Ulcerative Colitis Chronic Moderate, Ulcerative Colitis Chronic Severe
Conditions
Keywords
Inflammatory Bowel Disease (IBD)
Brief summary
The purpose of the study is to evaluate the safety, tolerability, and clinical efficacy of PN-943 450 mg twice daily \[BID\] and PN-943 150 mg BID, compared with placebo BID, in subjects with moderate to severe active Ulcerative Colitis (UC).
Detailed description
The study consists of a 12-week double-blind, placebo-controlled treatment period. Participants will be randomized in a 1:1:1 ratio to PN-943 450 mg BID, PN-943 150 mg BID, or matching placebo BID. Participants who successfully complete the double-blind period may be eligible for an extended treatment period of 40 weeks duration.
Interventions
DRUGPN-943
Administered by the oral route BID for the duration of the study.
DRUGPlacebo
Administered by the oral route BID for 12 weeks.
Sponsors
Protagonist Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
12-week randomized, double-blind, placebo-controlled, parallel design study in patients with moderate to severe active UC. It will be followed by 40 weeks of Extended Active Treatment.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Male and female subjects age 18 (or the minimum country specific age of consent if \>18) to 75 years. 2. Subject understands the study procedures and agrees to participate in the study by giving written informed consent. 3. Diagnosis of UC supported by appropriate documentation of biopsy results consistent with UC. 4. Moderate to severe active UC. 5. Demonstrated inadequate response, loss of response, or intolerance of at least 1 of oral aminosalicylates (5-ASAs), corticosteroids, immunomodulators, or a biologic (excluding vedolizumab). Key
Exclusion criteria
1. Subject with a current diagnosis of Crohn's disease (CD), indeterminate colitis (IC), microscopic colitis, ischemic colitis, radiation colitis. 2. History of colonic dysplasia other than completely removed low-grade dysplastic lesion. 3. History of active bacterial, viral, fungal or mycobacterial infection requiring hospitalization or IV antibiotic/anti-infective treatment within 4 weeks of screening or oral antibiotics/anti-infectives within 2 weeks of screening. 4. Prior treatment with vedolizumab, natalizumab, or any agent targeting the α4β7 or β1 integrin or planned during the study. 5. Positive stool test for C. difficile. 6. Chronic recurrent or serious infection. 7. Known primary or secondary immunodeficiency. 8. Pregnant or lactating female or considering becoming pregnant during the study or within 30 days after the last dose of study medication. 9. History of any major neurological disorders.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects achieving clinical remission at Week 12 compared to placebo. | Week 12 | Clinical remission is determined using the Adapted Mayo score (sum of 3 subscores from the Mayo score): * Stool frequency subscore (SFS) * Rectal bleeding subscore (RBS) * Endoscopic subscore (ESS) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison between PN-943 high-dose and low-dose individually to placebo. | Week 12 | 1. Proportion of subjects with endoscopic improvement. 2. Proportion of subjects achieving endoscopic remission. 3. Proportion of subjects with histological improvement. 4. Proportion of subjects achieving histological remission. 5. Proportion of subjects with mucosal healing. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects achieving clinical remission at Week 52. | Week 52 | Clinical remission is determined using the Adapted Mayo score (sum of 3 subscores from the Mayo score): * Stool frequency subscore (SFS) * Rectal bleeding subscore (RBS) * Endoscopic subscore (ESS) |
Countries
Austria, Bulgaria, Canada, Georgia, Germany, Hungary, Italy, Poland, Russia, Serbia, South Korea, Ukraine, United States
Outcome results
None listed