Efficacy and Safety of Ofatumumab in Treatment of Pemphigus Vulgaris
Condition: Pemphigus Vulgaris
MeSH terms: Pemphigus
Intervention: Ofatumumab; Placebo
Intervention description: 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.
Intervention MeSH terms: Ofatumumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Pemphigus; MAB; autoimmune disorder; human CD20 antigen; subcutaneous; vulgaris; Phase 3; monoclonal antibody; ofatumumab; PV; rare disease; OMB157; adult

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.
    

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.