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

Chronic Graft Versus Host Disease Clinical Trial

Official title:

A Phase 2, Open-label, Single-arm, Intra-subject Dose-escalation Study to Investigate the Biological Activity, Safety, Tolerability, and Pharmacokinetics of Ponesimod in Subjects With Symptomatic Moderate or Severe Chronic GVHD Inadequately Responding to First or Second Line Therapy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02461134
• Other study ID #: AC-058C202
• Status: Terminated
• Phase: Phase 2
• Start date: September 29, 2016
• Est. completion date: March 3, 2017

Study information

• Verified date: April 2018
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: March 3, 2017
• Est. primary completion date: March 2, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

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

Related Conditions & MeSH terms

• Chronic Graft Versus Host Disease
• Graft vs Host Disease

Intervention

Drug:
• Ponesimod
Oral film-coated tablets at the doses of 2, 3, 4, 5, 6, 7, 8, 9, 10, and 20 mg. One tablet of ponesimod at any dose will be taken orally once daily.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Assessment of a Partial or Complete Overall Response at Week 24	The exploratory efficacy endpoint is based on the 2014 NIH Consensus Development Project response criteria. A complete overall response is defined as a resolution of all reversible manifestations due to chronic GVHD in each organ as defined per NIH Consensus Development Project response criteria. A partial overall response is defined as improvement in a measure for at least one organ without progression in measures for any other organ.	At Week 24
Primary	Change in Peripheral Absolute Lymphocyte Count From Baseline to Week 4, 8 and 12	The primary pharmacodynamic endpoint assesses intra-subject dose response during the first 12 weeks of treatment.	From baseline to Week 12
Secondary	Incident Rate of Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	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.	From the first study drug intake up to 30 days after last study drug intake (Week 24)