Back to resultsClinical Study to Investigate the Biological Activity, Safety, Tolerability, and Pharmacokinetics of Ponesimod in Subjects With Symptomatic Chronic GVHD
Primary Purpose
Chronic Graft Versus Host Disease
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ponesimod
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Graft Versus Host Disease focused on measuring GVHD, ponesimod
Eligibility Criteria
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
Sites / Locations
- Virginia Piper Cancer Institute
- Moore Cancer Center - UCSD
- David Geffen School of Med at UCLA
- Northwestern University
- Indiana University Simon Cancer Center
- National Cancer Institute
- University of Minnesota - Masonic Cancer CTR CLIN TRIALS CTR
- Washington Univ School of Med, Oncology (St.Louis)
- Stony Brook Univ. Medical Center
- Fred Hutchinson Cancer Res CTR
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Ponesimod
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02461134
Brief Title
Clinical Study to Investigate the Biological Activity, Safety, Tolerability, and Pharmacokinetics of Ponesimod in Subjects With Symptomatic Chronic GVHD
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2018
Overall Recruitment Status
Terminated
Why Stopped
Low recruitment
Study Start Date
September 29, 2016 (Actual)
Primary Completion Date
March 2, 2017 (Actual)
Study Completion Date
March 3, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Actelion
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Graft Versus Host Disease
Keywords
GVHD, ponesimod
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ponesimod
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Ponesimod
Other Intervention Name(s)
ACT-128800
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in Peripheral Absolute Lymphocyte Count From Baseline to Week 4, 8 and 12
Description
The primary pharmacodynamic endpoint assesses intra-subject dose response during the first 12 weeks of treatment.
Time Frame
From baseline to Week 12
Secondary Outcome Measure Information:
Title
Incident Rate of Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
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.
Time Frame
From the first study drug intake up to 30 days after last study drug intake (Week 24)
Other Pre-specified Outcome Measures:
Title
Assessment of a Partial or Complete Overall Response at Week 24
Description
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.
Time Frame
At Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniele D'Ambrosio, MD, PhD
Organizational Affiliation
Actelion
Official's Role
Study Chair
Facility Information:
Facility Name
Virginia Piper Cancer Institute
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
Moore Cancer Center - UCSD
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
David Geffen School of Med at UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Indiana University Simon Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
National Cancer Institute
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892-1203
Country
United States
Facility Name
University of Minnesota - Masonic Cancer CTR CLIN TRIALS CTR
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Washington Univ School of Med, Oncology (St.Louis)
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Stony Brook Univ. Medical Center
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794
Country
United States
Facility Name
Fred Hutchinson Cancer Res CTR
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-1023
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Clinical Study to Investigate the Biological Activity, Safety, Tolerability, and Pharmacokinetics of Ponesimod in Subjects With Symptomatic Chronic GVHD
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