Methylmalonic Acidemia, Propionic Acidemia
Conditions
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.
Interventions
DRUGCarglumic Acid
Carglumic Acid 50 mg/kg/day (twice daily)
Sponsors
King Abdullah International Medical Research Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 15 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of emergency visits due to hyperammonemia within 24 months period | 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Plasma ammonia levels over the study treatment period. | 24 months |
| Number of days of hospitalization | 24 months |
| Time to first visit to the ER due to hyperammonemia from starting the treatment. | 24 months |
| Measuring urine organic acid levels for both diseases. | 24 months |
| Measuring Plasma aminoacids' levels for both diseases | 24 months |
| Acylcarnitine level for all patients | once on screening visit |
Countries
Saudi Arabia
Outcome results
None listed