Efficacy and Safety of Ofatumumab Compared to Placebo in Patients With Relapsing Multiple Sclerosis Followed by Extended Treatment With Open-label Ofatumumab
Study Details
Study Description
Brief Summary
The study provided efficacy, safety, and pharmacokinetics (PK) data for patients with relapsing multiple sclerosis (RMS) in Japan and the other countries
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: OMB 20 mg Ofatumumab 20 mg subcutaneous injection on Days 1,7, 14 and every 4 weeks for 24 weeks in Core. Core placebo patients received loading dose at Weeks 25 and 26 and then all Extension patients received dose every 4 Weeks up to Week 48. |
Drug: Ofatumumab
Provided in pre-filled syringes for subcutaneous injection (s.c.) administration containing 20 mg ofatumumab (50 mg/mL, 0.4 mL content)
|
| Placebo Comparator: Placebo Placebo subcutaneous injection matching to ofatumumab every 4 weeks for 24 weeks in Core |
Drug: Matching placebo of ofatumumab
Matching placebo in pre-filled syringes
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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 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.
- 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).
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Toon-city | Ehime | Japan | 791-0295 |
| 2 | Novartis Investigative Site | Fukuoka city | Fukuoka | Japan | 812-8582 |
| 3 | Novartis Investigative Site | Sapporo city | Hokkaido | Japan | 063-0005 |
| 4 | Novartis Investigative Site | Morioka | Iwate | Japan | 020-8505 |
| 5 | Novartis Investigative Site | Sendai city | Miyagi | Japan | 980 8574 |
| 6 | Novartis Investigative Site | Sendai city | Miyagi | Japan | 983 8512 |
| 7 | Novartis Investigative Site | Kawagoe | Saitama | Japan | 350 8550 |
| 8 | Novartis Investigative Site | Kodaira | Tokyo | Japan | 187-8551 |
| 9 | Novartis Investigative Site | Shinjuku-ku | Tokyo | Japan | 160 8582 |
| 10 | Novartis Investigative Site | Chiba | Japan | 260 8677 | |
| 11 | Novartis Investigative Site | Niigata | Japan | 951 8520 | |
| 12 | Novartis Investigative Site | Osaka | Japan | 556-0016 | |
| 13 | Novartis Investigative Site | Kazan | Russian Federation | 420021 | |
| 14 | Novartis Investigative Site | Novosibirsk | Russian Federation | 630007 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
None specified.Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- COMB157G1301
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Patients where randomized in a 2:1 ratio to ofatumumab or placebo in the Core Part |
| Arm/Group Title | OMB 20 mg | Placebo - OMB 20 mg |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Period Title: Double-blind Treatment (Core Part) | ||
| STARTED | 43 | 21 |
| COMPLETED | 40 | 19 |
| NOT COMPLETED | 3 | 2 |
| Period Title: Double-blind Treatment (Core Part) | ||
| STARTED | 40 | 19 |
| COMPLETED | 38 | 19 |
| NOT COMPLETED | 2 | 0 |
Baseline Characteristics
| Arm/Group Title | OMB 20 mg | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | 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 | 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 | Total of all reporting groups |
| Overall Participants | 43 | 21 | 64 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
35.0
(9.49)
|
35.5
(8.93)
|
35.2
(9.24)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
36
83.7%
|
19
90.5%
|
55
85.9%
|
| Male |
7
16.3%
|
2
9.5%
|
9
14.1%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| Asian |
21
48.8%
|
11
52.4%
|
32
50%
|
| White |
22
51.2%
|
10
47.6%
|
32
50%
|
| Country of Enrollment (Count of Participants) | |||
| Japan |
21
48.8%
|
11
52.4%
|
32
50%
|
| Russia |
22
51.2%
|
10
47.6%
|
32
50%
|
| Number of relapses in the past 12 months prior to screening (Number of relapses) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Number of relapses] |
1.6
(0.90)
|
1.2
(0.70)
|
1.5
(0.85)
|
| Number of Gd-enhancing T1 lesions (lesions) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [lesions] |
1.3
(2.62)
|
1.0
(1.47)
|
1.2
(2.29)
|
Outcome Measures
| Title | Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Core Part |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (participants with missing baseline or post-baseline MRI data could not be included in the analysis) |
| Arm/Group Title | OMB 20 mg | Placebo |
|---|---|---|
| Arm/Group Description | CORE PART: Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter. | CORE PART: Placebo s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter. |
| Measure Participants | 39 | 20 |
| Number (95% Confidence Interval) [lesions per scan] |
0.0670
|
1.0413
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | OMB 20 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | negative binominal regression model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate ratio |
| Estimated Value | 0.064 | |
| Confidence Interval |
(2-Sided) 95% 0.018 to 0.232 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Japan vs Non-Japan - Core Part |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (participants with missing baseline or post-baseline MRI data could not be included in the analysis) |
| Arm/Group Title | OMB 20 mg Japan | Placebo Japan | OMB 20 mg Non-Japan | Placebo Non-Japan |
|---|---|---|---|---|
| Arm/Group Description | CORE PART: Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter - Japanese patients | CORE PART: Placebo s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter - Japanese patients | CORE PART: Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter - non-Japanese patients | CORE PART: Placebo s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter - non-Japanese patients |
| Measure Participants | 19 | 10 | 20 | 10 |
| Number (95% Confidence Interval) [lesions per scan] |
0.1999
|
1.4682
|
0.0000
|
0.6774
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | OMB 20 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.003 |
| Comments | Statistical significance (2-sided) at the 0.05 level | |
| Method | negative binomial regression | |
| Comments | ||
| Method of Estimation | Estimation Parameter | rate ratio |
| Estimated Value | 0.136 | |
| Confidence Interval |
(2-Sided) 95% 0.036 to 0.513 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | OMB 20 mg Non-Japan, Placebo Non-Japan |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | ||
| Method | negative binominal regression | |
| Comments | Indicates statistical significance (2-sided) at the 0.05 level. | |
| Method of Estimation | Estimation Parameter | rate ratio |
| Estimated Value | 0.000 | |
| Confidence Interval |
(2-Sided) 95% 0.000 to 0.000 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of New or Enlarging T2 Lesions on MRI Scans (Annualized T2 Lesion Rate) - Core Part |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (participants with missing baseline or post-baseline MRI data could not be included in the analysis) |
| Arm/Group Title | OMB 20 mg | Placebo |
|---|---|---|
| Arm/Group Description | 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 | CORE PART: Placebo s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter |
| Measure Participants | 40 | 20 |
| Number (95% Confidence Interval) [T2 lesions per year] |
3.7344
|
13.1533
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | OMB 20 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | negative binominal regression | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate ratio |
| Estimated Value | 0.284 | |
| Confidence Interval |
(2-Sided) 95% 0.130 to 0.620 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Annualized Relapse Rate (ARR) - Core Part |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | OMB 20 mg | Placebo |
|---|---|---|
| Arm/Group Description | CORE PART: Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter | CORE PART: Placebo s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter |
| Measure Participants | 43 | 21 |
| Number (95% Confidence Interval) [relapses in a year] |
0.2640
|
0.6286
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | OMB 20 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.119 |
| Comments | ||
| Method | negative binominal regression | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate ratio |
| Estimated Value | 0.420 | |
| Confidence Interval |
(2-Sided) 95% 0.141 to 1.250 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | OMB 20 mg Japan | OMB 20 mg Non-Japan | OMB 20 mg - All Patients |
|---|---|---|---|
| Arm/Group Description | CORE PART: Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter - Japanese patients | CORE PART: Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter - non - Japanese patients | CORE PART: Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter |
| Measure Participants | 21 | 22 | 43 |
| Baseline n=21,22,43 |
0.03
(0.07)
|
0.9
(.39)
|
.06
(.28)
|
| Day 2 n=21,22,43 |
.43
(.38)
|
.24
(.32)
|
0.33
(.36)
|
| Day 5 n=21,22,43 |
.88
(.40)
|
.60
(.46)
|
.73
(.45)
|
| Day 7 n=21,22,43 |
.84
(.39)
|
0.48
(.34)
|
0.66
(.40)
|
| Day 14 n=21,22,43 |
2.17
(.63)
|
1.71
(1.00)
|
1.93
(.86)
|
| Week 4 n=21,22,43 |
2.69
(.86)
|
2.03
(1.14)
|
2.35
(1.05)
|
| Week 12 n=20,21,41 |
.66
(.62)
|
0.38
(.38)
|
.51
(.53)
|
| Week 24 n=20,20,40 |
.84
(.60)
|
.64
(.46)
|
.74
(.54)
|
| Title | B-cell Counts - Japan vs Non-Japan - Core Part |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety set |
| Arm/Group Title | OMB 20 mg Japan | Placebo Japan | OMB 20 mg Non-Japan | Placebo Non-Japan |
|---|---|---|---|---|
| Arm/Group Description | CORE PART: Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter - Japanese patients | CORE PART: Placebo s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter - Japanese patients | CORE PART: Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter- non-Japanese participants | CORE PART: Placebo s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter - non-Japanese patients |
| Measure Participants | 21 | 11 | 22 | 10 |
| Baseline n=21,11,22,9 |
207
|
205
|
208
|
244
|
| Day 2 n=21,11,21,9 |
3.0
|
319.0
|
14.0
|
292.0
|
| Day 5 n=20,10,14,7 |
3.0
|
216.5
|
8.5
|
257.0
|
| Day 7 n=21,11,22,9 |
3.0
|
209.0
|
3.5
|
228.0
|
| Day 14 n=21,11,19,8 |
2
|
266.0
|
3.0
|
226.0
|
| Week 4 n=21,10,21,8 |
1.0
|
235.5
|
1.0
|
179.5
|
| Week 12 n=20,10,18,9 |
1.0
|
211.0
|
1.0
|
200.0
|
| Week 24 n=19,8,19,8 |
0.0
|
227.5
|
1.0
|
224.5
|
| Title | Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Extension Part |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Extension full analysis set |
| Arm/Group Title | OMB 20 mg | Placebo (Core) - OMB 20 mg (Extension) |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 38 | 19 |
| Number [lesions per scan] |
0.027
|
0.025
|
| Title | Number of New or Enlarging T2 Lesions on MRI Scans (Annualized T2 Lesion Rate) - Extension Part |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Extension full analysis set |
| Arm/Group Title | OMB 20 mg | Placebo (Core) - OMB 20 mg (Extension) |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 40 | 19 |
| Number [T2 lesions per year] |
0.230
|
0.813
|
| Title | Annualized Relapse Rate (ARR) - Extension Part |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Extension full analysis set |
| Arm/Group Title | OMB 20 mg | Placebo (Core) - OMB 20 mg (Extension) |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 40 | 19 |
| Number [relapses in a year] |
0.081
|
0.083
|
| Title | Pharmacokinetic (PK) Concentrations of Ofatumumab - Extension Part |
|---|---|
| Description | Blood samples were collected at the scheduled visits. Summary statistics of PK concentrations from trough samples. |
| Time Frame | Weeks 24, 28, 36, 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Extension full analysis set |
| Arm/Group Title | OMB 20 mg Japan | OMB 20 mg Non-Japan |
|---|---|---|
| Arm/Group Description | 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 - Japanese patients | 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 - non-Japanese patients |
| Measure Participants | 20 | 20 |
| Week 24 |
.84
(.60)
|
.64
(.46)
|
| Week 28 n=19,19 |
0.64
(.36)
|
.61
(.48)
|
| Week 36 n=19,19 |
.97
(.53)
|
.72
(.56)
|
| Week 48 n=18,19 |
1.11
(.56)
|
.94
(.76)
|
| Title | B-cell Counts - Extension Part |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Extension safety set |
| Arm/Group Title | OMB 20 mg | Placebo (Core) - OMB 20 mg (Extension) |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 40 | 19 |
| Week 24 n=40,18 |
0.0
|
1.0
|
| Week 36 n=38, 9 |
0.5
|
1.0
|
| Week 48 n=38,1 |
1.0
|
4.0
|
| Title | Participants With Confirmed Relapse - Core and Extension Parts |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Extension full analysis set |
| Arm/Group Title | OMB 20 mg | Placebo (Core) - OMB 20mg (Extension) |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 40 | 19 |
| Day 1 to Week 12 |
3
7%
|
2
9.5%
|
| >Week 12 to Week 24 |
1
2.3%
|
4
19%
|
| >Week 24 to Week 36 |
1
2.3%
|
0
0%
|
| >Week 36 to Week 48 |
0
0%
|
0
0%
|
Adverse Events
| Time Frame | Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of approximately 638 days | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | OMB 20mg Core | Placebo Core | OMB 20mg Continued | OMB 20mg Switched (From Placebo) | ||||
| Arm/Group Description | CORE PART: Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter | 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 every 4 weeks | EXTENSION PART: Ofatumumab 20 mg s.c. injections at Week 24, Week 25, Week 26 and every 4 weeks thereafter | ||||
All Cause Mortality |
||||||||
| OMB 20mg Core | Placebo Core | OMB 20mg Continued | OMB 20mg Switched (From Placebo) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/43 (0%) | 0/21 (0%) | 0/40 (0%) | 0/19 (0%) | ||||
Serious Adverse Events |
||||||||
| OMB 20mg Core | Placebo Core | OMB 20mg Continued | OMB 20mg Switched (From Placebo) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/43 (2.3%) | 0/21 (0%) | 1/40 (2.5%) | 0/19 (0%) | ||||
| Cardiac disorders | ||||||||
| Cardiac failure acute | 0/43 (0%) | 0/21 (0%) | 1/40 (2.5%) | 0/19 (0%) | ||||
| Nervous system disorders | ||||||||
| Chronic inflammatory demyelinating polyradiculoneuropathy | 1/43 (2.3%) | 0/21 (0%) | 0/40 (0%) | 0/19 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| OMB 20mg Core | Placebo Core | OMB 20mg Continued | OMB 20mg Switched (From Placebo) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 23/43 (53.5%) | 15/21 (71.4%) | 23/40 (57.5%) | 11/19 (57.9%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/43 (0%) | 0/21 (0%) | 0/40 (0%) | 2/19 (10.5%) | ||||
| Lymphadenitis | 0/43 (0%) | 0/21 (0%) | 0/40 (0%) | 1/19 (5.3%) | ||||
| Gastrointestinal disorders | ||||||||
| Constipation | 0/43 (0%) | 3/21 (14.3%) | 1/40 (2.5%) | 1/19 (5.3%) | ||||
| Dental caries | 0/43 (0%) | 2/21 (9.5%) | 2/40 (5%) | 0/19 (0%) | ||||
| Diarrhoea | 0/43 (0%) | 1/21 (4.8%) | 2/40 (5%) | 0/19 (0%) | ||||
| Gastritis | 0/43 (0%) | 0/21 (0%) | 2/40 (5%) | 0/19 (0%) | ||||
| Gastrooesophageal reflux disease | 0/43 (0%) | 0/21 (0%) | 1/40 (2.5%) | 1/19 (5.3%) | ||||
| General disorders | ||||||||
| Injection site reaction | 1/43 (2.3%) | 2/21 (9.5%) | 2/40 (5%) | 1/19 (5.3%) | ||||
| Physical deconditioning | 0/43 (0%) | 0/21 (0%) | 0/40 (0%) | 1/19 (5.3%) | ||||
| Infections and infestations | ||||||||
| Bronchitis | 1/43 (2.3%) | 0/21 (0%) | 1/40 (2.5%) | 1/19 (5.3%) | ||||
| Gastroenteritis | 0/43 (0%) | 0/21 (0%) | 0/40 (0%) | 1/19 (5.3%) | ||||
| Influenza | 1/43 (2.3%) | 1/21 (4.8%) | 2/40 (5%) | 0/19 (0%) | ||||
| Nasopharyngitis | 6/43 (14%) | 4/21 (19%) | 7/40 (17.5%) | 4/19 (21.1%) | ||||
| Oral herpes | 4/43 (9.3%) | 0/21 (0%) | 2/40 (5%) | 0/19 (0%) | ||||
| Rhinitis | 2/43 (4.7%) | 0/21 (0%) | 1/40 (2.5%) | 1/19 (5.3%) | ||||
| Varicella | 0/43 (0%) | 0/21 (0%) | 0/40 (0%) | 1/19 (5.3%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Contusion | 1/43 (2.3%) | 0/21 (0%) | 0/40 (0%) | 1/19 (5.3%) | ||||
| Injection related reaction | 9/43 (20.9%) | 4/21 (19%) | 1/40 (2.5%) | 4/19 (21.1%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 0/43 (0%) | 1/21 (4.8%) | 2/40 (5%) | 0/19 (0%) | ||||
| Glucose urine present | 0/43 (0%) | 0/21 (0%) | 0/40 (0%) | 1/19 (5.3%) | ||||
| Lymphocyte count decreased | 0/43 (0%) | 0/21 (0%) | 0/40 (0%) | 1/19 (5.3%) | ||||
| Weight increased | 0/43 (0%) | 0/21 (0%) | 0/40 (0%) | 1/19 (5.3%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 3/43 (7%) | 1/21 (4.8%) | 0/40 (0%) | 1/19 (5.3%) | ||||
| Myalgia | 0/43 (0%) | 0/21 (0%) | 0/40 (0%) | 1/19 (5.3%) | ||||
| Neck pain | 0/43 (0%) | 2/21 (9.5%) | 0/40 (0%) | 0/19 (0%) | ||||
| Nervous system disorders | ||||||||
| Headache | 2/43 (4.7%) | 1/21 (4.8%) | 1/40 (2.5%) | 1/19 (5.3%) | ||||
| Tension headache | 4/43 (9.3%) | 3/21 (14.3%) | 2/40 (5%) | 0/19 (0%) | ||||
| Psychiatric disorders | ||||||||
| Insomnia | 0/43 (0%) | 3/21 (14.3%) | 1/40 (2.5%) | 0/19 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Endometriosis | 0/43 (0%) | 0/21 (0%) | 0/40 (0%) | 1/19 (5.3%) | ||||
| Menorrhagia | 0/43 (0%) | 0/21 (0%) | 0/40 (0%) | 1/19 (5.3%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Dermatitis allergic | 0/43 (0%) | 0/21 (0%) | 0/40 (0%) | 1/19 (5.3%) | ||||
| Dermatitis contact | 0/43 (0%) | 0/21 (0%) | 0/40 (0%) | 1/19 (5.3%) | ||||
| Pruritus | 0/43 (0%) | 0/21 (0%) | 0/40 (0%) | 1/19 (5.3%) | ||||
| Rash | 1/43 (2.3%) | 0/21 (0%) | 3/40 (7.5%) | 0/19 (0%) | ||||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | + 1 862 778 8300 |
| Novartis.email@Novartis.com |
- COMB157G1301