Clinical trial NCT02613910: Long-Term Extension Study of Ofatumumab in Subjects With Pemphigus Vulgaris
Official title: OPV117059: A Long-Term Extension Study of Ofatumumab Injection for Subcutaneous Use in Subjects With Pemphigus Vulgaris
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Pemphigus
Keywords: Ofatumumab
Pemphigus Vulgaris
Long-Term Extension Study
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2015-11-25
Enrollment: 1
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).

Primary outcomes:
measure: Number of Participants With Adverse Events(AEs) and AEs Leading to Permanent Discontinuation of Ofatumumab SC (AELD)
timeFrame: Up to Week 60
measure: Number of Participants With Severe Adverse Events
timeFrame: Up to Week 60
measure: Number of Participants With Adverse Events Related to Ofatumumab SC
timeFrame: Up to Week 60
measure: Number of Participants With Serious Adverse Events (SAEs) and AEs of Special Interest (AESI)
timeFrame: Up to Week 156
measure: Number of Participants Withdrawn Due to Treatment-related AEs
timeFrame: Up to Week 60
measure: Number of Participants With Infections
timeFrame: Up to Week 60
measure: Number of Participants With Post-injection Systemic Reactions
timeFrame: Up to Week 60
measure: Number of Participants With Injection Site Reactions
timeFrame: Up to Week 60
measure: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points
timeFrame: Baseline (Week 0) and up to Week 60
measure: Change From Baseline in Heart Rate at the Indicated Time Points
timeFrame: Baseline (Week 0) and up to Week 60
measure: Change From Baseline in Body Temperature at the Indicated Time Points
timeFrame: Baseline (Week 0) and up to Week 60
measure: Number of Participants With Vital Signs of Clinical Concern
timeFrame: Up to Week 60
measure: Number of Participants With Clinically-significant Electrocardiogram (ECG) Abnormalities
timeFrame: Up to Week 60
measure: Change From Baseline in Hemoglobin at the Indicated Time Points
timeFrame: Up to Week 156
measure: Change From Baseline in Hematocrit at the Indicated Time Points
timeFrame: Up to Week 156
measure: Change From Baseline in White Blood Cell (WBC) Count, Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte, Platelet Count, Bands, Cluster of Differentiation (CD)19+ B-lymphocyte Counts, CD3, CD4 and CD8 at the Indicated Time Points
timeFrame: Up to Week 156
measure: Change From Baseline in CD4: CD8 Ratio at the Indicated Time Points
timeFrame: Up to Week 156
measure: Change From Baseline in Red Blood Cell (RBC) Count and Nucleated RBCs at the Indicated Time Points
timeFrame: Up to Week 156
measure: Change From Baseline in Total Protein and Albumin at the Indicated Time Points
timeFrame: Up to Week 156
measure: Change From Baseline in Total Bilirubin and Creatinine at the Indicated Time Points
timeFrame: Up to Week 156
measure: Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points
timeFrame: Up to Week 156
measure: Change From Baseline in Sodium, Potassium, Chloride, Calcium, Glucose, Bicarbonate and Blood Urea Nitrogen at the Indicated Time Points
timeFrame: Up to Week 156
measure: Change From Baseline in Creatinine Clearance (Calculated) at the Indicated Time Points
timeFrame: Up to Week 156
measure: Number of Participants With Change in Urinalysis Results
timeFrame: Up to Week 60
measure: Change From Baseline in Urine Power of Hydrogen (pH) at the Indicated Time Points
timeFrame: Up to Week 60
measure: Change From Baseline in Specific Gravity of Urine
timeFrame: Up to Week 60
measure: Number of Participants With Laboratory Results of Potential Clinical Concern
timeFrame: Up to Week 156
measure: Change From Baseline in Immunoglobulin (Ig) A, IgM, and IgG Levels
timeFrame: Up to Week 156
Secondary outcomes:
measure: Time to Sustained Remission on Minimal Steroid Therapy
timeFrame: Up to Week 60
measure: Duration of Remission on Minimal Steroid Therapy
timeFrame: Up to Week 60
measure: Number of Participants Achieving Sustained Remission on Minimal Steroid Therapy by Week 60
timeFrame: Up to Week 60
measure: Time to Remission Off Steroid Therapy by Week 60
timeFrame: Up to Week 60
measure: Number of Participants Achieving Remission While Off Steroid Therapy by Week 60
timeFrame: Up to Week 60
measure: Number of Participants Achieving Remission on Minimal Steroid Therapy
timeFrame: Up to Week 60
measure: Time to Remission on Minimal Steroid Therapy
timeFrame: Up to Week 60
measure: Duration of Remission After Completing the Ofatumumab SC Treatment Course
timeFrame: Up to Week 156
measure: Time to Initial Flare/Relapse by Week 60
timeFrame: Up to Week 60
measure: Number of Participants Who do Not Flare/Relapse
timeFrame: Up to Week 60
measure: Number of Participants Who do Not Flare/Relapse on Minimal Steroid Therapy
timeFrame: Up to Week 60
measure: Time to Initial Flare/Relapse After Completing the Ofatumumab SC Treatment Course
timeFrame: Up to Week 60
measure: Time to Initial Flare/Relapse After Completing the Ofatumumab SC Treatment Course During the Individualized Follow-up Period
timeFrame: Up to Week 156
measure: Number of Days Minimal Steroid Therapy is Maintained by Week 60
timeFrame: Up to Week 60
measure: Number of Days a Participant is Off Steroid Therapy by Week 60
timeFrame: Up to Week 60
measure: Cumulative Dose of Corticosteroids
timeFrame: Up to Week 60
measure: Number of Participants With Positive Human Anti-human Antibody (HAHA) Immune Response
timeFrame: Up to Week 72
measure: Titer of Human Anti-human Antibody
timeFrame: Up to Week 72
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Ann Arbor
country: United States
facility: GSK Investigational Site
state: Michigan
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: