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

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ClinicalTrials.gov Identifier: NCT02461134
Recruitment Status : Terminated (Low recruitment)
First Posted : June 3, 2015
Results First Posted : May 9, 2018
Last Update Posted : May 9, 2018
Sponsor:
Information provided by (Responsible Party):
Actelion

Tracking Information
First Submitted Date  ICMJE April 28, 2015
First Posted Date  ICMJE June 3, 2015
Results First Submitted Date  ICMJE March 2, 2018
Results First Posted Date  ICMJE May 9, 2018
Last Update Posted Date May 9, 2018
Actual Study Start Date  ICMJE September 29, 2016
Actual Primary Completion Date March 2, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 9, 2018)
Change in Peripheral Absolute Lymphocyte Count From Baseline to Week 4, 8 and 12 [ Time Frame: From baseline to Week 12 ]
The primary pharmacodynamic endpoint assesses intra-subject dose response during the first 12 weeks of treatment.
Original Primary Outcome Measures  ICMJE
 (submitted: June 1, 2015)
To investigate the dose response in peripheral total lymphocyte count reduction with ponesimod in subjects with chronic graft versus host disease (GVHD) [ Time Frame: baseline to end of treatment (week 24) ]
Change History Complete list of historical versions of study NCT02461134 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 9, 2018)
Incident Rate of Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 1, 2015)
  • profile: Treatment-emergent adverse events, serious adverse events, and adverse events of special interest such as: [ Time Frame: baseline to end of treatment (week 24) ]
    • Effect on HR and rhythm related adverse events
    • Cardiovascular related adverse events
    • Hypertension related adverse events
    • Hepatobiliary disorders / liver enzyme abnormality related adverse events
    • Pulmonary related AEs
    • Eye disorders related AEs
    • Infection related AEs
    • Skin malignancy related AEs
    • Non-skin malignancy related AEs
  • Adverse events leading to premature discontinuation of study drug [ Time Frame: baseline to end of treatment (week 24) ]
  • Achievement of a partial or complete overall response at 24 weeks post-enrollment, based on the 2014 NIH Consensus Development Project response criteria [ Time Frame: baseline to end of treatment (week 24) ]
Current Other Pre-specified Outcome Measures
 (submitted: April 9, 2018)
Assessment of a Partial or Complete Overall Response at Week 24 [ Time Frame: 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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clinical Study to Investigate the Biological Activity, Safety, Tolerability, and Pharmacokinetics of Ponesimod in Subjects With Symptomatic Chronic GVHD
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Graft Versus Host Disease
Intervention  ICMJE 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 Name: ACT-128800
Study Arms  ICMJE 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.
Intervention: Drug: Ponesimod
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 30, 2018)
1
Original Estimated Enrollment  ICMJE
 (submitted: June 1, 2015)
30
Actual Study Completion Date  ICMJE March 3, 2017
Actual Primary Completion Date March 2, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02461134
Other Study ID Numbers  ICMJE AC-058C202
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Actelion
Study Sponsor  ICMJE Actelion
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Daniele D'Ambrosio, MD, PhD Actelion
PRS Account Actelion
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP