Pdh-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 Phenylbutyrate (Ravicti®)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18], Diseases [C] - Nervous System Diseases [C10]

Trial duration

1 Oct 2025 → ongoing

Decision date (initial)

2025-04-22

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: Safety, Efficacy

Evaluation of the efficacy of Glycerol Phenylbutyrate treatment on fatigue at 6 months

Secondary objectives 8

1. Evaluation of the efficacy of Glycerol Phenylbutyrate treatment on fatigue at 3 months.
2. Evaluation of the efficacy of Glycerol Phenylbutyrate treatment on polyhandicap at 6 months.
3. Evaluation of the efficacy of Glycerol Phenylbutyrate treatment on neurodevelopmental functioning symptoms (behaviour and learning capacity) at 6 months
4. Evaluation of the efficacy of Glycerol Phenylbutyrate treatment on the number of seizures for epileptic patients at 6 months.
5. Evaluation of the efficacy of Glycerol Phenylbutyrate treatment on quality of life for persons with polyhandicap, at 3 and 6 months.
6. Evaluation of the efficacy of Glycerol Phenylbutyrate treatment on the biological balance by quantification of the decrease in pyruvate concentration, marker of PDH deficiency, and lactate concentration (points Redox performed before and after 3 meals), and the quantification of amino acids in plasma notably alanine and proline (markers of hyperlactatemia) (aminoacid chromatography) at 3 and 6 months.
7. Glycerol Phenylbutyrate treatment tolerance assessment at 3 and 6 months [allergy, side effects, amino acid chromatography (glutamine and other amino acid levels) in plasma].
8. Assessment of Glycerol Phenylbutyrate treatment compliance by dosage of 4-phenylbutyrate in plasma at 3 and 6 months.

Conditions and MedDRA coding

Pyruvate dehydrogenase deficiency

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Child from 2 to 17 years of age or Adult from 18 to 25 years of age
2. With a PDH deficiency confirmed by molecular biology: a class 4 or 5- missense variant at hemizygous or heterozygous state 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 gene (including non-sense and frameshift variants, and intragenic deletions)
3. 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 7 days after the end of study. For male, an effective method of contraception (sexual abstinence, condom) until 7 days after the end of study
4. Signature of the legal representative
5. Beneficiary of a social security coverage (affiliated or entitled)

Exclusion criteria 11

1. Patient with E3 deficiency due to pathogenic mutation in DLD gene
2. Patient with non-sense mutation on PDHB or DLAT gene, and male patient with non-sense mutation on PDHA1 gene
3. Treatment change during the last 3 months prior inclusion (ketogenic diet and/or B1 vitamin
4. Hypersensitivity to Glycerol Phenylbutyrate or to any of the excipients
5. No disease requiring Glycerol Phenylbutyrate (Hyperammonemia due to urea cycle disease or other aetiology)
6. History of hepatocellular insufficiency or renal insufficiency
7. Pregnant or breastfeeding women
8. Participation to another clinical interventional trial on medicinal products for human use
9. Ketogenic diet and B1 vitamin introduced less than 3 months prior
10. Patient with planned hip or scoliosis surgery during the study timeframe
11. Patient whose parents/legal representative refuse flu vaccine

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The efficacy of Glycerol Phenylbutyrate treatment on fatigue at 6 months will be evaluated by the Pediatric Quality of Life Inventory™ Multidimensional Fatigue Scale (PedsQL™ MFS, appendix 4 to 6). Difference between the total score at M0 and M6 will be calculated. Improving the overall score of 20% between M0 and M6 will reflect the impact of treatment on fatigue (success of the treatment).

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pascale DE LONLAY

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pascale DE LONLAY

Locations

1 EU/EEA country · 5 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 24 files

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

Application history

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