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

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ClinicalTrials.gov Identifier: NCT05791864
Recruitment Status : Active, not recruiting
First Posted : March 30, 2023
Last Update Posted : November 30, 2023
Sponsor:
Information provided by (Responsible Party):
REGENXBIO Inc.

Study Description
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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
Neuronal Ceroid Lipofuscinosis Type 2 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
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Study Type : Interventional  (Clinical Trial)
Estimated 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
Actual Study Start Date : May 17, 2023
Estimated Primary Completion Date : May 20, 2025
Estimated Study Completion Date : October 15, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Gene Therapy (AAV9.CB7.hCLN2)


Outcome Measures
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Primary Outcome Measures :
  1. Safety: Number of participants with ocular and overall AE and SAEs [ Time Frame: 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 [ Time Frame: 360 days ]
    To assess retinal structural changes with SD-OCT

  2. Pharmacodynamics: TPP1 Expression [ Time Frame: 360 days ]
    To assess TPP1 expression as measured in Aqueous Humor

  3. Vector Shedding [ Time Frame: 360 days ]
    As detected by qualitative polymerase chain reaction (qPCR) in urine and tears


Eligibility Criteria
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Ages Eligible for Study:   12 Months to 144 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05791864


Locations
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United Kingdom
Greater Ormond Street Hospital
London, United Kingdom, Wc1N 3JH
Sponsors and Collaborators
REGENXBIO Inc.
More Information
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Responsible Party: REGENXBIO Inc.
ClinicalTrials.gov Identifier: NCT05791864    
Other Study ID Numbers: RGX-381-1102
2021-000173-92 ( EudraCT Number )
First Posted: March 30, 2023    Key Record Dates
Last Update Posted: November 30, 2023
Last Verified: June 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Neuronal Ceroid-Lipofuscinoses
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Nervous System Diseases
Genetic Diseases, Inborn
 Lipidoses
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Lipid Metabolism Disorders
Metabolic Diseases