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Gene Therapy for Children With CLN3 Batten Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03770572
Recruitment Status : Active, not recruiting
First Posted : December 10, 2018
Last Update Posted : July 20, 2022
Information provided by (Responsible Party):
Amicus Therapeutics

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
CLN3 Batten Disease Genetic: AT-GTX-502 Phase 1 Phase 2

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 second and third years. 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 7 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:

Single Treatment Group (AAV9-CLN3) - 2 Cohort Assignment (Low-dose, High-dose)

Dose escalation in this study will begin with low-dose, determined to be the minimal efficacious dose as determined in non-clinical studies. Dose escalation to a high-dose (2x the minimally effective dose (MED) as evaluated in Cohort 1) will proceed as part of Cohort 2 of the study upon demonstration of safety of the low-dose in Cohort 1 of the study.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/IIa Gene Transfer Clinical Trial for Juvenile Neuronal Ceroid Lipofuscinosis, Delivering the CLN3 Gene by Self-Complementary AAV9
Actual Study Start Date : November 13, 2018
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : September 2023

Arm Intervention/treatment
Experimental: Open-label, single-dose, dose-escalation study of AT-GTX-502

Cohort 1: AT-GTX-502 Low-Dose

Cohort 2: AT-GTX-502 High-Dose

Genetic: AT-GTX-502
Subjects with diagnosis of CLN3 Batten disease will receive a single dose of AT-GTX-502 at low dose or high dose.

Primary Outcome Measures :
  1. 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.

  2. 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.

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 10 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

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): NCT03770572

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United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43201
Sponsors and Collaborators
Amicus Therapeutics
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Study Director: Clinical Research Amicus Therapeutics

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Responsible Party: Amicus Therapeutics
ClinicalTrials.gov Identifier: NCT03770572    
Other Study ID Numbers: AT-GTX-502-01
First Posted: December 10, 2018    Key Record Dates
Last Update Posted: July 20, 2022
Last Verified: July 2022
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
Keywords provided by Amicus Therapeutics:
Neuronal ceroid lipofuscinosis
Gene Transfer
Additional relevant MeSH terms:
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Neuronal Ceroid-Lipofuscinoses
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Lipid Metabolism Disorders
Metabolic Diseases