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Oral Ponesimod Versus Teriflunomide In Relapsing MUltiple Sclerosis (OPTIMUM)

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ClinicalTrials.gov Identifier: NCT02425644
Recruitment Status : Completed
First Posted : April 24, 2015
Results First Posted : June 11, 2021
Last Update Posted : June 11, 2021
Sponsor:
Information provided by (Responsible Party):
Actelion

Tracking Information
First Submitted Date  ICMJE April 21, 2015
First Posted Date  ICMJE April 24, 2015
Results First Submitted Date  ICMJE April 2, 2021
Results First Posted Date  ICMJE June 11, 2021
Last Update Posted Date June 11, 2021
Actual Study Start Date  ICMJE June 4, 2015
Actual Primary Completion Date May 16, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 18, 2021)
Annualized Confirmed Relapse Rate [ Time Frame: From randomization to end of study (Week 108) ]
Relapse: occurrence of acute episode of one or more new symptoms 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).
Original Primary Outcome Measures  ICMJE
 (submitted: April 21, 2015)
Annualized relapse rate (ARR) [ Time Frame: baseline to end of treatment (week 108) ]
defined as the number of confirmed relapses per subject-year
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 18, 2021)
  • Change From Baseline in Fatigue-related Symptoms as Measured by the Symptoms Domain of the Fatigue Symptom and Impact Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS) Score to Week 108 [ Time Frame: Baseline to Week 108 ]
    The FSIQ-RMS is a 20-item Patient Reported Outcomes (PRO) measure to evaluate fatigue-related symptoms and the impacts of those symptoms on the lives of people. The FSIQ-RMS symptom domain (FSIQ-RMS-S) consists of seven items assessing fatigue-related symptoms daily with a recall period of 24 hours measured on an 11-point numeric rating scale; the (normalized) symptom domain score ranges from 0 to 100 with a higher score indicating greater fatigue. This domain was completed on 7 consecutive days. A negative change from baseline indicates an improvement in fatigue symptoms.
  • Cumulative Number of Combined Unique Active Lesions (CUAL) Per Year From Baseline to Week 108 [ Time Frame: Baseline to Week 108 ]
    CUALs was calculated as sum of new Gadolinium-enhanced (Gd+) T1 lesions plus new or enlarging T2 lesions (without double-counting of lesions) from baseline based on the Magnetic resonance imaging (MRI) scans up to Week 108. Average number of lesions per year were reported.
  • 12-Week Confirmed Disability Accumulation (CDA) Assessed From Baseline to EOS [ Time Frame: Baseline to Week 60 and 108 Weeks ]
    A 12-week CDA 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).
  • 24-Week Confirmed Disability Accumulation (CDA) Assessed From Baseline to EOS [ Time Frame: Baseline to 60 Weeks and 108 Weeks ]
    A 24-week CDA was defined as an increase of at least 1.5 in 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 >= 5.5, which was confirmed after 24 weeks. Baseline EDSS was defined as the last EDSS score recorded prior to randomization. The EDSS is an ordinal scale ranging from 0 (normal neurological exam) to 10 (death to MS).
Original Secondary Outcome Measures  ICMJE
 (submitted: April 21, 2015)
  • Time to 12-week confirmed disability accumulation (CDA) [ Time Frame: baseline to end of treatment (week 108) ]
  • Percent change in brain volume (PCBV) [ Time Frame: baseline to end of treatment (week 108) ]
  • Time to first confirmed relapse [ Time Frame: baseline to end of treatment (week 108) ]
  • Cumulative number of combined unique active lesions [ Time Frame: baseline to end of treatment (week 108) ]
    (CUAL; defined as new Gd+ T1 lesions plus new or enlarging T2 lesions [without double-counting of lesions])
  • Change from baseline to Week 108 in fatigue-related symptoms [ Time Frame: baseline to end of treatment (week 108) ]
    measured by the symptoms domain of the Fatigue Symptoms and Impact Questionnaire - Relapsing Multiple Sclerosis (FSIQ-RMS)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Oral Ponesimod Versus Teriflunomide In Relapsing MUltiple Sclerosis
Official Title  ICMJE Multicenter, Randomized, Double-blind, Parallel-group, Active-controlled, Superiority Study to Compare the Efficacy and Safety of Ponesimod to Teriflunomide in Subjects With Relapsing Multiple Sclerosis
Brief Summary International clinical trial to compare ponesimod and teriflunomide in relapsing multiple sclerosis
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Multiple Sclerosis
Intervention  ICMJE
  • Drug: ponesimod
    film-coated tablet with 20 mg ponesimod, administered orally once daily in the morning
    Other Name: ACT-128800
  • Drug: teriflunomide
    film-coated tablet with 14 mg teriflunomide, administered orally once daily in the morning
Study Arms  ICMJE
  • Experimental: Ponesimod
    Subjects to receive 20 mg ponesimod
    Intervention: Drug: ponesimod
  • Active Comparator: Teriflunomide
    Subjects to receive 14 mg teriflunomide
    Intervention: Drug: teriflunomide
Publications * Kappos L, Fox RJ, Burcklen M, Freedman MS, Havrdová EK, Hennessy B, Hohlfeld R, Lublin F, Montalban X, Pozzilli C, Scherz T, D'Ambrosio D, Linscheid P, Vaclavkova A, Pirozek-Lawniczek M, Kracker H, Sprenger T. Ponesimod Compared With Teriflunomide in Patients With Relapsing Multiple Sclerosis in the Active-Comparator Phase 3 OPTIMUM Study: A Randomized Clinical Trial. JAMA Neurol. 2021 May 1;78(5):558-567. doi: 10.1001/jamaneurol.2021.0405.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 5, 2019)
1133
Original Estimated Enrollment  ICMJE
 (submitted: April 21, 2015)
1100
Actual Study Completion Date  ICMJE May 16, 2019
Actual Primary Completion Date May 16, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Male and female subjects aged 18 to 55 years with established diagnosis of MS McDonald 2010 with relapsing course from onset (i.e., RRMS and SPMS with superimposed relapses).

Subjects must have active disease evidenced by one or more MS attacks with onset within the period of 12 to 1 months prior to randomization, or by two or more MS attacks with onset within the 24 to 1 months prior to randomization, or with one or more gadolinium-enhancing (Gd+) lesion(s) of the brain on an MRI performed within 6 months prior to randomization.

Enrolled subjects must be ambulatory (EDSS score of up to 5.5 inclusive) and may be treatment-naïve or previously treated with MS disease modifying therapy.

Exclusion Criteria:

Subjects with significant medical conditions or therapies for such conditions (e.g., cardiovascular, pulmonary, immunological, hepatic,ophthalmological conditions) or lactating or pregnant women are not eligible to enter the study.

Subjects with contraindications to MRI or with clinically relevant medical or surgical conditions that, in the opinion of the investigator, would put the subject at risk by participating in the study are not eligible to enter the study.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belarus,   Bosnia and Herzegovina,   Bulgaria,   Canada,   Croatia,   Czechia,   Finland,   France,   Georgia,   Germany,   Greece,   Hungary,   Israel,   Italy,   Latvia,   Lithuania,   Mexico,   Poland,   Portugal,   Romania,   Russian Federation,   Serbia,   Spain,   Sweden,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries Argentina,   Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02425644
Other Study ID Numbers  ICMJE AC-058B301
2012-000540-10 ( EudraCT Number )
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  ICMJE Not Provided
Responsible Party Actelion
Study Sponsor  ICMJE Actelion
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Tatiana Scherz, MD, PhD Actelion
PRS Account Actelion
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP