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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03072953




Registration number
NCT03072953
Ethics application status
Date submitted
17/02/2017
Date registered
8/03/2017
Date last updated
31/05/2019

Titles & IDs
Public title
Efficacy and Safety of APD334 in Patients With Pyoderma Gangrenosum
Scientific title
A Phase 2a, Open-label, Proof of Concept Study to Determine the Efficacy and Safety of Etrasimod (APD334) in Patients With Pyoderma Gangrenosum
Secondary ID [1] 0 0
APD334-011
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pyoderma Gangrenosum 0 0
Condition category
Condition code
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - APD334

Other: APD334 - APD334 active treatment for 12 weeks.


Treatment: Drugs: APD334
APD334 active treatment

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Exploratory endpoint - Change from baseline in: Physician Global Assessments for active skin manifestations. - Assessment of target lesion/ulceration:
(score 0) Total resolution of target ulcer with no signs of active PG
(score 1) Almost completely healed target ulcer with only minimal signs of active PG
(score 2) Evidence of target ulcer healing which involves at least 50% of ulcer/ulcer margin
(score 3) Evidence of target ulcer healing which involves less than 50% of ulcer/ulcer margin
(score 4) No evidence of target ulcer healing
Timepoint [1] 0 0
Week 12
Primary outcome [2] 0 0
Exploratory endpoint - Change from baseline in Patient Global Assessments for active skin manifestations: visual analog scale for assessment of severity of the disease and severity of pain by patient.
Timepoint [2] 0 0
Week 12
Primary outcome [3] 0 0
Exploratory endpoint - Change from baseline in Dermatology Life Quality Index (to measure how much a patient's life is affected through their skin problems).
Timepoint [3] 0 0
Week 12
Primary outcome [4] 0 0
Exploratory endpoint - Change from baseline in C-reactive protein levels.
Timepoint [4] 0 0
Week 12
Primary outcome [5] 0 0
Exploratory endpoint - Assessments of target lesions. - Changes in surface area
Timepoint [5] 0 0
Week 12
Primary outcome [6] 0 0
Exploratory endpoint - Assessment of punch biopsies. - Changes in histology.
Timepoint [6] 0 0
Week 12

Eligibility
Key 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. Diagnosis of PG with active, non-healing ulcer.

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

1. A screening physical examination with no clinically significant abnormalities
unrelated to PG.

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

3. Liver function tests (alanine aminotransferase/aspartate aminotransferase,
bilirubin and alkaline phosphatase) < 2x the upper limit of normal.

4. 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 24.

5. No clinical abnormalities noted in the12-lead electrocardiogram in the opinion of
the investigator (Refer also to exclusion criterion 13).

6. 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.

5. Eligible male and female participants 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 participants who are sexually active must take adequate contraception measures.
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. 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 1.

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

3. History of severe renal or severe hepatic impairment.

4. Current active or latent tuberculosis (TB).

5. A positive diagnostic TB test at screening.

6. Exposure to B-cell or T-cell targeted therapies (such as natalizumab, rituximab,
abatacept) within 5 half-lives prior to Day 1.

7. Exposure to other immunosuppressive, immunomodulating or antineoplastic agents.

8. Receipt of any investigational agent within 30 days or 5 half lives (whichever is
longer), prior to Day 1.

9. Use of moderate to strong inhibitors of CYP2C9.

10. Abnormal forced expiratory volume (FEV1) or forced vital capacity (FVC).

11. Any known history of congenital or acquired immuno-deficiency.

12. 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.

13. 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.

14. Congestive heart failure (NYHA III or NYHA IV)

15. Any surgical procedure requiring general anesthesia within 30 days prior to Day 1 or
plans to undergo major surgery during the study period.

16. History of retinal macular edema.

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

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

19. Participants without documented positive varicella zoster virus (VZV) IgG antibody
status or participants who have not completed VZV vaccination within 6 weeks prior to
Day 1.

20. Receipt of live vaccine within 6 weeks prior to Day 1.

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

22. History of malignancy except for adequately treated basal cell skin cancer and in situ
carcinoma of the cervix of the uterus that have been completely excised with
documented, clear margins.

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

24. Leukopenia or lymphopenia at screening.

25. Current or recent history (within 1 year prior to Day 1) of alcohol dependence or
illicit drug use.

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

27. History of any other clinically significant medical condition that, in the
investigator's opinion, would preclude participant from safe participation in the
study.

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

29. Prior exposure to etrasimod (APD334) or prior participation in any study of etrasimod
(APD334).

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Westmead Hospital - Westmead
Recruitment hospital [2] 0 0
Veracity Clinical Research - Woolloongabba
Recruitment hospital [3] 0 0
Eastern Clinical Research Unit - Box Hill
Recruitment hospital [4] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [5] 0 0
Fremantle Dermatology - Fremantle
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
3128 - Box Hill
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment postcode(s) [5] 0 0
6160 - Fremantle
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Hamilton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Arena Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03072953
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Arena CT.gov Administrator
Address 0 0
Arena Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03072953