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Batten CLN6 Gene Therapy

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 : January 23, 2019
Sponsor:
Collaborator:
Gray Foundation
Information provided by (Responsible Party):
Jerry R. Mendell, Nationwide Children's Hospital

Tracking Information
First Submitted Date  ICMJE March 16, 2016
First Posted Date  ICMJE April 1, 2016
Last Update Posted Date January 23, 2019
Study Start Date  ICMJE March 2016
Estimated Primary Completion Date March 2019   (Final data collection date for primary outcome measure)
Current 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02725580 on ClinicalTrials.gov Archive Site
Current 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.
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 Batten CLN6 Gene Therapy
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 The proposed clinical trial is the first human, open-label, single dose study of self-complementary AAV9 carrying the CLN6 gene delivered one-time intrathecally inserted by a lumbar puncture into Batten CLN6 Disease subjects. One cohort of patients with Batten CLN6 Disease, with confirmed diagnosis, will undergo gene transfer. A minimum of twelve patients will be enrolled into the cohort.
Detailed Description The proposed clinical trial is the first human, open-label, single dose study of self-complementary AAV9 carrying the CLN6 gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter (scAAV9.CB.CLN6) delivered one-time through an intrathecal catheter inserted by a lumbar puncture into the interspinous into the subarachnoid space of the lumbar thecal sac. All twelve patients will receive a dose equivalent to (1.5 x10^13 vg). This will be administered premixed with 2.5 mL of the contrast Omnipaque™ at a concentration of 180 mgI/mL of the contrast via a 10 mL syringe and a Spinal Needle. If no clinically significant improvement without toxicity is observed, the possibility of adding an additional escalation cohort at a higher dose will be discussed with the FDA, DSMB and relevant oversight regulatory agencies.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Batten Disease
  • CLN6
Intervention  ICMJE Drug: scAVV9.CB.CLN6
Twelve subjects with diagnosis of CLN6 disease will receive scAVV9.CB.CLN6 administered by intrathecal injection.
Study Arms  ICMJE Experimental: Cohort 1
Twelve (n=12) Batten CLN6 subjects will receive a single injection of scAAV9.CB.CLN6 via intrathecal delivery. Subjects will receive a total dose of 1.5 x 10^13 vg.
Intervention: Drug: scAVV9.CB.CLN6
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
Actual Enrollment  ICMJE
 (submitted: November 21, 2017)
12
Original Estimated Enrollment  ICMJE
 (submitted: March 28, 2016)
6
Estimated Study Completion Date  ICMJE March 2019
Estimated Primary Completion Date March 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of CLN6 disease determined by genotype available at Screening
  • Quantitative clinical assessment of the Hamburg motor-language aggregate score at Screening on CLN2 disease motor-language scale, as defined in the Ratings Assessment Guideline.
  • Age ≥1 year
  • Written informed consent from parent or legal guardian and assent from subject, if appropriate.
  • Ability to comply with protocol required assessments (laboratory sample collection, EEG, ECG, MRI, etc.

Exclusion Criteria:

  • Another inherited neurologic disease, e.g., other forms of CLN or seizures unrelated to CLN2 disease (patients with febrile seizures may be eligible)
  • Another neurological illness that may have caused cognitive decline (e.g., trauma, meningitis, hemorrhage) before screening
  • Active viral infection
  • Has received stem cell or bone marrow transplantation for CLN6 disease
  • Contraindications for spinal tap procedure (e.g., spina bifida, meningitis, impairment, or clotting abnormalities)
  • Contraindications for MRI scans (e.g., cardiac pacemaker, metal fragment or chip in the eye, aneurysm clip in the brain)
  • Episode of generalized motor status epilepticus within 4 weeks before the First Dose visit
  • Severe infection (e.g., pneumonia, pyelonephritis, or meningitis) within 4 weeks before the First Dose visit (enrollment may be postponed)
  • Has received any investigational medication within 30 days before the first infusion of study drug
  • Patients with Anti-AAV9 antibody titers ≥ 1:50 as determined by ELISA binding immunoassay.
  • 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
  • Pregnancy any time during the study; a female subject judged by the investigator to be of childbearing potential will be tested for pregnancy
  • Abnormal laboratory values considered clinically significant (GGT > 3XULN, Bilirubin ≥ 3.0 mg/dL , Creatinine ≥ 1.8 mg/dL, Hgb < 8 or > 18 g/Dl; WBC > 15,000 per cmm)
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 IRB15-00963
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jerry R. Mendell, Nationwide Children's Hospital
Study Sponsor  ICMJE Nationwide Children's Hospital
Collaborators  ICMJE Gray Foundation
Investigators  ICMJE
Principal Investigator: Jerry R Mendell, MD PI
PRS Account Nationwide Children's Hospital
Verification Date January 2019

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