Long-Term Extension Study of Ofatumumab in Subjects With Pemphigus Vulgaris

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02613910
• Date of registration: 23/11/2015
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: Long-Term Extension Study of Ofatumumab in Subjects With Pemphigus Vulgaris
• Scientific title: OPV117059: A Long-Term Extension Study of Ofatumumab Injection for Subcutaneous Use in Subjects With Pemphigus Vulgaris
• Date of first enrolment: December 23, 2015
• Target sample size: 1
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02613910
• Study type: Interventional
• Study design: Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion 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).



Age minimum: N/A
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Pemphigus

Intervention(s)

Drug: Antihistamine (cetirizine or equivalent)

Drug: Acetaminophen/paracetamol

Drug: Ofatumumab

Drug: Prednisone/Prednisolone

Primary Outcome(s)

Change From Baseline in Sodium, Potassium, Chloride, Calcium, Glucose, Bicarbonate and Blood Urea Nitrogen at the Indicated Time Points [Time Frame: Up to Week 156]

Change From Baseline in Specific Gravity of Urine [Time Frame: Up to Week 60]

Change From Baseline in Total Bilirubin and Creatinine at the Indicated Time Points [Time Frame: Up to Week 156]

Number of Participants With Laboratory Results of Potential Clinical Concern [Time Frame: Up to Week 156]

Change From Baseline in Immunoglobulin (Ig) A, IgM, and IgG Levels [Time Frame: Up to Week 156]

Change From Baseline in Red Blood Cell (RBC) Count and Nucleated RBCs at the Indicated Time Points [Time Frame: Up to Week 156]

Change From Baseline in Total Protein and Albumin at the Indicated Time Points [Time Frame: Up to Week 156]

Number of Participants With Clinically-significant Electrocardiogram (ECG) Abnormalities [Time Frame: Up to Week 60]

Change From Baseline in Urine Power of Hydrogen (pH) at the Indicated Time Points [Time Frame: Up to Week 60]

Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points [Time Frame: Up to Week 156]

Change From Baseline in Creatinine Clearance (Calculated) at the Indicated Time Points [Time Frame: Up to Week 156]

Number of Participants With Change in Urinalysis Results [Time Frame: Up to Week 60]

Number of Participants With Vital Signs of Clinical Concern [Time Frame: Up to Week 60]

Change From Baseline in Heart Rate at the Indicated Time Points [Time Frame: Baseline (Week 0) and up to Week 60]

Number of Participants With Serious Adverse Events (SAEs) and AEs of Special Interest (AESI) [Time Frame: Up to Week 156]

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 [Time Frame: Up to Week 156]

Change From Baseline in Body Temperature at the Indicated Time Points [Time Frame: Baseline (Week 0) and up to Week 60]

Number of Participants With Infections [Time Frame: Up to Week 60]

Number of Participants With Adverse Events(AEs) and AEs Leading to Permanent Discontinuation of Ofatumumab SC (AELD) [Time Frame: Up to Week 60]

Number of Participants With Severe Adverse Events [Time Frame: Up to Week 60]

Number of Participants Withdrawn Due to Treatment-related AEs [Time Frame: Up to Week 60]

Change From Baseline in CD4: CD8 Ratio at the Indicated Time Points [Time Frame: Up to Week 156]

Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points [Time Frame: Baseline (Week 0) and up to Week 60]

Change From Baseline in Hematocrit at the Indicated Time Points [Time Frame: Up to Week 156]

Change From Baseline in Hemoglobin at the Indicated Time Points [Time Frame: Up to Week 156]

Number of Participants With Adverse Events Related to Ofatumumab SC [Time Frame: Up to Week 60]

Number of Participants With Injection Site Reactions [Time Frame: Up to Week 60]

Number of Participants With Post-injection Systemic Reactions [Time Frame: Up to Week 60]

Secondary Outcome(s)

Time to Remission Off Steroid Therapy by Week 60 [Time Frame: Up to Week 60]

Duration of Remission on Minimal Steroid Therapy [Time Frame: Up to Week 60]

Number of Days Minimal Steroid Therapy is Maintained by Week 60 [Time Frame: Up to Week 60]

Duration of Remission After Completing the Ofatumumab SC Treatment Course [Time Frame: Up to Week 156]

Number of Participants Who do Not Flare/Relapse on Minimal Steroid Therapy [Time Frame: Up to Week 60]

Time to Initial Flare/Relapse After Completing the Ofatumumab SC Treatment Course During the Individualized Follow-up Period [Time Frame: Up to Week 156]

Time to Initial Flare/Relapse After Completing the Ofatumumab SC Treatment Course [Time Frame: Up to Week 60]

Number of Days a Participant is Off Steroid Therapy by Week 60 [Time Frame: Up to Week 60]

Number of Participants Achieving Remission on Minimal Steroid Therapy [Time Frame: Up to Week 60]

Number of Participants Achieving Sustained Remission on Minimal Steroid Therapy by Week 60 [Time Frame: Up to Week 60]

Number of Participants Achieving Remission While Off Steroid Therapy by Week 60 [Time Frame: Up to Week 60]

Number of Participants Who do Not Flare/Relapse [Time Frame: Up to Week 60]

Number of Participants With Positive Human Anti-human Antibody (HAHA) Immune Response [Time Frame: Up to Week 72]

Time to Sustained Remission on Minimal Steroid Therapy [Time Frame: Up to Week 60]

Cumulative Dose of Corticosteroids [Time Frame: Up to Week 60]

Time to Initial Flare/Relapse by Week 60 [Time Frame: Up to Week 60]

Titer of Human Anti-human Antibody [Time Frame: Up to Week 72]

Time to Remission on Minimal Steroid Therapy [Time Frame: Up to Week 60]

Secondary ID(s)

117059

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 14/06/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02613910