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

• Sponsor: Arena Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03139032
• Collaborator: (none)
• Enrollment: 1
• Locations: 3
• Arm: 1
• Actual Duration (Months): 4.7
• Patients Per Site: 0.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Inflammatory Bowel Diseases; Skin Extra-intestinal Manifestations	Drug: APD334	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Proof of concept, open labelProof of concept, open label
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Jul 17, 2017
• Actual Primary Completion Date: Dec 6, 2017
• Actual Study Completion Date: Dec 6, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: APD334 APD334 active treatment for 12 weeks.	Drug: APD334; APD334 active treatment for 12 weeks.; Other Names: Etrasimod

Outcome Measures

Primary Outcome Measures

1. Exploratory Endpoint - Change From Baseline in Endoscopic Improvement/Histologic Healing Using Endoscopy or Flexible Proctosigmoidoscopy [Weeks 12]

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

2. Exploratory Endpoint - Change From Baseline in Level of Fecal Calprotectin [Weeks 4, 8, and 12]

3. 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]

4. Exploratory Endpoint - Change From Baseline in Patient Global Assessments for Active Skin EIM [Weeks 1, 2, 4, 8, and 12]

5. Exploratory Endpoint - Change From Baseline in the Dermatology Life Quality Index Score [Weeks 1, 2, 4, 8, and 12]

6. Exploratory Endpoint - Change From Baseline in Inflammatory Bowel Disease Questionnaire Score [Weeks 2, 4, 8, and 12]

7. Exploratory Endpoint - Change From Baseline in C-reactive Protein [Weeks 1, 2, 4, 8, 12 and the 2-week follow-up visit]

8. Exploratory Endpoint - Change From Baseline in Leucocyte Characterization [Weeks 8 and 12]

9. Exploratory Endpoint - Change From Baseline in Stool Frequency at Ulcerative Colitis Endpoint [Weeks 1, 2, 4, 8, and 12]

10. Exploratory Endpoint - Change From Baseline in Rectal Bleeding at Ulcerative Colitis Endpoint [Weeks 1, 2, 4, 8, and 12]

11. Exploratory Endpoint - Change From Baseline in Physicians Global Assessments at Ulcerative Colitis Endpoint [Weeks 1, 2, 4, 8, and 12]

12. Exploratory Endpoint - Change From Baseline in Lymphocyte Counts [Weeks 1, 2, 4, 8, and 12]

13. Exploratory Endpoint - Change From Baseline in Disease Activity Score at Crohn's Disease Endpoint [Weeks 1, 2, 4, 8, and 12]

14. Exploratory Endpoint - Change From Baseline in Psoriasis Area and Severity Index at Psoriasis Endpoint [Weeks 1, 2, 4, 8, and 12]

15. 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.]

16. 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 Outcome Measures

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]

   Planned safety evaluations included clinical laboratory tests (chemistry, hematology, and urinalysis), vital signs (blood pressure, pulse, respiratory rate, and oral temperature), physical examination (assessment of general appearance, skin, head [eyes, ears, nose and throat], neck, thyroid, lungs, heart, abdomen, back, lymph nodes, and extremities, and body weight), 12-lead electrocardiograms, adverse event reporting, concomitant medication, and lymphocyte counts.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female (18-80 years).

2. Able to provide a signed informed consent prior to any study related procedure being conducted.

3. Considered to be in stable health in the opinion of the investigator as determined by:

4. A pre-study physical examination with no clinically significant abnormalities unrelated to IBD.

5. Vital signs at screening: pulse rate ≥ 55 bpm, systolic blood pressure ≥ 90, and diastolic blood pressure ≥ 55 mmHg.

6. Liver function tests (ALT/AST, bilirubin and alkaline phosphatase) < 2x the upper limit of normal.

7. 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.

8. 12-lead electrocardiogram showing no clinically significant abnormalities in the opinion of the investigator (for confirmation please refer to exclusion criterion

22).

1. 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).

2. 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.

3. Patients receiving stable treatment for IBD and EIM.

4. 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.

5. Diagnosis of ulcerative colitis or Crohn's disease established prior to screening by clinical and endoscopic evidence.

6. 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.

Exclusion Criteria:

1. Evidence of abdominal abscess or toxic megacolon at the screening visit.

2. 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).

3. Previous extensive colonic resection (subtotal or total colectomy).

4. Current evidence of adenomatous colonic polyps that have not been removed.

5. Current evidence of colonic mucosal dysplasia.

6. Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine or stoma.

7. Clinical significant infection as judged by the investigator in the previous 6 weeks before enrollment.

8. Evidence of or treatment for C. difficile infection within 60 days, or other intestinal pathogen within 30 days, prior to randomization.

9. Exposure to natalizumab or rituximab within 5 half-lives prior to randomization.

10. 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).

11. Receipt of any investigational agent within 30 days or 5 half-lives (whichever is longer) prior to randomization.

12. Currently require or are anticipated to require surgical intervention for IBD during the study.

13. Abnormal (< 80% of predicted values) forced expiratory volume (FEV1) or forced vital capacity (FVC).

14. Infection with hepatitis C virus anytime in the past; confirmed active infection with hepatitis B virus at screening.

15. Active or latent tuberculosis (TB), regardless of treatment history, as evidenced by any of the following:

16. History of TB

17. A positive diagnostic TB test within one month of randomization

18. Chest X-ray within 12 months of randomization in which active or latent TB cannot be excluded.

19. Any known history of congenital or acquired immunodeficiency.

20. Clinically significant extra-intestinal infection (e.g., pneumonia, pyelonephritis) within 30 days prior to randomization.

21. Recent history (within 6 months of screening visit) of cardio- or cerebrovascular disease, acute coronary syndrome, myocardial infarction, unstable angina, cerebro-vascular accident, including transient ischemic attack.

22. Any surgical procedure requiring general anesthesia within 30 days prior to randomization or plans to undergo major surgery during the study period.

23. History of retinal macular edema.

24. History of or signs and symptoms of progressive multifocal leukoencephalopathy (PML) as assessed by the PML checklist.

25. History or presence of cardiac arrhythmia, conduction system disease, or use of Class Ia or Class III anti arrhythmic agents, or baseline QTc ≥ 500 msec.

26. Infection requiring hospitalization or intravenous antimicrobial therapy, or opportunistic infection within 4 weeks of screening.

27. History of more than one episode of herpes zoster or any episode of disseminated zoster.

28. Without documented positive varicella zoster virus (VZV) IgG antibody status or who have completed VZV vaccination within 30 days prior to randomization.

29. Receipt of live vaccine within 4 weeks prior to screening.

30. History of lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorder, or multiple myeloma.

31. History of malignancy except for adequately treated basal cell skin cancer.

32. History of severe allergic or anaphylactic reactions requiring medical attention.

33. Current or recent history (within one year prior to randomization) of alcohol dependence or illicit drug use.

34. History of clinically significant leukopenia or lymphopenia at screening.

35. Active psychiatric problems that, in the investigator's opinion, may interfere with compliance with the study procedures.

36. History of any clinically significant medical condition that, in the investigator's opinion, would preclude participation in the study.

37. Use of moderate to strong inhibitors of CYP2C9.

38. History of severe renal or hepatic impairment.

39. Inability to attend all the study visits or comply with study procedures.

40. Prior exposure to etrasimod (APD334).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arena 2001	Leuven		Belgium
2	Arena 1001	Hamburg		Germany
3	Arena 3001	Belgrade		Serbia

Sponsors and Collaborators

• Arena Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 11, 2017

More Information

Publications

None provided.

• Responsible Party: Arena Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03139032
• Other Study ID Numbers: APD334-006
• First Posted: May 3, 2017
• Last Update Posted: Dec 31, 2020
• Last Verified: Dec 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Intestinal Diseases; Inflammatory Bowel Diseases

Study Results

Participant Flow

Arm/Group Title	Etrasimod
Arm/Group Description	Participants received active treatment for 12 weeks.
Period Title: Overall Study
STARTED	1
COMPLETED	1
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Etrasimod
Arm/Group Description	Participants received active treatment for 12 weeks.
Overall Participants	1
Age, Customized (Count of Participants)
Between 18 to 80 years	1 100%
Sex: Female, Male (Count of Participants)
Female	NA NaN
Male	NA NaN
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	NA NaN
Not Hispanic or Latino	NA NaN
Unknown or Not Reported	NA NaN
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	NA NaN
Asian	NA NaN
Native Hawaiian or Other Pacific Islander	NA NaN
Black or African American	NA NaN
White	NA NaN
More than one race	NA NaN
Unknown or Not Reported	NA NaN

Outcome Measures

1. Primary Outcome

Title	Exploratory Endpoint - Change From Baseline in Endoscopic Improvement/Histologic Healing Using Endoscopy or Flexible Proctosigmoidoscopy
Description	Only if there are signs of inflammation at screening another evaluation was planned to be performed at week 12.
Time Frame	Weeks 12

Outcome Measure Data

Analysis Population Description

Efficacy analyses were not conducted due to low enrollment (N=1). In order to protect participant's privacy, the results from a single participant cannot be reported.

Arm/Group Title	Etrasimod
Arm/Group Description	Participants received active treatment for 12 weeks.
Measure Participants	0

2. Primary Outcome

Title	Exploratory Endpoint - Change From Baseline in Level of Fecal Calprotectin
Time Frame	Weeks 4, 8, and 12

Outcome Measure Data

Analysis Population Description

Efficacy analyses were not conducted due to low enrollment (N=1). In order to protect participant's privacy, the results from a single participant cannot be reported.

Arm/Group Title	Etrasimod
Arm/Group Description	Participants received active treatment for 12 weeks.
Measure Participants	0

3. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Efficacy analyses were not conducted due to low enrollment (N=1). In order to protect participant's privacy, the results from a single participant cannot be reported.

Arm/Group Title	Etrasimod
Arm/Group Description	Participants received active treatment for 12 weeks.
Measure Participants	0

4. Primary Outcome

Title	Exploratory Endpoint - Change From Baseline in Patient Global Assessments for Active Skin EIM
Time Frame	Weeks 1, 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

Efficacy analyses were not conducted due to low enrollment (N=1). In order to protect participant's privacy, the results from a single participant cannot be reported.

Arm/Group Title	Etrasimod
Arm/Group Description	Participants received active treatment for 12 weeks.
Measure Participants	0

5. Primary Outcome

Title	Exploratory Endpoint - Change From Baseline in the Dermatology Life Quality Index Score
Time Frame	Weeks 1, 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

Efficacy analyses were not conducted due to low enrollment (N=1). In order to protect participant's privacy, the results from a single participant cannot be reported.

Arm/Group Title	Etrasimod
Arm/Group Description	Participants received active treatment for 12 weeks.
Measure Participants	0

6. Primary Outcome

Title	Exploratory Endpoint - Change From Baseline in Inflammatory Bowel Disease Questionnaire Score
Time Frame	Weeks 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

Efficacy analyses were not conducted due to low enrollment (N=1). In order to protect participant's privacy, the results from a single participant cannot be reported.

Arm/Group Title	Etrasimod
Arm/Group Description	Participants received active treatment for 12 weeks.
Measure Participants	0

7. Primary Outcome

Title	Exploratory Endpoint - Change From Baseline in C-reactive Protein
Time Frame	Weeks 1, 2, 4, 8, 12 and the 2-week follow-up visit

Outcome Measure Data

Analysis Population Description

Efficacy analyses were not conducted due to low enrollment (N=1). In order to protect participant's privacy, the results from a single participant cannot be reported.

Arm/Group Title	Etrasimod
Arm/Group Description	Participants received active treatment for 12 weeks.
Measure Participants	0

8. Primary Outcome

Title	Exploratory Endpoint - Change From Baseline in Leucocyte Characterization
Time Frame	Weeks 8 and 12

Outcome Measure Data

Analysis Population Description

Efficacy analyses were not conducted due to low enrollment (N=1). In order to protect participant's privacy, the results from a single participant cannot be reported.

Arm/Group Title	Etrasimod
Arm/Group Description	Participants received active treatment for 12 weeks.
Measure Participants	0

9. Primary Outcome

Title	Exploratory Endpoint - Change From Baseline in Stool Frequency at Ulcerative Colitis Endpoint
Time Frame	Weeks 1, 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

Efficacy analyses were not conducted due to low enrollment (N=1). In order to protect participant's privacy, the results from a single participant cannot be reported.

Arm/Group Title	Etrasimod
Arm/Group Description	Participants received active treatment for 12 weeks.
Measure Participants	0

10. Primary Outcome

Title	Exploratory Endpoint - Change From Baseline in Rectal Bleeding at Ulcerative Colitis Endpoint
Time Frame	Weeks 1, 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

Efficacy analyses were not conducted due to low enrollment (N=1). In order to protect participant's privacy, the results from a single participant cannot be reported.

Arm/Group Title	Etrasimod
Arm/Group Description	Participants received active treatment for 12 weeks.
Measure Participants	0

11. Primary Outcome

Title	Exploratory Endpoint - Change From Baseline in Physicians Global Assessments at Ulcerative Colitis Endpoint
Time Frame	Weeks 1, 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

Efficacy analyses were not conducted due to low enrollment (N=1). In order to protect participant's privacy, the results from a single participant cannot be reported.

Arm/Group Title	Etrasimod
Arm/Group Description	Participants received active treatment for 12 weeks.
Measure Participants	0

12. Primary Outcome

Title	Exploratory Endpoint - Change From Baseline in Lymphocyte Counts
Time Frame	Weeks 1, 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

Efficacy analyses were not conducted due to low enrollment (N=1). In order to protect participant's privacy, the results from a single participant cannot be reported.

Arm/Group Title	Etrasimod
Arm/Group Description	Participants received one active treatment for 12 weeks.
Measure Participants	0

13. Primary Outcome

Title	Exploratory Endpoint - Change From Baseline in Disease Activity Score at Crohn's Disease Endpoint
Time Frame	Weeks 1, 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

Efficacy analyses were not conducted due to low enrollment (N=1). In order to protect participant's privacy, the results from a single participant cannot be reported.

Arm/Group Title	Etrasimod
Arm/Group Description	Participants received active treatment for 12 weeks.
Measure Participants	0

14. Primary Outcome

Title	Exploratory Endpoint - Change From Baseline in Psoriasis Area and Severity Index at Psoriasis Endpoint
Time Frame	Weeks 1, 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

Efficacy analyses were not conducted due to low enrollment (N=1). In order to protect participant's privacy, the results from a single participant cannot be reported.

Arm/Group Title	Etrasimod
Arm/Group Description	Participants received active treatment for 12 weeks.
Measure Participants	0

15. Primary Outcome

Title	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.

Outcome Measure Data

Analysis Population Description

Efficacy analyses were not conducted due to low enrollment (N=1). To protect participant's privacy, the results from a single participant cannot be reported.

Arm/Group Title	Etrasimod
Arm/Group Description	Participants received active treatment for 12 weeks.
Measure Participants	0

16. Primary Outcome

Title	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.

Outcome Measure Data

Analysis Population Description

Efficacy analyses were not conducted due to low enrollment (N=1). In order to protect participant's privacy, the results from a single participant cannot be reported.

Arm/Group Title	Etrasimod
Arm/Group Description	Participants received active treatment for 12 weeks.
Measure Participants	0

17. Other Pre-specified Outcome

Title	Safety Measured by Number of Participants With Adverse Events and Serious Adverse Events
Description	Planned safety evaluations included clinical laboratory tests (chemistry, hematology, and urinalysis), vital signs (blood pressure, pulse, respiratory rate, and oral temperature), physical examination (assessment of general appearance, skin, head [eyes, ears, nose and throat], neck, thyroid, lungs, heart, abdomen, back, lymph nodes, and extremities, and body weight), 12-lead electrocardiograms, adverse event reporting, concomitant medication, and lymphocyte counts.
Time Frame	From date of first dose of study treatment to the safety follow-up visit, approximately 14 weeks

Outcome Measure Data

Analysis Population Description

There were no analysis populations in the single participant study. Safety results for the single participant are reported.

Arm/Group Title	Etrasimod
Arm/Group Description	Participants received active treatment for 12 weeks.
Measure Participants	1
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	From first dose of study treatment until the follow-up safety visit, approximately 14 weeks.
Arm/Group Title	Etrasimod
Arm/Group Description	Participants received active treatment for 12 weeks.
All Cause Mortality
	Etrasimod
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Serious Adverse Events
	Etrasimod
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	Etrasimod
	Affected / at Risk (%)	# Events
Total	0/1 (0%)

Limitations/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.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.