Ulcerative Colitis
Conditions
Keywords
ulcerative colitis, inflammatory bowel diseases, Auto-Immune Diseases, CD127/IL-7Rα Antagonist
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.
Interventions
DRUGOSE-127
mAb antagonist to CD127 receptor (or IL-7Rα)
DRUGPlacebo
Normal saline
Sponsors
OSE Immunotherapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
During the Double-blind phase all participants will be blinded to treatment assignment.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Modified Mayo Score (MMS) at Week 10 | From Baseline to Week 10 | The Mayo Score measures disease activity for UC. The modified questionnaire has 3 domains (instead of the usual 4): 2 with questions answered by the patient (stool frequency and rectal bleeding) and 1 answered by an endoscopist (mucosal appearance at endoscopy). Each domain is graded from 0 to 3, higher values representing a worse outcome. Total score for modified Mayo Score is calculated as the sum of the three sub-scores, and ranges from 0 to 9. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Remission Rate at Week 10 | Week 10 | Clinical remission rate\*: percentage of participants in clinical remission, defined as MMS ≤ 2 points and no individual sub-score of \> 1 point and a rectal bleeding at 0. \*The clinical remission rate is reported with imputation. |
| Endoscopic Remission Rate at Week 10 | Week 10 | Endoscopic remission rate\*: percentage of participants with an endoscopic remission, defined by an endoscopic Mayo sub-score = 0. \*The endoscopic remission rate is reported with imputation. |
Countries
Belarus, Belgium, Bulgaria, Croatia, Georgia, Hungary, Latvia, Poland, Russia, South Africa, Ukraine
Contacts
STUDY_DIRECTORSilvia Comis, MD
OSE Immunotherapeutics
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 123 Participants |
| Age, Continuous | 41.6 years STANDARD_DEVIATION 14.4 |
| Modified Mayo Score (MMS) | 6.4 units on a scale STANDARD_DEVIATION 1.2 |
| Race and Ethnicity Not Collected | 0 Participants |
| Sex: Female, Male Female | 57 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 36 | 1 / 49 | 0 / 120 |
| other Total, other adverse events | 7 / 51 | 9 / 36 | 12 / 49 | 49 / 120 |
| serious Total, serious adverse events | 3 / 51 | 3 / 36 | 3 / 49 | 10 / 120 |
Outcome results
None listed