Study for the Treatment for CLN7 Disease (CLN7)
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|ClinicalTrials.gov Identifier: NCT04737460|
Recruitment Status : Recruiting
First Posted : February 3, 2021
Last Update Posted : May 18, 2021
This is a phase 1 open-label, single-administration of gene therapy agent AAV9/CLN7, administered intrathecally into the lumbar spinal cord region of pediatric patients with CLN7 Batten disease.
This study consists of a one-time injection of AAV9/CLN7. There are two Cohorts with a low dose and a high dose.
The primary objective for this clinical study is to evaluate safety. The secondary objective is to determine the efficacy of AAV9/CLN7.
The secondary outcome measures include motor, cognition and intelligence assessments.
The exploratory outcome measures include visual impairment assessment, cognitive evaluations, Brain magnetic resonance imaging (MRI), electroencephalogram (EEG), electrocardiogram (ECG) and echocardiogram (ECHO).
|Condition or disease||Intervention/treatment||Phase|
|CLN7||Genetic: AAV9/CLN7||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||4 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||An initial low dose cohort followed by a subsequent a high dose cohort|
|Masking:||None (Open Label)|
|Official Title:||Phase 1 Intrathecal Lumbar Administration of AAV9/CLN7 for Treatment of CLN7 Disease|
|Actual Study Start Date :||May 4, 2021|
|Estimated Primary Completion Date :||February 1, 2028|
|Estimated Study Completion Date :||February 1, 2029|
AAV9/CLN7 is an intrathecally administered AAV9-based gene therapy vector that expresses the fully functional form of MFSD8 under the control of a synthetic promoter. AAV9/CLN7 is designed to achieve stable, potentially life-long expression of MFSD8 in non-dividing cells.
The first participant will receive a low dose of 5X1014 vg, subsequent participants will receive a higher dose of 1x1015 vg of the AAV9/CLN7 agent.
Enrollees will receive gene therapy via a viral vector
- Safety measured by the incidence and severity of treatment related serious adverse events [ Time Frame: Day 0 to 720 ]Adverse event collection at scheduled visits. Lab results at scheduled visits. MRI Brain at Days 90, 180, 360, 720. Lumbar Puncture with Cerebral Spinal Fluid analysis at Days 90, 180, 360 and 720.
- Mean change in disease burden as measured by Clinical Global Impression Scale (CGI-S) [ Time Frame: Baseline, 24 months ]
Clinical Global Impression Scale (CGI) a 3 item observer rated scale that measures illness severity global improvement or change and therapeutic response.
The CGI-S is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients).
Possible score ranges from 1-7, with highest score indicating the most severely ill patients.
- Mean change in disease burden as measured by Early Clinical Drug Evaluation Program (ECDEU) [ Time Frame: Baseline, 24 months ]
The Early Clinical Drug Evaluation Program (ECDEU) version of the CGI asks that the clinician rate the patient relative to their past experience with other patients with the same diagnosis. Treatment response ratings should take account of both therapeutic efficacy and treatment-related adverse events and range from 0 (marked improvement and no side effects) to 4 (unchanged or worse and side effects outweigh the therapeutic effects).
Possible scores range from 0-4, with lower score indicating more improvement.
- Mean change in motor function as measured by 2- minute Walk Test [ Time Frame: Baseline, 24 months ]
Ataxia and Motor Function Assessments include a 2 - minute Walk test measuring endurance.
The timed walk test will be completed by participants who can ambulate sufficiently. The Two Minute Walk Test (2MWT) measures the distance that an individual over age 3 can walk on a flat surface in a period of 2 minutes, and assesses endurance relative to the musculoskeletal, pulmonary, and cardiovascular systems.
- Mean change in motor function as measured by 6- minute Walk Test [ Time Frame: Baseline, 24 months ]
Ataxia and Motor Function Assessments include a 6- minute Walk test measuring endurance.
The Six Minute Walk Test (6MWT) measures endurance in a similar fashion using a time interval of 6 minutes and is a commonly used measure for evaluating outcomes in research for multiple different populations of children and adults.
- Mean change in motor function as measured by Pediatric Balance scale [ Time Frame: Baseline, 24 months ]
The Pediatric Balance Scale is a 14-item test used to evaluate functional balance in children.
It is an adapted version of the Berg Balance Scale.
Possible score ranges from 0-56 , with highest score indicating better performance.
- Mean change in motor function as measured by Gross Motor Function Measure-88 [ Time Frame: Baseline, 24 months ]
Gross Motor Function Measure is used to measure self initiated movement in ambulatory and non-ambulatory participants to evaluate changes in gross motor function over time.
Possible score ranges from 0-3, with higher score indicating better motor function.
- Mean change in Neuropsychological state as measured by Mullen scales. [ Time Frame: Baseline, 24 months ]
The Mullen Scales of Early Learning is a comprehensive Neuropsychological assessment of early language, motor and cognitive abilities. T scores are given for individual scales and the four cognitive scales (visual reception, fine motor, receptive language and expressive language) are combined to to yield a composite score of Early Learning. Each scale is comprised of interactive tasks with a scoring range for each item of zero to 5 points.
Test ages are converted to normalized T-scores by using tables based on the child's age. T scores have the same meaning regardless of a child's age.
Possible score ranges from 1-100 for percentile ranking, with higher score indicating higher performance.
- Mean change in Neuropsychological state as measured by Vineland Adaptive Behavior Scales [ Time Frame: Baseline, 24 months ]
The Vineland Adaptive Behavior Scale is one of the most well-known and well-validated Neuropsychological measures of adaptive functioning. Four key domains will be rated including communication skills, daily living skills, social skills and motor skills. The combination of these makes up the overall Adaptive Behavior Composite (ABC). Scores are based on standard scores for the domains and age-equivalents meaning the scores are compared to that of others that are his or her age.
The score is a percentile ranking in an individual's normative age group. The higher the percentage ranking indicates a better outcome on the scale.
Possible score ranges from 1 -100 for percentile ranking, with higher score indicating higher performance.
- Mean change of Quality of life as measured by Quality of Life Inventory - Disability questionnaire [ Time Frame: Baseline, 24 months ]
Quality of Life Inventory - Disability (QI-Disability) questionnaire measures quality of life with 32-item measures that includes - a child's social interactions, positive emotions, physical health, negative emotions, leisure skills, and independence. Scores are a 5-point Likert scale and then are transformed to a scale of 0 to 100.
Possible scores range from 0-100, with higher scores indicating better quality of life.
- Mean change of Quality of life as measured by Infant and Toddler Quality of Life Questionnaire (ITQOL) [ Time Frame: Baseline, 24 months ]
The ITQOL Short Form is a 47-item measure to assess physical and psychosocial functioning of children ages 2 months to 5 years. It contains 12 scales including physical functioning, growth and development, bodily pain, temperament and moods, general behavior, getting along, general health perceptions, parental impact-emotional, parental impact-time, family activities, family cohesion, and change in health. Scores are transformed to a scale of 0 to 100.
Possible scores range from 0-100, with higher scores indicating better quality of life.
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 ClinicalTrials.gov identifier (NCT number): NCT04737460
|Contact: Souad Messahel, PhD||214-648-0143||Souad.firstname.lastname@example.org|
|Contact: Kimberly Krohn, RN||Kimberly.email@example.com|
|United States, Texas|
|Dallas, Texas, United States, 75390|
|Contact: Souad Messahel, PhD 214-648-0143 Souad.firstname.lastname@example.org|
|Contact: Kimberly Krohn, RN Kimberly.email@example.com|
|Principal Investigator: Benjamin Greenberg, MD|
|Principal Investigator:||Benjamin Greenberg, MD||University of Texas Southwestern Medical Center|