Efficacy and Safety Assessment of Stiripentol in Patients Aged 6 and Older with Primary Hyperoxaluria Types 1, 2, or 3
- Trial ID
- 2023-508062-15-00
- Protocol
- STP226
- Sponsor
- Biocodex
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of stiripentol in decreasing urinary oxalate excretion in patients aged 6 years and older with **Primary Hyperoxaluria** (PH) types 1, 2, or 3. This is clinically relevant as reducing urinary oxalate excretion can potentially mitigate the risk of kidney stone formation and subsequent renal damage, which are significant complications associated with PH.
Secondary objectives include:
- Characterizing the effect of stiripentol on levels of urinary oxalate excretion in 24-hour collection.
- Evaluating the effect of stiripentol on kidney function.
- Assessing changes in kidney stones.
- Evaluating urinary spot collections for oxalate, creatinine, and other urinary parameters indicating the risk of lithiasis.
- Assessing the quality of life (QoL) of the participants.
Participants
The clinical trial involves a total of **23 participants** diagnosed with **Primary Hyperoxaluria** (PH) of all subtypes, including PH1, PH2, and PH3. The study population comprises both male and female subjects aged 6 years and older, with a confirmed diagnosis of the disease through genetic testing. Participants are required to be receiving optimal management of the disease through standard care strategies, such as increased fluid intake, vitamin B6, and potassium citrate, with or without approved target medications like lumasiran. The trial includes individuals with a mean 24-hour urinary oxalate excretion of at least 0.70 mmol/24h/1.73m² and an estimated Glomerular Filtration Rate of at least 45 mL/min/1.73 m². The study population was selected based on their ability to understand and comply with study requirements, and they must provide written informed consent. Pubescent patients and adult female subjects of childbearing potential are required to have a negative pregnancy test prior to participation. The trial includes a vulnerable population, ensuring that legal guardians provide consent for participants under the age of legal consent, with the participants providing assent as per local and national requirements.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy and safety of **stiripentol** in patients aged 6 years and older diagnosed with **primary hyperoxaluria** types 1, 2, or 3. This is a phase III, randomized, double-blind, placebo-controlled study. The trial will involve the administration of **Diacomit** 250 mg and 500 mg hard capsules, with a matched placebo consisting of capsules similar in appearance but without the active ingredient. The trial is expected to commence recruitment on March 4, 2024, and conclude by December 4, 2028.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, genetic confirmation of the disease subtype, and baseline urinary oxalate excretion levels. Following successful screening, participants will be randomized to receive either the active treatment or placebo. The primary endpoint is the percent change in 24-hour urinary oxalate excretion corrected for body surface area from baseline to Month 6. Secondary endpoints include changes in urinary oxalate excretion at Month 3, changes in the urine oxalate/creatinine ratio, and the occurrence of kidney stone events.
Study visits will occur at baseline, Month 3, and Month 6, with assessments including urine and blood tests, kidney function evaluation, and quality of life questionnaires. The expected duration of participant involvement is approximately 6 months. Conditions that may lead to early termination from the study include non-compliance with study procedures, adverse events, or withdrawal of consent. The trial aims to provide comprehensive data on the potential benefits of stiripentol in managing primary hyperoxaluria, contributing to the understanding and treatment of this rare condition.
Treatment
The clinical trial involves the administration of **stiripentol** in the form of hard capsules, marketed under the name Diacomit. Two dosage strengths are utilized: 250 mg and 500 mg capsules. The pharmaceutical form is a hard capsule, and the route of administration is oral. The maximum daily dose is 3000 mg, with a total treatment period of up to 60 days. The capsules are not marked to ensure blinding during the trial. The active substance, stiripentol, is of chemical origin and is authorized for use in Norway under the marketing authorization number EU/1/06/367/002 for the 250 mg capsules and EU/1/06/367/005 for the 500 mg capsules. The manufacturer of Diacomit is BIOCODEX.
A matched placebo is also employed in the study, consisting of capsules similar in appearance to the 250 mg and 500 mg stiripentol capsules but containing no active ingredient. The placebo is used to maintain blinding and assess the efficacy of stiripentol in comparison to a non-active treatment. The placebo capsules are administered orally, following the same dosing schedule as the active treatment, to ensure consistency in the trial protocol.
Efficacy
The efficacy of **stiripentol** in the clinical trial will be assessed primarily by evaluating the percent change in 24-hour urinary oxalate excretion corrected for body surface area (BSA) from baseline to Month 6. Secondary endpoints include the percent change in 24-hour urinary oxalate excretion corrected for BSA from baseline to Month 3, absolute change in 24-hour urinary oxalate excretion corrected for BSA from baseline to Month 3 and Month 6, and change in 24-hour urine oxalate/creatinine ratio from baseline to Month 3 and Month 6. Additionally, the proportion of patients achieving near normalization and normalization of 24-hour urinary oxalate levels corrected for BSA at Month 3 and Month 6 will be evaluated.
Other secondary endpoints include changes in estimated glomerular filtration rate (eGFR) from baseline to Month 6, occurrence and frequency of kidney stone events during follow-up, and changes in urine oxalate/creatinine ratios as assessed in spot urine collections between baseline and Month 6. The trial will also assess changes in biological parameters related to kidney stone formation and quality of life measures using the Pediatric Quality of Life Inventory (PedsQL) for patients under 18 years and the Kidney Disease Quality of Life Questionnaire (KDQOL) for patients 18 years and older. Additionally, changes in the Euro Quality of Life Health State Profile Questionnaire (EQ-5D) and EQ-5D Visual Analog Scale (VAS) will be measured.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male or female subjects aged ≥6 years at the time of consent signature
- 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)
- 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 2009 in pediatric patients and CKD-EPI in adults)
- 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.
- 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
- 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 if such 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: 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
- 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 or hypersensitivity to the study treatments
- 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
- 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
- Contraindications to stiripentol as defined in the applicable Investigator Brochure
- Patient at risk of pregnancy, pregnant or breastfeeding female patient
- 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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Yet Recruiting | 04 Mar 2024 | 4 |
 France | Recruiting | 04 Mar 2024 | 7 |
 Italy | Not Yet Recruiting | 04 Mar 2024 | 8 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Diacomit 250 mg hard capsules | Test | HARD CAPSULES | ORAL USE | 3000 | 60 | PRD3378114 |
Matched Placebo will consist in caspules similar to the 250 and 500 mg capsules of stiripentol but with no active ingredient | Placebo | N/A | — | — | — | N/A |
Diacomit 500 mg hard capsules | Test | HARD CAPSULES | ORAL USE | 3000 | 60 | PRD3394461 |