Chronic Graft Versus Host Disease
Conditions
Keywords
GVHD, ponesimod
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.
Interventions
DRUGPonesimod
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.
Sponsors
Actelion
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Assessment of a Partial or Complete Overall Response at Week 24 | 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. |
Participant flow
Recruitment details
11 subjects were screened at 5 different sites. 1 subject was finally recruited into the study. The study was prematurely terminated due to poor recruitment.
Pre-assignment details
The protocol-defined study population included male and female subjects aged 18 to 70 years with chronic Graft versus Host disease (GVHD). It was planned to recruit 30 subjects.
Participants by arm
| Arm | Count |
|---|---|
| Ponesimod It was planned that enrolled subjects receive ponesimod in escalating doses of 5, 10 and 20 mg over the course of the treatment period of 24 weeks in total (4 weeks of 5 mg incl. up-titration, 4 weeks of 10 mg incl. up-titration and 16 weeks of 20 mg). | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Ponesimod | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 1 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 1 Participants | — |
| Sex: Female, Male Male | 0 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 |
Outcome results
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.
Time frame: From baseline to Week 12
Population: Due to the premature termination of the study and consequent lack of meaningful data, no analyses were performed. The statistical analysis plan issued is obsolete, it was not finalized and was therefore not executed.
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.
Time frame: From the first study drug intake up to 30 days after last study drug intake (Week 24)
Population: The premature termination of the study led to a consequent lack of meaningful data. As the statistical analysis plan issued was not finalized and was not executed, no statistical analyses were performed. As there was only 1 patient enrolled in the study, the safety events reported occur with 100% frequency.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ponesimod | Incident Rate of Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants discontinued prematurely study drug | 1 Participants |
| Ponesimod | Incident Rate of Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 1 Participants |
| Ponesimod | Incident Rate of Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 1 Participants |
Other Pre-specified
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.
Time frame: At Week 24
Population: Due to the premature termination of the study and consequent lack of meaningful data, no analyses were performed. The statistical analysis plan issued is obsolete, it was not finalized and was therefore not executed.