Long-term Safety, Tolerability and Effectiveness Study of Ofatumumab in Patients With Relapsing MS

Study Overview
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Brief Summary
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The purpose of this study is to collect long-term safety, tolerability, effectiveness and health outcomes data in eligible subjects who have participated in a Novartis ofatumumab clinical MS study. Vaccination sub-study The purpose of this research sub-study is to find out the effects of ofatumumab on the development of antibody responses to selected vaccines and keyhole limpet hemocyanin (KLH) neo-antigen in subjects with relapsing multiple sclerosis (RMS).

Official Title
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An Open-label, Single Arm, Multi-center Extension Study Evaluating Long-term Safety, Tolerability and Effectiveness of Ofatumumab in Subjects With Relapsing Multiple Sclerosis

Conditions
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Relapsing Multiple Sclerosis

Intervention / Treatment
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* Biological: Ofatumumab
* Biological: Tetanus toxoid (TT) containing vaccine (Td, Tdap)
* Biological: 13-valent pneumococcal conjugate vaccine (13-PCV)
* Biological: 23-valent pneumococcal polysaccharide vaccine (23-PPV)
* Biological: Seasonal Quadrivalent influenza vaccine
* Biological: Keyhole limpet hemocyanin (KLH) neo-antigen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have completed a selected Novartis MS study which dosed ofatumumab 20 mg sc every 4 weeks Written informed consent Exclusion Criteria: Emergence of any clinically significant condition/disease during the previous ofatumumab study in which study participation might result in safety risk for the subject Subjects with active systemic bacterial, viral or fingal infections, or chronic infection (e.g. AIDS) Subjects taking medications prohibited by the protocol Pregnant or nursing (lactating) women Other protocol-defined inclusion/exclusion criteria may apply Vaccination sub-study: Inclusion criteria Informed consent Actively enrolled in the COMB157G2399 Study 12 weeks of continuous treatment within the COMB157G2399 Study prior vaccination history as per protocol-defined Exclusion criteria known hypersensitivity or history of systemic allergic, neurologic or other reactions to vaccines allergies to egg or shellfish any safety findings including low IgG/IgM requiring ofatumumab interruption within 12 weeks prior to vaccination sub-study start any major episode of infection requiring hospitalization or treatment with intravenous antibiotics within 2 weeks of the first vaccination sub-study visit Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ofatumumab<br>Subcutaneous injection | Biological: Ofatumumab<br>* subcutaneous injection of 20 mg ofatumumab every 4 weeks<br>Biological: Tetanus toxoid (TT) containing vaccine (Td, Tdap)<br>* 0.5mL Vial/Syringe Containing 5 limit of flocculation (LF) tetanus toxoid<br>Biological: 13-valent pneumococcal conjugate vaccine (13-PCV)<br>* 0.5mL Vial/Syringe<br>Biological: 23-valent pneumococcal polysaccharide vaccine (23-PPV)<br>* 0.5mL Vial/Syringe<br>Biological: Seasonal Quadrivalent influenza vaccine<br>* Seasonal 2020-2021 0.5mL Vial/Syringe (trivalent may be used where quadrivalent is not available)<br>Biological: Keyhole limpet hemocyanin (KLH) neo-antigen<br>* 1mg Vial<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients that experience an adverse event or abnormal laboratory, vital and/or ECG results and positive suicidiality outcomes |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of relapse rates per year | Annual Relapse Rate (ARR) time calculated as number of confirmed relapses divided by time in study per year and will also be presented for the entire duration | Core studies up to 5 years from first dose of ofatumumab (depending on if first dose was in the core or in this extension study or comparator randomization) | 
| Patients with confirmed 3 and 6 month disability worsening | A confirmed disability worsening is an increase from baseline in Expanded Disability Status Scale (EDSS) score sustained for at last 3, or 6 months EDSS consists of seven functional systems and an ambulation score that are then combined to determine the EDSS steps (ranging from 0 (normal) to 10 (death due to MS)). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, and Cerebral functions (Fatigue contributes). | Duration of the study, approximately 5 years | 
| Patients with confirmed 6, 12 and 24 month disability improvement and improvement until end of study | Confirmed disability improvement is a decrease from baseline in Expanded Disability Status Scale (EDSS) score sustained for at least 6, 12 or 24 months EDSS consists of seven functional systems and an ambulation score that are then combined to determine the EDSS steps (ranging from 0 (normal) to 10 (death due to MS)). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, and Cerebral functions (Fatigue contributes). | Duration of the study, approximately 5 years | 
| Patients with changes in Expanded Disability Status Scale (EDSS) scores | Score changes in Expanded Disability Status Scale (EDSS) over time EDSS consists of seven functional systems and an ambulation score that are then combined to determine the EDSS steps (ranging from 0 (normal) to 10 (death due to MS)). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, and Cerebral functions (Fatigue contributes). | Core studies up to 5 years from first dose of ofatumumab (depending on if first dose was in the core or in this extension study or comparator randomization) | 
| Changes in and time to 6 month confirmed worsening of Symbol Digit Modalities Test Scores | Score changes and confirmed 4-point worsening sustained for 6 months in Symbol Digit Modalities Test (SDMT) scores The Symbol Digit Modalities Test is a neuropsychological, timed test for sustained attention and concentration. 3 versions will be used, alternating at each visit where done. The number of correct responses will be counted for the score. | Duration of the study, approximately 5 years | 
| Changes in the Magnetic Resonance Image (MRI) related to brain volume loss | Percent change from baseline in brain volume loss (BVL) | Core studies up to 5 years from first dose of ofatumumab (depending on if first dose was in the core or in this extension study or comparator randomization) | 
| Changes in the Magnetic Resonance Image (MRI) related to T2 lesions | Number of new or enlarging T2 lesions | Core studies up to 5 years from first dose of ofatumumab (depending on if first dose was in the core or in this extension study or comparator randomization) | 
| Changes in the Magnetic Resonance Image (MRI) related to Gd-enhancing lesions | Total number of Gd-enhancing lesions on all MRI scans adjusted for different time of scan versus follow up time in study | Core studies up to 5 years from first dose of ofatumumab (depending on if first dose was in the core or in this extension study or comparator randomization) | 
| Changes in neurofilament light change serum concentration | Extent of neurofilament light change concentration in blood NfL is a component of the neuronal cytoskeleton and is released into the cerebrospinal fluid and into subsequently blood following neuro-axonal damage | Core studies up to 5 years from first dose of ofatumumab (depending on if first dose was in the core or in this extension study or comparator randomization) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ofatumumab, relapsing multiple sclerosis