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Trial record 2 of 31 for:    Protocol AH

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
Sponsor:
Collaborators:
Boston Children's Hospital
Icahn School of Medicine at Mount Sinai
Information provided by (Responsible Party):
Nicholas Ah Mew, Children's National Research Institute

Brief Summary:
The purpose of this study is to conduct post-marketing surveillance of carglumic acid (Carbaglu) to obtain long-term clinical safety information. Carglumic acid was approved by the United States Food and Drug Administration (FDA) for treatment of acute hyperammonemia due to N-acetylglutamate synthase (NAGS) deficiency. Much of the FDA-required data is already collected through the Longitudinal Study of Urea Cycle Disorders (RDCRN Protocol #5101). This study will collect additional data on adverse events (interim events), adverse reactions, pregnancy, and fetal outcomes.

Condition or disease
N-acetylglutamate Synthase (NAGS) Deficiency

Detailed Description:

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.

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 30 participants
Observational Model: Cohort
Time Perspective: Prospective
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

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. IQ [ Time Frame: 15 years ]
    IQ will be monitored in participants taking Carbaglu to ensure there are no significant adverse changes

  3. Height [ Time Frame: 15 years ]
    Height (cm) will be monitored in participants taking Carbaglu to ensure there are no significant adverse changes

  4. Weight [ Time Frame: 15 years ]
    Weight (kg) will be monitored in participants taking Carbaglu to ensure there are no significant adverse changes

  5. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Confirmed diagnosis of NAGS deficiency or suspicion of NAGS deficiency, taking Carbaglu for the treatment of NAGS, and enrolled in the Longitudinal Study of Urea Cycle Disorders (RDCRN protocol #5101)
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of NAGS deficiency or suspicion of NAGS deficiency
  • Carbaglu intake for the treatment of NAGS
  • Enrolled in the Longitudinal Study of Urea Cycle Disorders (RDCRN protocol #5101)

Exclusion Criteria:

  • Cases of hyperammonemia caused by other urea cycle disorders
  • Organic acidemia, lysinuric protein intolerance
  • Mitochondrial disorders
  • Congenital lactic acidemia,
  • Fatty acid oxidation defects
  • Primary liver disease will be excluded
  • Individuals with extreme low birth weight (<1,500 grams) will be also excluded.

Information from the National Library of Medicine

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


Contacts
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Contact: Jennifer Seminara 2023066489 jseminar@childrensnational.org
Contact: Katie Rice, MPH 2026210062 krice3@childrensnational.org

Locations
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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    ksimpson@childrensnational.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.horn2@mssm.edu   
Principal Investigator: George A. Diaz, MD         
Sponsors and Collaborators
Nicholas Ah Mew
Boston Children's Hospital
Icahn School of Medicine at Mount Sinai
Investigators
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Principal Investigator: Nicholas Ah Mew, MD Children's National Health System
Additional Information:
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Responsible Party: Nicholas Ah Mew, Principal Investigator, Children's National Research Institute
ClinicalTrials.gov Identifier: NCT03409003    
Other Study ID Numbers: UCDC5111
First Posted: January 24, 2018    Key Record Dates
Last Update Posted: February 17, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: This is a post-marketing surveillance study being performed so that Orphan Europe (OE) can meet its post FDA approval reporting obligations. Data will be shared with OE who will then report to the FDA. There are no other plans to make this data available to other researchers.
Keywords provided by Nicholas Ah Mew, Children's National Research Institute:
urea cycle disorder