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Efficacy and Safety of Ofatumumab in Treatment of Pemphigus Vulgaris

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ClinicalTrials.gov Identifier: NCT01920477
Recruitment Status : Terminated (Novartis has acquired the rights to ofatumumab and terminated the OPV116910 and OPV117059 studies. This decision is not linked to any safety consideration.)
First Posted : August 12, 2013
Results First Posted : June 6, 2019
Last Update Posted : June 6, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:

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 was 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 was 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 would result.


Condition or disease Intervention/treatment Phase
Pemphigus Vulgaris Biological: Ofatumumab Biological: Placebo Phase 3

Detailed Description:
Novartis terminated the development of the PV program and this study was terminated for non-safety reasons

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, 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
Actual Study Start Date : August 13, 2013
Actual Primary Completion Date : April 13, 2016
Actual Study Completion Date : January 11, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pemphigus
Drug Information available for: Ofatumumab

Arm Intervention/treatment
Experimental: Ofatumumab
Subject received subcutaneous administration of ofatumumab 20 mg once every 4 weeks through Week 56, with an additional 20 mg dose (that is 40mg total) at both Week 0 and Week 4.
Biological: Ofatumumab
Ofatumumab (human monoclonal antibody) was provided in prefilled glass syringes initial syringes contained 0.6ml (60mg) of concentration 100 mg/m: drug product subsequently modified to 0.4 mL (20mg) concentration (50mg/ML) drug product

Placebo Comparator: Placebo
Subject received subcutaneous administration of matching placebo of ofatumumab once every 4 weeks through Week 56, with an additional dose at both Week 0 and Week 4.
Biological: Placebo
Placebo to match the active doses will consist of prefilled glass syringes filled with normal saline.




Primary Outcome Measures :
  1. Number of Subjects Who Experienced Sustained Remission on Minimal Steroid Therapy [ Time Frame: Baseline up to approximately 60 weeks ]
    Sustained remission = time from randomization to the time of the subject's initial reduction of prednisone/prednisolone dose to <=10 mg/day and maintenance of a dose <=10 mg/day with no new or nonhealing lesions for >=8 weeks and maintenance of the status until Week 60.

  2. Duration of Remission on Minimal Steroid Therapy [ Time Frame: Baseline up to approximately 60 weeks ]
    Sum of all periods of absence of new or nonhealing lesions while on an oral prednisone/prednisolone dose of <=10 mg/day up to Week 60 was assessed.


Secondary Outcome Measures :
  1. Percentage of Subjects Achieving Remission on Minimal Steroid Therapy at Week 60 [ Time Frame: Week 60 ]
    Percentage of subjects who achieved absence of new or nonhealing lesions while on an oral prednisone/prednisolone dose of <=10 mg/day for > or = 8 weeks at Week 60 was assessed. Time to remission was not estimable.

  2. Time to Remission While on Minimal Steroid Therapy by Week 60. [ Time Frame: Baseline up to approximately 60 weeks ]
    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 lesions for >=8 weeks by Week 60 was assessed

  3. Percentage of Subjects Achieving Remission While Off Steroid Therapy by Week 60 [ Time Frame: Baseline up to approximately 60 weeks ]
    Percentage of subjects with initial reduction of all steroids for >=8 weeks with an absence of new or nonhealing (established) lesions by Week 60 were to be assessed. All subjects remained on prednisone/prednisolone so this endpoint could not be analyzed.Time to remission off steroid therapy also could not be analyzed

  4. Number of Days a Subject Maintained Minimal Steroid Therapy by Week 60. [ Time Frame: Baseline up to approximately 60 weeks ]
    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.

  5. Time to Initial Flare/Relapse by Week 60 [ Time Frame: Baseline up to approximately 60 weeks ]
    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 was assessed

  6. Percentage of Participants With no Flare/Relapse by Week 60 [ Time Frame: Baseline up to approximately 60 weeks ]
    Percentage of participants achieving absence of new or nonhealing 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 was assessed

  7. Plasma Trough Concentrations of Ofatumumab [ Time Frame: 4 hours post baseline, Days 1-4,7,14, Weeks 4,8,12,16,20,24,36,48,52,56, up to approximately 60 weeks ]
    Only plasma (trough) concentrations of ofatumumab were presented

  8. Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A [ Time Frame: Baseline up to approximately 60 weeks ]
    Assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response

  9. Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G [ Time Frame: Baseline up to approximately 60 weeks ]
    Assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response

  10. Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M [ Time Frame: Baseline up to approximately 60 weeks ]
    Assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response

  11. Largest Mean Decrease From Baseline for Immunoglobulin A, G and M [ Time Frame: Baseline up to approximately 60 weeks ]
    Immunoglobulins A, G and M were assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response

  12. Change From Baseline for CD19+ B Cell Count [ Time Frame: Baseline up to approximately 60 weeks ]
    CD19+ B cell count will be performed using Flow Cytometry



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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 immunosuppressant or immunomodulation agents within the protocol specified periods
  • Evidence or history of clinically significant infections

For Japan: Evidence or history of clinically significant infection or medical condition including: Pneumocystis pneumonia or interstitial pneumonia

  • 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).
  • 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)
  • Woman who is breastfeeding.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01920477


Locations
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United States, California
Novartis Investigational Site
Los Angeles, California, United States, 90045
United States, Georgia
Novartis Investigational Site
Atlanta, Georgia, United States, 30322
United States, Michigan
Novartis Investigational Site
Ann Arbor, Michigan, United States, 48103
United States, New York
Novartis Investigational Site
Buffalo, New York, United States, 14203
United States, North Carolina
Novartis Investigational Site
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Novartis Investigational Site
Pittsburgh, Pennsylvania, United States, 15213
United States, Utah
Novartis Investigational Site
Salt Lake City, Utah, United States, 84132
Australia, Victoria
Novartis Investigational Site
East Melbourne, Victoria, Australia, 3002
Novartis Investigational Site
Melbourne, Victoria, Australia, 3050
Greece
Novartis Investigational Site
Thessalonica, Greece, 54643
Israel
Novartis Investigational Site
Ramat-Gan, Israel, 52621
Novartis Investigational Site
Tel Aviv, Israel, 64239
Italy
Novartis Investigational Site
Milano, Lombardia, Italy, 20122
Japan
Novartis Investigational Site
Tokyo, Japan, 160-8582
Poland
Novartis Investigational Site
Warszawa, Poland, 02-008
Romania
Novartis Investigational Site
Cluj-Napoca, Romania, 400006
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] September 5, 2016
Statistical Analysis Plan  [PDF] March 29, 2018


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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01920477     History of Changes
Other Study ID Numbers: 116910
First Posted: August 12, 2013    Key Record Dates
Results First Posted: June 6, 2019
Last Update Posted: June 6, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Pemphigus
MAB
autoimmune disorder
human CD20 antigen
subcutaneous
vulgaris
Phase 3
monoclonal antibody
ofatumumab
PV
rare disease
OMB157
adult

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