Not yet recruitingRare disease

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

Verified siteRegistered drugNo placebo

Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

What is this trial about?

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

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.

The research process

The trial runs in 8 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 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).
Step 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.
Step 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.
Step 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.
Step 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.
Step 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.
Step 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.
Step 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 trial?

7 criteria

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 trial?

15 criteria

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.

Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

Tell us about your condition – we search every trial in Europe and connect you with the right site.

We usually reply within a few days

Verified sites

All sites with verified contact details – recruitment status may not be available; ask directly

Hospital Sant Joan De Deu Barcelona
Verified
Esplugues De Llobregat, Spain

Trial locations

Where you can join this trial

Countries are shaded by recruitment status. Click a recruiting country to ask about joining there.

Not yet recruiting

Not finding your country?

Not sure what to do next?

Joining a clinical trial can seem overwhelming. We guide you step by step, so you know exactly what to expect and how we support you through the process.

See the full process and FAQ

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.

Tacrolimus

What is already known about the treatment

Prednisone
Prednisone is administered through an intravenous (IV) infusion, delivering the drug directly into the bloodstream. It is a well‑established synthetic steroid that is widely used and described in medical literature. It is mainly prescribed to reduce inflammation and suppress an overactive immune system in conditions such as asthma, arthritis, and allergic reactions. It works by binding to steroid receptors inside cells, which then turn off genes that cause inflammation; it belongs to the class of glucocorticoids.
Melpida
Melpida is given by intrathecal injection, meaning it is injected directly into the fluid surrounding the spinal cord. It is an experimental gene‑therapy vector that is currently being studied in clinical trials for hereditary spastic paraplegia type 50 (SPG50). Its intended use is to deliver a functional copy of the missing gene to nerve cells, aiming to slow or stop disease progression. The vector carries genetic material that enters cells and produces the needed protein, classifying it as a gene‑transfer therapy.
Tacrolimus
Tacrolimus is delivered by IV infusion, allowing it to enter the body quickly through the veins. It is an approved immunosuppressant that has been used for many years to prevent organ‑rejection after transplants. It is mainly used to calm the immune system in transplant patients and certain autoimmune disorders. The drug binds to a protein inside immune cells, stopping the activation of a key signaling pathway that would otherwise cause an immune attack; it is classified as a calcineurin inhibitor.
Diphenhydramine
Diphenhydramine is taken by mouth as a tablet or liquid. It is an over‑the‑counter antihistamine that has been widely used for decades to relieve allergy symptoms and to help with sleep. It is commonly used for sneezing, itching, watery eyes, and as a short‑term sleep aid. The medication blocks histamine receptors in the brain and body, preventing the allergic response, and it belongs to the class of first‑generation antihistamines.
Methylprednisolone
Methylprednisolone acetate is given by IV infusion, often mixed with lidocaine, a local anesthetic that eases pain at the injection site. It is a synthetic steroid that has long been used in hospitals for severe inflammation, such as in asthma attacks, severe allergies, and certain autoimmune diseases. It works by attaching to steroid receptors inside cells, turning off genes that cause inflammation, and it is classified as a glucocorticoid.
Paracetamol
The paracetamol combination (with buclizine and codeine) is administered by IV infusion. It is a pain‑relieving and fever‑reducing medicine that has been in clinical use for many years. It is mainly used to treat mild to moderate pain and to lower fever after surgery or injury. Paracetamol works by blocking the production of pain‑related chemicals in the brain, while codeine adds a mild opioid effect and buclizine helps with nausea; together they belong to the analgesic and antipyretic class.

Investigated diseases

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.