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
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 35
- 试验地点
- 16
- 主要终点
- Number of Subjects Who Experienced Sustained Remission on Minimal Steroid Therapy
研究概览
简要总结
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.
详细描述
Novartis terminated the development of the PV program and this study was terminated for non-safety reasons
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Placebo (Biological)
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.
干预措施: Ofatumumab (Biological)
结局指标
主要结局
Number of Subjects Who Experienced Sustained Remission on Minimal Steroid Therapy
时间窗: 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.
Duration of Remission on Minimal Steroid Therapy
时间窗: 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.
次要结局
- Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin M(Baseline up to approximately 60 weeks)
- Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin A(Baseline up to approximately 60 weeks)
- Number of Participants With Values Below Lower Limit of Normal for Immunoglobulin G(Baseline up to approximately 60 weeks)
- Time to Remission While on Minimal Steroid Therapy by Week 60.(Baseline up to approximately 60 weeks)
- Plasma Trough Concentrations of Ofatumumab(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(Week 60)
- Time to Initial Flare/Relapse by Week 60(Baseline up to approximately 60 weeks)
- Percentage of Participants With no Flare/Relapse by Week 60(Baseline up to approximately 60 weeks)
- Largest Mean Decrease From Baseline for Immunoglobulin A, G and M(Baseline up to approximately 60 weeks)
- Change From Baseline for CD19+ B Cell Count(Baseline up to approximately 60 weeks)
- Percentage of Subjects Achieving Remission While Off Steroid Therapy by Week 60(Baseline up to approximately 60 weeks)
- Number of Days a Subject Maintained Minimal Steroid Therapy by Week 60.(Baseline up to approximately 60 weeks)