Clinical Trial

Disease: Ornithine Transcarbamylase Deficiency, OTC, (NCT06255782)

Disease info:

Ornithine Transcarbamylase deficiency (OTCD) is an inherited metabolic disorder that causes ammonia to accumulate in the blood. OTCD is caused by genetic variants in the OTC gene that encodes a liver enzyme responsible for detoxification of ammonia. The consequential build-up of excess levels of ammonia in the blood can lead to severe disease symptoms such as cumulative and irreversible neurological damage, coma and death.  OTCD is the most common urea cycle disorder involving various processes that occur in liver cells. It processes excess nitrogen that is produced by protein metabolism to make urea that is excreted by the kidneys. The ornithine transcarbamylase enzyme catalyses a specific reaction within this process.

The severe form of the condition is detectable just a few days after birth and is more common in boys than girls and is referred to as the neonatal-onset form. Other forms of the condition may become apparent later in life and may vary in severity. Mutations in OTC that result in complete loss of enzymatic activity results in the severe, neonatal-onset form while mutations leading to decreased OTC activity result in the late-onset phenotypes.

OTCD is an X-linked disorder involving mutations in the OTC gene (Xp21.1) that provides instructions for making the ornithine transcarbamylase enzyme.

Infants with neonatal-onset OTCD may be lacking in energy, unwilling to eat, and have a poorly-controlled breathing rate or body temperature. Infants with this disorder may be described as "floppy" and can experience seizures or coma. Other developmental symptoms may include developmental delay and intellectual disability and progressive liver damage. Symptoms can vary in severity and onset with some individuals developing symptoms much later in life. The late-onset form of the disorder occurs in both males and females equally and symptoms include mental delirium, erratic behaviour, headaches, vomiting, aversion to protein foods, and seizures can also occur in this form of the disorder.

Prevalence of OTC deficiency is estimated to range from 1 in 14,000 to 1 in 77,000 people.
Official title:
A Phase I/II First-in-Human, Open-Label, Dose-Escalation Study to Evaluate the Safety and Efficacy of a Single Intravenous (IV) Administration of ECUR-506 in Males Less Than 9 Months of Age With Genetically Confirmed Neonatal Onset Ornithine Transcarbamylase (OTC) Deficiency


Name: George Diaz, M.D., Ph.D.    

Phone: 1-877-694-3558    



Trial Recruitment    


No information

Study start:
Apr. 1, 2024
13 participants
Gene editing method:
ARCUSĀ® nuclease
Type of edit:
Gene insertion
Ornithine Transcarbamylase (OTC)
Delivery method:
Adeno-associated virus (AAV) - In-vivo
IND Enabling Pre-clinical
Phase I Safety
Phase II Safety and Dosing
Phase III Safety and Efficacy

Status: Not yet recruiting


This is a Phase 1/2, open-label, multicenter, safety and dose finding study of ECUR-506 in male babies with neonatal onset OTC deficiency. The primary objective of this study is to evaluate the safety and tolerability of up to two dose levels of ECUR-506 following intravenous (IV) administration of a single dose.

The study drug, ECUR-506, is an investigational gene editing therapy. Gene editing is a way to repair, replace, or introduce new copies of genes that don't work. The study drug contains a working copy of the OTC gene that will be delivered by an IV infusion. It also contains a gene to encode the editing enzyme which is the part of the study drug that can cut DNA so that the OTC gene can be inserted. The study drug was designed to introduce a working copy of the OTC gene and a gene to encode the editing enzyme. A gene cannot enter cells by itself, it needs a delivery mechanism to move the gene into the cells. In this study, the carrier is called adeno-associated virus (AAVs) that is able to enter cells and deliver these genes. This is a commonly found virus that has been changed to make it essentially harmless.

Last updated: Mar. 25, 2024
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