Evaluation of the Efficacy and Safety of Stiripentol in Patients 6 Years and Older With Primary Hyperoxaluria Type 1, 2 or 3

NCT06465472 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: CRYSTAL - STP2262023-508062-15-00
• Study Type: interventional
• Target: 42
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Primary Hyperoxaluria Type 1; Primary Hyperoxaluria Type 2; Primary Hyperoxaluria Type 3

Keywords

Stiripentol; Primary Hyperoxaluria; Oxalate

Outcome Measures

Primary Outcomes (1)

• % 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 Outcomes (14)

• % 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.

Other Outcomes (18)

• Height in meters

  At baseline and every 3 months until the end of the study (Month 60)

• 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)

  From start of participation of the patient to the end of the study

Study Arms (2)

Stiripentol

EXPERIMENTAL

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).

Drug: Stiripentol Oral Capsule; Biological: Urine samples collect; Biological: Blood samples collect; Other: Kidney imaging; Other: Quality of Life questionnaires

Placebo

PLACEBO COMPARATOR

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).

Drug: Placebo Oral Capsule; Biological: Urine samples collect; Biological: Blood samples collect; Other: Kidney imaging; Other: Quality of Life questionnaires

Interventions

Stiripentol Oral Capsule DRUG

The target dose of stiripentol will be 50 mg/kg/day with a maximum dose of 3,000 mg/day. Patients allocated to the Stiripentol group will receive this treatment during the first 6 months, and in continuation up to 12 months.

Stiripentol

Placebo Oral Capsule DRUG

Placebo capsules will be administered for the first 6 months. Then patients will switch to stiripentol over the 6- to 12-month period.

Placebo

Urine samples collect BIOLOGICAL

Collections of urine over 24 hours and the first urine in the morning (spot urines) will be carried out. Urine collections will be performed either during hospitalizations, or at home if appropriate conditions are met.

Placebo; Stiripentol

Blood samples collect BIOLOGICAL

Series of blood samples will be taken (serum pregnancy test, Primary Hyperoxaluria genetic characterization, clinical laboratory assessments, vitamin B6 dosage, plasma oxalate dosage, stiripentol pharmacokinetics)

Placebo; Stiripentol

Kidney imaging OTHER

Kidney imaging will be obtained. Renal ultrasounds will be compulsory for all patients.

Placebo; Stiripentol

Quality of Life questionnaires OTHER

Kidney Disease Quality of Life Questionnaire : KDQOL-36 for patients ≥18 years of age at screening, and the Pediatric Quality of Life Inventory (PedsQL) including the generic and KF modules (parent and/or self-report versions) for patients \<18 years of age at screening. EQ-5D: a standardized instrument consisting of a questionnaire and a visual analog scale pertaining to 5 dimensions. Scoring of the questionnaire is based on degrees of disability. 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. The EQ-5D-5L questionnaire (will be utilized in patients ≥18 years of age at screening, and the EQ-5D-Y questionnaire will be utilized in patients \<18 years of age at screening, where available.

Placebo; Stiripentol

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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

You may not qualify if:

• \. 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

Sponsors & Collaborators

• Biocodex: lead
• Exystat: collaborator

MeSH Terms

Conditions

Primary hyperoxaluria type 1; Primary hyperoxaluria type 2; Hyperoxaluria, Primary

Interventions

stiripentol

Condition Hierarchy (Ancestors)

Hyperoxaluria; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Oana BERNARD, MD

  Chief Scientific Officer

  STUDY DIRECTOR

Central Study Contacts

Pauline DECIMA

CONTACT

03.44.86.82.28; p.decima@biocodex.fr

Carine FRANCOIS

CONTACT

03.44.86.82.28; c.francois@biocodex.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will be conducted in 2 periods: a 6-month, placebo-controlled, double-blind treatment period on which the primary endpoint will be evaluated (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 4 years open-label extension (OLE) part of the study to continue to assess the long-term efficacy and safety of stiripentol.

Study Record Dates

• First Submitted: June 3, 2024
• First Posted: June 18, 2024
• Study Start: August 1, 2024
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): August 1, 2030
• Last Updated: June 18, 2024

Record last verified: 2024-06