RecruitingPhase 2NCT06887777

Efficacy and Safety of the Treatment of Pyruvate Dehydrogenase Deficiency Patients With Glycerol Phenylbutyrate (RAVICTI)

A Phase II, Multicentric, Prospective, Non-comparative Clinical Trial to Assess the Efficacy and Safety of the Treatment of Pyruvate Dehydrogenase Deficiency (PDH) Patients With Glycerol Phenybutyrate (RAVICTI®)

Sponsor

Assistance Publique - Hôpitaux de Paris

Enrollment

15 participants

Start Date

Oct 1, 2025

Study Type

INTERVENTIONAL

Conditions

Pyruvate Dehydrogenase Complex Deficiency Disease

Summary

This is a phase II, multicenter, prospective, non-comparative clinical trial to assess the efficacy and safety of the treatment of pyruvate dehydrogenase deficiency (PDH) patients with glycerol phenylbutyrate (Ravicti®). The trial will be conducted with three visits: 3 day hospitalizations including clinical consultations and paramedical procedures at Month 0 (M0), Month 3 (M3), Month 6 (M6). During all the research, AE/SAE and treatment compliance will be recorded. Patients will keep their usual treatment during the study time: vitamin B1, ketogenic diet, possible anti-epileptic and/or dystonic treatment(s). The efficacy on fatigue, polyhandicap, neurodevelopmental functioning, quality of life and seizure amount for epileptic patients will be evaluated at 0, 3 and 6 months. Biological balance will be assed with regular quantification of PDH deficiency markers, lactate concentration and amino acid plasma quantification.

Eligibility

Min Age: 2 YearsMax Age: 25 Years

Inclusion Criteria9

Child from 2 to 17 years of age Or
Adult from 18 to 25 years of age
With a PDH deficiency confirmed by molecular biology:
a class 4 or 5- missense variant on the PDHA1 gene or
one homozygous variant or two mixed heterozygous variants of class 4 or 5 that are missense variants on PDHB or DLAT genes or
one homozygous variant or two mixed heterozygous variants of class 4 or 5 on PDHX genes (including non-sense and frameshift variants, and intragenic deletions
For females of childbearing potential, negative bHCG and effective method of contraception (sexual abstinence, hormonal contraception containing ethinylestradiol and levonorgestrel, intrauterine device or hormone-releasing system, cap, diaphragm or sponge with spermicide, condom) until 30 days after the end of study. For male, an effective method of contraception (sexual abstinence, condom) until 30 days after the end of study
Signature of consent by the legal representative
Beneficiary of a social security coverage (affiliated or entitled)

Exclusion Criteria9

Patient with E3 deficiency due to pathogenic mutation in DLD gene
Patient with non-sense mutation on PDHB or DLAT gene, and male patient with non-sense mutation or PDHA1 gene.
Patient with planned hip or scoliosos surgery during the study timeframe.
Patient whose parents / legal representative refuse flu vaccine.
Treatment change during the last 3 months prior inclusion (ketogenic diet and/or B1 vitamin)
Hypersensitivity to Glycerol Phenylbutyrate or to any of the excipients
No disease requiring Glycerol Phenylbutyrate (Hyperammonemia due to urea cycle disease or other aetiology)
Pregnant or breastfeeding women
Participation to another clinical trial on medicinal products for human use