An Interventional, Prospective Open-Label Study of Immunosuppressive Therapies to Mitigate Immune-Mediated Loss of Therapeutic Response to Asfotase Alfa (STRENSIQ®) for Hypophosphatasia (RESTORE)
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 入组人数
- 8
- 主要终点
- Number of Participants Who Achieve Immunosuppressive Therapy (IST) Complete Response at Week 100
研究概览
简要总结
The primary objective of this study is to evaluate the effect of immunosuppressive therapy (IST) in participants treated with asfotase alfa who demonstrate immune-mediated loss of effectiveness (LoE).
详细描述
The administration of biological drugs to patients, especially for chronic conditions, carries a risk of eliciting anti-drug antibodies. Neutralizing antibodies can neutralize the clinical benefit of the agent. In postmarketing safety surveillance, some patients treated with asfotase alfa demonstrated an initial response, but subsequently recurrence and progression of disease. Consequently, the FDA requested a study to assess a potential serious risk of immune-mediated loss of effectiveness.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Reoccurrence or worsening of rickets for at least the past 3 months in participants who showed an initial efficacy response to asfotase alfa after at least 6 months of continuous treatment and currently receiving asfotase alfa. RSS will be used to determine severity at Baseline.
- •Presence of ADAs, with or without NAbs, irrespective of their titers.
- •Confirmation by the TMB that both the clinical evidence and immunogenicity-mediated association noted above are present.
- •Female participants of childbearing potential and male participants with partners of childbearing potential must follow protocol-specified contraception guidance as described in Section 10.
- •Participant, or participant's legal guardian, is capable of signing informed consent or assent as described in Section 10.1.3, which includes compliance with the requirements and restrictions listed in the informed consent or assent form and in this protocol.
排除标准
- •Known history of human immunodeficiency virus (HIV) infection (evidenced by HIV type 1 or type 2 [HIV 1, HIV 2] antibody) or hepatitis B or C viral infection.
- •Known or suspected history of drug or alcohol abuse or dependence within 1 year prior to Screening.
- •Inability of the participant, or the participant's legal guardian, to provide informed consent.
- •Pregnant, breastfeeding, or intending to conceive during the course of the study.
- •Inability to travel to the clinic for specified visits during the Treatment Period caused by disease per se or logistics (does not apply to external travel restrictions).
- •The participant is at risk of reactivation or has an active significant viral infection such as hepatitis B, cytomegalovirus, herpes simplex, human polyomavirus (also known as John Cunningham [JC] virus), parvovirus, or Epstein Barr virus.
- •The participant is at risk of reactivation of tuberculosis or has regular contact (eg, in the household) with individuals who are being actively treated for tuberculosis.
- •The participant has had or is required to have any live vaccination within 1 month prior to enrollment.
研究组 & 干预措施
Pediatric participants with HPP
Pediatric participants who have been receiving asfotase alfa treatment for their HPP, and who demonstrate immune-mediated LoE.
干预措施: methotrexate (Drug)
Pediatric participants with HPP
Pediatric participants who have been receiving asfotase alfa treatment for their HPP, and who demonstrate immune-mediated LoE.
干预措施: rituximab (Drug)
Pediatric participants with HPP
Pediatric participants who have been receiving asfotase alfa treatment for their HPP, and who demonstrate immune-mediated LoE.
干预措施: bortezomib (Drug)
Pediatric participants with HPP
Pediatric participants who have been receiving asfotase alfa treatment for their HPP, and who demonstrate immune-mediated LoE.
干预措施: IVIg (Drug)
Pediatric participants with HPP
Pediatric participants who have been receiving asfotase alfa treatment for their HPP, and who demonstrate immune-mediated LoE.
干预措施: Folic Acid (Drug)
结局指标
主要结局
Number of Participants Who Achieve Immunosuppressive Therapy (IST) Complete Response at Week 100
时间窗: Week 100
次要结局
- ADA and NAb Titer Levels(Baseline Through Week 100)
- Number Participants with Antidrug Antibodies (ADAs) and Neutralizing Antibodies (NAbs)(Baseline Through Week 100)
- Serum Concentration of Asofatase Alfa (Measured as Enzyme Activity)(Baseline Through Week 100)
- Plasma Concentration of Pyridoxal-5ˈ-Phosphate (PLP)(Baseline Through Week 100)
- Plasma Concentration of Inorganic Pyrophosphates (PPi)(Baseline Through Week 100)
- Number of Participants with Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events(Baseline Through Week 104)