Ability to provide informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A diagnosis of Crohn's disease or Inflammatory Bowel Disease - Unspecified (IBD-U, a&#xD;
             diagnostic classification formerly termed &quot;indeterminate colitis&quot;).&#xD;
&#xD;
          -  Requirement for immediate surgical, endoscopic or radiological intervention for toxic&#xD;
             megacolon, massive hemorrhage, perforation, sepsis, or intra-abdominal or perianal&#xD;
             abscess.&#xD;
&#xD;
          -  Ileostomy, proctocolectomy or subtotal colectomy with ileorectal anastomosis.&#xD;
&#xD;
          -  History of colorectal cancer or dysplasia.&#xD;
&#xD;
          -  Positive stool test for Clostridium difficile.&#xD;
&#xD;
          -  Current medically significant infection.&#xD;
&#xD;
          -  Significant laboratory abnormalities, including;&#xD;
&#xD;
               1. Hb &lt; 8.0 g/dL, WBC &lt; 2.5 x 103/mm3, Plt &lt; 100 x 103/mm3.&#xD;
&#xD;
               2. Creatinine ≥ 1.5x institutional upper limit of normal (ULN).&#xD;
&#xD;
               3. Total bilirubin &gt; 2.0 mg/dL, ALT &gt; 2x institutional ULN, GGT &gt; 2x institutional&#xD;
                  ULN. Elevated unconjugated bilirubin related to Gilbert's syndrome is allowed.&#xD;
&#xD;
               4. Abnormal thyroid function tests.&#xD;
&#xD;
          -  Positive serology for HIV, hepatitis B virus (HBV) or HCV.&#xD;
&#xD;
          -  Positive screening test for tuberculosis (TB).&#xD;
&#xD;
          -  First dose of an anti-TNF medication within 4 weeks of anticipated study commencement,&#xD;
             or a subsequent dose within 2 weeks of commencement; or ciclosporin or tacrolimus&#xD;
             within 2 weeks of anticipated study commencement.&#xD;
&#xD;
          -  Received another investigational new drug (IND) within 5 half-lives of that agent&#xD;
             before the planned commencement of SC IL-2.&#xD;
&#xD;
          -  Malignancy within the last 5 years.&#xD;
&#xD;
          -  Allergy to any component of the study drug.&#xD;
&#xD;
          -  Pregnant or lactating women.&#xD;
&#xD;
          -  Inability to comply with the study protocol or inability to give informed consent.&#xD;
&#xD;
          -  Prior exposure to IL-2.&#xD;
&#xD;
          -  Uncontrolled cardiac angina or symptomatic congestive cardiac failure (NYHA Class III&#xD;
             or IV).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Scott B Snapper, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Boston Children's Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jessica R Allegretti, MD, MPH</last_name>
    <role>Study Director</role>
    <affiliation>Brigham and Women's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Boston Children's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brigham &amp; Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Koreth J, Matsuoka K, Kim HT, McDonough SM, Bindra B, Alyea EP 3rd, Armand P, Cutler C, Ho VT, Treister NS, Bienfang DC, Prasad S, Tzachanis D, Joyce RM, Avigan DE, Antin JH, Ritz J, Soiffer RJ. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med. 2011 Dec 1;365(22):2055-66. doi: 10.1056/NEJMoa1108188.</citation>
    <PMID>22129252</PMID>
  </reference>
  <reference>
    <citation>Matsuoka K, Koreth J, Kim HT, Bascug G, McDonough S, Kawano Y, Murase K, Cutler C, Ho VT, Alyea EP, Armand P, Blazar BR, Antin JH, Soiffer RJ, Ritz J. Low-dose interleukin-2 therapy restores regulatory T cell homeostasis in patients with chronic graft-versus-host disease. Sci Transl Med. 2013 Apr 3;5(179):179ra43. doi: 10.1126/scitranslmed.3005265.</citation>
    <PMID>23552371</PMID>
  </reference>
  <reference>
    <citation>Saadoun D, Rosenzwajg M, Joly F, Six A, Carrat F, Thibault V, Sene D, Cacoub P, Klatzmann D. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. N Engl J Med. 2011 Dec 1;365(22):2067-77. doi: 10.1056/NEJMoa1105143. Erratum In: N Engl J Med. 2014 Feb 20;370(8):786.</citation>
    <PMID>22129253</PMID>
  </reference>
  <reference>
    <citation>Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987 Dec 24;317(26):1625-9. doi: 10.1056/NEJM198712243172603.</citation>
    <PMID>3317057</PMID>
  </reference>
  <reference>
    <citation>Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005 Dec 8;353(23):2462-76. doi: 10.1056/NEJMoa050516. Erratum In: N Engl J Med. 2006 May 18;354(20):2200.</citation>
    <PMID>16339095</PMID>
  </reference>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>July 22, 2014</study_first_submitted>
  <study_first_submitted_qc>July 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 25, 2014</study_first_posted>
  <results_first_submitted>November 21, 2020</results_first_submitted>
  <results_first_submitted_qc>December 17, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">December 19, 2020</results_first_posted>
  <last_update_submitted>June 12, 2023</last_update_submitted>
  <last_update_submitted_qc>June 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Boston Children's Hospital</investigator_affiliation>
    <investigator_full_name>Scott B. Snapper, MD PHD</investigator_full_name>
    <investigator_title>Associate Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Ulcerative colitis</keyword>
  <keyword>Inflammatory bowel disease</keyword>
  <keyword>Interleukin 2</keyword>
  <keyword>Interleukin-2</keyword>
  <keyword>IL-2</keyword>
  <keyword>Regulatory T Cells</keyword>
  <keyword>Tregs</keyword>
  <keyword>T-Lymphocytes, Regulatory</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colitis</mesh_term>
    <mesh_term>Colitis, Ulcerative</mesh_term>
    <mesh_term>Ulcer</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aldesleukin</mesh_term>
    <mesh_term>Interleukin-2</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 11, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/45/NCT02200445/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Interleukin-2 Dose A</title>
          <description>Study drug: Interleukin-2 (aldesleukin, Proleukin, IL-2).&#xD;
The dose levels will be as follows:&#xD;
Cohort 1: 0.3x10^6 IU/m^2/day.</description>
        </group>
        <group group_id="P2">
          <title>Interleukin-2 Dose B</title>
          <description>- Cohort 2: 1.0x10^6 IU/m^2/day.</description>
        </group>
        <group group_id="P3">
          <title>Interleukin-2 Dose C</title>
          <description>- Cohort 3: 1.5x10^6 IU/m^2/day</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="17"/>
                <participants group_id="P3" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="13"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Interleukin-2 Dose A</title>
          <description>Study drug: Interleukin-2 (aldesleukin, Proleukin, IL-2).&#xD;
The dose levels will be as follows:&#xD;
Cohort 1: 0.3x10^6 IU/m^2/day.</description>
        </group>
        <group group_id="B2">
          <title>Interleukin-2 Dose B</title>
          <description>- Cohort 2: 1.0x10^6 IU/m^2/day.</description>
        </group>
        <group group_id="B3">
          <title>Interleukin-2 Dose C</title>
          <description>- Cohort 3: 1.5x10^6 IU/m^2/day</description>
        </group>
        <group group_id="B4">
          <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="4"/>
            <count group_id="B2" value="17"/>
            <count group_id="B3" value="5"/>
            <count group_id="B4" value="26"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="36.7" lower_limit="27" upper_limit="57"/>
                    <measurement group_id="B2" value="43" lower_limit="18" upper_limit="69"/>
                    <measurement group_id="B3" value="46.6" lower_limit="25" upper_limit="71"/>
                    <measurement group_id="B4" value="38.7" lower_limit="18" upper_limit="71"/>
                  </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="2"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="18"/>
                  </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="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="25"/>
                  </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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </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="4"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Extent</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Ulcerative Proctitis</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Left-sided</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Pancolitis</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Subjects With Serious and Non-serious Adverse Events.</title>
        <description>Enumeration of the serious and non-serious adverse events seen in the study. Enumeration of any dose limiting toxicity seen in the study.</description>
        <time_frame>8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Interleukin-2 Dose A</title>
            <description>Study drug: Interleukin-2 (aldesleukin, Proleukin, IL-2).&#xD;
The dose levels will be as follows:&#xD;
Cohort 1: 0.3x10^6 IU/m^2/day.</description>
          </group>
          <group group_id="O2">
            <title>Interleukin-2 Dose B</title>
            <description>- Cohort 2: 1.0x10^6 IU/m^2/day.</description>
          </group>
          <group group_id="O3">
            <title>Interleukin-2 Dose C</title>
            <description>- Cohort 3: 1.5x10^6 IU/m^2/day</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects With Serious and Non-serious Adverse Events.</title>
          <description>Enumeration of the serious and non-serious adverse events seen in the study. Enumeration of any dose limiting toxicity seen in the study.</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="4"/>
                <count group_id="O2" value="17"/>
                <count group_id="O3" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Clinical Response</title>
        <description>A decrease from baseline in the total Mayo score of at least 3 points and at least 30% , with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore for rectal bleeding of 0 or 1</description>
        <time_frame>8 weeks.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Interleukin-2 Dose A</title>
            <description>Study drug: Interleukin-2 (aldesleukin, Proleukin, IL-2).&#xD;
The dose levels will be as follows:&#xD;
Cohort 1: 0.3x10^6 IU/m^2/day.</description>
          </group>
          <group group_id="O2">
            <title>Interleukin-2 Dose B</title>
            <description>- Cohort 2: 1.0x10^6 IU/m^2/day.</description>
          </group>
          <group group_id="O3">
            <title>Interleukin-2 Dose C</title>
            <description>- Cohort 3: 1.5x10^6 IU/m^2/day</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinical Response</title>
          <description>A decrease from baseline in the total Mayo score of at least 3 points and at least 30% , with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore for rectal bleeding of 0 or 1</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="4"/>
                <count group_id="O2" value="17"/>
                <count group_id="O3" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Clinical response criteria met</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Clinical Response criteria not met</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>withdrew from trial</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Clinical Remission</title>
        <description>A total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point</description>
        <time_frame>8 Weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Interleukin-2 Dose A</title>
            <description>Study drug: Interleukin-2 (aldesleukin, Proleukin, IL-2).&#xD;
The dose levels will be as follows:&#xD;
Cohort 1: 0.3x10^6 IU/m^2/day.</description>
          </group>
          <group group_id="O2">
            <title>Interleukin-2 Dose B</title>
            <description>- Cohort 2: 1.0x10^6 IU/m^2/day.</description>
          </group>
          <group group_id="O3">
            <title>Interleukin-2 Dose C</title>
            <description>- Cohort 3: 1.5x10^6 IU/m^2/day</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinical Remission</title>
          <description>A total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point</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="4"/>
                <count group_id="O2" value="17"/>
                <count group_id="O3" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Clinical Remission criteria met</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Clinical Remission criteria not met</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>withdrew from trial</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from Baseline of study until subjects withdrew, were lost to follow-up, or completed the study up to week 8 and through the OLE up to week 52.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Interleukin-2 Dose A</title>
          <description>Study drug: Interleukin-2 (aldesleukin, Proleukin, IL-2).&#xD;
The dose levels will be as follows:&#xD;
Cohort 1: 0.3x10^6 IU/m^2/day.</description>
        </group>
        <group group_id="E2">
          <title>Interleukin-2 Dose B</title>
          <description>- Cohort 2: 1.0x10^6 IU/m^2/day.</description>
        </group>
        <group group_id="E3">
          <title>Interleukin-2 Dose C</title>
          <description>- Cohort 3: 1.5x10^6 IU/m^2/day</description>
        </group>
      </group_list>
      <serious_events>
        <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="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <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="4" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="17"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Uveitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>bloating</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>IBD Flare</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Increased Bowel Movements</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>achiness/chills</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="17"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Thrush</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>fever</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="17"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Flu-like symptoms</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>joint pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>numbness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>migraine</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Upper respiratory Tract Infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>sore throat</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>strep throat</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="4"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="17"/>
                <counts group_id="E3" events="6" subjects_affected="5" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Papular rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>macular rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>pityriasis rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Eczematous rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>cellulitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Hives</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </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 NOT 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. Jessica Allegretti</name_or_title>
      <organization>Brigham and Women's Hospital</organization>
      <phone>617-732-5500</phone>
      <email>jallegretti@bwh.harvard.edu</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/NCT02200445
org study id: IRB-P00009599
secondary id: 2015P000016
nct id: NCT02200445
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to determine the safety and maximum effective dose (MED) of
      Interleukin-2 in subjects with moderate-to-severe ulcerative colitis.
Interleukin-2 (IL-2) is a T cell growth factor. IL-2 is currently licensed for the treatment
      of metastatic renal cell carcinoma and metastatic melanoma, where it promotes the expansion
      of anti-cancer cytotoxic T cells and natural killer (NK) cells. However at low doses
      (100-times lower than those used in cancer therapy), IL-2 promotes the selective expansion of
      regulatory T cells (Tregs): an immune modulating subset of CD4+ lymphocytes.

      A recent phase 1 clinical trial from our collaborators at the Dana Farber Cancer Institute
      showed that low-dose IL-2 selectively expands Tregs in patients with treatment-resistant
      Graft vs. Host Disease (GvHD), and that low-dose IL-2 is safe in this condition. A detailed
      immunological analysis of samples from this study showed that low-dose IL-2 treatment was
      associated with increased Treg proliferation, increased de novo thymic generation of Tregs,
      and a resolution of defects in intracellular signalling and apoptosis seen in Tregs in
      chronic GvHD. A recent phase 1 study from another group showed that low-dose IL-2 is safe in
      the treatment of HCV-associated vasculitis. Low-dose IL-2 has also been shown to be
      well-tolerated in subjects with HIV.

      Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. Evidence from
      pre-clinical models of intestinal inflammation, and also from patients with monogenetic
      defects in Treg function, suggests that Tregs play a role in the prevention of inflammation
      in the intestine.

      The treatment (or intervention) in this study is a once-daily, subcutaneous injection of
      IL-2, for a total of 8 weeks. The first 2 doses of the study drug will be administered by
      research nurses at Boston Children's Hospital. Further doses will be self-administered, at
      home. Training will be provided for correct self-administration.

      This is a 3+3 dose escalation study of IL-2 in moderate-to-severe UC. This study design is
      powered to identify the MED of low-dose IL-2 in UC. Once the MED is identified, a further 10
      subjects will receive IL-2 at that dose. Recruitment of between 2 and 28 patients is planned.
      The maximum tolerated dose (MED) is the highest tolerated dose level at which a minimum of 6
      subjects have been evaluated, with fewer than 2 evaluable subjects in 6 experiencing a dose
      limiting toxicity (DLT); i.e. DLT in >1/6 evaluable subjects. In addition to the above at
      least 1 patient should meet the criteria for response or remission for it to be considered
      the MED.

      Dose levels are based on the experience of our collaborators in GvHD. In addition to
      determining the MED, this study will determine if low-dose IL-2 is safe and well-tolerated in
      patients with moderate-to-severe ulcerative colitis. A detailed immunological analysis of
      samples obtained from this study will determine if low-dose IL-2 expands Tregs in vivo, in
      patients with moderate-to-severe UC. Immunological changes will then be correlated with
      clinical response.

      The study will take place at Boston Children's Hospital. The study will involve 10 study
      visits. Most of the study visits involve blood tests. A flexible sigmoidoscopy or colonoscopy
      will be performed as part of the screening process. A flexible sigmoidoscopy will also be
      performed on completion of therapy, to determine clinical response.

      The first two subjects to receive the study drug will be admitted overnight following the
      first dose. Subsequent doses will be administered on an out-patient basis. All other subjects
      will receive IL-2 on an out-patient basis.

      Responders (with an acceptable side-effect profile) will be allowed to continue the study
      drug for at least 1 year. Compensation will be provided for participants.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Subjects With Serious and Non-serious Adverse Events.
time frame: 8 weeks
description: Enumeration of the serious and non-serious adverse events seen in the study. Enumeration of any dose limiting toxicity seen in the study.
measure: Number of Participants With Clinical Response
time frame: 8 weeks.
description: A decrease from baseline in the total Mayo score of at least 3 points and at least 30% , with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore for rectal bleeding of 0 or 1
measure: Number of Participants With Clinical Remission
time frame: 8 Weeks
description: A total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point
arm group label: Interleukin-2
arm group type: Experimental
description: Study drug: Interleukin-2 (aldesleukin, Proleukin, IL-2).
Each subject will receive an 8-week course of once-daily, subcutaneously administered IL-2. There will be three dose cohorts. Each subject will be recruited into a single dose cohort and receive a single dose level of IL-2 throughout the study.
The dose levels will be as follows:
Cohort 1: 0.3x10^6 IU/m^2/day.
Cohort 2: 1.0x10^6 IU/m^2/day.
Cohort 3: 1.5x10^6 IU/m^2/day.
Up to 6 subjects will be recruited to each dose cohort.
Once the maximum effective dose has been identified, a further 10 subjects will receive IL-2 at the maximum effective dose.
intervention type: Drug
intervention name: Interleukin-2 (aldesleukin).
description: Description of intervention is covered in "Arm", above.
arm group label: Interleukin-2
other name: Proleukin.
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Scott B Snapper, MD PhD
role: Principal Investigator
affiliation: Boston Children's Hospital
last name: Jessica R Allegretti, MD, MPH
role: Study Director
affiliation: Brigham and Women's Hospital
facility: 
facility: 
country: United States
citation: Koreth J, Matsuoka K, Kim HT, McDonough SM, Bindra B, Alyea EP 3rd, Armand P, Cutler C, Ho VT, Treister NS, Bienfang DC, Prasad S, Tzachanis D, Joyce RM, Avigan DE, Antin JH, Ritz J, Soiffer RJ. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med. 2011 Dec 1;365(22):2055-66. doi: 10.1056/NEJMoa1108188.
PMID: 22129252
citation: Matsuoka K, Koreth J, Kim HT, Bascug G, McDonough S, Kawano Y, Murase K, Cutler C, Ho VT, Alyea EP, Armand P, Blazar BR, Antin JH, Soiffer RJ, Ritz J. Low-dose interleukin-2 therapy restores regulatory T cell homeostasis in patients with chronic graft-versus-host disease. Sci Transl Med. 2013 Apr 3;5(179):179ra43. doi: 10.1126/scitranslmed.3005265.
PMID: 23552371
citation: Saadoun D, Rosenzwajg M, Joly F, Six A, Carrat F, Thibault V, Sene D, Cacoub P, Klatzmann D. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. N Engl J Med. 2011 Dec 1;365(22):2067-77. doi: 10.1056/NEJMoa1105143. Erratum In: N Engl J Med. 2014 Feb 20;370(8):786.
PMID: 22129253
citation: Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987 Dec 24;317(26):1625-9. doi: 10.1056/NEJM198712243172603.
PMID: 3317057
citation: Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005 Dec 8;353(23):2462-76. doi: 10.1056/NEJMoa050516. Erratum In: N Engl J Med. 2006 May 18;354(20):2200.
PMID: 16339095
responsible party type: Sponsor-Investigator
investigator affiliation: Boston Children's Hospital
investigator full name: Scott B. Snapper, MD PHD
investigator title: Associate Professor of Medicine
mesh term: Colitis
mesh term: Colitis, Ulcerative
mesh term: Ulcer
mesh term: Aldesleukin
mesh term: Interleukin-2
sharing ipd: Undecided
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 