Administration of MELPIDA to Determine the Safety and Efficacy for Patients With Spastic Paraplegia Type 50

NCT ID: NCT06069687

Last Updated: 2025-05-14

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-11
• Study Completion Date: 2027-03-31

Brief Summary

This will be a first-in-human Phase I, open-label, single dose clinical study of MELPIDA administered intrathecally (IT) through a lumbar puncture (LP) to a single subject with confirmed pathogenic mutations in the Adaptor Related Protein Complex 4 Subunit Mu 1 (AP4M1) gene. The primary outcome will be the determination of the safety and tolerability of MELPIDA in patients with SPG50, based on development of toxicity.

The secondary outcome will be a preliminary exploration of efficacy of the treatment.

MELPIDA, is a recombinant serotype 9 adeno-associated virus (AAV) encoding a codon-optimized human AP4M1 transgene and will be administer to the patient via a single intrathecal infusion of 10 mL at 1E14 vg/mL for a total dose of 1E15 vg.

The total study duration is 5 years post dosing and the participant will be tested at screening/baseline (-28 to -7 days), return for dosing, and then follow-up visits post-dosing on Days 7 (+/-2), 30 (+/-2), 60 (+/-2), 90 (+/-14), 180 (+/-14), 270 (+/-14), 360 (+/-14), 540 (+/-14), and 720 (+/-14) days, then annually for the last 3 years.

Conditions

Spastic Paraplegia Type 50

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

MELPIDA

A single intrathecal infusion of 10 mL at 1E14 vg/mL for a total dose of 1E15 vg (open-label)

Group Type: EXPERIMENTAL

MELPIDA

Intervention Type: BIOLOGICAL

A single intrathecal infusion of 10 mL at 1E14 vg/mL for a total dose of 1E15 vg

Interventions

MELPIDA

A single intrathecal infusion of 10 mL at 1E14 vg/mL for a total dose of 1E15 vg

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Age < 5 years old
• Confirmed diagnosis of SPG50 disease by:
• Genomic DNA mutation analysis demonstrating homozygous or compound heterozygous, pathogenic and/or potentially 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

Exclusion Criteria

• 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 central nervous system (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 × Upper Limit of Normal (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. Patients with an elevated bilirubin level that is unequivocally the result of neonatal jaundice shall not be excluded

• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 4 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

The Hospital for Sick Children

OTHER

Sponsor Role: lead

Responsible Party

Gregory Costain

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The Hospital for Sick Children

Toronto, Ontario, Canada

Countries

Canada

References

Dowling JJ, Pirovolakis T, Devakandan K, Stosic A, Pidsadny M, Nigro E, Sahin M, Ebrahimi-Fakhari D, Messahel S, Varadarajan G, Greenberg BM, Chen X, Minassian BA, Cohn R, Bonnemann CG, Gray SJ. AAV gene therapy for hereditary spastic paraplegia type 50: a phase 1 trial in a single patient. Nat Med. 2024 Jul;30(7):1882-1887. doi: 10.1038/s41591-024-03078-4. Epub 2024 Jun 28.

Reference Type: DERIVED

PMID: 38942994 (View on PubMed)

Other Identifiers

1000079110

Identifier Type: -

Identifier Source: org_study_id