A Single Arm Study Evaluating the Efficacy, Safety and Tolerability of Ofatumumab in Patients With Relapsing Multiple Sclerosis

This was a single-arm, multicenter, prospective, study in participants with relapsing multiple sclerosis (MS) who had been previously treated with intravenous (i.v.) anti-CD20 monoclonal antibody (aCD20 mAb) therapy and had received at least 2 consecutive courses of intravenously administered ocrelizumab or rituximab every 6 months, and the last dose was within 4 to 9 months before Baseline/Day 1. In this study, participants could have enrolled only if discontinuing i.v. aCD20 mAb therapy for reasons other than lack of efficacy or due to certain treatment-emergent adverse events (TEAEs). Reasons for switching could have included but were not limited to physician/participant preference, access to commercial drug (e.g. insurance coverage issues), or for other logistical reasons (e.g. geographical relocation, travel, etc.).

Eligible participants received open label ofatumumab 20 mg subcutaneous (s.c.) once monthly for 12 months following initial loading regimen of 20 mg s.c. doses on Days 1, 7, and 14. After the 12-Month Treatment Period there was a Telephone Safety Follow-up call 30 days after last dose of study treatment. The Core phase covered a 28-day Screening Period, 12-Month Treatment Period, and 30-Day Telephone Safety Follow-up.

Upon completing the study, participants could opt to continue ofatumumab therapy through commercial services. Participants who did not continue into the ofatumumab commercial patient services hub within 1 month of the end of study visit or who did not switch to another therapy had to continue into the Post-Treatment Safety Follow-up period, consisting of every 3 month visits including B cell monitoring, until they were able to start on commercial ofatumumab, until they switched to another therapy, or until their B cells were repleted (defined as a B cell concentration greater than the individual participant's baseline value prior to starting the i.v. aCD20 mAb or greater than the lower limit of normal).

Primary Outcome Measures

1. Percentage of Participants With no Change or a Reduction From Baseline in the Number of Gadolinium Enhancing (GdE) Lesions at Month 12 Using Non-responder Imputation
   Magnetic Resonance Imaging (MRI) was used to measure presence of new or reduction in number of gadolinium enhancing T1 lesions. Each MRI scan was previewed by a local neuroradiologist. The quality of each scan performed was assessed by a central MRI reading center and evaluated for quality, completeness and adherence to the protocol. A nonresponder imputation (NRI) for missing data approach was applied. NRI assumes that a participant was a treatment failure, i.e. non-responder, if they did not have a valid Month 12 MRI assessment, or if they discontinued the study prematurely and did not have a valid Month 12 MRI assessment.
2. Percentage of Participants With no Change or a Reduction From Baseline in the Number of Gadolinium Enhancing (GdE) Lesions at Month 12 Based on Observed Data
   Magnetic Resonance Imaging (MRI) was used to measure presence of new or reduction in number of gadolinium enhancing T1 lesions. Each MRI scan was previewed by a local neuroradiologist. The quality of each scan performed was assessed by a central MRI reading center and evaluated for quality, completeness and adherence to the protocol. A sensitivity analysis of the primary endpoint was performed based on an observed data approach.

Secondary Outcome Measures

1. Number of Participants Who Continued Study Treatment From Baseline to Months 6 and 12
   Retention on study treatment from baseline to Month 6 and to Month 12 was based on the number of participants who continued study treatment.
2. Change From Baseline in CD19+ B Cell Counts Obtained by FACS
   Changes from baseline in lymphocytes, including total CD19+ B cell counts and CD20+CD3+ T cell counts, were obtained by fluorescence-activated cell sorting (FACS), which is a specific type of flow cytometry.
3. Change From Baseline in CD20+ CD3+ T Cell Counts Obtained by FACS
   Changes from baseline in lymphocytes, including total CD19+ B cell counts and CD20+CD3+ T cell counts, were obtained by fluorescence-activated cell sorting (FACS), which is a specific type of flow cytometry.
4. Number of Participants With Suicidal Ideation or Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS)
   The Columbia-Suicide Severity Rating Scale (C-SSRS) is a questionnaire that assesses suicidal ideation and suicidal behavior. The suicidal ideation section includes 5 items (Categories 1 to 5), and the suicidal behavior section includes 5 items (Categories 6 to 10). Additionally, there is one item about Self-injurious behavior, without suicidal intent. The C-SSRS was given multiple times throughout the study from baseline up to Month 12. The number of participants who answered 'Yes' to any of the items in C-SSRS at baseline and at any timepoint post-baseline is summarized in this record. Baseline refers to all prior history.
5. Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) Scores at Baseline, Month 6 and Month 12
   The Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) is a 9-item general instrument that measures the major dimensions of satisfaction with a medication. The questionnaire consists of 3 domains: effectiveness (items 1 to 3), convenience (items 4 to 6) and global satisfaction (items 7 to 9). The scores of each domain range from 0 to 100 with higher scores representing higher satisfaction on that domain.
6. Number of Participants With Treatment Emergent Adverse Events (TEAEs)
   TEAEs are defined as any adverse events (AEs) that started on or after the day of first dose of study drug, or before 30 days after the treatment end date, if severity at baseline was missing or if postbaseline severity was greater than baseline severity.