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

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

Tracking Information

• First Submitted Date: June 2, 2016
• First Posted Date: June 7, 2016
• Last Update Posted Date: August 14, 2020
• Actual Study Start Date: August 26, 2016
• Actual Primary Completion Date: July 10, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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 (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: Efficacy and Safety of Ofatumumab Compared to Teriflunomide in Patients With Relapsing Multiple Sclerosis.
• Official Title: 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: 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: Relapsing Multiple Scelrosis

Intervention

• 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

• 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.

Recruitment Information

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

Eligibility Criteria

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

• 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: 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

Administrative Information

• NCT Number: NCT02792231
• Other Study ID Numbers: COMB157G2302; 2015-005419-33 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Study Sponsor: Novartis Pharmaceuticals
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis

• PRS Account: Novartis
• Verification Date: August 2020