Pemphigus Vulgaris
Conditions
Keywords
Pemphigus, MAB, autoimmune disorder, human CD20 antigen, subcutaneous, vulgaris, Phase 3, monoclonal antibody, ofatumumab, PV, rare disease, OMB157, adult
Brief summary
Pemphigus vulgaris (PV) is a rare, chronic, debilitating, and potentially life-threatening autoimmune disorder that is characterized by mucocutaneous blisters. Ofatumumab is a novel monoclonal antibody (mAb) that specifically binds to the human CD20 antigen, which is expressed only in B lymphocytes. The purpose of this study was to evaluate the efficacy, tolerability, and safety of ofatumumab injection for subcutaneous use (ofatumumab SC) 20 milligrams (mg) administered once in every 4 weeks, (with an additional 20 mg loading dose \[i.e. 40 mg total\] at both Week 0 and Week 4) in subjects with PV. It was anticipated that with sustained B-cell depletion in the presence of ofatumumab SC, and the resultant reduction of pathogenic anti Dsg (desmoglein) autoantibodies in PV, that clinical remission of the disease would result.
Detailed description
Novartis terminated the development of the PV program and this study was terminated for non-safety reasons
Interventions
BIOLOGICALOfatumumab
Ofatumumab (human monoclonal antibody) was provided in prefilled glass syringes initial syringes contained 0.6ml (60mg) of concentration 100 mg/m: drug product subsequently modified to 0.4 mL (20mg) concentration (50mg/ML) drug product
BIOLOGICALPlacebo
Placebo to match the active doses will consist of prefilled glass syringes filled with normal saline.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Adults (18 through 70 years of age) with clinically-documented diagnosis of PV for \>2 months and \<10 years. * History of biopsy consistent with PV (Hematoxylin and Eosin staining and direct immunofluorescence). If no history, a biopsy may be performed during the Screening Period. * At least 1 previous episode of a failed steroid taper (ie, disease flare/relapse) at a prednisone/prednisolone dose \>10 mg/day. The following criteria must have been met as evidence of disease severity at the time of the failed steroid taper: a) A Pemphigus Severity of Clinical Disease score of moderate (2) or severe (3) (may be historical/retrospective assessment). b) Required a treatment change at the time of the failed steroid taper of at least one of the following: i) A steroid increase to \>=20 mg/day OR ii) The addition of immunosuppressive/immunomodulatory agent/treatment OR iii) A dose increase of immunosuppressive/immunomodulatory agent/treatment * Screening anti-Dsg antibodies consistent with a diagnosis of PV (ie, elevated antiDsg3 antibodies). * Has initiated and received a stable dose of prednisone/prednisolone from a minimum of 20 mg/day (example: 0.25 mg/kg/day for an 80 kg person) up to a maximum of 120 mg/day or 1.5 mg/kg/day (whichever is higher) for \>=2 weeks prior to randomization. * Has exhibited PV disease control, defined as no new lesions for \>=2 weeks. * A female subject is eligible to enter the study if she: Is of non-child bearing potential, who is either surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or post-hysterectomy) or is postmenopausal without menses for \>2 years. Women who are \<2 years postmenopausal are required to have menopausal status confirmed by follicle-stimulating hormone (FSH) and estradiol levels at the screening evaluation. If FSH and estradiol levels do not provide confirmation of menopause, subject will be considered to be of childbearing potential.
Exclusion criteria
* Diagnosis of pemphigus foliaceus, paraneoplastic pemphigus, or other autoimmune blistering disease (other than pemphigus vulgaris). * Past or current history of hypersensitivity to components of the investigational product or medically significant adverse effects (including allergic reactions) from cetirizine (or antihistamine equivalent) or paracetamol/acetaminophen. * Prior treatment with rituximab without achieving disease control within 6 months of initiating rituximab dosing. * Prior treatment with immunosuppressant or immunomodulation agents within the protocol specified periods * Evidence or history of clinically significant infections For Japan: Evidence or history of clinically significant infection or medical condition including: Pneumocystis pneumonia or interstitial pneumonia * Past or current malignancy, except for cervical carcinoma Stage 1B or less, noninvasive basal cell and squamous cell skin carcinoma and cancer diagnoses with a duration of complete response (remission) \>5 years * Significant concurrent, uncontrolled medical condition that could affect the subject's safety, impair the subject's reliable participation in the study, impair the evaluation of endpoints, or necessitate the use of medication not allowed by the protocol. This includes subjects who require any systemic steroid treatment for a concurrent medical condition (other than pemphigus vulgaris). * Use of an investigational drug or other experimental therapy within 4 weeks, 5 pharmacokinetic half-lives, or the duration of biological effect (whichever is longer) prior to Screening. * Electrocardiogram (ECG) showing a clinically significant abnormality or showing a QTc interval ≥450 msec (≥480 msec for subjects with a bundle branch block) * Woman who is breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Experienced Sustained Remission on Minimal Steroid Therapy | Baseline up to approximately 60 weeks | Sustained remission = time from randomization to the time of the subject's initial reduction of prednisone/prednisolone dose to \<=10 mg/day and maintenance of a dose \<=10 mg/day with no new or nonhealing lesions for \>=8 weeks and maintenance of the status until Week 60. |
| Duration of Remission on Minimal Steroid Therapy | Baseline up to approximately 60 weeks | Sum of all periods of absence of new or nonhealing lesions while on an oral prednisone/prednisolone dose of \<=10 mg/day up to Week 60 was assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Achieving Remission While Off Steroid Therapy by Week 60 | Baseline up to approximately 60 weeks | Percentage of subjects with initial reduction of all steroids for \>=8 weeks with an absence of new or nonhealing (established) lesions by Week 60 were to be assessed. All subjects remained on prednisone/prednisolone so this endpoint could not be analyzed.Time to remission off steroid therapy also could not be analyzed |
| Number of Days a Subject Maintained Minimal Steroid Therapy by Week 60. | Baseline up to approximately 60 weeks | Number of days a subject maintained minimal steroid therapy (an oral prednisone/prednisolone dose of ≤10 mg/day in the absence of new or nonhealing lesions) by Week 60. |
| Time to Initial Flare/Relapse by Week 60 | Baseline up to approximately 60 weeks | Time from randomization to the time of appearance of \>=3 new lesions within 1 month that did not heal spontaneously within 1 week, or to the time when there was an extension of lesions that were present at the randomization by Week 60 was assessed |
| Percentage of Participants With no Flare/Relapse by Week 60 | Baseline up to approximately 60 weeks | Percentage of participants achieving absence of new or nonhealing lesions while on an oral prednisone/prednisolone dose of \<=10 mg/day and did not subsequently have a appearance of \>=3 new lesions within 1 month that did not heal spontaneously within 1 week, or to the time when there was an extension of lesions that were present at the randomization by Week 60 was assessed |
| Plasma Trough Concentrations of Ofatumumab | 4 hours post baseline, Days 1-4,7,14, Weeks 4,8,12,16,20,24,36,48,52,56, up to approximately 60 weeks | Only plasma (trough) concentrations of ofatumumab were presented |
| Percentage of Subjects Achieving Remission on Minimal Steroid Therapy at Week 60 | Week 60 | Percentage of subjects who achieved absence of new or nonhealing lesions while on an oral prednisone/prednisolone dose of \<=10 mg/day for \> or = 8 weeks at Week 60 was assessed. Time to remission was not estimable. |
| Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G | Baseline up to approximately 60 weeks | Assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response |
| Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M | Baseline up to approximately 60 weeks | Assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response |
| Largest Mean Decrease From Baseline for Immunoglobulin A, G and M | Baseline up to approximately 60 weeks | Immunoglobulins A, G and M were assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response |
| Change From Baseline for CD19+ B Cell Count | Baseline up to approximately 60 weeks | CD19+ B cell count will be performed using Flow Cytometry |
| Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A | Baseline up to approximately 60 weeks | Assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response |
| Time to Remission While on Minimal Steroid Therapy by Week 60. | Baseline up to approximately 60 weeks | Time from randomization to the time of the subject's initial reduction of prednisone/prednisolone dose to \<=10 mg/day and maintained dose at \<=10 mg/day with no new or nonhealing lesions for \>=8 weeks by Week 60 was assessed |
Countries
Australia, Greece, Israel, Italy, Japan, Poland, Romania, United States
Participant flow
Pre-assignment details
Sixty-nine subjects were screened.
Participants by arm
| Arm | Count |
|---|---|
| Ofatumumab Subject will receive subcutaneous administration of ofatumumab 20 mg once every 4 weeks through Week 56, with an additional 20 mg dose (that is 40mg total) at both Week 0 and Week 4. | 17 |
| Placebo Subject will receive subcutaneous administration of matching placebo of ofatumumab once every 4 weeks through Week 56, with an additional dose at both Week 0 and Week 4. | 18 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Study closed/terminated | 14 | 15 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | Ofatumumab |
|---|---|---|---|
| Age, Continuous | 47.1 years STANDARD_DEVIATION 11.2 | 48.3 years STANDARD_DEVIATION 10 | 49.6 years STANDARD_DEVIATION 8.7 |
| Race/Ethnicity, Customized African American/African Heritage | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 2 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized White - White/ Caucasian/ European Heritage | 14 Participants | 24 Participants | 10 Participants |
| Sex: Female, Male Female | 8 Participants | 18 Participants | 10 Participants |
| Sex: Female, Male Male | 10 Participants | 17 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 18 |
| other Total, other adverse events | 14 / 17 | 8 / 18 |
| serious Total, serious adverse events | 1 / 17 | 1 / 18 |
Outcome results
Primary
Duration of Remission on Minimal Steroid Therapy
Sum of all periods of absence of new or nonhealing lesions while on an oral prednisone/prednisolone dose of \<=10 mg/day up to Week 60 was assessed.
Time frame: Baseline up to approximately 60 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ofatumumab | Duration of Remission on Minimal Steroid Therapy | 168.0 days | Standard Deviation 73.33 |
| Placebo | Duration of Remission on Minimal Steroid Therapy | 122.0 days | — |
Primary
Number of Subjects Who Experienced Sustained Remission on Minimal Steroid Therapy
Sustained remission = time from randomization to the time of the subject's initial reduction of prednisone/prednisolone dose to \<=10 mg/day and maintenance of a dose \<=10 mg/day with no new or nonhealing lesions for \>=8 weeks and maintenance of the status until Week 60.
Time frame: Baseline up to approximately 60 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ofatumumab | Number of Subjects Who Experienced Sustained Remission on Minimal Steroid Therapy | 0 participants |
| Placebo | Number of Subjects Who Experienced Sustained Remission on Minimal Steroid Therapy | 0 participants |
Secondary
Change From Baseline for CD19+ B Cell Count
CD19+ B cell count will be performed using Flow Cytometry
Time frame: Baseline up to approximately 60 weeks
Population: number of participants varied across visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ofatumumab | Change From Baseline for CD19+ B Cell Count | Week 12 | -0.24940 10^9 cells/L | Standard Deviation 0.228704 |
| Ofatumumab | Change From Baseline for CD19+ B Cell Count | Week 24 | -0.28607 10^9 cells/L | Standard Deviation 0.265327 |
| Ofatumumab | Change From Baseline for CD19+ B Cell Count | Week 36 | -0.20525 10^9 cells/L | Standard Deviation 0.052703 |
| Ofatumumab | Change From Baseline for CD19+ B Cell Count | Week 48 | -0.19717 10^9 cells/L | Standard Deviation 0.061436 |
| Ofatumumab | Change From Baseline for CD19+ B Cell Count | Week 52 | -0.16300 10^9 cells/L | Standard Deviation 0.023335 |
| Ofatumumab | Change From Baseline for CD19+ B Cell Count | Week 56 | -0.16300 10^9 cells/L | Standard Deviation 0.023335 |
| Ofatumumab | Change From Baseline for CD19+ B Cell Count | Week 60/Early withdrawal | -0.21403 10^9 cells/L | Standard Deviation 0.190282 |
| Placebo | Change From Baseline for CD19+ B Cell Count | Week 60/Early withdrawal | 0.00367 10^9 cells/L | Standard Deviation 0.190375 |
| Placebo | Change From Baseline for CD19+ B Cell Count | Week 48 | -0.00200 10^9 cells/L | — |
| Placebo | Change From Baseline for CD19+ B Cell Count | Week 12 | 0.03080 10^9 cells/L | Standard Deviation 0.072358 |
| Placebo | Change From Baseline for CD19+ B Cell Count | Week 16 | 0.08000 10^9 cells/L | — |
| Placebo | Change From Baseline for CD19+ B Cell Count | Week 56 | 0.01000 10^9 cells/L | — |
| Placebo | Change From Baseline for CD19+ B Cell Count | Week 24 | -0.04022 10^9 cells/L | Standard Deviation 0.197867 |
| Placebo | Change From Baseline for CD19+ B Cell Count | Week 52 | 0.09600 10^9 cells/L | — |
| Placebo | Change From Baseline for CD19+ B Cell Count | Week 36 | -0.10033 10^9 cells/L | Standard Deviation 0.021385 |
Secondary
Largest Mean Decrease From Baseline for Immunoglobulin A, G and M
Immunoglobulins A, G and M were assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response
Time frame: Baseline up to approximately 60 weeks
Population: number of participants varied across visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ofatumumab | Largest Mean Decrease From Baseline for Immunoglobulin A, G and M | Immunoglobulin A | -0.185 g/L | Standard Deviation 0.1181 |
| Ofatumumab | Largest Mean Decrease From Baseline for Immunoglobulin A, G and M | Immunoglobulin G | -1.172 g/L | Standard Deviation 0.939 |
| Ofatumumab | Largest Mean Decrease From Baseline for Immunoglobulin A, G and M | Immunoglobulin M | -0.231 g/L | Standard Deviation 0.1152 |
| Placebo | Largest Mean Decrease From Baseline for Immunoglobulin A, G and M | Immunoglobulin A | -0.472 g/L | Standard Deviation 0.7116 |
| Placebo | Largest Mean Decrease From Baseline for Immunoglobulin A, G and M | Immunoglobulin G | -0.955 g/L | Standard Deviation 0.6205 |
| Placebo | Largest Mean Decrease From Baseline for Immunoglobulin A, G and M | Immunoglobulin M | -0.263 g/L | Standard Deviation 0.3053 |
Secondary
Number of Days a Subject Maintained Minimal Steroid Therapy by Week 60.
Number of days a subject maintained minimal steroid therapy (an oral prednisone/prednisolone dose of ≤10 mg/day in the absence of new or nonhealing lesions) by Week 60.
Time frame: Baseline up to approximately 60 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ofatumumab | Number of Days a Subject Maintained Minimal Steroid Therapy by Week 60. | 168 days | Standard Deviation 73.33 |
| Placebo | Number of Days a Subject Maintained Minimal Steroid Therapy by Week 60. | 122.0 days | — |
Secondary
Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A
Assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response
Time frame: Baseline up to approximately 60 weeks
Population: number of participants varied across visits
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A | Week 52 | 1 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A | Week 36 | 1 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A | Week 56 | 1 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A | Week 24 | 1 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A | Week 60/Early withdrawal | 0 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A | Week 48 | 1 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A | First 12 weeks of therapy | 1 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A | Week 12 | 1 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A | During on therapy period | 1 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A | Baseline | 1 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A | First 12 weeks of therapy | 0 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A | During on therapy period | 0 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A | Baseline | 0 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A | Week 12 | 0 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A | Week 16 | 0 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A | Week 24 | 0 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A | Week 36 | 0 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A | Week 48 | 0 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A | Week 52 | 0 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A | Week 56 | 0 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A | Week 60/Early withdrawal | 0 Participants |
Secondary
Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G
Assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response
Time frame: Baseline up to approximately 60 weeks
Population: number of participants varied across visits
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G | Week 52 | 0 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G | Week 36 | 0 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G | Week 56 | 0 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G | Week 24 | 0 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G | Week 60/Early withdrawal | 0 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G | Week 48 | 0 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G | First 12 weeks of therapy | 1 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G | Week 12 | 0 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G | During on therapy period | 1 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G | Baseline | 1 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G | First 12 weeks of therapy | 3 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G | During on therapy period | 4 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G | Baseline | 2 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G | Week 12 | 1 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G | Week 16 | 1 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G | Week 24 | 1 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G | Week 36 | 0 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G | Week 48 | 0 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G | Week 52 | 0 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G | Week 56 | 0 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G | Week 60/Early withdrawal | 2 Participants |
Secondary
Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M
Assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response
Time frame: Baseline up to approximately 60 weeks
Population: number of participants varied across visits
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M | Week 52 | 2 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M | Week 36 | 4 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M | Week 56 | 2 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M | Week 24 | 4 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M | Week 60/Early withdrawal | 6 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M | Week 48 | 3 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M | First 12 weeks of therapy | 4 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M | Week 12 | 4 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M | During on therapy period | 6 Participants |
| Ofatumumab | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M | Baseline | 1 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M | First 12 weeks of therapy | 1 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M | During on therapy period | 2 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M | Baseline | 1 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M | Week 12 | 1 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M | Week 16 | 0 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M | Week 24 | 0 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M | Week 36 | 0 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M | Week 48 | 0 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M | Week 52 | 0 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M | Week 56 | 0 Participants |
| Placebo | Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M | Week 60/Early withdrawal | 2 Participants |
Secondary
Percentage of Participants With no Flare/Relapse by Week 60
Percentage of participants achieving absence of new or nonhealing lesions while on an oral prednisone/prednisolone dose of \<=10 mg/day and did not subsequently have a appearance of \>=3 new lesions within 1 month that did not heal spontaneously within 1 week, or to the time when there was an extension of lesions that were present at the randomization by Week 60 was assessed
Time frame: Baseline up to approximately 60 weeks
Population: number of participants varied across visits
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 28 no new/nonhealing lesions | 17.6 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 6 no flare | 70.6 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 32 no flare | 35.3 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 12 no new/nonhealing lesions | 35.3 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 32 no new/nonhealing lesions | 17.6 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 4 no flare | 88.2 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 36 no flare | 23.5 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 16 no flare | 52.9 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 36 no new/nonhealing lesions | 5.9 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 6 no new/nonhealing lesions | 41.2 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 40 no flare | 17.6 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 16 no new/nonhealing lesions | 23.5 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 40 no new/nonhealing lesions | 11.8 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 2 no flare | 100.0 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 44 no flare | 17.6 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 20 no flare | 47.1 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 44 no new/nonhealing lesions | 5.9 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 8 no flare | 64.7 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 48 no flare | 17.6 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 20 no new/nonhealing lesions | 29.4 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 48 no new/nonhealing lesions | 0 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 4 no new/nonhealing lesions | 47.1 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 52 no flare | 11.8 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 8 no new/nonhealing lesions | 35.3 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 52 no new/nonhealing lesions | 11.8 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 24 no new/nonhealing lesions | 35.3 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 56 no flare | 11.8 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 2 no new/nonhealing lesions | 47.1 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 56 no new/nonhealing lesions | 5.9 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 28 no flare | 29.4 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 60 no flare | 88.2 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 12 no flare | 58.8 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 60 no new/nonhealing lesions | 52.9 percentage of participants |
| Ofatumumab | Percentage of Participants With no Flare/Relapse by Week 60 | Week 24 no flare | 47.1 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 60 no new/nonhealing lesions | 33.3 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 2 no new/nonhealing lesions | 22.2 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 2 no flare | 94.4 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 4 no flare | 83.3 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 4 no new/nonhealing lesions | 38.9 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 6 no flare | 77.8 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 6 no new/nonhealing lesions | 33.3 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 8 no flare | 72.2 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 8 no new/nonhealing lesions | 33.3 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 12 no flare | 55.6 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 12 no new/nonhealing lesions | 16.7 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 16 no flare | 61.1 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 16 no new/nonhealing lesions | 16.7 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 20 no flare | 50.0 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 20 no new/nonhealing lesions | 16.7 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 24 no flare | 38.9 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 24 no new/nonhealing lesions | 16.7 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 28 no flare | 22.2 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 28 no new/nonhealing lesions | 11.1 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 32 no flare | 27.8 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 32 no new/nonhealing lesions | 5.6 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 36 no flare | 11.1 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 36 no new/nonhealing lesions | 5.6 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 40 no flare | 5.6 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 40 no new/nonhealing lesions | 0 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 44 no flare | 5.6 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 44 no new/nonhealing lesions | 0 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 48 no flare | 0 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 48 no new/nonhealing lesions | 0 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 52 no flare | 5.6 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 52 no new/nonhealing lesions | 0 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 56 no flare | 0 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 56 no new/nonhealing lesions | 0 percentage of participants |
| Placebo | Percentage of Participants With no Flare/Relapse by Week 60 | Week 60 no flare | 83.3 percentage of participants |
Secondary
Percentage of Subjects Achieving Remission on Minimal Steroid Therapy at Week 60
Percentage of subjects who achieved absence of new or nonhealing lesions while on an oral prednisone/prednisolone dose of \<=10 mg/day for \> or = 8 weeks at Week 60 was assessed. Time to remission was not estimable.
Time frame: Week 60
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ofatumumab | Percentage of Subjects Achieving Remission on Minimal Steroid Therapy at Week 60 | 17.6 percentage of participants |
| Placebo | Percentage of Subjects Achieving Remission on Minimal Steroid Therapy at Week 60 | 5.6 percentage of participants |
Secondary
Percentage of Subjects Achieving Remission While Off Steroid Therapy by Week 60
Percentage of subjects with initial reduction of all steroids for \>=8 weeks with an absence of new or nonhealing (established) lesions by Week 60 were to be assessed. All subjects remained on prednisone/prednisolone so this endpoint could not be analyzed.Time to remission off steroid therapy also could not be analyzed
Time frame: Baseline up to approximately 60 weeks
Population: All participants remained on steroid therapy
Secondary
Plasma Trough Concentrations of Ofatumumab
Only plasma (trough) concentrations of ofatumumab were presented
Time frame: 4 hours post baseline, Days 1-4,7,14, Weeks 4,8,12,16,20,24,36,48,52,56, up to approximately 60 weeks
Population: number of participants varied across visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | 4 hours post dose SS | 56.60 ng/mL | — |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Day 1 Steady State (SS) | 1917.50 ng/mL | — |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Day 2 Steady State (SS) | 2994.20 ng/mL | — |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Day 3 Steady State (SS) | 3553.80 ng/mL | — |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Day 4 Steady State (SS) | 3619.20 ng/mL | — |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Day 7 Steady State (SS) | 3434.90 ng/mL | — |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Day 14 Steady State (SS) | 2055.30 ng/mL | — |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Week 4 | 311.59 ng/mL | Standard Deviation 278.011 |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Week 4 SS | 1132.70 ng/mL | — |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Week 8 | 1253.60 ng/mL | Standard Deviation 439.574 |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Week 8 SS | 1456.95 ng/mL | Standard Deviation 668.994 |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Week 12 | 727.01 ng/mL | Standard Deviation 430.834 |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Week 12 SS | 900.00 ng/mL | Standard Deviation 455.93 |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Week 16 | 512.88 ng/mL | Standard Deviation 377.189 |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Week 16 SS | 1043.40 ng/mL | — |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Week 20 | 415.88 ng/mL | Standard Deviation 303.307 |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Week 20 SS | 720.10 ng/mL | Standard Deviation 246.356 |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Week 24 | 461.72 ng/mL | Standard Deviation 437.717 |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Week 24 SS | 686.10 ng/mL | Standard Deviation 329.699 |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Week 36 | 477.63 ng/mL | Standard Deviation 378.112 |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Week 36 SS | 931.20 ng/mL | — |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Week 48 | 352.95 ng/mL | Standard Deviation 300.591 |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Week 48 SS | 1230.40 ng/mL | — |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Week 52 SS | 897.30 ng/mL | — |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Week 56 | 436.40 ng/mL | Standard Deviation 511.662 |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Week 60 | 76.40 ng/mL | Standard Deviation 32.244 |
| Ofatumumab | Plasma Trough Concentrations of Ofatumumab | Early withdrawal | 925.91 ng/mL | Standard Deviation 971.715 |
Secondary
Time to Initial Flare/Relapse by Week 60
Time from randomization to the time of appearance of \>=3 new lesions within 1 month that did not heal spontaneously within 1 week, or to the time when there was an extension of lesions that were present at the randomization by Week 60 was assessed
Time frame: Baseline up to approximately 60 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ofatumumab | Time to Initial Flare/Relapse by Week 60 | 448 days |
| Placebo | Time to Initial Flare/Relapse by Week 60 | 169.0 days |
Secondary
Time to Remission While on Minimal Steroid Therapy by Week 60.
Time from randomization to the time of the subject's initial reduction of prednisone/prednisolone dose to \<=10 mg/day and maintained dose at \<=10 mg/day with no new or nonhealing lesions for \>=8 weeks by Week 60 was assessed
Time frame: Baseline up to approximately 60 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ofatumumab | Time to Remission While on Minimal Steroid Therapy by Week 60. | NA days |
| Placebo | Time to Remission While on Minimal Steroid Therapy by Week 60. | NA days |