An Observational Study of Carbaglu® for the Treatment of MMA and PA in Adults and Pediatrics

A Non-Interventional Post-Authorization Safety Study (PASS) of Carbaglu® for the Treatment of Hyperammonemia Due to Methylmalonic Acidemia (MMA) and Propionic Acidemia (PA) in Adult and Pediatric Patient Populations

To obtain short-term and long-term clinical safety information, in pediatric and adult patients with PA and MMA treated with Carbaglu®.

Study Overview

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

Detailed Description

This study is being conducted to obtain short-term and long-term clinical safety information from adult and pediatric patients treated for hyperammonemia due to Methylmalonic Acidemia (MMA) and Propionic Acidemia (PA). This is an observational/non-interventional study. Patients will be treated per the prescribing information and routine medical practice.

Only available data will be collected as part of the study including developmental outcomes, details of treatment with Carbaglu® and other treatments for hyperammonemia including dietary and protein management, plasma ammonia levels, pregnancy and maternal complications, adverse effects on the developing fetus and neonate, adverse effects on the infant through first year of life.

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Anne Marie Cesario; Phone Number: 908-849-4907; Email: cesario.a@recordati.com

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Recruiting
      • Children's National Hospital
      • Principal Investigator: Nicholas Ah Mew, MD
      • Contact: Kara Simpson; Phone Number: 202-545-2503; Email: ksimpson@childrensnational.org
  • Florida
    • Tampa, Florida, United States, 33606
      • Recruiting
      • University of South Florida
      • Contact: Farideh Oberheu; Phone Number: 813-250-2292; Email: faljalla@usf.edu
      • Principal Investigator: Amarilis Sanchez-Valle, MD
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Ann & Robert H. Lurie Children's Hospital of Chicago
      • Principal Investigator: Joshua Baker, MD
      • Contact: Michael Sawin; Phone Number: 312-227-2816; Email: Msawin@luriechildrens.org
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Riley Children's Hospital
      • Contact: Susan Romie; Phone Number: 317-278-6650; Email: sromie@iu.edu
      • Principal Investigator: Melissa Lah, MD
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mt. Sinai
      • Contact: Colleen Donnelly; Phone Number: 212-241-5983; Email: Colleen.donnelly@mssm.edu
      • Principal Investigator: Margo Breilyn, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with PA or MMA of any age and gender, including pregnant women, are eligible for enrollment in the study as long as they meet the eligibility criteria.

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent/assent form
2. Prescribed and treated with Carbaglu®

3. Have an established diagnosis of PA or MMA defined as follows:

   • Diagnosed with PA by semi quantitative urine organic acid analysis, defined as presence of elevated methylcitric acid and normal methylmalonic acid levels and no evidence of biotin related disorders in the organic acid analysis; OR
   • Diagnosed with MMA by semi quantitative urine organic acid analysis, defined as elevation of methylmalonic acid and no evidence of vitamin B12 dependent disorder on plasma amino acid analysis (vitamin B12 dependency is defined by documented vitamin B12 responsiveness).

AND/OR

• Confirmation by molecular genetic testing

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Male and Female Adult and Pediatric Participants; Patients treated with Carbaglu for the treatment for hyperammonemia due to Methylmalonic Acidemia (MMA) and Propionic Acidemia (PA)	Drug: Carglumic Acid; Current or previous treatment with Carbaglu, the dose of Carbaglu® prescribed will be determined by the investigator for each individual patient.; Other Names: Carbaglu®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of Carbaglu® on plasma ammonia levels	Multiple plasma ammonia levels will be collected only during treatment with Carbaglu® according to prescribing information and routine medical practice in terms of visit frequency.	Patients treated with Carbaglu® will be managed chronically (out-patient) or acutely (hospital in-patient). In both cases, data will be collected for approximately 1 year following discontinuation of Carbaglu treatment.
Adverse Event frequency and severity	Any Carbaglu® related adverse events will be be collected and reported	Patients treated with Carbaglu® will be managed chronically (out-patient) or acutely (hospital in-patient). In both cases, data will be collected for approximately 1 year following discontinuation of Carbaglu treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fetal Outcomes and Pregnancy Outcomes	Pregnancy risks including maternal complications, adverse effects on the developing fetus and neonate, and adverse effects on the infant (through the first year of life).	Collection of pregnancy information for patients who becomes pregnant while participating in the trial or at time of enrollment. Pregnancy reports and reports involving neonates and infants up to 1 year of age must be reported to RRD Pharmacovigilance.

Collaborators and Investigators

• Sponsor: Recordati Rare Diseases
• Collaborators: Target PharmaSolutions, Inc.
• Investigators: Principal Investigator: Nicholas Ah Mew, MD, Children's National Research Institute; Study Director: William Ludlum, MD, Recordati Rare Diseases Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2022
• Primary Completion (Estimated): June 30, 2032
• Study Completion (Estimated): June 30, 2032

Study Registration Dates

• First Submitted: June 16, 2021
• First Submitted That Met QC Criteria: September 9, 2021
• First Posted (Actual): September 10, 2021

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: PA & MMA
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Acid-Base Imbalance; Acidosis; Propionic Acidemia; Hyperammonemia; Amino Acid Metabolism, Inborn Errors
• Other Study ID Numbers: CARBAGLU-RRDUS-PASS-0573

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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