Carglumic Acid in Methylmalonic Acidemia and Propionic Acidemia

NCT02426775 | Completed Phase 3 DMC

• 1 other identifier: RC 13/116
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 2

Brief Summary

A Phase IIIb (Three b), Randomized Multicentre Comparative Trial to Evaluate the Long Term Effectiveness \& Safety of the use of Carglumic Acid (Carbaglu®) in Patients with Propionic Acidemia (PA) or Methylmalonic Acidemia (MMA). Carbaglu® clinical experience in Organic Acidemia (OA) is limited to a non-comparative retrospective collection of data from patients who had received Carbaglu® for 1 to 15 days. There is no current evidence supporting the use of carglumic acid for the chronic management of patients with OA. The investigators are proposing a randomized multicentre prospective clinical trial to evaluate long-term effects of the use of Carbaglu® (50mg/kg/day) combined with standard chronic therapy in patients with PA and MMA compared to standard chronic therapy alone.

Conditions

Propionic Acidemia; Methylmalonic Acidemia

Outcome Measures

Primary Outcomes (1)

• Number of emergency visits due to hyperammonemia within 24 months period

  24 months

Secondary Outcomes (6)

• Time to first visit to the ER due to hyperammonemia from starting the treatment.

  24 months

• Plasma ammonia levels over the study treatment period.

  24 months

• Number of days of hospitalization

  24 months

• Acylcarnitine level for all patients

  once on screening visit

• Measuring urine organic acid levels for both diseases.

  24 months

Study Arms (4)

Methylmalonic Acidemia Control Arm

NO INTERVENTION

patients with Methylmalonic Acidemia will receive standard therapy only (protein restricted diet, L-carnitine, metronidazole and vitamin B12)

Methylmalonic Acidemia Active arm

EXPERIMENTAL

patients with Methylmalonic Acidemia will receive Carglumic Acid in addition to standard therapy (protein restricted diet, L-carnitine, metronidazole and vitamin B12)

Drug: Carglumic Acid

Propionic Acidemia Control Arm

NO INTERVENTION

patients with Propionic Acidemia will receive standard therapy only (protein restricted diet, L-carnitine, metronidazole and biotin)

Propionic Acidemia Active arm

EXPERIMENTAL

patients with Propionic Acidemia will receive Carglumic Acid in addition to standard therapy (protein restricted diet, L-carnitine, metronidazole and biotin)

Drug: Carglumic Acid

Interventions

Carglumic Acid DRUG

Carglumic Acid 50 mg/kg/day (twice daily)

Also known as: Carbaglu

Methylmalonic Acidemia Active arm; Propionic Acidemia Active arm

Eligibility Criteria

• Age: Up to 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female Children of 15 years old or less
• Parent or legal guardian agree to participate and to sign the (Institutional Review Board) IRB approved Informed Consent Form (assent forms will be waived due to the mental disability of those children)
• Not participating in any other clinical trial in the previous 30 days
• PA or MMA confirmed using the following criteria:
• PA confirmed by the measurement of acylcarnitine profile, urine organic acid, measurement of propionyl Co-A carboxylase in leukocytes or cultured fibroblasts or by DNA molecular testing of PCCA (Propionyl CoA Carboxylase, Alpha Polypeptide) or PCCB (propionyl CoA carboxylase, beta polypeptide) gene
• MMA confirmed by the measurement of acylcarnitine profile, urine organic acid, measurement of methymalonyl Co-A mutase in culture fibroblasts or DNA molecular testing of mutgene.
• Expected survival of at least 6 months, for the purpose of this study Survival expectance will be defined as patient not admitted to the Pediatric Intensive Care Unit (PICU) due to hyperammonemia more than 2 times per year or asymptomatic patients diagnosed by newborn screening program or stable chronic patients who are followed up at outpatient clinic.

You may not qualify if:

• Patients with other organic acidemia or any other cause of hyperammonemia
• Patient receiving other investigational therapy for PA or MMA
• Past history of hypersensitivity or drug allergy to Carbaglu®
• Patient with PA or MMA and other inherited genetic conditions or congenital anomalies

Sponsors & Collaborators

• King Abdullah International Medical Research Center: lead

Study Sites (2)

King Abdullah Specialist Children Hospital, King Abdulaziz Medical City

Riyadh, 11426, Saudi Arabia

Location

King Fahad Medical City

Riyadh, Saudi Arabia

Location

Related Publications (1)

• Nashabat M, Obaid A, Al Mutairi F, Saleh M, Elamin M, Ahmed H, Ababneh F, Eyaid W, Alswaid A, Alohali L, Faqeih E, Aljeraisy M, Hussein MA, Alasmari A, Alfadhel M. 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. BMC Pediatr. 2019 Jun 13;19(1):195. doi: 10.1186/s12887-019-1571-y.

  PMID: 31196016 DERIVED

MeSH Terms

Conditions

Propionic Acidemia; Methylmalonic acidemia

Interventions

carglumic acid

Condition Hierarchy (Ancestors)

Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Majid A. Alfadhel, MD

  King Abdulaziz Medical City, National Guard / Riyadh-Saudi Arabia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head Genetics Division, Department of Pediatrics. Assistant Professor, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)

Study Record Dates

• First Submitted: April 22, 2015
• First Posted: April 27, 2015
• Study Start: November 1, 2015
• Primary Completion: March 19, 2019
• Study Completion: March 19, 2019
• Last Updated: April 25, 2019

Record last verified: 2019-04

Locations

SA (2)