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)

• ClinicalTrials.gov Identifier: NCT02907177
• Recruitment Status: Terminated
• First Posted: September 20, 2016
• Last Update Posted: April 6, 2020
• Sponsor: Actelion
• Information provided by (Responsible Party): Actelion

Tracking Information

• First Submitted Date: August 25, 2016
• First Posted Date: September 20, 2016
• Last Update Posted Date: April 6, 2020
• Actual Study Start Date: March 30, 2017
• Actual Primary Completion Date: March 26, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 15, 2016)

Annualized relapse rate (ARR) [ Time Frame: From randomization up to EOS; for a max. total time of approx. 167 weeks, i.e. 3.3 years ]

Number of confirmed relapses per subject-year

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 30, 2017)

• Time to 12-week confirmed disability accumulation (CDA) [ Time Frame: From baseline up to EOS; for a max. total time of approx. 167 weeks, i.e. 3.3 years ]
  Time to 12-week confirmed disability accumulation (CDA)
• Time to first confirmed relapse [ Time Frame: From baseline up to EOS; for a max. total time of approx. 167 weeks, i.e. 3.3 years ]
  Time to first confirmed relapse
• Mean number of combined unique active lesions (CUALs) per post-baseline scan [ Time Frame: From baseline up to EOS; for a max. total time of approx. 167 weeks, i.e. 3.3 years ]
  Mean number of combined unique active lesions (CUALs) per post-baseline scan
• Longitudinal change over time in fatigue-related symptoms as measured by the symptoms domain of the FSIQ-RMS [ Time Frame: From baseline up to EOS; for a max. total time of approx. 167 weeks, i.e. 3.3 years ]
  Longitudinal change over time in fatigue-related symptoms as measured by the symptoms domain of the FSIQ-RMS
• Longitudinal percent change from baseline over time in brain volume [ Time Frame: From baseline up to EOS; for a max. total time of approx. 167 weeks, i.e. 3.3 years ]
  Longitudinal percent change from baseline over time in brain volume

Original Secondary Outcome Measures (submitted: September 15, 2016)

• Time to 12-week confirmed disability accumulation (CDA) [ Time Frame: From baseline up to EOS; for a max. total time of approx. 167 weeks, i.e. 3.3 years ]
• Time to first confirmed relapse [ Time Frame: From baseline up to EOS; for a max. total time of approx. 167 weeks, i.e. 3.3 years ]
• Mean number of combined unique active lesions (CUALs) per post-baseline scan [ Time Frame: From baseline up to EOS; for a max. total time of approx. 167 weeks, i.e. 3.3 years ]
• Longitudinal change over time in fatigue-related symptoms as measured by the symptoms domain of the FSIQ-RMS [ Time Frame: From baseline up to EOS; for a max. total time of approx. 167 weeks, i.e. 3.3 years ]
• Longitudinal percent change from baseline over time in brain volume [ Time Frame: From baseline up to EOS; for a max. total time of approx. 167 weeks, i.e. 3.3 years ]

Current Other Pre-specified Outcome Measures (submitted: March 30, 2017)

Treatment-emergent adverse events (AEs) and serious AEs [ Time Frame: From time of first study drug intake up to 30 days after study treatment discontinuation ]

Treatment-emergent adverse events (AEs) and serious AEs

• Original Other Pre-specified Outcome Measures (submitted: September 15, 2016): Treatment-emergent adverse events (AEs) and serious AEs [ Time Frame: From time of first study drug intake up to 30 days after study treatment discontinuation ]

Descriptive Information

• Brief Title: 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®)
• 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®)
• 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®).
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Multiple Sclerosis

Intervention

• 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).
• Other: Placebo
  One tablet of matching placebo administered orally once daily in the morning

Study Arms

• Experimental: Ponesimod
  Ponesimod
  Intervention: Drug: Ponesimod
• Placebo Comparator: Placebo
  Placebo
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: December 20, 2019): 136
• Original Estimated Enrollment (submitted: September 15, 2016): 600
• Actual Study Completion Date: March 26, 2020
• Actual Primary Completion Date: March 26, 2020 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Bulgaria, Canada, Czechia, Denmark, France, Germany, Greece, Hungary, Italy, Mexico, Poland, Portugal, Russian Federation, Spain, Switzerland, United Kingdom, United States
• Removed Location Countries: Croatia, Czech Republic, Finland, Norway

Administrative Information

• NCT Number: NCT02907177
• Other Study ID Numbers: AC-058B302
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Actelion
• Study Sponsor: Actelion
• Collaborators: Not Provided

Investigators

• Study Director: Tatiana Scherz, MD, PhD; Actelion

• PRS Account: Actelion
• Verification Date: April 2020