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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Biocodex

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Decision date (initial)

2024-05-16

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Pharmacokinetic, Efficacy

To evaluate the efficacy of stiripentol in decreasing urinary oxalate excretion

Secondary objectives 5

1. To characterize the effect of stiripentol on levels of urinary oxalate excretion in 24-hour collection
2. To evaluate the effect of stiripentol on kidney function
3. To evaluate the change in kidney stones
4. To evaluate urinary spot collections (oxalate, creatinine and other urinary parameters indicating the risk of lithiasis)
5. To evaluate the quality of life (QoL)

Conditions and MedDRA coding

Primary Hyperoxaluria (PH) of all subtypes (PH1, PH2 and PH3)

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003200-PIP01-22

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Male or female subjects aged ≥6 years at the time of consent signature
2. Diagnosed with primary hyperoxaluria disease and subtype (type 1, 2 or 3) confirmed by genetic testing
3. 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)
4. With mean 24-hour urinary oxalate excretion from 2 valid 24-hour urine collections ≥0.70 mmol/24h/1.73m²
5. With estimated Glomerular Filtration Rate ≥ 45 mL/min/1.73 m2 (Schwartz 2009 in pediatric patients and CKD-EPI in adults)
6. 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.
7. 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 17

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 if such 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: 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
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 or hypersensitivity to the study treatments
10. 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
11. 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
12. Contraindications to stiripentol as defined in the applicable Investigator Brochure
13. Patient at risk of pregnancy, pregnant or breastfeeding female patient
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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent change in 24-hour urinary oxalate excretion corrected for body surface area (BSA) from baseline to Month 6

Secondary endpoints 11

1. Percent change in 24-hour urinary oxalate excretion corrected for body surface area (BSA) from baseline to Month 3
2. Absolute change in 24-hour urinary oxalate excretion corrected for body surface area (BSA) from baseline to Month 3 and Month 6
3. Change in 24-hour urine oxalate/creatinine ratio from baseline to Month 3 and Month 6
4. 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
5. Proportion of patients with normalisation of 24-hour urinary oxalate level corrected for BSA at Month 3 and Month 6
6. Change in estimated glomerular filtration rate (eGFR) from baseline to Month 6
7. Occurrence and frequency of kidney stone events during the follow-up
8. Change in urine oxalate/creatinine ratios as assessed in spot urine collections between baseline and Month 6
9. Change in biological parameters related to kidney stone formation between baseline and Month 6
10. 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)
11. Change in Euro Quality of Life Health State Profile Questionnaire (EQ-5D) and EQ-5D Visual Analog Scale (VAS)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Biocodex

Sponsor organisation

Biocodex

Address

22 Rue Des Aqueducs

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Biocodex

Contact name

Laurent Chancharme

Public contact point

Organisation

Biocodex

Contact name

Pauline Decima

Third parties 3

Locations

3 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 125 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications