Last updated: 11/03/2018 19:45:56
This product has been transferred to Novartis. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov.
OPV116910: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Investigate the Efficacy and Safety of Ofatumumab Injection for Subcutaneous Use in Subjects with Pemphigus Vulgaris
GSK study ID
116910
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Trial overview
Official title: OPV116910: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Investigate the Efficacy and Safety of Ofatumumab Injection for Subcutaneous Use in Subjects with Pemphigus Vulgaris
Trial description: Pemphigus vulgaris (PV) is a rare, chronic, debilitating, and potentially life-threatening autoimmune disorder that is characterized by mucocutaneous blisters. Ofatumumab is a novel monoclonal antibody (mAb) that specifically binds to the human CD20 antigen, which is expressed only in B lymphocytes. The purpose of this study is to evaluate the efficacy, tolerability, and safety of ofatumumab injection for subcutaneous use (ofatumumab SC) 20 milligrams (mg) administered once in every 4 weeks, (with an additional 20 mg loading dose [i.e. 40 mg total] at both Week 0 and Week 4) in subjects with PV. It is anticipated that with sustained B-cell depletion in the presence of ofatumumab SC, and the resultant reduction of pathogenic anti Dsg (desmoglein) autoantibodies in PV, that clinical remission of the disease will result.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Time to sustained remission on minimal steroid therapy
Timeframe: Up to 60 weeks
Duration of remission on minimal steroid therapy
Timeframe: Up to 60 weeks
Secondary outcomes:
Proportion of subjects achieving remission on minimal steroid therapy at Week 60
Timeframe: Week 60
Time to remission while on minimal steroid therapy by Week 60.
Timeframe: Up to 60 weeks
Time to remission off steroid therapy by Week 60
Timeframe: Up to 60 weeks
Proportion of subjects achieving remission while off steroid therapy by Week 60
Timeframe: Up to 60 weeks
Number of days a subject maintained minimal steroid therapy by Week 60.
Timeframe: Up to 60 weeks
Time to initial flare/relapse by Week 60
Timeframe: Up to 60 weeks
Proportion of subjects with no flare/relapse by Week 60
Timeframe: Up to 60 weeks
Cumulative dose of corticosteroids
Timeframe: Up to 60 weeks
Change from Baseline in B-lymphocyte counts in peripheral blood
Timeframe: Up to 60 weeks
Time to repletion of CD19+ B-cells to either >=Baseline level or >=Lower Limit of Normal (LLN) , whichever
Timeframe: Up to 2 years
Composite of population pharmacokinetics (PK) of ofatumumab
Timeframe: Up to 60 weeks
Immunogenicity of ofatumumab
Timeframe: Up to 60 weeks
Safety and tolerability of ofatumumab assessed by Adverse events (AEs).
Timeframe: Up to 60 weeks
Change from Baseline in Vital signs
Timeframe: Up to 60 weeks
Change from Baseline in laboratory parameters
Timeframe: Up to 60 weeks
Effect of demographic factors, including Baseline covariates on PK parameters of ofatumumab as data permits.
Timeframe: Up to 60 weeks
Frequency of Vital signs of Clinical Concern
Timeframe: Up to 60 weeks
Interventions:
Enrollment:
35
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Pemphigus
Product
ofatumumab, prednisolone, prednisone
Collaborators
None
Study date(s)
August 2013 to September 2017
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
18 - 70 Year
Accepts healthy volunteers
none
- Inclusion criteria
- Adults (18 through 70 years of age) with clinically-documented diagnosis of PV for >2 months and <10 years.
Inclusion and exclusion criteria
Inclusion criteria:
- Inclusion criteria
- Adults (18 through 70 years of age) with clinically-documented diagnosis of PV for >2 months and <10 years.
- History of biopsy consistent with PV (Hematoxylin and Eosin staining and direct immunofluorescence). If no history, a biopsy may be performed during the Screening Period.
- At least 1 previous episode of a failed steroid taper (ie, disease flare/relapse) at a prednisone/prednisolone dose >10 mg/day. The following criteria must have been met as evidence of disease severity at the time of the failed steroid taper: a) A Pemphigus Severity of Clinical Disease score of moderate (2) or severe (3) (may be historical/retrospective assessment). b) Required a treatment change at the time of the failed steroid taper of at least one of the following: i) A steroid increase to >=20 mg/day OR ii) The addition of immunosuppressive/immunomodulatory agent/treatment OR iii) A dose increase of immunosuppressive/immunomodulatory agent/treatment
- Screening anti-Dsg antibodies consistent with a diagnosis of PV (ie, elevated antiDsg3 antibodies).
- Has initiated and received a stable dose of prednisone/prednisolone from a minimum of 20 mg/day (example: 0.25 mg/kg/day for an 80 kg person) up to a maximum of 120 mg/day or 1.5 mg/kg/day (whichever is higher) for >=2 weeks prior to randomization.
- Has exhibited PV disease control, defined as no new lesions for >=2 weeks.
- A female subject is eligible to enter the study if she: Is of non-child bearing potential, who is either surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or post-hysterectomy) 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 screening 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, defined as a woman who has functional ovaries, ducts, and a uterus with no documented impairment that would cause sterility. This includes women with oligomenorrhea (even severe), women who are perimenopausal, and women who have just begun to menstruate. Subject must have a negative serum pregnancy test at screening and must agree to the consistent and correct use of acceptable methods of contraception during heterosexual intercourse, beginning when the subject provides informed consent and lasting until 12 months after last dose of investigational product. Acceptable methods of contraception are limited to the oral contraceptives (either combined or progesterone only), injectable progesterone, levonorgestrel implants, estrogenic vaginal ring, percutaneous contraceptive patches, intrauterine device or intrauterine system with a documented failure rate of <1% per year, male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject’s entry into the study; this male must be the subject’s sole partner, double barrier method (condom and an occlusive cap [diaphragm or cervical/vault caps] with a vaginal spermicidal agent [foam/gel/film/cream/suppository]) and complete abstinence from heterosexual intercourse, For Japan subjects, in the list of acceptable methods of contraception, the following methods are not applicable in Japan: oral contraceptives with progestogen alone, injectable progesterone, levonorgestrel implants, estrogenic vaginal ring, percutaneous contraceptive patches, vaginal spermicidal foam, gel, film, and cream French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category. Exclusion Criteria:
- Diagnosis of pemphigus foliaceus, paraneoplastic pemphigus, or other autoimmune blistering disease (other than pemphigus vulgaris).
- 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 rituximab without achieving disease control within 6 months of initiating rituximab dosing.
- Prior treatment with with any of the following within the specified periods: any time: ofatumumab, total body irradiation, bone marrow transplantation, anti-CD4 ; within 2 weeks: systemic steroids (except for prednisone/prednisolone) ; within 6 weeks: live vaccine ; within 8 weeks: azathioprine, cyclosporine, dapsone, mycophenolate, methotrexate and tacrolimus; within 6 months:cladribine, cyclophosphamide, plasmapheresis, immunoabsorption or immunoglobulin therapy, alemtuzumab, mitoxantrone; and within 18 months: Rituximab or other drugs affecting the number and function of B-cells- Confirmed progressive multifocal leukoencephalopathy (PML), or neurological findings potentially consistent with PML
- Evidence or history of clinically significant infection 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 (anti-HBc/HBcAb positive (regardless of hepatitis B surface antibody [HbsAb] status), an HBV deoxyribonucleic acid (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; History of positive serology for human immunodeficiency virus; Previous serious opportunistic or atypical infections; Prior history, or suspicion, of tuberculosis (TB); For Japan: Evidence or history of clinically significant infection or medical condition including: Pneumocystis pneumonia or interstitial pneumonia (based on results of screening posterior-anterior chest X-ray, KL-6, and beta-D glucan). Order these tests from a local laboratory during screening and as part of a work-up for a subject with signs or symptoms of potential concern during the study; Based on the Japanese Guideline for Hepatitis B, for subjects who are HBsAg negative, anti-HBc (HBcAb) negative, but HBsAb positive, an HBV DNA test will be performed and the subject will be excluded from the study if results are positive; If any of the following criteria for TB screening are met:Past medical history for latent or active TB before screening; Sign(s) or symptom(s) suggestive of active TB in medical history on examination; Recent close contact with a patient with active TB; Positive interferon-gamma release assay or tuberculin skin test within 1 month before the first dose of study treatment; Chest x-ray, taken within 3 months before first dose of study treatment, shows evidence indicating currently active or previous TB. For South Korea: Evidence or history of clinically significant infection including: For subjects who are HBsAg negative, anti-HBc (HBcAb) negative, but HBsAb positive, an HBV DNA test will be performed and the subject will be excluded from the study if results are positive; If any of the following criteria for TB screening are met: Past medical history for latent or active TB before screening, Sign(s) or symptom(s) suggestive of active TB in medical history on examination; Recent close contact with a patient with active TB; Positive interferon-gamma release assay or tuberculin skin test within 1 month before the first dose of study treatment; Chest x-ray, taken within 3 months before first dose of study treatment, shows evidence indicating currently active or previous TB.
- Past or current malignancy, except for cervical carcinoma Stage 1B or less, noninvasive basal cell and squamous cell skin carcinoma and cancer diagnoses with a duration of complete response (remission) >5 years
- 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. This includes subjects who require any systemic steroid treatment for a concurrent medical condition (other than pemphigus vulgaris).
- White blood cells (WBC) <3.8 GI/L (<3800/mm^3), neutrophils <2 GI/L (<2000/mm^3), platelets <130 GI/L (130,000/mm^3), circulating IgG, IgA, or IgM levels <10% of the LLN and requiring treatment in the opinion of the investigator, alanine aminotransferase (ALT) >2.0 times the upper limit of normal (ULN), aspartate aminotransferase (AST) >2.0 X ULN, alkaline phosphatase (ALP) >1.5 X ULN, bilirubin >1.5 X ULN (except in cases of isolated predominantly indirect hyperbilirubinemia due to Gilbert’s syndrome).
- Use of an investigational drug or other experimental therapy within 4 weeks, 5 pharmacokinetic half-lives, or the duration of biological effect (whichever is longer) prior to Screening.
- Electrocardiogram (ECG) showing a clinically significant abnormality or showing a QTc interval ≥450 msec (≥480 msec for subjects with a bundle branch block) (ECG to be obtained during Screening/prior to receiving the first dose of study drug).
- Woman who is breastfeeding.
Trial location(s)
This study does not involve prospective enrollment of participants.
Study documents
No study documents available.
Results overview
Study Results yet to be posted
Recruitment status
No longer a GSK study
Actual primary completion date
Not applicable
Actual study completion date
Not applicable
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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