Gene Therapy for Children With CLN3 Batten Disease

August 25, 2023 updated by: Amicus Therapeutics

Phase I/IIa Gene Transfer Clinical Trial for Juvenile Neuronal Ceroid Lipofuscinosis, Delivering the CLN3 Gene by Self-Complementary AAV9

This is a phase 1/2, open-label, single dose, dose-escalation clinical trial to evaluate the safety and efficacy of AT-GTX-502 (previous NCH Code: scAAV9.P546.CLN3) delivered intrathecally into the lumbar spinal cord region of subjects with CLN3 Batten disease.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a phase 1/2, open-label, single-dose, dose-escalation study of AT-GTX-502 administered intrathecally into the lumbar spinal cord region of pediatric patients with CLN3 Batten disease.

This study consists of a one-time injection of AT-GTX-502 with follow-up visits on Day 7, 14, 21, and 30, followed by every 3 months through 1 year post-dose, and then every 6 months through the fifth year. There are two Cohorts with a low dose and a high dose.

The primary outcome for this clinical study is to evaluate safety. The co-primary objective is to determine the efficacy of AT-GTX-502 as measured by United Batten Disease Rating Scale (UBDRS) physical subscale.

The secondary outcome measures include Pediatric Quality of Life (PedsQL) inventory, seizure subscale of the UBDRS and global impression subscale of the UBDRS.

The exploratory outcome measures include visual impairment assessment, cognitive evaluations, Brain magnetic resonance imaging (MRI), electroencephalogram (EEG), electrocardiogram (ECG) and echocardiogram (ECHO).

For more information about this study, please contact Amicus Therapeutics Patient Advocacy at clinicaltrials@amicusrx.com or +1 609-662-2000.

Study Type

Interventional

Enrollment (Estimated)

7

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 Locations

  • United States
    • Ohio
      • Columbus, Ohio, United States, 43201
        • Nationwide Children's 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

3 years to 10 years (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  1. Diagnosis of CLN3 Batten disease determined by genotype available at screening by a College of American Pathologists/Clinical Laboratory Improvement Amendments (CAP/CLIA)-certified laboratory (or a non-US laboratory with an equivalent national accreditation/certification)
  2. Aged ≥ 3 to < 11 years
  3. UBDRS physical impairment score of ≤ 7
  4. Able to walk independently at least 50 feet

Exclusion Criteria

  1. Presence of another inherited neurologic or metabolic disease, eg, other forms of Batten disease (also known as neuronal ceroid lipofuscinosis; NCL) or seizures unrelated to CLN3 Batten disease (subjects with febrile seizures may be eligible at the discretion of the investigator)
  2. Presence of another neurological illness that may have caused cognitive decline (eg, trauma, meningitis, hemorrhage) before screening
  3. Active viral infection (includes HIV or serology positive for hepatitis B or C)
  4. Subjects with 2 consecutive aminotransaminase liver tests > 3 times the upper limit of normal or > 1.5 times the upper limit of normal if taking valproic acid at Visit 1 (screening/baseline)
  5. Subjects with anti-AAV9 antibody titers > 1:400 as determined by ELISA (enzyme-linked immunosorbent assay) binding immunoassay
  6. Abnormal laboratory values considered clinically significant
  7. Presence of immunologic disease
  8. Has received stem cell or bone marrow transplantation
  9. Has received any form of organ transplant
  10. History of or current chemotherapy, radiotherapy, or other immunosuppression therapy within the past 30 days (corticosteroid treatment may be permitted at the discretion of the investigator)
  11. Current use of cannabinoids and any by-products
  12. Contraindications for intrathecal administration of the product or lumbar puncture (for collection of CSF), such as bleeding disorders or other medical conditions (eg, spina bifida, meningitis, or clotting abnormalities)
  13. Contraindications for MRI scans (eg, cardiac pacemaker, metal fragment or chip in the eye, aneurysm clip in the brain)
  14. Poorly controlled seizures - intractable epilepsy
  15. Episode of generalized motor status epilepticus within 4 weeks before the Gene Transfer visit
  16. History of corneal or intraocular surgery
  17. Severe infection (eg, upper respiratory tract infection, pneumonia, pyelonephritis, or meningitis) within 4 weeks before the Gene Transfer visit (Enrollment may be postponed.)
  18. Has received any investigational medication within 30 days before the infusion of study drug
  19. Has a medical condition or extenuating circumstance that, in the opinion of the investigator, might compromise the subject's ability to comply with the protocol required testing or procedures or compromise the subject's wellbeing, safety, or clinical interpretability
  20. Pregnancy at screening or Day 0. Any female subject judged by the investigator to be of childbearing potential will be tested for pregnancy.
  21. Family does not want to disclose subject's study participation with primary care physician and other medical providers

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: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1: AT-GTX-502 Low-Dose
No more than 5 mL of 6 x 1013 vg AT-GTX-502 administered via intrathecal injection
Genetic: Low dose AT-GTX-502
Subjects with diagnosis of CLN3 Batten disease will receive a single dose of AT-GTX-502 at low dose
Experimental: Cohort 2: AT-GTX-502 High-Dose
No more than 10 mL of 1.2 x 1014 vg of AT-GTX-502 administered via intrathecal injection
Genetic: High dose AT-GTX-502
Subjects with diagnosis of CLN3 Batten disease will receive a single dose of AT-GTX-502 at high dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety evaluation based on the development of dose-limiting toxicity (DLT).
Time Frame: 36 Months
The DLT is defined as any unanticipated AE that is considered related to AT-GTX-502 and is Common Terminology Criteria for Adverse Events Grade 3 or higher.
36 Months
Efficacy: Change in rating as determined using the Unified Batten Disease Rating Scale (UBDRS) rating scale.
Time Frame: 36 months
The UBDRS is a clinical ratings instrument used specifically to assess motor, seizure, behavioral and functional capabilities. The "Physical Assessment" is a 20 item subscale that measures vision, speech, motor strength, gait, abnormal involuntary movements and balance. Each item has a score range of 0 to 4. The minimum score is 0 and the maximum score is 112. The items are summed up to obtain a total score.The higher the score, the more severe the disability and worse the outcome.
36 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
QOL: Change in Quality of Life (QOL) as determined using the Pediatric Quality of Life (PedsQL™) scale.
Time Frame: 36 months
The PedsQL is used to assess physical, emotional, social, and school functioning of pediatric subjects in ranging from 2 years to 18 years of age.
36 months
Seizures: Change is seizure subscore as determined using Seizure subscale of the UBDRS scale.
Time Frame: 36 months
The UBDRS seizure subscale is used to assess seizure history, type, frequency, duration, and frequency of seizure-related injury.
36 months
Global impression: Change in disease severity using the UBDRS clinical global impression (CGI) subscale.
Time Frame: 36 months
The clinical global impression subscale includes assessment of motor, seizure, behavioral and cognitive function in NCL subjects.
36 months

Collaborators and Investigators

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

Sponsor

Amicus Therapeutics

Investigators

  • Study Director: Clinical Research, Amicus Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

November 13, 2018

Primary Completion (Estimated)

September 30, 2024

Study Completion (Estimated)

September 30, 2024

Study Registration Dates

First Submitted

December 7, 2018

First Submitted That Met QC Criteria

December 7, 2018

First Posted (Actual)

December 10, 2018

Study Record Updates

Last Update Posted (Actual)

August 29, 2023

Last Update Submitted That Met QC Criteria

August 25, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AT-GTX-502-01

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

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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