Gene therapy for treating SPG50 in children

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.

This study is testing a new gene therapy called MELPIDA to see if it can safely help children with Spastic Paraplegia Type 50 feel better and reduce their symptoms.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 4 (estimated)
• Ages: 4 Months to 10 Years
• Sex: All
• Sponsor: Elpida Therapeutics SPC (industry)
• Locations: 1 site (Dallas, Texas)
• Trial ID: NCT05518188 on ClinicalTrials.gov

What this trial studies

MELPIDA is a gene therapy designed to treat Spastic Paraplegia Type 50 (SPG50) by delivering a functional copy of the human AP4M1 gene directly to neuronal cells through intrathecal injection. This Phase 1/2 trial aims to evaluate the safety and tolerability of a single dose of MELPIDA, while also assessing its efficacy in reducing disease burden. The study focuses on children aged 4 months to 10 years who have a confirmed diagnosis of SPG50, characterized by progressive neurodegeneration and associated symptoms. The trial will monitor treatment-related adverse events and serious adverse events as primary outcomes.

Who should consider this trial

Good fit: Ideal candidates for this study are children aged 4 months to 10 years with a confirmed diagnosis of SPG50 due to pathogenic variants in the AP4M1 gene.

Not a fit: Patients with other forms of spastic paraplegia or those unable to undergo lumbar puncture may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could significantly improve the quality of life for children suffering from SPG50 by addressing the underlying genetic cause of the disease.

How similar studies have performed: While gene therapy for rare genetic disorders is an emerging field, this specific approach for SPG50 is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Age 4 months-10 years old
2. Confirmed diagnosis of SPG50 disease by:

   1. Genomic DNA mutation analysis demonstrating homozygous or compound heterozygous, confirmed pathogenic variants in the AP4M1 gene
   2. Clinical history or examination features consistent with SPG50 and that include neurologic dysfunction
3. Parent/legal guardian willing to provide written informed consent for their child prior to participation in the study
4. Subject able to comply with all protocol requirements and procedures
5. Ability to stand for more than 5 seconds OR
6. Ability to take 5 steps independently or with a walker OR
7. Modified Ashworth Scale score 2 or below (Ankles).

Exclusion Criteria:

1. Inability to participate in study procedures (as determined by the site investigator)
2. Presence of a concomitant medical condition that precludes lumbar puncture (LP) or use of anesthetics
3. History of bleeding disorder or any other medical condition or circumstance in which lumbar puncture is contraindicated according to local institutional policy
4. Inability to be safely sedated in the opinion of the clinical anesthesiologist
5. Active infection, at the time of dosing, based on clinical observations
6. Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer
7. Inability of the patient to undergo MRI according to local institutional policy
8. Inability of the patient to undergo any other procedure required in this study
9. 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
10. 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.
11. Enrollment and participation in another interventional clinical trial
12. Contraindication to MELPIDA or any of its ingredients
13. Contraindication to any of the immune suppression medications used in this study
14. 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.

Where this trial is running

Dallas, Texas

• Children's Medical Center Dallas — Dallas, Texas, United States (RECRUITING)

Study contacts

• Principal investigator: Susan T. Iannaccone, MD, FAAN — University of Texas Southwestern Medical Center
• Study coordinator: Sydney Cooper, MSc

Conditions: Spasticity, Muscle, Microcephaly, Intellectual Deficiency, Growth Retardation, SPG50, Spastic Paraplegia