Clinical Study to Investigate the Biological Activity, Safety, Tolerability, and Pharmacokinetics of Ponesimod in Subjects With Symptomatic Chronic GVHD

Phase 2

Terminated

Brief Summary: Chronic graft versus host diseasre (GVHD) is a serious reaction that might occur in a person (the host) who has received cells or organs (graft) from another person because the graft attacks the host's cells. Currently there are no approved therapies for chronic GVHD in the USA, and patients with chroninc GVHD are treated with immunosuppressant drugs. T-lymphocytes (a type of white blood cells) are likely to play a role in the development of chronic GVHD. Due to the capacity of ponesimod to block the traffic of T-lymphocytes, ponesimod may be a new therapeutic approach to treat chroninc GVHD.

The main objective of this study is to assess the effectiveness and safety of several doses of ponesimod in subjects with chronic GVHD who did not respond to standard available treatments.

Recruitment & Eligibility

Inclusion Criteria

Signed informed consent
Symptomatic moderate or severe chronic GVHD patients in need of a change of systemic immunosuppressant (IS) therapy
Women of child bearing potential must have a negative pregnancy test and use reliable methods of contraception

Exclusion Criteria

Clinically significant medical conditions including active or uncontrolled infections, new or recurrent malignancy, serious cardiac, pulmonary, or renal disease, and uncontrolled diabetes.
Karnofsky Performance Score < 60.
Immunosuppressant therapies other than allowed background therapy
Anti-arrhythmic and heart rate lowering drugs.
Any other circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol

Arm && Interventions

Group	Intervention	Description
Ponesimod	Ponesimod	Study treatment consists of 3 consecutive periods: 5 mg ponesimod treatment period (including up-titration), 10 mg treatment period (including up-titration) and a 20 mg treatment period.

Primary Outcome Measures

Name	Time	Method
Change in Peripheral Absolute Lymphocyte Count From Baseline to Week 4, 8 and 12	From baseline to Week 12	The primary pharmacodynamic endpoint assesses intra-subject dose response during the first 12 weeks of treatment.

Secondary Outcome Measures

Name	Time	Method
Incident Rate of Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	From the first study drug intake up to 30 days after last study drug intake (Week 24)	This outcome measure reports the occurrence of adverse events (AEs), and serious adverse events (SAEs) during the treatment period and the follow-up period, and AEs leading to premature discontinuation of study drug. A treatment-emergent AE is any AE temporally associated with the use of study treatment whether or not considered by the investigator as related to study treatment.

Locations (10): Fred Hutchinson Cancer Res CTR
🇺🇸
Seattle, Washington, United States
Virginia Piper Cancer Institute
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Scottsdale, Arizona, United States
Moore Cancer Center - UCSD
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La Jolla, California, United States
Northwestern University
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Chicago, Illinois, United States
Indiana University Simon Cancer Center
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Indianapolis, Indiana, United States
National Cancer Institute
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Bethesda, Maryland, United States
University of Minnesota - Masonic Cancer CTR CLIN TRIALS CTR
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Minneapolis, Minnesota, United States
Washington Univ School of Med, Oncology (St.Louis)
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Saint Louis, Missouri, United States
Stony Brook Univ. Medical Center
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Stony Brook, New York, United States
David Geffen School of Med at UCLA
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Los Angeles, California, United States