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

The Hospital for Sick Children

Status and phase

Active, not recruiting

Phase 1

Conditions

Spastic Paraplegia Type 50

Treatments

Biological: MELPIDA

Study type

Interventional

Funder types

Other

Identifiers

NCT06069687

1000079110

Details and patient eligibility

About

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.

Enrollment

1 patient

Sex

Male

Ages

Under 4 years old

Volunteers

No Healthy Volunteers

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