Relapsing Multiple Sclerosis
Conditions
Keywords
double-blind, placebo controlled, ofatumumab, relapsing multiple sclerosis, Japanese patients, MS, RMS, adult, OMB157
Brief summary
The study provided efficacy, safety, and pharmacokinetics (PK) data for patients with relapsing multiple sclerosis (RMS) in Japan and the other countries
Detailed description
This study had 2 parts: A controlled Core and an open-label Extension. * Core part: A 24-week, randomized, double-blind, placebo controlled, parallel-group, multicenter study evaluated the efficacy, safety and tolerability and PK of ofatumumab in patients with RMS. * Extension part: The Core part was followed by an Extension part in which all patients received open-label ofatumumab. In the Extension part, patients were treated for at least 24 weeks and no longer than 48 weeks. Sixty-four patients were randomized in a 2:1 ratio to ofatumumab or placebo in the Core part; half of the study patients were from Japan and the other half from the other countries.
Interventions
DRUGOfatumumab
Provided in pre-filled syringes for subcutaneous injection (s.c.) administration containing 20 mg ofatumumab (50 mg/mL, 0.4 mL content)
DRUGMatching placebo of ofatumumab
Matching placebo in pre-filled syringes
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of multiple sclerosis (MS) * Relapsing MS (RMS) * At least 1 appearance of a new neurological abnormality or worsening of pre-existing neurological abnormality during the previous 2 years prior to Screening AND an MRI activity (Gd-enhancing T1 lesions or new or enlarging T2 lesions) in brain during the previous 1 year prior to randomization * EDSS score of 0 to 5.5
Exclusion criteria
* Primary progressive MS or SPMS without disease activity * Patients with an active chronic disease of the immune system other than MS * Patients at risk of developing or having reactivation of hepatitis * Patients with active systemic infections or with neurological findings consistent with PML
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Core Part | Baseline up to Week 24 | Total number of Gd-enhancing T1 lesions across scans at Week 12, 16, 20, and 24 were adjusted for the different numbers of scans. This was calculated as a rate for population, rather than at patient level, using a negative binomial regression model with log link. The model included each patient's total number of Gd-enhancing T1 lesions as the response variable, and treatment, region, and subgroup of baseline number of Gd-enhancing T1 lesions (0 or \>=1) as explanatory variables, and logarithm of the patient's number of scans as the offset variable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of New or Enlarging T2 Lesions on MRI Scans (Annualized T2 Lesion Rate) - Core Part | Baseline up to Week 24 | Number of new/enlarging T2 lesions on the last available MRI scan in the Core Part (up to Week 24) relative to baseline, adjusted for different follow-up times. This was calculated as a rate for population, rather than at patient level, using a negative binomial regression model with log-link. The model included each patient's last available number of new or enlarging T2 lesions relative to baseline as the response variable, and treatment, region, subgroup of baseline number of Gd-enhancing T1 lesions (0 or \>=1), and baseline volume of T2 lesions as explanatory variables, and the patient's follow-up time as the offset variable. |
| Annualized Relapse Rate (ARR) - Core Part | Baseline up to Week 24 | ARR was the number of confirmed MS relapses in a year. A confirmed MS relapse was 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). ARR was calculated as a rate for population, rather than at patient-level, using a negative binomial regression model with log-link. The model included each patient's number of confirmed relapses as the response variable, and treatment and region as explanatory variables, and the patient's follow-up time as the offset variable. |
| Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Pre-dose at Baseline, Days 2, 5, 7, 14, Weeks 4, 12, 24 | Blood samples were collected at the scheduled visit. Summary statistics of PK concentrations from trough samples. |
| B-cell Counts - Japan vs Non-Japan - Core Part | Baseline, Days 2, 5, 7, 14, Weeks 4, 12, 24 | Blood samples were collected at the scheduled visits. The CD19+ B-cell counts were measured by the central laboratory. |
| Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Extension Part | Week 24 up to Week 48 | Total number of Gd-enhancing T1 lesions per scan during the Extension Part (up to Week 48) calculated as a rate for population, rather than at patient-level. It was calculated as sum of each patient's total number of Gd-enhancing T1 lesions across scans at Week 36 and 48, divided by sum of each patient's total number of scans. |
| Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Japan vs Non-Japan - Core Part | Baseline up to Week 24 | Total number of Gd-enhancing T1 lesions across scans at Week 12, 16, 20, and 24 were adjusted for the different numbers of scans. This was calculated as a rate for population, rather than at patient level, using a negative binomial regression model with log link. The model included each patient's total number of Gd-enhancing T1 lesions as the response variable, and treatment, region, subgroup of baseline number of Gd-enhancing T1 lesions (0 or \>=1), and the treatment-by-region interaction term as explanatory variables, and the patient's number of scans as the offset variable. |
| Annualized Relapse Rate (ARR) - Extension Part | Week 24 up to Week 48 | ARR was the number of confirmed MS relapses in a year. A confirmed MS relapse was 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). ARR (time-based) was calculated by summing each patient's number of confirmed relapses observed during the Extension part, divided by the total number of each patient's days in a study of all patients during the Extension part, and multiplied by 365.25. |
| Pharmacokinetic (PK) Concentrations of Ofatumumab - Extension Part | Weeks 24, 28, 36, 48 | Blood samples were collected at the scheduled visits. Summary statistics of PK concentrations from trough samples. |
| B-cell Counts - Extension Part | Weeks 24, 36 and 48 | Blood samples were collected at the scheduled visits. The CD19+ B-cell counts were measured by the central laboratory. |
| Participants With Confirmed Relapse - Core and Extension Parts | Baseline up to Week 48 | A confirmed MS relapse was 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). |
| Number of New or Enlarging T2 Lesions on MRI Scans (Annualized T2 Lesion Rate) - Extension Part | Week 24 up to Week 48 | Number of new/enlarging T2 lesions on the last available MRI scan in the Extension Part (up to Week 48) relative to Week 24, adjusted for different follow-up times. Annualized rate of new or enlarging T2 lesions was calculated by dividing the sum of each patient's number of new or enlarging T2 lesions relative to Week 24 by the sum of each patient's number of MRI assessment days during the Extension part, and then multiplying it by 365.25. |
Countries
Japan, Russia
Participant flow
Pre-assignment details
Patients where randomized in a 2:1 ratio to ofatumumab or placebo in the Core Part
Participants by arm
| Arm | Count |
|---|---|
| OMB 20 mg CORE PART: Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter. EXTENSION PART: Ofatumumab 20 mg s.c. injections every 4 weeks | 43 |
| Placebo CORE PART: Placebo s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter. EXTENSION PART: Ofatumumab 20 mg s.c. injections at Week 24, Week 25, Week 26 and every 4 weeks thereafter | 21 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind Treatment (Core Part) | Lack of Efficacy | 1 | 1 |
| Double-blind Treatment (Core Part) | Lost to Follow-up | 1 | 0 |
| Double-blind Treatment (Core Part) | Subject/guardian decision | 1 | 1 |
| Open-label Treatment (Extension Part) | Adverse Event | 2 | 0 |
Baseline characteristics
| Characteristic | OMB 20 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 35.0 years STANDARD_DEVIATION 9.49 | 35.5 years STANDARD_DEVIATION 8.93 | 35.2 years STANDARD_DEVIATION 9.24 |
| Country of Enrollment Japan | 21 Participants | 11 Participants | 32 Participants |
| Country of Enrollment Russia | 22 Participants | 10 Participants | 32 Participants |
| Number of Gd-enhancing T1 lesions | 1.3 lesions STANDARD_DEVIATION 2.62 | 1.0 lesions STANDARD_DEVIATION 1.47 | 1.2 lesions STANDARD_DEVIATION 2.29 |
| Number of relapses in the past 12 months prior to screening | 1.6 Number of relapses STANDARD_DEVIATION 0.9 | 1.2 Number of relapses STANDARD_DEVIATION 0.7 | 1.5 Number of relapses STANDARD_DEVIATION 0.85 |
| Race/Ethnicity, Customized Asian | 21 Participants | 11 Participants | 32 Participants |
| Race/Ethnicity, Customized White | 22 Participants | 10 Participants | 32 Participants |
| Sex: Female, Male Female | 36 Participants | 19 Participants | 55 Participants |
| Sex: Female, Male Male | 7 Participants | 2 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 21 | 0 / 40 | 0 / 19 |
| other Total, other adverse events | 23 / 43 | 15 / 21 | 23 / 40 | 11 / 19 |
| serious Total, serious adverse events | 1 / 43 | 0 / 21 | 1 / 40 | 0 / 19 |
Outcome results
Primary
Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Core Part
Total number of Gd-enhancing T1 lesions across scans at Week 12, 16, 20, and 24 were adjusted for the different numbers of scans. This was calculated as a rate for population, rather than at patient level, using a negative binomial regression model with log link. The model included each patient's total number of Gd-enhancing T1 lesions as the response variable, and treatment, region, and subgroup of baseline number of Gd-enhancing T1 lesions (0 or \>=1) as explanatory variables, and logarithm of the patient's number of scans as the offset variable.
Time frame: Baseline up to Week 24
Population: Full analysis set (participants with missing baseline or post-baseline MRI data could not be included in the analysis)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OMB 20 mg | Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Core Part | 0.0670 lesions per scan |
| Placebo | Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Core Part | 1.0413 lesions per scan |
p-value: <0.00195% CI: [0.018, 0.232]negative binominal regression model
Secondary
Annualized Relapse Rate (ARR) - Core Part
ARR was the number of confirmed MS relapses in a year. A confirmed MS relapse was 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). ARR was calculated as a rate for population, rather than at patient-level, using a negative binomial regression model with log-link. The model included each patient's number of confirmed relapses as the response variable, and treatment and region as explanatory variables, and the patient's follow-up time as the offset variable.
Time frame: Baseline up to Week 24
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OMB 20 mg | Annualized Relapse Rate (ARR) - Core Part | 0.2640 relapses in a year |
| Placebo | Annualized Relapse Rate (ARR) - Core Part | 0.6286 relapses in a year |
p-value: 0.11995% CI: [0.141, 1.25]negative binominal regression
Secondary
Annualized Relapse Rate (ARR) - Extension Part
ARR was the number of confirmed MS relapses in a year. A confirmed MS relapse was 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). ARR (time-based) was calculated by summing each patient's number of confirmed relapses observed during the Extension part, divided by the total number of each patient's days in a study of all patients during the Extension part, and multiplied by 365.25.
Time frame: Week 24 up to Week 48
Population: Extension full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OMB 20 mg | Annualized Relapse Rate (ARR) - Extension Part | 0.081 relapses in a year |
| Placebo | Annualized Relapse Rate (ARR) - Extension Part | 0.083 relapses in a year |
Secondary
B-cell Counts - Extension Part
Blood samples were collected at the scheduled visits. The CD19+ B-cell counts were measured by the central laboratory.
Time frame: Weeks 24, 36 and 48
Population: Extension safety set
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| OMB 20 mg | B-cell Counts - Extension Part | Week 24 n=40,18 | 0.0 cells/uL |
| OMB 20 mg | B-cell Counts - Extension Part | Week 36 n=38, 9 | 0.5 cells/uL |
| OMB 20 mg | B-cell Counts - Extension Part | Week 48 n=38,1 | 1.0 cells/uL |
| Placebo | B-cell Counts - Extension Part | Week 24 n=40,18 | 1.0 cells/uL |
| Placebo | B-cell Counts - Extension Part | Week 36 n=38, 9 | 1.0 cells/uL |
| Placebo | B-cell Counts - Extension Part | Week 48 n=38,1 | 4.0 cells/uL |
Secondary
B-cell Counts - Japan vs Non-Japan - Core Part
Blood samples were collected at the scheduled visits. The CD19+ B-cell counts were measured by the central laboratory.
Time frame: Baseline, Days 2, 5, 7, 14, Weeks 4, 12, 24
Population: Safety set
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| OMB 20 mg | B-cell Counts - Japan vs Non-Japan - Core Part | Day 2 n=21,11,21,9 | 3.0 cells/uL |
| OMB 20 mg | B-cell Counts - Japan vs Non-Japan - Core Part | Day 5 n=20,10,14,7 | 3.0 cells/uL |
| OMB 20 mg | B-cell Counts - Japan vs Non-Japan - Core Part | Week 4 n=21,10,21,8 | 1.0 cells/uL |
| OMB 20 mg | B-cell Counts - Japan vs Non-Japan - Core Part | Day 14 n=21,11,19,8 | 2 cells/uL |
| OMB 20 mg | B-cell Counts - Japan vs Non-Japan - Core Part | Week 24 n=19,8,19,8 | 0.0 cells/uL |
| OMB 20 mg | B-cell Counts - Japan vs Non-Japan - Core Part | Day 7 n=21,11,22,9 | 3.0 cells/uL |
| OMB 20 mg | B-cell Counts - Japan vs Non-Japan - Core Part | Week 12 n=20,10,18,9 | 1.0 cells/uL |
| OMB 20 mg | B-cell Counts - Japan vs Non-Japan - Core Part | Baseline n=21,11,22,9 | 207 cells/uL |
| Placebo | B-cell Counts - Japan vs Non-Japan - Core Part | Week 24 n=19,8,19,8 | 227.5 cells/uL |
| Placebo | B-cell Counts - Japan vs Non-Japan - Core Part | Day 14 n=21,11,19,8 | 266.0 cells/uL |
| Placebo | B-cell Counts - Japan vs Non-Japan - Core Part | Week 4 n=21,10,21,8 | 235.5 cells/uL |
| Placebo | B-cell Counts - Japan vs Non-Japan - Core Part | Day 2 n=21,11,21,9 | 319.0 cells/uL |
| Placebo | B-cell Counts - Japan vs Non-Japan - Core Part | Baseline n=21,11,22,9 | 205 cells/uL |
| Placebo | B-cell Counts - Japan vs Non-Japan - Core Part | Day 5 n=20,10,14,7 | 216.5 cells/uL |
| Placebo | B-cell Counts - Japan vs Non-Japan - Core Part | Week 12 n=20,10,18,9 | 211.0 cells/uL |
| Placebo | B-cell Counts - Japan vs Non-Japan - Core Part | Day 7 n=21,11,22,9 | 209.0 cells/uL |
| OMB 20 mg Non-Japan | B-cell Counts - Japan vs Non-Japan - Core Part | Week 4 n=21,10,21,8 | 1.0 cells/uL |
| OMB 20 mg Non-Japan | B-cell Counts - Japan vs Non-Japan - Core Part | Week 12 n=20,10,18,9 | 1.0 cells/uL |
| OMB 20 mg Non-Japan | B-cell Counts - Japan vs Non-Japan - Core Part | Day 2 n=21,11,21,9 | 14.0 cells/uL |
| OMB 20 mg Non-Japan | B-cell Counts - Japan vs Non-Japan - Core Part | Week 24 n=19,8,19,8 | 1.0 cells/uL |
| OMB 20 mg Non-Japan | B-cell Counts - Japan vs Non-Japan - Core Part | Day 5 n=20,10,14,7 | 8.5 cells/uL |
| OMB 20 mg Non-Japan | B-cell Counts - Japan vs Non-Japan - Core Part | Baseline n=21,11,22,9 | 208 cells/uL |
| OMB 20 mg Non-Japan | B-cell Counts - Japan vs Non-Japan - Core Part | Day 7 n=21,11,22,9 | 3.5 cells/uL |
| OMB 20 mg Non-Japan | B-cell Counts - Japan vs Non-Japan - Core Part | Day 14 n=21,11,19,8 | 3.0 cells/uL |
| Placebo Non-Japan | B-cell Counts - Japan vs Non-Japan - Core Part | Week 24 n=19,8,19,8 | 224.5 cells/uL |
| Placebo Non-Japan | B-cell Counts - Japan vs Non-Japan - Core Part | Baseline n=21,11,22,9 | 244 cells/uL |
| Placebo Non-Japan | B-cell Counts - Japan vs Non-Japan - Core Part | Day 2 n=21,11,21,9 | 292.0 cells/uL |
| Placebo Non-Japan | B-cell Counts - Japan vs Non-Japan - Core Part | Day 5 n=20,10,14,7 | 257.0 cells/uL |
| Placebo Non-Japan | B-cell Counts - Japan vs Non-Japan - Core Part | Day 7 n=21,11,22,9 | 228.0 cells/uL |
| Placebo Non-Japan | B-cell Counts - Japan vs Non-Japan - Core Part | Day 14 n=21,11,19,8 | 226.0 cells/uL |
| Placebo Non-Japan | B-cell Counts - Japan vs Non-Japan - Core Part | Week 4 n=21,10,21,8 | 179.5 cells/uL |
| Placebo Non-Japan | B-cell Counts - Japan vs Non-Japan - Core Part | Week 12 n=20,10,18,9 | 200.0 cells/uL |
Secondary
Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Extension Part
Total number of Gd-enhancing T1 lesions per scan during the Extension Part (up to Week 48) calculated as a rate for population, rather than at patient-level. It was calculated as sum of each patient's total number of Gd-enhancing T1 lesions across scans at Week 36 and 48, divided by sum of each patient's total number of scans.
Time frame: Week 24 up to Week 48
Population: Extension full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OMB 20 mg | Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Extension Part | 0.027 lesions per scan |
| Placebo | Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Extension Part | 0.025 lesions per scan |
Secondary
Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Japan vs Non-Japan - Core Part
Total number of Gd-enhancing T1 lesions across scans at Week 12, 16, 20, and 24 were adjusted for the different numbers of scans. This was calculated as a rate for population, rather than at patient level, using a negative binomial regression model with log link. The model included each patient's total number of Gd-enhancing T1 lesions as the response variable, and treatment, region, subgroup of baseline number of Gd-enhancing T1 lesions (0 or \>=1), and the treatment-by-region interaction term as explanatory variables, and the patient's number of scans as the offset variable.
Time frame: Baseline up to Week 24
Population: Full analysis set (participants with missing baseline or post-baseline MRI data could not be included in the analysis)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OMB 20 mg | Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Japan vs Non-Japan - Core Part | 0.1999 lesions per scan |
| Placebo | Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Japan vs Non-Japan - Core Part | 1.4682 lesions per scan |
| OMB 20 mg Non-Japan | Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Japan vs Non-Japan - Core Part | 0.0000 lesions per scan |
| Placebo Non-Japan | Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Japan vs Non-Japan - Core Part | 0.6774 lesions per scan |
p-value: 0.00395% CI: [0.036, 0.513]negative binomial regression
p-value: <0.00195% CI: [0, 0]negative binominal regression
Secondary
Number of New or Enlarging T2 Lesions on MRI Scans (Annualized T2 Lesion Rate) - Core Part
Number of new/enlarging T2 lesions on the last available MRI scan in the Core Part (up to Week 24) relative to baseline, adjusted for different follow-up times. This was calculated as a rate for population, rather than at patient level, using a negative binomial regression model with log-link. The model included each patient's last available number of new or enlarging T2 lesions relative to baseline as the response variable, and treatment, region, subgroup of baseline number of Gd-enhancing T1 lesions (0 or \>=1), and baseline volume of T2 lesions as explanatory variables, and the patient's follow-up time as the offset variable.
Time frame: Baseline up to Week 24
Population: Full analysis set (participants with missing baseline or post-baseline MRI data could not be included in the analysis)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OMB 20 mg | Number of New or Enlarging T2 Lesions on MRI Scans (Annualized T2 Lesion Rate) - Core Part | 3.7344 T2 lesions per year |
| Placebo | Number of New or Enlarging T2 Lesions on MRI Scans (Annualized T2 Lesion Rate) - Core Part | 13.1533 T2 lesions per year |
p-value: 0.00295% CI: [0.13, 0.62]negative binominal regression
Secondary
Number of New or Enlarging T2 Lesions on MRI Scans (Annualized T2 Lesion Rate) - Extension Part
Number of new/enlarging T2 lesions on the last available MRI scan in the Extension Part (up to Week 48) relative to Week 24, adjusted for different follow-up times. Annualized rate of new or enlarging T2 lesions was calculated by dividing the sum of each patient's number of new or enlarging T2 lesions relative to Week 24 by the sum of each patient's number of MRI assessment days during the Extension part, and then multiplying it by 365.25.
Time frame: Week 24 up to Week 48
Population: Extension full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OMB 20 mg | Number of New or Enlarging T2 Lesions on MRI Scans (Annualized T2 Lesion Rate) - Extension Part | 0.230 T2 lesions per year |
| Placebo | Number of New or Enlarging T2 Lesions on MRI Scans (Annualized T2 Lesion Rate) - Extension Part | 0.813 T2 lesions per year |
Secondary
Participants With Confirmed Relapse - Core and Extension Parts
A confirmed MS relapse was 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).
Time frame: Baseline up to Week 48
Population: Extension full analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| OMB 20 mg | Participants With Confirmed Relapse - Core and Extension Parts | Day 1 to Week 12 | 3 Participants |
| OMB 20 mg | Participants With Confirmed Relapse - Core and Extension Parts | >Week 12 to Week 24 | 1 Participants |
| OMB 20 mg | Participants With Confirmed Relapse - Core and Extension Parts | >Week 24 to Week 36 | 1 Participants |
| OMB 20 mg | Participants With Confirmed Relapse - Core and Extension Parts | >Week 36 to Week 48 | 0 Participants |
| Placebo | Participants With Confirmed Relapse - Core and Extension Parts | >Week 36 to Week 48 | 0 Participants |
| Placebo | Participants With Confirmed Relapse - Core and Extension Parts | Day 1 to Week 12 | 2 Participants |
| Placebo | Participants With Confirmed Relapse - Core and Extension Parts | >Week 24 to Week 36 | 0 Participants |
| Placebo | Participants With Confirmed Relapse - Core and Extension Parts | >Week 12 to Week 24 | 4 Participants |
Secondary
Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part
Blood samples were collected at the scheduled visit. Summary statistics of PK concentrations from trough samples.
Time frame: Pre-dose at Baseline, Days 2, 5, 7, 14, Weeks 4, 12, 24
Population: Full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OMB 20 mg | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Baseline n=21,22,43 | 0.03 ug/mL | Standard Deviation 0.07 |
| OMB 20 mg | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Day 2 n=21,22,43 | .43 ug/mL | Standard Deviation 0.38 |
| OMB 20 mg | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Day 5 n=21,22,43 | .88 ug/mL | Standard Deviation 0.4 |
| OMB 20 mg | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Day 7 n=21,22,43 | .84 ug/mL | Standard Deviation 0.39 |
| OMB 20 mg | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Day 14 n=21,22,43 | 2.17 ug/mL | Standard Deviation 0.63 |
| OMB 20 mg | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Week 4 n=21,22,43 | 2.69 ug/mL | Standard Deviation 0.86 |
| OMB 20 mg | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Week 12 n=20,21,41 | .66 ug/mL | Standard Deviation 0.62 |
| OMB 20 mg | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Week 24 n=20,20,40 | .84 ug/mL | Standard Deviation 0.6 |
| Placebo | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Day 5 n=21,22,43 | .60 ug/mL | Standard Deviation 0.46 |
| Placebo | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Week 12 n=20,21,41 | 0.38 ug/mL | Standard Deviation 0.38 |
| Placebo | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Day 7 n=21,22,43 | 0.48 ug/mL | Standard Deviation 0.34 |
| Placebo | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Day 14 n=21,22,43 | 1.71 ug/mL | Standard Deviation 1 |
| Placebo | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Week 4 n=21,22,43 | 2.03 ug/mL | Standard Deviation 1.14 |
| Placebo | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Baseline n=21,22,43 | 0.9 ug/mL | Standard Deviation 0.39 |
| Placebo | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Day 2 n=21,22,43 | .24 ug/mL | Standard Deviation 0.32 |
| Placebo | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Week 24 n=20,20,40 | .64 ug/mL | Standard Deviation 0.46 |
| OMB 20 mg Non-Japan | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Day 5 n=21,22,43 | .73 ug/mL | Standard Deviation 0.45 |
| OMB 20 mg Non-Japan | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Day 2 n=21,22,43 | 0.33 ug/mL | Standard Deviation 0.36 |
| OMB 20 mg Non-Japan | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Baseline n=21,22,43 | .06 ug/mL | Standard Deviation 0.28 |
| OMB 20 mg Non-Japan | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Day 7 n=21,22,43 | 0.66 ug/mL | Standard Deviation 0.4 |
| OMB 20 mg Non-Japan | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Week 12 n=20,21,41 | .51 ug/mL | Standard Deviation 0.53 |
| OMB 20 mg Non-Japan | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Week 4 n=21,22,43 | 2.35 ug/mL | Standard Deviation 1.05 |
| OMB 20 mg Non-Japan | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Day 14 n=21,22,43 | 1.93 ug/mL | Standard Deviation 0.86 |
| OMB 20 mg Non-Japan | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part | Week 24 n=20,20,40 | .74 ug/mL | Standard Deviation 0.54 |
Secondary
Pharmacokinetic (PK) Concentrations of Ofatumumab - Extension Part
Blood samples were collected at the scheduled visits. Summary statistics of PK concentrations from trough samples.
Time frame: Weeks 24, 28, 36, 48
Population: Extension full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OMB 20 mg | Pharmacokinetic (PK) Concentrations of Ofatumumab - Extension Part | Week 24 | .84 ug/mL | Standard Deviation 0.6 |
| OMB 20 mg | Pharmacokinetic (PK) Concentrations of Ofatumumab - Extension Part | Week 28 n=19,19 | 0.64 ug/mL | Standard Deviation 0.36 |
| OMB 20 mg | Pharmacokinetic (PK) Concentrations of Ofatumumab - Extension Part | Week 36 n=19,19 | .97 ug/mL | Standard Deviation 0.53 |
| OMB 20 mg | Pharmacokinetic (PK) Concentrations of Ofatumumab - Extension Part | Week 48 n=18,19 | 1.11 ug/mL | Standard Deviation 0.56 |
| Placebo | Pharmacokinetic (PK) Concentrations of Ofatumumab - Extension Part | Week 48 n=18,19 | .94 ug/mL | Standard Deviation 0.76 |
| Placebo | Pharmacokinetic (PK) Concentrations of Ofatumumab - Extension Part | Week 24 | .64 ug/mL | Standard Deviation 0.46 |
| Placebo | Pharmacokinetic (PK) Concentrations of Ofatumumab - Extension Part | Week 36 n=19,19 | .72 ug/mL | Standard Deviation 0.56 |
| Placebo | Pharmacokinetic (PK) Concentrations of Ofatumumab - Extension Part | Week 28 n=19,19 | .61 ug/mL | Standard Deviation 0.48 |