Clinical Trial: Efficacy and Safety of Ofatumumab in Treatment of Pemphigus Vulgaris
Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional
Official Title: OPV116910: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Investigate the Efficacy and Safety of Ofatumumab Injection for Subcutaneous Use in Subjects With 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 is 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 is 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 will result.
Detailed Summary:
Sponsor: Stiefel, a GSK Company
Current Primary Outcome:
- Time to sustained remission on minimal steroid therapy [ Time Frame: Up to 60 weeks ]Time from randomization to the time of the subject's initial reduction of prednisone/prednisolone dose to <=10 mg/day and maintained a dose <=10 mg/day with no new or nonhealing (established) lesions for >=8 weeks and maintained the status until Week 60 will be assessed
- Duration of remission on minimal steroid therapy [ Time Frame: Up to 60 weeks ]Sum of all periods of absence of new or nonhealing (established) lesions while on an oral prednisone/prednisolone dose of <=10 mg/day up to Week 60 will be assessed.
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Proportion of subjects achieving remission on minimal steroid therapy at Week 60 [ Time Frame: Week 60 ]Proportion of subjects achieving absence of new or nonhealing (established) lesions while on an oral prednisone/prednisolone dose of <=10 mg/day at Week 60 will be assessed.
- Time to remission while on minimal steroid therapy by Week 60. [ Time Frame: Up to 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 (established) lesions for >=8 weeks by Week 60 will be assessed
- Time to remission off steroid therapy by Week 60 [ Time Frame: Up to 60 weeks ]Time from randomization to the time of the subjects initial reduction of all steroids for >=8 weeks with an absence of new or nonhealing (established) lesions by Week 60 will be assessed
- Proportion of subjects achieving remission while off steroid therapy by Week 60 [ Time Frame: Up to 60 weeks ]Proportion of subjects with initial reduction of all steroids for >=8 weeks with an absence of new or nonhealing (established) lesions by Week 60 will be assessed
- Number of days a subject maintained minimal steroid therapy by Week 60. [ Time Frame: Up to 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 [ Time Frame: Up to 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 will be assessed
- Proportion of subjects with no flare/relapse by Week 60 [ Time Frame: Up to 60 weeks ]Proportion of subjects achieving absence of new or nonhealing (established) 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 will be assessed
- Cumulative dose of corticosteroids [ Time Frame: Up to 60 weeks ]Exposure to corticosteroids over a period of 60 weeks will be assessed
- Change from Baseline in B-lymphocyte counts in peripheral blood [ Time Frame: Up to 60 weeks ]Change from Baseline in B-lymphocyte counts in peripheral blood at prespecified time points (Day 0 and every four weeks till Week 60) and at the time of any opportunistic infection will be assessed
- Time to repletion of CD19+ B-cells to either >=Baseline level or >=Lower Limit of Normal (LLN) , whichever [ Time Frame: Up to 2 years ]Time to repletion of CD19+ B-cells to either >=Baseline level (observation at Week 0) or >=LLN (110 cell/mcgL), whichever is lower will be assessed
- Composite of population pharmacokinetics (PK) of ofatumumab [ Time Frame: Up to 60 weeks ]Plasma (trough) concentrations of ofatumumab, Exposure-response relationship, PK parameters include: Maximum concentration (Cmax); time to maximum concentration (tmax); and area under the time-concentration curve (AUC).
- Immunogenicity of ofatumumab [ Time Frame: Up to 60 weeks ]Immunogenicity will be assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response
- Safety and tolerability of ofatumumab assessed by Adverse events (AEs). [ Time Frame: Up to 60 weeks ]AEs assessment include: Frequency and severity of AE, AE relationship to IP, frequency and severity of SAE, AE of special interest, Frequency and severity of infections, Percentage of subject withdrawals due to treatment-related AEs, AEs leading to permanent discontinuation of study drug, Postinjection systemic reactions, Injection site reactions
- Change from Baseline in Vital signs [ Time Frame: Up to 60 weeks ]Vital signs include: pulse rate, temperature, systolic and diastolic blood pressure.
- Change from Baseline in laboratory parameters [ Time Frame: Up to 60 weeks ]Laboratory parameters include: hematology, clinical chemistry, and urinalysis
- Effect of demographic factors, including Baseline covariates on PK parameters of ofatumumab as data permits. [ Time&nb
Original Secondary Outcome:
- Proportion of subjects achieving remission on minimal steroid therapy at Week 60 [ Time Frame: Week 60 ]Proportion of subjects achieving absence of new or nonhealing (established) lesions while on an oral prednisone/prednisolone dose of <=10 mg/day at Week 60 will be assessed.
- Time to remission while on minimal steroid therapy by Week 60. [ Time Frame: Up to 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 (established) lesions for >=8 weeks by Week 60 will be assessed
- Time to remission off steroid therapy by Week 60 [ Time Frame: Up to 60 weeks ]Time from randomization to the time of the subjects initial reduction of all steroids for >=8 weeks with an absence of new or nonhealing (established) lesions by Week 60 will be assessed
- Proportion of subjects achieving remission while off steroid therapy by Week 60 [ Time Frame: Up to 60 weeks ]Proportion of subjects with initial reduction of all steroids for >=8 weeks with an absence of new or nonhealing (established) lesions by Week 60 will be assessed
- Number of days a subject maintained minimal steroid therapy by Week 60. [ Time Frame: Up to 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 [ Time Frame: Up to 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 will be assessed
- Proportion of subjects with no flare/relapse by Week 60 [ Time Frame: Up to 60 weeks ]Proportion of subjects achieving absence of new or nonhealing (established) 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 will be assessed
- Cumulative dose of corticosteroids [ Time Frame: Up to 60 weeks ]Exposure to corticosteroids over a period of 60 weeks will be assessed
- Change from Baseline in B-lymphocyte counts in peripheral blood [ Time Frame: Up to 60 weeks ]Change from Baseline in B-lymphocyte counts in peripheral blood at prespecified time points (Day 0 and every four weeks till Week 60) and at the time of any opportunistic infection will be assessed
- Time to repletion of CD19+ B-cells to either >=Baseline level or >=Lower Limit of Normal (LLN) , whichever [ Time Frame: Up to 2 years ]Time to repletion of CD19+ B-cells to either >=Baseline level (observation at Week 0) or >=LLN (110 cell/mcgL), whichever is lower will be assessed
- Composite of pharmacokinetic (PK) of ofatumumab [ Time Frame: Up to 60 weeks ]PK parameters include: Maximum concentration (Cmax); time to maximum concentration (tmax); and area under the time-concentration curve (AUC).
- Immunogenicity of ofatumumab [ Time Frame: Up to 60 weeks ]Immunogenicity will be assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response
- Safety and tolerability of ofatumumab assessed by Adverse events (AEs). [ Time Frame: Up to 60 weeks ]AEs assessment include: Frequency and severity of AE, AE relationship to IP, frequency and severity of SAE, AE of special interest, Frequency and severity of infections, Percentage of subject withdrawals due to treatment-related AEs, AEs leading to permanent discontinuation of study drug, Postinjection systemic reactions, Injection site reactions
- Change from Baseline in Vital signs [ Time Frame: Up to 60 weeks ]Vital signs include: pulse rate, temperature, systolic and diastolic blood pressure.
- Change from Baseline in laboratory parameters [ Time Frame: Up to 60 weeks ]Laboratory parameters include: hematology, clinical chemistry, and urinalysis
- Effect of demographic factors, including Baseline covariates on PK parameters of ofatumumab as data permits. [ Time Frame: Up to 60 weeks ]Demograph
Information By: GlaxoSmithKline
Dates:
Date Received: July 3, 2013
Date Started: August 13, 2013
Date Completion: September 30, 2017
Last Updated: April 7, 2017
Last Verified: April 2017
- Proportion of subjects achieving remission on minimal steroid therapy at Week 60 [ Time Frame: Week 60 ]