A Phase IIb, Non-Profit, Open-label Trial for the Intrathecal Administration of AAV9/AP4M1 for Hereditary Spastic Paraplegia Type 50 (SPG50)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Rigshospitalet, Elpida Therapeutics SPC

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2026-06-23

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Elpida Therapeutics SPC (Provider) · Sammen for August (trial)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective of this study is to demonstrate the efficacy of a single lumbar intrathecal ad-ministration of AAV9/AP4M1 in subjects with SPG50

Secondary objectives 1

1. The secondary objective of this study is to evaluate the effect of a single lumbar intrathecal admin-istration of AAV9/AP4M1 in subjects with SPG50 on: • Disease modification, • Safety and tolerability.

Conditions and MedDRA coding

Heriditary spastic paraplegia (SPG50)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. • Male or female subjects aged ≥ 6 years at the time of screen-ing.
2. • Molecularly confirmed diagnosis of SPG50, defined as bi-allelic pathogenic variants in the AP4M1 gene, as deter-mined 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 histo-ry and physical examination
5. • Stable dosing of concomitant medications – including anti-spasticity medications, anti-epileptic medications, behav-ioral 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 in-formed 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 the 30 days post treatment, subjects must reside within 200 km of the clinical site.

Exclusion criteria 18

1. • Inability to participate in the clinical evaluation, as deter-mined by the Principal Investigators.
2. • Clinically significant abnormal laboratory values (i.e., hemo-globin < 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 circum-stance in which lumbar puncture is contraindicated, per lo-cal institutional policy.
5. • Documented cardiomyopathy or significant congenital heart abnormalities.
6. • Inability to undergo sedation safely, in the opinion of the clin-ical anesthesiologist.
7. • History of severe or life-threatening allergic reactions to sirolimus, tacrolimus, corticosteroids, or gadolinium.
8. • Concomitant illness or requirement for chronic drug treat-ment that, in the opinion of the Principal Investigator, poses undue risk during gene transfer.
9. • Concomitant chronic drug treatment that would cause clini-cally significant interactions with study immunosuppressive agents.
10. • Any condition that would contraindicate MRI, per local insti-tutional 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 scien-tific rigor or interpretation of study results.
13. • Laboratory abnormalities deemed potentially clinically sig-nificant.
14. • Recent or planned elective surgical procedures that could confound the scientific rigor or interpretation of study re-sults.
15. • Failure to obtain valid informed consent.
16. • Reason to believe that the subject or the parents of the sub-ject 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 clini-cal 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 Mile-stones derived from the Gross Motor Function Measure (GMFM)-88 from baseline at W156.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rigshospitalet

Sponsor organisation

Rigshospitalet

Address

Blegdamsvej 9

City

Copenhagen Oe

Postcode

2100

Country

Denmark

Scientific contact point

Organisation

Rigshospitalet

Contact name

Alfred Peter Born

Public contact point

Organisation

Rigshospitalet

Contact name

Alfred Peter Born

Third parties 5

Elpida Therapeutics SPC

Sponsor organisation

Elpida Therapeutics SPC

Address

16501 Ventura Boulevard Suite 400

City

Encino

Postcode

91436-2067

Country

United States

Scientific contact point

Organisation

Elpida Therapeutics SPC

Contact name

Rachel Thomas

Public contact point

Organisation

Elpida Therapeutics SPC

Contact name

Rachel Thomas

Sponsor responsibilities

Article 77 compliance

Rigshospitalet

Contact point sponsor

Rigshospitalet

Article 77 implementation

Rigshospitalet

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 18 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