Efficacy and Safety of APD334 in Patients With Pyoderma Gangrenosum
Condition: Pyoderma Gangrenosum
MeSH terms: Pyoderma; Pyoderma Gangrenosum
Intervention: APD334
Intervention description: APD334 active treatment
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Open label
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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.

        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).