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Recruiting NCT06692712

Phase 3 Efficacy Study With Concurrent Control of IT MELPIDA in SPG50.Concurrent Controls.

Phase III Interventional Hereditary Spastic Paraplegia Type 50

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: MELPIDA.
Who it may be relevant to
Registry conditions: Hereditary Spastic Paraplegia Type 50. Basic parameters: 4 months — 72 months · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States, Spain
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

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

Overview

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.

Interventions

  • Genetic MELPIDA
    Gene Therapy agent

Primary outcome measures

  • Gross Motor Function Measure (GMFM-88) Defined Major Milestones [Time frame: 156 weeks]
Secondary outcome measures (6)
  • 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]

Eligibility criteria

Inclusion:

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,
  • 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.

Exclusion

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
  • #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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Non-randomized
Model
Parallel assignment
Masking
Open label
Primary purpose
Treatment

Study locations

United States · 1 center
  • University of Texas Southwestern Medical Center — Dallas
Spain · 1 center
  • Sant Joan de Deu — Barcelona

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. PMID 41491634

Identifiers

NCT: NCT06692712 · MELPIDA -Pivotal Trial

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗