Stiripentol for Primary hyperoxaluria (PH) (PH1, PH2, PH3)

Inclusion criteria

• {"criterion_text":"- Male or female subjects aged ≥6 years at the time of consent signature\n- Diagnosed with primary hyperoxaluria disease and subtype (type 1, 2 or 3) confirmed by genetic testing\n- 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)\n- With mean 24-hour urinary oxalate excretion from 2 valid 24-hour urine collections ≥0.70 mmol/24h/1.73m²\n- With estimated Glomerular Filtration Rate ≥ 45 mL/min/1.73 m2 (Schwartz 2009 in pediatric patients and CKD-EPI in adults)\n- Pubescent patients and adult female subjects 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 subject to be eligible.\n- Able to understand and willing to comply with study requirements and to provide written informed consent. In the case of patient under the age of legal consent, the legal guardian(s) must provide informed consent and the patient should provide assent per local and national requirements"}

Exclusion criteria

• {"criterion_text":"- 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\n- Treatment affecting hepatic metabolism (i.e., cimetidine, ketoconazole, fluconazole, itraconazole, phenytoine, rifampicine, rifabutine) that is ongoing or has been taken in the month prior to the selection visit\n- Treatment affecting the renal tubule (probénécide, β-lactames, etc.,) that is ongoing or has been taken in the two weeks prior to the start of the study\n- Contraindications to stiripentol as defined in the applicable Investigator Brochure\n- Patient at risk of pregnancy, pregnant or breastfeeding female patient\n- Patient under guardianship or curatorship\n- Patient under the protection of the Court or deprived of liberty\n- 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\n- Patient whose current state of health does not allow him/her to give consent\n- 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 if such change is planned it should not occur during the first 12 months of the study\n- History of kidney or liver transplant\n- Presenting any of the following liver function tests abnormalities during the screening period: a) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 × upper limit of normal (ULN) b) 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\n- Recent (4 weeks before the screening visit) or planned change in eating habits\n- Intermittent fasting planned during the 6 first months of the study period (e.g., Ramadan)\n- Other medical conditions or comorbidities, treatment, which in the opinion of the Investigator, would interfere with study compliance or data interpretation\n- Presenting any significant biological or clinical anomalies that are not compatible with participation in the study according to the investigator\n- History of severe allergy, asthma, skin rashes or hypersensitivity to the study treatments"}

Primary endpoints

• {"endpoint_text":"- Percent change in 24-hour urinary oxalate excretion corrected for body surface area (BSA) from baseline to Month 6","definition_or_measurement_approach":"Measured using 24-hour urinary oxalate excretion collections corrected for body surface area (BSA) from baseline to Month 6 (baseline assessment uses mean of 2 valid 24-hour urine collections as per eligibility criteria)."}

Secondary endpoints

• {"endpoint_text":"- Percent change in 24-hour urinary oxalate excretion corrected for body surface area (BSA) from baseline to Month 3","definition_or_measurement_approach":"Measured using 24-hour urinary oxalate excretion collections corrected for BSA from baseline to Month 3."}
• {"endpoint_text":"- Absolute change in 24-hour urinary oxalate excretion corrected for body surface area (BSA) from baseline to Month 3 and Month 6","definition_or_measurement_approach":"Measured using absolute values from 24-hour urinary oxalate excretion collections corrected for BSA at baseline, Month 3 and Month 6."}
• {"endpoint_text":"- Change in 24-hour urine oxalate/creatinine ratio from baseline to Month 3 and Month 6","definition_or_measurement_approach":"Assessed using 24-hour urine collections to calculate oxalate/creatinine ratio at baseline, Month 3 and Month 6."}
• {"endpoint_text":"- Proportion 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","definition_or_measurement_approach":"Proportion defined by 24-hour urinary oxalate corrected for BSA being <1.5 x ULN at Month 3 and Month 6."}
• {"endpoint_text":"- Proportion of patients with normalisation of 24-hour urinary oxalate level corrected for BSA at Month 3 and Month 6","definition_or_measurement_approach":"Proportion defined by 24-hour urinary oxalate corrected for BSA reaching normalisation at Month 3 and Month 6 (normalisation criteria as per protocol)."}
• {"endpoint_text":"- Change in estimated glomerular filtration rate (eGFR) from baseline to Month 6","definition_or_measurement_approach":"Change in eGFR from baseline to Month 6 (eGFR estimation methods referenced elsewhere in protocol: Schwartz 2009 in pediatric patients and CKD-EPI in adults)."}
• {"endpoint_text":"- Occurrence and frequency of kidney stone events during the follow-up","definition_or_measurement_approach":"Recorded occurrence and frequency of kidney stone events during study follow-up (as documented during follow-up visits)."}
• {"endpoint_text":"- Change in urine oxalate/creatinine ratios as assessed in spot urine collections between baseline and Month 6","definition_or_measurement_approach":"Assessed using spot urine collections to determine oxalate/creatinine ratios at baseline and Month 6."}
• {"endpoint_text":"- Change in biological parameters related to kidney stone formation between baseline and Month 6","definition_or_measurement_approach":"Assessed changes in relevant biological parameters related to kidney stone formation between baseline and Month 6 as defined in protocol."}
• {"endpoint_text":"- 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) or in the Kidney Disease Quality of Life Questionnaire (KDQOL) for patients ≥ 18 years of age (at screening)","definition_or_measurement_approach":"Quality of life measured by PedsQL (generic and kidney failure modules) for patients <18 and KDQOL for patients ≥18, absolute change from baseline."}
• {"endpoint_text":"- Change in Euro Quality of Life Health State Profile Questionnaire (EQ-5D) and EQ-5D Visual Analog Scale (VAS)","definition_or_measurement_approach":"EQ-5D and EQ-5D VAS scores change from baseline as recorded by the questionnaires."}

Italy

Earliest CTIS Part Ii Submission Date

12-04-2024

Latest Decision Or Authorization Date

16-12-2024

Processing Time Days

248

Number Of Sites

2

Number Of Participants

8

France

Earliest CTIS Part Ii Submission Date

02-04-2024

Latest Decision Or Authorization Date

29-04-2026

Processing Time Days

757

Number Of Sites

5

Number Of Participants

7

Belgium

Earliest CTIS Part Ii Submission Date

16-04-2024

Latest Decision Or Authorization Date

22-04-2026

Processing Time Days

736

Number Of Sites

2

Number Of Participants

4

Primary sponsor

Full Name

Biocodex

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Third parties

• {"country":"France","full_name":"Eurofins Adme Bioanalyses","duties_or_roles":"Sponsor duties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Exystat","duties_or_roles":"Sponsor duties codes: 15 (Statistics), 6, 7","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Voisin Consulting Life Sciences","duties_or_roles":"Sponsor duties codes: 12, 15 (Submissions)","organisation_type":"Pharmaceutical company"}