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

Study Overview
=================
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.

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)

Conditions
-----------------
Ulcerative Colitis

Intervention / Treatment
-----------------
* Drug: OSE-127
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures Willingness to refrain from live or attenuated vaccines during the study and for 12 weeks after last dose Male or female 18 to 75 years of age, inclusive 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: a rectal bleeding score ≥ 1, a stool frequency score ≥ 1 (sub-score calculated before bowel preparation), and an endoscopic sub-score ≥ 2 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: Corticosteroids Immunosuppressive agents OR Previous or current biologic therapy Exclusion Criteria: Stoma, proctocolectomy, or subtotal colectomy Physician judgment that patient is likely to require any surgery for UC during the study duration, or double-blind phase duration at least Evidence of fulminant colitis, toxic megacolon, or perforation Current or recent (within 4 weeks prior to screening) hospitalization for UC care and/or treatment with IV steroids The following laboratory results at screening: 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 Platelet count < 100,000/mm3 Hemoglobin (Hgb) < 8.5 g/dL Neutrophils < 1500/mm3 Lymphocytes < 800/mm3 Absolute white blood cell (WBC) count < 3000/mm3 Crohn's disease or indeterminate colitis or any other diagnosis not consisting with UC History or evidence of incompletely resected colonic dysplasia or unconventional lesion at risk of colonic adenocarcinoma 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. 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. Breastfeeding Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) from screening through the end of the study 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) 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) 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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in modified Mayo Score | 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 | Baseline and Week 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Remission | 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 | Week 10 | 
| Clinical efficacy of OSE-127 vs placebo | 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 | Week 10 | 
| Efficacy of OSE-127 vs placebo on endoscopic remission | Number and proportion of patients with an endoscopic remission defined by an endoscopic Mayo sub-score =0 | Week 10 | 
| Efficacy of OSE-127 vs placebo on endoscopic improvement | Number and proportion of patients with endoscopic response or improvement defined by an endoscopic subscore of Mayo ≤ 1 point | Week 10 | 
| Efficacy of OSE-127 vs placebo on endoscopic improvement | Mean change from baseline in the endoscopic activity measured by the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) | Week 10 | 
| Overall safety and tolerability of OSE-127 in patients with moderate to severe UC | Frequency and severity of reported treatment-emergent adverse events, serious adverse events | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CD127/IL-7Rα Antagonist, ulcerative colitis, inflammatory bowel diseases, Auto-Immune Diseases