Hereditary Spastic Paraplegia Type 50Phase 3SPG50NCT06692712
Phase 3 Efficacy Study With Concurrent Control of IT MELPIDA in SPG50.Concurrent Controls.
A Phase 3 study testing MELPIDA in people with Hereditary Spastic Paraplegia Type 50, run by Elpida Therapeutics SPC at 2 sites in 2 countries.
Trial summary
Phase 3, open-label study to assess the efficacy and safety of a single lumbar intrathecal administration of MELPIDA in individuals with Hereditary Spastic Paraplegia Type 50 (SPG50). Read more about this study
- Who is it for?
- Ages 4 to 72 months
- Conditions the study is for
- Hereditary Spastic Paraplegia Type 50
- What is being tested?
- MELPIDA
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 1 Apr 2026to 1 Jun 2032
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 72 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- For the treatment group
- Male and females between the ages of 4 months to 72 months at the time of screening.
- Molecularly-confirmed diagnosis of SPG50 (confirmed by a CLIA certified, CE-marked, or equivalent lab): Genomic DNA mutation analysis demonstrating bi-allelic pathogenic or likely pathogenic variants in the AP4M1 gene.
- Subjects must have features of neurologic dysfunction by clinical history and physical examination.
- Stable doses of concomitant medications such as anti-spasticity medications, anti-seizure medications, behavioral management medications, sleep medications, and special diets, supplements, or nutritional support for at least 3 months prior to Screening. If recent changes (< 3 months) in medications, the subject may be allowed per Investigator judgement.
- Parent/legal guardian willing to provide written informed consent for their child prior to participation in the study,
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- Subjects and caregivers must demonstrate the ability to travel to the study center. For the 30 days post treatment subjects must reside within 100 miles (approximately 160 km) of the clinical site.
- For the control group
- Male and females between the ages of 4 to 72 months at the time of screening.
- A molecularly confirmed diagnosis of SPG47, SPG50 or SPG52 (confirmed by a CLIA certified, CE-marked, or equivalent lab). Genomic DNA mutation analysis demonstrating bi-allelic pathogenic variants in the AP4B1, AP4M1, or AP4S1 gene,
- Subjects must have features of neurologic dysfunction by clinical history and physical examination.
- Parent/legal guardian willing to provide written informed consent for their child prior to participation in the study.
- Subject able to comply with all protocol requirements and procedures.
- Subjects and caregivers must demonstrate the ability to travel to the study center.
Who cannot join
- For the treatment group
- Loss of one of the 8 major motor milestones within the last 12 months. Milestones defined as:
- #24: Sit on mat: Maintain, arms free, 3 seconds
- #44: 4 Point: Crawls or hitches forward 1.8m (6')
- #53: Standing: Maintains, arms free, 3 seconds
- #67: Standing: 2 hands held: walks forward 10 steps
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- #69: Standing: Walks forward 10 steps
- #84: Standing: Holding 1 rail: walks up 4 steps, holding 1 rail, alternating feet
- #85: Standing: Holding 1 rail: walks down 4 steps, holding 1 rail, alternating feet
- #88: Standing on 15cm (6") step: Jumps off, both feet simultaneously
- Inability to participate in the clinical evaluation as determined by the principal investigators.
- Clinically significant abnormal laboratory values (hemoglobin < 6 or > 20 g/dL; white blood cell > 20,000 per cmm, platelets count < 100,000 per cmm; INR > ULN; GGT, ALT, and AST or total bilirubin > 1.5 × ULN, creatinine ≥ 1.5 mg/dL) prior to gene replacement therapy.
- Presence of a concomitant medical condition (eg, scoliosis or bleeding disorder) that precludes a lumbar puncture or use of anesthetics for sedated procedures.
- Documented cardiomyopathy or significant congenital heart abnormalities.
- History of severe/life-threatening allergic reaction to sirolimus, tacrolimus, corticosteroids, or gadolinium.
- Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer, or interactions with the immunosuppressive agents.
- Any item which would exclude the subject from being able to undergo MRI according to local institutional policy, or any other procedure.
- The presence of significant AP-4 related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study.
- Recent or planned elective surgical procedures (within 6 months) that would confound the scientific rigor or interpretation of results of the study.
- Failure to obtain appropriate informed consent.
- Reason to believe that the subject or parents of the subject will not comply with the study procedures outlined in the study protocol.
- Have received an investigational drug within 30 days prior to screening or plan to receive an investigational drug (other than gene therapy) during the study.
- Enrollment and participation in another interventional clinical trial 90 days before first visit (screening).
- For the control group
- Loss of one of the 8 major motor milestones within the last 12 months. Milestones defined as:
- #24: Sit on mat: Maintain, arms free, 3 seconds
- #44: 4 Point: Crawls or hitches forward 1.8m (6')
- #53: Standing: Maintains, arms free, 3 seconds
- #67: Standing: 2 hands held: walks forward 10 steps
- #69: Standing: Walks forward 10 steps
- #84: Standing: Holding 1 rail: walks up 4 steps, holding 1 rail, alternating feet
- #85: Standing: Holding 1 rail: walks down 4 steps, holding 1 rail, alternating feet
- #88: Standing on 15cm (6") step: Jumps off, both feet simultaneously
- Inability to participate in the clinical evaluation as determined by the principal investigators.
- Any other situation that would exclude the subject from undergoing any other procedure required in this study.
- The presence of significant AP-4 related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study.
- Recent or planned elective surgical procedures that would confound the scientific rigor or interpretation of results of the study.
- Failure to obtain appropriate informed consent.
- Reason to believe that the subject or parents of the subject will not comply with the study procedures outlined in the study protocol.
- Have received an investigational drug within 30 days prior to screening or plans to receive an investigational drug (other than gene therapy) during the study.
- Enrollment and participation in another interventional clinical trial 90 days before first visit (screening).
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
United States1 site, 1 recruiting
- Recruiting
University of Texas Southwestern Medical Center
Dallas, Texas, 75025
About this study
Official title: Intrathecal Administration of MELPIDA (AAV9/AP4M1) For Hereditary Spastic Paraplegia Type 50 (SPG50): A Phase 3, Open-Label Trial With Matched Prospective Concurrent Control Arm
Phase 3, open-label study to assess the efficacy and safety of a single lumbar intrathecal administration of MELPIDA in individuals with Hereditary Spastic Paraplegia Type 50 (SPG50).
Read the detailed description
MELPIDA is an AAV9-based gene therapy vector that expresses the fully functional form of AP4M1 under the control of a synthetic promoter. MELPIDA will be delivered intrathecally and is designed to achieve stable, potentially life-long expression of AP4M1 in non-dividing cells. This clinical study is a pivotal open-label phase 3 study designed to assess safety and efficacy of MELPIDA in individuals with SPG50.
- Conditions
- Hereditary Spastic Paraplegia Type 50
- Being tested
- MELPIDA
- Keywords
- SPG50, Spastic Paraplegia, Gene Therapy, Phase 3
- Medical subject headings
- Paraplegia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MELPIDAGenetic
Gene Therapy agent
| Study group | Role | What they receive |
|---|---|---|
| MELPIDA Treatment | Experimental | Eligible subjects (N=8) will receive a single open-label intrathecal administration of MELPIDA and follow up to week 260. Receives: Genetic: MELPIDA |
| Matched Prospective Concurrent Control Arm | No intervention | Approximately 16 untreated age- and disease- matched controls with confirmed AP-4-related disease (SPG47, SPG50, or SPG52) will be enrolled and attend study visits concurrent with the MELPIDA treatment arm. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gross Motor Function Measure (GMFM-88) Defined Major Milestones
Change in total percent score of the 8 Major Motor Milestone Scores from baseline in treated group compared to change in total percent score of the 8 Major Motor Milestone Scores from baseline in untreated controls
- #24: Sit on mat: Maintain, arms free, 3 seconds
- #38: Prone: Creeps forward 1.8m (6')
- #52: On the floor: Pulls to stand at large bench
- #67: Standing: 2 hands held: walks forward 10 steps
- #69: Standing: Walks forward 10 steps
- #84: Standing: Holding 1 rail: walks up 4 steps, holding 1 rail, alternating feet
- #85: Standing: Holding 1 rail: walks down 4 steps, holding 1 rail, alternating feet
- #88: Standing on 15cm (6") step: Jumps off, both feet simultaneously
Measured: 156 weeks
Secondary outcomes (6)
Composite Endpoint Defined by the Win Ratio
Composite Endpoint Defined by the Win Ratio using matching criteria after 156 Weeks of Follow-up of the 8 selected items and the raw scores of the Cognitive domain of the Bayley Scale of Infant and Toddler Development 4th Edition (Bayley-4).
Measured: 156 weeks
Developmental Milestones- Bayley-4 Cognitive Domain
Developmental Milestones- Bayley-4 Cognitive Domain-Change in Total Raw Score from Baseline
Measured: 156 weeks
Gross and Fine Motor Function (GMFM-88 full scale)
Gross and Fine Motor Function (GMFM-88 full scale) - Change in Total Score from Baseline.
Measured: 156 weeks
Disease Severity (Spastic Paraplegia Rating Scale )
Disease Severity (Spastic Paraplegia Rating Scale ). Change in Total Score from Baseline.
Measured: 156 weeks
Disease Severity (Clinical Global Impression)
Disease Severity (Clinical Global Impression) Change in Physician-assessed Clinical Global Impression) from Baseline.
Measured: 156 weeks
Muscle Spasticity (Modified Ashworth Scale)
Change from Baseline in Muscle Spasticity (Modified Ashworth Scale) Score
Measured: 156 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2024
- Study start1 Apr 2026
- Primary completion28 Feb 2032 (estimated)
- Study completion1 Jun 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hereditary Spastic Paraplegia Type 50Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Elpida Therapeutics SPC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of Texas Southwestern Medical Center, Hospital Sant Joan de Deu
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06692712
- Sponsor's protocol ID
- MELPIDA -Pivotal Trial
- Acronym
- SPG50
- Status last verified
- Apr 2026
- First submitted
- 14 Nov 2024
- Last updated
- 20 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Will be posted on Elpida Therapeutics website
Publications
Agianda HAP, Kim HM, Battaglia N, Rong J, Tam A, Gonzalez Saez-Diez E, Boerkoel CF, Saffari A, Quiroz V, Schierbaum L, Zaman Z, Bernardi K, Ebrahimi-Fakhari D. Diagnostic Utility of the ATG9A Ratio in AP-4-Associated Hereditary Spastic Paraplegia. Ann Clin Transl Neurol. 2026 Apr;13(4):834-839. doi: 10.1002/acn3.70308. Epub 2026 Jan 5.
PubMed 41491634
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intrathecal Administration of MELPIDA (AAV9/AP4M1) For Hereditary Spastic Paraplegia Type 50 (SPG50): A Phase 3, Open-Label Trial With Matched Prospective Concurrent Control Arm
- ClinicalTrials.gov ID
- NCT06692712
- Acronym / sponsor ID
- SPG50 / MELPIDA -Pivotal Trial
- Conditions
- Hereditary Spastic Paraplegia Type 50
- Keywords
- SPG50, Spastic Paraplegia, Gene Therapy, Phase 3
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Elpida Therapeutics SPCIndustry (pharma, biotech, devices)
- Collaborators
- University of Texas Southwestern Medical Center, Hospital Sant Joan de Deu
- Study start
- 1 Apr 2026 (actual)
- Primary completion
- 28 Feb 2032 (estimated)
- Study completion
- 1 Jun 2032 (estimated)
- First posted
- 18 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase 3, open-label study to assess the efficacy and safety of a single lumbar intrathecal administration of MELPIDA in individuals with Hereditary Spastic Paraplegia Type 50 (SPG50).
Detailed description
MELPIDA is an AAV9-based gene therapy vector that expresses the fully functional form of AP4M1 under the control of a synthetic promoter. MELPIDA will be delivered intrathecally and is designed to achieve stable, potentially life-long expression of AP4M1 in non-dividing cells. This clinical study is a pivotal open-label phase 3 study designed to assess safety and efficacy of MELPIDA in individuals with SPG50.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MELPIDA Treatment | Experimental | Genetic: MELPIDAEligible subjects (N=8) will receive a single open-label intrathecal administration of MELPIDA and follow up to week 260. |
| Matched Prospective Concurrent Control Arm | No intervention | –Approximately 16 untreated age- and disease- matched controls with confirmed AP-4-related disease (SPG47, SPG50, or SPG52) will be enrolled and attend study visits concurrent with the MELPIDA treatment arm. |
Who may qualify
- Ages
- 4 to 72 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (14 listed)
- For the treatment group
- Male and females between the ages of 4 months to 72 months at the time of screening.
- Molecularly-confirmed diagnosis of SPG50 (confirmed by a CLIA certified, CE-marked, or equivalent lab): Genomic DNA mutation analysis demonstrating bi-allelic pathogenic or likely pathogenic variants in the AP4M1 gene.
- Subjects must have features of neurologic dysfunction by clinical history and physical examination.
- Stable doses of concomitant medications such as anti-spasticity medications, anti-seizure medications, behavioral management medications, sleep medications, and special diets, supplements, or nutritional support for at least 3 months prior to Screening. If recent changes (< 3 months) in medications, the subject may be allowed per Investigator judgement.
Key exclusion criteria (41 listed)
- For the treatment group
- Loss of one of the 8 major motor milestones within the last 12 months. Milestones defined as:
- Inability to participate in the clinical evaluation as determined by the principal investigators.
- Clinically significant abnormal laboratory values (hemoglobin < 6 or > 20 g/dL; white blood cell > 20,000 per cmm, platelets count < 100,000 per cmm; INR > ULN; GGT, ALT, and AST or total bilirubin > 1.5 × ULN, creatinine ≥ 1.5 mg/dL) prior to gene replacement therapy.
- Presence of a concomitant medical condition (eg, scoliosis or bleeding disorder) that precludes a lumbar puncture or use of anesthetics for sedated procedures.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MELPIDAGene Therapy agent | Genetic | MELPIDA Treatment |
Primary outcome
Gross Motor Function Measure (GMFM-88) Defined Major Milestones
Time frame: 156 weeks
Change in total percent score of the 8 Major Motor Milestone Scores from baseline in treated group compared to change in total percent score of the 8 Major Motor Milestone Scores from baseline in untreated controls 1. #24: Sit on mat: Maintain, arms free, 3 seconds 2. #38: Prone: Creeps forward 1.8m (6') 3. #52: On the floor: Pulls to stand at large bench 4. #67: Standing: 2 hands held: walks forward 10 steps 5. #69: Standing: Walks forward 10 steps 6. #84: Standing: Holding 1 rail: walks up 4 steps, holding 1 rail, alternating feet 7. #85: Standing: Holding 1 rail: walks down 4 steps, holding 1 rail, alternating feet 8. #88: Standing on 15cm (6") step: Jumps off, both feet simultaneously
6 secondary outcomes
Composite Endpoint Defined by the Win Ratio
Time frame: 156 weeks
Developmental Milestones- Bayley-4 Cognitive Domain
Time frame: 156 weeks
Gross and Fine Motor Function (GMFM-88 full scale)
Time frame: 156 weeks
Disease Severity (Spastic Paraplegia Rating Scale )
Time frame: 156 weeks
Disease Severity (Clinical Global Impression)
Time frame: 156 weeks
Muscle Spasticity (Modified Ashworth Scale)
Time frame: 156 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2026.
- Derived from this study: PubMed 41491634Agianda HAP, Kim HM, Battaglia N, Rong J, Tam A, Gonzalez Saez-Diez E, Boerkoel CF, Saffari A, Quiroz V, Schierbaum L, Zaman Z, Bernardi K, Ebrahimi-Fakhari D. Diagnostic Utility of the ATG9A Ratio in AP-4-Associated Hereditary Spastic Paraplegia. Ann Clin Transl Neurol. 2026 Apr;13(4):834-839. doi: 10.1002/acn3.70308. Epub 2026 Jan 5.
- Individual participant dataSharing planned: Yes. Will be posted on Elpida Therapeutics website
Related trials for Hereditary Spastic Paraplegia Type 50
RecruitingPhase 1/2
Melpida: Recombinant Adeno-associated Virus (Serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
Spasticity, Muscle, Microcephaly
Not yet recruitingPhase 1/2
Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients With AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47)
HSP, Hereditary Spastic Paraplegia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing MELPIDA in people with Hereditary Spastic Paraplegia Type 50, run by Elpida Therapeutics SPC at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rachel Thomas (+1-833-335-7432, studyinfo@elpidatx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gross Motor Function Measure (GMFM-88) Defined Major Milestones (time frame: 156 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06692712, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2026.