Evaluation of the Efficacy and Safety of Stiripentol in Patients 6 Years and Older With Primary Hyperoxaluria Type 1, 2 or 3
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- Biocodex
- 入组人数
- 42
- 主要终点
- % change in 24-hour urinary oxalate excretion corrected for body surface area (BSA) determined from 24-hour urine sample collections
研究概览
简要总结
Evaluation of the efficacy and safety of stiripentol in patients 6 years and older with primary hyperoxaluria type 1, 2 or 3.
详细描述
A multicenter randomized, double-blind, placebo-controlled phase 3 study The study is designed to compare the efficacy of stiripentol to a placebo in patients 6 years and older with primary hyperoxaluria type 1, 2 or 3.
The study will be conducted in 2 periods: a 6-month, placebo-controlled, double-blind treatment period (period 1) followed by a 6-month open-label treatment period with blind maintained on results (period 2).
Patients who benefit from the treatment after the first 12 months of study treatment will be proposed to enter the open-label extension (OLE) part of the study to continue to assess the long-term efficacy and safety of stiripentol.
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)
盲法说明
All Sponsor personnel will be blinded to study drug treatment until the 6-month treatment period data is unblinded for the primary analysis. To ensure that blinding will be maintained along the study, the following measures are implemented:
- the capsules are identical for both products
- all packaging items, bottles (primary packagings) and boxes (secondary, tertiary and quaternary packagings) are identical bearing similar study specific labels.
At the start of the open-label Period 2), in order to maintain the blind to treatment assignment, gradual initiation of treatment will be done in all patients over the first three days as follows: 30 mg/kg/day at Day1, 40 mg/kg/day at Day 2 and 50 mg/kg/day from Day 3 (with a maximum dose of 3,000 mg/day).
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed with primary hyperoxaluria disease and subtype (type 1, 2 or 3) confirmed by genetic testing
- •Receiving optimal management of the disease through standard of care strategies (e.g., increased fluid intake, vitamin B6, potassium citrate) with or without approved target medications (e.g., lumasiran). Patients not receiving lumasiran can only be enrolled if they are not eligible for treatment with lumasiran for the specific following reasons: contraindications, previous treatment discontinued due to lack of efficacy or poor tolerability, not meeting national or regional eligibility criteria for treatment, investigator judgement
- •With mean 24-hour urinary oxalate excretion from 2 valid 24-hour urine collections ≥ 0.70 mmol/24h/1.73m²
- •With estimated Glomerular Filtration Rate ≥ 45 mL/min/1.73 m2 (Schwartz et al., 2009 in pediatric patients and CKD-EPI in adults)
- •Pubescent and adult female patients must have a negative urine or serum pregnancy test within 60 days prior to first dose of study treatment if of childbearing potential. If the urine pregnancy test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the patient to be eligible
- •In France, patient affiliated with or who benefits from a social security scheme
排除标准
- •Any relevant change in the use of any component of the standard of care (fluid intake, vitamin B6, potassium citrate) in the 4 weeks prior to inclusion or if such change is planned to occur during the first 6 months of the study
- •If under approved targeted medications (e.g., lumasiran), treatment should have been administered for at least 6 months, with no change in dose or regimen in the 3 months prior to inclusion or ifsuch change is planned it should not occur during the first 12 months of the study
- •History of kidney or liver transplant
- •Presenting any of the following liver function tests abnormalities during the screening period:
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST)> 2 × upper limit of normal (ULN)
- •Total bilirubin > 1.5 x ULN. Patients with elevated total bilirubin that is secondary to documented Gilbert's syndrome are eligible if the total bilirubin is < 2 x ULN
- •Recent (4 weeks before the screening visit) or planned change in eating habits
- •Intermittent fasting planned during the 6 first months of the study period (e.g., Ramadan)
- •Other medical conditions or comorbidities, treatment, which in the opinion of the investigator, would interfere with study compliance or data interpretation
- •Presenting any significant biological or clinical anomalies that are not compatible with participation in the study according to the investigator
- •History of severe allergy, asthma, skin rashes, intolerance to lactose or hypersensitivity to the study treatments
- •Treatment affecting hepatic metabolism (i.e., cimetidine, ketoconazole, fluconazole, itraconazole, phenytoin, rifampicin, rifabutin) that is ongoing or has been taken in the month prior to the selection visit
- •Treatment affecting the renal tubule (probenecid, β-lactam, etc.,) that is ongoing or has been taken in the two weeks prior to the start of the study
- •Contraindications to stiripentol as defined in the applicable Investigator's Brochure (i.e. patients presenting a hypersensitivity to the active substance or any excipients)
- •Patient at risk of pregnancy, pregnant or breastfeeding female
- •Patient under guardianship or curatorship
- •Patient under the protection of the Court or deprived of liberty
- •Patient participating in another interventional clinical trial which could interfere with the trial's results or impact the other trial's results; or within the last 30 days or 5 half-lives of the study investigational treatment, whichever is longer, prior to the urinary sampling during the screening period, or are in follow-up of another clinical study prior to randomization
- •Patient whose current state of health does not allow him/her to give consent
研究组 & 干预措施
Stiripentol
Patients in this arms will receive 50 mg/kg/day oral stiripentol during the first 6 months double-blind placebo-controlled study period 1 (Day 1 through Month 6) then continue the same treatment for the following 6 months (period 2).
干预措施: Stiripentol Oral Capsule (Drug)
Stiripentol
Patients in this arms will receive 50 mg/kg/day oral stiripentol during the first 6 months double-blind placebo-controlled study period 1 (Day 1 through Month 6) then continue the same treatment for the following 6 months (period 2).
干预措施: Urine samples collect (Biological)
Stiripentol
Patients in this arms will receive 50 mg/kg/day oral stiripentol during the first 6 months double-blind placebo-controlled study period 1 (Day 1 through Month 6) then continue the same treatment for the following 6 months (period 2).
干预措施: Blood samples collect (Biological)
Stiripentol
Patients in this arms will receive 50 mg/kg/day oral stiripentol during the first 6 months double-blind placebo-controlled study period 1 (Day 1 through Month 6) then continue the same treatment for the following 6 months (period 2).
干预措施: Kidney imaging (Other)
Stiripentol
Patients in this arms will receive 50 mg/kg/day oral stiripentol during the first 6 months double-blind placebo-controlled study period 1 (Day 1 through Month 6) then continue the same treatment for the following 6 months (period 2).
干预措施: Quality of Life questionnaires (Other)
Placebo
Patients in this arms will receive 50 mg/kg/day oral placebo during the first 6 months double-blind placebo-controlled study period 1 (Day 1 through Month 6) then patients receiving placebo will switch over the 6 to 12 month-period to stiripentol (period 2).
干预措施: Placebo Oral Capsule (Drug)
Placebo
Patients in this arms will receive 50 mg/kg/day oral placebo during the first 6 months double-blind placebo-controlled study period 1 (Day 1 through Month 6) then patients receiving placebo will switch over the 6 to 12 month-period to stiripentol (period 2).
干预措施: Urine samples collect (Biological)
Placebo
Patients in this arms will receive 50 mg/kg/day oral placebo during the first 6 months double-blind placebo-controlled study period 1 (Day 1 through Month 6) then patients receiving placebo will switch over the 6 to 12 month-period to stiripentol (period 2).
干预措施: Blood samples collect (Biological)
Placebo
Patients in this arms will receive 50 mg/kg/day oral placebo during the first 6 months double-blind placebo-controlled study period 1 (Day 1 through Month 6) then patients receiving placebo will switch over the 6 to 12 month-period to stiripentol (period 2).
干预措施: Kidney imaging (Other)
Placebo
Patients in this arms will receive 50 mg/kg/day oral placebo during the first 6 months double-blind placebo-controlled study period 1 (Day 1 through Month 6) then patients receiving placebo will switch over the 6 to 12 month-period to stiripentol (period 2).
干预措施: Quality of Life questionnaires (Other)
结局指标
主要结局
% change in 24-hour urinary oxalate excretion corrected for body surface area (BSA) determined from 24-hour urine sample collections
时间窗: % change in 24-hour urinary oxalate excretion between baseline value and value at month 6
% change in 24-hour urinary oxalate excretion in mg/kg corrected for body surface area (BSA) between baseline and Month 6 and determined from 24-hour urine sample collections
次要结局
- % change in 24-hour urinary oxalate excretion corrected for body surface area (BSA) determined from 24-hour urine sample collections(% change in 24-hour urinary oxalate excretion between baseline value and value at month 3)
- Absolute change in 24-hour urinary oxalate excretion in mg/kg corrected for body surface area (BSA) from baseline to Month 3 and Month 6(Absolute change in 24-hour urinary oxalate excretion between baseline value to Month 3 and Month 6 values.)
- Change in 24-hour urine oxalate/creatinine ratio from baseline to Month 3 and Month 6(Change in 24-hour urine oxalate/creatinine ratio between baseline value to month 3 and month 6 values)
- % of patients with urinary oxalate lower than 1.5 x upper limit of normal (ULN)) at Month 3 and Month 6(At 3 and 6 months of treatment.)
- % of patients with normalisation of 24-hour urinary oxalate level corrected for bode surface area at Month 3 and Month 6(At 3 and 6 months of treatment.)
- Blood samples for assessment of change in estimated glomerular filtration rate (eGFR in mL/min/1.73m2) from baseline to Month 6(Change in estimated glomerular filtration rate (eGFR) between baseline value and month 6 value)
- Occurrence of and frequency of kidney stone events during the follow-up of the patient(From start of participation of the patient to end of the study (Month 60))
- Change in urine oxalate/creatinine ratios as assessed in spot urine collections between baseline and Month 6(From start of participation of the patient to end of the study (Month 60))
- Change in biological parameters : oxalate concentration measured in urinary spots collections between baseline and Month 6(From baseline to 6 months of treatment.)
- Change in biological parameters : creatinine concentration measured in urinary spots collections between baseline and Month 6(From baseline to 6 months of treatment.)
- Absolute change in quality of life measured by the Pediatric Quality of Life Inventory (PedsQL) questionnaire(At baseline and every 6 months until the end of the study (Month 60))
- Absolute change in quality of life measured by the Kidney Disease Quality of Life Questionnaire (KDQOL)(At baseline and every 6 months until the end of the study (Month 60))
- Change in quality of life measured by the Euro Quality of Life Health State Profile Questionnaire (EQ-5D)(At baseline and every 6 months until the end of the study (Month 60))
- Change in quality of life measured by the Euro Quality of Life Health State Profile Visual Analog Scale (VAS) : EQ-5D(At baseline and every 6 months until the end of the study (Month 60))