A Phase 2a, Proof of Concept, Open-label Study Evaluating the Efficacy and Safety of Etrasimod (APD334) in Inflammatory Bowel Disease Patients With Active Skin Extra-intestinal Manifestations
Overview
- Phase
- Phase 2
- Intervention
- APD334
- Conditions
- Inflammatory Bowel Diseases
- Sponsor
- Arena Pharmaceuticals
- Enrollment
- 1
- Locations
- 3
- Primary Endpoint
- Exploratory Endpoint - Change From Baseline in Disease Activity Score at Crohn's Disease Endpoint
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
Brief Summary
The purpose of this phase 2a, proof of concept, open-label clinical study is to evaluate the efficacy and safety of etrasimod (APD334) in inflammatory bowel disease patients with active skin extra-intestinal manifestations.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female (18-80 years).
- •Able to provide a signed informed consent prior to any study related procedure being conducted.
- •Considered to be in stable health in the opinion of the investigator as determined by:
- •A pre-study physical examination with no clinically significant abnormalities unrelated to IBD.
- •Vital signs at screening: pulse rate ≥ 55 bpm, systolic blood pressure ≥ 90, and diastolic blood pressure ≥ 55 mmHg.
- •Liver function tests (ALT/AST, bilirubin and alkaline phosphatase) \< 2x the upper limit of normal.
- •All other pre-study clinical laboratory findings within normal range, or if outside of the normal range are not deemed clinically significant in the opinion of the investigator.
- •12-lead electrocardiogram showing no clinically significant abnormalities in the opinion of the investigator (for confirmation please refer to exclusion criterion # 22).
- •A chest x- ray showing no evidence of active pulmonary disease (a chest x-ray taken within the previous 12 months from the screening visit may also be used).
- •Ophthalmology evaluation (by an ophthalmologist) without evidence of macular edema, supported with optical coherence tomography where available (dependent on site capability) no later than 3 months prior to screening.
Exclusion Criteria
- •Evidence of abdominal abscess or toxic megacolon at the screening visit.
- •Patients with history of extensive colitis or pancolitis (duration \> 8 years) or left-sided colitis (duration \> 12 years) must have documented evidence that a surveillance colonoscopy was performed within 12 months of the initial screening visit (if not, the patient should undergo a colonoscopy in lieu of a flexible proctosigmoidoscopy during screening).
- •Previous extensive colonic resection (subtotal or total colectomy).
- •Current evidence of adenomatous colonic polyps that have not been removed.
- •Current evidence of colonic mucosal dysplasia.
- •Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine or stoma.
- •Clinical significant infection as judged by the investigator in the previous 6 weeks before enrollment.
- •Evidence of or treatment for C. difficile infection within 60 days, or other intestinal pathogen within 30 days, prior to randomization.
- •Exposure to natalizumab or rituximab within 5 half-lives prior to randomization.
- •Treatment of underlying disease within 30 days prior to randomization (5-ASA, corticosteroids, TNF-alpha inhibitors, probiotics, antidiarrheals, azathioprine and 6-mercaptopurine may be allowed under certain conditions).
Arms & Interventions
APD334
APD334 active treatment for 12 weeks.
Intervention: APD334
Outcomes
Primary Outcomes
Exploratory Endpoint - Change From Baseline in Disease Activity Score at Crohn's Disease Endpoint
Time Frame: Weeks 1, 2, 4, 8, and 12
Exploratory Endpoint - Change From Baseline in the Dermatology Life Quality Index Score
Time Frame: Weeks 1, 2, 4, 8, and 12
Exploratory Endpoint - Change From Baseline in Inflammatory Bowel Disease Questionnaire Score
Time Frame: Weeks 2, 4, 8, and 12
Exploratory Endpoint - Change From Baseline in Rectal Bleeding at Ulcerative Colitis Endpoint
Time Frame: Weeks 1, 2, 4, 8, and 12
Exploratory Endpoint - Change From Baseline in Physicians Global Assessments at Ulcerative Colitis Endpoint
Time Frame: Weeks 1, 2, 4, 8, and 12
Exploratory Endpoint - Change From Baseline in Psoriasis Area and Severity Index at Psoriasis Endpoint
Time Frame: Weeks 1, 2, 4, 8, and 12
Exploratory Endpoint - Change From Baseline in Endoscopic Improvement/Histologic Healing Using Endoscopy or Flexible Proctosigmoidoscopy
Time Frame: Weeks 12
Only if there are signs of inflammation at screening another evaluation was planned to be performed at week 12.
Exploratory Endpoint - Change From Baseline in Level of Fecal Calprotectin
Time Frame: Weeks 4, 8, and 12
Exploratory Endpoint - Change From Baseline in Physician Global Assessments for Active Skin Extra-intestinal Manifestations (EIM) (PG, EN and Psoriasis)
Time Frame: Weeks 1, 2, 4, 8, and 12
Exploratory Endpoint - Change From Baseline in Patient Global Assessments for Active Skin EIM
Time Frame: Weeks 1, 2, 4, 8, and 12
Exploratory Endpoint - Change From Baseline in C-reactive Protein
Time Frame: Weeks 1, 2, 4, 8, 12 and the 2-week follow-up visit
Exploratory Endpoint - Change From Baseline in Leucocyte Characterization
Time Frame: Weeks 8 and 12
Exploratory Endpoint - Change From Baseline in Stool Frequency at Ulcerative Colitis Endpoint
Time Frame: Weeks 1, 2, 4, 8, and 12
Exploratory Endpoint - Change From Baseline in Lymphocyte Counts
Time Frame: Weeks 1, 2, 4, 8, and 12
Exploratory Endpoint - Changes in Degree of Immune Cell Infiltration as Assessed From Skin Punch Biopsies (From Healthy Skin and From Target Lesion)
Time Frame: Weeks -1, 8, and 12.
Exploratory Endpoint -Changes in Levels of Cytokine Expression as Assessed From Skin Punch Biopsies (From Healthy Skin and From Target Lesion)
Time Frame: Weeks -1, 8 and 12.