A study to evaluate the safety, tolerability, processing by the body and mechanism of action of RO7486967 in participants with ulcerative colitis
- Conditions
- lcerative colitisDigestive System
- Registration Number
- ISRCTN16847938
- Lead Sponsor
- Roche (Switzerland)
- Brief Summary
2023 Results article in https://pubmed.ncbi.nlm.nih.gov/37962000/ (added 16/11/2023)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 19
1. Between the ages of 18 to 75 years (inclusive)
2. Diagnosis of UC at least 12 weeks prior to screening.
3. Participants with active moderate to severe ulcerative colitis as measured by partial >= MCS 3, with stool frequency subscore >=1, rectal bleeding subscore >=1, and fecal calprotectin >=150 mcg/g.
4. Most recent colonoscopy within the preceding 3 years at the time of screening.
5. Body mass index (BMI) within the range of 18-35 kg/m² (inclusive).
1. Diagnosis of fulminant UC, Crohn’s disease or indeterminate colitis, microscopic colitis, segmental colitis associated with diverticulosis, ischemic colitis, or radiation-induced colitis based on medical history, endoscopy, and/or histological findings.
2. Active infections requiring systemic therapy with antibiotic, antiviral, or antifungal medication or febrile illness within 7 days before Day 1.
3. History of primary or acquired immunodeficiency.
4. History of chronic pulmonary disease with resultant clinically significant abnormal pulmonary function.
5. History of clinically significant cardiac or cardiovascular disease or uncontrolled hypertension.
6. Presence of chronic liver disease.
7. Evidence of colonic dysplasia that cannot be completely removed.
8. History of tuberculosis or a positive Quantiferon® Gold test.
9. History of clinically significant severe drug allergies, multiple drug allergies, or allergy to any constituent of the investigational medicinal product (IMP).
10. Lymphoma, leukemia, or any malignancy within the past 10 years, except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years and in situ carcinoma of the cervix that was completely removed surgically.
11. History or presence of clinically significant ECG abnormalities before study drug administration (e.g., PQ/PR interval >=220 ms, QT corrected for heart rate using Fridericia’s correction factor (QTcF),<350 or >=450 ms) or clinically significant cardiovascular disease (e.g., cardiac insufficiency, coronary artery disease, cardiomyopathy, congestive heart failure, family history of congenital long QT interval syndrome, family history of sudden death).
12. Fecal microbiota transplant, defined as receipt of any product derived from the feces of another human and administered per oral, per nasogastric or nasoduodenal, or per rectum within the last 6 months.
13. Bowel surgery within 12 months prior to study start.
14. History of colectomy or partial colectomy.
15. History of known bleeding disorder or diseases with an increased risk of bleeding tendency.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1. Percentage of participants with adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0), measured throughout the study.<br>2. Pharmacokinetic (PK) parameters of RO7486967 using blood samples at predose, 30 min., 1, 2, 4, 6 and 10 h on days 1 and 5; predose on days 2, 3, 4, 6 and 7; early withdrawal and follow up visit.<br>The following PK parameters will be calculated if data allows: <br>Time to maximum observed concentration (Tmax), maximum concentration (Cmax), concentration measured at the end of the dosing interval prior to the next drug administration (Ctrough), area under the concentration-time curve extrapolated to infinity (AUC0-inf) and over the dosing interval (AUCtau), apparent clearance after the first dose administration (CL/F = dose/AUCinf) as well as at steady-state (CLss/F = dose/AUCtau), apparent volume of distribution (V/F), and estimates of T1/2.
- Secondary Outcome Measures
Name Time Method 1. Changes in c-reactive protein (CRP) in blood and calprotectin in stool at check-in, on days 1, 2, 5 and 6 at 6 h, early withdrawal and follow up visit.