ENVISION: A Phase 3 Randomized, Double-blind, Placebo-Controlled Multicenter Study With an Open-label Extension to Evaluate the Efficacy and Safety of Givosiran in Patients With Acute Hepatic Porphyrias
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 94
- 试验地点
- 1
- 主要终点
- Annualized Rate of Porphyria Attacks in Participants With Acute Intermittent Porphyria (AIP)
研究概览
简要总结
The purpose of this study is to evaluate the effect of subcutaneous givosiran (ALN-AS1), compared to placebo, on the rate of porphyria attacks in patients with Acute Hepatic Porphyrias (AHP).
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥ 12 years of age
- •Diagnosed with Acute Hepatic Porphyria (Acute Intermittent Porphyria, Hereditary Corproporhyria, Variegate Porphyria, aminolevulinic acid (ALA) dehydratase deficient porphyria)
- •Elevated urinary or plasma porphobilinogen (PBG) or ALA values within the past year,
- •Have active disease, with at least 2 documented porphyria attacks within the last 6 months
- •Willing to discontinue or not initiate the use of prophylactic hemin throughout the study.
- •Women of child bearing potential must have a negative serum pregnancy test, not be nursing, and use acceptable contraception
排除标准
- •Clinically significant abnormal laboratory results
- •Anticipated liver transplantation
- •History of multiple drug allergies or intolerance to subcutaneous injections
- •Active HIV, hepatitis C virus, or hepatitis B virus infection(s)
- •History of recurrent pancreatitis
研究组 & 干预措施
Givosiran/Givosiran
Givosiran 2.5 mg/kg administered subcutaneously (SC), monthly (QM), for 6 months during the 6-Month Double-blind (DB) Period, followed by givosiran 2.5 mg/kg or 1.25 mg/kg SC, QM for 29 months during the Open-label Extension (OLE) Period.
干预措施: Givosiran (Drug)
Givosiran/Givosiran
Givosiran 2.5 mg/kg administered subcutaneously (SC), monthly (QM), for 6 months during the 6-Month Double-blind (DB) Period, followed by givosiran 2.5 mg/kg or 1.25 mg/kg SC, QM for 29 months during the Open-label Extension (OLE) Period.
干预措施: Placebo (Drug)
Placebo/Givosiran
Matching placebo (normal saline [0.9% NaCl]) was administered SC, QM, for 6 months during the 6-Month DB Period, followed by givosiran 2.5 mg/kg or 1.25 mg/kg SC, QM for 29 months during the OLE period.
干预措施: Givosiran (Drug)
Placebo/Givosiran
Matching placebo (normal saline [0.9% NaCl]) was administered SC, QM, for 6 months during the 6-Month DB Period, followed by givosiran 2.5 mg/kg or 1.25 mg/kg SC, QM for 29 months during the OLE period.
干预措施: Placebo (Drug)
结局指标
主要结局
Annualized Rate of Porphyria Attacks in Participants With Acute Intermittent Porphyria (AIP)
时间窗: 6 months
Porphyria attacks were defined as meeting all of the following criteria: an acute episode of neurovisceral pain in the abdomen, back, chest, extremities and/or limbs, no other medically determined cause, and required treatment with intravenous (IV) dextrose or hemin, carbohydrates, or analgesics, or other medications such as antiemetics at a dose or frequency beyond the participant's usual daily porphyria management. The annualized rate of porphyria attacks is a composite endpoint which included porphyria attacks requiring hospitalization, urgent healthcare visit, or IV hemin administration at home.
次要结局
- The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) in Participants With AIP(3 and 6 months)
- The PD Effect of Givosiran on Urine Levels of Porphobilinogen (PBG) in Participants With AIP(6 months)
- Annualized Rate of Porphyria Attacks in Participants With AHP(6 months)
- Area Under the Curve (AUC) of the Change From Baseline in Weekly Mean Score of Daily Worst Pain as Measured by the Brief Pain Inventory-Short Form (BPI-SF) Numeric Rating Scale (NRS) in Participants With AIP(Baseline and 6 months)
- Average Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP(Baseline and 6 months)
- Annualized Rate of Hemin Administration in Participants With AIP(6 months)
- Average Change From Baseline in Weekly Mean Score of Daily Worst Pain as Measured by the Brief Pain Inventory-Short Form (BPI-SF) Numeric Rating Scale (NRS) in Participants With AIP(Baseline and 6 months)
- AUC of the Change From Baseline in Weekly Mean Score of Daily Worst Fatigue Score as Measured by the Brief Fatigue Inventory-Short Form (BFI-SF) NRS in Participants With AIP(Baseline and 6 months)
- Average Change From Baseline in Weekly Mean Score of Daily Worst Fatigue Score as Measured by the Brief Fatigue Inventory-Short Form (BFI-SF) NRS in Participants With AIP(Baseline and 6 months)
- AUC of the Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP(Baseline and 6 months)
- Change From Baseline in the Physical Component Summary (PCS) of the 12-Item Short Form Survey (SF-12) in Participants With AIP(Baseline and 6 months)