Efficacy and Safety of Etrasimod (APD334) in Inflammatory Bowel Disease Patients With Active Skin Extra-intestinal Manifestations

NCT03139032 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: APD334-006
• Study Type: interventional
• Target: 1
• Locations: 3 countries
• Sites: 3

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.

Conditions

Inflammatory Bowel Diseases; Skin Extra-intestinal Manifestations

Outcome Measures

Primary Outcomes (16)

• Exploratory Endpoint - Change From Baseline in Endoscopic Improvement/Histologic Healing Using Endoscopy or Flexible Proctosigmoidoscopy

  Only if there are signs of inflammation at screening another evaluation was planned to be performed at week 12.

  Weeks 12

• Exploratory Endpoint - Change From Baseline in Level of Fecal Calprotectin

  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)

  Weeks 1, 2, 4, 8, and 12

• Exploratory Endpoint - Change From Baseline in Patient Global Assessments for Active Skin EIM

  Weeks 1, 2, 4, 8, and 12

• Exploratory Endpoint - Change From Baseline in the Dermatology Life Quality Index Score

  Weeks 1, 2, 4, 8, and 12

• Exploratory Endpoint - Change From Baseline in Inflammatory Bowel Disease Questionnaire Score

  Weeks 2, 4, 8, and 12

• Exploratory Endpoint - Change From Baseline in C-reactive Protein

  Weeks 1, 2, 4, 8, 12 and the 2-week follow-up visit

• Exploratory Endpoint - Change From Baseline in Leucocyte Characterization

  Weeks 8 and 12

• Exploratory Endpoint - Change From Baseline in Stool Frequency at Ulcerative Colitis Endpoint

  Weeks 1, 2, 4, 8, and 12

• Exploratory Endpoint - Change From Baseline in Rectal Bleeding at Ulcerative Colitis Endpoint

  Weeks 1, 2, 4, 8, and 12

• Exploratory Endpoint - Change From Baseline in Physicians Global Assessments at Ulcerative Colitis Endpoint

  Weeks 1, 2, 4, 8, and 12

• Exploratory Endpoint - Change From Baseline in Lymphocyte Counts

  Weeks 1, 2, 4, 8, and 12

• Exploratory Endpoint - Change From Baseline in Disease Activity Score at Crohn's Disease Endpoint

  Weeks 1, 2, 4, 8, and 12

• Exploratory Endpoint - Change From Baseline in Psoriasis Area and Severity Index at Psoriasis Endpoint

  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)

  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)

  Weeks -1, 8 and 12.

Other Outcomes (1)

• Safety Measured by Number of Participants With Adverse Events and Serious Adverse Events

  From date of first dose of study treatment to the safety follow-up visit, approximately 14 weeks

Study Arms (1)

APD334

EXPERIMENTAL

APD334 active treatment for 12 weeks.

Drug: APD334

Interventions

APD334 DRUG

APD334 active treatment for 12 weeks.

Also known as: Etrasimod

APD334

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• Patients receiving stable treatment for IBD and EIM.
• Diagnosis of active psoriasis, erythema nodosum or pyoderma gangrenosum by Investigator assessments. After the enrollment of 10 patients with active EIM, patients with active psoriasis due to anti TNF-alpha therapy can also be included.
• Diagnosis of ulcerative colitis or Crohn's disease established prior to screening by clinical and endoscopic evidence.
• Eligible male and female patients must agree not to participate in a conception process (i.e. active attempt to let female partner to become pregnant or to impregnate, sperm donation, oocyte donation, in vitro fertilization) for at least 30 days after the last dose of study drug.
• Non-sterile patients who are sexually active must take adequate contraception measures.

You may not qualify if:

• 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).
• Receipt of any investigational agent within 30 days or 5 half-lives (whichever is longer) prior to randomization.
• Currently require or are anticipated to require surgical intervention for IBD during the study.
• Abnormal (\< 80% of predicted values) forced expiratory volume (FEV1) or forced vital capacity (FVC).
• Infection with hepatitis C virus anytime in the past; confirmed active infection with hepatitis B virus at screening.
• Active or latent tuberculosis (TB), regardless of treatment history, as evidenced by any of the following:

Sponsors & Collaborators

• Arena Pharmaceuticals: lead

Study Sites (3)

Arena 2001

Leuven, Belgium

Location

Arena 1001

Hamburg, Germany

Location

Arena 3001

Belgrade, Serbia

Location

MeSH Terms

Conditions

Inflammatory Bowel Diseases

Interventions

etrasimod

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Limitations and Caveats

Due to limited enrollment (N=1), this clinical trial was terminated by the Sponsor and no efficacy analyses were conducted. To protect the single participant's privacy, demography and efficacy data are not reported.

Results Point of Contact

• Title: Head of Document Operations
• Organization: Arena Pharmaceuticals, Inc.

ct.gov@arenapharm.com

858-453-7200

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Proof of concept, open label

Study Record Dates

• First Submitted: April 26, 2017
• First Posted: May 3, 2017
• Study Start: July 17, 2017
• Primary Completion: December 6, 2017
• Study Completion: December 6, 2017
• Last Updated: December 31, 2020
• Results First Posted: December 31, 2020

Record last verified: 2020-12

Locations

BE (1); DE (1); SE (1)