Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)

NCT05518188 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IND No 028202; Serial No 0000
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

MELPIDA is proposed for the treatment of subjects with SPG50 and targets neuronal cells to deliver a fully functional human AP4M1 cDNA copy via intrathecal injection to counter the associated neuronal loss. Outcomes will evaluate the safety and tolerability of a single dose of MELPIDA, which will be measured by the treatment-associated adverse events (AEs) and serious adverse events (SAEs). Secondarily, the trial will explore efficacy in terms of disease burden assessments.

Conditions

Spasticity, Muscle; Microcephaly; Intellectual Deficiency; Growth Retardation; SPG50; Spastic Paraplegia

Outcome Measures

Primary Outcomes (1)

• Incidence of unanticipated treatment-related toxicities, Grade 3 or higher in participants with SPG50

  Incidence of unanticipated treatment-related toxicities, Grade 3 or higher, in participants with SPG50 will be determined from the collection of occurrence and severity of serious adverse events (SAEs). Adverse events will be determined according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.

  60 months

Secondary Outcomes (2)

• Stability or improvement in spasticity in participants with SPG50 as measured by the Modified Ashworth scale (MAS)

  60 months

• Stability or improvement in spasticity in participants with SPG50 as measured by the Tardieu scale

  60 months

Study Arms (1)

Treatment Arm

EXPERIMENTAL

MELPIDA, a gene therapy product

Biological: MELPIDA

Interventions

MELPIDA BIOLOGICAL

MELPIDA, a recombinant serotype 9 adeno-associated virus (AAV) encoding a codon-optimized human AP4M1 transgene

Treatment Arm

Eligibility Criteria

• Age: 4 Months - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 4 months-10 years old
• Confirmed diagnosis of SPG50 disease by:
• Genomic DNA mutation analysis demonstrating homozygous or compound heterozygous, confirmed pathogenic variants in the AP4M1 gene
• Clinical history or examination features consistent with SPG50 and that include neurologic dysfunction
• 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
• Ability to stand for more than 5 seconds OR
• Ability to take 5 steps independently or with a walker OR
• Modified Ashworth Scale score 2 or below (Ankles).

You may not qualify if:

• Inability to participate in study procedures (as determined by the site investigator)
• Presence of a concomitant medical condition that precludes lumbar puncture (LP) or use of anesthetics
• History of bleeding disorder or any other medical condition or circumstance in which lumbar puncture is contraindicated according to local institutional policy
• Inability to be safely sedated in the opinion of the clinical anesthesiologist
• Active infection, at the time of dosing, based on clinical observations
• Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer
• Inability of the patient to undergo MRI according to local institutional policy
• Inability of the patient to undergo any other procedure required in this study
• The presence of significant non-SPG50 related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study
• 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
• Contraindication to MELPIDA or any of its ingredients
• Contraindication to any of the immune suppression medications used in this study
• Clinically significant abnormal laboratory values (GGT, ALT, and AST, or total bilirubin \> 3 × ULN, creatinine ≥ 1.5 mg/dL, hemoglobin \[Hgb\] \< 6 or \> 20 g/dL; white blood cell \[WBC\] \> 20,000 per cmm) prior to gene replacement therapy.

Sponsors & Collaborators

• Elpida Therapeutics SPC: lead
• University of Texas Southwestern Medical Center: collaborator

Study Sites (1)

Children's Medical Center Dallas

Dallas, Texas, 75235, United States

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

Muscle Spasticity; Microcephaly; Paraplegia

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Paralysis

Study Officials

• Susan T. Iannaccone, MD, FAAN

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sydney Cooper, MSc

CONTACT

214-250-0174; Sydney.Cooper@UTSouthwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2022
• First Posted: August 26, 2022
• Study Start: February 15, 2023
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2030
• Last Updated: October 8, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: End of study

Locations

US (1)