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

November 28, 2023 updated by: REGENXBIO Inc.

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

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).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

16

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United Kingdom
      • London, United Kingdom, Wc1N 3JH
        • Greater Ormond Street Hospital

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.

Eligibility Criteria

Ages Eligible for Study

1 year to 12 years (Child)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Single

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
360 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
360 days
Pharmacodynamics: TPP1 Expression
Time Frame: 360 days
To assess TPP1 expression as measured in Aqueous Humor
360 days
Vector Shedding
Time Frame: 360 days
As detected by qualitative polymerase chain reaction (qPCR) in urine and tears
360 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

REGENXBIO Inc.

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 Major Dates

Study Start (Actual)

May 17, 2023

Primary Completion (Estimated)

May 20, 2025

Study Completion (Estimated)

October 15, 2025

Study Registration Dates

First Submitted

March 17, 2023

First Submitted That Met QC Criteria

March 17, 2023

First Posted (Actual)

March 30, 2023

Study Record Updates

Last Update Posted (Actual)

November 30, 2023

Last Update Submitted That Met QC Criteria

November 28, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RGX-381-1102
  • 2021-000173-92 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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