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Gene Therapy for Children With Variant Late Infantile Neuronal Ceroid Lipofuscinosis 6 (vLINCL6) 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: NCT02725580
Recruitment Status : Active, not recruiting
First Posted : April 1, 2016
Last Update Posted : April 13, 2020
Sponsor:
Information provided by (Responsible Party):
Amicus Therapeutics

Tracking Information
First Submitted Date  ICMJE March 16, 2016
First Posted Date  ICMJE April 1, 2016
Last Update Posted Date April 13, 2020
Actual Study Start Date  ICMJE March 2016
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 26, 2019)
Safety evaluation based on the development of dose-limiting toxicity (DLT). [ Time Frame: 24 months ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 28, 2016)
Development of unacceptable toxicity, defined as the occurrence of any one Grade III or higher, unanticipated, treatment-related toxicity. [ Time Frame: 2 years ]
This is evaluated based on the development of unacceptable toxicity, defined as the occurrence of any one Grade III or higher, unanticipated, treatment-related toxicity.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 9, 2020)
  • Hamburg Scale [ Time Frame: 24 months ]
    The Hamburg scale is an established tool to capture the rate of decline or regression.
  • Unified Batten Disease Rating Scale (UBDRS) [ Time Frame: 24 months ]
    The UBDRS scale was developed to monitor rate of progression. This scale includes assessment of extrapyramidal movement behavior and seizures.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 28, 2016)
  • Magnetic resonance imaging to document progression of the disease. [ Time Frame: Baseline and 24 months ]
    Volumetric imaging to monitor progression of the disease. The investigators will utilize 3D MP-RAGE scan, which is a T1-weighted volumetric scan of the whole brain. Investigators will also include T2 weighted Gradient Echo and diffusion- weighted axial images.
  • Cognitive testing [ Time Frame: Baseline, 6 months, 12 months, 24 months ]
    A retrospective review of cases indicates that language delay and cognitive regression are the earliest manifestations of the disease. The investigators will perform Stanford-Binet for mild, asymptomatic patients.
  • Cognitive testing [ Time Frame: Baseline, 6 months, 12 months, 24 months ]
    A retrospective review of cases indicates that language delay and cognitive regression are the earliest manifestations of the disease. The investigators will perform Mullen scales of Early learning for mild to moderate patients.
  • Language Delay [ Time Frame: Baseline, 6 months, 12 months, 24 months ]
    The investigators will use the Preschool Language scale -5 to monitor language.
  • Visual Failure [ Time Frame: ERG: Baseline, Day 30, 12 months, 24 months OCT: Baseline and 24 months ]
    This will be assessed via electroretinograms (ERG) or ocular computerized tomography.
  • EEG Monitoring [ Time Frame: Baseline, 12 months, 24 months ]
    24 hour EEG long term monitoring to monitor progression of encephalopathy and epileptiform activity.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Gene Therapy for Children With Variant Late Infantile Neuronal Ceroid Lipofuscinosis 6 (vLINCL6) Disease
Official Title  ICMJE Phase I/IIa Gene Transfer Clinical Trial for Variant Late Infantile Neuronal Ceroid Lipofuscinosis, Delivering the CLN6 Gene by Self-Complementary AAV9
Brief Summary 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).
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Variant Late-Infantile Neuronal Ceroid Lipofuscinosis
Intervention  ICMJE Genetic: AT-GTX-501
CLN6 Gene delivered by Self-Complementary AAV9
Other Name: scAAV9.CB.CLN6
Study Arms  ICMJE 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.
Intervention: Genetic: AT-GTX-501
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: August 26, 2019)
13
Original Estimated Enrollment  ICMJE
 (submitted: March 28, 2016)
6
Estimated Study Completion Date  ICMJE November 2021
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02725580
Other Study ID Numbers  ICMJE AT-GTX-501-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Amicus Therapeutics
Study Sponsor  ICMJE Amicus Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Research Amicus Therapeutics
PRS Account Amicus Therapeutics
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP