A Clinical Study of ABO-101 for Patients with Primary Hyperoxaluria Type 1

Primary Hyperoxaluria Type 1 (PH1) is a rare genetic condition caused by a mutation (change in the DNA) within the AGXT gene. This mutation leads to the liver not producing enough of a special protein, resulting in high levels of oxalate. Normally, oxalate can be processed and eliminated by the kidneys. However, when oxalate levels become too high, it can form crystals that may cause stones in the urinary tract and in the kidneys. Symptoms may include pain when urinating, blood in urine and urinary tract infections. Chronic formation of stones can lead to kidney disease and potentially progress to kidney failure.

If kidney function declines significantly, oxalate can build up in other parts of the body, leading to crystal formation in areas such as the eyes, skin, or heart.

PH1 is an inherited condition, meaning that it can be passed down in families.

Current management options aim to reduce crystal formation caused by oxalate overproduction, helping to slow down kidney damage and decrease stone formation. Your doctor may recommend drinking a lot of fluids, making dietary changes, and in some cases taking vitamin B6 (pyridoxine). When available, your doctor may prescribe medicines to lower oxalate levels in urine (for example, lumasiran [Oxlumo™] or nedosiran [Rivfloza™]). If kidney stones cause pain or block urine flow, they may need to be removed or broken down so they can pass in the urine. In some people with PH1, their kidneys may work less effectively over time. In those cases, a treatment called dialysis may be recommended.   

In certain cases, liver transplant, with or without kidney transplant may be considered curative for PH1. However, this is a significant surgical procedure with notable risks, including the need for lifelong immunosuppression, and it is only indicated in some patients.  

Research into new treatments for PH1 is ongoing.

Gene editing is a type of genetic medicine that can directly change individual genes to treat a disease.

One of the most researched methods is called CRISPR. This tool can find and precisely edit specific genes.

ABO-101 is being studied as a potential one-time CRISPR gene-editing therapy.

Gene editing is approved by the Food and Drug Administration (FDA) in the U.S. for the treatment of sickle cell disease, while in Europe, the European Medicines Agency (EMA) has approved it for both sickle cell disease and beta thalassemia.

Gene editing is also being investigated in other regions for transthyretin amyloidosis (a rare heart and nerve disease), hypercholesterolemia (high cholesterol), and immune disorders.

Clinical trials are clinical research studies that evaluate the safety, tolerability, and effectiveness of investigational therapies. They play a crucial role in developing treatments with the aim of improving patient health. Watch  our video to learn more. 
 
Clinical trials are essential to ensure treatments are safe for the public, determine optimal administration methods, and enhance scientific knowledge of diseases for better health outcomes.

The term ‘investigational medicine’ or ‘study drug’ refers to a trial medication that has not yet received approval from regulatory authorities, such as the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). As a result, it can only be utilized in clinical research studies and is not available for general use. These studies aim to evaluate the safety and efficacy of an investigational medicine before it can potentially become approved for widespread medical use.

Clinical trials have specific criteria, known as clinical trial eligibility criteria, which determine who can participate. These criteria are designed to identify individuals with specific symptoms or a particular diagnosis, while excluding those for whom trial participation would be inappropriate. By enrolling participants who are similar in their characteristics, such as the type of mutation and disease progression, clinical trial eligibility criteria ensure that the outcomes of the trial accurately reflect the effects of the investigational drug being evaluated. Furthermore, these criteria play a crucial role in ensuring the safety of the participants involved.

Clinical trials carry potential risks like treatment side effects, unknown treatment effectiveness, extra medical tests, and time commitments. These are carefully assessed and monitored, and risks and benefits are weighed by the Ethics Committees reviewing and approving the trial’s conduct. Clinical trials follow a specific set of standards and are closely regulated to help ensure the safety of all participants. Safety measures and informed consent processes help participants understand and manage these risks.

People take part in clinical trials for different reasons. Some may take part because they want to learn more about their disease and potential new treatments. Others volunteer to take part because they want to help researchers learn more about (the treatment of) a disease to potentially help them and others in the future.

Yes. Participants receive detailed trial information, can ask questions, and decide freely. Informed consent ensures they understand the trial and can withdraw at any time without affecting their care or rights.

At myTomorrows, we assign a dedicated Patient Navigator to each patient. Your Patient Navigator will provide comprehensive support throughout the entire process, from assessing your trial eligibility to addressing any questions you may have during your clinical trial journey. Our Patient Navigators have a medical background and are closely supervised by our team of medical doctors. While they are trained to explain complex medical concepts, they cannot give medical advice. Our Patient Navigator team offers dependable, multilingual support covering all time zones, ensuring effective communication and understanding with patients from diverse backgrounds.

Yes, besides servicing pre-screening for specific clinical trials, myTomorrows also offers other free of charge services regarding providing unbiased information about clinical trials or other pre-approval treatment options and how to access them. This is always free of charge.

The purpose of this study is to evaluate the safety, tolerability, and preliminary efficacy of an investigational gene editing drug in people with Primary Hyperoxaluria Type 1 (PH1).

This is a dose escalation study, which means that it will involve testing several different doses of the medication. Initial adult participants will receive a low dose. If that dose is well-tolerated, the next group of participants will receive an intermediate dose, and if that dose is also well-tolerated, a higher dose will be given to the following group. This process helps us determine the safest and most effective dose. Once we identify a safe and effective dose in adults, all subsequent participants will receive this dose, including pediatric patients.

ABO-101, a potential one-time CRISPR gene editing investigational treatment, is the study drug being evaluated in the redePHine study.

ABO-101 is a potential one-time CRISPR gene editing investigational therapy designed to specifically edit the HAO1 gene to permanently stop it from working. Previous PH1 clinical studies have shown that inhibiting HAO1 results in lower oxalate levels in people with PH1. Since PH1 leads to high levels of oxalate, reducing these levels may help manage symptoms of this condition and lower the chance of kidney stones and kidney damage.

Yes, all participants in the clinical research study will receive investigational therapy. There is no placebo dose in this study.

Adult participants may receive a low, medium, or high dose of the drug. Once we identify a safe and effective dose in adults, all subsequent participants will receive this investigational dose, including pediatric patients.

Eligible participants must: 

• Be between 18 and 64 to be included in the adult cohorts. 
• Be between 6 to 17 to be included in the pediatric cohort. 
• Diagnosed with PH1 as determined by genetic analysis confirming pathogenic mutations on the alanine-glyoxylate aminotransferase (AGXT) gene. 
• Weigh equal or less than 90 kg (200 Ibs) 

There are additional requirements, which the study doctor will discuss with potentially eligible individuals interested in participating. 

If you may potentially qualify, you can be connected to the study site closest to you to minimize travel and burden. However, if you do need to travel nationally or internationally, reimbursement for expenses will be provided to facilitate your participation. The study site will work with you to ensure you receive this.

For the first phase of the study, you will receive a single dose of the study drug (ABO- 101) and your health will be closely monitored for the first 2 years. Following that, there will be a long-term follow-up period lasting up to 13 years post-study drug (ABO-101) administration to study the continued safety and efficacy of this new gene editing therapy. 

This study will include:  

• Informed Consent: You will be asked to review, consider and if acceptable, sign an Informed Consent Form, which explains the potential risks and benefits of your participation in the study. 
• Screening period: This period lasts up to 60 days. Certain tests and procedures may be done to make sure the potential participant is eligible to participate in the study.  
• Hospital Stay: Participants in the clinical study will need to stay in the hospital for 5 days for the study drug (ABO-101) administration. A single dose of the study drug (ABO-101) will be administered intravenously (IV) over a ~2-hour duration. Before and after the study drug (ABO-101) administration, participants will receive anti-inflammatory and immunosuppressant medications to minimize the risk of an immune response to the investigational drug. 
• Post-infusion: your health will be closely monitored for the first 2 years after receiving the study drug (ABO-101). Following that, there will be a long-term followup period lasting up to 13 years post-study drug administration to study the continued safety and efficacy of this new gene editing therapy. Study visits will take place every 6 months for the first two years, yearly for the next three years, and after year five, data will be provided via telephone calls and questionnaires. If international travel is required for this time period, this will be arranged with you, the site and the patient concierge service. 
• Throughout the study, the research team will closely monitor your health and response to the study drug (ABO-101). The study doctor may perform many tests and procedures, including vital sign measurements, physical exams, weight check, 24-hour urine collections, electrocardiograms and clinical laboratory analyses. Clinical laboratory analyses include blood tests, urine tests and tests to assess your kidney function.