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

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

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Graft Versus Host Disease
• Intervention / Treatment: Drug: Ponesimod

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Virginia Piper Cancer Institute
  • California
    • La Jolla, California, United States, 92093
      • Moore Cancer Center - UCSD
    • Los Angeles, California, United States, 90095
      • David Geffen School of Med at UCLA
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Simon Cancer Center
  • Maryland
    • Bethesda, Maryland, United States, 20892-1203
      • National Cancer Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota - Masonic Cancer CTR CLIN TRIALS CTR
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington Univ School of Med, Oncology (St.Louis)
  • New York
    • Stony Brook, New York, United States, 11794
      • Stony Brook Univ. Medical Center
  • Washington
    • Seattle, Washington, United States, 98109-1023
      • Fred Hutchinson Cancer Res CTR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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.; Other Names: ACT-128800

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Study Chair: Daniele D'Ambrosio, MD, PhD, Actelion

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2016
• Primary Completion (Actual): March 2, 2017
• Study Completion (Actual): March 3, 2017

Study Registration Dates

• First Submitted: April 28, 2015
• First Submitted That Met QC Criteria: June 1, 2015
• First Posted (Estimate): June 3, 2015

Study Record Updates

• Last Update Posted (Actual): May 9, 2018
• Last Update Submitted That Met QC Criteria: April 9, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: GVHD; ponesimod
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Sphingosine 1 Phosphate Receptor Modulators; Ponesimod
• Other Study ID Numbers: AC-058C202

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No