A Randomized, Part A Partial Blinded and Part B Double Blinded, Placebo-controlled 24-week Clinical Study to Evaluate the Efficacy and Safety of Nomacopan Therapy in Adult Patients With Bullous Pemphigoid Receiving Adjunct Oral Corticosteroid Therapy (ARREST-BP)
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 试验地点
- 12
- 主要终点
- Achievement of Complete Disease Remission
研究概览
简要总结
A phase III two-part study of nomacopan, a bifunctional inhibitor of complement component C5 and leukotriene B4 (LTB4), for the treatment of moderate and severe bullous pemphigoid. There is evidence that both terminal complement activation (via C5) and the lipid mediator LTB4 may have a central role in driving the disease. In this study patients will be randomized to receive either nomacopan plus oral corticosteroids (OCS) or placebo plus OCS for a treatment period of 24 weeks. OCS will be tapered over the course of the treatment if the symptoms of disease improve.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female between 18 and 89 years of age inclusive at the time of consent with Karnofsky score of 50% or more at screening
- •Male or female ≥90 years of age at the time of consent with Karnofsky score of 70% or more at screening
- •Diagnosis of Bullous Pemphigoid either newly diagnosed or relapsing
- •Patients with confirmed atypical Bullous Pemphigoid
- •Bullous Pemphigoid classified as either moderate or severe on the basis of the Investigator Global Assessment (IGA) at randomisation
- •Willing to receive immunisation against Neisseria meningitidis and/or antibiotic prophylaxis
- •Provision of voluntary written informed consent
排除标准
- •Patients with recalcitrant BP that have never achieved CDA or who have never been in complete disease remission despite long term treatment with super potent topical steroid or oral cotricosteroid
- •Epidermolysis bullosa acquisita, mucous membrane pemphigoid, or anti p200 pemphigoid
- •Mucosal lesions BPDAI score accounts for ≥30% of total BPDAI activity score at randomisation
- •BP considered to be drug induced, in particular diagnosis of BP made within two months of starting a drug well known to induce BP
- •Treatment with BP-directed biologics including: a) Any cell-depleting agents including, but not limited to, rituximab within 12 months prior to baseline, b) Other biologics within five half-lives (if known) or 16 weeks prior to the baseline, whichever is longer, or c) Intravenous immunoglobulin within 16 weeks prior to the baseline.
- •Taking > 0.3 mg/kg/day OCS at screening
- •Treatment with systemic immunomodulators such as dapsone or doxycycline within four half-lives of the drugs prior to baseline Day 1
- •Treatment with immunosuppressants within the last two weeks prior to baseline
- •Treatment with an anti-complement therapy or with Zileuton within the last three months prior to baseline
- •OCS dose no more than 0.3mg/kg/day in the 7 days before screening visit
- •Taking super-potent topical corticosteroids and unable to discontinue them at or before the screening assessment
- •Active systemic or organ system bacterial or fungal infection or progressive severe infection
- •Known congenital immunodeficiency or a history of acquired immunodeficiency including a positive human immunodeficiency virus (HIV) test
- •Active infection with hepatitis B or C
- •Positive nasal throat swab for Neisseria species
- •Known hypersensitivity to nomacopan and any of its excipients
- •Receipt of live attenuated vaccines within 2 weeks of Day 1
研究组 & 干预措施
nomacopan (rVA576)
PART A:
High dose nomacopan (standard complement ablating doses on Day 1 followed by 45 mg qd) administered by subcutaneous injection, plus a starting dose of 0.5 mg/kg/day OCS qd
or
Low dose nomacopan (standard complement ablating doses on Day 1 followed by 15 mg qd) administered by subcutaneous injection, plus a starting dose of 0.5 mg/kg/day OCS
PART B:
Nomacopan (standard complement ablating doses on Day 1 followed by to be confirmed mg qd) administered by subcutaneous injection, plus a starting dose of 0.5 mg/kg/day OCS qd
干预措施: nomacopan (rVA576) (Drug)
Placebo
PART A:
Placebo (matching standard complement ablating doses on Day 1 and then matching injection volume of 45mg dose qd) administered by subcutaneous injection, plus a starting dose of 0.5 mg/kg/day oral corticosteroid (OCS) qd
or
Placebo (matching standard complement ablating doses on Day 1 and then matching injection volume of 15mg dose qd) administered by subcutaneous injection, plus a starting dose of 0.5 mg/kg/day oral corticosteroid (OCS) qd
PART B:
Placebo (matching standard complement ablating doses on Day 1 and then matching injection volume of active dose qd) administered by subcutaneous injection, plus a starting dose of 0.5 mg/kg/day oral corticosteroid (OCS) qd
干预措施: Placebo (Other)
结局指标
主要结局
Achievement of Complete Disease Remission
时间窗: weeks 16 - 24
Proportion of patients in Complete Disease Remission
次要结局
- Achievement Partial Disease Remission(weeks 16 - 24)
- Time to onset of Complete Disease Remission(week 6 to 24)
- Investigator Global Assessment (IGA) score(weeks 6 - 24)
- Steroid-related AEs(Day 1 to Week 28)
- Dermatology Life Quality Index (DLQI)(Randomisation to week 24)
- Proportion of patients requiring rescue therapy(Randomization to 24 weeks)
- Adverse Events(Day 1 to Week 28)
- Incidence of treatment-emergent anti-drug antibody (ADA) responses and titre and neutralising potential assessed in vitro at baseline and every 4 weeks(Day 1 to Week 28)
- Cumulative oral corticosteroid, OCS, during treatment(Randomization to 24 weeks)
- Duration of Complete and Partial Disease Remission(week 6 to 24)