Long-Term Extension Study of Ofatumumab in Subjects With Pemphigus Vulgaris
Condition: Pemphigus
MeSH terms: Pemphigus
Intervention: Ofatumumab; Acetaminophen/paracetamol; Antihistamine (cetirizine or equivalent); Prednisone/Prednisolone
Intervention description: Ofatumumab (human monoclonal antibody) will be provided as a liquid concentrate in a prefilled glass syringe with staked needle, stopper, and plunger containing 0.4 millilitre (mL) (20 mg) drug product of 50 mg/mL concentration; Acetaminophen/paracetamol will be supplied by study centre as 1 gram tablet, caplet, capsule or liquid for oral administration; Antihistamine (cetirizine or equivalent) will be supplied by study center as 10 mg tablet, caplet, capsule or liquid for oral administration; Prednisone/Prednisolone will be supplied from the dose range 2.5, 5, 7.5, 10, 12.5, 15, 17.5, 20, 25, 30, 40, 50, 60, 80, 100, 120, 140, 160, 180, 200, 220 and 240 mg for oral administration
Intervention MeSH terms: Acetaminophen; Cetirizine; Prednisone; Prednisolone; Ofatumumab; Histamine Antagonists; Histamine H1 Antagonists
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Healthy volunteers: No
Keywords: Ofatumumab; Pemphigus Vulgaris; Long-Term Extension Study

Summary:

      This study is designed as a multi-country, multicenter, open label extension to Phase III
      trial OPV116910. The primary objective is to provide continued treatment with ofatumumab
      subcutaneous (SC) for eligible subjects who complete the OPV116910 trial in order to obtain
      further long term safety and tolerability information in subjects with pemphigus vulgaris
      receiving ofatumumab SC every 4 weeks (wk).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult with clinically documented diagnosis of PV.

          -  Completed Study OPV116910 through Week 60 with one of the following outcomes:

        Did not achieve remission by Week 60 of OPV116910. Achieved remission on a steroid dose >10
        milligrams/day. Achieved remission on minimal steroid therapy, but is experiencing a
        disease flare/relapse while participating in the first year (yr)of the OPV116910
        Individualized Follow up Period (It is recommended subjects are transitioned to the
        extension study before the steroid dose is increased).

          -  A woman is eligible to enter the study if she:

        Is of non-childbearing potential: documented as surgically sterile (bilateral tubal
        ligation, bilateral oophorectomy, hysterectomy, or hysteroscopic tubal occlusion procedure
        with follow-up confirmation of bilateral tubal occlusion) 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 baseline
        evaluation. If FSH and estradiol levels do not provide confirmation of menopause, subject
        will be considered to be of childbearing potential.

        Is of childbearing potential, with a negative pregnancy test at baseline, and agrees to the
        consistent and correct use of acceptable methods of contraception (Highly-Effective Methods
        for Avoiding Pregnancy) during heterosexual intercourse, beginning when the subject
        provides informed consent and lasting until 12 months after last dose of ofatumumab SC.

        Exclusion Criteria:

          -  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 any of the following within the specified periods:

        Medication and Other Treatment Restrictions Prior to OPV117059 Baseline Any time-
        Ofatumumab (Intravenous), total body irradiation, bone marrow transplantation, anti CD4; 6
        weeks -Live vaccine 8 weeks- Immunosuppressive or immunomodulatory agents, including:
        azathioprine, cyclosporine, dapsone, mycophenolate, methotrexate, tacrolimus 6 months-
        Cyclophosphamide, cladribine, plasmapheresis, immunoabsorption, or immunoglobulin therapy,
        alemtuzumab, mitoxantrone 18 months -Rituximab or other anti CD20 treatments

          -  Confirmed PML or neurological findings potentially consistent with PML.

          -  Evidence or history of clinically significant infection or medical condition
             including:

        Chronic or ongoing active infectious disease requiring long term systemic treatment,
        including, but not limited to, chronic renal infection, chronic chest infection with
        bronchiectasis, or active hepatitis C.

        Positive test for hepatitis B surface antigen (HbsAg). For HbsAg negative, but hepatitis B
        core antibody positive (anti-HBc) (regardless of hepatitis B surface antibody [HbsAb]
        status), a hepatitis B virus deoxyribonucleic acid (HBV DNA) test will be performed and the
        subject will be excluded if results are positive. Consult with a physician experienced in
        the care and management of subjects with hepatitis B to manage/treat subjects who are anti
        HBc positive. Subjects who are anti-HBc positive and HBV DNA negative will continue to be
        monitored throughout the study.

        History of positive serology for human immunodeficiency virus. Previous serious
        opportunistic or atypical infections. Prior history, or suspicion, of tuberculosis. A
        radiograph of the chest taken within 3 months before the first administration of
        investigational product suggests no evidence indicating current active tuberculosis or
        previous tuberculosis.

          -  Past or current malignancy, except for: Cervical carcinoma Stage 1B or less;
             Noninvasive basal cell and squamous cell skin carcinoma; Cancer diagnoses with a
             duration of complete response (remission) >5 years.

          -  Clinical chemistry and/or hematology laboratory values of clinical concern, in the
             investigator's opinion.

        For subjects transitioning directly from the OPV116910 study, review central chemistry and
        hematology laboratory reports from the Week 48 through Week 56 visits of OPV116910.

        For subjects transitioning from the Individualized Follow-up Period of OPV116910, review
        central chemistry and hematology laboratory reports from the most recent OPV116910
        Individualized Follow-up visit. If the date of that laboratory report is more than 12 weeks
        from the extension study Screening visit, then the laboratory assessments need to be
        repeated.

        For subjects with neutropenia (absolute neutrophil count <1 Giga units per liter, the
        neutropenia must resolve before the first dose of ofatumumab, which should occur within 4
        weeks of the screening assessments.

          -  Electrocardiogram (ECG) showing a clinically significant abnormality or showing a
             Corrected QT Interval (QTc) interval >=450 millisecond (msec) (>=480 msec for subjects
             with bundle branch block) (ECG will be obtained during Week 60 visit of OPV116910;
             Repeat ECG if more than 12 weeks have elapsed).

          -  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.

          -  In the Investigator's opinion, there is a reason why the subject would not be eligible
             for this study (eg, the subject is unable to comply with the visit schedule).