Carglumic Acid in Methylmalonic Acidemia and Propionic Acidemia (CAMP)

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.

Study Overview

• Status: Completed
• Conditions: Propionic Acidemia; Methylmalonic Acidemia
• Intervention / Treatment: Drug: Carglumic Acid

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 3

Contacts and Locations

Study Locations

• Saudi Arabia
  • Riyadh, Saudi Arabia, 11426
    • King Abdullah Specialist Children Hospital, King Abdulaziz Medical City
  • Riyadh, Saudi Arabia
    • King Fahad Medical City

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Methylmalonic Acidemia Control Arm; patients with Methylmalonic Acidemia will receive standard therapy only (protein restricted diet, L-carnitine, metronidazole and vitamin B12)
Experimental: Methylmalonic Acidemia Active arm; 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; Carglumic Acid 50 mg/kg/day (twice daily); Other Names: Carbaglu
No Intervention: Propionic Acidemia Control Arm; patients with Propionic Acidemia will receive standard therapy only (protein restricted diet, L-carnitine, metronidazole and biotin)
Experimental: Propionic Acidemia Active arm; patients with Propionic Acidemia will receive Carglumic Acid in addition to standard therapy (protein restricted diet, L-carnitine, metronidazole and biotin)	Drug: Carglumic Acid; Carglumic Acid 50 mg/kg/day (twice daily); Other Names: Carbaglu

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of emergency visits due to hyperammonemia within 24 months period	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
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
Measuring Plasma aminoacids' levels for both diseases	24 months

Collaborators and Investigators

• Sponsor: King Abdullah International Medical Research Center
• Investigators: Principal Investigator: Majid A. Alfadhel, MD, King Abdulaziz Medical City, National Guard / Riyadh-Saudi Arabia

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): March 19, 2019
• Study Completion (Actual): March 19, 2019

Study Registration Dates

• First Submitted: April 22, 2015
• First Submitted That Met QC Criteria: April 24, 2015
• First Posted (Estimate): April 27, 2015

Study Record Updates

• Last Update Posted (Actual): April 25, 2019
• Last Update Submitted That Met QC Criteria: April 24, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Acid-Base Imbalance; Acidosis; Propionic Acidemia; Amino Acid Metabolism, Inborn Errors
• Other Study ID Numbers: RC 13/116