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.
Novartis terminated the development of the PV program and this study was terminated for non-safety reasons
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
35
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
Placebo to match the active doses will consist of prefilled glass syringes filled with normal saline.
Novartis Investigational Site
Los Angeles, California, United States
Novartis Investigational Site
Atlanta, Georgia, United States
Novartis Investigational Site
Ann Arbor, Michigan, United States
Novartis Investigational Site
Buffalo, New York, United States
Novartis Investigational Site
Durham, North Carolina, United States
Novartis Investigational Site
Pittsburgh, Pennsylvania, United States
Novartis Investigational Site
Salt Lake City, Utah, United States
Novartis Investigational Site
East Melbourne, Victoria, Australia
Novartis Investigational Site
Melbourne, Victoria, Australia
Novartis Investigational Site
Thessaloniki, Greece
...and 6 more locations
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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