Study of Melpida with drug combination 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, a rare inherited condition that leads to increasing stiffness and weakness in the legs, making walking and movement difficult. Participants will receive the investigational gene‑based therapy called MELPIDA, which is delivered by an intrathecal injection, meaning the medicine is placed directly into the fluid that surrounds the spinal cord. The aim of the trial is to determine whether this treatment is safe and can improve motor abilities and overall disease severity.

During the trial, participants will receive the study medication at scheduled visits over a period of about three years, with regular check‑ups to monitor health and progress. Simple tests will be used to measure changes in walking, balance, and everyday skills, including a movement assessment that looks at major milestones such as standing and walking, and a developmental test that evaluates thinking and learning abilities. The study is a phase 3 trial, which means it is a large‑scale test designed to confirm the benefits and safety of the therapy before it may become widely available.

1 enrollment and consent

after joining the study you will sign an informed consent form that explains the purpose of the trial and what is expected of you.

the study team will confirm that you meet the eligibility criteria for hereditary spastic paraplegia type 50 (spg50).

2 baseline assessments

a series of evaluations will be performed before any treatment is given.

motor milestone testing using the gross motor function measure (gmfm‑88) will be recorded.

cognitive testing with the bayley‑3 scale, spasticity rating (spastic paraplegia rating scale), and caregiver quality‑of‑life questionnaires will be completed.

blood samples will be taken to measure biomarkers such as plasma neurofilament light chain and other laboratory values.

magnetic resonance imaging with gadoterate contrast may be performed to assess brain and spinal cord structures.

3 intrathecal administration of melpida

the study drug, melpida, will be given as a single intrathecal injection, which means the medication is delivered directly into the fluid surrounding the spinal cord.

the dose is 1,000,000,000,000,000 vector genomes per milliliter (vg/mL).

the injection is performed by a trained clinician in a sterile environment.

4 immediate post‑administration monitoring

after the injection you will be observed for several hours to monitor vital signs and any immediate reactions.

nurses will check blood pressure, heart rate, temperature, and watch for signs of discomfort or allergic reaction.

5 scheduled follow‑up visits

you will return for regular clinic visits over the next three years.

initial visits are typically at weeks 4, 12, and 24 after treatment, followed by visits every 12 weeks until week 156.

each visit includes physical examination, vital‑sign checks, and review of any side effects.

6 repeated efficacy assessments

at each follow‑up visit the same motor and cognitive tests performed at baseline will be repeated, including the gmfm‑88, bayley‑3 cognitive domain, spastic paraplegia rating scale, and caregiver questionnaires.

the 10‑meter walk test and other functional measures are also repeated to track changes over time.

7 safety laboratory monitoring

blood samples will be collected at scheduled visits to measure biomarkers such as plasma neurofilament light chain, as well as routine safety labs (complete blood count, liver and kidney function).

any abnormal findings will be evaluated by the study physician.

8 final evaluation at week 156

at the end of the 156‑week (approximately three‑year) study period a comprehensive assessment will be performed.

the final gmfm‑88 score, cognitive scores, spasticity rating, and quality‑of‑life measures will be compared with baseline values to determine the overall effect of the treatment.

the study team will discuss the results with you and outline any further care that may be needed.

Who Can Join the Study?

Child must be a boy or girl who is between 4 months and 72 months old when screened.
Parent or legal guardian must sign a written informed consent form agreeing for the child to join the study.
Child must be able to follow all study procedures and visits.
Child and their caregivers must be able to travel to the study center, and for the first 30 days after treatment the family must live within about 100 miles (160 km) of the site.
Child must have a molecularly‑confirmed diagnosis of the condition, meaning a laboratory test has identified two disease‑causing changes (called bi‑allelic pathogenic variants) in the AP4M1 gene (or, for the control group, similar changes in the AP4B1 or AP4S1 genes that cause SPG47 or SPG52).
Child must show signs of neurologic dysfunction, such as problems with movement, muscle tone, or other nervous system symptoms, as noted in medical history and physical exam.
Any other medicines the child is taking for muscle stiffness (anti‑spasticity medications), seizures (anti‑seizure medications), behavior, sleep, special diets, supplements, or nutritional support must have been at the same dose for at least 3 months before screening, unless the doctor decides a change is acceptable.

Who Cannot Join the Study?

Loss of any of the eight major motor milestones in the past 12 months – these milestones include sitting without support for 3 seconds, crawling or moving forward 1.8 m, standing without support for 3 seconds, walking 10 steps with assistance, walking 10 steps independently, climbing up or down four steps while holding a rail, and jumping off a 15 cm step with both feet.
Having an elective (planned) surgery scheduled or performed within the last 6 months that could affect the study results.
Inability to obtain proper informed consent (or, for a child, inability of the parents/guardians to give consent).
Reason to believe the participant or the parents will not be able to follow the study procedures as required.
Use of any investigational (experimental) drug within 30 days before screening or plans to use one during the study (gene‑therapy drugs are excluded from this rule).
Participation in another interventional clinical trial within 90 days before the first screening visit.
Being judged by the investigators as unable to take part in the required clinical evaluations.
Having significant AP‑4 related central nervous system problems or behavioral disturbances that could interfere with the study results.
Having lab test results that are outside safe ranges, such as very low or very high hemoglobin (blood’s oxygen‑carrying protein), very high white‑blood‑cell count, low platelet count, abnormal clotting test (INR), liver enzymes (GGT, ALT, AST) or bilirubin more than 1.5 times the normal limit, or high creatinine indicating reduced kidney function.
Having a medical condition (for example, scoliosis – a curvature of the spine – or a bleeding disorder) that would prevent a lumbar puncture (spinal tap) or the safe use of anesthesia for sedated procedures.
Having documented cardiomyopathy (disease of the heart muscle) or major congenital heart abnormalities.
History of a severe or life‑threatening allergic reaction to medicines such as sirolimus, tacrolimus, corticosteroids, or gadolinium (a contrast agent used in imaging).
Having a chronic illness or taking ongoing medication that, in the investigator’s opinion, creates unnecessary risk for gene therapy or could interact with the study’s immunosuppressive drugs.
Any condition that would prevent the participant from safely undergoing an MRI scan, according to the hospital’s policies.
Any other situation that would stop the participant from completing any required study procedure.

Where you can join this trial?

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Verified Sites

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Other Sites

Site Name	City	Country	Status
Hospital Sant Joan De Deu Barcelona	Esplugues De Llobregat	Spain

Trial status

Country	Status	Recruitment Start
Spain	Not yet recruiting	01.08.2026

Trial locations

Investigated Drugs:

Prednisone is a steroid medication given by intravenous infusion. In this trial it is used as part of the standard background treatment to reduce inflammation and help control the immune response.

Tacrolimus is an immunosuppressive drug given by intravenous infusion. It is included in the background regimen to prevent the body’s immune system from reacting strongly to the study treatment.

Diphenhydramine is an antihistamine taken by mouth. It is used in the background therapy to help reduce allergic reactions or itching that might occur during the trial.

Methylprednisolone is a strong anti‑inflammatory steroid that is given by intravenous infusion, often combined with a local anesthetic (lidocaine). It is part of the standard care to control swelling and pain around the time of the study treatment.

Paracetamol (also known as acetaminophen) is a pain‑relieving and fever‑reducing medication given by intravenous infusion. It may also contain a mild antihistamine (buclizine) and a small amount of codeine for extra pain control. It is used in the background regimen to keep participants comfortable.

Sirolimus is an immunosuppressive agent given by intravenous infusion. It helps prevent the immune system from attacking the study drug and is included as part of the background therapy.

Gadoteric acid is a contrast agent used during imaging procedures. It is given by intravenous infusion to allow doctors to see the spinal area clearly on scans, helping them guide the study treatment safely.

Melpida is the experimental therapy being tested. It is a gene‑based product delivered directly into the spinal fluid (intrathecally). The goal of Melpida is to provide a missing or faulty gene that causes hereditary spastic paraplegia type 50, with the aim of improving nerve function and reducing symptoms.

Hereditary spastic paraplegia type 50 (SPG50) – Hereditary spastic paraplegia type 50 (SPG50) is a genetic disorder that primarily affects the nerves controlling movement in the lower limbs. It causes increasing stiffness and weakness in the legs, making walking more difficult over time. As the condition progresses, individuals may experience reduced ability to perform motor milestones such as standing, crawling, or walking. The disease can also lead to gradual loss of coordination and balance, affecting daily activities.

Trial ID:

2025-524576-28-00

Protocol code:

CT-MEL-03

Trial Phase:

Therapeutic confirmatory (Phase III)

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Study of Melpida with drug combination in patients with Hereditary Spastic Paraplegia Type 50 (SPG50)

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?