Carglumic Acid for Methylmalonic and Propionic Acidemia

Recruiting at 6 trial locations

Overseen By Anne Marie Cesario, MS

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: RECORDATI GROUP

Must be taking: Carbaglu

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to gather safety information on using Carbaglu® (Carglumic Acid) for treating hyperammonemia, a condition with high ammonia levels in the blood, caused by Methylmalonic Acidemia (MMA) and Propionic Acidemia (PA). Participants will include both children and adults diagnosed with either MMA or PA. Ideal candidates for this trial are those already being treated with Carbaglu® and have a confirmed diagnosis of MMA or PA, as shown by specific urine or genetic tests. As a Phase 4 trial, the study focuses on understanding how Carbaglu® benefits more patients, as it is already FDA-approved and proven effective.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What is the safety track record for this treatment?

Research shows that carglumic acid, sold as Carbaglu®, is generally safe for treating high ammonia levels in the blood, known as hyperammonemia. It is approved for use in both adults and children. Studies indicate that it can be used long-term to manage conditions like Methylmalonic Acidemia (MMA) and Propionic Acidemia (PA), which also cause high ammonia levels.

Most people tolerate the treatment well, experiencing no serious side effects. However, like any medication, some individuals might experience side effects such as an upset stomach, vomiting, or diarrhea. Serious side effects are rare.

Overall, research supports the safety of carglumic acid for managing high ammonia levels in conditions like MMA and PA. For those considering participation in a trial with this treatment, current evidence suggests it is a safe option. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Carbaglu® (Carglumic Acid) because it offers a targeted approach to treating hyperammonemia due to Methylmalonic Acidemia (MMA) and Propionic Acidemia (PA). Unlike most standard treatments that manage ammonia levels indirectly, Carbaglu® works by directly activating a specific enzyme, N-acetylglutamate synthase, which plays a crucial role in the urea cycle to reduce ammonia buildup effectively. This direct mechanism could potentially provide quicker and more efficient relief from symptoms, making it a promising option for both adults and children affected by these metabolic disorders.

What evidence suggests that Carbaglu® might be an effective treatment for hyperammonemia due to MMA and PA?

Research has shown that carglumic acid, which participants in this trial will receive, can help treat high ammonia levels in the blood for people with Methylmalonic Acidemia (MMA) and Propionic Acidemia (PA). Studies have found that using carglumic acid alongside regular treatments significantly reduces emergency room visits caused by high ammonia levels. Specifically, data indicates that after at least one year of treatment, patients experienced lower peak ammonia levels and fewer sudden illness episodes due to the body's difficulty in processing certain nutrients. These findings suggest that carglumic acid could be a promising option for managing MMA and PA. ^{4 6 7 8 9}

Who Is on the Research Team?

William Ludlum, MD

Principal Investigator

Recordati Rare Diseases Inc.

Nicholas Ah Mew, MD

Principal Investigator

Children's National Research Institute

Are You a Good Fit for This Trial?

Inclusion Criteria

Provision of signed and dated informed consent/assent form

Prescribed and treated with Carbaglu®

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).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients are treated with Carbaglu® for hyperammonemia due to MMA and PA according to prescribing information and routine medical practice

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and plasma ammonia levels

1 year

Long-term safety monitoring

Collection of long-term safety data, including developmental outcomes and pregnancy-related risks

What Are the Treatments Tested in This Trial?

Interventions

• Carglumic Acid

How Is the Trial Designed?

Group I: Male and Female Adult and Pediatric Participants Experimental Treatment 1 Intervention

Patients treated with Carbaglu for the treatment for hyperammonemia due to Methylmalonic Acidemia (MMA) and Propionic Acidemia (PA)

Who Is Running the Clinical Trial?

RECORDATI GROUP

Lead Sponsor

Trials

13

Recruited

4,500+

Recordati Rare Diseases

Lead Sponsor

Trials

14

Recruited

540+

Target PharmaSolutions, Inc.

Industry Sponsor

Trials

17

Recruited

5,667,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34635114/

Long-term effectiveness of carglumic acid in patients with ... Conclusion: Using carglumic acid in addition to standard treatment over the long term significantly reduces the number of ER admissions because ...

2. ojrd.biomedcentral.com ojrd.biomedcentral.com/articles/10.1186/s13023-021-02032-8

Long-term effectiveness of carglumic acid in patients with ... Using carglumic acid in addition to standard treatment over the long term significantly reduces the number of ER admissions because of hyperammonemia in ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02426775

Carglumic Acid in Methylmalonic Acidemia and Propionic ... The investigators are proposing a randomized multicentre prospective clinical trial to evaluate long-term effects of the use of Carbaglu® (50mg/kg/day) combined ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31196016/

study protocol for a randomized controlled trial This clinical trial will determine the long-term safety and efficacy of carglumic acid in the management of PA and MMA.

5. link.springer.com link.springer.com/article/10.1007/s40268-023-00449-z

Real-World Experience of Carglumic Acid for ... The data indicate that treatment with carglumic acid for at least 1 year reduces peak plasma ammonia levels and the frequency of metabolic ...

6. carbaglu.com carbaglu.com/hcp/important-safety-information-hcp/

CARBAGLU® (carglumic acid) CARBAGLU (carglumic acid) is a carbamoyl phosphate synthetase 1 (CPS 1) activator indicated in adult and pediatric patients as acute and chronic hyperammonemia.

7. carbaglu.com carbaglu.com/hcp/about-carbaglu/

Treatment of Hyperammonemia Review efficacy & safety data, MOA, & Important Safety Information for CARBAGLU (carglumic acid) in the treatment of hyperammonemia due to NAGS deficiency.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8507242/

Long-term effectiveness of carglumic acid in patients with ... In the EU, it is approved for the treatment of hyperammonemia due to NAGS deficiency, Isovaleric acidemia (IVA), PA, or MMA, including long-term ...

9. ojrd.biomedcentral.com ojrd.biomedcentral.com/articles/10.1186/s13023-024-03468-4

Role of carglumic acid in the long-term management of ... Carglumic acid (CGA) is a synthetic structural analog of human NAG and is approved for the treatment of patients with hyperammonemia due to PA or MMA.