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Clinical Study to Compare the Efficacy and Safety of Ponesimod to Placebo in Subjects With Active Relapsing Multiple Sclerosis Who Are Treated With Dimethyl Fumarate (Tecfidera®) (POINT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02907177
Recruitment Status : Terminated (sponsor decision due to low recruitment)
First Posted : September 20, 2016
Results First Posted : May 18, 2021
Last Update Posted : May 18, 2021
Sponsor:
Information provided by (Responsible Party):
Actelion

Brief Summary:
This clinical study compares the efficacy, safety, and tolerability of therapy with ponesimod vs placebo in subjects with active RMS who are treated with DMF (Tecfidera®).

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Drug: Ponesimod Other: Placebo Phase 3

Detailed Description:
The study will assess the efficacy, safety, and tolerability of add-on therapy with ponesimod 20 mg vs placebo in adult participants with active relapsing multiple sclerosis (RMS) who are treated with dimethyl fumarate (DMF). Approximately 600 participants who have been receiving DMF for at least 6 months will be randomized in a 1:1 ratio to ponesimod 20 mg or placebo. The study consists of the following study periods: Pre-randomization period; Treatment period; Post-treatment observation period. The study includes one ponesimod treatment arm at the maintenance dose of 20 mg o.d. corresponding to the optimal dose when used as monotherapy based on the Phase 2 dose-finding trial and its ongoing extension. The study includes a placebo comparator arm, but all patients will remain on DMF background therapy throughout the study. Moreover, participants who experience a confirmed relapse or an event of 24-week confirmed disability accumulation (DMF) while on study drug will have the option to switch to an alternative treatment. The treatment period has a variable duration from a minimum of 60 weeks (for the last subject randomized) to a maximum of 156 weeks for the first subjects randomized in the trial and includes a gradual up-titration of ponesimod from a 2 mg starting dose to a 20 mg maintenance dose over a period of 14 days. The total duration of the study will be approximately up to 167 weeks.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 136 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Multicenter, Randomized, Double-blind, Parallel-group, add-on, Superiority Study to Compare the Efficacy and Safety of Ponesimod to Placebo in Subjects With Active Relapsing Multiple Sclerosis Who Are Treated With Dimethyl Fumarate (Tecfidera®)
Actual Study Start Date : March 30, 2017
Actual Primary Completion Date : March 26, 2020
Actual Study Completion Date : March 26, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ponesimod
Ponesimod
Drug: Ponesimod
One tablet of ponesimod 20 mg administered orally once daily in the morning from Day 15 to EOT. To reduce the first-dose effect of ponesimod, an uptitration scheme will be implemented from Day 1 to Day 14 (with dose strength increasing from 2 mg to 20 mg).

Placebo Comparator: Placebo
Placebo
Other: Placebo
One tablet of matching placebo administered orally once daily in the morning




Primary Outcome Measures :
  1. Annualized Confirmed Relapse Rate (ARR) [ Time Frame: Through study completion, an average of 68 weeks ]
    Relapse: occurrence of acute episode of one or more new or worsened symptoms of Multiple sclerosis (MS), not associated with fever/infection and lasting 24 hours after stable 30 days period. Confirmed relapse: increase from baseline at least 0.5 point Expanded Disability Status Scale (EDSS) score or increase of one point in one, two or three Functional Systems (FS), excluding bowel/bladder and cerebral/mental FS. EDSS and FS scores are based on neurological examination for assessing its impairment in MS. Among eight FS, seven are ordinal clinical rating scales ranging from 0-5 or 6 with higher scale indicates overall functional impairment assessing Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel/Bladder and Cerebral functions. Rating individual FS scores is used to rate EDSS in conjunction with observations and information concerning gait and use of assistance. EDSS is ordinal clinical rating scale ranging from 0 (normal neurological examination) to 10(death due to MS).


Secondary Outcome Measures :
  1. Percentage of Participants With 12-Week Confirmed Disability Accumulation (CDA) as Assessed by Kaplan Meier Estimate at Week 96 [ Time Frame: Week 96 ]
    Percentage of participants with 12-week CDA as assessed by Kaplan Meier estimate at week 96 was defined as an increase of at least 1.5 in Expanded Disability Status Scale (EDSS) for participants with a baseline EDSS score of 0.0 or an increase of at least 1.0 in EDSS for participants with a baseline EDSS score of 1.0 to 5.0, or an increase of at least 0.5 in EDSS for participants with a baseline EDSS score greater than or equal to (>=) 5.5, which was confirmed after 12 weeks. Baseline EDSS was defined as the last EDSS score recorded prior to randomization. EDSS is an ordinal clinical rating scale ranging from 0 (normal neurological examination) to 10 (death due to MS).

  2. Percentage of Participants Experiencing a Confirmed Relapse as Assessed by Kaplan Meier Estimate at Week 96 [ Time Frame: Week 96 ]
    Percentage of participants experiencing a confirmed relapse as assessed by Kaplan Meier estimate at week 96 was reported. The time to first confirmed relapse (in days) is defined as [Date of first confirmed relapse minus Date of randomization plus 1] in days. Relapse: Occurrence of acute episode of one or more new symptoms or worsened symptoms of Multiple sclerosis (MS), not related with fever/infection and lasting 24 hours after 30 days stable period.

  3. Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability [ Time Frame: Up to 147 Weeks ]
    An AE is any untoward medical event that occurs in a participants administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent prior to initiation of any study-mandated procedure.
  • Women of childbearing potential must have a negative pregnancy test and use reliable methods of contraception
  • Presenting with a diagnosis of MS as defined by the revised (2010) McDonald Diagnostic Criteria for MS with relapsing course from onset (i.e., relapsing-remitting multiple sclerosis (RRMS), or secondary progressive multiple sclerosis (SPMS) with superimposed relapses).
  • Ongoing treatment with DMF for at least 6 months prior to screening
  • Active disease after at least 3 months of DMF treatment
  • Ambulatory and with an EDSS score between 0 and 6.0 (inclusive).

Exclusion Criteria:

  • Lactating or pregnant women and women intending to become pregnant during the study.
  • Presenting with a diagnosis of MS with progressive course from onset (i.e., primary progressive MS or progressive relapsing MS).
  • Evidence of a relapse of MS with onset within 30 days prior to baseline EDSS assessment.
  • Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02907177


Locations
Show Show 119 study locations
Sponsors and Collaborators
Actelion
Investigators
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Study Director: Tatiana Scherz, MD, PhD Actelion
  Study Documents (Full-Text)

Documents provided by Actelion:
Study Protocol  [PDF] December 21, 2017
Statistical Analysis Plan  [PDF] June 16, 2020

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Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT02907177    
Other Study ID Numbers: AC-058B302
First Posted: September 20, 2016    Key Record Dates
Results First Posted: May 18, 2021
Last Update Posted: May 18, 2021
Last Verified: April 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Ponesimod
Sphingosine 1 Phosphate Receptor Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs