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CompletedNCT02725580Updated Oct 24, 2025Results posted

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

A Phase 1/2 interventional study of AT-GTX-501 in Variant Late-Infantile Neuronal Ceroid Lipofuscinosis, sponsored by Emily de los Reyes. Completed at 1 site in United States. Open to participants aged 1 Year and older. Per ClinicalTrials.gov, last updated 2025-10-24.

Sponsored by Emily de los Reyes · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
13
Allocation
Not applicable
Ages
1 Year and older
Sex
All
01

Study 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 participants with mild to moderate variant late infantile neuronal ceroid lipofuscinosis associated with mutation(s) in the CLN6 gene (vLINCL6 disease).

Read the 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. Participants 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.

02

Conditions studied

  • Variant Late-Infantile Neuronal Ceroid Lipofuscinosis

Keywords

  • Neuronal ceroid lipofuscinosis (NCL)
  • CLN6
  • vLINCL6
  • Gene Transfer
  • CLN6 Batten Disease
  • Batten Disease
03

Who can participate

Ages eligible
1 Year and older
Sexes eligible
All
Accepts healthy volunteers
No

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 scale at screening
  3. Aged ≥ 1 year
  4. Ambulatory or able to walk with assistance

Exclusion criteria

Exclusion Criteria:

  1. Presence of another inherited neurologic disease, for example, other forms of Batten disease (also known as NCL) or seizures unrelated to vLINCL6 disease (participants with febrile seizures may be eligible at discretion of the investigator.)
  2. Presence of another neurological illness that may have caused cognitive decline (for example, trauma, meningitis, hemorrhage) before screening
  3. Active viral infection (includes human immunodeficiency virus 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 (for example, spina bifida, meningitis, or clotting abnormalities)
  6. Contraindications for magnetic resonance imaging scans (for example, 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 (for example, 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 enzyme-linked immunosorbent assay
  11. Has a medical condition or extenuating circumstance that, in the opinion of the investigator, might compromise the participant's ability to comply with the protocol-required testing or procedures or compromise the participant's wellbeing, safety, or clinical interpretability
  12. Pregnancy any time during the study (Any female participant 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 > 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 participant'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.
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
13 participants (actual)

Study arms

  • Experimental
    Open Label

    Participants with diagnosis of vLINCL6 Batten disease will receive a single intrathecal injection of AT-GTX-501 into the lumbar spinal cord region.

    Genetic: AT-GTX-501

Interventions

  • GeneticAT-GTX-501

    CLN6 Gene delivered by Self-Complementary AAV9

    Also known as: scAAV9.CB.CLN6

05

What researchers measure

Primary outcomes

  1. Incidence And Severity Of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device (medicinal products). An SAE is an AE occurring during any study phase (for example, baseline, treatment, or follow-up) that fulfils any of the following: results in death; is life-threatening; requires inpatient hospitalization or prolongs existing hospitalization; results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; and results in a congenital anomaly/birth defect. All AEs that occurred after receipt of AT-GTX-501 are classified as TEAEs. A summary of serious and all other non-SAEs, regardless of causality, is located in the Reported Adverse Events module.

    Time frame: Up to 38.7 months

Secondary outcomes

  1. Change From Baseline In Hamburg Motor And Language Scores at Month 24

    The Hamburg scale is an established tool to capture the rate of decline or regression. This tool was developed to document by rating motor, language, and visual functions in participants with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) Batten disease, and to collect their incidence of grand mal seizures. To assess disease progression and evaluate efficacy, the combined score of the motor and language domains of the Hamburg scale was used. Each domain was scored from 0 (no function) to 3 (normal function) for a maximal possible score of 6 for the combined score, referred to as the Hamburg Motor + Language aggregate score. The rate of decline in Hamburg Motor + Language aggregate, Motor, and Language scores were summarized using descriptive statistics.

    Time frame: Screening (Day -30 up to -2) up to Month 24

  2. Change From Baseline In Unified Batten Disease Rating Scale (UBDRS) Scores At Month 24

    The Unified Batten Disease Rating Scale (UBDRS) was developed to monitor rate of progression. This scale includes assessment of extrapyramidal movement abnormalities and seizures, behavioral and capability assessments (Actual Vision), as well as history relevant to variant late infantile neuronal ceroid lipofuscinosis associated with mutation(s) in the CLN6 gene (vLINCL6) disease and scoring for global impression of symptom severity. A higher UBDRS subscale score indicated greater physical impairment, with zero indicating a better outcome. Subscales included Physical Assessment (range 0-84), Seizure Assessment (range 0-54), Behavioral Assessment (range 0-55) and Capability Assessment of Actual Vision and Normal Vision (range 0-14). A positive change from baseline score indicates increased impairment and a negative score indicates decreased impairment.

    Time frame: Screening (Day -30 up to -2) and Day 30 up to Month 24

  3. Change From Baseline In Mullen (Age-Equivalent) Scales Of Early Learning At Month 24

    The Mullen Scales of Early Learning were utilized to assess cognitive and motor ability in 4 areas (visual reception, fine motor, expressive language, and receptive language) in infants and children. Raw scores range from 0-50 for visual reception, 0-49 for fine motor, 0-50 for expressive language, and 0-48 for receptive language. Lower scores from baseline indicated increased developmental delay and higher scores from baseline indicated decreased developmental delay. A positive change from baseline score indicates decreased developmental delay and a negative score indicates increased developmental delay.

    Time frame: Screening (Day -30 up to -2) and Month 24

  4. Change From Baseline In Preschool Language Scales-5th Edition (PLS-5) (Age-Equivalent) At Month 24

    The Preschool Language Scales-5th Edition (PLS-5) (Age-Equivalent) was a comprehensive developmental language assessment. Standard scores from each domain (auditory comprehension, expressive communication, and total language) range from 50-150. Standard scores between 85 and 115 are considered to be within normal limits. Total scores are the sum of standard scores for auditory comprehension and expressive communication, which is then converted to a total standard score using PLS-5 Appendix B. Age-equivalent scores in each area were summarized by study visit with descriptive statistics. Higher scores represent better language development and lower scores reflect a possible language delay or disorder. A positive change from baseline score indicates better language development.

    Time frame: Screening (Day -30 up to -2) and Month 24

  5. Change From Baseline In Development Profile-3 At Month 24

    The Development Profile-3 was used to screen for developmental delays in 5 areas (physical \[score range 0-35\], adaptive behavior \[0-37\], social-emotional \[0-36\], cognitive \[0-38\], communication \[0-34\]), where lower scores indicated increased developmental delay. The General Development Score is obtained by adding the sum of standard scores for the five scales together (range 0-180). Standard Score ranges are \<70 Delayed, 70-84 Below Average, 85-115 Average, 116-130 Above Average, and \>130 Well Above Average. A positive change from baseline score indicates decreased developmental delay and a negative score indicates increased developmental delay.

    Time frame: Screening (Day -30 up to -2) and Month 24

06

Results

Posted Mar 8, 2023
Limitations and caveats
Due to the nature of the disease, coupled with the impact of a global pandemic, adjustments were made to the study design to prioritize collection of primary safety and efficacy data, including development assessments through remote telehealth visits. The results of this data are presented in this posting.

Participant flow

Participant flow — Overall Study
MilestoneAT-GTX-501
Started13
Received at least 1 dose of study drug13
Completed13
Not completed0

Outcome measures

PrimaryIncidence And Severity Of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device (medicinal products). An SAE is an AE occurring during any study phase (for example, baseline, treatment, or follow-up) that fulfils any of the following: results in death; is life-threatening; requires inpatient hospitalization or prolongs existing hospitalization; results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; and results in a congenital anomaly/birth defect. All AEs that occurred after receipt of AT-GTX-501 are classified as TEAEs. A summary of serious and all other non-SAEs, regardless of causality, is located in the Reported Adverse Events module.

Time frame:
Up to 38.7 months
Reported as:
Count of participants · Participants
Incidence And Severity Of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
ParticipantsAT-GTX-501
Participants with TEAEs13
Participants with Grade 3 (Severe) or 4 (Life-threatening) TEAEs5
Participants with SAEs7
Participants with TESAEs7
SecondaryChange From Baseline In Hamburg Motor And Language Scores at Month 24

The Hamburg scale is an established tool to capture the rate of decline or regression. This tool was developed to document by rating motor, language, and visual functions in participants with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) Batten disease, and to collect their incidence of grand mal seizures. To assess disease progression and evaluate efficacy, the combined score of the motor and language domains of the Hamburg scale was used. Each domain was scored from 0 (no function) to 3 (normal function) for a maximal possible score of 6 for the combined score, referred to as the Hamburg Motor + Language aggregate score. The rate of decline in Hamburg Motor + Language aggregate, Motor, and Language scores were summarized using descriptive statistics.

Time frame:
Screening (Day -30 up to -2) up to Month 24
Reported as:
Mean · score on a scale
Change From Baseline In Hamburg Motor And Language Scores at Month 24
score on a scaleAT-GTX-501
Motor0.71 ± 0.576
Language0.32 ± 0.745
Motor + Language Aggregate1.03 ± 1.138
SecondaryChange From Baseline In Unified Batten Disease Rating Scale (UBDRS) Scores At Month 24

The Unified Batten Disease Rating Scale (UBDRS) was developed to monitor rate of progression. This scale includes assessment of extrapyramidal movement abnormalities and seizures, behavioral and capability assessments (Actual Vision), as well as history relevant to variant late infantile neuronal ceroid lipofuscinosis associated with mutation(s) in the CLN6 gene (vLINCL6) disease and scoring for global impression of symptom severity. A higher UBDRS subscale score indicated greater physical impairment, with zero indicating a better outcome. Subscales included Physical Assessment (range 0-84), Seizure Assessment (range 0-54), Behavioral Assessment (range 0-55) and Capability Assessment of Actual Vision and Normal Vision (range 0-14). A positive change from baseline score indicates increased impairment and a negative score indicates decreased impairment.

Time frame:
Screening (Day -30 up to -2) and Day 30 up to Month 24
Reported as:
Mean · score on a scale
Change From Baseline In Unified Batten Disease Rating Scale (UBDRS) Scores At Month 24
score on a scaleAT-GTX-501
Physical Assessment16.77 ± 13.953
Seizure Assessment2.2 ± 4.49
Behavioral Assessment-0.4 ± 3.95
Capability Assuming Normal Vision-1.2 ± 3.96
Capability with Actual Vision-0.8 ± 4.22
SecondaryChange From Baseline In Mullen (Age-Equivalent) Scales Of Early Learning At Month 24

The Mullen Scales of Early Learning were utilized to assess cognitive and motor ability in 4 areas (visual reception, fine motor, expressive language, and receptive language) in infants and children. Raw scores range from 0-50 for visual reception, 0-49 for fine motor, 0-50 for expressive language, and 0-48 for receptive language. Lower scores from baseline indicated increased developmental delay and higher scores from baseline indicated decreased developmental delay. A positive change from baseline score indicates decreased developmental delay and a negative score indicates increased developmental delay.

Time frame:
Screening (Day -30 up to -2) and Month 24
Reported as:
Mean · score on a scale
Change From Baseline In Mullen (Age-Equivalent) Scales Of Early Learning At Month 24
score on a scaleAT-GTX-501
Visual Reception-9.8 ± 10.94
Fine Motor-6.8 ± 6.27
Receptive Language-9.9 ± 10.69
Expressive Language-7.2 ± 10.74
SecondaryChange From Baseline In Preschool Language Scales-5th Edition (PLS-5) (Age-Equivalent) At Month 24

The Preschool Language Scales-5th Edition (PLS-5) (Age-Equivalent) was a comprehensive developmental language assessment. Standard scores from each domain (auditory comprehension, expressive communication, and total language) range from 50-150. Standard scores between 85 and 115 are considered to be within normal limits. Total scores are the sum of standard scores for auditory comprehension and expressive communication, which is then converted to a total standard score using PLS-5 Appendix B. Age-equivalent scores in each area were summarized by study visit with descriptive statistics. Higher scores represent better language development and lower scores reflect a possible language delay or disorder. A positive change from baseline score indicates better language development.

Time frame:
Screening (Day -30 up to -2) and Month 24
Reported as:
Mean · score on a scale
Change From Baseline In Preschool Language Scales-5th Edition (PLS-5) (Age-Equivalent) At Month 24
score on a scaleAT-GTX-501
Auditory Comprehension-7.8 ± 12.02
Expressive Communication-3.9 ± 10.21
Total Language Score-5.7 ± 11.61
SecondaryChange From Baseline In Development Profile-3 At Month 24

The Development Profile-3 was used to screen for developmental delays in 5 areas (physical \[score range 0-35\], adaptive behavior \[0-37\], social-emotional \[0-36\], cognitive \[0-38\], communication \[0-34\]), where lower scores indicated increased developmental delay. The General Development Score is obtained by adding the sum of standard scores for the five scales together (range 0-180). Standard Score ranges are \<70 Delayed, 70-84 Below Average, 85-115 Average, 116-130 Above Average, and \>130 Well Above Average. A positive change from baseline score indicates decreased developmental delay and a negative score indicates increased developmental delay.

Time frame:
Screening (Day -30 up to -2) and Month 24
Reported as:
Mean · score on a scale
Change From Baseline In Development Profile-3 At Month 24
score on a scaleAT-GTX-501
Physical-18.0 ± NA
Adaptive Behavior-42.0 ± NA
Social-Emotional-38.5 ± 14.85
Cognitive-31.0 ± 11.31
Communication-19.5 ± 17.68
General Development-32.0 ± NA

Adverse events

Collected over Up to 38.7 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
AT-GTX-5010/13 (0%)7/13 (53.8%)13/13 (100%)
Most frequent serious events
Showing 10 of 13
Most frequent serious events
EventAT-GTX-501
VomitingGastrointestinal disorders2/13
PyrexiaGeneral disorders2/13
DehydrationMetabolism and nutrition disorders2/13
Abdominal painGastrointestinal disorders1/13
Abdominal pain upperGastrointestinal disorders1/13
HypersensitivityImmune system disorders1/13
Epstein-Barr virus infectionInfections and infestations1/13
Gastroenteritis viralInfections and infestations1/13
SynovitisMusculoskeletal and connective tissue disorders1/13
Myoclonic epilepsyNervous system disorders1/13
Most frequent other events
Showing 10 of 98
Most frequent other events
EventAT-GTX-501
Upper respiratory tract infectionInfections and infestations9/13
VomitingGastrointestinal disorders5/13
ConstipationGastrointestinal disorders4/13
Viral infectionInfections and infestations4/13
SeizureNervous system disorders4/13
InsomniaPsychiatric disorders4/13
HaematuriaRenal and urinary disorders4/13
DiarrhoeaGastrointestinal disorders3/13
Back painMusculoskeletal and connective tissue disorders3/13
Myoclonic epilepsyNervous system disorders3/13

Baseline characteristics

Safety population: all participants who were treated with AT-GTX-501.

Age, Continuous
Age, Continuous(months)AT-GTX-501
Mean54.6 ± 17.93
Sex: Female, Male
Sex: Female, Male(Participants)AT-GTX-501
Female7
Male6
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)AT-GTX-501
Hispanic or Latino2
Not Hispanic or Latino11
Unknown or Not Reported0
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)AT-GTX-501
American Indian or Alaska Native0
Asian0
Black or African American1
Native Hawaiian or Other Pacific Islander0
White9
Multiple2
Other1
07

Study locations

1 site
  • Nationwide Children's Hosptial
    Columbus, Ohio 43205, United States
08

References and documents

Study documents

  • Study protocol · May 20, 2020
  • Statistical analysis plan · Mar 2, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT02725580
Lead sponsor
Emily de los Reyes
Responsible party
Emily de los Reyes (Dr. Emily De Los Reyes, Nationwide Children's Hospital) — Sponsor-investigator
First posted
Apr 1, 2016
Start date
May 2016
Primary completion
Oct 2022
Completion
Oct 2024
Results posted
Mar 8, 2023
Last update
Oct 24, 2025

Study contacts

Emily de los Reyes, MD
principal investigator · Nationwide Children's Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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