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

Tracking Information
First Submitted Date ICMJE	June 2, 2016
First Posted Date ICMJE	June 7, 2016
Last Update Posted Date	September 11, 2018
Actual Study Start Date ICMJE	August 26, 2016
Estimated Primary Completion Date	May 15, 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	Complete list of historical versions of study NCT02792231 on ClinicalTrials.gov Archive Site
Current 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
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	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	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	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 *	Not Provided
* 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	Recruiting
Estimated Enrollment ICMJE; (submitted: June 2, 2016)	900
Original Estimated Enrollment ICMJE	Same as current
Estimated Study Completion Date	May 15, 2019
Estimated Primary Completion Date	May 15, 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	Sexes Eligible for Study: All
Ages	18 Years to 55 Years (Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact: Novartis Pharmaceuticals 1-888-669-6682 Contact: Novartis Pharmaceuticals +41613241111
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	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	September 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP