Orphan Europe Carbaglu® Surveillance Protocol
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|ClinicalTrials.gov Identifier: NCT03409003|
Recruitment Status : Recruiting
First Posted : January 24, 2018
Last Update Posted : February 17, 2020
|Condition or disease|
|N-acetylglutamate Synthase (NAGS) Deficiency|
Among the urea cycle disorders, N-acetylglutamate synthase (NAGS) deficiency is the rarest type. In 2010, carglumic acid (Carabglu) was approved by the United States Food and Drug Administration (FDA) "as an adjunctive therapy for the treatment of acute hyperammonemia due to the deficiency of the hepatic enzyme NAGS, and as maintenance therapy for chronic hyperammonemia due to NAGS deficiency." As post-marketing requirements, the US FDA requests that Orphan Europe (OE) conduct:
1604-2: A registry of patients, with NAGS deficiency being treated with carglumic acid to obtain long-term clinical safety information. Data will include patient demographics, details of treatment with carglumic acid, other therapies for hyperammonemia, dietary protein management, clinical status, neurocognitive and psychomotor status, growth and development status, and adverse events. Information from this registry is submitted to the FDA annually (in annual reports) with a final report submitted at 15 years post-approval.
1604-3: A study of the effects of carglumic acid on pregnancy and fetal outcomes. This study can be performed as a sub-study within the registry for all patients with NAGS deficiency. Information on pregnancy and fetal outcomes should be submitted annually (in annual reports) with a final report submission at 15 years post-approval.
This patient registry or surveillance protocol will be facilitated by collaboration with the existing National Institutes of Health (NIH) sponsored Urea Cycle Disorders Consortium (UCDC) Longitudinal Study of Urea Cycle Disorders (RDCRN Protocol #5101) (including NAGS deficiency) in the United States. The Longitudinal Study is sponsored by the NIH and other philanthropic sources. It is an academically governed network with the objective to conduct a longitudinal multidisciplinary investigation of the natural history, morbidity and mortality in people with UCD. It therefore aims to collect data on all patients with NAGS deficiency in the US. Measures in the Longitudinal Study are compatible with a Carbaglu post-marketing study including: developmental outcome, medical history, interval medical history, adverse events (interim events), pregnancy history, physical exam, vital signs, laboratory evaluation, dietary history, and medication records. Additional data on drug related adverse events and pregnancy outcomes will is collected for OE for FDA reporting.
|Study Type :||Observational [Patient Registry]|
|Estimated Enrollment :||30 participants|
|Target Follow-Up Duration:||15 Years|
|Official Title:||Orphan Europe Carbaglu® Surveillance Protocol|
|Study Start Date :||April 2012|
|Estimated Primary Completion Date :||July 2026|
|Estimated Study Completion Date :||January 2027|
- Carbaglu related adverse events and adverse reactions [ Time Frame: 15 years ]The primary outcome measure is to monitor adverse events and adverse reactions, which will be reported to the FDA to fulfill post-marketing surveillance requirements.
- Number of hyperammonemic events [ Time Frame: 15 years ]The number of hyperammonemic events (ammonia > 100 umol/L) will be monitored in participants taking Carbaglu to ensure there are no significant adverse changes
- IQ [ Time Frame: 15 years ]IQ will be monitored in participants taking Carbaglu to ensure there are no significant adverse changes
- Height [ Time Frame: 15 years ]Height (cm) will be monitored in participants taking Carbaglu to ensure there are no significant adverse changes
- Weight [ Time Frame: 15 years ]Weight (kg) will be monitored in participants taking Carbaglu to ensure there are no significant adverse changes
- Abnormal physical and neurological findings [ Time Frame: 15 years ]Any abnormal physical and neurological findings reported will be investigated as potential adverse reactions/adverse events (see primary outcome measure). Investigators conducts a review of systems and indicates whether findings are normal, abnormal or not assessed. Each abnormal finding is coded using SNOMED codes.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03409003
|Contact: Jennifer Seminarafirstname.lastname@example.org|
|Contact: Katie Rice, MPHemail@example.com|
|United States, District of Columbia|
|Children's National Medical Center||Recruiting|
|Washington, District of Columbia, United States, 20010|
|Contact: Kara Simpson, MS, CGC 202-476-6216 firstname.lastname@example.org|
|Principal Investigator: Nicholas Ah Mew, MD|
|United States, Massachusetts|
|Children's Hospital Boston (UCDC New England Center)||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Vera Anastasoaie 617-355-7346 Vera.Anastasoaie@childrens.harvard.edu|
|Principal Investigator: Susan Waisbren, MD|
|Sub-Investigator: Harvey Levy, MD|
|United States, New York|
|Icahn School of Medicine at Mount Sinai||Recruiting|
|New York, New York, United States, 10029|
|Contact: Melanie Horn 212-659-8540 Melanie.email@example.com|
|Principal Investigator: George A. Diaz, MD|
|Principal Investigator:||Nicholas Ah Mew, MD||Children's National Health System|