Relapsing Multiple Sclerosis
Conditions
Keywords
RMS, MS, multiple sclerosis, relapsing multiple sclerosis, OMB157, adult, secondary progressive MS, SPMS
Brief summary
Open-label study to evaluate the effectiveness of treatment with ofatumumab in subjects transitioning from any fumarate-based RMS approved therapy or fingolimod due to breakthrough disease.
Detailed description
This was a single arm, prospective, multicentre and open-label, 96-week study to evaluate the treatment effectiveness of ofatumumab (OMB) in subjects with relapsing multiple sclerosis (RMS) transitioning from fumarate-based RMS approved therapies, such as dimethyl fumarate (DMF), diroximel fumarate (DRF), and monomethyl fumarate (MMF), or fingolimod due to breakthrough disease activity.
Interventions
BIOLOGICALOfatumumab
Subjects will receive ofatumumab injections in an autoinjector (AI) for subcutaneous administration containing 20 mg ofatumumab (50 mg/ml, 0.4 ml content)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of MS according to the 2017 Revised McDonald criteria * Relapsing MS: relapsing forms of MS (RMS) including RMS and secondary progressive MS (SPMS) * Disability status at screening defined by Expanded Disability Status Scale (EDSS) score of 0 to 4 (inclusive) * MS treatment history with a maximum of 3 Disease Modifying Therapies (DMTs), where all fumarates are considered as one DMT * Subject transitioning from either any fumarate-based RMS approved therapies, such as dimethyl fumarate (DMF) or diroximel fumarate (DRF), or fingolimod which was administered for a period of at least 6 months, as their last DMT before first study drug administration * Breakthrough disease activity while the participant was adequately using fumarates or fingolimod prior to transitioning for a minimum of 6 months as evidenced by one or more clinically reported relapses or one or more signs of Magnetic Resonance Imaging (MRI) activity (e.g. Gd+ enhancement, new or enlarging T2 lesions) * Neurologically stable within one month prior to first study drug administration
Exclusion criteria
* Subjects with primary progressive MS or SPMS without disease activity * Subjects meeting criteria for neuromyelitis optica * Disease duration of more than 10 years since diagnosis * Pregnant or nursing (lactating) women * Women of child-bearing potential unless they are using highly effective forms of contraception during dosing and for at least 6 months after stopping study medication * Subjects with active chronic disease of the immune system other than MS or with immunodeficiency syndrome * Subjects with active systemic bacterial, fungal or viral infections (such as hepatitis, HIV, COVID-19), or known to have Acquired Immunodeficiency Syndrome (AIDS) * Subjects with neurological symptoms consistent with Progressive Multifocal Leukoencephalopathy (PML) or with confirmed PML * Subjects at risk of developing or having reactivation of syphilis or tuberculosis (e.g. subjects with known exposure to, or history of syphilis, or active or latent tuberculosis, even if previously treated), as confirmed by medical history or per local practice * Subjects with active hepatitis B and C disease, assessed locally * Have received any live or live-attenuated vaccines within 4 weeks prior to first study drug administration * Have been treated with medications as specified or within timeframes specified (e.g. corticosteroids, ofatumumab, rituximab, ocrelizumab, alemtuzumab, natalizumab, daclizumab, cyclophosphamide, teriflunomide etc.) * Subjects suspected of not being able or willing to cooperate or comply with study protocol requirements in the opinion of the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Relapse Rate (ARR) | Up to 96 weeks from baseline | 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). Confirmed relapses are those accompanied by a clinically relevant change in the expanded disability status scale (EDSS). ARR was estimated from fitting a negative binomial regression model with log-link, and adjusted for prior MS therapies as a factor, number of relapses in previous year, baseline EDSS, baseline number of T1 Gd-enhancing lesions and the subject's age at baseline as covariates. The primary analysis describes the ARR with one-sided 95% confidence bound and test for null hypothesis (H0): ARR \>=0.18 versus alternative hypothesis (H1): ARR\<0.18. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From treatment day 1 to 100 days after last treatment up to approximatelly 26.6 months | Number of of participants with treatment emergent AEs and SAEs including injection related reactions, abnormal laboratory results or vital signs reported and qualifying as AEs. |
Countries
Argentina, Australia, Austria, Belgium, Bulgaria, Canada, Czechia, Estonia, Germany, Greece, Hungary, Italy, Latvia, Lebanon, Mexico, Norway, Poland, Portugal, Russia, Saudi Arabia, Slovakia, Slovenia, Spain, Switzerland, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled in 27 countries.
Pre-assignment details
666 subjects were screened and 562 subjects were enrolled. Study had an up to 60 days screening period including baseline.
Participants by arm
| Arm | Count |
|---|---|
| Ofatumumab Ofatumumab 20 mg subcutaneous injections every 4 weeks, following loading of 3 doses in the first 14 days | 562 |
| Total | 562 |
Baseline characteristics
| Characteristic | Ofatumumab |
|---|---|
| Age, Continuous | 36.3 years STANDARD_DEVIATION 9.65 |
| Age, Customized 18 to 30 years | 185 Participants |
| Age, Customized 31 to 40 years | 181 Participants |
| Age, Customized 41 to 55 years | 190 Participants |
| Age, Customized >55 years | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 68 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 480 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 14 Participants |
| Number of relapses in the last 12 months prior to screening | 0.9 relapses STANDARD_DEVIATION 0.71 |
| Number of relapses in the last 12 to 24 months prior to screening | 0.8 relapses STANDARD_DEVIATION 1.04 |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 550 Participants |
| Sex: Female, Male Female | 369 Participants |
| Sex: Female, Male Male | 193 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 562 |
| other Total, other adverse events | 466 / 562 |
| serious Total, serious adverse events | 34 / 562 |
Outcome results
Primary
Annualized Relapse Rate (ARR)
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). Confirmed relapses are those accompanied by a clinically relevant change in the expanded disability status scale (EDSS). ARR was estimated from fitting a negative binomial regression model with log-link, and adjusted for prior MS therapies as a factor, number of relapses in previous year, baseline EDSS, baseline number of T1 Gd-enhancing lesions and the subject's age at baseline as covariates. The primary analysis describes the ARR with one-sided 95% confidence bound and test for null hypothesis (H0): ARR \>=0.18 versus alternative hypothesis (H1): ARR\<0.18.
Time frame: Up to 96 weeks from baseline
Population: The Full Analysis Set (FAS) comprises all subjects to whom study treatment has been assigned and who received at least one dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ofatumumab | Annualized Relapse Rate (ARR) | 0.06 relapses/ participant-year |
Comparison: The null hypothesis (H0): ARR \>= 0.18p-value: <0.0001negative binomial regresion
Secondary
Number of of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of of participants with treatment emergent AEs and SAEs including injection related reactions, abnormal laboratory results or vital signs reported and qualifying as AEs.
Time frame: From treatment day 1 to 100 days after last treatment up to approximatelly 26.6 months
Population: The Safety Set (SAF) includes all subjects who received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ofatumumab | Number of of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE causing study treatment interruption | 33 Participants |
| Ofatumumab | Number of of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events (AEs) | 509 Participants |
| Ofatumumab | Number of of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious Adverse Events (SAEs) | 33 Participants |
| Ofatumumab | Number of of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Treatment related AEs | 374 Participants |
| Ofatumumab | Number of of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE causing study treatment discontinuation | 5 Participants |