A Phase 2a Safety and Efficacy Open-Label Study of PRA023 in Subjects With Moderately to Severely Active Crohn's Disease

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the safety and efficacy of PRA023 in participants with moderately to severely active Crohn's Disease. After the completion of the 12-week induction period, all participants have the option to continue in the open-label extension for another 38 weeks.

Official Title
-----------------
A Phase 2a, Multi-Center, Open-Label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of PRA023 in Subjects With Moderately to Severely Active Crohn's Disease

Conditions
-----------------
Crohn Disease

Intervention / Treatment
-----------------
* Drug: PRA023 IV
* Device: Companion diagnostic (CDx)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Confirmed diagnosis of Crohn's disease Moderately to severely active CD as defined by Crohn's disease activity index (CDAI) score and centrally read endoscopy 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-tumor necrosis factor (TNF), anti-integrin, or anti-interleukin (IL)12/23 Able to provide written informed consent and understand and comply with the requirements of the study Exclusion Criteria: Women of child bearing potential (WOCBP) and men with female partner of childbearing potential who are unwilling to use two highly effective methods of contraception to avoid pregnancy for the entire study period and up to 12 weeks after the last dose of study drug Diagnosis of ulcerative colitis (UC) or indeterminate colitis CD isolated to the stomach, duodenum, jejunum, or perianal region, without colonic and/or illeal involvement Suspected or diagnosed intra-abdominal or perianal abscess at screening Current stoma or need for colostomy or ileostomy Previous small bowel resection with a combined resected length of >100 cm or previous colonic resection of > 2 segments 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
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRA023<br>Participants to receive PRA023 administered by intravenous (IV) infusion. | Drug: PRA023 IV<br>* PRA023 administered at timepoints as directed by the protocol<br>* Other names: PRA023 administered by IV Infusion;Device: Companion diagnostic (CDx)<br>* CDx+ or CDx-<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Number of participants who experienced treatment-emergent adverse events (AEs) | Week 12 | 
| Serious Adverse Events | Number of participants who experienced serious adverse events (SAEs) | Week 12 | 
| Adverse Events Leading to Discontinuation | Number of participants who experienced AEs leading to discontinuation | Week 12 | 
| Endoscopic Improvement | Number of participants achieving induction of endoscopic improvement (decrease in simple endoscopy score for Crohn's disease [SES-CD] ≥ 50% from Baseline) | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Remission | Number of participants achieving clinical remission, as defined by Crohn's disease activity index [CDAI] score < 150 | Week 12 | 
| Endoscopic and Clinical Improvement | Number of participants who achieved a decrease in SES-CD ≥ 50% AND reduction in CDAI ≥ 100 points from Baseline or CDAI<150 | Week 12 | 
| Number of Participants Achieving a Composite Response | Composite response is defined as a decrease by at least 50% in hsCRP or fecal calprotectin from baseline and a reduction of either CDAI ≥ 100 points from Baseline or CDAI<150 in subjects with at least one elevated biomarker at baseline. | Week 12 | 
| Normalization of C-reactive Protein | Number of participants with normalization of hsCRP (as defined by hsCRP < 5 mg/L), among subjects with elevated concentrations at Baseline, at Week 12 | Week 12 | 
| Normalization of Fecal Calprotectin | Number of participants with normalization of fecal calprotectin (fecal calprotectin < 250 ug/g), among subjects with elevated concentrations at Baseline, at Week 12 | Week 12 | 
| Clinical Response | Clinical response is defined as either a reduction of either CDAI ≥ 100 points from Baseline or CDAI<150. | Week 12 | 
| Two Component Patient-reported Outcome (PRO-2) Remission | Number of subjects with PRO-2 remission (defined as average daily abdominal pain score ≤ 1 point and average daily stool frequency ≤ 3 points with abdominal pain and stool frequency no worse than Baseline) at Week 12. | Week 12 | 
| Change From Baseline in Simple Endoscopy Score for Crohn's Disease (SES-CD) | Assessment of change in simple endoscopy score for Crohn's Disease (SES-CD) from Baseline. Measure Description: The SES-CD evaluates 4 endoscopic variables (ulcer size, ulcerated surface, affected surface, and narrowing, each on a scale from 0 (none) to 3 in 5 segments assessed during ileocolonoscopy (ileum, right colon, transverse colon, sigmoid and left colon, and rectum). The total score is the sum of the 4 endoscopic variable scores and ranges from 0 to 56, where higher scores indicate more severe disease. | Baseline and Week 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
APOLLO-CD, APOLLO, Crohn's Disease