A Phase 2a, Open-label, Proof of Concept Study to Determine the Efficacy and Safety of Etrasimod (APD334) in Patients With Pyoderma Gangrenosum
Overview
- Phase
- Phase 2
- Intervention
- APD334
- Conditions
- Pyoderma Gangrenosum
- Sponsor
- Arena Pharmaceuticals
- Enrollment
- 2
- Locations
- 6
- Primary Endpoint
- Exploratory Endpoint - Change From Baseline in Dermatology Life Quality Index (DLQI) Score
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
Brief Summary
The purpose of this Phase 2a, open label, proof-of-concept clinical study is to assess the efficacy and safety of etrasimod (APD334) in patients with Pyoderma Gangrenosum.
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.
- •Diagnosis of PG with active, non-healing ulcer.
- •Considered to be in stable health in the opinion of the investigator as determined by:
- •A screening physical examination with no clinically significant abnormalities unrelated to PG.
- •Vital signs at screening: pulse rate ≥ 55 bpm, systolic blood pressure ≥ 90 mmHg, and diastolic blood pressure ≥ 55 mmHg.
- •Liver function tests (alanine aminotransferase/aspartate aminotransferase, 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 with exemption to leucopenia and lymphopenia - please refer to exclusion criterion
- •No clinical abnormalities noted in the12-lead electrocardiogram in the opinion of the investigator (Refer also to exclusion criterion 13).
- •No evidence of macular edema in an ophthalmology evaluation (performed by an ophthalmologist), supported with optical coherence tomography, where available (dependent on site capability) at screening.
Exclusion Criteria
- •Clinically significant infection as judged by the investigator with an end date less than 6-weeks prior to treatment start (Day 1). In case of infection requiring hospitalization or intravenous antimicrobial therapy, or opportunistic infection, this infection must have ended at least 8 weeks prior to Day
- •Infection with hepatitis C virus anytime in the past; confirmed active infection with hepatitis B virus at screening.
- •History of severe renal or severe hepatic impairment.
- •Current active or latent tuberculosis (TB).
- •A positive diagnostic TB test at screening.
- •Exposure to B-cell or T-cell targeted therapies (such as natalizumab, rituximab, abatacept) within 5 half-lives prior to Day
- •Exposure to other immunosuppressive, immunomodulating or antineoplastic agents.
- •Receipt of any investigational agent within 30 days or 5 half lives (whichever is longer), prior to Day
- •Use of moderate to strong inhibitors of CYP2C
- •Abnormal forced expiratory volume (FEV1) or forced vital capacity (FVC).
Arms & Interventions
APD334
APD334 active treatment for 12 weeks.
Intervention: APD334
Outcomes
Primary Outcomes
Exploratory Endpoint - Change From Baseline in Dermatology Life Quality Index (DLQI) Score
Time Frame: Week 12
The DLQI questionnaire assessed how much a participant's life is affected through their skin problem in the last week, and includes the following parameters: symptoms and feelings, daily activities, leisure and sport activities, work or school activities, personal relationships and treatment- related feelings. Participants responded to the 10 questions on a scale from 0 (not at all) to 3 (very much) with a total score ranging from 0 to 30. Higher scores indicated that the skin problem had an extremely large effect on the participant's life whereas lower scores indicated that the disease has minimal to no effect at all.
Exploratory Endpoint - Change From Baseline in C-reactive Protein Levels
Time Frame: Week 12
Exploratory Endpoint - Assessments of Target Lesions
Time Frame: Week 12
Changes in surface area
Exploratory Endpoint - Assessment of Punch Biopsies
Time Frame: Week 12
Changes in histology.
Exploratory Endpoint - Change From Baseline in Physician Global Assessments for Active Skin Manifestations
Time Frame: Week 12
The physician's global assessment for active skin manifestations recorded the number of ulcers, target lesion noted for endpoint evaluation, diameters of each target lesion and score of evaluation at each visit. The scores ranged from 0 (total resolution) to 4 (no evidence of healing).
Exploratory Endpoint - Change From Baseline in Patient Global Assessments for Active Skin Manifestations
Time Frame: Week 12
The patient global assessment for active skin manifestation recorded the disease and pain severity using a visual analogue to mark the participant's score. Participants were asked to rate their disease severity from "not severe" to "extremely severe" and pain levels from "no pain at all' to "worst pain imaginable" in the past one week.