Efficacy and Safety of Ofatumumab in Treatment of Pemphigus Vulgaris

Phase 3

Terminated

Conditions: Pemphigus Vulgaris

Interventions: Biological: Ofatumumab
Biological: Placebo

Registration Number: NCT01920477

Lead Sponsor: Novartis Pharmaceuticals

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

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 35

Inclusion Criteria

Not provided

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ofatumumab	Ofatumumab	Subject received 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.
Placebo	Placebo	Subject received 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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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
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
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
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
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
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.
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
Change From Baseline for CD19+ B Cell Count	Baseline up to approximately 60 weeks	CD19+ B cell count will be performed using Flow Cytometry