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

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ClinicalTrials.gov Identifier: NCT03770572
Recruitment Status : Recruiting
First Posted : December 10, 2018
Last Update Posted : December 17, 2018
Sponsor:
Collaborator:
Amicus Therapeutics
Information provided by (Responsible Party):
Emily de los Reyes, Nationwide Children's Hospital

Tracking Information
First Submitted Date  ICMJE December 7, 2018
First Posted Date  ICMJE December 10, 2018
Last Update Posted Date December 17, 2018
Actual Study Start Date  ICMJE November 13, 2018
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 13, 2018)
  • Safety: Incidence of any one Grade III or higher, unanticipated, treatment-related toxicity [ Time Frame: 36 Months ]
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 7, 2018)
  • Safety: Incidence of any one Grade III or higher, unanticipated, treatment-related toxicity [ Time Frame: 36 Months ]
  • Efficacy: Change in rating as determined using the Unified Batten Disease Rating Scale (UBDRS) rating scale. The UBDRS is a clinical ratings instrument used specifically to assess motor, seizure, behavioral and functional capabilities. [ Time Frame: 36 months ]
Change History Complete list of historical versions of study NCT03770572 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 7, 2018)
  • 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 ]
  • 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 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Gene Transfer Study of AAV9-CLN3 for Treatment NCL Type 3
Official Title  ICMJE Phase I/IIa Gene Transfer Clinical Trial for Juvenile Neuronal Ceroid Lipofuscinosis, Delivering the CLN3 Gene by Self-Complementary AAV9
Brief Summary Open-label, single dose, dose-escalation clinical trial AAV9-CLN3 via intrathecal injection in NCL type 3 subjects
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE 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
Condition  ICMJE CLN3-Related Neuronal Ceroid-Lipofuscinosis
Intervention  ICMJE Biological: AAV9-CLN3
A single dose of AAV9-CLN3 will be delivered via an intrathecal injection.
Study Arms  ICMJE
  • Experimental: Cohort 1

    AAV-CLN3 Low-Dose

    (Minimally Effective Dose (MED)

    Intervention: Biological: AAV9-CLN3
  • Experimental: Cohort 2

    AAV-CLN3 High-Dose

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

    Intervention: Biological: AAV9-CLN3
Publications *

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 7, 2018)
7
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years to 10 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lisa Moffitt, RN 614-722-2650 lisa.moffitt@nationwidechildrens.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03770572
Other Study ID Numbers  ICMJE IRB18-00725
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 Not Provided
Responsible Party Emily de los Reyes, Nationwide Children's Hospital
Study Sponsor  ICMJE Nationwide Children's Hospital
Collaborators  ICMJE Amicus Therapeutics
Investigators  ICMJE
Principal Investigator: Emily de los Reyes, MD Nationwide Children's Hospital
PRS Account Nationwide Children's Hospital
Verification Date December 2018

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