ARCT-810 for OTC Deficiency

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Arcturus Therapeutics, Inc.

Must be taking: Ammonia scavengers

Must not be taking: Corticosteroids, Urea inhibitors

Disqualifiers: Hypertension, Diabetes, Cardiac disorders, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 12 weeks

9 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you must have been on a stable treatment for OTC deficiency for at least 28 days before joining. Changes in these therapies close to the trial start are not allowed.

How is the drug ARCT-810 unique in treating OTC deficiency?

ARCT-810 is unique because it uses mRNA technology to provide instructions for making a modified version of the ornithine transcarbamylase enzyme, potentially addressing the root cause of the deficiency rather than just managing symptoms. ^{1 2 3 4 5}

What is the purpose of this trial?

Evaluate the safety and pharmacodynamics of multiple doses of ARCT-810 in adolescent and adult participants with OTC deficiency.

Eligibility Criteria

This trial is for adolescents and adults aged 12 or older with Ornithine Transcarbamylase Deficiency (OTCD). Participants must be on a stable diet and/or medication regimen for OTCD, in good health, and willing to follow the study's procedures. They cannot have severe allergies to liposomal/PEG products, drug/alcohol abuse history, certain infections or uncontrolled conditions like hypertension.

Inclusion Criteria

Willingness and ability to comply with all the protocol requirements, complete all study visits and sign informed consent

I have been on a stable diet and treatment for OTC deficiency for at least 28 days.

I have been diagnosed with OTC deficiency.

Exclusion Criteria

History of severe allergic reaction to a liposomal or PEG-containing product

Abuse of medications, illicit drugs or alcohol

Involved in study conduct or an immediate family member of an individual involved in the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Diet Stabilization

Participants undergo a diet stabilization period before treatment

4 weeks

Treatment

Participants receive up to 5 IV infusions of ARCT-810 every two weeks

12 weeks

Visits on Days 1, 15, 29, 43, 57, 71, and 85

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ARCT-810

Trial Overview The trial tests multiple doses of ARCT-810 to see how it affects people with OTCD. It looks at safety and how the body responds to the treatment (pharmacodynamics). The goal is to find out if this new intervention can help manage symptoms related to OTCD more effectively.

Participant Groups

Group I: ARCT-810 Experimental Treatment 1 Intervention

Participants will receive up to 5 IV infusions of ARCT-810 administered at 14-day intervals.

Who Is Running the Clinical Trial?

Arcturus Therapeutics, Inc.

Lead Sponsor

Trials

14

Recruited

22,300+

Findings from Research

A 23-year-old male with ornithine transcarbamylase deficiency (OTCD) was found to have a likely pathogenic promoter variant in the OTC gene, which was not detected by standard Sanger sequencing or MLPA, highlighting the importance of comprehensive genetic testing.

Three patients with late-onset OTCD, identified through this new testing approach, have managed their condition effectively with a protein-restricted diet, and none have experienced significant neurological damage, suggesting that early dietary management can lead to positive outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A serendipitous journey to a promoter variant: The c.-106C>A variant and its role in late-onset ornithine transcarbamylase deficiency. Hertzog, A., Selvanathan, A., Halligan, R., et al.[2022]

A specific mutation in the OTC gene, identified in patients with ornithine transcarbamylase (OTC) deficiency, leads to significantly reduced enzyme activity (1.3% and 3.5% of normal) but does not prevent normal development in affected individuals.

The mutation can be rapidly diagnosed using a unique MspI restriction site loss, which aids in genetic testing and understanding the inheritance patterns, as it was transmitted by the mother in one family and arose de novo in another.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Demonstration of the spf-ash mutation in Spanish patients with ornithine transcarbamylase deficiency of moderate severity. García-Pérez, MA., Sanjurjo, P., Rubio, V.[2019]

All three male patients with late onset ornithine transcarbamylase deficiency (OTCD) were found to have mutations in the OTC gene, confirming the genetic basis of their condition.

A novel mutation, c.800G> C(p.S267T), was identified in one patient, which affects a critical part of the OTC protein, indicating it is likely pathogenic and contributes to the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Analysis of ornithine transcarbamylase gene mutations in three boys affected with late-onset ornithine transcarbamylase deficiency]. Chen, Z., Wen, P., Wang, G., et al.[2014]

A novel missense mutation, E122G, was identified in the OTC gene of a Chinese family, which may be responsible for late onset ornithine transcarbamylase (OTC) deficiency.

The study utilized polymerase chain reaction and direct sequencing methods to confirm the mutation, highlighting the importance of genetic analysis in understanding metabolic disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Molecular characterization of a new mutation E122G of human ornithine transcarbamylase gene]. Gao, H., Li, W., Yan, ZH., et al.[2006]

In a study of nine Italian patients with ornithine transcarbamylase deficiency (OTCD), researchers identified three novel mutations and six previously reported mutations in the OTC gene, highlighting the genetic diversity of this disorder.

One novel mutation, E98K, was found near the carbamyl phosphate binding site of the OTC protein, which may impact the enzyme's function and contribute to the severity of the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic analysis in nine unrelated Italian patients affected by OTC deficiency: detection of novel mutations in the OTC gene. Bisanzi, S., Morrone, A., Donati, MA., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

A serendipitous journey to a promoter variant: The c.-106C>A variant and its role in late-onset ornithine transcarbamylase deficiency. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Demonstration of the spf-ash mutation in Spanish patients with ornithine transcarbamylase deficiency of moderate severity. [2019]

3. China pubmed.ncbi.nlm.nih.gov

[Analysis of ornithine transcarbamylase gene mutations in three boys affected with late-onset ornithine transcarbamylase deficiency]. [2014]

4. China pubmed.ncbi.nlm.nih.gov

[Molecular characterization of a new mutation E122G of human ornithine transcarbamylase gene]. [2006]

5. United States pubmed.ncbi.nlm.nih.gov

Genetic analysis in nine unrelated Italian patients affected by OTC deficiency: detection of novel mutations in the OTC gene. [2019]