Clinical trial NCT02426775: Carglumic Acid in Methylmalonic Acidemia and Propionic Acidemia
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Propionic Acidemia
Methylmalonic Acidemia
Lead sponsor: King Abdullah International Medical Research Center
Sponsor class: OTHER
First posted: 2015-04-27
Enrollment: 33
Sex: ALL
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of emergency visits due to hyperammonemia within 24 months period
timeFrame: 24 months
Secondary outcomes:
measure: Time to first visit to the ER due to hyperammonemia from starting the treatment.
timeFrame: 24 months
measure: Plasma ammonia levels over the study treatment period.
timeFrame: 24 months
measure: Number of days of hospitalization
timeFrame: 24 months
measure: Acylcarnitine level for all patients
timeFrame: once on screening visit
measure: Measuring urine organic acid levels for both diseases.
timeFrame: 24 months
measure: Measuring Plasma aminoacids' levels for both diseases
timeFrame: 24 months
Other outcomes:
Locations:
city: Riyadh
country: Saudi Arabia
facility: King Abdullah Specialist Children Hospital, King Abdulaziz Medical City
city: Riyadh
country: Saudi Arabia
facility: King Fahad Medical City
Study officials:
affiliation: King Abdulaziz Medical City, National Guard / Riyadh-Saudi Arabia
name: Majid A. Alfadhel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.