Evaluation of the Efficacy and Safety of Stiripentol in Patients 6 Years and Older With Primary Hyperoxaluria Type 1, 2 or 3
NCT Number: NCT06465472
Acronym: CRYSTAL
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Primary Hyperoxaluria Type 1|Primary Hyperoxaluria Type 2|Primary Hyperoxaluria Type 3
Interventions: DRUG: Stiripentol Oral Capsule|DRUG: Placebo Oral Capsule|BIOLOGICAL: Urine samples collect|BIOLOGICAL: Blood samples collect|OTHER: Kidney imaging|OTHER: Quality of Life questionnaires
Sponsor: Biocodex
Collaborators: Exystat
Sex: ALL
Age: CHILD, ADULT, OLDER_ADULT
Enrollment: 42
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-08
Completion Date: 2030-08

Summary:
Evaluation of the efficacy and safety of stiripentol in patients 6 years and older with primary hyperoxaluria type 1, 2 or 3.

Primary Outcome Measures: % 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 in mg/kg corrected for body surface area (BSA) between baseline and Month 6 and determined from 24-hour urine sample collections, % change in 24-hour urinary oxalate excretion between baseline value and value at month 6
Secondary Outcome Measures: % 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 in mg/kg corrected for body surface area (BSA) from baseline to Month 3 and 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 in mg/kg corrected for 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, Concentration of 24-hour urine oxalate and 24-hour urine creatinine will be combined to report urine oxalate/creatinine ratio from baseline to Month 3 and Month 6. The concentrations will be determined using a validated assay, 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, %of patients with near normalisation of 24-hour urinary oxalate level corrected for BSA (defined as 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, % of patients with near normalisation of 24-hour urinary oxalate level corrected for BSA (defined as 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.|Blood samples for assessment of change in estimated glomerular filtration rate (eGFR in mL/min/1.73m2) from baseline to Month 6, Blood samples for assessment of change in estimated glomerular filtration rate (eGFR). EGFR (mL/min/1.73m2) will be calculated 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, Number of and frequency of kidney stone events reported 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, Urine oxalate/creatinine ratios will be calculated from the oxalate and creatinine levels measured in spot urine collected during patients' hospitalizations or at home. The concentrations will be determined using a validated assay., 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, Change in oxalate concentration, related to kidney stone formation, 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, Change in creatinine concentration, related to kidney stone formation, 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, Absolute change in the Pediatric Quality of Life Inventory (PedsQL \[the generic and kidney failure (KF) modules\]) for patients \< 18 years of age (at screening) which is a 23 items 5-point Likert scale from: 0 (Never) to 4 (Almost always). Scores are transformed on a scale from 0 to 100 so higher score means better health., 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), Absolute changes in the Kidney Disease Quality of Life Questionnaire (KDQOL) for patients ≥ 18 years of age (at screening) which is a 36 items survey with five subscales. Scores are transformed on a scale from 0 to 100 so higher score means better health., 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), Change in Euro Quality of Life Health State Profile Questionnaire (EQ-5D) is a standardized instrument consisting of a questionnaire. Scoring of the questionnaire is based on degrees of disability. Higher scores indicate better health status., 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, Change in EQ-5D Visual Analog Scale EQ-5D is a standardized instrument consisting of a visual analog scale pertaining to 5 dimensions. Scoring of the visual analog scale is based on a visual scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). Higher scores indicate better health status., At baseline and every 6 months until the end of the study (Month 60)
Other Outcome Measures: Height in meters, Changes in height in meters, At baseline and every 3 months until the end of the study (Month 60)|Weight in kilograms, Changes in weight in kilograms, At baseline and every 3 months until the end of the study (Month 60)|Changes in liver function tests (clinical laboratory parameters), Changes in liver function tests (AST, ALT, GGT, ALP, Bilirubin (total and direct)), From start of participation of the patient to the end of the study|Complete blood count with differential, Changes in complete blood count with differential ( blood test results), At baseline and every months until the end of the study (Month 60)|Frequency and nature of adverse events, Collect of the frequency and nature of adverse events, From baseline to the end of the study (Month 60)|Change in 24-hour urinary glyoxylate, glycine and glycolate, Change in 24-hour urinary glyoxylate, glycine and glycolate, From start of participation of the patient to end of the study (Month 60)|Change from baseline (percent and absolute) in 24-hour urine oxalate excretion, percentage of time that 24-hour urinary oxalate ≤ 1.5 x ULN, 24-hour urine oxalate/creatinine ratios and eGFR, Change from baseline (percent and absolute) in 24-hour urine oxalate excretion, percentage of time that 24-hour urinary oxalate ≤ 1.5 x ULN, 24-hour urine oxalate/creatinine ratios and eGFR, From start of participation of the patient to end of the study (Month 60)|PK parameters : volume of distribution of stiripentol, PK parameters : volume of distribution of stiripentol based on appropriate PK sampling scheme (on Month 0, Month 6 and Month 12), and further determined through a population PK (popPK) approach, From start of participation of the patient to end of the study (Month 60)|PK parameters : clearance of stiripentol, PK parameters : clearance of stiripentol based on appropriate PK sampling scheme (on Month 0, Month 6 and Month 12), and further determined through a population PK (popPK) approach, From start of participation of the patient to end of the study (Month 60)|Exposure parameters : Peak Plasma Concentration (Cmax) of stiripentol, Peak Plasma Concentration (Cmax) of stiripentol based on appropriate PK sampling scheme (on Month 0, Month 6 and Month 12), and further determined through a population PK (popPK) approach, From start of participation of the patient to end of the study (Month 60)|Exposure parameters : Minimum Plasma Concentration (Cmin) of stiripentol, Minimum Plasma Concentration (Cmin) of stiripentol based on appropriate PK sampling scheme (on Month 0, Month 6 and Month 12), and further determined through a population PK (popPK) approach, From start of participation of the patient to end of the study (Month 60)|Exposure parameters : Area under the plasma concentration versus time curve (AUC) of stiripentol, Area under the plasma concentration versus time curve (AUC) of stiripentol based on appropriate PK sampling scheme (on Month 0, Month 6 and Month 12), and further determined through a population PK (popPK) approach, From start of participation of the patient to end of the study (Month 60)|Change in plasma oxalate concentrations, Change in plasma oxalate concentrations, At baseline and every three Months until month 12|Change in plasma vitamin B6 concentrations, Change in plasma vitamin B6 concentrations, At baseline and every three Months until month 12|Change in nephrocalcinosis as assessed by kidney imaging, Change in nephrocalcinosis as assessed by kidney imaging, At baseline and every 6 months until the end of the study (Month 60)|Change in bone conditions during the follow-up, Change in bone conditions during the follow-up based on questions from the investigator to the patient collected in the CRF, At Baseline and at Month 3,6 and 12|Prediction of urinary oxalate excretion at exposure of clinical interest for stiripentol from a PK/PD model, Prediction of urinary oxalate excretion at exposure of clinical interest for stiripentol from a PK/PD model, At baseline and every 6 months until month 12|Change in patient, caregiver and investigator impact and experiences as evaluated by patient and investigator experience surveys, Change in patient, caregiver and investigator impact and experiences as evaluated by patient and investigator experience surveys, At baseline and every 6 months until end of the study (Month 60)