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Gene Transfer Study of AAV9-CLN3 for Treatment NCL Type 3

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03770572
Recruitment Status : Recruiting
First Posted : December 10, 2018
Last Update Posted : December 17, 2018
Amicus Therapeutics
Information provided by (Responsible Party):
Emily de los Reyes, Nationwide Children's Hospital

Brief Summary:
Open-label, single dose, dose-escalation clinical trial AAV9-CLN3 via intrathecal injection in NCL type 3 subjects

Condition or disease Intervention/treatment Phase
CLN3-Related Neuronal Ceroid-Lipofuscinosis Biological: AAV9-CLN3 Phase 1 Phase 2

Detailed Description:
Open-label, dose escalation clinical trial including two study cohorts of NCL type 3 (CLN3 disease) subjects. Cohort 1 will evaluate a one-time low-dose via intrathecal injection of AAV-CLN3 and Cohort 2 evaluating a one-time high-dose intrathecal injection of AAV-CLN3 vector construct containing human CLN3 transgene. This study will be monitored by a Data Safety Monitoring Committee (DSMB). Cohort 2 subjects (high-dose) will proceed with treatment after evaluation by the DSMB of AAV9-CLN3 in Cohort 1 (low-dose) subjects. Both subject cohorts will participate in the ongoing study for a period of at least three years. Periodic assessments including clinical, laboratory, cognitive and medical imaging assessment will be performed. Participating subjects will be asked to participate in a separate long term follow-up study for a total duration of approximately 5 years from the time of completion of the active phase of the current study.

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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 : December 2022
Estimated Study Completion Date : December 2022

Arm Intervention/treatment
Experimental: Cohort 1

AAV-CLN3 Low-Dose

(Minimally Effective Dose (MED)

Biological: AAV9-CLN3
A single dose of AAV9-CLN3 will be delivered via an intrathecal injection.

Experimental: Cohort 2

AAV-CLN3 High-Dose

(Escalated Dose, 2x, Minimally Effective Dose, MED)

Biological: AAV9-CLN3
A single dose of AAV9-CLN3 will be delivered via an intrathecal injection.

Primary Outcome Measures :
  1. Safety: Incidence of any one Grade III or higher, unanticipated, treatment-related toxicity [ Time Frame: 36 Months ]
  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 disability subscale is a 21 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 84. The higher the score, the more severe the disability and worse the outcome. The items are summed up to obtain a total score.

Secondary Outcome Measures :
  1. QOL: Change in Quality of Life (QOL) as determined using the Pediatric Quality of Life (PedsQL™) scale. 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. [ Time Frame: 36 months ]
  2. Seizures: Change is seizure subscore as determined using Seizure subscale of the UBDRS scale. The UBDRS seizure subscale is used to assess seizure history, type, frequency, duration, and frequency of seizure-related injury. [ Time Frame: 36 months ]
  3. Global impression: Change in disease severity using the UBDRS clinical global impression (CGI) subscale. The clinical global impression subscale includes assessment of motor, seizure, behavioral and functional measures in NCL subjects. [ Time Frame: 36 months ]

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:

  • CLN3 diagnosis, confirmed by the presence of a mutation in the CLN3 gene as determined by gene sequencing from a laboratory certified by the Clinical Laboratory Improvement Act/Amendment (CLIA) or an equivalent organization.
  • Age ≥3 years through 10 years of age
  • UBDRS physical impairment score of ≤7
  • Mobility: Independently walking for a distance of at least 50 feet

Exclusion Criteria:

  • Presence of another neurologic, metabolic or immunologic disease
  • Presence of another neurological illness resulting in cognitive decline
  • Recent generalized motor status epilepticus
  • Prior corneal or intraocular surgery
  • Active viral infection or severe bacterial infection
  • Hepatic laboratory values (ALT) outside of the protocol required range
  • Pre-existing Anti-AAV9 antibody titers above the protocol-required limit
  • Clinically significant abnormal laboratory values as defined in the protocol
  • Prior stem cell or bone marrow or organ transplantation
  • Recent Chemotherapy, radiotherapy or other immunosuppression therapy
  • Current use of cannabinoids and any by-products
  • Contraindications for intrathecal injection procedure
  • Contraindications for MRI scans
  • Recent participation in a clinical trial of an investigational treatment

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 identifier (NCT number): NCT03770572

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Contact: Lisa Moffitt, RN 614-722-2650

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United States, Ohio
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43201
Sponsors and Collaborators
Nationwide Children's Hospital
Amicus Therapeutics
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Principal Investigator: Emily de los Reyes, MD Nationwide Children's Hospital


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Responsible Party: Emily de los Reyes, Professor of Neurology, Nationwide Children's Hospital Identifier: NCT03770572     History of Changes
Other Study ID Numbers: IRB18-00725
First Posted: December 10, 2018    Key Record Dates
Last Update Posted: December 17, 2018
Last Verified: December 2018

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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 Emily de los Reyes, Nationwide Children's Hospital:
Batten Disease (Juvenile Onset)
Spielmeyer-Sjogren disease
Vogt-Spielmeyer disease
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