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

NCT ID: NCT06465472

Last Updated: 2024-06-18

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-31
• Study Completion Date: 2030-08-31

Brief Summary

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

Detailed Description

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: EXPERIMENTAL

Stiripentol Oral Capsule

Intervention Type: 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.

Urine samples collect

Intervention Type: 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.

Blood samples collect

Intervention Type: 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)

Kidney imaging

Intervention Type: OTHER

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

Quality of Life questionnaires

Intervention Type: 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

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).

Group Type: PLACEBO_COMPARATOR

Placebo Oral Capsule

Intervention Type: DRUG

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

Urine samples collect

Intervention Type: 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.

Blood samples collect

Intervention Type: 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)

Kidney imaging

Intervention Type: OTHER

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

Quality of Life questionnaires

Intervention Type: 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.

Interventions

Stiripentol Oral Capsule

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.

Intervention Type: DRUG

Placebo Oral Capsule

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

Intervention Type: DRUG

Urine samples collect

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.

Intervention Type: BIOLOGICAL

Blood samples collect

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)

Intervention Type: BIOLOGICAL

Kidney imaging

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

Intervention Type: OTHER

Quality of Life questionnaires

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 1. Diagnosed with primary hyperoxaluria disease and subtype (type 1, 2 or 3) confirmed by genetic testing
• 2. 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
• 3. With mean 24-hour urinary oxalate excretion from 2 valid 24-hour urine collections ≥ 0.70 mmol/24h/1.73m²
• 4. With estimated Glomerular Filtration Rate ≥ 45 mL/min/1.73 m2 (Schwartz et al., 2009 in pediatric patients and CKD-EPI in adults)
• 5. 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
• 6. In France, patient affiliated with or who benefits from a social security scheme

Exclusion Criteria

• 1. 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
• 2. 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
• 3. History of kidney or liver transplant
• 4. Presenting any of the following liver function tests abnormalities during the screening period:

1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST)> 2 × upper limit of normal (ULN)

2. 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

• 5. Recent (4 weeks before the screening visit) or planned change in eating habits
• 6. Intermittent fasting planned during the 6 first months of the study period (e.g., Ramadan)
• 7. Other medical conditions or comorbidities, treatment, which in the opinion of the investigator, would interfere with study compliance or data interpretation
• 8. Presenting any significant biological or clinical anomalies that are not compatible with participation in the study according to the investigator
• 9. History of severe allergy, asthma, skin rashes, intolerance to lactose or hypersensitivity to the study treatments
• 10. 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
• 11. 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
• 12. Contraindications to stiripentol as defined in the applicable Investigator's Brochure (i.e. patients presenting a hypersensitivity to the active substance or any excipients)
• 13. Patient at risk of pregnancy, pregnant or breastfeeding female
• 14. Patient under guardianship or curatorship
• 15. Patient under the protection of the Court or deprived of liberty
• 16. 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
• 17. Patient whose current state of health does not allow him/her to give consent

• Minimum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Exystat

OTHER

Sponsor Role: collaborator

Biocodex

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Oana BERNARD, MD

Role: STUDY_DIRECTOR

Chief Scientific Officer

Central Contacts

Pauline DECIMA

Role: CONTACT

p.decima@biocodex.fr

03.44.86.82.28 ext. +33

Carine FRANCOIS

Role: CONTACT

c.francois@biocodex.fr

03.44.86.82.28 ext. +33

Other Identifiers

2023-508062-15-00

Identifier Type: CTIS

Identifier Source: secondary_id

CRYSTAL - STP226

Identifier Type: -

Identifier Source: org_study_id