Clincosm LogoSign in Get a demo

A First-in-Human Study in Pediatric Patients With Ocular CLN2 Disease

Sponsor
REGENXBIO Inc. (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05791864
Collaborator
(none)
16
Enrollment
1
Location
5
Arms
30.4
Anticipated Duration (Months)
0.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a first-in-human, open-label, single ascending dose study of RGX-381 for the treatment of ocular manifestations of CLN2 (Batten disease).

Condition or Disease Intervention/Treatment Phase
  • Genetic: RGX-381
 Phase 1/Phase 2

Detailed Description

This is a first-in-human, open-label, single ascending dose study of RGX-381, a gene therapy for the potential treatment of ocular manifestations of CLN2 (Batten disease). RGX-381 is being studied as a potential treatment of ocular manifestations of neuronal ceroid lipofuscinosis type 2 (CLN2) disease. Children with CLN2 disease have a non-working gene (set of instructions) that causes an enzyme called tripeptidyl-peptidase 1 (TPP1) to be missing or not working in their bodies. Without enough TPP1, cells cannot break down certain molecules in the body, so these storage materials build up and start to hurt the body, particularly the central nervous system (the brain and spine) and retinal cells (eyes); cause seizures; and change how children with CLN2 disease grow, act, think, and see. After eligibility has been confirmed, the participant's eyes will be assigned as the treated eye and the control fellow eye. Due to the symmetry in the clinical course of CLN2 ocular disease, untreated fellow eyes will serve as controls for the contralateral, treated eyes.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
16 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
Single (Outcomes Assessor)
Masking Description:
In order to minimize the effect of potential bias, wherever possible, endpoints will be measured or interpreted by masked evaluators.
Primary Purpose:
Treatment
Official Title:
A First-in-Human, Open-Label, Dose-Escalation Study to Evaluate the Safety and Tolerability of Gene Therapy With RGX 381 for the Ocular Manifestations Associated With Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) Disease
Anticipated Study Start Date :
Apr 3, 2023
Anticipated Primary Completion Date :
May 20, 2025
Anticipated Study Completion Date :
Oct 15, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cohort 1: Main Treatment Arm

2×10^10 GC/eye

Genetic: RGX-381
One time subretinal dose in study eye
Other Names:
  • Gene Therapy (AAV9.CB7.hCLN2)

    		•
    Experimental: Cohort 2: Main Treatment Arm

    6×10^10 GC/eye

    Genetic: RGX-381
    One time subretinal dose in study eye
    Other Names:
  • Gene Therapy (AAV9.CB7.hCLN2)

    		•
    Experimental: Expansion Cohort: Early Treatment Arm

    Dose level to be determined based on Independent Data Monitoring Committee review.

    Genetic: RGX-381
    One time subretinal dose in study eye
    Other Names:
  • Gene Therapy (AAV9.CB7.hCLN2)

    		•
    Experimental: Expansion Cohort: Main Treatment Arm

    Dose level to be determined based on Independent Data Monitoring Committee review.

    Genetic: RGX-381
    One time subretinal dose in study eye
    Other Names:
  • Gene Therapy (AAV9.CB7.hCLN2)

    		•
    Experimental: Expansion Cohort: Late Treatment Arm

    Dose level to be determined based on Independent Data Monitoring Committee review.

    Genetic: RGX-381
    One time subretinal dose in study eye
    Other Names:
  • Gene Therapy (AAV9.CB7.hCLN2)

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Safety: Number of participants with ocular and overall AE and SAEs [360 days]

      To evaluate the safety and tolerability of RGX-381 through Day 360 in participants with CLN2 disease

    Secondary Outcome Measures

    1. Efficacy: Change in SD-OCT measures and appearance of retinal layers over-time [360 days]

      To assess retinal structural changes with SD-OCT

    2. Pharmacodynamics: TPP1 Expression [360 days]

      To assess TPP1 expression as measured in Aqueous Humor

    3. Vector Shedding [360 days]

      As detected by qualitative polymerase chain reaction (qPCR) in urine and tears

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Months to 144 Months
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    A participant is eligible to be included in the study only if all of the following criteria apply:

    • Has biallelic CLN2 mutations.

    • Has decreased leukocyte TPP1 activity.

    • Has clinical signs or symptoms consistent with CLN2 disease (eg, developmental delay, developmental decline, seizure, vision loss, or other signs/symptoms) OR an older sibling with confirmed CLN2 diagnosis.

    • Is currently receiving biweekly ICV ERT treatment with cerliponase alfa.

    • Meets baseline disease condition according to age, retinal thickness, and visual acuity criteria ( varies by treatment arm)

    Exclusion Criteria:
    Participants are excluded from the study if any of the following criteria apply:

    • Any ocular or systemic condition that, in the opinion of the investigator, would prevent administration and evaluation of the investigational product or interpretation of participant safety or study results (eg, significant lens or corneal opacities, glaucoma, amblyopia, gross retinal anatomical abnormality, etc).

    • Prior participation in a gene therapy study

    • Prior participation in another ocular clinical trial, except an intravitreal cerliponase alfa trial where a subject has received a maximum of 3 injections

    • Prior intraocular injections of any kind, except an intravitreal cerliponase alfa trial where a subject has received a maximum of 3 injections

    • Participation in a clinical study with an investigational drug in the past six months prior to screening, except for intracerebroventricular cerliponase alfa.

    • Ocular surgery within the prior six months.

    • Known sensitivity or contraindications to medications planned for use in the peri-operative period.

    • Contraindications to systemic immunosuppression

    • Any other condition that would not allow the potential participant to complete follow-up examinations during the study or, in the opinion of the investigator, makes the potential participant unsuitable for the study

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Greater Ormond Street Hospital London United Kingdom Wc1N 3JH

    Sponsors and Collaborators

    • REGENXBIO Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    REGENXBIO Inc.
    ClinicalTrials.gov Identifier:
    NCT05791864
    Other Study ID Numbers:
    • RGX-381-1102
    • 2021-000173-92
    First Posted:
    Mar 30, 2023
    Last Update Posted:
    Mar 30, 2023
    Last Verified:
    Mar 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by REGENXBIO Inc.
    CLN2
    Batten Disease
    Additional relevant MeSH terms:
    Neuronal Ceroid-Lipofuscinoses

    Study Results

    No Results Posted as of Mar 30, 2023