Trial record 5 of 8 for:    Open Studies | "Pemphigus"

Efficacy and Safety of Ofatumumab in Treatment of Pemphigus Vulgaris

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by GlaxoSmithKline
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline ( Stiefel, a GSK Company )
ClinicalTrials.gov Identifier:
NCT01920477
First received: July 3, 2013
Last updated: October 13, 2014
Last verified: October 2014
  Purpose

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 every 4 weeks, (with an additional 20 mg loading dose [i.e. 40 mg total] at both Week 0 and Week 4) to 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.


Condition Intervention Phase
Pemphigus
Biological: Ofatumumab
Biological: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Time to sustained remission on minimal steroid therapy [ Time Frame: Up to 60 weeks ] [ Designated as safety issue: No ]
    Time from randomization to the time of the subject's initial reduction of prednisone/prednisolone dose to <=10 mg/day and maintained a dose <=10 mg/day with no new or nonhealing (established) lesions for >=8 weeks and maintained the status until Week 60 will be assessed

  • Duration of remission on minimal steroid therapy [ Time Frame: Up to 60 weeks ] [ Designated as safety issue: No ]
    Sum of all periods of absence of new or nonhealing (established) lesions while on an oral prednisone/prednisolone dose of <=10 mg/day up to Week 60 will be assessed.


Secondary Outcome Measures:
  • Proportion of subjects achieving remission on minimal steroid therapy at Week 60 [ Time Frame: Week 60 ] [ Designated as safety issue: No ]
    Proportion of subjects achieving absence of new or nonhealing (established) lesions while on an oral prednisone/prednisolone dose of <=10 mg/day at Week 60 will be assessed.

  • Time to remission while on minimal steroid therapy by Week 60. [ Time Frame: Up to 60 weeks ] [ Designated as safety issue: No ]
    Time from randomization to the time of the subject's initial reduction of prednisone/prednisolone dose to <=10 mg/day and maintained dose at <=10 mg/day with no new or nonhealing (established) lesions for >=8 weeks by Week 60 will be assessed

  • Time to remission off steroid therapy by Week 60 [ Time Frame: Up to 60 weeks ] [ Designated as safety issue: No ]
    Time from randomization to the time of the subjects initial reduction of all steroids for >=8 weeks with an absence of new or nonhealing (established) lesions by Week 60 will be assessed

  • Proportion of subjects achieving remission while off steroid therapy by Week 60 [ Time Frame: Up to 60 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects with initial reduction of all steroids for >=8 weeks with an absence of new or nonhealing (established) lesions by Week 60 will be assessed

  • Number of days a subject maintained minimal steroid therapy by Week 60. [ Time Frame: Up to 60 weeks ] [ Designated as safety issue: No ]
    Number of days a subject maintained minimal steroid therapy (an oral prednisone/prednisolone dose of ≤10 mg/day in the absence of new or nonhealing lesions) by Week 60.

  • Time to initial flare/relapse by Week 60 [ Time Frame: Up to 60 weeks ] [ Designated as safety issue: No ]
    Time from randomization to the time of appearance of >=3 new lesions within 1 month that did not heal spontaneously within 1 week, or to the time when there was an extension of lesions that were present at the randomization by Week 60 will be assessed

  • Proportion of subjects with no flare/relapse by Week 60 [ Time Frame: Up to 60 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects achieving absence of new or nonhealing (established) lesions while on an oral prednisone/prednisolone dose of <=10 mg/day and did not subsequently have a appearance of >=3 new lesions within 1 month that did not heal spontaneously within 1 week, or to the time when there was an extension of lesions that were present at the randomization by Week 60 will be assessed

  • Cumulative dose of corticosteroids [ Time Frame: Up to 60 weeks ] [ Designated as safety issue: Yes ]
    Exposure to corticosteroids over a period of 60 weeks will be assessed

  • Change from Baseline in B-lymphocyte counts in peripheral blood [ Time Frame: Up to 60 weeks ] [ Designated as safety issue: No ]
    Change from Baseline in B-lymphocyte counts in peripheral blood at prespecified time points (Day 0 and every four weeks till Week 60) and at the time of any opportunistic infection will be assessed

  • Time to repletion of CD19+ B-cells to either >=Baseline level or >=Lower Limit of Normal (LLN) , whichever [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Time to repletion of CD19+ B-cells to either >=Baseline level (observation at Week 0) or >=LLN (110 cell/mcgL), whichever is lower will be assessed

  • Composite of pharmacokinetic (PK) of ofatumumab [ Time Frame: Up to 60 weeks ] [ Designated as safety issue: No ]
    PK parameters include: Maximum concentration (Cmax); time to maximum concentration (tmax); and area under the time-concentration curve (AUC).

  • Immunogenicity of ofatumumab [ Time Frame: Up to 60 weeks ] [ Designated as safety issue: Yes ]
    Immunogenicity will be assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response

  • Safety and tolerability of ofatumumab assessed by Adverse events (AEs). [ Time Frame: Up to 60 weeks ] [ Designated as safety issue: Yes ]
    AEs assessment include: Frequency and severity of AE, AE relationship to IP, frequency and severity of SAE, AE of special interest, Frequency and severity of infections, Percentage of subject withdrawals due to treatment-related AEs, AEs leading to permanent discontinuation of study drug, Postinjection systemic reactions, Injection site reactions

  • Change from Baseline in Vital signs [ Time Frame: Up to 60 weeks ] [ Designated as safety issue: Yes ]
    Vital signs include: pulse rate, temperature, systolic and diastolic blood pressure.

  • Change from Baseline in laboratory parameters [ Time Frame: Up to 60 weeks ] [ Designated as safety issue: Yes ]
    Laboratory parameters include: hematology, clinical chemistry, and urinalysis

  • Effect of demographic factors, including Baseline covariates on PK parameters of ofatumumab as data permits. [ Time Frame: Up to 60 weeks ] [ Designated as safety issue: No ]
    Demographic factors such as age, race, and sex.

  • Frequency of Vital signs of Clinical Concern [ Time Frame: Up to 60 weeks ] [ Designated as safety issue: Yes ]
    Vital signs of Clinical Concern are a subset based on pre-defined levels.


Estimated Enrollment: 136
Study Start Date: August 2013
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ofatumumab
Subject will receive subcutaneous administration of ofatumumab 20 mg once every 4 weeks through Week 56, with an additional 20 mg dose [i.e. 40mg total] at both Week 0 and Week 4.
Biological: Ofatumumab
Ofatumumab (human monoclonal antibody) will be provided as a liquid concentrate in a prefilled glass syringe with staked needle, stopper, and plunger containing 0.6 mL (60mg) of concentration 100 mg/mL drug product
Placebo Comparator: Placebo
Subject will receive subcutaneous administration of matching placebo of ofatumumab once every 4 weeks through Week 56, with an additional 20mg dose [i.e. 40mg total] at both Week 0 and Week 4.
Biological: Placebo
Placebo to match the active doses will consist of normal saline (sterile, pyrogen-free 0.9% NaCl) filled to 0.6 mL in prefilled glass syringes with staked needle, stopper, and plunger.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male of female (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.
  • History of at least 1 previous episode of a failed steroid taper (ie, disease flare/relapse at a prednisone/prednisolone dose >10 mg/day).
  • 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 (approximately 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, 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 6 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
  • 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 PV, 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 ofatumumab, total body irradiation, bone marrow transplant, anti-CD4, live vaccine (within 6 weeks), azathioprine, cyclosporine, dapsone, mycophenolate and methotrexate (within 8 weeks), cladribine, cyclophosphamide, plasmapheresis, immunoabsorption, or immunoglobulin therapy (within 6 months) and Rituximab (within 18 months)
  • 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, tuberculosis, or active hepatitis C; Positive test for hepatitis B antigen (HBsAg). For HBsAg negative, but hepatitis Ab (HBcAb positive (regardless of HBsAb status), an 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.
  • History of positive serology for human immunodeficiency virus; Previous serious opportunistic or atypical infections; Prior history, or suspicion, of tuberculosis;
  • 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.
  • 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).
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01920477

Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

Locations
United States, California
GSK Investigational Site Recruiting
Los Angeles, California, United States, 90045
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
United States, Michigan
GSK Investigational Site Recruiting
Ann Arbor, Michigan, United States, 48103
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Sponsors and Collaborators
Stiefel, a GSK Company
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline ( Stiefel, a GSK Company )
ClinicalTrials.gov Identifier: NCT01920477     History of Changes
Other Study ID Numbers: 116910
Study First Received: July 3, 2013
Last Updated: October 13, 2014
Health Authority: United States: Food and Drug Administration
Japan: PMDA (Pharmaceuticals and Medical Devices Agency)
Europe: European Medicines Agency

Keywords provided by GlaxoSmithKline:
monoclonal antibody
Pemphigus vulgaris
ofatumumab

Additional relevant MeSH terms:
Pemphigus
Autoimmune Diseases
Immune System Diseases
Skin Diseases
Skin Diseases, Vesiculobullous
Antibodies, Monoclonal
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 22, 2014