N-acetylglutamate Synthase (NAGS) DeficiencyNCT03409003
Orphan Europe Carbaglu® Surveillance Protocol
An observational study of N-acetylglutamate Synthase (NAGS) Deficiency, run by Nicholas Ah Mew at 3 sites in United States.
Trial 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)… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- N-acetylglutamate Synthase (NAGS) Deficiency
- How many people
- 30 participants
- Where
- 3 sitesUnited States
- Study dates
- Apr 2012to Jan 2027
- How long will I take part?
- 15 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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)
Who may be able to join
- 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)
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
Children's Hospital Boston (UCDC New England Center)
Boston, Massachusetts, 02115
Debbie Fu, 617-919-7631, yu-ting.fu@childrens.harvard.edu
Gerry Berry, MD
- Recruiting
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Alison Horn, 212-659-8540, alison.tiao@mssm.edu
Margo Breilyn, MD
- Recruiting
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Kara Simpson, MS, CGC, 202-476-6216, ksimpson@childrensnational.org
Nicholas Ah Mew, MD
About this study
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.
Read the 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.
- Keywords
- urea cycle disorder
- Medical subject headings
- Urea Cycle Disorders, Inborn
What is being measured
The primary outcome is the main question the study is designed to answer.
Carbaglu related adverse events and adverse reactions
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.
Measured: 15 years
Secondary outcomes (5)
Number of hyperammonemic events
The number of hyperammonemic events (ammonia > 100 umol/L) will be monitored in participants taking Carbaglu to ensure there are no significant adverse changes
Measured: 15 years
IQ
IQ will be monitored in participants taking Carbaglu to ensure there are no significant adverse changes
Measured: 15 years
Height
Height (cm) will be monitored in participants taking Carbaglu to ensure there are no significant adverse changes
Measured: 15 years
Weight
Weight (kg) will be monitored in participants taking Carbaglu to ensure there are no significant adverse changes
Measured: 15 years
Abnormal physical and neurological findings
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.
Measured: 15 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2018
- Study startApr 2012
- Primary completionJul 2026 (estimated)
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for N-acetylglutamate Synthase (NAGS) DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
- Target duration
- 15 Years
Sponsor and investigators
- Lead sponsor
- Nicholas Ah Mew
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Nicholas Ah Mew, Children's National Research Institute
- Investigators
- Nicholas Ah Mew, MD, Principal investigator, Children's National Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03409003
- Sponsor's protocol ID
- UCDC5111
- Status last verified
- Feb 2024
- First submitted
- 18 Nov 2016
- Last updated
- 7 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: 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.
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Orphan Europe Carbaglu® Surveillance Protocol
- ClinicalTrials.gov ID
- NCT03409003
- Acronym / sponsor ID
- UCDC5111
- Keywords
- urea cycle disorder
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Nicholas Ah MewUniversity, hospital or other
- Collaborators
- Boston Children's Hospital, Icahn School of Medicine at Mount Sinai
- Study start
- Apr 2012
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Jan 2027 (estimated)
- First posted
- 24 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 15 Years
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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)
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (7 listed)
- Cases of hyperammonemia caused by other urea cycle disorders
- Organic acidemia, lysinuric protein intolerance
- Mitochondrial disorders
- Congenital lactic acidemia,
- Fatty acid oxidation defects
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
5 secondary outcomes
Number of hyperammonemic events
Time frame: 15 years
IQ
Time frame: 15 years
Height
Time frame: 15 years
Weight
Time frame: 15 years
Abnormal physical and neurological findings
Time frame: 15 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2024.
- 5111: Orphan Europe Carbaglu® Surveillance Protocol In Collaboration with the Longitudinal Study of Urea Cycle DisordersLink provided by the sponsor.
- Orphan Europe Products - CarbagluLink provided by the sponsor.
- Individual participant dataSharing planned: No. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nicholas Ah Mew, MD principal investigator
Children's National Research Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of N-acetylglutamate Synthase (NAGS) Deficiency, run by Nicholas Ah Mew at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jennifer Seminara, MPH (2023066489, jseminar@childrensnational.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Carbaglu related adverse events and adverse reactions (time frame: 15 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2024.