Phase IIb Open‑Label Study of Intrathecal MELPIDA (AAV9/AP4M1) in Patients with Hereditary Spastic Paraplegia Type 50 (SPG50)

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What is this study about?

The study focuses on Hereditary spastic paraplegia type 50 (SPG50), a rare condition that causes progressive stiffness and weakness in the legs, making walking difficult. The investigational therapy being evaluated is a gene‑based product called Melpida, which contains the experimental agent AAV9/AP4M1. This therapy is designed to deliver a normal copy of the missing gene directly to the nervous system.

The purpose of the trial is to determine whether a single intrathecal injection of the study drug into the fluid surrounding the spinal cord in the lower back can improve leg function. Participants will receive the injection once and then be monitored over several years with regular visits to assess changes in walking and other motor skills using a standard motor‑function test. Throughout the study, safety checks and simple questionnaires will be used to track any side effects and overall health.

1 enrollment and consent

after joining the trial, a written agreement is signed to confirm understanding of the study procedures.

the participant receives an overview of the trial purpose and what will be required.

2 baseline evaluation

a series of tests are performed to record the current level of motor function and overall health.

the results serve as the reference point for later comparisons.

3 single intrathecal administration of <b>melpida</b>

the medication is delivered as a one‑time injection into the fluid surrounding the spinal cord (intrathecal route).

the dose is 100000000000000 vector genomes per milliliter, provided as a solution for injection.

the injection is performed in the lower back (lumbar region) by a qualified clinician.

4 immediate post‑procedure monitoring

after the injection, vital signs and any immediate reactions are observed for several hours.

the participant remains in the clinic until the health care team confirms stability.

5 scheduled follow‑up visits

regular clinic visits are scheduled to assess safety and motor function over time.

the visits may occur at intervals such as weeks 4, 12, 24, and then every three months thereafter.

each visit includes physical examinations, questionnaires, and possibly imaging studies.

6 final assessment at week 156

at week 156 (approximately three years after the injection), a comprehensive evaluation measures changes in motor milestones.

the primary outcome is the change in the total percent score of the eight major motor milestones derived from the gross motor function measure‑88.

Who Can Join the Study?

Be a male or female who is at least 6 years old when screened.
Have a confirmed diagnosis of SPG50 through a genetic test that shows disease‑causing changes in both copies of the AP4M1 gene (the test looks at the DNA to find the specific mutation).
Be able to sit up on your own for at least three seconds (this is measured by a standard test called the Gross Motor Function Measure (GMFM‑88)).
Show signs of neurological problems based on your medical history and a physical exam (meaning the doctor has observed symptoms that affect the nervous system).
Have been taking any other medicines (such as anti‑spasticity, anti‑epileptic, behavioral, sleep medicines, special diets, supplements, or nutritional support) at the same doses for at least three months before screening, unless the doctor decides otherwise.
Have two legally able parents or legal representatives who can give informed consent (agree to the study after understanding it) and, if only one parent has legal authority, that parent must be able to take part in the consent process.
The parents or legal representatives must be able to attend all study visits and report on the participant’s symptoms and how they are doing.
Both the participant and the caregivers must be able to travel to the study center, and for the 30 days after treatment the participant must live within about 200 km of the clinical site.

Who Cannot Join the Study?

If the doctors decide you cannot take part in the study assessments.
If you have any health problem that makes an MRI (a scan that uses strong magnets) unsafe for you.
If any other medical condition would stop you from completing the required study steps.
If you have significant brain or nerve problems related to AP‑4, or behavior issues that would affect the study results.
If routine lab tests show abnormal results that could be important for your health.
If you have had, or plan to have, a non‑emergency surgery that might interfere with the study.
If you cannot give proper written permission (informed consent) to join the study.
If there is reason to think you or your parents might not follow the study procedures.
If you have taken any experimental (investigational) drug within 30 days before screening, or plan to take one (except the gene therapy being studied) during the trial.
If you have been enrolled in another experimental treatment study within the past 90 days.
If your blood tests show any of the following serious abnormalities: very low or very high hemoglobin, white blood cell count over 20,000 per cmm, platelet count below 100,000 per cmm, INR (a clotting test) above the normal limit, liver enzymes (GGT, ALT, AST) or total bilirubin more than 1.5 times the normal limit, or creatinine (a kidney test) 1.5 mg/dL or higher.
If you have a medical condition that prevents a lumbar puncture (a spinal tap) or the use of anesthetic drugs for procedures that require deep sedation.
If you have a bleeding disorder or any condition that makes a lumbar puncture unsafe.
If you have a diagnosed cardiomyopathy (disease of the heart muscle) or a major congenital (present at birth) heart defect.
If the anesthesiologist believes you cannot safely undergo deep sedation.
If you have had a severe or life‑threatening allergic reaction to any of the following medicines used in the study: sirolimus, tacrolimus, corticosteroids, or gadolinium (a contrast agent used in imaging).
If you have another ongoing illness or need long‑term medication that the study doctor thinks could pose too much risk during the gene‑therapy procedure.
If any of your regular medicines could interact badly with the study’s immunosuppressive drugs.

Where you can join this trial?

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Verified Sites

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Other Sites

Site Name	City	Country	Status
Rigshospitalet	Copenhagen	Denmark

Trial status

Country	Status	Recruitment Start
Denmark	Not yet recruiting	01.08.2026

Trial locations

Melpida
Melpida is a gene therapy that is given as a single injection into the fluid around the spinal cord (intrathecal administration). It uses a harmless virus (AAV9) to deliver a normal copy of the AP4M1 gene directly to the nervous system. The goal of the therapy is to replace the missing or faulty gene that causes hereditary spastic paraplegia type 50 (SPG50), with the hope of improving muscle control and slowing disease progression. Participants receive the treatment once, and doctors will monitor them closely to see how well it works and to check for any side effects.

Hereditary spastic paraplegia (SPG50) – Hereditary spastic paraplegia is a genetic disorder that causes progressive stiffness and weakness in the legs. It results from degeneration of the nerve fibers that control movement. Symptoms typically begin in childhood or early adulthood and slowly worsen over time. Affected individuals experience increasing difficulty walking, frequent falls, and reduced ability to perform daily tasks. As the disease advances, balance and coordination may also become impaired.

Trial ID:

2025-524481-15-00

Protocol code:

AAV9/AP4M1-DK01

Trial Phase:

Therapeutic exploratory (Phase II)

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Phase IIb Open‑Label Study of Intrathecal MELPIDA (AAV9/AP4M1) in Patients with Hereditary Spastic Paraplegia Type 50 (SPG50)

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?