Efficacy and Safety of Ofatumumab in Treatment of Pemphigus Vulgaris

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01920477
• Date of registration: 03/07/2013
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• 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
• Date of first enrolment: August 13, 2013
• Target sample size: 35
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT01920477
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Australia, Croatia, France, Greece, Israel, Italy, Japan, Korea, Republic of, Poland, Romania, Russian Federation, Ukraine, United States

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Pemphigus Vulgaris

Intervention(s)

Biological: Ofatumumab

Biological: Placebo

Primary Outcome(s)

Number of Subjects Who Experienced Sustained Remission on Minimal Steroid Therapy [Time Frame: Baseline up to approximately 60 weeks]

Duration of Remission on Minimal Steroid Therapy [Time Frame: Baseline up to approximately 60 weeks]

Secondary Outcome(s)

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

Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A [Time Frame: Baseline up to approximately 60 weeks]

Largest Mean Decrease From Baseline for Immunoglobulin A, G and M [Time Frame: Baseline up to approximately 60 weeks]

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

Percentage of Participants With no Flare/Relapse by Week 60 [Time Frame: Baseline up to approximately 60 weeks]

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]

Percentage of Subjects Achieving Remission on Minimal Steroid Therapy at Week 60 [Time Frame: Week 60]

Change From Baseline for CD19+ B Cell Count [Time Frame: Baseline up to approximately 60 weeks]

Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G [Time Frame: Baseline up to approximately 60 weeks]

Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M [Time Frame: Baseline up to approximately 60 weeks]

Percentage of Subjects Achieving Remission While Off Steroid Therapy by Week 60 [Time Frame: Baseline up to approximately 60 weeks]

Time to Remission While on Minimal Steroid Therapy by Week 60. [Time Frame: Baseline up to approximately 60 weeks]

Secondary ID(s)

116910

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 06/06/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01920477