Relapsing Multiple Sclerosis
Conditions
Keywords
Relapsing multiple sclerosis, open-label, interventional, efficacy and safety, ofatumumab, China, adult, OMB157
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.
Interventions
BIOLOGICALOfatumumab
Solution for injection in an autoinjector (pre-filled pen) containing 20 mg ofatumumab
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Participant Based Annualized Relapse Rate (ARR) | Baseline up to approximately 12 months | A relapse is an appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event which is present for at least 24 hours in the absence of fever or infection. A relapse is confirmed by the treating physician when it is accompanied by an increase of at least 0.5 on the Expanded Disability Status Scale (EDSS) or an increase of 1 point on two different Functional Systems (FS) of the EDSS or 2 points on one of the FS (excluding Bowel/Bladder or Cerebral FS). Participant-based ARR was calculated by taking the total number of relapses observed for a participant divided by the total number of days in study of that participant and multiplied by 365.25. |
| Time Based Annualized Relapse Rate (ARR) | Baseline up to approximately 12 months | A relapse is an appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event which is present for at least 24 hours in the absence of fever or infection. A relapse is confirmed by the treating physician when it is accompanied by an increase of at least 0.5 on the Expanded Disability Status Scale (EDSS) or an increase of 1 point on two different Functional Systems (FS) of the EDSS or 2 points on one of the FS (excluding Bowel/Bladder or Cerebral FS). Time-based ARR was calculated by taking the total number of relapses observed for all subjects within an age group divided by the total number of days in study of all subjects within the group and multiplied by 365.25 days. |
Countries
China
Participant flow
Recruitment details
Participants were enrolled at 19 sites in China
Pre-assignment details
There were up to 30 days of screening period (day -30 to -1) before first treatment (day 1).
Participants by arm
| Arm | Count |
|---|---|
| Ofatumumab Ofatumumab 20 mg subcutaneous injections at Week 0, 1, 2 and monthly thereafter starting at Week 4 | 99 |
| Total | 99 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Post-treatment follow up period | Participant decision | 3 |
| Treatment period | Participant decision | 3 |
| Treatment period | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Ofatumumab |
|---|---|
| Age, Continuous | 32.6 years STANDARD_DEVIATION 8.98 |
| Age, Customized 18 to 30 years | 46 Participants |
| Age, Customized < 18 years | 0 Participants |
| Age, Customized 31 to 40 years | 38 Participants |
| Age, Customized 41 to 55 years | 15 Participants |
| Age, Customized > 55 years | 0 Participants |
| Number of relapses in 12 to 24 months prior to screening | 0.6 relapses/year STANDARD_DEVIATION 0.8 |
| Number of relapses in the last 12 months prior to screening | 1.1 relapses/year STANDARD_DEVIATION 0.59 |
| Race/Ethnicity, Customized Chinese | 99 Participants |
| Sex: Female, Male Female | 63 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 99 |
| other Total, other adverse events | 69 / 99 |
| serious Total, serious adverse events | 0 / 99 |
Outcome results
Primary
Adjusted Annualized Relapse Rate (ARR) Based on Confirmed Relapses
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).
Time frame: Baseline up to approximately 12 months
Population: Full analysis set (FAS): comprised of all participants who had signed the Informed Consent and who have had received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ofatumumab | Adjusted Annualized Relapse Rate (ARR) Based on Confirmed Relapses | 0.05 relapses per participant-year |
Secondary
Annualized Rate of New or Enlarging T2 Lesions
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.
Time frame: Baseline up to approximately 12 months
Population: Participants in the Full analysis set (FAS) with available results for this outcome measure. FAS comprised all participants who had signed the Informed Consent and who have had received at least one dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ofatumumab | Annualized Rate of New or Enlarging T2 Lesions | Relative to baseline | 1.95 Lesions per participant-year |
| Ofatumumab | Annualized Rate of New or Enlarging T2 Lesions | Relative to Month 3 | 0.21 Lesions per participant-year |
Secondary
Change in T2 Lesion Volume Relative to Baseline
T2 lesion volume as measured by MRI and calculated as post-baseline value - baseline value
Time frame: Baseline up to approximately 12 months
Population: Participants in the Full analysis set (FAS) with available results for this outcome measure. FAS comprised all participants who had signed the Informed Consent and who have had received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ofatumumab | Change in T2 Lesion Volume Relative to Baseline | Month 3 | -0.03 milliliters | Standard Deviation 1.172 |
| Ofatumumab | Change in T2 Lesion Volume Relative to Baseline | Month 12 | -0.32 milliliters | Standard Deviation 1.116 |
Secondary
Number of Adverse Events and Serious Adverse Events
Adverse events and SAEs, including clinically significant laboratory data and vital signs which meet the definition of adverse events
Time frame: Baseline to safety cut-off up to approximately 15.2 months
Population: Safety set (SAF): was identical to FAS in this study. FAS: comprised of all participants who had signed the Informed Consent and who have had received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ofatumumab | Number of Adverse Events and Serious Adverse Events | AEs leading to treatment interruption | 3 Participants |
| Ofatumumab | Number of Adverse Events and Serious Adverse Events | Adverse events (AEs) | 69 Participants |
| Ofatumumab | Number of Adverse Events and Serious Adverse Events | Serious adverse events (SAEs) | 0 Participants |
| Ofatumumab | Number of Adverse Events and Serious Adverse Events | AEs related to treatment | 52 Participants |
| Ofatumumab | Number of Adverse Events and Serious Adverse Events | AEs leading to treatment discontinuation | 0 Participants |
Secondary
Number of Gadolinium (Gd)-Enhancing T1 Lesions Per MRI Scan
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.
Time frame: Baseline up to approximately 12 months
Population: Participants in the Full analysis set (FAS) with available results for this outcome measure. FAS comprised all participants who had signed the Informed Consent and who have had received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ofatumumab | Number of Gadolinium (Gd)-Enhancing T1 Lesions Per MRI Scan | 0.04 lesions per scan |
Secondary
Percentage Change in T2 Lesion Volume Relative to Baseline
T2 lesion volume as measured by MRI and percent change calculated as post baseline value - baseline value divided by baseline value multiplied by 100.
Time frame: Baseline up to approximately 12 months
Population: Participants in the Full analysis set (FAS) with available results for this outcome measure. FAS comprised all participants who had signed the Informed Consent and who have had received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ofatumumab | Percentage Change in T2 Lesion Volume Relative to Baseline | Month 3 | 1.50 Percent change from baseline | Standard Deviation 8.681 |
| Ofatumumab | Percentage Change in T2 Lesion Volume Relative to Baseline | Month 12 | -1.88 Percent change from baseline | Standard Deviation 7.083 |
Other Pre-specified
Participant Based Annualized Relapse Rate (ARR)
A relapse is an appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event which is present for at least 24 hours in the absence of fever or infection. A relapse is confirmed by the treating physician when it is accompanied by an increase of at least 0.5 on the Expanded Disability Status Scale (EDSS) or an increase of 1 point on two different Functional Systems (FS) of the EDSS or 2 points on one of the FS (excluding Bowel/Bladder or Cerebral FS). Participant-based ARR was calculated by taking the total number of relapses observed for a participant divided by the total number of days in study of that participant and multiplied by 365.25.
Time frame: Baseline up to approximately 12 months
Population: Full analysis set (FAS): comprised of all participants who had signed the Informed Consent and who have had received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ofatumumab | Participant Based Annualized Relapse Rate (ARR) | Confirmed relapses | 0.058 relapses per participant-year | Standard Deviation 0.2528 |
| Ofatumumab | Participant Based Annualized Relapse Rate (ARR) | All relapses | 0.090 relapses per participant-year | Standard Deviation 0.3066 |
Other Pre-specified
Time Based Annualized Relapse Rate (ARR)
A relapse is an appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event which is present for at least 24 hours in the absence of fever or infection. A relapse is confirmed by the treating physician when it is accompanied by an increase of at least 0.5 on the Expanded Disability Status Scale (EDSS) or an increase of 1 point on two different Functional Systems (FS) of the EDSS or 2 points on one of the FS (excluding Bowel/Bladder or Cerebral FS). Time-based ARR was calculated by taking the total number of relapses observed for all subjects within an age group divided by the total number of days in study of all subjects within the group and multiplied by 365.25 days.
Time frame: Baseline up to approximately 12 months
Population: Full analysis set (FAS): comprised of all participants who had signed the Informed Consent and who have had received at least one dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ofatumumab | Time Based Annualized Relapse Rate (ARR) | Confirmed relapses | 0.056 relapses per participant-year |
| Ofatumumab | Time Based Annualized Relapse Rate (ARR) | All relapses | 0.089 relapses per participant-year |