Study of Efficacy and Safety of Ofatumumab in Relapsing Multiple Sclerosis (RMS) Patients in China

Phase 4

Completed

Conditions: Relapsing Multiple Sclerosis

Interventions: Biological: Ofatumumab

Registration Number: NCT05199571

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: The purpose of this study was to evaluate the efficacy and safety of ofatumumab s.c. in adult participants with relapsing multiple sclerosis (RMS) in China.

Detailed Description: This study consisted of three periods, Screening (up to 30 days), Treatment (12 months) and Post-treatment follow-up (6 months). It was an open-label single-arm study so all participants received the study drug. The first dose was administered in the clinic and the remaining doses were administered at home. The doses were administered at Baseline/Week 0, Week 1, Week 2, and followed by subsequent monthly dosing starting at Week 4.

Participants were required to come into the clinic for one screening visit, and 5 visits during the Treatment period for clinical evaluation and lab tests. Participants who completed the 12-month treatment had Post treatment Follow-Up visits at End of Study plus 3 months (EOS + 3M) and EOS + 6M, unless the participants decided to continue with commercially available ofatumumab treatment outside of the study.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 99

Inclusion Criteria

Male or female Chinese aged 18-55 years (inclusive) at their enrollment of the study (signing the study consent form).
Clinical definite diagnosis of RMS according to the 2017 Revised McDonald criteria (Thompson et al 2018, and the documentation prior to their enrollment to the study (signing the study consent form) of:
- Two documented relapses during the past 2 years, or
- One documented relapse during the last year, or
- A positive Gd-enhancing MRI scan during the year prior to Screening. Note: Screening MRI scan may be used if no positive Gd-enhancing scan exists from prior year.
Disability status with an EDSS score of 0 - 5.5 (inclusive) at Screening.
Neurologically stable within 1 month prior to both Screening and Baseline (including no MS relapse in this period).

Exclusion Criteria

Participants with primary progressive MS (PPMS) or secondary progressive MS (SPMS) without disease activity
Participants meeting criteria for neuromyelitis optica spectrum disorder (NMOSD)
Pregnant or nursing (lactating) women
Women of child-bearing potential unless using effective methods of contraception while taking study treatment and for at least 6 months after stopping medication
Participants with an active chronic disease of the immune system other than MS
Participants with neurological findings consistent with PML or confirmed PML
Participants with active hepatitis B disease
Participants with active systemic infections (including but not limited to active COVID-19 infection) or known to have AIDS or to test positive for HIV antibody at Screening
Participants at high risk of developing or having reactivation of syphilis or tuberculosis
Have received any live or live-attenuated vaccines within four weeks prior to first study drug administration
Have been treated with medications as specified or within timeframes specified in the protocol
Any other disease or condition that could interfere with participation in the study according to the study protocol, or with the ability of the participants to cooperate and comply with the study procedures.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ofatumumab	Ofatumumab	Ofatumumab 20 mg subcutaneous injections at Week 0, 1, 2 and monthly thereafter starting at Week 4

Primary Outcome Measures

Name	Time	Method
Adjusted Annualized Relapse Rate (ARR) Based on Confirmed Relapses	Baseline up to approximately 12 months	A confirmed MS relapse is defined as one accompanied by a clinically-relevant change in the EDSS performed by the Independent EDSS rater, i.e. an increase of at least 0.5 points on the EDSS score, or an increase of 1 point on two functional scores or 2 points on one functional score (excluding changes involving bowel/bladder or cerebral functional system). Adjusted ARR was obtained from fitting a negative binomial regression model adjusted for number of relapses in the previous year, baseline number of T1 Gd-enhancing lesions and baseline age as continuous covariates (offset: Natural log of time in study in years).

Secondary Outcome Measures

Name	Time	Method
Number of Adverse Events and Serious Adverse Events	Baseline to safety cut-off up to approximately 15.2 months	Adverse events and SAEs, including clinically significant laboratory data and vital signs which meet the definition of adverse events
Number of Gadolinium (Gd)-Enhancing T1 Lesions Per MRI Scan	Baseline up to approximately 12 months	Obtained from fitting a negative binomial regression model with log-link function, the total number of Gd-enhancing T1 lesions during the treatment period (per participant) as the response variable. The model includes baseline age and number of Gd-enhancing T1 lesions at baseline as continuous covariates. Natural log of the number of MRI scans is used as the offset. MRI scans were performed at screening, month 3 and 12 (end of study) and end of follow up for participants that discontinued treatment. Unscheduled MRIs could be performed at the investigator's judgement.
Annualized Rate of New or Enlarging T2 Lesions	Baseline up to approximately 12 months	Obtained from fitting a negative binomial regression model with log link function, the total number of new or enlarged T2 lesions (relative to baseline/month 3 scan) during the Month 3/treatment period (per participant) as the response variable. Natural log of time from screening scan in years is used as the offset. The model will include baseline age and baseline volume of T2 lesions as continuous covariates.
Change in T2 Lesion Volume Relative to Baseline	Baseline up to approximately 12 months	T2 lesion volume as measured by MRI and calculated as post-baseline value - baseline value
Percentage Change in T2 Lesion Volume Relative to Baseline	Baseline up to approximately 12 months	T2 lesion volume as measured by MRI and percent change calculated as post baseline value - baseline value divided by baseline value multiplied by 100.