Long-term Safety, Tolerability and Effectiveness Study of Ofatumumab in Patients With Relapsing MS
- Conditions
- Relapsing Multiple Sclerosis
- Interventions
- 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 vaccineBiological: Keyhole limpet hemocyanin (KLH) neo-antigen
- Registration Number
- NCT03650114
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
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).
COVID-19 sub-study:
The purpose of this research sub-study is to explore the immune response following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination in a subset of subjects on long-term ofatumumab 20 mg sc. Note: Novartis is not supplying the SARS-CoV-2 vaccine.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1882
- Must have completed a selected Novartis MS study which dosed ofatumumab 20 mg sc every 4 weeks
- Written informed consent
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Ofatumumab Tetanus toxoid (TT) containing vaccine (Td, Tdap) Subcutaneous injection Ofatumumab Keyhole limpet hemocyanin (KLH) neo-antigen Subcutaneous injection Ofatumumab 23-valent pneumococcal polysaccharide vaccine (23-PPV) Subcutaneous injection Ofatumumab 13-valent pneumococcal conjugate vaccine (13-PCV) Subcutaneous injection Ofatumumab Seasonal Quadrivalent influenza vaccine Subcutaneous injection Ofatumumab Ofatumumab Subcutaneous injection
- Primary Outcome Measures
Name Time Method Number of patients that experience an adverse event or abnormal laboratory, vital and/or ECG results and positive suicidiality outcomes Up to 8 years
- Secondary Outcome Measures
Name Time Method Number of relapse rates per year Data from the core studies through the first 5 years in this study. 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
Patients with confirmed 3 and 6 month disability worsening During the first 5 years of treatment in the study. 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).
Patients with confirmed 6, 12, and 24 month disability improvement and improvement during the first 5 years of the study. During the first 5 years of treatment in the 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).
Patients with changes in Expanded Disability Status Scale (EDSS) scores Data from the core studies through the first 5 years in this study, (depending on if first dose was in the core or in this extension study or comparator randomization) 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).
Changes in and time to 6 month confirmed worsening of Symbol Digit Modalities Test Scores During the first 5 years of the study. 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.
Changes in the Magnetic Resonance Image (MRI) related to brain volume loss Data from the core studies through the first 5 years in this study. Percent change from baseline in brain volume loss (BVL)
Changes in the Magnetic Resonance Image (MRI) related to T2 lesions Data from the core studies through the first 5 years in this study. Number of new or enlarging T2 lesions
Changes in the Magnetic Resonance Image (MRI) related to Gd-enhancing lesions Data from the core studies through the first 5 years in this study. Total number of Gd-enhancing lesions on all MRI scans adjusted for different time of scan versus follow up time in study
Changes in neurofilament light change serum concentration Data from the core studies through the first 5 years in this study. 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
Trial Locations
- Locations (85)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
North Central Neurology Associates PC
🇺🇸Cullman, Alabama, United States
Barrow Neurological Clinics at St Josephs Hospital and MC
🇺🇸Phoenix, Arizona, United States
Fullerton Neuro and Headache Ctr
🇺🇸Fullerton, California, United States
University of California Davis
🇺🇸Sacramento, California, United States
CU Anschutz Med Campus
🇺🇸Aurora, Colorado, United States
Mountain Neuro Research Center PC
🇺🇸Basalt, Colorado, United States
Alpine Clinical Research Center
🇺🇸Boulder, Colorado, United States
Colorado Springs Neurological Associates
🇺🇸Colorado Springs, Colorado, United States
Colorado Neurological Research PC
🇺🇸Denver, Colorado, United States
Scroll for more (75 remaining)University of Alabama at Birmingham🇺🇸Birmingham, Alabama, United States