RECRUITING

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

Conditions

Spasticity, Muscle Microcephaly Intellectual Deficiency Growth Retardation SPG50 Spastic Paraplegia

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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.

Quick Facts

Study Start:2023-02-15

Study Completion:2030-10-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05518188

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:4 Months to 10 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD

Inclusion Criteria	Exclusion 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).	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.

Inclusion Criteria

Exclusion 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).

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.

Contacts and Locations

Study Contact

Sydney Cooper, MSc

CONTACT

214-250-0174

Sydney.Cooper@UTSouthwestern.edu

Principal Investigator

Susan T. Iannaccone, MD, FAAN

PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Study Locations (Sites)

Children's Medical Center Dallas

Dallas, Texas, 75235

United States

Collaborators and Investigators

Sponsor: Elpida Therapeutics SPC

Susan T. Iannaccone, MD, FAAN, PRINCIPAL_INVESTIGATOR, UT Southwestern Medical Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-02-15

Study Completion Date2030-10-01

Study Record Updates

Study Start Date2023-02-15

Study Completion Date2030-10-01

Terms related to this study

Additional Relevant MeSH Terms

Spasticity, Muscle
Microcephaly
Intellectual Deficiency
Growth Retardation
SPG50
Spastic Paraplegia