The OTC-HOPE Phase 1/2 clinical trial is for baby boys diagnosed with neonatal onset ornithine transcarbamylase (OTC) deficiency, a rare genetic disorder in which the absence of functional OTC enzyme drives the buildup of toxic ammonia in the blood stream.
ECUR-506 is an investigational medicine and has not been approved for commercial use in the United States or any other country for any indication.
OTC-HOPE is a clinical research study to evaluate the safety and potential effect of an investigational therapy in males less than nine months of age with a genetically confirmed diagnosis of neonatal onset OTC deficiency. This is the first time this investigational therapy has been tested in humans. It is an open-label clinical trial, which means the participants’ parents/caregivers, researchers and healthcare professionals know which therapy is being given to the participant.
To learn more about this OTC deficiency clinical research study, scroll down or visit ClinicalTrials.gov, a resource and registry of ongoing clinical studies with additional details and contact information.
The OTC-HOPE clinical research study is evaluating ECUR-506, an investigational gene editing therapy, designed to directly address the underlying genetic cause of OTC deficiency. By evaluating the safety and potential benefit of ECUR-506, this study aims to advance the understanding and management of OTC deficiency and learn more about a potential treatment option for affected babies.
Your baby may be eligible to participate in the OTC-HOPE study if he meets the following criteria (among others):
Additional eligibility criteria will be discussed with you during the screening process. Your study doctor and the study team will carefully assess your baby’s eligibility and provide further guidance on whether participation in the OTC-HOPE study is an option for your baby.
The OTC-HOPE study is being conducted at participating hospitals across the following countries:
Los Angeles, CA, United States
Principal Investigator: Dr. Gerald Lipshutz
Contact Info: Monserrath Campos
Aurora, CO, United States
Principal Investigator: Dr. Shawn McCandless
Contact Info: Lanie Dougherty
London, United Kingdom
Principal Investigator: Dr. Julien Baruteau
Contact Info: Christopher Jackson
Newcastle, United Kingdom
Sydney, NSW, Australia
Principal Investigator: Dr. Shanti Balasubramaniam
Contact Info: Dr. Shanti Balasubramaniam
Barcelona, Spain
Principal Investigator: Dr. Angels Garcia Cazorla
Contact Info: Dr. Angels Garcia Cazorla
Madrid, Spain
Principal Investigator: Dr. Marcello Bellusci
Contact Info: Dr. Marcello Bellusci
Parkville, VIC, Australia
Principal Investigator: Dr. Heidi Peters
Coming Soon
Philadelphia, PA, United States
Principal Investigator: Dr. Can Ficicioglu
Coming Soon
Portland, OR, United States
Principal Investigator: Dr. Cary Harding
Coming Soon
Chicago, IL, United States
Principal Investigator: Dr. Joshua Baker
Coming Soon
New York, NY, United States
Principal Investigator: Dr. Margo Breilyn
Coming Soon
For additional information on this clinical research study, visit ClinicalTrials.gov.
The OTC-HOPE clinical trial has been authorized to proceed in the United States, Australia, the United Kingdom and the European Union (Spain). Patients meeting eligibility criteria from around the globe are able to participate in the OTC-HOPE study. Please reach out to clinicaltrials@iecure.com for more information and we can work to connect you with the nearest clinical trial site.
Your DNA contains thousands of genes. Most of these genes give you the characteristics that make you unique and provide instructions to ensure the cells in your body are functioning properly. Sometimes at birth, the whole or part of a gene is damaged or missing. When this happens, the genes are not able to give the right instructions to the body, and in some cases, this can lead to illnesses.
Gene editing, a type of gene therapy, is a medical treatment approach that targets the underlying cause of these illnesses at the genetic level. This approach has the potential to replace and restore the function of a damaged or missing gene by inserting a functional copy of that gene. This could offer a long-lasting working gene with long term and possibly curative therapeutic benefit. This may be significant to those living with rare genetic diseases and potentially remove the need for ongoing treatments or the burden of daily disease management.
Gene editing has the potential to offer durable gene expression and long term, possibly curative, therapeutic benefit.
The study drug, ECUR-506, is an investigational gene editing therapy designed to permanently restore a damaged or missing OTC gene with a functional copy, potentially restoring function and addressing the underlying cause of the disorder.
Through a one-time intravenous (IV) infusion, ECUR-506 is designed to deliver two active components into the liver cells of a baby with OTC deficiency: a working copy of the OTC gene and a nuclease enzyme, the part of the study drug that makes a cut into a patient’s DNA to allow the working copy of the OTC gene to be introduced into a patient’s DNA.
A gene cannot enter cells by itself; it needs a carrier called a vector to move the gene into the cells. For the study drug, ECUR-506, we use a type of virus called adeno-associated virus (AAV). AAVs provide the most common method of gene delivery being explored in gene therapy clinical studies today. After administration with ECUR-506 and as the baby’s liver cells divide, the AAV vector containing the nuclease will be lost over time, but the cells containing the inserted gene have been designed to provide a potentially permanent source of functional OTC enzyme that will break down ammonia.
Through extensive preclinical studies in animals, we have obtained evidence of ECUR-506’s potential activity and tolerability. The OTC-HOPE study will be the first evaluation of ECUR-506 in humans. It is hoped that the study drug ECUR-506 will introduce a working copy of the OTC gene so that your baby will make the OTC enzyme on his own, reducing the risk of dangerous ammonia elevations. However, there is no guarantee that your baby will benefit from participating in this trial. It is yet unknown if the potential benefit of ECUR-506 will outweigh the potential risks and whether ECUR-506 will overcome the limitations inherent in the current treatment approach.
OTC deficiency is a rare genetic disorder that affects the urea cycle, a crucial process in the body that removes toxic ammonia, which is a natural substance formed when breaking down the proteins we eat. This condition is caused by changes in the OTC gene, which provides the instructions to cells for the production of the OTC enzyme. In people with OTC deficiency, the damaged or missing gene disrupts the production or function of the OTC enzyme. As a result, ammonia builds up in the body, leading to potentially severe complications.
OTC deficiency can present at any age. The most severe form occurs in the first few days of life, usually following a protein feeding (e.g., milk, formula). This neonatal onset form of OTC deficiency usually affects newborn boys; it is very rare in newborn girls. Initial symptoms of neonatal onset OTC deficiency can include vomiting, refusal to eat, tiredness, and irritability. If left untreated, symptoms can progress rapidly to coma, seizures, irreversible brain damage, and possibly death.
Current treatment focuses on preventing excessive ammonia from being formed, through low protein diets and removing excessive ammonia using scavenger medications.
These current treatment options do not correct the underlying cause of the disease and do not eliminate the risk of life-threatening symptoms or high ammonia episodes.
In severe cases, a liver transplant may be necessary as the only known curative treatment. However, liver transplantation carries significant risks and challenges associated with immune suppression.
If your child has been diagnosed with OTC deficiency, it is important to consult with your healthcare provider to understand available management strategies. OTC deficiency is a complex genetic disorder that requires comprehensive medical care and ongoing support. Your healthcare provider can guide you in exploring treatment options, managing symptoms, and addressing the unique needs associated with OTC deficiency.
*These resources are for informational purposes only. Inclusion of these resources does not indicate endorsement by iECURE, Inc. of an organization or its communications. The list is not intended to be a comprehensive list of resources, nor are the resources intended to provide medical advice. Ask your doctor any questions you may have about your disease or treatment plan.
Why is the OTC-HOPE study being conducted?
The OTC-HOPE study will be the first time ECUR-506 will be administered to humans with neonatal onset OTC deficiency. The primary purpose of this study is to find out if ECUR-506 is safe. The secondary purpose is to assess how effective ECUR-506 is for the treatment of neonatal onset OTC deficiency by evaluating disease-specific markers, developmental milestones and quality of life. The information we get from this study may help improve the future treatment of people with the same condition.
Who is conducting the OTC-HOPE study?
iECURE, Inc. is a clinical-stage biotech company and sponsor of the OTC-HOPE study. The trial is being conducted at several hospitals globally by experts in OTC deficiency.
Why does the OTC-HOPE study exclusively focus on males?
Neonatal onset includes onset in the first month of life. The incidence of early onset or neonatal onset OTC deficiency in females in recent studies is between 3-7%. The eligibility criterion in the OTC-HOPE study is more restrictive, including onset only in the first week of life which reduces the proportion of female affected babies even further. Considering the disease epidemiology and the underlying differences in genetic architecture between males and females, research will focus on eligible male newborns at this stage of clinical development.
Why does the OTC-HOPE study focus on babies who are nine months of age and younger?
The appropriate population for this first-in-human safety and efficacy study is male newborns less than nine months of age. This group was selected for two reasons. Firstly, when considering the biology and mechanism of action of ECUR-506, the safety and efficacy of ECUR-506 is more likely to be evaluable in this population. ECUR-506 is a gene editing product specifically designed to correct the genetic defect in patients with OTC deficiency by insertion of a therapeutic OTC transgene. This mechanism optimally functions in rapidly dividing cells (in this case, hepatocytes). Rapidly dividing hepatocytes are present in neonates or early age infants who are undergoing rapid somatic growth whereas hepatocyte replication in adults is significantly slower. Secondly, the infantile OTC deficiency population, with their high risk of early death and irreversible brain injury, reflects the highest unmet need and is an appropriate target population in considering the relative risk/benefit profile. Therefore, the development program of ECUR-506 will entirely focus on infants with neonatal onset OTC deficiency.
What is the difference between gene editing and other gene therapies?
Gene therapy is the use of genetic material to treat or prevent disease. Some gene therapy approaches work by delivering a working gene into cells to provide the cell with new instructions to function properly. Gene editing is a type of gene therapy approach that directly edits pieces of DNA within the cell. This changes the instructions that the DNA encodes for to correct the protein produced by the DNA and restore proper cell function.
How common is OTC deficiency?
OTC deficiency is the most common type of urea cycle disorder, occurring in about 1 in every 14,000 to 77,000 individuals worldwide. The occurrence of this disease various by region and populations. It is primarily inherited in an X-linked recessive pattern, meaning that it mostly affects males, who only have one copy of the X chromosome. Females, who have two X chromosomes, can be carriers of the condition. Some females may experience milder OTC symptoms, or they may have no symptoms.
What is a clinical study?
A clinical study (also known as a clinical trial) is an experiment designed to evaluate an investigational drug for the treatment or prevention of a specific disease or medical condition in humans. The results of clinical studies can help health authorities decide if an investigational drug is safe and effective and whether it should be made available to patients. Volunteer involvement in clinical studies is a key part in the development and advancement of future therapies.
How are clinical studies for infants different from clinical studies for other age groups?
Clinical trials in children are very important because they help researchers discover the best way to treat children. Children are not just small adults – their bodies work in very different ways and they often undergo many changes as they grow from infancy towards adolescence and adulthood. Because their bodies work differently, it’s important to create child-specific medicines and treatments instead of just modifying adult doses and therapies.
Since infants in particular are vulnerable and cannot give consent, researchers must be able to demonstrate a prospect of direct benefit for the potential participants through nonclinical studies.
OTC-HOPE is called a Phase 1/2 trial. What does this mean?
Clinical trials are divided into three phases. Traditionally, Phase I is designed to assess safety of the intervention in healthy individuals, Phase II is designed to test the safety and dosage in individuals with the disease, and Phase III assesses efficacy with a larger group at the determined dose. In rare diseases, such as OTC deficiency, where there are low numbers of patients and limited treatment options, researchers may combine Phase I/II and test for safety and efficacy at the same time in people who have the disorder.
How long is this study?
The main study lasts up to 10 months and is divided into several parts. After the main study, there is a long-term follow-up study to follow your baby’s health over the next 14.5 years as recommended by global regulatory agencies for gene editing studies.
What are some of the activities that will be required to take part in this study?
The main study will occur in a series of stages over a 10-month period, including screening, stabilization, dosing eligibility, study drug administration, and follow-up. During these stages, enrolled participants will visit a study doctor for a variety of standard and specific medical tests such as laboratory tests, vital sign review, and ECG. An intravenous infusion (IV) of the study drug and liver biopsy will be performed at applicable time points during the study. Some visits will require overnight stays at the study site. The full list of all medical tests, exams, and procedures can be discussed with the study site staff.
Are there costs related to participating in the study?
You will not have to pay for the study drug, study visits, or for the procedures or tests that are needed as part of the main study or the long-term follow-up study. For patients meeting applicable criteria, iECURE will pay for reasonable travel-related costs required for study visits. You or your insurance company will have to pay for the procedures or tests that are part of your child’s standard medical care, including procedures and non-study medications that your study doctor or personal doctor requires as part of your child’s standard medical care. It is important that you inform your insurance company if you plan for your child to participate in the main study and the long-term follow up study.
Where can I learn more about clinical research studies?
You can start by asking your physician about clinical studies that might be right for you. If you are part of a patient support group or organization, they may have resources or know of other clinical studies you may be interested in. Clinical trials sponsored by iECURE and other organizations are listed on ClinicalTrials.gov.
Where is this trial being conducted? Will I have to travel?
You do not need to live close to a clinical trial site in order to participate in the OTC-HOPE study. There are clinical trial sites around the world, including the United States, United Kingdom and Australia. Should your infant qualify for the trial, iECURE will work to assist you with travel to participate in the trial.
Please use this form to contact us if you would like to receive updates on the OTC-HOPE study.
