Clinical trial NCT01920477: Efficacy and Safety of Ofatumumab in Treatment of Pemphigus Vulgaris
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Pemphigus Vulgaris
Keywords: Pemphigus
MAB
autoimmune disorder
human CD20 antigen
subcutaneous
vulgaris
Phase 3
monoclonal antibody
ofatumumab
PV
rare disease
OMB157
adult
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-08-12
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Eligibility 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.

Primary outcomes:
measure: Number of Subjects Who Experienced Sustained Remission on Minimal Steroid Therapy
timeFrame: Baseline up to approximately 60 weeks
measure: Duration of Remission on Minimal Steroid Therapy
timeFrame: Baseline up to approximately 60 weeks
Secondary outcomes:
measure: Percentage of Subjects Achieving Remission on Minimal Steroid Therapy at Week 60
timeFrame: Week 60
measure: Time to Remission While on Minimal Steroid Therapy by Week 60.
timeFrame: Baseline up to approximately 60 weeks
measure: Percentage of Subjects Achieving Remission While Off Steroid Therapy by Week 60
timeFrame: Baseline up to approximately 60 weeks
measure: Number of Days a Subject Maintained Minimal Steroid Therapy by Week 60.
timeFrame: Baseline up to approximately 60 weeks
measure: Time to Initial Flare/Relapse by Week 60
timeFrame: Baseline up to approximately 60 weeks
measure: Percentage of Participants With no Flare/Relapse by Week 60
timeFrame: Baseline up to approximately 60 weeks
measure: Plasma Trough Concentrations of Ofatumumab
timeFrame: 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
measure: Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A
timeFrame: Baseline up to approximately 60 weeks
measure: Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G
timeFrame: Baseline up to approximately 60 weeks
measure: Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M
timeFrame: Baseline up to approximately 60 weeks
measure: Largest Mean Decrease From Baseline for Immunoglobulin A, G and M
timeFrame: Baseline up to approximately 60 weeks
measure: Change From Baseline for CD19+ B Cell Count
timeFrame: Baseline up to approximately 60 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Novartis Investigational Site
state: California
city: Atlanta
country: United States
facility: Novartis Investigational Site
state: Georgia
city: Ann Arbor
country: United States
facility: Novartis Investigational Site
state: Michigan
city: Buffalo
country: United States
facility: Novartis Investigational Site
state: New York
city: Durham
country: United States
facility: Novartis Investigational Site
state: North Carolina
city: Pittsburgh
country: United States
facility: Novartis Investigational Site
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Novartis Investigational Site
state: Utah
city: East Melbourne
country: Australia
facility: Novartis Investigational Site
state: Victoria
city: Melbourne
country: Australia
facility: Novartis Investigational Site
state: Victoria
city: Thessalonica
country: Greece
facility: Novartis Investigational Site
city: Ramat-Gan
country: Israel
facility: Novartis Investigational Site
city: Tel Aviv
country: Israel
facility: Novartis Investigational Site
city: Milano
country: Italy
facility: Novartis Investigational Site
state: Lombardia
city: Tokyo
country: Japan
facility: Novartis Investigational Site
city: Warszawa
country: Poland
facility: Novartis Investigational Site
city: Cluj-Napoca
country: Romania
facility: Novartis Investigational Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: