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

Pemphigus Clinical Trial

Official title:

OPV117059: A Long-Term Extension Study of Ofatumumab Injection for Subcutaneous Use in Subjects With Pemphigus Vulgaris

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02613910
• Other study ID #: 117059
• Status: Terminated
• Phase: Phase 3
• First received: November 23, 2015
• Last updated: March 9, 2017
• Start date: December 2015
• Est. completion date: March 2016

Study information

• Verified date: March 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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).

Related Conditions & MeSH terms

• Pemphigus

Intervention

Drug:
• Ofatumumab
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
Acetaminophen/paracetamol will be supplied by study centre as 1 gram tablet, caplet, capsule or liquid for oral administration
• Antihistamine (cetirizine or equivalent)
Antihistamine (cetirizine or equivalent) will be supplied by study center as 10 mg tablet, caplet, capsule or liquid for oral administration
• Prednisone/Prednisolone
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

Locations

Country	Name	City	State
United States	GSK Investigational Site	Ann Arbor	Michigan
United States	GSK Investigational Site	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects with adverse events(AEs)		Up to Week 60
Primary	Severity of adverse events		Up to Week 60
Primary	Number of subjects with adverse events related to ofatumumab SC		Up to Week 60
Primary	Number of subjects with Serious adverse events (SAEs)		Up to Week 156
Primary	Number of subjects withdrawn due to treatment-related AEs		Up to Week 60
Primary	Number of subjects with AEs leading to permanent discontinuation of ofatumumab SC		Up to Week 60
Primary	Number of subjects with AEs of special interest	AEs of special interest includes opportunistic infections, serious post-injection (inj) systemic reactions, progressive multifocal leukoencephalopathy (PML), hepatitis B infection or reactivation, severe mucocutaneous reactions, cytopenias, and cardiovascular events	Up to Week 156
Primary	Number of subjects with Infections		Up to Week 60
Primary	Number of subjects with Post-injection systemic reactions		Up to Week 60
Primary	Number of subjects with injection site reactions		Up to Week 60
Primary	Change from Baseline in blood pressure	Blood pressure includes systolic and diastolic blood pressure measured after at least 5 minutes of rest	Baseline (Week 0) and up to Week 60
Primary	Change from Baseline in heart rate		Baseline (Week 0) and up to Week 60
Primary	Change from Baseline in temperature		Baseline (Week 0) and up to Week 60
Primary	Number of subjects with vital signs of clinical concern		Up to Week 60
Primary	Number of subjects with clinically-significant Electrocardiogram (ECG) abnormalities		Week 60
Primary	Change from Baseline in Hematology parameters	The following hematology assessments will be performed: platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, nucleated RBCs, white blood cells (WBC) count, WBC differential (automated), neutrophils, bands, lymphocytes, monocytes, eosinophils, basophils, cluster of differentiation (CD)19+ B-lymphocyte counts (LC), CD3, CD4, CD8, CD4:CD8 ratio	Baseline (Week 0) and up to Week 156
Primary	Change from Baseline in Chemistry parameters	The following chemistry assessments will be performed: total protein, albumin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, total bilirubin, blood urea nitrogen, creatinine, creatinine clearance (calculated), sodium, potassium, chloride, calcium, bicarbonate and glucose	Baseline (Week 0) and up to Week 156
Primary	Change from Baseline in Urinalysis parameters	The following urinalysis assessments will be performed appearance, specific gravity, pH, protein, glucose, leukocyte esterase (leukocytes), ketones, hemoglobin (RBCs), microalbumin, creatinine, microalbumin: creatinine ratio, microscopy.	Baseline (Week 0) and up to Week 156
Primary	Number of subjects with laboratory results of potential clinical concern		Up to Week 156
Primary	Change from Baseline in immunoglobulins (Ig)	Blood samples for IgA, IgM, and IgG analysis will be collected at Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156	Baseline (Week 0) and up to Week 156
Secondary	Time to sustained remission on minimal steroid therapy	It is time from baseline (Week 0) to the time the subject initially tapered his/her oral prednisone/prednisolone dose to <=10 milligram (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	Up to Week 60
Secondary	Duration of remission on minimal steroid therapy	It is total time (sum) of all periods of remission while on minimal steroid therapy (oral prednisone/prednisolone dose <=10 mg/day) up to Week 60	Up to Week 60
Secondary	Proportion of subjects achieving sustained remission on minimal steroid therapy by Week 60	Sustained remission on minimal steroid therapy is the time from baseline to the time the subject 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 nonhealing (established) lesions for >=8 weeks and maintained that status until Week 60	Up to Week 60
Secondary	Time to remission off steroid therapy by Week 60	Remission is defined as absence of new or non-healing (established) lesions for >=8 weeks	Up to Week 60
Secondary	Proportion of subjects achieving remission while off steroid therapy by Week 60		Up to Week 60
Secondary	Proportion of subjects achieving remission on minimal steroid therapy	Remission is defined as absence of new or nonhealing (established) lesions for >=8 weeks and minimal steroid therapy is defined as an oral prednisone/prednisolone dose of <=10 mg/day	Up to Week 60
Secondary	Time to remission on minimal steroid therapy	Time from baseline to the time the subject 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 nonhealing (established) lesions for >=8 weeks by Week 60	Up to Week 60
Secondary	Duration of remission after completing the ofatumumab SC treatment course (i.e., during the Individualized Follow-up Period)	Subjects who are in remission on minimal steroid therapy by Week 60 of the extension study	Up to Week 60
Secondary	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	Up to Week 60
Secondary	Proportion of subjects who do not flare/relapse	Appearance of >= 3 new lesions within 1 month that do not heal spontaneously within 1 week, or when there is an extension (worsening) of lesions that were present at the baseline visit	Up to Week 60
Secondary	Proportion of subjects who do not flare/relapse on minimal steroid therapy		Up to Week 60
Secondary	Time to initial flare/relapse after completing the ofatumumab SC treatment course that is during the Individualized Follow-up Period	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	Up to Week 60
Secondary	Number of days minimal steroid therapy is maintained by Week 60	Minimal steroid therapy is an oral prednisone/prednisolone dose of <= 10 mg/day	Up to Week 60
Secondary	Number of days a subject is off steroid therapy by Week 60		Up to Week 60
Secondary	Cumulative dose of corticosteroids		Up to Week 60
Secondary	Immunogenicity as measured by the incidence, titer, and type of human anti human antibody (HAHA) immune response	Blood samples for HAHA analysis will be collected at Weeks 12, 24, 36, 48, 60, 72.	Up to Week 72