Clinical trial with Phenilbutirrate to reduce lactic acid in patients affected with Melas Syndrome and PHD deficency encephalopathy

Phenylbutyrate Therapy in Mitochondrial Disease with lactic acidosis: an opel label clinical trial in MELAS and PHD deficiency patients - PHEMI

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2018-001094-25-IT

Enrollment

Registered

2021-05-20

Start date

2019-09-12

Completion date

Unknown

Last updated

2024-10-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Melas Syndrome and PDH deficency enchephalopathy MedDRA version: 20.0 Level: PT Classification code 10053872 Term: MELAS syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.0 Level: PT Classification code 10053872 Term: MELAS syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.0 Level: LLT Classification code 10062950 Term: Leigh syndrome System Organ Class: 10010331 - Congenital, familial and

Interventions

Trade Name: Feburane Product Name: pheburane Product Code: [A042917017] Pharmaceutical Form: Granules for oral suspension Current Sponsor code: A042917017 Concentration unit: mg/g milligram(s)/gram Co

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: The inclusion criteria are: 1. Age between 3 and 65 years old 2. Confirmed molecular diagnosis: mutations in PDHA1 and m.3 243A>G mtDNA point mutation 3. Plasma lactic acid =2100 umol/l (normal value . 580-2100) 4. Availability of brain MRI and MRSI at baseline (pre-treatment); 5. Availability of PDH residual activity in cultured fibroblasts in PDH1A patients at baseline (pre-treatment) 6. Written informed consent (and assent when applicable) obtained from subject or subject’s legal representative and ability for subject to comply with the requirements of the study. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 5 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1

Exclusion criteria

Exclusion criteria: The exclusion criteria will be: 1) Comorbidity with other chronic diseases. 2) Other experimental treatment in the previous 6 months. 3) Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study 4) At Screening, the estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2. 5) At Screening presence of history of liver failure. 6) Subject has undergone an in-patient hospitalization within the 30 days prior to the Baseline Visit or has a planned hospitalization or a surgical procedure during the trial. 7) Subject has a history of active substance abuse during the year before the Baseline Visit, in the opinion of the Investigator. 8) Subject has any prior or current medical condition that, would prevent the subject from safely participating in and/or completing all trial requirements . 9) The patient will be excluded from the study if he presents a hart insufficiency ( FE < 40% ) severe renal failure (GRF GFR between 29 and 15 ml/min) clinical conditions in which sodium retention is found with edema, fructose intolerance, glucose / galactose malabsorption or saccharose or isomaltase enzyme deficiencies. 10) Hypersensitivity to the drug or to the excipients. 11) Not able to obtain written informed consent (and assent when applicable) from subject or subject’s legal representative and ability for subject to comply with the requirements of the study.

Design outcomes

Primary

Measure	Time frame
Main Objective: The primary objective is to investigate the efficiency and safety of PB in patients with PDH deficiency and MELAS .;Secondary Objective: The secondary objectives are to identify novel biomarkers for these two diseases and to evaluate whether the clinical/biochemical efficacy detected in patients correlates with the response observed in the skin fibroblasts of PDH deficiency/MELAS patients and in cybrids from MELAS patients incubated with PB.;Primary end point(s): The primary endpoint of the study is the reduction of lactic acidosis.;Timepoint(s) of evaluation of this end point: All along the trial	—

Measure

Time frame

Main Objective: The primary objective is to investigate the efficiency and safety of PB in patients with PDH deficiency and MELAS .;Secondary Objective: The secondary objectives are to identify novel biomarkers for these two diseases and to evaluate whether the clinical/biochemical efficacy detected in patients correlates with the response observed in the skin fibroblasts of PDH deficiency/MELAS patients and in cybrids from MELAS patients incubated with PB.;Primary end point(s): The primary endpoint of the study is the reduction of lactic acidosis.;Timepoint(s) of evaluation of this end point: All along the trial

—

Secondary

Measure	Time frame
Secondary end point(s): A. Clinical efficiency of PB B. To evaluate the biochemical efficiency of PB,;Timepoint(s) of evaluation of this end point: All along the trial	—

Countries

Italy

Contacts

Public ContactDipartimento di Ricerca e Sviluppo

Fondazione IRCCS Istituto Neurologico Carlo Besta

crc@istituto-besta.it0223943568

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026