A trial to investigate the safety and efficacy of PN-943 in patients withmoderate or severe Ulcerative Colitis (a long-term condition where thecolon and rectum become inflamed)
- Conditions
- lcerative colitis (US) is a chronic relapsing inflammatory bowel disease of the large intestine characterized by bloody diarrhoea, abdominal cramps and fatigue. UC is characterized by inflammation and ulceration of mainly the mucosal and occasionally submucosal intestinal layers.MedDRA version: 20.1Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 100000004856Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2019-004469-41-IT
- Lead Sponsor
- Protagonist Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 150
Part 1 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 for = 8 weeks prior to screening supported by appropriate documentation of biopsy results consistent with UC, in the opinion of the investigator; if UC has been present for > 10 years, a total colonoscopy with biopsy must have been performed within 2 years of screening to rule out dysplasia. Subjects must be up-to-date on colorectal cancer surveillance per local standards and guidelines. The colorectal cancer screening may be performed during screening colonoscopy.
4. Moderate to severe active UC with an Adapted Mayo Score of 5 to 9, rectal bleeding subscore (RBS) =1, stool frequency subscore (SFS) =1, and endoscopic subscore (ESS) =2 at baseline (pre-randomization) as determined by blinded central read. ESS of =2 must be observed at =15 cm from the anal verge.
5. Demonstrated inadequate response, loss of response, or intolerance of at least 1 of the following treatments including oral corticosteroids, immunomodulators, IL-12/23 antagonists, and/or TNFa antagonists as defined in the protocol at inclusion criterias section
6. A female participant must be:
a) Not of childbearing potential OR
b) Of childbearing potential and practicing a highly effective method of contraception (failure rate of <1% when used consistently and correctly) and agrees to remain on a highly effective method while receiving study medication and until 30 days after receiving the last dose of study medication. (Appendix 6).
7. A female participant must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 30 days after receiving the last dose of study medication.
8. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and a negative urine pregnancy test at Day 1 prior to the first dose of study medication.
9. Men with partners of child bearing potential must agree to use a highly effective method of contraception (failure rate of <1% when used consistently and correctly) and agree to remain on a highly effective method while receiving study medication and until 90 days after receiving last dose of study medication (Appendix 6).
10. A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 90 days after receiving the last dose.
11. Subject is eligible according to the tuberculosis (TB) screening criteria as stated in the protocol (Appendix 3).
For Inclusion criteria of Part 2, please refer to Study protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 135
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15
For exclusion criteria related to Part 1 and 2 of study protocol please refer to the study protocol, as the text space in the Appendix is not sufficient.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Evaluate safety, tolerability and efficacy of PN-943 treatment in subjects with moderate to severe active ulcerative colitis compared to placebo.;Secondary Objective: Evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and biomarker responses to PN-943 in subjects with moderate to severe active ulcerative colitis.;Primary end point(s): Efficacy<br>Proportion of subjects achieving clinical remission at Week 12 compared to placebo.;Timepoint(s) of evaluation of this end point: 12 weeks
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Comparison of PN-943 high dose and low dose individually to placebo:<br>a) Proportion of subjects with endoscopic improvement at Week 12<br>b) Proportion of subjects achieving endoscopic remission at Week 12<br>c) Proportion of subjects with histological improvement at Week 12<br>d) Proportion of subjects achieving histological remission at Week 12 <br><br>• Proportion of subjects achieving clinical remission at Week 52. Clinical remission is determined using the Adapted Mayo score (sum of 3 subscores from the Mayo score):<br> - Stool frequency subscore (SFS)<br> - Rectal bleeding subscore (RBS)<br> - Endoscopic subscore (ESS);Timepoint(s) of evaluation of this end point: Weeks 12 and 52