Study of OSE-127 vs Placebo in Patients With Moderate to Severe Active Ulcerative Colitis (CoTikiS)

• ClinicalTrials.gov Identifier: NCT04882007
• Recruitment Status: Unknown
• First Posted: May 11, 2021
• Last Update Posted: June 28, 2021
• Sponsor: OSE Immunotherapeutics
• Information provided by (Responsible Party): OSE Immunotherapeutics

Tracking Information

• First Submitted Date: April 13, 2021
• First Posted Date: May 11, 2021
• Last Update Posted Date: June 28, 2021
• Actual Study Start Date: October 2, 2020
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 8, 2021)

Change in modified Mayo Score [ Time Frame: Baseline and Week 10 ]

Change in modified Mayo Score between baseline and Week 10 clinical symptoms (stool frequency and rectal bleeding sub-scores) additionally to the endoscopic sub-score

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 8, 2021)

• Clinical Remission [ Time Frame: Week 10 ]
  Number and proportion of patients achieving clinical remission at Week 10, defined as a modified Mayo score of ≤ 2 points and with no individual sub-score of > 1 point and a rectal bleeding at 0, therefore a stool frequency score of 0 or 1 and an endoscopic score of 0 or 1
• Clinical efficacy of OSE-127 vs placebo [ Time Frame: Week 10 ]
  Number and proportion of patients with a clinical response defined as a reduction in the modified Mayo score of ≥ 3 points and of ≥ 30% from baseline, with an accompanying decrease from baseline in the rectal bleeding sub-score of ≥ 1 point or an absolute rectal bleeding sub-score of ≤ 1 point
• Efficacy of OSE-127 vs placebo on endoscopic remission [ Time Frame: Week 10 ]
  Number and proportion of patients with an endoscopic remission defined by an endoscopic Mayo sub-score =0
• Efficacy of OSE-127 vs placebo on endoscopic improvement [ Time Frame: Week 10 ]
  Number and proportion of patients with endoscopic response or improvement defined by an endoscopic subscore of Mayo ≤ 1 point
• Efficacy of OSE-127 vs placebo on endoscopic improvement [ Time Frame: Week 10 ]
  Mean change from baseline in the endoscopic activity measured by the Ulcerative Colitis Endoscopic Index of Severity (UCEIS)
• Overall safety and tolerability of OSE-127 in patients with moderate to severe UC [ Time Frame: Week 0 to Week 22 for patients not participating in the optional extension, and Week 0 to Week 50 for patients participating in the optional extension ]
  Frequency and severity of reported treatment-emergent adverse events, serious adverse events

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of OSE-127 vs Placebo in Patients With Moderate to Severe Active Ulcerative Colitis
• Official Title: Randomized, Double-blind, Phase 2 Study to Evaluate the Efficacy and the Safety of OSE-127 Versus Placebo in Subjects With Moderate to Severe Active Ulcerative Colitis Who Have Failed or Are Intolerant to Previous Treatment(s)
• Brief Summary: This is a phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group study in patients with moderate to severe active ulcerative colitis.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

During the Double-blind phase all participants will be blinded to treatment assignment.

Primary Purpose: Treatment

• Condition: Ulcerative Colitis

Intervention

• Drug: OSE-127
  mAb antagonist to CD127 receptor (or IL-7Rα)
• Drug: Placebo
  Normal saline

Study Arms

• Experimental: OSE-127 High dose induction phase
  OSE-127 mAb antagonist to CD127 receptor (or IL-7Rα) intravenous infusion 3 total infusions, weeks 0, 2, and 6
  Intervention: Drug: OSE-127
• Experimental: OSE-127 Low dose induction phase
  OSE-127 mAb antagonist to CD127 receptor (or IL-7Rα) intravenous infusion 3 total infusions, weeks 0, 2, and 6
  Intervention: Drug: OSE-127
• Placebo Comparator: Placebo induction phase
  Normal saline intravenous infusion 3 total infusions, weeks 0, 2, and 6
  Intervention: Drug: Placebo
• Experimental: OSE-127 High dose optional extension phase
  OSE-127 mAb antagonist to CD127 receptor (or IL-7Rα) intravenous infusion 7 total infusions, weeks 10, 14, 18, 22, 26, 30, and 34
  Intervention: Drug: OSE-127

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: May 8, 2021): 150
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2023
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Provision of signed and dated informed consent document indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrollment
2. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
3. Willingness to refrain from live or attenuated vaccines during the study and for 12 weeks after last dose
4. Male or female 18 to 75 years of age, inclusive

5. Diagnosis of moderate to severe active UC made at least 3 months before the screening visit. The diagnosis of UC must have been confirmed by endoscopy, with a minimal extent of 15 cm from anal margin and histology (Moderate to severe active UC is defined by a modified Mayo score between 4 and 9, inclusive. The modified Mayo score is defined by the addition of the rectal bleeding subscore, the stool frequency sub-score, and the endoscopic sub-score. Thus, to be included, a patient must have the following:

   1. a rectal bleeding score ≥ 1,
   2. a stool frequency score ≥ 1 (sub-score calculated before bowel preparation), and
   3. an endoscopic sub-score ≥ 2

6. No previous biologic therapy (i.e., TNF antagonists, vedolizumab or ustekinumab) and prior or current UC documented medication history that includes at least 1 of the following:

   1. Corticosteroids
   2. Immunosuppressive agents

OR

Previous or current biologic therapy

Exclusion Criteria:

1. Stoma, proctocolectomy, or subtotal colectomy
2. Physician judgment that patient is likely to require any surgery for UC during the study duration, or double-blind phase duration at least
3. Evidence of fulminant colitis, toxic megacolon, or perforation
4. Current or recent (within 4 weeks prior to screening) hospitalization for UC care and/or treatment with IV steroids

5. The following laboratory results at screening:

   1. Elevation at screening of aminotransferase (AST), alanine aminotransferase (ALT) > 3 × the upper limit of normal (ULN) or total bilirubin > 2 × ULN (unless due to Gilbert's disease) or evidence of chronic liver disease
   2. Platelet count < 100,000/mm3
   3. Hemoglobin (Hgb) < 8.5 g/dL
   4. Neutrophils < 1500/mm3
   5. Lymphocytes < 800/mm3
   6. Absolute white blood cell (WBC) count < 3000/mm3
6. Crohn's disease or indeterminate colitis or any other diagnosis not consisting with UC
7. History or evidence of incompletely resected colonic dysplasia or unconventional lesion at risk of colonic adenocarcinoma
8. Stool culture or other examination positive for enteric pathogen, including Clostridium difficile (C. diff) toxin. If positive, the patient should be treated and rescreening is allowed.
9. Men or women with childbearing potential not willing to use adequate birth control during the study. Adequate birth control includes surgical sterilization, intrauterine device, oral contraceptive, contraceptive patch, long-acting injectable contraceptive, partner's vasectomy, double-barrier method (condom, diaphragm with spermicide), or abstinence during study and 30 days following the last follow-up visit. Women of childbearing potential will enter the study after a negative pregnancy test.
10. Breastfeeding
11. Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) from screening through the end of the study
12. Use of topical steroids and/or topical 5-aminosalicylic acid preparations within 2 weeks before the screening visit (all such medications should be withdrawn at least 2 weeks prior to the screening visit)
13. Use of antidiarrheals within 2 weeks before the screening visit (all such medications should be withdrawn at least 2 weeks prior to the screening visit)
14. Treatment with azathioprine, 6-MP, methotrexate (MTX), cyclosporin, tacrolimus, sirolimus, leflunomide and/or mycophenolate mofetil within 4 weeks before the screening visit (all such medications should be withdrawn at least 4 weeks prior to the screening visit)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belarus, Belgium, Bulgaria, Croatia, Georgia, Hungary, Latvia, Poland, Russian Federation, South Africa, Ukraine

Administrative Information

• NCT Number: NCT04882007
• Other Study ID Numbers: OSE-127-C201; 2020-001398-59 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: OSE Immunotherapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: OSE Immunotherapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Frederique Corallo, MD; OSE Immunotherapeutics

• PRS Account: OSE Immunotherapeutics
• Verification Date: June 2021