Gene Therapy for Children With Variant Late Infantile Neuronal Ceroid Lipofuscinosis 6 (vLINCL6) Disease

Phase I/IIa Gene Transfer Clinical Trial for Variant Late Infantile Neuronal Ceroid Lipofuscinosis, Delivering the CLN6 Gene by Self-Complementary AAV9

This is a phase 1/2, open-label, single dose study to evaluate the safety and efficacy of AT-GTX-501 delivered intrathecally into the lumbar spinal cord region of subjects with mild to moderate variant late infantile neuronal ceroid lipofuscinosis associated with mutation(s) in the CLN6 gene (vLINCL6 disease).

Study Overview

• Status: Completed
• Conditions: Variant Late-Infantile Neuronal Ceroid Lipofuscinosis
• Intervention / Treatment: Genetic: AT-GTX-501

Detailed Description

This is an open-label, single-dose study of AT-GTX-501 administered by a single intrathecal injection. Safety and efficacy are evaluated over a 2 year period. The efficacy assessments in this study are to evaluate motor, language, visual, and cognitive function, as well as survival and other outcome measures. Subjects are tested at baseline, receive AT-GTX-501 on Day 0, and return for visits on Days 7, 14, 21, and 30, and then every 3 months until Month 24. Following completion of this study, there is a long-term follow up study in which data will continue to be collected (Study AT-GTX-501-02 / NCT04273243).

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 (Actual): 13
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hosptial

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of vLINCL6 disease determined by genotype available at screening
2. A score of ≥ 3 on the quantitative clinical assessment of the Hamburg motor-language aggregate score at screening
3. Aged ≥ 1 year
4. Ambulatory or able to walk with assistance

Exclusion Criteria:

1. Presence of another inherited neurologic disease, eg, other forms of Batten disease (also known as NCL) or seizures unrelated to vLINCL6 disease (Subjects with febrile seizures may be eligible at 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. Has received stem cell or bone marrow transplantation for vLINCL6 disease
5. Contraindications for intrathecal administration of the product or lumbar puncture, such as bleeding disorders or other medical conditions (eg, spina bifida, meningitis, or clotting abnormalities)
6. Contraindications for magnetic resonance imaging (MRI) scans (eg, cardiac pacemaker, metal fragment or chip in the eye, aneurysm clip in the brain)
7. Episode of generalized motor status epilepticus within 4 weeks before the gene transfer visit (Visit 2)
8. Severe infection (eg, pneumonia, pyelonephritis, or meningitis) within 4 weeks before the gene transfer visit (Visit 2) (Enrollment may be postponed.)
9. Has received any investigational medication within 30 days before the gene transfer visit (Visit 2)
10. Anti-AAV9 antibody titers > 1:50 as determined by ELISA (enzyme-linked immunosorbent assay)
11. 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
12. Pregnancy any time during the study (Any female subject judged by the investigator to be of childbearing potential will be tested for pregnancy.)
13. Abnormal laboratory values from screening considered clinically significant (gamma glutamyl transferase [GGT] > 3 times the upper limit of normal, bilirubin ≥ 3.0 mg/dL, creatinine ≥ 1.8 mg/dL, hemoglobin < 8 or > 18 g/dL, white blood cells > 15,000 per cmm)
14. Family does not want to disclose subject's study participation with primary care physician and other medical providers.
15. History of or current chemotherapy, radiotherapy, or other immunosuppression therapy within the 30 days preceding screening (Corticosteroid treatment may be permitted at the discretion of the investigator.)
16. Has 2 consecutive abnormal liver tests at screening (> 2 times the upper limit of normal). Liver enzymes will be re-tested once if abnormal upon initial screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Open Label; Subjects with diagnosis of vLINCL6 Batten disease will receive a single intrathecal injection into the lumbar spinal cord region of AT-GTX-501.	Genetic: AT-GTX-501; CLN6 Gene delivered by Self-Complementary AAV9; Other Names: scAAV9.CB.CLN6

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).	The DLT is defined as any unanticipated AE that is considered related to AT-GTX-501 and is Common Terminology Criteria for Adverse Events Grade 3 or higher.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamburg Scale	The Hamburg scale is an established tool to capture the rate of decline or regression.	24 months
Unified Batten Disease Rating Scale (UBDRS)	The UBDRS scale was developed to monitor rate of progression. This scale includes assessment of extrapyramidal movement behavior and seizures.	24 months

Collaborators and Investigators

• Sponsor: Amicus Therapeutics

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2016
• Primary Completion (ACTUAL): October 1, 2021
• Study Completion (ACTUAL): October 1, 2021

Study Registration Dates

• First Submitted: March 16, 2016
• First Submitted That Met QC Criteria: March 28, 2016
• First Posted (ESTIMATE): April 1, 2016

Study Record Updates

• Last Update Posted (ACTUAL): January 24, 2022
• Last Update Submitted That Met QC Criteria: January 21, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Batten Disease; Gene Transfer; Neuronal ceroid lipofuscinosis (NCL); CLN6; vLINCL6; CLN6 Batten Disease
• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Neurodegenerative Diseases; Metabolism, Inborn Errors; Heredodegenerative Disorders, Nervous System; Lipid Metabolism Disorders; Lipidoses; Lipid Metabolism, Inborn Errors; Neuronal Ceroid-Lipofuscinoses
• Other Study ID Numbers: AT-GTX-501-01

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