RecruitingPhase 1Phase 2NCT05518188

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

A Phase 1/2 Open-label Intrathecal Administration of MELPIDA to Determine Its Safety and Efficacy for Patients with Spastic Paraplegia Type 50 (SPG50) Caused by Mutation in the AP4M1 Gene.

Sponsor

Elpida Therapeutics SPC

Enrollment

4 participants

Start Date

Feb 15, 2023

Study Type

INTERVENTIONAL

Conditions

Spasticity, Muscle Spastic Paraplegia Microcephaly SPG50 Growth Retardation Intellectual Deficiency

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.

Eligibility

Min Age: 4 MonthsMax Age: 10 Years

Inclusion Criteria9

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).

Exclusion Criteria14

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.