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

NCT06692712 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: MELPIDA -Pivotal Trial
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 2

Brief 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).

Conditions

Hereditary Spastic Paraplegia Type 50

Keywords

SPG50; Spastic Paraplegia; Gene Therapy; Phase 3

Outcome Measures

Primary Outcomes (1)

• 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 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

  156 weeks

Secondary Outcomes (6)

• Composite Endpoint Defined by the Win Ratio

  156 weeks

• Developmental Milestones- Bayley-4 Cognitive Domain

  156 weeks

• Gross and Fine Motor Function (GMFM-88 full scale)

  156 weeks

• Disease Severity (Spastic Paraplegia Rating Scale )

  156 weeks

• Disease Severity (Clinical Global Impression)

  156 weeks

Study Arms (2)

MELPIDA Treatment

EXPERIMENTAL

Eligible subjects (N=8) will receive a single open-label intrathecal administration of MELPIDA and follow up to week 260.

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.

Interventions

MELPIDA GENETIC

Gene Therapy agent

MELPIDA Treatment

Eligibility Criteria

• Age: 4 Months - 72 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Elpida Therapeutics SPC: lead
• Hospital Sant Joan de Deu: collaborator
• University of Texas Southwestern Medical Center: collaborator

Study Sites (2)

University of Texas Southwestern Medical Center

Dallas, Texas, 75025, United States

RECRUITING

Sant Joan de Deu

Barcelona, 08950, Spain

ACTIVE NOT RECRUITING

Related Publications (1)

• 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 Jan 5. doi: 10.1002/acn3.70308. Online ahead of print.

  PMID: 41491634 DERIVED

MeSH Terms

Conditions

Paraplegia

Condition Hierarchy (Ancestors)

Paralysis; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Rachel Thomas

CONTACT

+1-833-335-7432; studyinfo@elpidatx.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2024
• First Posted: November 18, 2024
• Study Start: April 1, 2026
• Primary Completion (Estimated): February 28, 2032
• Study Completion (Estimated): June 1, 2032
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: 12 months after start date for protocol. CSR 12 months after completion of study

Locations

US (1); ES (1)