Publication Details

Title :

Evaluation of long-term effectiveness of the use of carglumic acid in patients with propionic acidemia (PA) or methylmalonic acidemia (MMA): study protocol for a randomized controlled trial

Journal:

BMC Pediatr.

Impact Factor:

1.983

Authors:

Nashabat M1, Obaid A1, Al Mutairi F1, Saleh M2, Elamin M2, Ahmed H1, Ababneh F1, Eyaid W1, Alswaid A1, Alohali L1, Faqeih E2, Aljeraisy M3, Hussein MA4, Alasmari A2, Alfadhel M5.

Affiliations:

1 Genetics Division, Department of Pediatrics, King Abdullah International Medical Research Centre, King Saud bin Abdulaziz University for Health Science, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs (NGHA), PO Box 22490 11426, Riyadh, Saudi Arabia.

2 Medical Genetic Section, King Fahad Medical City, Children’s Hospital, Riyadh, Saudi Arabia.

3 King Abdullah International Medical Research Centre, King Saud bin Abdulaziz University for Health Science, College of Pharmacy, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia.

4 Department Biostatistics and Bioinformatics, King Abdullah International Medical Research Centre, King Saud bin Abdulaziz University for Health Science, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia.

5 Genetics Division, Department of Pediatrics, King Abdullah International Medical Research Centre, King Saud bin Abdulaziz University for Health Science, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs (NGHA), PO Box 22490 11426, Riyadh, Saudi Arabia.

Year of Publication:

2019

DOI:

10.1186/s12887-019-1571-y.

Abstract:

INTRODUCTION:
Propionic acidemia (PA) and methylmalonic acidemia (MMA) are rare autosomal recessive inborn errors of metabolism characterized by hyperammonemia due to N-acetylglutamate synthase (NAGS) dysfunction. Carglumic acid (Carbaglu®; Orphan Europe Ltd.) is approved by the US Food and Drug Administration (USFDA) for the treatment of hyperammonemia due hepatic NAGS deficiency. Here we report the rationale and design of a phase IIIb trial that is aimed at determining the long-term efficacy and safety of carglumic acid in the management of PA and MMA.

METHODS:
This prospective, multicenter, open-label, randomized, parallel group phase IIIb study will be conducted in Saudi Arabia. Patients with PA or MMA (≤15 years of age) will be randomized 1:1 to receive twice daily carglumic acid (50 mg/kg/day) plus standard therapy (protein-restricted diet, L-carnitine, and metronidazole) or standard therapy alone for a 2-year treatment period. The primary efficacy outcome is the number of emergency room visits due to hyperammonemia. Safety will be assessed throughout the study and during the 1 month follow-up period after the study.

DISCUSSION:
Current guidelines recommend conservative medical treatment as the main strategy for the management of PA and MMA. Although retrospective studies have suggested that long-term carglumic acid may be beneficial in the management of PA and MMA, current literature lacks evidence for this indication. This clinical trial will determine the long-term safety and efficacy of carglumic acid in the management of PA and MMA.