Carglumic Acid in Methylmalonic Acidemia and Propionic Acidemia

Randomized Multicentre Comparative Trial to Evaluate the Long Term Effectiveness of the Use of Carbaglu® in Patients With Propionic Acidemia (PA) or Methylmalonic Acidemia (MMA)

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.

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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