A Phase 2a Safety and Efficacy Open-Label Study of PRA023 in Subjects With Moderately to Severely Active Crohn's Disease
- Conditions
- Crohn Disease
- Interventions
- Drug: PRA023 IVDevice: Companion diagnostic (CDx)
- Registration Number
- NCT05013905
- Lead Sponsor
- Prometheus Biosciences, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 55
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description PRA023 Companion diagnostic (CDx) Participants to receive PRA023 administered by intravenous (IV) infusion. PRA023 PRA023 IV Participants to receive PRA023 administered by intravenous (IV) infusion.
- Primary Outcome Measures
Name Time Method Serious Adverse Events Week 12 Number of participants who experienced serious adverse events (SAEs)
Adverse Events Leading to Discontinuation Week 12 Number of participants who experienced AEs leading to discontinuation
Adverse Events Week 12 Number of participants who experienced treatment-emergent adverse events (AEs)
Endoscopic Improvement Week 12 Number of participants achieving induction of endoscopic improvement (decrease in simple endoscopy score for Crohn's disease \[SES-CD\] ≥ 50% from Baseline)
- Secondary Outcome Measures
Name Time Method Endoscopic and Clinical Improvement Week 12 Number of participants who achieved a decrease in SES-CD ≥ 50% AND reduction in CDAI ≥ 100 points from Baseline or CDAI\<150
Clinical Remission Week 12 Number of participants achieving clinical remission, as defined by Crohn's disease activity index \[CDAI\] score \< 150
Normalization of C-reactive Protein Week 12 Number of participants with normalization of hsCRP (as defined by hsCRP \< 5 mg/L), among subjects with elevated concentrations at Baseline, at Week 12
Normalization of Fecal Calprotectin Week 12 Number of participants with normalization of fecal calprotectin (fecal calprotectin \< 250 ug/g), among subjects with elevated concentrations at Baseline, at Week 12
Change From Baseline in Simple Endoscopy Score for Crohn's Disease (SES-CD) Baseline and Week 12 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.
Serum Concentration of PRA023 (MK-7240) Week 12 Blood samples were obtained for PK analysis of the serum concentration of PRA023 at week 12.
Number of Participants Achieving a Composite Response Week 12 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.
Clinical Response Week 12 Clinical response is defined as either a reduction of either CDAI ≥ 100 points from Baseline or CDAI\<150.
Number of Participants With Positive Neutralizing Anti-Bodies (NAB) Up to approximately 12 weeks Blood samples were collected for the determination of NAB. The number of participants with positive NAB results at any visit during the study is presented.
Two Component Patient-reported Outcome (PRO-2) Remission Week 12 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.
Number of Participants Positive for Anti-drug Antibody (ADA) Up to approximately 12 weeks Blood samples were collected for the determination of anti-PR023 antibodies based on confirmatory assay. The number of participants with confirmed positive anti-PR023 antibodies results at any visit during the study is presented.
Trial Locations
- Locations (2)
Prometheus Biosciences Selected Center
🇵🇱Warsaw, Poland
Prometheus Biosciences Selected Site
🇵🇱Wrocław, Poland