A Phase 2 Safety and Efficacy Study of PRA023 in Subjects With Moderately to Severely Active Ulcerative Colitis

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and efficacy of PRA023 in participants with moderately to severely active Ulcerative Colitis. The purpose of Cohort 2 of the study is to assess the safety and efficacy of PRA023 in participants with moderately to severely active ulcerative colitis who are companion diagnostic positive. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for another 38 weeks.

Official Title
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A Phase 2, Multi-Center, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Induction Therapy With PRA023 in Subjects With Moderately to Severely Active Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: PRA023 IV
* Device: Companion Diagnostic (CDx) Testing
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of ulcerative colitis (UC) Moderately to severely active UC as defined by 3-component Modified Mayo score Must have corticosteroid dependence or have had no response, insufficient response, loss of response, and/or intolerance to at least one of the following therapies: corticosteroid, immunosuppressants, or an approved anti-TNF, anti-integrin, anti-IL12/23, JAK inhibitor, S1PR modulator. Able to provide written informed consent and understand and comply with the requirements of the study. Exclusion Criteria: WOCBP and men with female partners of childbearing potential who are unwilling or unable to use two highly effective methods of contraception to avoid pregnancy for the entire study period and for up to 12 weeks after the last dose of study drug Diagnosis of Crohn's disease or indeterminate colitis Current evidence of fulminant colitis, toxic megacolon, bowel perforation, total proctocoloectomy or partial colectomy Current or impending need for colostomy or ileostomy Surgical bowel resection within 3 months before screening Past or current evidence of definite low-grade or high-grade colonic dysplasia not completely removed Subjects in the opinion of the investigator are at an unacceptable risk for participation in the study Subjects who meet the protocol criteria for important laboratory exclusion criteria

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 PRA023<br>Participants randomized to receive PRA023 administered by intravenous (IV) infusion. | Drug: PRA023 IV<br>* PRA023 administered by IV infusion<br>|
| Placebo Comparator: Cohort 1 Placebo<br>Participant randomized to receive placebo administered by intravenous (IV) infusion. | Other: Placebo<br>* Placebo administered by IV infusion<br>|
| Experimental: CDx+ Expansion Cohort PRA023<br>Participants randomized to receive PRA023 administered by intravenous (IV) infusion. | Drug: PRA023 IV<br>* PRA023 administered by IV infusion<br>Device: Companion Diagnostic (CDx) Testing<br>* PRA023 CDx Genotyping Assay<br>|
| Placebo Comparator: CDx+ Expansion Cohort Placebo<br>Participant randomized to receive placebo administered by intravenous (IV) infusion. | Device: Companion Diagnostic (CDx) Testing<br>* PRA023 CDx Genotyping Assay<br>Other: Placebo<br>* Placebo administered by IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Induction of clinical remission | Proportion of participants achieving induction of clinical remission | Week 12 | 
| Safety and tolerability | Incidence of AE, SAE, AE leading to discontinuation | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Induction of endoscopic improvement | Proportion of participants achieving induction of endoscopic improvement | Week 12 | 
| Induction of clinical response | Proportion of participants achieving induction of clinical response | Week 12 | 
| Induction of clinical remission in CDx+ participants | Proportion of CDx+ participants achieving induction of clinical remission | Week 12 | 
| Induction of histologic remission | Proportion of participants achieving induction of histologic remission | Week 12 | 
| Induction of histologic-endoscopic mucosal improvement | Proportion of participants achieving induction of histologic- endoscopic mucosal improvement | Week 12 | 
| Induction of endoscopic improvement in CDx+ participants | Proportion of CDx+ participants achieving induction of endoscopic improvement | Week 12 | 
| Induction of clinical response in CDx+ participants | Proportion of CDx+ participants achieving induction of clinical response | Week 12 | 
| Induction of histologic remission in CDx+ participants | Proportion of CDx+ participants achieving induction of histologic remission | Week 12 | 
| Induction of histologic-endoscopic mucosal improvement in CDx+ participants | Proportion of CDx+ participants achieving induction of histologic-endoscopic mucosal | Week 12 | 
| Clinical remission in CDx+ vs. CDx- participants | Proportion of of CDx+ vs. CDx- participants achieving clinical remission | Week 12 | 
| Induction of mucosal healing | Proportion of participants achieving induction of mucosal healing | Week 12 | 
| Induction of mucosal healing in CDx+ participants | Proportion of CDx+ participants achieving induction of mucosal healing | Week 12 | 
| Change in IBDQ | Change from Baseline in IBDQ through Week 12 | Week 12 | 
| Change in IBDQ in CDx+ participants | Change from Baseline in IBDQ through Week 12 in CDx+ participants | Week 12 | 
| Induction of Clinical remission in CDx+ participants per alternative algorithm | Proportion of CDx+ participants per alternative algorithm achieving induction of Clinical remission. | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ARTEMIS-UC, ARTEMIS, Ulcerative Colitis