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Low recruitment
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ponesimod | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ponesimod | Drug | 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. |
|
| 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 |
| 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. |
| 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. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Daniele D'Ambrosio, MD, PhD | Actelion | Study Chair |
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | From baseline to Week 12 |
|
Study treatment was terminated on Day 81 and the subject was exposed to ponesimod for a total of 81 days (i.e., Day 1 to Day 81). None of the reported adverse events (AEs) were considered by the investigator to be related to the study drug. As there was only 1 patient enrolled in the study, all (S)AEs reported occur with 100% frequency.
All AEs were coded using MedDRA version 19.0. No AEs were reported during the screening period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastritis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial flutter | Cardiac disorders | MedDRA | Systematic Assessment |
The study was terminated early due to poor recruitment with 1 subject enrolled. Due to consequent lack of meaningful data, no conclusive analyses could be performed. The statistical analysis plan is obsolete and therefore not applicable.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Disclosure Desk | Actelion Pharmaceuticals Ltd | +41 61 565 6565 | clinical-trials-disclosure@its.jnj.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 5, 2016 | Mar 2, 2018 | Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D000092122 | Bronchiolitis Obliterans Syndrome |
| ID | Term |
|---|---|
| D000092124 | Organizing Pneumonia |
| D001989 | Bronchiolitis Obliterans |
| D001988 | Bronchiolitis |
| D001991 | Bronchitis |
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| ID | Term |
|---|---|
| C550169 | ponesimod |
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|
| From the first study drug intake up to 30 days after last study drug intake (Week 24) |
| At Week 24 |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Units | Counts |
|---|
| Participants |
|
| 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. | 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. | Posted | Count of Participants | Participants | From the first study drug intake up to 30 days after last study drug intake (Week 24) |
|
|
|
| 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. | 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. | Posted | At Week 24 |
|
|
| 0 |
| 1 |
| 1 |
| 1 |
| 1 |
| 1 |
| Virus infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Haematemesis, Parainfluenza | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Hip fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA | Systematic Assessment |
|
Any study-related publication written independently by investigators must be submitted to Actelion for review at least 30 days prior to submission for publication or presentation. Upon review, Actelion may provide comments, and may also request alterations and/or deletions for the sole purpose of protecting its confidential information and/or patent rights.
| D001982 |
| Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D006086 | Graft vs Host Disease |
| D007154 | Immune System Diseases |
| Title | Measurements |
|---|---|
|