Carglumic Acid in Methylmalonic Acidemia and Propionic Acidemia

Brief Title

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)

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.
    


Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Number of emergency visits due to hyperammonemia within 24 months period

Secondary Outcome

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

Condition

Propionic Acidemia

Intervention

Carglumic Acid

Study Arms / Comparison Groups

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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

33

Start Date

November 2015

Completion Date

March 19, 2019

Primary Completion Date

March 19, 2019

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
      

Gender

All

Ages

N/A - 15 Years

Accepts Healthy Volunteers

No

Contacts

Majid A. Alfadhel, MD, , 

Location Countries

Saudi Arabia

Location Countries

Saudi Arabia

Administrative Informations


NCT ID

NCT02426775

Organization ID

RC 13/116


Responsible Party

Principal Investigator

Study Sponsor

King Abdullah International Medical Research Center


Study Sponsor

Majid A. Alfadhel, MD, Principal Investigator, King Abdulaziz Medical City, National Guard / Riyadh-Saudi Arabia


Verification Date

April 2019