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

Tracking Information

• First Submitted Date: February 24, 2020
• First Posted Date: February 26, 2020
• Last Update Posted Date: February 26, 2020
• Actual Study Start Date: November 28, 2019
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 25, 2020)

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

Adverse Events

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: February 25, 2020)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Long-term Efficacy of Carglumic Acid in Organic Acidemia.
• 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).
• 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).

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
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Propionic Acidemia (PA) , Methylmalonic Acidemia (MMA)

Intervention

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.

Study Arms

Experimental: Receive Carglumic Acid

Experimental Case_ Carglumic Acid

Intervention: Drug: Carglumic Acid (Carbaglu®)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: February 25, 2020): 5
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2021
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

Eligibility 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®

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Taiwan

Administrative Information

• NCT Number: NCT04284917
• Other Study ID Numbers: 201810033MIPB
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: National Taiwan University Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: National Taiwan University Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: National Taiwan University Hospital
• Verification Date: November 2019