Not yet recruitingRare disease

Study of ASP2957 Gene Therapy for Male Patients with X-linked Myotubular Myopathy Who Require Breathing Support with Ventilators

Verified siteInvestigationalNo placebo

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What is this trial about?

A plain-language summary of the goals, design and what participants do

This study is for male patients with X-linked myotubular myopathy, a rare genetic condition that affects the muscles and makes it difficult to breathe without help. The disease is caused by changes in a gene called MTM1 that leads to weak muscles throughout the body. Patients with this condition often need machines called ventilators to help them breathe through a tube placed in their windpipe. The study will test a treatment called ASP2957, which is a gene therapy given as a single infusion directly into the vein. This treatment is designed to deliver a working copy of the MTM1 gene to the muscle cells so they can produce a protein called myotubularin that is missing or not working properly in patients with this disease.

The purpose of the study is to evaluate the safety and tolerability of ASP2957 and to determine the recommended dose level. The study will also look at whether the treatment shows early signs of helping patients by measuring changes in how many hours per day they need ventilator support. The study will start with lower doses of the treatment and may increase the dose in later groups of patients to find the best and safest amount to use. Before receiving the treatment, patients will have various tests including blood tests, liver ultrasound, heart tests using electrocardiogram and echocardiogram, and muscle imaging using MRI.

During the study, patients will be closely monitored for any side effects and to see how their body responds to the treatment. Doctors will check the patient's liver, heart, and muscles regularly through blood tests, imaging scans, and physical examinations. The study will also measure the amount of the gene therapy in different body samples such as blood, saliva, urine, stool, and muscle tissue. Additionally, the immune system's response to the treatment will be measured by testing for antibodies against the gene therapy. Patients will be followed for at least 52 weeks after receiving the treatment to carefully track their progress and safety.

The research process

The trial runs in 5 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Initial screening and assessments
Your child will undergo screening procedures to confirm eligibility for the study. This includes verification that your child is 36 months of age or younger at the time of treatment.
A molecular genetic test from an approved testing facility will be reviewed to confirm the diagnosis of X-linked myotubular myopathy (a rare genetic muscle disorder) and to verify the presence of a disease-causing change in the MTM1 gene.
Your child's ventilator use will be assessed to confirm that invasive ventilator support is required for at least 20 hours per day and that a tracheostomy tube is in place.
A liver ultrasound (an imaging test that uses sound waves to view the liver) will be performed to check for any abnormalities in the liver.
Blood tests will be conducted to measure liver function, including ALT and AST (liver enzymes), direct bilirubin (a substance processed by the liver), and serum total bile acids (substances produced by the liver). These values must be within acceptable ranges.
Your child's medical history for the past 2 months will be reviewed to ensure liver function has been stable.
Documentation will be reviewed to confirm that your child is current with recommended immunizations according to regional guidelines.
Step 2
Baseline assessments
Before receiving the study treatment, your child will undergo baseline assessments. These will serve as reference points for comparison throughout the study.
Clinical laboratory tests will be performed, including blood and other routine tests.
Heart function will be assessed using ECG (electrocardiogram, a test that measures the electrical activity of the heart) and ECHO (echocardiogram, an ultrasound of the heart).
Muscle imaging will be performed using muscle MRI (magnetic resonance imaging, a scan that creates detailed pictures of muscles).
A muscle biopsy (a procedure where a small sample of muscle tissue is removed for examination) may be performed to assess muscle condition.
A physical examination will be conducted.
The number of hours per day your child requires ventilation support will be recorded.
Step 3
Administration of study treatment
Your child will receive a single dose of ASP2957, which is an investigational gene therapy product.
ASP2957 will be administered as an intravenous infusion (given directly into a vein through a drip).
The product is a solution for infusion that will be given over a period of time determined by the study team.
The dose level will be determined based on the dose escalation phase of the study.
Step 4
Monitoring and follow-up through week 52
After receiving ASP2957, your child will be monitored closely for safety and response to treatment for 52 weeks (approximately 1 year).
Regular clinical laboratory tests will be performed to monitor blood counts, liver function, and other important markers.
Heart function will be monitored periodically using ECG and ECHO tests.
Muscle condition will be assessed using muscle MRI scans.
A muscle biopsy will be performed at week 52 to examine muscle tissue.
Physical examinations will be conducted at regular intervals.
The number of hours per day your child requires ventilation support will be recorded and compared to baseline.
Samples of blood (serum) will be collected regularly to measure the presence of ASP2957 vector DNA (genetic material from the study treatment).
Samples of saliva, urine, and stool will be collected to measure ASP2957 vector DNA.
Blood tests will be performed to check for immunogenicity (the body's immune response to the treatment). This includes testing for anti-MyoAAV3.8 antibodies (proteins the immune system may produce against the delivery vehicle) and anti-myotubularin antibodies (proteins the immune system may produce against the therapeutic protein).
Any treatment-emergent adverse events (side effects or health problems that occur after treatment) and adverse events of special interest (specific side effects that are being closely monitored) will be recorded and assessed for severity.
Step 5
Long-term follow-up
After the initial 52-week monitoring period, your child will continue to be followed as part of the study's long-term safety evaluation.
The study is estimated to continue until October 2027.
Ongoing monitoring will assess the long-term safety and durability of the treatment effect.

Who can join the trial?

6 criteria

The participant must be 36 months of age or younger (3 years or younger) at the time of receiving the treatment
The participant must have a genetic test report from an approved testing facility that confirms the diagnosis and shows a disease-causing change in the MTM1 gene (the gene responsible for this condition)
The participant must be dependent on a breathing machine and meet these requirements: needed breathing support from birth, requires at least 20 hours per day of breathing support through a machine connected to an airway tube, and has a tracheostomy tube (a tube placed in the windpipe to help with breathing)
The participant must have a liver ultrasound (an imaging test of the liver using sound waves) that shows no signs of hepatic peliosis (blood-filled spaces in the liver), increased brightness, or any other important abnormal findings as determined by the study doctor and liver specialist
The participant must have liver and bile system blood test results that meet specific limits during screening and for the past 2 months: ALT and AST (enzymes that measure liver function) must be less than 3 times the upper normal limit, direct bilirubin (a substance that shows how well the liver is working) must be at or below the upper normal limit, and serum total bile acids (substances made by the liver) must be less than 2 times the upper normal limit
The participant's parent or legal authorized representative (the person legally responsible for making medical decisions) must provide proof that the participant has received all recommended vaccines according to local health guidelines

Who cannot join the trial?

11 criteria

Females cannot participate in this study, only male patients are eligible
Patients who have received gene therapy (a treatment that introduces genetic material into cells to treat disease) in the past are not eligible
Patients with severe liver disease (problems with the organ that helps clean the blood and digest food) cannot participate
Patients with severe kidney disease (problems with the organs that filter waste from the blood) are not eligible
Patients who have a tracheostomy (a surgical opening in the neck to help with breathing) cannot participate
Patients requiring invasive ventilation (breathing support through a tube placed in the airway) for more than 16 hours per day are not eligible
Patients with active or uncontrolled infections (illnesses caused by germs that are not under control with treatment) cannot participate
Patients with known allergies to the study medication or its ingredients are not eligible
Patients who have participated in another clinical trial (research study testing new treatments) within 30 days before joining this study cannot participate
Patients with certain heart conditions (problems with the organ that pumps blood through the body) that could pose safety risks are not eligible
Patients with conditions that would prevent them from following study procedures or make it unsafe for them to participate are not eligible

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Verified
Hopital Beaujon
Clichy, France

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Investigated drugs

ASP2957 is an investigational medication being studied in this trial. It is being tested to see if it is safe and well-tolerated in male participants with a rare genetic muscle disorder called X-linked myotubular myopathy who require a ventilator to help them breathe. The study will look at different dose levels to find the most appropriate amount to give to patients. This medication is still experimental and is being evaluated to see if it might help people with this condition.

ASP2957

What is already known about the treatment

ASP2957 – ASP2957 is an investigational gene therapy currently being studied in early-phase clinical trials for the treatment of X-linked myotubular myopathy, a rare genetic muscle disorder that primarily affects males and often requires breathing support with a ventilator. This experimental medication is administered as a one-time infusion directly into the bloodstream and works by delivering a functional copy of the MTM1 gene to muscle cells, which helps restore the production of myotubularin protein that is missing or defective in patients with this condition. The therapy aims to improve muscle function and potentially reduce the need for mechanical breathing assistance, though it is still under investigation to determine its safety, appropriate dosing, and effectiveness.

Investigated diseases

X-linked Myotubular Myopathy – X-linked myotubular myopathy is a rare genetic muscle disorder that primarily affects males. The condition is caused by mutations in the MTM1 gene located on the X chromosome, which leads to problems with muscle cell development and function. Affected individuals typically show symptoms from birth or early infancy, including severe muscle weakness and low muscle tone. The weakness affects muscles throughout the body, particularly those used for breathing and movement. Many affected infants require breathing support due to weakness of the respiratory muscles. The condition results from abnormal development of muscle cells, which contain centrally located nuclei instead of the normal peripheral location, giving the muscle tissue a distinctive appearance under microscopic examination.