Efficacy and Safety of Ofatumumab in Treatment of Pemphigus Vulgaris

NCT ID: NCT01920477

Last Updated: 2019-06-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-13
• Study Completion Date: 2018-01-11

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

Conditions

Pemphigus Vulgaris

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Ofatumumab

Intervention Type: BIOLOGICAL

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

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Placebo to match the active doses will consist of prefilled glass syringes filled with normal saline.

Interventions

Ofatumumab

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

Intervention Type: BIOLOGICAL

Placebo

Placebo to match the active doses will consist of prefilled glass syringes filled with normal saline.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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

Novartis Investigational Site

Ramat Gan, , Israel

Novartis Investigational Site

Tel Aviv, , Israel

Novartis Investigational Site

Milan, Lombardy, Italy

Novartis Investigational Site

Tokyo, , Japan

Novartis Investigational Site

Warsaw, , Poland

Novartis Investigational Site

Cluj-Napoca, , Romania

Countries

United States; Australia; Greece; Israel; Italy; Japan; Poland; Romania

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

116910

Identifier Type: -

Identifier Source: org_study_id