A Phase 2 interventional study of N-carbamylglutamate and Standard of Care in Propionic Acidemia and Methylmalonic Acidemia, sponsored by Mendel Tuchman. Terminated at 7 sites in United States. Open to participants aged 1 Hour to 4 Weeks. Per ClinicalTrials.gov, last updated 2017-04-26.
Sponsored by Mendel Tuchman · Phase 2, Interventional, and Treatment
Background: Very few drugs exist that treat hyperammonemia, specifically PA and MMA. Diet restrictions and alternate pathway agents are the current primary treatments, but they frequently fail to prohibit brain damage.
Orthotopic liver transplantation cures the hyperammonemia of urea cycle disorders, but organ availability is limited and the procedure is highly invasive and requires life-long immunosuppression.
A drug that could repair or stimulate a dysfunctional urea cycle such as this would have several advantages over current therapy. A drug called N-carbamyl-L-glutamate, Carglumic acid (NCG or Carbaglu)has recently been found to be virtually curative of another urea cycle defect called NAGS deficiency. In this disorder, treatment with NCG alone normalizes ureagenesis, blood ammonia and glutamine levels, allows normal protein tolerance and restores health. Knowledge from this study is being applied to acquired hyperammonemia, specifically in patients with propionic PA and MMA, to try and improve neurodevelopmental outcomes by improving the hyperammonemia.
Aims: The overall objective of this project is to determine whether treatment of acute hyperammonemia with Carglumic acid in propionic acidemia (PA), methylmalonic acidemia (MMA) changes the long-term outcome of disease and to determine if it is effective in restoring urine ammonia levels to normal levels.
Methods/Design This 5-year, Phase II, double-blind study aims to recruit and enroll 34 PA and MMA patients during acute episodes of hyperammonemia.
The primary aim is to circumvent the long-term neurodevelopmental decline due to having a prolonged levels of ammonia during crisis in the blood and urine. After treatment and crisis resolution with Carbaglu or placebo and standard of care therapy, measures of neurodevelopmental outcomes (Bayley II and Functional Status Scale) are being measured at 9, 15,21 and 30 months post-discharge from the hospital. Safety of NCG treatment will also be monitored as measured by close examination of adverse events and laboratory blood tests. To test for the effectiveness of NCG, longitudinal models to evaluate the groupwise difference (NCG vs. Placebo) in the trajectory of change in neurodevelopmental outcomes and safety analyses between drug and placebo patients.
Subsequent Episodes At any time after the initial episode, participants may present to the hospital with PA- or MMA-associated symptoms. If the plasma ammonia level verified as a bonafide episode of HA (plasma ammonia is ≥ 100 µmol/l), that participant will receive the same study medication that they received during their initial episode in a double-blinded fashion, (i.e. If the participant received NCG at the time of initial randomization, he/she will continue to receive NCG at each subsequent HA episode. If the participant received PLBO at the time of initial randomization, he/she will continue to receive PLBO at each subsequent HA episode). Only the pharmacist will know if the participant receives NCG or PLBO. The same study assessments (previously stated) will be conducted at each qualifying HSA episode.
23 studies on the registry are indexed under Propionic Acidemia; 8 are open to participants now.
This study's enrollment of 1 is below the median of 30 across 12 interventional studies indexed under Propionic Acidemia.
Browse Propionic Acidemia studies →Mendel Tuchman is the lead sponsor of 3 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
PA or MMA presumed or established diagnosis as follows (one of the following):
Exclusion Criteria
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Active NCG \& Standard of Care
Drug: N-carbamylglutamate · Other: Standard of Care
Standard of Care therapy
Other: Standard of Care
Active NCG \& Standard of Care Chemical Composition: N-carbamyl-L-glutamic acid (NCG) The daily dose will be 100 mg/kg/ day. The doses are to be divided into 2 equal doses and administered orally or enterally by nasogastric or gastrostomy tube (standard of care will prevail when choosing the mode of drug administration). The tablets must be dispersed in a minimum of 2.5-10 ml of water and ingested immediately or administered by fast push through a syringe via a nasogastric or gastrostomy tube. The suspension has a slightly acidic taste. This drug will be administered for 7 days after admission or until discharge (whichever is sooner).
Also known as: Carbaglu, NCG
Standard of Care
Neurodevelopment
Neurodevelopmental outcome as measured by Cognitive Composite (Bayley III), Motor Composite (Bayley III) and Functional Status Scale and safety of NCG treatment as measured by adverse events and laboratory blood tests
Time frame: 30 months
Number of Participants With Adverse Events
Safety is measured by tracking and detailing the number and type of adverse events and their severity based on the CTCAE.
Time frame: Start of episode through 7 days or discharge (if earlier)
| Milestone | Carbaglu | Placebo |
|---|---|---|
| Started | 1 | 0 |
| Completed | 1 | 0 |
| Not completed | 0 | 0 |
Neurodevelopmental outcome as measured by Cognitive Composite (Bayley III), Motor Composite (Bayley III) and Functional Status Scale and safety of NCG treatment as measured by adverse events and laboratory blood tests
No measurements were reported for this outcome.
Safety is measured by tracking and detailing the number and type of adverse events and their severity based on the CTCAE.
| Participants | Carbaglu | Placebo |
|---|---|---|
| Number of Participants With Adverse Events | 1 | — |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Carbaglu | — | 0/1 (0%) | 1/1 (100%) |
| Placebo | — | — | — |
| Event | Carbaglu | Placebo |
|---|---|---|
| LethargyNervous system disorders | 1/1 | — |
| HyperventilationRespiratory, thoracic and mediastinal disorders | 1/1 | — |
| VomitingGastrointestinal disorders | 1/1 | — |
| KetosisMetabolism and nutrition disorders | 1/1 | — |
| AcidosisBlood and lymphatic system disorders | 1/1 | — |
| low white blood countsBlood and lymphatic system disorders | 1/1 | — |
| anemiaBlood and lymphatic system disorders | 1/1 | — |
One participant, infant under 1 month old, with organic acidemia.
| Age, Categorical(Participants) | Carbaglu | Placebo | Total |
|---|---|---|---|
| <=18 years | 1 | — | 1 |
| Between 18 and 65 years | 0 | — | 0 |
| >=65 years | 0 | — | 0 |
| Age, Continuous(days) | Carbaglu | Placebo | Total |
|---|---|---|---|
| Mean | 4 ± 0 | — | 4 ± 0 |
| Sex: Female, Male(Participants) | Carbaglu | Placebo | Total |
|---|---|---|---|
| Female | 0 | — | 0 |
| Male | 1 | — | 1 |
| Region of Enrollment(participants) | Carbaglu | Placebo | Total |
|---|---|---|---|
| United States | 1 | — | 1 |
| NH3(mcmol/L) | Carbaglu | Placebo | Total |
|---|---|---|---|
| Mean | 223 ± 0 | — | 223 ± 0 |
Plan to share: No — A single participant was enrolled before the study closed. There are no analyses and if data are shared, this may compromise the confidentiality of this single participant from a very rare disease.
No publications or documents are linked to this record.
The record gives a start of Sep 2012, a primary completion of Feb 2015 and a completion of Feb 2015. It does not say whether these dates are actual or estimated.
Results were first posted in Apr 2017, 2 years 2 months after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is terminated, as verified in Mar 2017. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Carglumic acid