Clinical trial NCT04882007: 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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Ulcerative Colitis
Keywords: ulcerative colitis
inflammatory bowel diseases
Auto-Immune Diseases
CD127/IL-7Rα Antagonist
Lead sponsor: OSE Immunotherapeutics
Sponsor class: INDUSTRY
First posted: 2021-05-11
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Change in modified Mayo Score
timeFrame: Baseline and Week 10
Secondary outcomes:
measure: Clinical Remission
timeFrame: Week 10
measure: Clinical efficacy of OSE-127 vs placebo
timeFrame: Week 10
measure: Efficacy of OSE-127 vs placebo on endoscopic remission
timeFrame: Week 10
measure: Efficacy of OSE-127 vs placebo on endoscopic improvement
timeFrame: Week 10
measure: Efficacy of OSE-127 vs placebo on endoscopic improvement
timeFrame: Week 10
measure: Overall safety and tolerability of OSE-127 in patients with moderate to severe UC
timeFrame: 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
Other outcomes:
Locations:
city: Brest
country: Belarus
facility: Brest Regional Hospital
city: Gomel
country: Belarus
facility: Gomel Regional Clinical Hospital
city: Grodno
country: Belarus
facility: Grodno University Hospital
city: Minsk
country: Belarus
facility: City Clinical Emergency Hospital
city: Vitebsk
country: Belarus
facility: Vitebsk Regional Clinical Hospital
city: Leuven
country: Belgium
facility: UZ Leuven - Department of Gastroenterology and Hepatology
city: Liège
country: Belgium
facility: CHU Liège
city: Liège
country: Belgium
facility: Groupe Santé CHC - Clinique du Mont Légia
city: Pleven
country: Bulgaria
facility: Medical Center Medconsult Pleven - OOD
city: Pleven
country: Bulgaria
facility: Medical Center Medconsult Pleven
city: Sofia
country: Bulgaria
facility: Acibadem City Clinic University Multiprofile Hospital for Active Treatment - EOOD, Clinic of Gastroenterology
city: Sofia
country: Bulgaria
facility: Medical Center Asklepion - Researches in humane medicine (EOOD)
city: Sofia
country: Bulgaria
facility: Medical Center Asklepion
city: Sofia
country: Bulgaria
facility: Medical Center Hera EOOD
city: Sofia
country: Bulgaria
facility: Medical Center Hera
city: Sofia
country: Bulgaria
facility: UMHAT Tsaritsa Yoanna - ISUL - EAD
city: Varna
country: Bulgaria
facility: Medical center VIP Clinic - OOD
city: Varna
country: Bulgaria
facility: Medical Center VIP Clinic
city: Split
country: Croatia
facility: University Hospital Center Split
city: Kutaisi
country: Georgia
facility: EVEX Hospitals JSC
city: Kutaisi
country: Georgia
facility: West Regional Center of Modern Medical Technologies Ltd
city: Tbilisi
country: Georgia
facility: Institute of Clinical Cardiology
city: Tbilisi
country: Georgia
facility: Israel-Georgia Medical Research Clinic Helsicore Ltd
city: Tbilisi
country: Georgia
facility: JSC Clinic Jerarsi
city: Tbilisi
country: Georgia
facility: Multiprofile Clinic Consilium Medulla Ltd
city: Budapest
country: Hungary
facility: Clinexpert SMO
city: Budapest
country: Hungary
facility: II. Sz. Belgyogyaszati Klinika, Semmelweis Egyetem
city: Debrecen
country: Hungary
facility: II. Sz Belgyogyasztai Intezet, Gasztroenterologia Debreceni Egyetem
city: Daugavpils
country: Latvia
facility: Polana-D
city: Liepāja
country: Latvia
facility: Liepāja Regional Hospital
city: Riga
country: Latvia
facility: Digestive Diseases Centre GASTRO
city: Riga
country: Latvia
facility: Pauls Stradins Clinical University Hospital
city: Ksawerów
country: Poland
facility: Centrum Opieki Zdrowotnej Orkan-med
city: Oświęcim
country: Poland
facility: Medicome Sp. z o.o.
city: Rzeszów
country: Poland
facility: Centrum Medyczne Medyk
city: Warszawa
country: Poland
facility: WIP Warsaw IBD Point Profesor Kierkus
city: Wrocław
country: Poland
facility: Melita Medical
city: Łódź
country: Poland
facility: Centrum Medyczne Med-Gastr
city: Łódź
country: Poland
facility: Oddział Kliniczny Gastroenterologii Ogólnej i Onkologicznej
city: Ekaterinburg
country: Russian Federation
facility: Ekaterinburg City Clinical Hospital No. 14
city: Krasnodar
country: Russian Federation
facility: Prof. S.V. Ochapovskiy Regional Clinical Hospital No.1
city: Moscow
country: Russian Federation
facility: Ryzhikh State Coloproctology Research Center
city: Novosibirsk
country: Russian Federation
facility: LLC Novosibirskiy Gastrocenter
city: Novosibirsk
country: Russian Federation
facility: Medical Center Healthy Family LLC
city: Pyatigorsk
country: Russian Federation
facility: State Budgetary Healthcare Institution of the Stavropol Region - Pyatigorsk Oncology Dispensary
city: Saratov
country: Russian Federation
facility: Saratov State Medical University
city: Cape Town
country: South Africa
facility: 301 Fairfield Medical Suite
city: Dnipro
country: Ukraine
facility: Dnipropetrovsk I.I. Mechnikov Regional Clinical Hospital - Dnipropetrovsk Regional Council
city: Kharkiv
country: Ukraine
facility: Prof. O.O. Salimov City Clinical Hospital #2 - Kharkiv City Council
city: Kryvyi Rih
country: Ukraine
facility: Kryvyi Rih City Clinical Hospital #2
city: Kyiv
country: Ukraine
facility: Kyiv Regional Clinical Hospital - Kyiv Regional Council
city: Kyiv
country: Ukraine
facility: Medical Center OK!Clinic+ of International Institute of Clinical Studies LLC
city: Ternopil
country: Ukraine
facility: Ternopil University Hospital - Ternopil Regional Council
city: Uzhhorod
country: Ukraine
facility: Andrii Novak Transcarpathian Regional Clinical Hospital
city: Zaporizhzhya
country: Ukraine
facility: Municipal Institution City Clinical Hospital #6 - Therapeutic Department
Study officials:
affiliation: OSE Immunotherapeutics
name: Frederique Corallo, MD
role: STUDY_DIRECTOR
References: