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®)
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.
• 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)