Pemphigus Vulgaris MedDRA version: 17.0 Level: LLT Classification code 10052802 Term: Pemphigus vulgaris System Organ Class: 100000004858
Conditions
Sponsors
Glaxo Group Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible for enrollment in the study, subjects must meet all of the following criteria: All Subjects 1. Adults (18 through 70 years of age) with clinically-documented diagnosis of PV for >2 months and 10 mg/day). Additional Criteria Prior to Randomization 4. Screening anti-Dsg antibodies consistent with a diagnosis of PV (ie, elevated anti-Dsg3 antibodies). 5. Has initiated and received a stable dose of prednisone/prednisolone from a minimum of 20 mg/day (eg, 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. (Note: subjects who are on every-other-day dosing regimens need to change to a daily dosing regimen for >= 2 weeks during the Screening Period in order to qualify.) 6. Has exhibited PV disease control, defined as no new lesions for >= 2 weeks. Additional Criteria for Female Subjects 7. A female subject is eligible to enter the study if she: a. Is of nonchildbearing potential, who is documented as either surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or post-hysterectomy) or is postmenopausal without menses for >2 years. Women who are =65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria will not be enrolled: 1. Diagnosis of pemphigus foliaceus, paraneoplastic pemphigus, or other autoimmune blistering disease (other than pemphigus vulgaris). 2. 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. 3. Prior treatment with rituximab without achieving disease control within 6 months of initiating rituximab dosing. 4. Prior treatment with any of the following within the specified periods (refer toprotocol, table page 32) 5. Confirmed PML, or neurological findings potentially consistent with PML. 6. 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 HBsAg. For HBsAg negative, but anti-HBc 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. 7. Past or current malignancy, except for: -Cervical carcinoma Stage 1B or less. -Noninvasive basal cell and squamous cell skin carcinoma. -Cancer diagnoses with a duration of complete response (remission) >5 years. Note: A history of hematologic malignancy excludes a subject from participation, regardless of response. 8. 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. 9. Any of the following screening laboratory values: -White blood cells (WBC) 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). 10. 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. 11. 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). 12. Woman who is breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy, based on disease remission, of ofatumumab SC at a dose of 20 mg administered every 4 weeks (with an additional 20-mg loading dose [ie, 40 mg total] at both Week 0 and Week 4) in subjects with PV.;Secondary Objective: -To evaluate the safety and tolerability of ofatumumab SC. -To evaluate disease flare/relapse during treatment with ofatumumab SC. -To evaluate reductions in steroid dose while maintaining disease control. -To determine the extent of B-cell depletion and repletion following ofatumumab SC. -To evaluate the immunogenicity of ofatumumab SC. -To assess the population pharmacokinetics of ofatumumab SC.;Primary end point(s): Two co-primary efficacy endpoints will be evaluated: -Time to SR on minimal steroid therapy (defined as time from randomization to the time the subject initially tapered his/her oral prednisone/prednisolone dose to =10 mg/day and maintained =10 mg/day of oral prednisone/prednisolone with no new or nonhealing lesions for =8 weeks AND maintained that status until Week 60). -Duration of remission on minimal steroid therapy (defined as total time [sum] of all periods of remission while on minimal steroid therapy [oral prednisone/prednisolone dose of =10 mg/day] up to Week 60).;Timepoint(s) of evaluation of this end point: week 60 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Proportion of subjects achieving remission on minimal steroid therapy (defined as subjects who had an absence of new or nonhealing lesions while on an oral prednisone/prednisolone dose of =10 mg/day for=8 weeks) at Week 60. -Time to remission while on minimal steroid therapy (defined as time from randomization to the time the subject initially tapered his/her oral prednisone/prednisolone dose to =10 mg/day and maintained =10 mg/day of oral prednisone/prednisolone with no new or nonhealing lesions for =8 weeks) by Week 60. -Time to initial flare/relapse (defined as the time from randomization to the time that =3 new lesions within 1 month appear and do not heal spontaneously within 1 week, or to the time when there is an extension of lesions that were present at the randomization visit) by Week 60. -Proportion of subjects who did not flare/relapse (defined as subjects who achieved remission on minimal steroid therapy and did not subsequently have a flare of disease) by Week 60. A flare/relapse is defined as new lesions that do not heal spontaneously within 1 week, or when there is an extension of lesions that were present at the randomization visit. -Time to remission off steroid therapy by Week 60 (defined as the time from randomization to the time the subject initially tapered off all steroids for =8 weeks with an absence of new or nonhealing lesions). -Proportion of subjects achieving remission while off steroid therapy by Week 60. -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. -Cumulative dose of corticosteroids.;Timepoint(s) of evaluation of this end point: week 60 | — |
Countries
Australia, China, Croatia, France, Greece, Israel, Italy, Japan, Korea, Republic of, Poland, Russian Federation, Ukraine, United States
Contacts
Public ContactClincial Trials Helpdesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed