Long-term Efficacy of Carglumic Acid in Organic Acidemia.

• ClinicalTrials.gov Identifier: NCT04284917
• Recruitment Status: Unknown
• First Posted: February 26, 2020
• Last Update Posted: February 26, 2020
• Sponsor: National Taiwan University Hospital
• Information provided by (Responsible Party): National Taiwan University Hospital

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Propionic Acidemia (PA) , Methylmalonic Acidemia (MMA)	Drug: Carglumic Acid (Carbaglu®)	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluate the Long Term Effectiveness & Safety of the Use of Carglumic Acid (Carbaglu®) in Patients With Propionic Acidemia (PA) or Methylmalonic Acidemia (MMA).
• Actual Study Start Date: November 28, 2019
• Estimated Primary Completion Date: December 2021
• Estimated Study Completion Date: December 2021

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Number of emergency visits due to hyperammonemia within 12 months period [ Time Frame: 12 months ]
   Adverse Events

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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®

Contacts and Locations

Locations

Taiwan

National Taiwan University Hospital

Taipei, Taiwan, 10041

Sponsors and Collaborators

National Taiwan University Hospital

Investigators

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

More Information

• Responsible Party: National Taiwan University Hospital
• ClinicalTrials.gov Identifier: NCT04284917
• Other Study ID Numbers: 201810033MIPB
• First Posted: February 26, 2020
• Last Update Posted: February 26, 2020
• Last Verified: November 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Taiwan University Hospital:

Carglumic Acid (Carbaglu®)

Additional relevant MeSH terms:

Amino Acid Metabolism, Inborn Errors; Propionic Acidemia; Acidosis; Acid-Base Imbalance; Metabolic Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn