A Randomized, Double-blind, Placebo-controlled, 12-month Phase 3 Study to Evaluate the Effect of Venglustat on Neuropathic and Abdominal Pain in Male and Female Participants ≥16 Years of Age With Fabry Disease Who Are Treatment-naïve or Untreated for at Least 6 Months
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Sanofi
- 入组人数
- 122
- 试验地点
- 58
- 主要终点
- Percent change from baseline at 6 months in the most bothersome symptom of 3 Fabry Disease Patient-Reported Outcome (FD-PRO) items (neuropathic pain in upper extremities, neuropathic pain in lower extremities, or abdominal pain)
研究概览
简要总结
This is a 12-month, parallel treatment, Phase 3, double-blind, randomized, placebo-controlled study to evaluate the effect of venglustat on neuropathic and abdominal pain symptoms of Fabry disease in participants ≥16 years of age with Fabry disease who are treatment-naïve or untreated for at least 6 months.
- Study visits will take place approximately every 3 months.
- The double-blind period will be followed by an open-label extension (OLE) during which participants who have completed the double-blind period will be treated with venglustat for an additional 12 months or until the Common Study End of Treatment Day (CSEOTD).
详细描述
Double blind period: the total duration will be up to approximately of 14 months (1 month of screening 12 month of treatment period, and a possible follow-up period of 1 month if no participation in the open label extension period)
Open-label extension period: the total duration will be approximately of 46 months (12 month of OLE treatment, additional OLE treatment until a common study end of treatment date (CSEOTD, approximately 33 months), and 1 month of follow-up period)
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)
盲法说明
Participants enrolled in the open-label extension will be treated with venglustat only.
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female adult patients 16 year of age or older, who have had a previously confirmed diagnosis of Fabry disease and a history of clinical symptoms of Fabry disease
- •Patients who are treatment-naïve or without prior treatment with an approved or experimental therapy for Fabry disease within at least 6 months prior to screening.
- •Average score of ≥3 (0=no symptom, 10=symptom as bad as you can imagine) on the participant-defined most-bothersome symptom (among neuropathic pain in upper extremities, neuropathic pain in lower extremities, or abdominal pain), as measured by the Fabry Disease Patient-Reported Outcome (FD-PRO) at screening.
- •Contraception (with double contraception methods) for male and female participants; not pregnant or breastfeeding for female participants; no sperm donation for male participants.
- •Weight ≥30 Kg
- •A signed informed consent must be provided prior to any study-related procedures.
排除标准
- •Any manifestations of Fabry disease that preclude placebo administration.
- •History of transient ischemic attack, stroke, myocardial infarction, heart failure, evidence of left ventricular hypertrophy and/or cardiac fibrosis, major cardiovascular surgery, or kidney transplantation.
- •History of clinically significant cardiac arrhythmia. Atrial fibrillation that is well controlled on a stable medical regimen for at least 12 months is not an exclusion if the CHA2DS2-VASc score is 0 for males or 1 for females.
- •Patients with hepatitis C, HIV, or hepatitis B infection.
- •Neuropathic pain in upper or lower extremities, or abdominal pain not related to Fabry disease.
- •History of seizures currently requiring treatment.
- •Uncontrolled hypertension over the past 12 months prior to screening, or systolic BP >=150 or diastolic BP >=100 at screening.
- •Estimated glomerular filtration rate <60 mL/min/1.73m².
- •Urine protein to creatinine ratio >= 1 g/g at screening.
- •Presence of severe depression as measured by Beck's Depression Inventory (BDI)-II >28 and/or a history of an untreated, unstable major affective disorder within 1 year of the screening visit.
- •Positive SARS-CoV-2 virus test within 2 weeks of enrollment, or COVID 19 requiring hospitalization within 6 months of enrollment.
- •Moderate to severe hepatic impairment.
- •History of drug and/or alcohol abuse.
- •History of or active hepatobiliary disease.
- •Liver enzymes (alanine aminotransferase (ALT)/aspartate aminotransferase (AST)) or total bilirubin >2 times the upper limit of normal (ULN).
- •Initiation of chronic treatment for pain, or change in pain medication regimen, within 3 months prior to randomization.
- •Strong or moderate inducers or inhibitors of cytochrome P450 3A within 14 days or 5 half-lives, whichever is longer, prior to randomization.
- •The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.
研究组 & 干预措施
Venglustat
Participant will receive venglustat dose once daily for 12 months
干预措施: Venglustat (GZ402671) (Drug)
Placebo
Participants will receive placebo once daily for 12 months
干预措施: Placebo (Drug)
结局指标
主要结局
Percent change from baseline at 6 months in the most bothersome symptom of 3 Fabry Disease Patient-Reported Outcome (FD-PRO) items (neuropathic pain in upper extremities, neuropathic pain in lower extremities, or abdominal pain)
时间窗: From baseline to 6 months
Percent change from baseline at 12 months in the most bothersome symptom of 3 Fabry Disease Patient-Reported Outcome (FD-PRO) items (neuropathic pain in upper extremities, neuropathic pain in lower extremities, or abdominal pain)
时间窗: From baseline to 12 months
次要结局
- Percent change in plasma globotriaosylsphingosine (lyso-GL-3)(From baseline to 6 month and 12 months)
- Frequency of rescue pain medication use(From baseline to 6 months and 12 months)
- Change in the percentage of days with at least 1 stool reflecting diarrhea (Bristol Stool Form Scale [BSFS] Type 6 or 7)(From baseline to 6 month and 12 months)
- Change in tiredness component of FD-PRO(From baseline to 6 month and 12 months)
- Proportion of responders in neuropathic or abdominal pain, as assessed by FD-PRO(At 6 months and 12 months)
- Number of participants with adverse event (AE) and serious adverse event (SAE)(From baseline to 6 month and 12 months)
- Change in the lens clarity (new or worsening lens opacities) by ophthalmological examination (by slit lamp exam at Visit 2 and Visit 6)(From baseline to 12 months)
- Change in Beck Depression Inventory-II (BDI-II) score(From baseline to 6 month and 12 months)
- Plasma venglustat concentrations at prespecified visits over the study duration(From baseline to 6 month and 12 months)
- Maximum venglustat plasma concentration (Cmax)(From baseline to 6 month and 12 months)
- Time to maximum venglustat plasma concentration (tmax)(From baseline to 6 month and 12 months)
- Area under the venglustat plasma concentration versus time curve from time 0 to 24 hours (AUC0-24)(From baseline to 6 month and 12 months)