Long-term Efficacy of Carglumic Acid in Organic Acidemia.

Evaluate the Long Term Effectiveness & Safety of the Use of Carglumic Acid (Carbaglu®) in Patients With Propionic Acidemia (PA) or Methylmalonic Acidemia (MMA).

Evaluate the Long Term Effectiveness & Safety of the use of Carglumic Acid (Carbaglu®) in Patients with Propionic Acidemia (PA) or Methylmalonic Acidemia (MMA).

Study Overview

• Status: Unknown
• Conditions: Propionic Acidemia (PA) , Methylmalonic Acidemia (MMA)
• Intervention / Treatment: Drug: Carglumic Acid (Carbaglu®)

Detailed Description

Study procedures:

A. Study period: 24 months; treatment period: 12 months.

B. Patients will receive Carglumic Acid (Carbaglu®) 50 mg/kg/day in addition to standard therapy (protein restricted diet, L-carnitine, metronidazole and vitamin B12).

C. Patients need to regularly come back for follow up examination on Day 0, month 3, month 6, and month 12.

D. Patients should report any adverse event that occur during treatment period.

E. Patients' number of emergency visits due to hyperammonemia, ammonia level, acylcarnitine, urinary organic acid analysis, plasma amino acid analysis will be recorded during treatment period.

• Study Type: Interventional
• Enrollment (Anticipated): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 10041
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. Male or female Children of 18 years old or less.
3. Had experienced Hyperammonemia(NH3 ≧100 uM) before.
4. Not participating in any other clinical trial in the previous 30 days

Exclusion Criteria:

1. Patients with other organic acidemia or any other cause of hyperammonemia
2. Patient receiving other investigational therapy for PA or MMA
3. Patient with PA or MMA and other inherited genetic conditions or congenital anomalies
4. Past history of hypersensitivity or drug allergy to Carbaglu®

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Receive Carglumic Acid; Experimental Case_ Carglumic Acid

Drug: Carglumic Acid (Carbaglu®); A. Study period: 24 months; treatment period: 12 months. B. Patients will receive Carglumic Acid (Carbaglu®) 50 mg/kg/day in addition to standard therapy (protein restricted diet, L-carnitine, metronidazole and vitamin B12) C. Patients need to regularly come back for follow up examination on Day 0, month 3, month 6, and month 12. (Check Plasma Amino Acid Analysis, Ammonia, acylcarnitine profile, Urinary organic acid analysis.) D. Patients should report any adverse event that occur during treatment period. E. Patients' number of emergency visits due to hyperammonemia, ammonia level, acylcarnitine, urinary organic acid analysis, plasma amino acid analysis will be recorded during treatment period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of emergency visits due to hyperammonemia within 12 months period	Adverse Events	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first visit to the ER due to hyperammonemia from starting the treatment	Adverse Events	12 months
Assessment of Plasma ammonia level	Plasma ammonia level over the study treatment period.	Baseline,3,6,9 and 12,months after receiving Carbaglu.
Number of days of hospitalization	Number of days of hospitalization during study treatment period.	12 months
Assessment of Acylcarnitine level	Acylcarnitine level for all patients	Baseline,3,6,9 and 12,months after receiving Carbaglu.
Assessment of urine organic acid level	Measuring urine organic acid level for both diseases.	Baseline,3,6,9 and 12,months after receiving Carbaglu.
Assessment of Plasma aminoacids' level	Measuring Plasma aminoacids' level for both diseases.	Baseline,3,6,9 and 12,months after receiving Carbaglu.

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Ni-Chung Lee, M.D., Ph.D, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2019
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: February 24, 2020
• First Submitted That Met QC Criteria: February 25, 2020
• First Posted (Actual): February 26, 2020

Study Record Updates

• Last Update Posted (Actual): February 26, 2020
• Last Update Submitted That Met QC Criteria: February 25, 2020
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Carglumic Acid (Carbaglu®)
• 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: 201810033MIPB

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No