Chronic Graft Versus Host DiseasePhase 2NCT02461134

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

A Phase 2 study testing Ponesimod in people with Chronic Graft Versus Host Disease, run by Actelion.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Chronic Graft Versus Host Disease
What is being tested?: Ponesimod
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1 participants
Where: No sites listed yet
Study dates: 29 Sep 2016to 3 Mar 2017
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

About this study

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

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.

Conditions: Chronic Graft Versus Host Disease
Being tested: Ponesimod
Keywords: GVHD, ponesimod
Medical subject headings: Bronchiolitis Obliterans Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PonesimodDrug
Also called ACT-128800
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.

Study groups in NCT02461134
Study group	Role	What they receive
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. Receives: Drug: Ponesimod

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: From baseline to Week 12

Secondary outcomes (1)

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.
Measured: From the first study drug intake up to 30 days after last study drug intake (Week 24)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

29 Sep 20163 Mar 2017

First posted3 Jun 2015 (estimated)
Study start29 Sep 2016
Primary completion2 Mar 2017
Study completion3 Mar 2017

Why it stopped: Low recruitment

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Chronic Graft Versus Host DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 1 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02461134
Sponsor's protocol ID: AC-058C202
Status last verified: Jan 2025
First submitted: 28 Apr 2015
Last updated: 4 Feb 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Chronic Graft Versus Host Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02461134
Acronym / sponsor ID: AC-058C202
Conditions: Chronic Graft Versus Host Disease
Keywords: GVHD, ponesimod
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Low recruitment
Enrolment: 1 participants (actual)
Lead sponsor: ActelionIndustry (pharma, biotech, devices)
Study start: 29 Sep 2016 (actual)
Primary completion: 2 Mar 2017 (actual)
Study completion: 3 Mar 2017 (actual)
First posted: 3 Jun 2015 (estimated)
Results: Posted 9 May 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Ponesimod	Experimental	Drug: PonesimodStudy 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.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PonesimodAlso: ACT-128800Oral 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.	Drug	Ponesimod

Primary outcome

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.

1 secondary outcome

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)

Results and safety

Results posted to the registry on 9 May 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ponesimod	1	0

Primary outcome: Change in Peripheral Absolute Lymphocyte Count From Baseline to Week 4, 8 and 12

Time frame: From baseline to Week 12

Population analysed: 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.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 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.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ponesimod	1 of 1 (100%)	1 of 1 (100%)	0 of 1

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Not yet recruiting
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Daniele D'Ambrosio, MD, PhD study chair

Actelion

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ponesimod in people with Chronic Graft Versus Host Disease, run by Actelion.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 4 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Peripheral Absolute Lymphocyte Count From Baseline to Week 4, 8 and 12 (time frame: From baseline to Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02461134.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2025.