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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01920477




Registration number
NCT01920477
Ethics application status
Date submitted
3/07/2013
Date registered
12/08/2013
Date last updated
6/06/2019

Titles & IDs
Public title
Efficacy and Safety of Ofatumumab in Treatment of Pemphigus Vulgaris
Scientific 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
Secondary ID [1] 0 0
116910
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pemphigus Vulgaris 0 0
Condition category
Condition code
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Ofatumumab
Treatment: Other - Placebo

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.

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.


Treatment: Other: 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

Treatment: Other: Placebo
Placebo to match the active doses will consist of prefilled glass syringes filled with normal saline.
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Subjects Who Experienced Sustained Remission on Minimal Steroid Therapy
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Baseline up to approximately 60 weeks
Primary outcome [2] 0 0
Duration of Remission on Minimal Steroid Therapy
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
Baseline up to approximately 60 weeks
Secondary outcome [1] 0 0
Percentage of Subjects Achieving Remission on Minimal Steroid Therapy at Week 60
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Week 60
Secondary outcome [2] 0 0
Time to Remission While on Minimal Steroid Therapy by Week 60.
Assessment method [2] 0 0
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
Timepoint [2] 0 0
Baseline up to approximately 60 weeks
Secondary outcome [3] 0 0
Percentage of Subjects Achieving Remission While Off Steroid Therapy by Week 60
Assessment method [3] 0 0
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
Timepoint [3] 0 0
Baseline up to approximately 60 weeks
Secondary outcome [4] 0 0
Number of Days a Subject Maintained Minimal Steroid Therapy by Week 60.
Assessment method [4] 0 0
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.
Timepoint [4] 0 0
Baseline up to approximately 60 weeks
Secondary outcome [5] 0 0
Time to Initial Flare/Relapse by Week 60
Assessment method [5] 0 0
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
Timepoint [5] 0 0
Baseline up to approximately 60 weeks
Secondary outcome [6] 0 0
Percentage of Participants With no Flare/Relapse by Week 60
Assessment method [6] 0 0
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
Timepoint [6] 0 0
Baseline up to approximately 60 weeks
Secondary outcome [7] 0 0
Plasma Trough Concentrations of Ofatumumab
Assessment method [7] 0 0
Only plasma (trough) concentrations of ofatumumab were presented
Timepoint [7] 0 0
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
Secondary outcome [8] 0 0
Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A
Assessment method [8] 0 0
Assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response
Timepoint [8] 0 0
Baseline up to approximately 60 weeks
Secondary outcome [9] 0 0
Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G
Assessment method [9] 0 0
Assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response
Timepoint [9] 0 0
Baseline up to approximately 60 weeks
Secondary outcome [10] 0 0
Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M
Assessment method [10] 0 0
Assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response
Timepoint [10] 0 0
Baseline up to approximately 60 weeks
Secondary outcome [11] 0 0
Largest Mean Decrease From Baseline for Immunoglobulin A, G and M
Assessment method [11] 0 0
Immunoglobulins A, G and M were assessed by the incidence, titer, and type of human anti-human antibody (HAHA) immune response
Timepoint [11] 0 0
Baseline up to approximately 60 weeks
Secondary outcome [12] 0 0
Change From Baseline for CD19+ B Cell Count
Assessment method [12] 0 0
CD19+ B cell count will be performed using Flow Cytometry
Timepoint [12] 0 0
Baseline up to approximately 60 weeks

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/08/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
11/01/2018
Sample size
Target
Accrual to date
Final
35
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Novartis Investigational Site - East Melbourne
Recruitment hospital [2] 0 0
Novartis Investigational Site - Melbourne
Recruitment postcode(s) [1] 0 0
3002 - East Melbourne
Recruitment postcode(s) [2] 0 0
3050 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Utah
Country [8] 0 0
Greece
State/province [8] 0 0
Thessalonica
Country [9] 0 0
Israel
State/province [9] 0 0
Ramat-Gan
Country [10] 0 0
Israel
State/province [10] 0 0
Tel Aviv
Country [11] 0 0
Italy
State/province [11] 0 0
Lombardia
Country [12] 0 0
Japan
State/province [12] 0 0
Tokyo
Country [13] 0 0
Poland
State/province [13] 0 0
Warszawa
Country [14] 0 0
Romania
State/province [14] 0 0
Cluj-Napoca

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
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


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT01920477