Efficacy and Safety of Ofatumumab in Treatment of Pemphigus Vulgaris
Efficacy and Safety of Ofatumumab in Treatment of Pemphigus Vulgaris
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
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.