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

Phase 3TerminatedNCT02613910

GlaxoSmithKline1 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Pemphigus

Interventions

OfatumumabDRUG

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/paracetamolDRUG

Acetaminophen/paracetamol will be supplied by study centre as 1 gram tablet, caplet, capsule or liquid for oral administration

Antihistamine (cetirizine or equivalent)DRUG

Antihistamine (cetirizine or equivalent) will be supplied by study center as 10 mg tablet, caplet, capsule or liquid for oral administration

Eligibility

Sex: ALL

Medical Language ↔ Plain English

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).

Locations (2)

GSK Investigational Site

Los Angeles, California, United States

GSK Investigational Site

Ann Arbor, Michigan, United States

Outcomes

Primary Outcomes

Number of Participants With Adverse Events(AEs) and AEs Leading to Permanent Discontinuation of Ofatumumab SC (AELD)

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with AEs and those with AEs leading to permanent discontinuation of ofatumumab SC (AELD) were to be summarized. Safety Population consists of all participants enrolled in the study. No safety events were reported for the one participant enrolled.

Time frame: Up to Week 60

Number of Participants With Severe Adverse Events

Severity is a category utilized for rating the intensity of an adverse event. Participants with severe AEs were to be summarized. No serious adverse events (SAEs) were reported for the one participant enrolled.

Time frame: Up to Week 60

Number of Participants With Adverse Events Related to Ofatumumab SC

Participants with AEs related to ofatumumab were to be summarized. No adverse events related to ofatumumab were reported for the one participant enrolled.

Time frame: Up to Week 60

Number of Participants With Serious Adverse Events (SAEs) and AEs of Special Interest (AESI)

Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention, events associated with liver injury and impaired liver function were to be categorized as SAE. AEs of special interest included any opportunistic infections, serious post injection systemic reactions, progressive multifocal leukoencephalopathy (PML), hepatitis B virus infection or reactivation, severe mucocutaneous reactions (e.g., toxic epidermal necrolysis and stevens-johnson syndrome), cytopenias and cardiovascular events. Participants with SAEs and AESI were to be summarized. No serious adverse events (SAEs) or adverse events of special interest (AESI) reported.

Data from ClinicalTrials.gov

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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

Time frame: Up to Week 156

Number of Participants Withdrawn Due to Treatment-related AEs

Participants withdrawn due to treatment related AEs were to be summarized. One participant was enrolled into the study and was withdrawn early due to study termination. The participant was not withdrawn due to treatment-related AEs.

Time frame: Up to Week 60

Number of Participants With Infections

All infections were planned to be monitored closely throughout the study and participants with infections were to be summarized. No cases of infection were reported for the one participant.

Time frame: Up to Week 60

Number of Participants With Post-injection Systemic Reactions

All serious post-injection systemic reactions were planned to be monitored closely throughout the study and number of participants with post-injection systemic reactions was to be summarized. No cases of post-injection systemic reactions were reported for the one participant.

Time frame: Up to Week 60

Number of Participants With Injection Site Reactions

Number of participants with injection site reactions were planned to be summarized. No cases of injection site reaction were reported for the one participant.

Time frame: Up to Week 60

Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points

SBP and DBP were to be taken at pre-dose and 4 hour post-dose on Week 4; pre-dose and 1 hour post-dose from Week 6 to Week 56; and at Follow-up visit (Week 60). Measurements were to be obtained after at least 5 minutes of rest. Baseline was to be considered as the measurement obtained on Week 0. The change from Baseline was to be calculated by subtracting the Baseline value from the individual post-randomization values. Due to the termination of this study, analysis of this information was not performed.

Time frame: Baseline (Week 0) and up to Week 60

Change From Baseline in Heart Rate at the Indicated Time Points

Heart rate was to be taken at pre-dose and 4 hour post-dose on Week 4; pre-dose and 1 hour post-dose from Week 6 to Week 56; and at Follow-up visit (Week 60). Measurements were to be obtained in the sitting position and at the time of the blood pressure measurement. Baseline was to be considered as the measurement obtained on Week 0. The change from Baseline was to be calculated by subtracting the Baseline value from the individual post-randomization values. Due to the termination of this study, analysis of this information was not performed

Time frame: Baseline (Week 0) and up to Week 60

Change From Baseline in Body Temperature at the Indicated Time Points

Body temperature was planned to be taken at pre-dose and 4 hour post-dose on Week 4; pre-dose and 1 hour post-dose from Week 6 to Week 56; and at Follow-up visit (Week 60). Baseline was to be considered as the measurement obtained on Week 0. The change from Baseline was to be calculated by subtracting the Baseline value from the individual post-randomization values. Due to termination of study, analysis of this information was not performed.

Time frame: Baseline (Week 0) and up to Week 60

Number of Participants With Vital Signs of Clinical Concern

Participants with vitals signs of clinical concern were planned to be summarized. No vital signs of clinical concerns were present for the one participant.

Time frame: Up to Week 60

Number of Participants With Clinically-significant Electrocardiogram (ECG) Abnormalities

12-lead ECG was planned to be taken on Baseline (Week 0) and at Follow-up visit (Week 60). No clinically significant ECG abnormalities were noted for the one participant.

Time frame: Up to Week 60

Change From Baseline in Hemoglobin at the Indicated Time Points

Blood samples were planned to be collected at Baseline (Week 0) and at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56 and at Follow-up visit (Week 60); and at individualized Follow-up visits at Week 72, 84, 96, 108, 120, 132, 144 and 156. Baseline was to be considered as the value obtained on Week 0. The change from Baseline was to be calculated by subtracting the Baseline value from the individual post-randomization values. Due to the termination of this study, analysis of this information was not performed.

Time frame: Up to Week 156

Change From Baseline in Hematocrit at the Indicated Time Points

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 CD4: CD8 Ratio at the Indicated Time Points

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

Blood samples were planned to be collected at Baseline (Week 0) and at Week 8, 20, 28, 36, 44, 52 and at Follow-up visit (Week 60); and at individualized Follow-up visits at Week 72, 84, 96, 108, 120, 132, 144 and 156. Baseline was to be considered as the value obtained on Week 0. The change from Baseline was to be calculated by subtracting the Baseline value from the individual post-randomization values. Due to the termination of this study, analysis of this information was not performed.

Time frame: Up to Week 156

Change From Baseline in Total Bilirubin and Creatinine at the Indicated Time Points

Time frame: Up to Week 156

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 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 Creatinine Clearance (Calculated) at the Indicated Time Points

Blood samples were plannedto be collected at Baseline (Week 0) and at Week 8, 20, 28, 36, 44, 52 and at Follow-up visit (Week 60); and at individualized Follow-up visits at Week 72, 84, 96, 108, 120, 132, 144 and 156. Baseline was to be considered as the value obtained on Week 0. The change from Baseline was to be calculated by subtracting the Baseline value from the individual post-randomization values. Due to the termination of this study, analysis of this information was not performed.

Time frame: Up to Week 156

Number of Participants With Change in Urinalysis Results

Urine samples were planned to be collected at Baseline (Week 0) and at Week 8, 20, 28, 36, 44, 52 and at Follow-up visit (Week 60) for evaluation of appearance, protein, glucose, leukocyte esterase, ketones, hemoglobin, microalbumin, creatinine, microalbumin:creatinine ratio and microscopy which included RBC/high powered field, WBC/ hight powered field, epithelial cells, trichomonas, bacteria, yeast, crystals, ammonium urates, mucous threads, amorphous sediment and casts. Baseline was to be considered as the measurement obtained on Week 0. The change from Baseline was to be calculated by subtracting the Baseline from the individual post-randomization measurements. Due to the termination of this study, analysis of this information was not performed.

Time frame: Up to Week 60

Change From Baseline in Urine Power of Hydrogen (pH) at the Indicated Time Points

Urine samples were plannedto be collected at Baseline (Week 0) and at Week 8, 20, 28, 36, 44, 52 and at Follow-up visit (Week 60) for evaluation of pH. Baseline was to be considered as the measurement obtained on Week 0. The change from Baseline was to be calculated by subtracting the Baseline from the individual post-randomization measurements. Due to the termination of this study, analysis of this information was not performed.

Time frame: Up to Week 60

Change From Baseline in Specific Gravity of Urine

Urine samples were planned to be collected at Baseline (Week 0) and at Week 8, 20, 28, 36, 44, 52 and at Follow-up visit (Week 60) for evaluation of urine specific gravity. Baseline was to be considered as the measurement obtained on Week 0. The change from Baseline was to be calculated by subtracting the Baseline from the individual post-randomization measurements. Due to the termination of this study, analysis of this information was not performed.

Time frame: Up to Week 60

Number of Participants With Laboratory Results of Potential Clinical Concern

Blood samples were planned to be collected at Baseline (Week 0) and at Week 8, 20, 28, 36, 44, 52 and at Follow-up visit (Week 60); and at individualized Follow-up visits at Week 72, 84, 96, 108, 120, 132, 144 and 156 for evaluation of clinical chemistry parameters; and at Baseline (Week 0) and at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56 and at Follow-up visit (Week 60); and at individualized Follow-up visits at Week 72, 84, 96, 108, 120, 132, 144 and 156 for evaluation of hematology parameters. No laboratory values of potential clinical concern were identified for this one participant.

Time frame: Up to Week 156

Change From Baseline in Immunoglobulin (Ig) A, IgM, and IgG Levels

Blood samples for IgA, IgM, and IgG analysis were planned to be collected at Baseline (Week 0) and at Week 12, 24, 36, 48 and at Follow-up visit (Week 60); and at individualized Follow-up visits at Week 72, 84, 96, 108, 120, 132, 144 and 156. Baseline was to be considered as the value obtained on Week 0. The change from Baseline was to be calculated by subtracting the Baseline value from the individual post-randomization values. Due to the termination of this study, analysis of this information was not performed.

Time frame: Up to Week 156

Secondary Outcomes

Time to Sustained Remission on Minimal Steroid Therapy

Time to sustained remission on minimal steroid therapy is the time from Baseline (Week 0) to the time the participant initially tapered his/her oral prednisone/prednisolone dose to \<=10 mg/day and maintained \<=10 mg/day of oral prednisone/prednisolone with no new or non-healing (established) lesions for \>= 8 weeks and maintained that status until Week 60. Due to the termination of this study, analysis of this information was not performed.

Time frame: Up to Week 60

Duration of Remission on Minimal Steroid Therapy

Duration of remission on minimal steroid therapy is the total time (sum) of all periods of remission while on minimal steroid therapy (oral prednisone/prednisolone dose \<=10 mg/day) up to Week 60. Due to the termination of this study, analysis of this information was not performed.

Time frame: Up to Week 60

Number of Participants Achieving Sustained Remission on Minimal Steroid Therapy by Week 60

Sustained remission on minimal steroid therapy is the time from Baseline (Week 0) to the time the participant initially tapered his/her oral prednisone/prednisolone dose to \<=10 mg/day and maintained \<=10 mg/day of oral prednisone/prednisolone with no new or non-healing (established) lesions for \>=8 weeks and maintained that status until Week 60. Due to the termination of this study, analysis of this information was not performed.

Time frame: Up to Week 60

Time to Remission Off Steroid Therapy by Week 60

Remission is the absence of new or non-healing (established) lesions for \>=8 weeks. Due to the termination of this study, analysis of this information was not performed.

Time frame: Up to Week 60

Number of Participants Achieving Remission While Off Steroid Therapy by Week 60

Remission is the absence of new or non-healing (established) lesions for \>=8 weeks. Due to the termination of this study, analysis of this information was not performed.

Time frame: Up to Week 60

Number of Participants Achieving Remission on Minimal Steroid Therapy

Remission is defined as absence of new or non-healing (established) lesions for \>=8 weeks and minimal steroid therapy is defined as an oral prednisone/prednisolone dose of \<=10 mg/day. Due to the termination of this study, analysis of this information was not performed.

Time frame: Up to Week 60

Time to Remission on Minimal Steroid Therapy

Time to remission on minimal steroid therapy is the time from Baseline to the time the participant initially tapered his/her oral prednisone/prednisolone dose to \<=10 mg/day and maintained \<=10 mg/day of oral prednisone/prednisolone with no new or non-healing (established) lesions for \>=8 weeks by Week 60. Due to the termination of this study, analysis of this information was not performed.

Time frame: Up to Week 60

Duration of Remission After Completing the Ofatumumab SC Treatment Course

Duration of remission after completing the ofatumumab SC treatment course was to be assessed during the individualized Follow-up period for participants who were in remission on minimal steroid therapy by Week 60. Due to the termination of this study, analysis of this information was not performed.

Time frame: Up to Week 156

Time to Initial Flare/Relapse by Week 60

Time to initial flare/relapse is time from Baseline to the time of appearance of \>= 3 new lesions within 1 month that do not heal spontaneously within 1 week, or to the time when there is an extension of lesions that were present at the Baseline visit. The appearance of 1 or 2 new lesions was not to be considered a flare/relapse. Due to the termination of this study, analysis of this information was not performed.

Time frame: Up to Week 60

Number of Participants Who do Not Flare/Relapse

It was planned to assess participants with out an appearance of \>= 3 new lesions within 1 month that do not heal spontaneously within 1 week, or an extension (worsening) of lesions that were present at the Baseline visit. Due to the termination of this study, analysis of this information was not performed.

Time frame: Up to Week 60

Number of Participants Who do Not Flare/Relapse on Minimal Steroid Therapy

It was planned to assess as participants who achieved remission on minimal steroid therapy and did not subsequently have a flare/relapse of disease by Week 60. Due to the termination of this study, analysis of this information was not performed.

Time frame: Up to Week 60

Time to Initial Flare/Relapse After Completing the Ofatumumab SC Treatment Course

It is the time from Baseline to the time of appearance of \>=3 new lesions within 1 month that do not heal spontaneously within 1 week, or to the time when there is an extension of lesions that were present at the Baseline visit. Due to the termination of this study, analysis of this information was not performed.

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

Number of Days Minimal Steroid Therapy is Maintained by Week 60

Minimal steroid therapy is an oral prednisone/prednisolone dose of \<= 10 mg/day. Due to the termination of this study, analysis of this information was not performed.

Time frame: Up to Week 60

Number of Days a Participant is Off Steroid Therapy by Week 60

Number of days, a participant did not require steroid therapy was observed and summarized. Due to the termination of this study, analysis of this information was not performed.

Time frame: Up to Week 60

Cumulative Dose of Corticosteroids

Cumulative dose of corticosteroids was calculated to evaluate steroid exposure and reductions in steroid dose while maintaining disease control. Due to the termination of this study, analysis of this information was not performed.

Time frame: Up to Week 60

Number of Participants With Positive Human Anti-human Antibody (HAHA) Immune Response

Blood samples for HAHA titer analysis were planned to be collected at Baseline (Week 0) and at Week 12, 24, 36, 48 and at Follow-up visit (Week 60); and at individualized Follow-up visit at Week 72. Due to the termination of this study, analysis of this information was not performed.

Time frame: Up to Week 72

Titer of Human Anti-human Antibody

Time frame: Up to Week 72