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Efficacy and Safety of Ofatumumab Compared to Teriflunomide in Patients With Relapsing Multiple Sclerosis. (ASCLEPIOS II)

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: NCT02792231
Recruitment Status : Active, not recruiting
First Posted : June 7, 2016
Last Update Posted : August 14, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE June 2, 2016
First Posted Date  ICMJE June 7, 2016
Last Update Posted Date August 14, 2020
Actual Study Start Date  ICMJE August 26, 2016
Actual Primary Completion Date July 10, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 2, 2016)
Annualized relapse rate (ARR) [ Time Frame: up to 2.5 years ]
ARR is the number of confirmed relapses in a year calculated based on cumulative number of relapses by patient adjusted for time-in-study by patient
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 30, 2019)
  • Time to 3-month confirmed disability worsening on EDSS [ Time Frame: Baseline, every 3 months up to 2.5 years ]
    A 3-month confirmed disability worsening is an increase from baseline in Expanded Disability Status Scale (EDSS) score sustained for at last 3 months.
  • Time to 6-month confirmed disability worsening on EDSS [ Time Frame: Baseline, every 3 months up to 2.5 years ]
    A 6-month confirmed disability worsening is an increase from baseline in Expanded Disability Status Scale (EDSS) score sustained for at last 6 months.
  • Time to 6-month confirmed disability improvement on EDSS [ Time Frame: Baseline, every 3 months up to 2.5 years ]
    A 6-month confirmed disability improvement is a decrease from baseline in Expanded Disability Status Scale (EDSS) score sustained for at least 6 months.
  • Number of gadolinium (Gd)-enhancing lesions per MRI scan [ Time Frame: Baseline, yearly up to 2.5 years ]
    Total number of Gd-enhancing lesions across all scans per patient adjusted for different number of scans due to variable follow up time in study
  • Number of new or enlarging T2 lesions on MRI per year (annualized lesion rate) [ Time Frame: Baseline, yearly up to 2.5 years ]
    Number of new/enlarging T2 lesions on last available MRI scan compared to baseline adjusted for different time of scans versus baseline due to variable follow up time in study
  • Neurofilament light chain (Nfl) concentration in serum [ Time Frame: Baseline, every 3 months up to 2.5 years ]
    The NfL concentration (geometric mean concentration) will be estimated by treatment and time point with using a repeated measures model on the basis of all evaluable log-transformed NfL values.
  • Rate of brain volume loss based on assessments of percentage brain volume change from baseline [ Time Frame: Baseline, yearly up to 2.5 years ]
    Percent change from baseline in brain volume loss (BVL) on all MRI scans adjusted for different time of scan versus baseline due to variable follow up time in study
Original Secondary Outcome Measures  ICMJE
 (submitted: June 2, 2016)
  • Time to 3-month confirmed disability worsening on EDSS [ Time Frame: Baseline, every 3 months up to 2.5 years ]
    A 3-month confirmed disability worsening is an increase from baseline in Expanded Disability Status Scale (EDSS) score sustained for at last 3 months.
  • Time to 6-month confirmed disability worsening on EDSS [ Time Frame: Baseline, every 3 months up to 2.5 years ]
    A 6-month confirmed disability worsening is an increase from baseline in Expanded Disability Status Scale (EDSS) score sustained for at last 6 months.
  • Time to 6-month confirmed disability improvement on EDSS [ Time Frame: Baseline, every 3 months up to 2.5 years ]
    A 6-month confirmed disability improvement is a decrease from baseline in Expanded Disability Status Scale (EDSS) score sustained for at least 6 months.
  • Number of gadolinium (Gd)-enhancing lesions per MRI scan [ Time Frame: Baseline, yearly up to 2.5 years ]
    Total number of Gd-enhancing lesions across all scans per patient adjusted for different number of scans due to variable follow up time in study
  • Number of new or enlarging T2 lesions on MRI per year (annualized lesion rate) [ Time Frame: Baseline, yearly up to 2.5 years ]
    Number of new/enlarging T2 lesions on last available MRI scan compared to baseline adjusted for different time of scans versus baseline due to variable follow up time in study
  • Rate of brain volume loss based on assessments of percentage brain volume change from baseline [ Time Frame: Baseline, yearly up to 2.5 years ]
    Percent change from baseline in brain volume loss (BVL) on all MRI scans adjusted for different time of scan versus baseline due to variable follow up time in study
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Ofatumumab Compared to Teriflunomide in Patients With Relapsing Multiple Sclerosis.
Official Title  ICMJE A Randomized, Double-blind, Double-dummy, Parallel-group Study Comparing the Efficacy and Safety of Ofatumumab Versus Teriflunomide in Patients With Relapsing Multiple Sclerosis.
Brief Summary To compare the efficacy and safety of ofatumumab administered subcutaneously (sc) every 4 weeks versus teriflunomide administered orally once daily in patients with relapsing multiple sclerosis
Detailed Description

This is a randomized, double-blind, double-dummy, active comparator-controlled, parallel-group, multicenter study with variable treatment duration in approximately 900 patients with relapsing MS. The maximal treatment duration in the study for an individual patient will be 2.5 years.

Eligible patients will be randomized to receive either experimental ofatumumab subcutaneous (sc) injections every 4 weeks or active comparator teriflunomide orally once daily. In order to blind for the different formulations, double-dummy masking will be used i.e. all patients will take injections (containing either active ofatumumab or placebo) and oral capsules (containing either active teriflunomide or placebo).

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 Relapsing Multiple Scelrosis
Intervention  ICMJE
  • Drug: Ofatumumab subcutaneous injection
    Patients randomized to the ofatumumab arm will receive subcutaneous injections of ofatumumab every 4 weeks
  • Drug: Placebo orally matching to teriflunomide
    Placebo orally, matching in appearance to teriflunomide, administered once daily
  • Drug: Teriflunomide orally
    Patients randomized to the teriflunomide arm will take teriflunomide orally once daily
    Other Name: Aubagio
  • Drug: Placebo subcutaneous injection matching to ofatumumab
    Placebo-containing syringes, matching in appearance to syringes containing ofatumumab, administered every 4 weeks
Study Arms  ICMJE
  • Experimental: Ofatumumab

    Syringes for subcutaneous injection

    Patients will also take a placebo capsule (matching in appearance to teriflunomide)

    Interventions:
    • Drug: Ofatumumab subcutaneous injection
    • Drug: Placebo orally matching to teriflunomide
  • Active Comparator: Teriflunomide

    Oral capsule

    Patients will also take subcutaneous injections of placebo (syringes matching in appearance to ofatumumab)

    Interventions:
    • Drug: Teriflunomide orally
    • Drug: Placebo subcutaneous injection matching to ofatumumab
Publications * Hauser SL, Bar-Or A, Cohen JA, Comi G, Correale J, Coyle PK, Cross AH, de Seze J, Leppert D, Montalban X, Selmaj K, Wiendl H, Kerloeguen C, Willi R, Li B, Kakarieka A, Tomic D, Goodyear A, Pingili R, Häring DA, Ramanathan K, Merschhemke M, Kappos L; ASCLEPIOS I and ASCLEPIOS II Trial Groups. Ofatumumab versus Teriflunomide in Multiple Sclerosis. N Engl J Med. 2020 Aug 6;383(6):546-557. doi: 10.1056/NEJMoa1917246.

*   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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 20, 2020)
957
Original Estimated Enrollment  ICMJE
 (submitted: June 2, 2016)
900
Estimated Study Completion Date  ICMJE August 21, 2020
Actual Primary Completion Date July 10, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of multiple sclerosis (MS)
  • Relapsing MS (RRMS or SPMS) course
  • At least 1 relapse during the previous 1 year or 2 relapses during the previous 2 years or a positive gadolinium-enhancing MRI scan in previous year
  • EDSS score of 0 to 5.5

Exclusion Criteria:

  • Primary progressive MS
  • Disease duration of more than 10 years in patients with an EDSS score of 2 or less
  • Patients with an active chronic disease of the immune system other than MS
  • Patients at risk of developing or having reactivation of hepatitis
  • Patients with active systemic infections or with neurological findings consistent with PML

Other protocol-defined inclusion/exclusion criteria may apply

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 Argentina,   Australia,   Austria,   Belgium,   Bulgaria,   Canada,   Croatia,   Czechia,   Finland,   France,   Germany,   Hungary,   India,   Italy,   Latvia,   Lithuania,   Mexico,   Norway,   Peru,   Poland,   Portugal,   Russian Federation,   Slovakia,   South Africa,   Spain,   Switzerland,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02792231
Other Study ID Numbers  ICMJE COMB157G2302
2015-005419-33 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis
PRS Account Novartis
Verification Date August 2020

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