Administration of a new gene therapy to patients affected by Hereditary Spastic Paraplegia Type 50 (SPG50)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10], Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Decision date (initial)

2026-02-06

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Fondazione Telethon ETS

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To determine the efficacy of a single lumbar intrathecal administration of AAV9/AP4M1 on subjects affected by SPG50

Secondary objectives 2

1. To evaluate the effect of AAV9/AP4M1 on disease modification.
2. To determine the safety and tolerability of AAV9/AP4M1 on subjects affected by SPG50

Conditions and MedDRA coding

Hereditary Spastic Paraplegia Type 50 (SPG50)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Male or female subjects aged ≥ 6 years at the time of screening
2. Molecularly confirmed diagnosis of SPG50, defined as bi-allelic pathogenic variants in the AP4M1 gene, as determined by genomic DNA mutation analysis performed in a CLIA-certified, CE-marked, or equivalent laboratory.
3. Ability to sit independently for three seconds (corresponding to item 24 of the Gross Motor Function Measure GMFM-88).
4. Evidence of neurological dysfunction based on clinical history and physical examination.
5. Stable dosing of concomitant medications – including anti-spasticity medications, anti-epileptic medications, behavioral management medications, sleep medications, and special diets, supplements or nutritional support – for at least three months prior to screening. Subjects with recent changes in medications (<3 months) may be included at the Investigator’s discretion.
6. Availability of two legally competent custodial parents or legally acceptable representatives capable of providing informed consent as approved by the EC. In cases where only one parent has sole legal authority to consent, that parent must be able to actively participate in the consent process.
7. Legally acceptable representatives must be able to attend all scheduled study visits and provide feedback regarding the subject’s symptoms and performance as described in the protocol.
8. Subjects and caregivers must demonstrate ability to travel to the study center. For safety reasons, during the 30 days following treatment, subjects must domiciled at a location that allows them to reach the clinical site within approximately 90 minutes. As a practical reference, this corresponds to a maximum distance of about 150 km from the site.
9. Any sexually active male or female subject must be willing to use highly effective contraceptive methods for the full 5 years of the study and use a barrier method of contraception for 6 months post dosing, regardless of any other contraceptive method or sexual orientation.

Exclusion criteria 18

1. Inability to participate in the clinical evaluation, as determined by the Principal Investigators.
2. Clinically significant abnormal laboratory values (i.e., hemoglobin < 6 or > 20 g/dL; white blood cell > 20,000 per cmm, platelets count < 100,000 per cmm; INR > ULN; GGT, ALT, and AST or total bilirubin > 1.5 × ULN, creatinine ≥ 1.5 mg/dL) prior to gene replacement therapy.
3. Presence of a concomitant medical condition that precludes lumbar puncture or administration of anesthetic agents for procedures under deep sedation.
4. Bleeding disorders or any other medical condition or circumstance in which lumbar puncture is contraindicated, per local institutional policy.
5. Documented cardiomyopathy or significant congenital heart abnormalities.
6. Inability to undergo sedation safely, in the opinion of the clinical anesthesiologist.
7. History of severe or life-threatening allergic reactions to sirolimus, tacrolimus, corticosteroids, or gadolinium.
8. Concomitant illness or requirement for chronic drug treatment that, in the opinion of the Principal Investigator, poses undue risk during gene transfer.
9. Concomitant chronic drug treatment that would cause clinically significant interactions with study immunosuppressive agents.
10. Any condition that would contraindicate MRI, per local institutional policy.
11. Any other condition that would preclude the subject from undergoing required study procedures.
12. Presence of significant AP-4-related CNS impairment or behavioral disturbances that would compromise the scientific rigor or interpretation of study results.
13. Laboratory abnormalities deemed potentially clinically significant.
14. Recent or planned elective surgical procedures that could confound the scientific rigor or interpretation of study results.
15. Failure to obtain valid informed consent.
16. Reason to believe that the subject or the parents of the subject will not comply with the procedures outlined in the study protocol.
17. Receipt of an investigational drug within 30 days prior to screening or plans to receive an investigational drug (other than gene therapy) during the study period.
18. Enrollment and participation in another interventional clinical trial 90 days before the first visit.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in total percent score of the eight Major Motor Milestones derived from the Gross Motor Function Measure (GMFM)-88 from baseline at W156.

Secondary endpoints 12

1. Developmental Milestones – Bayley Scale of Infant and Toddler Develop-ment 3rd Edition (Bayley-3) Cognitive Domain – Change in Total Raw Score from Baseline at W156.
2. Gross and Fine Motor Function (GMFM-88 full scale) – Change in Total Score from Baseline at W156.
3. Disease Severity (Spastic Paraplegia Rating Scale [SPRS]) – Change in Total Score from Baseline at W156.
4. Disease Severity (Clinical Global Impression [CGI-I]) – Change in Physician-assessed CGI-I from Baseline at W156.
5. Differential Ability Scales, 2nd Edition (DAS-II) - Change in Total Score from Baseline at W156.
6. Developmental Milestones (Developmental Quotients [DQs]) – Change in DQs for Gross Motor, Adaptive behavior and Cognitive Scores from Base-line.
7. Axonal Damage (Plasma neurofilament light chain levels [NfL]) – Change in Plasma NfL levels from Baseline.
8. Health Related Quality of Life (The Caregiver Priorities and Child Health In-dex of Life with Disabilities [CPCHILD]) – Change in Total Score from Base-line.
9. Disease Severity (Parent-rated Global Impression [PGI-I]) – Change in Glob-al Impression as assessed by the primary caregiver from Baseline.
10. Axonal Damage (Cerebrospinal fluid [CSF] neurofilament light chain levels [NfL]) – Change in CSF NfL levels from Baseline.
11. Serum and/or Plasma and CSF biomarkers – Change in Biomarker Levels from Baseline.
12. Developmental Milestones (Vineland Adaptive Behavior Scale 3rd Edition [Vineland-3]) – Change in Total Score from Baseline.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii

Sponsor organisation

Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii

Address

Piazza Oms 1

City

Bergamo

Postcode

24127

Country

Italy

Scientific contact point

Organisation

Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii

Contact name

Lorenzo D’Antiga

Public contact point

Organisation

Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii

Contact name

Lorenzo D’Antiga

Third parties 6

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 30 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications