Pilot Study of an Optic-to-Audio Device in a Pediatric Cohort With CLN3-related Conditions or Low Vision
Phase: NA
Conditions: CLN3-related Disorders, Non-CLN3 Related Low Vision
Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

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Abbreviated Title: Pediatric Optic-to-Audio Device Study 
Version Date: October 25, 2022 
Template version date 10.27.2020 
 
 
 
Abbreviated Title: Pediatric Optic-to-Audio Device Study 
NIH IRB #: 000414. 
Version Date: October 25, 2022 
 
Title: Pilot Study of an Optic-to-Audio Device in a Pediatric Cohort with CLN3-related 
conditions or Low Vision 
 
 
NIH Principal Investigator: 
An Ngoc Dang Do, MD PhD 
Office of the Clinical Director, NICHD 
Building 10, Rm 2-5132 
9000 Rockville Pike 
Bethesda, MD 20892 
Phone: 301.496.8849 
Fax: 301.402.0574 
E-mail: an.dangdo@nih.gov 
 
 
Investigational Agents (if applicable): 
 
Device Name: 
OrCam MyEye 2 
Sponsor: 
Not applicable 
Manufacturer: 
OrCam Technologies Ltd. 

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TABLE OF CONTENTS 
TABLE OF CONTENTS ................................................................................................................. 2 
STATEMENT OF COMPLIANCE ................................................................................................. 6 
1 
PROTOCOL SUMMARY ....................................................................................................... 7 
1.1 
Synopsis ............................................................................................................................. 7 
1.2 
Schema .............................................................................................................................. 8 
1.3 
Schedule of Activities (SOA) ............................................................................................ 9 
2 
INTRODUCTION .................................................................................................................. 11 
2.1 
Study Rationale ................................................................................................................ 11 
2.2 
Background ...................................................................................................................... 11 
2.3 
Risk/Benefit Assessment ................................................................................................. 13 
2.3.1 
Known Potential Risks ............................................................................................. 13 
2.3.2 
Known Potential Benefits ......................................................................................... 15 
2.3.3 
Assessment of Potential Risks and Benefits ............................................................. 15 
3 
OBJECTIVES AND ENDPOINTS ........................................................................................ 15 
4 
STUDY DESIGN ................................................................................................................... 17 
4.1 
Overall Design ................................................................................................................. 17 
4.2 
Scientific Rationale for Study Design ............................................................................. 17 
4.3 
Justification for Dose ....................................................................................................... 17 
5 
STUDY POPULATION ......................................................................................................... 17 
5.1 
Inclusion Criteria ............................................................................................................. 17 
5.2 
Exclusion Criteria ............................................................................................................ 18 
5.3 
Inclusion of Vulnerable Participants ................................................................................ 18 
5.3.1 
Participation of NIH Staff or family members of study team members ................... 18 
5.4 
Inclusion of Pregnant Women, fetuses or neonates ......................................................... 19 
5.5 
Lifestyle Considerations .................................................................................................. 19 
5.6 
Screen Failures ................................................................................................................. 19 
5.7 
Strategies for Recruitment and Retention ........................................................................ 19 
5.7.1 
Costs ......................................................................................................................... 19 
5.7.2 
Compensation ........................................................................................................... 19 
6 
STUDY INTERVENTION .................................................................................................... 20 
6.1 
Study Interventions(s) Administration ............................................................................. 20 

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6.1.1 
Study Intervention Description ................................................................................ 20 
6.1.2 
Dosing and Administration ...................................................................................... 20 
6.2 
Preparation/Handling/Storage/Accountability ................................................................. 20 
6.2.1 
Acquisition and Accountability ............................................................................... 20 
6.2.2 
Formulation, Appearance, Packaging, and Labeling ............................................... 20 
6.2.3 
Product Storage and Stability .................................................................................. 21 
6.2.4 
Preparation .............................................................................................................. 21 
6.3 
Measures to Minimize Bias: Randomization and Blinding ............................................ 21 
6.4 
Study Intervention Compliance ...................................................................................... 21 
6.5 
Concomitant Therapy ..................................................................................................... 21 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................................... 21 
7.1 
Discontinuation of Study Intervention ............................................................................ 21 
7.2 
Participant Discontinuation/Withdrawal from the Study ................................................ 22 
7.3 
Lost to Follow-up ............................................................................................................ 22 
8 
STUDY ASSESSMENTS AND PROCEDURES ................................................................. 23 
8.1 
Screening Procedures ...................................................................................................... 23 
8.1.1 
Screening activities performed prior to obtaining informed consent ...................... 23 
8.1.2 
Screening activities performed after a consent for screening has been signed ........ 23 
8.2 
Efficacy Assessments ..................................................................................................... 25 
8.2.1 
Clinical Evaluations ................................................................................................ 26 
8.2.2 
Biospecimen Evaluations ........................................................................................ 26 
8.2.3 
Correlative Studies for Research/Pharmacokinetic Studies .................................... 26 
8.2.4 
Samples for Genetic/Genomic Analysis .................................................................. 26 
8.3 
Safety and Other Assessments ........................................................................................ 27 
8.4 
Adverse Events and Serious Adverse Events .................................................................. 30 
8.4.1 
Definition of Adverse Event .................................................................................... 30 
8.4.2 
Definition of Serious Adverse Events (SAE) .......................................................... 30 
8.4.3 
Classification of an Adverse Event ......................................................................... 30 
8.4.4 
Time Period and Frequency for Event Assessment and Follow-Up ........................ 32 
8.4.5 
Adverse Event Reporting......................................................................................... 32 
8.4.6 
Serious Adverse Event Reporting ............................................................................ 33 

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8.4.7 
Events of Special Interest ........................................................................................ 33 
8.4.8 
Reporting of Pregnancy ........................................................................................... 33 
8.5 
Unanticipated Problems .................................................................................................. 33 
8.5.1 
Definition of Unanticipated Problems (UP) ............................................................ 33 
8.5.2 
Unanticipated Problem Reporting ........................................................................... 33 
8.5.3 
NIH Intramural IRB Reporting of IND Safety Reports........................................... 34 
9 
STATISTICAL CONSIDERATIONS .................................................................................. 34 
9.1 
Statistical Hypothesis ...................................................................................................... 34 
9.2 
Sample Size Determination ............................................................................................. 34 
9.3 
Populations for Analyses ................................................................................................ 34 
9.3.1 
Evaluable for toxicity .............................................................................................. 34 
9.3.2 
Evaluable for objective response ............................................................................. 34 
9.3.3 
Evaluable Non-Target Disease Response ................................................................ 34 
9.4 
Statistical Analyses ......................................................................................................... 35 
9.4.1 
General Approach .................................................................................................... 35 
9.4.2 
Analysis of the Primary Endpoints .......................................................................... 35 
9.4.3 
Analysis of the Secondary Endpoint(s) ................................................................... 35 
9.4.4 
Safety Analyses ....................................................................................................... 36 
9.4.5 
Baseline Descriptive Statistics ................................................................................ 37 
9.4.6 
Planned Interim Analyses ........................................................................................ 37 
9.4.7 
Sub-Group Analyses ................................................................................................ 37 
9.4.8 
Tabulation of individual Participant Data ............................................................... 37 
9.4.9 
Exploratory Analyses .............................................................................................. 37 
10 REGULATORY AND OPERATIONAL CONSIDERATIONS .......................................... 37 
10.1 
Informed Consent Process .......................................................................................... 37 
10.1.1 Consent/Assent Procedures and Documentation ..................................................... 37 
10.1.2 Consent for minors when they reach the age of majority ........................................ 38 
10.1.3 Considerations for Consent of NIH staff, or family members of study team 
members ................................................................................................................................ 39 
10.1.4 Consent of Subjects who are, or become, decisionally impaired ............................ 39 
10.2 
Study Discontinuation and Closure ............................................................................. 39 
10.3 
Confidentiality and Privacy ........................................................................................ 39 

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10.4 
Future use of Stored Specimens and Data .................................................................... 40 
10.5 
Safety Oversight ........................................................................................................... 40 
10.6 
Clinical Monitoring ...................................................................................................... 40 
10.7 
Quality Assurance and Quality Control........................................................................ 40 
10.8 
Data Handling and Record Keeping ............................................................................ 41 
10.8.1 Data Collection and Management Responsibilities .................................................. 41 
10.8.2 Study Records Retention .......................................................................................... 41 
10.9 
Protocol Deviations and Non-Compliance ................................................................... 41 
10.9.1 NIH Definition of Protocol Deviation ...................................................................... 41 
10.10 
Publication and Data Sharing Policy ............................................................................ 41 
10.10.1 Human Data Sharing Plan ........................................................................................ 41 
10.10.2 Genomic Data Sharing Plan ..................................................................................... 42 
10.11 
Collaborative Agreements ............................................................................................ 42 
10.11.1 Agreement Type ....................................................................................................... 42 
10.12 
Conflict of Interest Policy ............................................................................................ 42 
11 ABBREVIATIONS ................................................................................................................ 42 
12 REFERENCES ....................................................................................................................... 44 

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STATEMENT OF COMPLIANCE 
The trial will be carried out in accordance with International Conference on Harmonisation Good 
Clinical Practice (ICH GCP) and the following: 
• United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 
CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812) 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training. 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the Institutional Review Board (IRB) for review and approval. Approval of both 
the protocol and the consent form must be obtained before any participant is enrolled. Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study. In addition, all changes to the consent form will be IRB-approved; an 
IRB determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form. 

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1 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS 
Title: 
Pilot Study of an Optic-to-Audio Device in a Pediatric Cohort with 
CLN3-related conditions or Low Vision 
 
Study Description: 
This is a pilot study of an augmentative visual device, OrCam MyEye 
2 (OrCam), in pediatric individuals with CLN3-related conditions or 
low vision. We hypothesize that, given the relatively simple design 
and operating procedure of the device, the use of the OrCam by study 
participants will be safe and feasible. We also hypothesize that the 
device will enhance their ability to obtain visually based information. 
 
Objectives: 
Primary 
Assess the safety and feasibility of OrCam use by children with 
CLN3 or low vision. 
Secondary 
Assess the effectiveness of OrCam use by children with CLN3 or low 
vision. 
Exploratory 
Assess the feasibility and effectiveness of OrCam use in CLN3 
versus non-CLN3 groups. 
Optimize methods for assessing efficacy of visual 
accommodation/assistive devices for the CLN3/NCL population 
Endpoints: 
Primary 
1) Adverse events during the use of OrCam. 2) Feasibility test. 3) 
Feasibility questionnaire. 4) Device use diary. The assessment 
periods will be 1 week at study site and 1 month at home. 
Secondary 
1) Function test of using OrCam. 2) Ability questionnaire. 
Exploratory 
1) Function test. 2) Feasibility, Ability, Applicability questionnaires. 
 
Study Population: 
30 individuals age 6-18 years with low vision (20 with CLN3-related 
conditions, 10 without CLN3) of any gender, demographic, 
geographic location who meet study eligibility criteria. 
 
Phase: 
Not applicable 
 
Description of 
Sites/Facilities 
Enrolling Participants: 
Description of Study 
Intervention: 
The NIH Clinical Center will be the only site enrolling participants. 
 
The study uses the OrCam MyEye 2, a 22.5-g portable, eyeglass- 
mounted device that converts camera-captured inputs to auditory 
outputs. Its advertised functions include text reading, facial 
recognition, and product identification. The study participants and 

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parents/guardians will be trained on how to use the device. 
Evaluations for primary and secondary endpoints will be done 
following 1 week and 1 month of device use. 
 
Study Duration: 
24-36 months. 
 
Participant Duration: 
1-2 months 
 
 
1.2    SCHEMA
 

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1.3  SCHEDULE OF ACTIVITIES (SOA) 
 
Procedures 
Screeninga,d 
Up to Day -1 
Enrollment 
Baseline 
Day 1 
Day 2b 
Day 3 to 4b 
1-Week 
Evaluations 
Day 5b 
Day 6-11b 
Day 12b 
Day 13-18b 
Day 19b 
Day 20-25b 
Day 26b 
Day 27-32b 
1-Month 
Evaluations 
Day 33b,c 
Informed consentc 
X 
Demographicsc 
X 
Medical historyc 
X 
Physical examd 
X 
Vital signsd 
X 
Ophthalmic evaluationd 
X 
Neuropsychologic evaluationc 
X 
Xd or h 
Audiologic evaluationd 
X 
UBDRSc,e 
X 
Device trainingc,f 
Xd 
Xd 
Xd or h 
Xd 
Xh 
Xh 
Xh 
Device useg 
Xd or h 
Xd or h 
Xh 
Xh 
Xh 
Xh 
Xh 
Xh 
Xh 
Adverse events reviewc 
Xd or h 
Xh 
Xh 
Xh 
Xd or h 
Feasibility testc,i 
Xd 
Xd 
Xd or h 
Feasibility questionnairec,j 
Xd or h 
Xd or h 
Function testk 
Xl, d 
Xl, d 
Xm, d or h 
Ability questionnairen 
Xd 
Xd or h 
Xd or h 
Applicability questionnaireo 
Xd 
Quality of Life questionnairesp 
Xd 
Xd or h 
Phlebotomyd 
X 
Research biospecimen collectionq 
X 
a Screening evaluations can be done under 18-CH-0002 protocol if participant consented to co-enroll, or under this protocol. 
Previous evaluations/procedures within stated time frames (Section 8.1.2) will be accepted in lieu of repeating. 

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b +/- 2 days, except for Day 2 to 4 range may be +2 days 
c By in-person or remote technology methods 
d At NIH CC 
e Only in participants with CLN3-related conditions who are not co-enrolled in study 18-CH-0002. 
f Appendix J - OrCam MyEye 2 User Guide, Software Version 8.2-EN, Jan 2020. 
g By participant for minimum of 15-30 minutes per day. If participant/parents/guardians encounter issues with device use, they may 
contact the study team and a video- or audioconference will be scheduled as appropriate. 
h At home 
i Appendix A. To be administered by study team to participant 
j Appendix B. To be administered by study team to participant if able, and parents/guardians 
k Appendix C. To be administered by study team to participants. 
l Full Function Test done with evaluator and participant at NIH CC or partial Function Test done via remote technology (e.g., 
videoconferencing). 
m Full or partial Function Test if participant cannot return to NIH CC 
n Appendix D. To be administered by study team to parents/guardians 
o Appendix E. To be administered by study team to parents/guardians 
p Appendices G - I. To be administered by study team to participants if appropriate, and parents/guardians 
q If not already done as part of CLN3 natural history protocol (18-CH-0002). Includes at the most: cheek swab (at home or NIH), 
saliva (at home or NIH), skin biopsy (at NIH), urine (at NIH) 

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2 
INTRODUCTION 
2.1 
STUDY RATIONALE 
CLN3 is a fatal, lysosomal disease that results in progressive neurodegeneration. It is the most 
common type of the 13 disorders of neuronal ceroid lipofuscinosis with incidence estimates 
ranging from 1/12,500 to 1/100,000 in European and USA populations. The initial clinical 
presentation is vision loss, resulting in legal blindness by 7-8 years of age in most individuals with 
classic CLN3 disease. Cognitive impairment and behavioral dysfunctions are also early presenting 
symptoms, followed by seizures and motor dysfunction. Current life-expectancy for affected 
individuals is in to the second to third decade of life. 
The early and relatively rapid visual changes significantly impact the quality of life of 
individuals with CLN3. Current standard accommodative approaches for the progressive 
blindness, i.e., enlarged fonts, Braille, sign language, have limited applicability given the multiple 
disabilities associated with the neurodegeneration. Though treatment trials are in development, 
none specifically targets low vision. Thus, approaches to provide means for obtaining vision- 
related inputs are needed. Additionally, better understanding of parental goals for their child in 
terms of ability to perform vision-related tasks will inform the development of future 
accommodations. To begin addressing these knowledge gaps, this protocol will assess the safety, 
feasibility, and efficacy of the use of an augmentative visual device in a cohort of children and 
adolescents with CLN3, low vision, and intellectual disability. This protocol will further explore 
parental objectives for their child’s function, and the potential of the device in addressing these. 
Information on the use of the OrCam MyEye 2 device in the pediatric population with low 
vision is not available. Thus, to evaluate the feasibility and effectiveness of this device in children 
with low vision, and no concomitant neurodegenerative process, we will include a cohort of 
pediatric individuals with low vision but without a CLN3-related disorder. 
2.2 
BACKGROUND 
CLN3 (JNCL, Batten Disease, MIM 204300) is an autosomal recessive, fatal, lysosomal 
disease that results in progressive neurodegeneration.[1-3] It is one of 13 disorders categorized as 
neuronal ceroid lipofuscinosis. In aggregate, these are considered the most common 
neurodegenerative disorders in children, with incidence estimates ranging from 1/12,500 to 
1/100,000 in European and USA populations.[2, 4] 
The disease presentation typically involves vision loss observed around pre-school years, with 
eventual progression to blindness within 1-3 years.[5-7] The underlying pathophysiology involves 
intracellular accumulation of ceroid lipofuscin materials in retinal ganglions, and possibly in 
photoreceptors.[8-10] This manifests on ophthalmic measures as decreased electrical responses to 
stimuli on electroretinogram [5, 7, 11] and thinning of the retinal cell layers on pathology and 
optical coherence tomography [7, 9, 12]. Neurocognitive development plateaus around 7-10 years 
of age and progresses to dementia starting in the early teen years.[13-15] Behavioral, psychiatric, 
seizure, and motor disorders are also common findings in individuals with CLN3.[1, 16] Current 
estimated average life expectancy is in the 20-30’s.[2] There are no therapies for this devastating 
disorder. Therapeutic trials using gene therapy or small molecules are in the early stages of 
implementation.[17] Pathogenic variants in CLN3 have also been associated with a non-syndromic 
phenotype that appears to affect vision only.[18, 1

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Figure 1. Visual ability of CLN3 natural history 
study participants (n=22). 
To augment the development of biomarker 
discovery for application in diagnosis and 
therapeutic trial monitoring, we initiated a 
Natural History study of individuals with CLN3 
(NCT03307304). The study includes extensive 
evaluations 
including 
ophthalmologic, 
 
neurodevelopmental, 
audiologic, functional visual and occupational 
therapy measures. Of the initial 22 study 
participants enrolled, all but two have vision 
qualifying for legal blindness status (Figure 1). 
Vineland-3 adaptive behavior composite (ABC) 
assessment, a parental report measure of an 
individual’s real-world functioning with good 
correlation with standard IQ testing, showed 
that a significant number of the study 
participants older than 8 years of age scored in 
the range of intellectual disability (≤ -2 SD; Figure 2, left panel), with daily living skill scores also 
significantly below the mean standard score (Figure 2, right panel). 
The loss of a major means of sensory input likely contributes to some of the behavior dysfunctions 
such as anxiety and perseveration in children with CLN3.[20] Quality of life for the affected child 
and family members is profoundly impacted as they adapt to the blindness and disease.[20, 21] 
When asked to rank in order (1=most desirable) the symptoms they would like to see being 
addressed by future interventions, 37% of mothers (n=19) and 47% of fathers (n=15) in the Natural 
History study cohort chose vision as number one. 
 
 
 
 
 
Figure 2. Adaptive behavior of CLN3 natural history study participants as measured by 
Vineland-3 parental interview (n=22). Left panel: Adaptive behavior composite standardized 
scores. Right panel: Daily Living Skill standardized sub-scores. Mean score = 100. Standard 
deviation (SD) = 15.  
 
Current approaches towards therapeutic intervention for CLN3 appropriately focus on 
addressing neurologic or systemic symptoms. [22-24] However, these approaches have unclear 
impact on visual ability as information on the effectiveness of blood-retinal barrier delivery has 
not been published. While many of the study participants were initially started on Braille, the 

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concomitant intellectual disability limited them from attaining the skill level necessary for efficient 
use. Other alternative and augmentative modes for communication and sensory inputs such as 
auditory (e.g. books on tape) and tactile (e.g. textured 
objects) may be more applicable[21]. Study participants in 
the NICHD natural history cohort have preserved hearing 
ability and are reported by parents to maintain interests in 
listening to stories or movies on their electronic devices. 
The OrCam MyEye 2[25] is a portable, optic-to-audio 
assistive vision device that contains features likely 
applicable to the CLN3 cohort. The eyeglass-mounted 
device (Figure 3) is advertised to allow users to read text, 
and to identify faces, objects and colors by pointing and 
aiming the camera at the intended target[25]. A pilot study 
Figure 3. OrCam MyEye 2. 
https://www.orcam.com/en/blog/cate 
gory/general/, on 3/8/2020. 
 
using the OrCam in 12 adults with low vision and intact cognition showed improved ability in 
reading and daily function tasks[26]. The adult study participants also found the OrCam to be easy 
to use and would recommend it to others with low vision. No study in children or in individuals 
with CLN3 is available. 
2.3 
RISK/BENEFIT ASSESSMENT 
 
2.3.1 Known Potential Risks 
Efforts will be made to reduce physical and psychological stress associated with study 
participation. These procedures will be explained to the individual participants and to their 
parents/guardians. 
 
A. OrCam MyEye 2 Device and Use. Non-significant risks are associated with the use of 
the device when following the manufacturer’s User Guide (Appendix J). The device is 
worn as an accessory to regular eyeglass frames. The relative proportion of the device to 
a pediatric participant is shown in Appendix K. If an individual does not have glasses, they 
may experience discomfort with wearing glasses for the first time. The increase in auditory 
inputs may be irritating. The device use acclimation process may be frustrating. These are 
expected to improve with repeated use. 
B. Medical Evaluations. Minimal risks are associated with the physical, the Unified Batten 
Disease Rating Scale (UBDRS), and neuropsychologic examinations. Multiple 
independent evaluations may be stressful to a child or an impaired participant. 
C. Ophthalmologic Evaluation. 
A standard ophthalmologic exam includes dilation. Iris dilation can make participants 
transiently sensitive to light.  
D. Audiologic Evaluation. For the hearing test the participant will wear headphones or soft 
foam earplugs. They will then be exposed to tones and words which vary in loudness and 
asked to respond to the sounds. This testing involves minimal discomfort. 
Acoustic reflex measurement allows the audiologist to further examine the integrity of 
the acoustic reflex arc which relies on functional integrity of the middle ear system, inner 
ear, seventh and eighth cranial nerves and auditory pathways in the lower brainstem. For 
this test, very brief, somewhat loud tones are presented to each ear. In a normal-hearing 
ear, the stapedius muscle in the middle ear contracts in response to loud sounds presented 

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at levels of about 70-100 dB HL (decibels hearing level). In this test, the audiologist 
presents tones at these levels and determines whether there is an acoustic reflex and what 
level of sound is required to produce the reflex. This is a standard audiologic test. 
The audiologic evaluation will include measurement of auditory evoked potentials. For 
this test, the participants will wear either headphones or soft, foam earplugs. Electrodes 
will be taped to the participants’ head and the electrical response to sound will be recorded. 
This testing involves minimal discomfort and risk. 
E. Neuropsychologic Evaluations. Participants may fatigue or get frustrated from answering 
many questions. Breaks will be provided to minimize these potential issues. 
F. Phlebotomy. An anesthetic cream such as EMLA may be used to decrease discomfort. 
Infection and bruising are possible at the site of the blood draw. 
G. Cheek swab/Saliva collection. The collection may be inconvenient. The cheek swab may 
cause temporary oozing of blood that should be minimal. 
H. Urine collection. This collection may be inconvenient. 
I. Skin biopsy. The biopsy may hurt. This can be minimized by administration of local 
anesthetics. The site may leave a faint scar. Individuals with history of excessive keloid 
formation will not have a skin biopsy done. Bleeding and infection are minimal risks. 
J. Genetic Testing. Genetic information obtained from participation in research could be 
misused for discriminatory purposes. However, state and federal laws provide some 
protections against genetic discrimination. Researchers who will have access to genetic 
information about the participants will take measures to maintain the confidentiality of this 
information. Individuals enrolled in this protocol would already have the diagnosis of 
CLN3-related conditions or a genetic cause of low vision, with its attendant risks of 
insurance and employment discrimination. If the underlying genetic cause for the low 
vision is not known and it is applicable to identify, then the participant will be referred to 
protocol “Evaluation of Patients with Genetic Disorders” (16-CH-0103). To the fullest 
extent possible, the investigators will not disclose to third parties any information about the 
participants without their expressed consent. 
K. Sample confidentiality. Specimens not being used for clinical care or standard clinical 
tests which are sent to various laboratories will have identifiers removed and be coded. 
This code and clinical data will be maintained on password protected computers and in 
locked offices. 
L. Psychological Harms. This protocol may reveal unexpected medical findings. If these 
medical findings can be evaluated and treated at the NIH-CC we will provide short term 
care for these findings. For any unanticipated medical findings that result in psychological 
stress, the medical team will provide counseling and support to the participant and the 
parents/guardians. If needed, the medical team can be reached by letter, phone, and email 
to address other uncertainties.  
M. Risk to Family Relationships. This protocol is not likely to reveal unexpected family 
relationships such as adoption or misplaced paternity. If these issues do arise, we will not 
mention them to the participant or family members unless the issue is of clinical 
significance for the participant. Every attempt will be made to uphold the objective of 
privacy and participant autonomy. 

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2.3.2 Known Potential Benefits 
This is a feasibility study of using the OrCam by children with CLN3 or low vision. No 
previous study of this device in this population has been done, thus information on known potential 
benefits are limited to the following:  
1) The device provides an approach to augment visual inputs by translating these into 
auditory inputs, a sensory system apparently unaffected in children with CLN3 or low 
vision. 
2) In adults with low vision, the device improves their ability to read text and recognize 
products[26]. It is advertised to improve the ability to recognize faces, colors, and 
report dates and times. These are functions integral in basic daily life tasks. 
3) Appropriate use of the device may allow children with CLN3 or low vision to regain 
independence in some basic daily tasks and decrease care burden for family members. 
2.3.3 Assessment of Potential Risks and Benefits 
This protocol provides an intervention with the potential for benefits. The risk of the 
intervention, use of OrCam, is minimal. The research evaluations (Ophthalmology, 
Neuropsychologic, Audiology) are required to determine eligibility and carry minimal risks. The 
research evaluations (UBDRS, collection of biospecimens, genetic testing) add to the general 
understanding of the natural history of CLN3. For the non-CLN3 cohort the collection of 
biospecimens and genetic testing will serve as important pediatric control samples. These 
proposed procedures carry minimal risks. 
 
3 
OBJECTIVES AND ENDPOINTS 
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR ENDPOINTS 
Primary 
To assess: 
a) safety and 
b) feasibility of using 
OrCam MyEye 2 by 
children with CLN3 or low 
vision. 
a) Adverse events 
b) Feasibility test, 
Feasibility 
questionnaire, and 
Device use diary 
(see Section 9.4.2) 
The assessment periods 
will be 1 week at study 
site and 1 month at 
home. 
a) Collection of adverse event data is 
a standard method for evaluating 
safety in clinical trials. 
b) No validated, standardized tool is 
available to evaluate the feasibility 
of augmentative communication 
devices such as the OrCam. We 
modified the feasibility questionnaire 
used in an adult study [26] to 
provide appropriate adaptation for 
the pediatric cohort. 
Secondary 
To assess the efficacy of 
using the OrCam by 
1) Function Test – 
Efficacy Scores 
(see Section 9.4.3) 
No validated, standardized tool is 
available to evaluate the efficacy of 
augmentative communication 

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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR ENDPOINTS 
children with CLN3 or low 
vision. 
2) Ability 
questionnaire (see 
Section 9.4.3) 
The assessment periods 
will be 1 week at study 
site and 1 month at 
home. 
devices such as the OrCam. We 
developed a Function Test based on 
the device’s advertised functions, our 
observations of the pediatric cohort 
in the Natural History study, and the 
one used in an adult study [26], to 
provide age and ability appropriate 
assessments. 
Exploratory 
1) To compare the 
feasibility and efficacy 
of using the device 
between the CLN3 and 
non-CLN3 groups. 
2) To optimize methods for 
assessing efficacy of 
visual 
accommodation/assistive 
devices for the 
CLN3/NCL population 
3)  To characterize parental 
objectives relating to 
vision-based functions 
for a child with CLN3 
4) To assess unanticipated 
adaptive functions of 
using the OrCam. 
5) To discover biochemical 
markers relevant to 
disease 
1) Function test – 
Feasibility Scores, 
Feasibility, Ability, 
Applicability 
questionnaires 
2) Function test – 
Feasibility Scores, 
Neuropsychologic 
evaluation (1- 
month), Feasibility, 
Ability, 
Applicability 
questionnaires 
3) Ability, 
Applicability, 
Quality of Life 
questionnaires 
4) Device use diary 
5) Samples collection 
to complement 
Natural History 
1) Individuals with CLN3 also have 
neurocognitive disability, 
whereas the non-CLN3 may not. 
These evaluations would provide 
perspectives on differences in the 
two groups. 
2) Participants’ and caregivers’ 
perspective will be important 
towards informing future 
development of studies and 
interventions for visual function 
in the CLN3 cohort . 
3) Collection of biospecimens will 
allow increase in numbers and 
statistical power for the 
biomarker discovery 
4 
STUDY DESIGN 
4.1 
OVERALL DESIGN 
Individuals with CLN3 are anticipated to have vision loss and intellectual disability, but with 
preserved auditory function. We hypothesize that an auditory-based assistive technology with 
a simple operating procedure, such as the OrCam, will be safe and feasible for use in a 
pediatric population, including those with CLN3, and will enhance their ability to obtain 
visually based information. We propose a pilot study of 20 study participants to evaluate the 
safety, feasibility, and efficacy of using the OrCam in a cohort of the CLN3 pediatric population. 
Since no information is available on the safety, feasibility and efficacy of the OrCam in the 

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pediatric population, we also propose enrolling 10 pediatric participants with low vision from non- 
CLN3-related causes. The primary and secondary objectives will be assessed using data from all 
30 participants. 
In this 2-cohort (CLN3 and non-CLN3), open-label, single-center study, we aim to determine: 
1) the safety and feasibility 
2) the potential clinical efficacy 
of the use of OrCam in children, including individuals with CLN3. 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
Currently, there is no device similar to the OrCam available or in accepted use for individuals 
with CLN3. In addition, there is also no data available on the use of this device in children with 
low vision. Thus, a combined cohort of pediatric participants with and without CLN3-related 
disorders will optimize recruitment potential, and provide preliminary information for evaluation 
of feasibility and efficacy in pediatrics, and specifically in individuals with CLN3-related 
conditions. To assess efficacy, we will use the study participants’ baseline data as controls. This 
option encompasses the least number of confounding factors for a cohort of small size. 
In the CLN3 natural history study (18-CH-0002), accrual rate averages at 8-10 per year. Not 
all of these individuals will meet the eligibility criteria for this proposed study. However, we 
anticipate, based on experience with interventional trials of other rare diseases, that families 
hesitant to participate in an observational study would be more open to participating in an 
interventional study. Given these considerations, we anticipate an accrual rate of 5 participants per 
year and a reasonable potential to enroll 20 CLN3 participants over 2-3 years. We have also 
discussed potential eligible participants with local Ophthalmology groups (Howard University, 
Johns Hopkins, NEI), and the anticipated number for pediatric individuals with low vision and not 
CLN3-related condition is estimated to be in the same range. We plan to screen up to 50 
participants. 
4.3 
JUSTIFICATION FOR DOSE 
Not applicable. 
5 
0-STUDY POPULATION 
5.1 
INCLUSION CRITERIA 
To participate in the screening portion of this study, an individual must meet all of the 
following criteria: 
1. Has a diagnosis or suspected diagnosis of any genetically based condition causing low 
vision to the level specified in criteria 2. 
If the genetic condition is CLN3-related, the individual must have one of the following: 
a. Two CLN3 pathogenic variants, 
b. One CLN3 pathogenic variant AND 
i) clinical presentation suggestive of CLN3, OR 
ii) characteristic electron microscopy (EM) findings (such as curvilinear body, 
fingerprint profile, granular osmiophilic deposits). 
2. Has an estimated visual acuity in the better seeing eye < 20/200, without the use of an 
assistive or augmentative device. 
3. Is between 6 to 18 years of age. 

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To participate in the intervention/device use portion of this study, an individual must meet the 
above screening criteria and the following criteria: 
Has an appropriate cognitive developmental ability to participate based on Investigators’ 
screening assessment. 
5.2 
EXCLUSION CRITERIA 
An individual who meets any of the following criteria will be excluded from participation in 
this study: 
1. Has any of the following auditory dysfunctions: non-reversible or non-correctable hearing 
loss, tinnitus that is chronic or occurring daily, auditory hallucinations that occur daily. 
2. Uses an optic-to-audio assistive device at the time or within 3 months of screening and 
enrollment. 
3. Is unable to travel to the NIH because of medical condition for required in-person portions 
of the study. 
4. Is unable to comply with or have medical conditions that would potentially increase the 
risk of participation. 
5.3 
INCLUSION OF VULNERABLE PARTICIPANTS 
 
5.3.1 Participation of NIH Staff or family members of study team members 
Family members of NIH staff or of individuals on the study team may be enrolled in this study 
if meeting the study entry criteria. Neither participation nor refusal to participate as a subject in 
the research will have an effect, either beneficial or adverse, on the participant’s family member’s 
employment or position at NIH. 
Every effort will be made to protect participant information, but such information may be 
available in medical records and may be available to authorized users outside of the study team in 
both an identifiable an unidentifiable manner. 
The NIH Information Sheet on NIH Staff Research Participation will be made available. 
Please see section 10.1.3 for consent of NIH Staff. 
 
5.3.2 Participation of children and cognitively impaired children 
CLN3 is a disease with typical onset in childhood. For age- and visual severity level- 
appropriate comparisons, individuals with low vision but not CLN3 will also be children. The 
procedures included in the protocol are reasonably commensurate with those that children with 
CLN3 or low vision would encounter in their expected medical care. Participants may benefit 
directly from the use of the OrCam. We will follow procedures outlined in Section 10.1 Informed 
Consent Process for consenting children. 
5.4 
INCLUSION OF PREGNANT WOMEN, FETUSES OR NEONATES 
Not applicable. 

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5.5 
LIFESTYLE CONSIDERATIONS 
During this study, participants are asked to wear the OrCam device, attached to an eyeglass 
frame (Appendices I and J), for a minimum of 30 minutes each day while performing device- 
supported activities. 
5.6 
SCREEN FAILURES 
Screen failures are defined as participants who consent to participate in the clinical trial but are 
not subsequently assigned to the study intervention or entered in the study. A minimal set of screen 
failure information is required to ensure transparent reporting of screen failure participants, to meet 
the Consolidated Standards of Reporting Trials (CONSORT) publishing requirements, and to 
respond to queries from regulatory authorities. Minimal information includes demography, screen 
failure details, eligibility criteria, and any serious adverse event (SAE). 
Individuals who do not meet the criteria for participation in this trial (screen failure) because 
of a temporary or reversible deficit in hearing ability may be rescreened. Rescreened participants 
should be assigned the same participant number as for the initial screening. 
5.7 
STRATEGIES FOR RECRUITMENT AND RETENTION 
Participants will be recruited from the current 18-CH-0002 CLN3 Natural History protocol, 
through patient and professional organizations, at conferences, and through other healthcare 
providers. Study participants and parents/guardians may also contact the study team directly. We 
will also distribute information of this protocol through the NIH OPR, posting on clinicaltrials.gov, 
postings on social media websites, and referencing of this study website in presentations on CLN3- 
related topics. We plan to screen up to 50 participants for the duration of the study and enroll 5-10 
per year for a total accrual goal of 30 participants. 
 
5.7.1 Costs 
All study-related procedures and interventions done at the NIH CC will be provided at no 
charge. If the study participants must be referred to an outside facility for further evaluations and 
treatments, the medical cost associated with these interventions will be covered by the participants’ 
primary insurance. 
 
5.7.2 Compensation 
Coverage for travel, lodging, and food will be provided per NICHD’s guideline. 
Table 1. Time-based calculations for proposed compensation to participants in protocol 000414. 
(Reference: Policy 302) 
$ 
Screening 
Baseline/ 
Training 
1-Week 
1-Month (in- 
person) 
1-Month 
(remote) 
16 hours 
12 hours 
8 hours 
3 hours 
2 hours 
Outpatient – 1st 
hour ($) 
20 
40 
40 
20 
20 
20 

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Outpatient Time – 
Per Additional 
Hour ($) 
10 
140 
100 
70 
20 
10 
Escort Fee – Per 
Outpatient Visit 
($) 
20 
40 
40 
20 
20 
0 
Time Totals ($) 
220 
180 
110 
60 
30 
 
 
Based on the above calculations, the compensation scheme would be as below for each future 
enrolled participant. For incomplete participations, the compensation amount will be prorated 
based on the number of hours participated. 
1. $220 for completing the Screening evaluations. 
2. $180 for completing the Baseline and Training visits. 
3. $110 for completing the 1-Week visit. 
4. $60 for completing the 1-Month visit in-person, or $30 for completing the 1-Month visit 
remotely. 
6 
STUDY INTERVENTION 
6.1 
STUDY INTERVENTIONS(S) ADMINISTRATION 
 
6.1.1 Study Intervention Description 
OrCam 
MyEye 
2 
is 
an 
FDA 
class 
1 
device 
(https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRL/rl.cfm?lid=397540&lpcd=HPG). The 
main components include a 13 megapixels camera, a 3.7V DC (nominal 320mAH) battery, and 
ancillary charging and glass-mounting supplies. The OrCam MyEye 2 is available in only one size 
that has dimensions of 76x21x14.9 mm, and weighs 22.5 g. Additional visual and descriptions of 
the device, its set-up and functions are provided in Appendices I-K. The use of the OrCam in this 
study will be according to the manufacturer’s specifications. The device is not intended as an 
implant and does not present potential for serious risk to the health, safety, or welfare of a subject. 
Due to its risk profile, the device should be considered a non-significant risk device. 
Participants will be trained and asked to use the device for at least 30 minutes daily as indicated 
in the Schedules of Activities. All participants meeting eligibility criteria will enroll in the 1- 
week study and be exposed to the device use for 5 days. Participants may enter the additional 1- 
month study if parents/guardians/participants endorse desire to continue using the device at home. 
 
6.1.2 Dosing and Administration 
Not applicable. 

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6.1.2.1 Dose Escalation 
6.1.2.2 Dose Limiting Toxicity 
Not applicable. 
6.1.2.3 Dose Modifications 
Not applicable. 
6.1.2.4 Drug Administration 
Not applicable. 
6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
Handling and use of the device must follow the manufacturer’s recommendation as described 
in the User Guide. 
 
6.2.1 Acquisition and Accountability 
An OrCam MyEye 2 device will be provided to participants for the duration of the study. The 
device must be returned in the appropriate postage-paid packaging provided by the study team 
following the end of study assessments. 
 
6.2.2 Formulation, Appearance, Packaging, and Labeling 
OrCam MyEye 2 is manufactured by OrCam Technologies Ltd. 
 
6.2.3 Product Storage and Stability 
Device handling and storage is as described in the User Guide. 
 
6.2.4 Preparation 
Device assembly and use instructions are as described in the User Guide. 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
This is an open-label study. Participation in the 1-month extension is on a voluntary basis. 
6.4 
STUDY INTERVENTION COMPLIANCE 
Participants or parents/guardians will complete a Device Use Diary (Appendix F) in either 
paper or web-based format. The use log will be cross-checked with the participants/parents/ 
guardians by a study team member daily for the 1-week study, and at weekly adverse events review 
contacts for the 1-month study. 
6.5 
CONCOMITANT THERAPY 
For this protocol, a prescription medication is defined as a medication that can be prescribed 
only by a properly authorized/licensed clinician. Medications to be reported in the Case Report 
Form (CRF) are concomitant prescription medications, over-the-counter medications and 
supplements. 

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7 
STUDY 
INTERVENTION 
DISCONTINUATION 
AND 
PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1 
DISCONTINUATION OF STUDY INTERVENTION 
Discontinuation from daily use of the OrCam does not mean discontinuation from the study, 
and remaining study procedures should be completed as indicated by the study protocol. If a 
clinically significant finding is identified (including, but not limited to changes from baseline) after 
enrollment, the investigator or qualified designee will determine if any change in participant 
management is needed. Any new clinically relevant finding will be reported as an adverse event 
(AE). 
The data to be collected at the time of study intervention discontinuation will include the 
following: 
• Feasibility questionnaire (if participant has completed device training) 
• Ability and Applicability questionnaires 
• Adverse events 
• Quality of Life questionnaires 
Participants are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue or withdraw a participant from the study for the following 
reasons: 
• Completion of study intervention 
• Disease progression which requires discontinuation of the study intervention 
• If any clinical adverse event (AE), laboratory abnormality, or other medical condition or 
situation occurs such that continued participation in the study would not be in the best 
interest of the participant 
• Investigator discretion 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Prior to removal from study, effort will be made to have all participants complete a safety 
evaluation approximately 1 week following the last use of study device. 
Participants are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue or withdraw a participant from the study for the following 
reasons: 
• Significant study intervention non-compliance 
• If the participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
• Participant has completed the study follow-up period 
• Death 
• Screen Failure 
The reason for participant discontinuation or withdrawal from the study will be recorded on 
the Discontinuation/Withdrawal Case Report Form (CRF). Participants who sign the informed 
consent form but do not receive the study intervention, i.e. the activities on enrollment/baseline 

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day, may be replaced. Participants who sign the informed consent form, receive the study 
intervention, and subsequently withdraw, or are withdrawn or discontinued from the study, will 
not be replaced. 
7.3 
LOST TO FOLLOW-UP 
A participant will be considered lost to follow-up if he or she fails to return for two weekly 
scheduled check-in calls and is unable to be contacted by the study site staff. 
The following actions must be taken if a participant fails to present for a required study 
appointment: 
• The site will attempt to contact the participant within +/- 2 days of the scheduled 
appointment and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain if the participant wishes to or should continue in the study. 
• Before a participant is deemed lost to follow-up, the investigator or designee will make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, if 
necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the participant’s 
medical record or study file. 
• Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
8 
STUDY ASSESSMENTS AND PROCEDURES 
8.1 
SCREENING PROCEDURES 
 
8.1.1 Screening activities performed prior to obtaining informed consent 
Minimal risk activities that may be performed before the subject has signed a consent include 
the following: 
• Email, written, in person or telephone communications with prospective subjects. 
• Review of existing medical records to include H&P, laboratory studies, etc. 
• Review of existing MRI, x-ray, or CT images. 
• Review of existing photographs or videos. 
• Review of existing pathology specimens/reports from a specimen obtained for diagnostic 
purposes. 
 
To determine CLN3 disease status, we will review medical or research records evaluations 
done for diagnostic purposes. If this information is not available from the CLN3 Natural History 
protocol 18-CH-0002, we will request them via written or verbal query. If genetic sequencing has 
not been done, it can be done under this protocol as part of the screening evaluations or under 
protocol 18-CH-0002. 
 
8.1.2 Screening activities performed after a consent for screening has been signed 
Screening procedures as listed in the Schedule of Activities will be done on-site at the NIH CC 
to determine study eligibility. Results of the below evaluations within the time frame and from 
sources indicated in Table 2 will be reviewed by the corresponding collaborating specialists and 

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accepted for purpose of determining eligibility as applicable. All other procedures listed in the 
Schedule of Activities for the screening visit can be done within 6 months of study enrolment. 
Table 2. Types of evaluations and results acceptable for use in determining study eligibility. 
 
Procedures 
Acceptable 
Time prior to enrolment 
Route 
Ophthalmology 
within 3-4 months 
18-CH-0002; NEI protocols (e.g. 08- 
EI-0102, 13-EI-0049, 15-EI-0128) 
Neuropsychologic 
within 6 months 
18-CH-0002; outside or NIH records 
Audiology 
within 3-4 months 
18-CH-0002; outside or NIH records 
 
1. Ophthalmologic Evaluation. We will collaborate with the NEI team to obtain an age- 
appropriate eye examination in study participants, with documentation of best uncorrected 
and corrected visual acuity. The evaluations will be adjusted based on applicability of 
available records as listed in Table 2. No sedation will be used under this protocol. 
 
2. Neuropsychologic Evaluation. We will assess cognitive function in study participants, by 
using clinical judgment based on age and/or developmental level, to prioritize use of the 
following instruments, if possible: 
A Wechsler IQ test 
Wechsler Preschool and Primary Scale of Intelligence, 4th edition for children ranging 
from 2.6-3.11 and 4.0-7.7, or 
Wechsler Intelligence Scale for Children-Fifth Edition (WISC-V) for 6 to 16 years of 
age, or 
Wechsler Adult Intelligence Scale—Fourth Edition (WAIS-IV) for individuals over age 
16 will be the preference. 
The Wechsler Abbreviated Scale of Intelligence-Second Edition, or the Wechsler 
Nonverbal Scale of Ability (WNSA) will be used when necessary. 
Further for younger individuals or those with significant cognitive impairments, the 
following tests will be used: 
Mullen Scales of Early Learning (MSEL). The Mullen Scales of Early Learning is a 
standardized developmental test for children birth to 5 years, 8 months. The measure 
consists of five scales: Gross Motor, Visual Reception, Fine Motor, Receptive 
Language, and Expressive Language; all scales with the exception of the Gross Motor 
scale provide an estimate of developmental functioning, the Early Learning Composite. 
For assessment of adaptive behavior, The Vineland Adaptive Behavior Scales, Third 
Edition, based on parent interview, will be employed. This may be done by methods that 

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do not require in-person meetings (such as via a phone call) to provide adaptability to the 
protocol and to maximize ability to collect meaningful longitudinal data. 
Other neuropsychological assessments that may be used include: 
Wide Range Assessment of Memory and Learning, 2nd edition (WRAML-2) for 
individuals 5 – 90 years of age 
Clinical Evaluation of Language Fundamentals, 5th edition (CELF-5) for individuals 
5-21 years of age 
Participants, legal guardians and informants will be allowed to take parent/informant and 
self-report measures on the day of the testing appointment, and return them by self- 
addressed, stamped envelope if they are not able to complete them on the day of the 
evaluation. The self-reported measures may also be completed via a web-based format. The 
evaluations will be adjusted based on applicability of available records as listed in Table 
2. It is anticipated that parent interview and completion of the parent report forms will take 
approximately 1 to 1.5 hours. 
3. Audiologic evaluation. An audiologic evaluation may include behavioral assessment of 
pure-tone and speech thresholds, and word recognition ability using test techniques 
appropriate for age and condition. Physiologic measures that do not require a behavioral 
response will be used to evaluate middle ear function (tympanometry), acoustic reflex 
thresholds, and cochlear function (otoacoustic emissions). The auditory evoked potentials 
will be used to assess functional integrity of the auditory nerve and auditory central nervous 
system pathways. This evaluation takes approximately 2 hours, and will be adjusted based 
on applicability of available records as listed in Table 2. 
8.2 
EFFICACY ASSESSMENTS 
The specific timing of procedures/evaluations to be done at each study visit are captured in 
Section 1.3, Schedule of Activities. Direct evaluations (e.g., Function test) at Screening, 
Enrollment Baseline Day 1, Device Training Day 2, and 1-Week Evaluations Day 5 visits will be 
done onsite at the NIH CC. Non-direct evaluations (e.g., surveys and questionnaires) and 
evaluations on other study days can be done onsite or at home. Non-direct evaluations may be 
completed using paper or web-based format. 
 
8.2.1 Clinical Evaluations 
1. Function Test. The study participants will be asked to complete tasks relating to device- 
supported daily activities (Appendix C). These include identification of printed words 
(e.g., books, documents, menus, labels, signs) and identification of faces and colors. 
At Days 1 (baseline) and 5 (1-week evaluation), the Function Test will be done in its 
entirety via face-to-face encounters. A sub-group of the Function Test items may be done 
via the use of remote technologies (e.g., videoconferencing). At the 1-month evaluation, if 
the study participants are able to come to the NIH the Function Test will be done as on 
Days 1 and 5. If study participants are not able to come for an in-person visit, the sub- 
group of the Function Test items will be done remotely. 
2. Ability 
and 
Applicability 
Questionnaires. 
Parents/Guardians 
will 
complete 
questionnaires of their child’s ability to accomplish the tasks in the Function Test without 
help, and their ratings of how important it would be for their child to accomplish these 

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tasks without help. (Appendices D, E). The questionnaires may be completed using paper 
or web-based format. 
3. Neuropsychologic Evaluation. We will assess adaptive behavior using The Vineland 
Adaptive Behavior Scales, Third Edition, Daily Living Scale, based on parent interview. 
This may be done by methods that do not require in-person meetings (such as via a phone 
call) to provide adaptability to the protocol and to maximize ability to collect meaningful 
longitudinal data. 
4. Quality of Life Questionnaires. Parents/Guardians will complete age-appropriate 
PedEyeQ[27], PROMIS[28], and Low Vision QOL[29] questionnaires (Appendices G - 
I). The questionnaires may be completed using paper or web-based format. 
8.2.2 Biospecimen Evaluations 
Not applicable. Biological specimen collected will be for future research use and not for 
efficacy assessment. 
 
8.2.3 Correlative Studies for Research/Pharmacokinetic Studies 
Not applicable. 
 
8.2.4 Samples for Genetic/Genomic Analysis 
8.2.4.1 Description of the scope of genetic/genomic analysis 
DNA may be obtained for CLN3 genotyping and stored for future molecular analysis of other 
genes that may influence the CLN3 phenotype. DNA will be obtained from blood, buccal swab, 
or saliva. Exome/genome or other forms of next-generation sequencing may be performed. 
DNA analysis is not restricted to standard DNA sequencing. For example, methylation patterns 
may be studied, or new technologies applied. Any mutation analysis reported to the participant or 
participant’s family will be confirmed in a CLIA approved laboratory. 
RNA analysis may be performed. This analysis is not limited to mRNA but may include other 
RNAs such as miRNA and ncRNA. 
8.2.4.2 Description of how privacy and confidentiality of medical information/biological 
specimens will be maximized 
Data or biomaterials will be shared with collaborating research groups or laboratories at the 
NIH or outside the NIH. The data will be anonymized using a unique code generated for each 
study participant using cryptographic methods that cannot be reversed. Collaborating sites may 
use the same methods to generate the unique code. Thus, participants common to collaborating 
sites can be linked by the unique identifier. However, participants who have not been seen at a 
collaborating site will remain unknown (de-identified). 
The protocols at the NIH and other sites will describe the coding mechanism described above 
and allow for data sharing with outside institutions. The collaborating institutions will have IRB 
oversight for their activities with identifiable data and samples. The Consent forms will inform 
the study participants that their coded data and samples will be shared with institutions who may 
be able to re-identify them. 
Biomaterials may be used in multi-omic studies to identify potential biomarkers correlating to 
CLN3 disease and progression. Biomaterials sent to groups outside of the NIH may be coded (“de- 
identified”) or unlinked from an identifying code (“anonymized”). Outside laboratories may be 

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provided with coded or anonymized demographic, phenotypic and genotypic data necessary to 
fully interpret the experimental results. For biomaterials sent to groups outside of the NIH 
appropriate Material Transfer Agreements will be obtained. 
Coded or anonymized data may be submitted to NIH-designated repositories (such as DASH) 
or databases per NIH data sharing policy. Repositories receiving data from this protocol may be 
open- or restricted-access. 
8.2.4.3 Management of Results 
Participants will be contacted if a clinically actionable gene variant is discovered on research 
testing. Clinically actionable findings for the purpose of this study are defined as disorders 
appearing in the American College of Medical Genetics and Genomics recommendations for the 
return of incidental findings that is current at the time of primary analysis. Participants will be 
contacted at this time with a request to provide a blood sample to be sent to a CLIA certified 
laboratory. A provider on the study team with training or practice experience in genetics will 
discuss the results with the participants. 
This is the only time during the study that incidental findings will be returned. No 
interrogations regarding clinically actionable findings will be made after the primary analysis. 
8.2.4.4 Genetic counseling 
Genetic counseling and discussion of results will be done by a provider on the study team with 
training or practice experience in genetics. 
8.3 
SAFETY AND OTHER ASSESSMENTS 
The specific timing of procedures/evaluations to be done at each study visit are captured in 
Section 1.3, Schedule of Activities. Direct evaluations (e.g., Device training, Feasibility test) at 
Screening, Enrollment Baseline Day 1 and 1-Week Evaluations Day 5 visits will be done onsite at 
the NIH CC. Non-direct evaluations (e.g., surveys and questionnaires) and evaluations on other 
study days can be done onsite or at home. 
 
1. Medical History and Physical Exam. A medical history and physical exam will be 
obtained. For CLN3 participants, medical history will ascertain information that is being 
collected 
as 
part 
of 
a 
national 
CLN3 
registry 
(https://rarediseases.info.nih.gov/diseases/5897/neuronal-ceroid-lipofuscinosis-3). 
Participation in the registry is not a requirement and caretakers or participants will be given 
the option of having medical information submitted to the registry. The history forms 
contain common data elements recommended for rare diseases research. Parents and 
participants may also be asked what elements of the disease are clinically relevant to them, 
in order to obtain insight into pertinent outcome measures in designing future therapeutic 
trials. Information from outside records or NIH visits, and from reports by participants and 
family members will be collected and reviewed. 
2. Anthropomorphic Measures and Clinical Photography. Anthropomorphic measures 
including weight, length/height, and head circumference will be obtained at each visit. 
3. Feasibility Questionnaire. Participants/parents/guardians will be asked to complete a 
questionnaire relating to their experience using the OrCam device (Appendix B). The 
questionnaire can be completed on paper or web-based format at the time points indicated 
in the Schedule of Activities. 

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4. Device Training. A study team member will provide verbal instructions to participant and 
parents/guardians on the assembly, set-up, and use of the OrCam. The instructions will be 
based on the User Guide (Appendix J). At the end of the training session, understanding 
of how to use the device will be documented by the trainer. 
5. Device Use Diary. As described in Section 6.4 Study Intervention Compliance. 
6. Adverse Events Review. A study team member will contact the family at the times 
indicated in the Schedule of Activities to collect information on adverse events relating to 
the use of OrCam MyEye 2. During this interaction, study team member will also review 
the Device Use Diary with the family and provide assistance to trouble shoot any issue 
relating to the use of the device. 
7. Clinical Staging. For CLN3 participants not co-enrolled in protocol 18-CH-0002, clinical 
staging will be performed using the Unified Batten Disease Rating Scale (UBDRS). The 
UBDRS was developed to provide a tool to quantify physical, behavioral and functional 
aspects of juvenile neuronal ceroid lipofuscinosis [30]. Data from the ophthalmological, 
neurological, neurocognitive and speech evaluations will be integrated to obtain a UBDRS 
score for each participant. This tool has been shown to be a reliable instrument [30] and 
has been utilized in a retrospective evaluation of flupirtine [31] and prospectively for 
mycophenolate 
mofetil 
(https://clinicaltrials.gov/ct2/show/NCT01399047?term=CLN3&rank=2) 
8. Biomaterials Collection. To complement the CLN3 Natural History (18-CH-0002) 
protocol’s objective to identify biochemical markers, biospecimens will be collected from 
CLN3 participants who are not co-enrolled in 18-CH-0002. Participants will be consented 
for broad use and future research on the collected biomaterials. The method of analysis for 
biomarker discovery is not specified. Applicable technologies include but are not limited 
to proteomics, lipidomics, expression analysis, gene/exome/genome/transcriptome 
sequencing, metabolomics, and multi-analytes profiling. Subcomponents of a sample, such 
as exosomes, may be isolated and studied. Comparisons will be made to age similar control 
samples, made up in part by those collected from the non-CLN3 participants in this study. 
Since the function of CLN3 protein is incompletely understood, the objectives for 
biomarker discoveries are broad and may include those such as identifications of 
compounds in the plasma or urine whose level correlate with disease progression or with 
future therapeutic interventions. 
Collected cells may be used to produce cellular derivatives such as lymphoblasts, 
immortalized cell lines, or induced pluripotent stem cells. Coded samples will be 
maintained in the NICHD Biorepository and will be made available to collaborating 
laboratories with appropriate IRB and MTA clearance. 
Biomaterials collected as part of this study will include the following: 
-blood (such as serum, EDTA plasma and heparin plasma) 
-urine 
-DNA for CLN3 genotyping, modifier gene analysis or exome/genome sequencing 
-dried blood spots on newborn screening cards 
-peripheral mononuclear cells 
-cheek swabs/scrapings 
-saliva 

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-skin biopsy (3mm or smaller) 
Although efforts will be made to obtain as complete a collection as possible, since these 
samples are collected for discovery research and not for safety monitoring not obtaining a 
specific sample will not be considered a protocol deviation. Except for blood-related 
samples, all other biomaterials will only be collected if not already done so under protocol 
18-CH-0002. 
Identified biospecimens obtained at outside institutions corresponding to study participants 
already enrolled in the study may be acquired under this protocol. These samples could be 
obtained secondary to clinical procedures (such as surgical specimens, clinical blood 
testing, or autopsy) or obtained as part of another ongoing clinical trial. Study participants 
will be consented to allow for the identifiable samples to be sent to NIH. These samples 
will be treated the same as a research specimen that was collected at the NIH Clinical 
Center. Unless needed for an ongoing experiment or requiring specific storage conditions 
other than -80 degrees Celsius, samples will be coded and stored in the NICHD 
Biorepository. 
9. Phlebotomy. We anticipate collecting a maximum of 80 mL (5-6 tablespoons) of blood 
per participant. If more than one blood collections are needed (e.g., because of severe 
hemolysis) we will not exceed the 5 ml/kg/day, or 9.5 mL/kg over any 8-week period limits. 
Nursing staff will monitor blood-drawing volumes. 
10. Cheek swabbing/scraping and saliva collection. We will use commercially available kits 
and follow the manufacturer’s instructions. 
11. Skin biopsy. A local anesthetic may be applied prior to the procedure. A 2-3 mm punch 
biopsy of the skin will be removed using sterile technique, and the wound will be dressed. 
12. Urine collection. We may use a urine cup or toilet hat to collect urine. Participants will 
not be catheterized for this study. 
13. Outside records. Under this protocol we may collect non-NIH Clinical Center outside 
records such as medical and research corresponding to participants or family members of 
participants. Typically, these records will be provided directly by the participant/guardian. 
A release of records request signed by the participant/guardian will be used if obtaining 
records from other health care providers. Information from these records may be 
incorporated into study databases. These records and personal identifying information will 
be maintained confidentially. 
14. Future Research. Biomaterials, records, and data collected as part of this protocol may be 
used for future research not specifically specified in this protocol by both NIH and non- 
NIH investigators. Samples sent to outside laboratories will be coded, unless a standard 
clinical test is being performed. Materials Transfer Agreements will be obtained as 
applicable for samples sent to collaborators. 
15. Return of results and community engagement. Participants will have access to all 
clinical testing and evaluation results through the NIH Clinical Center Portal. Protocol 
status is reviewed with participating families. Research results will be presented to the 
disease community via presentations or updates to the family support groups. Copies of 
publications related to this research will also be made available to the family support 
groups. The trial will be registered on clinicaltrials.gov and results will be posted per 
standard requirements. 

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The concept for this study arose from parental responses from the CLN3 natural history 
study. When asked to rank in order (1=most desirable) the symptoms they would like to 
see being addressed by future interventions, 37% of mothers (n=19) and 47% of fathers 
(n=15) chose vision as number one. A family of a child with CLN3 brought the OrCam 
MyEye 2 device to the study team’s attention, and their observations on its use has been 
incorporated into the study design. 
8.4 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
 
8.4.1 Definition of Adverse Event 
Adverse event means any untoward medical occurrence associated with the use of an 
intervention in humans, whether or not considered intervention-related (21 CFR 312.32 (a)). 
 
8.4.2 Definition of Serious Adverse Events (SAE) 
An adverse event (AE) or suspected adverse reaction is considered "serious" if, in the view of 
either the investigator or sponsor, it results in any of the following outcomes: death, a life- 
threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a 
persistent or significant incapacity or substantial disruption of the ability to conduct normal life 
functions, or a congenital anomaly/birth defect. Important medical events that may not result in 
death, be life-threatening, or require hospitalization may be considered serious when, based upon 
appropriate medical judgment, they may jeopardize the participant and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition. Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an emergency room 
or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse. 
 
8.4.3 Classification of an Adverse Event 
8.4.3.1 Severity of Event 
For adverse events (AEs) not included in the protocol defined grading system, the following 
guidelines will be used to describe severity. 
• Mild – Events require minimal or no treatment and do not interfere with the participant’s 
daily activities. 
• Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
• Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually potentially life-threatening or 
incapacitating. Of note, the term “severe” does not necessarily equate to “serious”. 
8.4.3.2 Relationship to Study Intervention 
All adverse events (AEs) must have their relationship to study intervention assessed by the 
investigator who examines and evaluates the participant based on temporal relationship and his/her 
clinical judgment. The degree of certainty about causality will be graded using the categories 
below. In a clinical trial, the study product must always be suspect. 

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• Related – The AE is known to occur with the study intervention, there is a reasonable 
possibility that the study intervention caused the AE, or there is a temporal relationship 
between the study intervention and event. Reasonable possibility means that there is 
evidence to suggest a causal relationship between the study intervention and the AE. 
• Not Related – There is not a reasonable possibility that the administration of the study 
intervention caused the event, there is no temporal relationship between the study 
intervention and event onset, or an alternate etiology has been established. 
OR 
• Definitely Related – There is clear evidence to suggest a causal relationship, and other 
possible contributing factors can be ruled out. The clinical event, including an abnormal 
laboratory test result, occurs in a plausible time relationship to study intervention 
administration and cannot be explained by concurrent disease or other drugs or chemicals. 
The response to withdrawal of the study intervention (dechallenge) should be clinically 
plausible. The event must be pharmacologically or phenomenologically definitive, with 
use of a satisfactory rechallenge procedure if necessary. 
• Probably Related – There is evidence to suggest a causal relationship, and the influence 
of other factors is unlikely. The clinical event, including an abnormal laboratory test result, 
occurs within a reasonable time after administration of the study intervention, is unlikely 
to be attributed to concurrent disease or other drugs or chemicals, and follows a clinically 
reasonable response on withdrawal (dechallenge). Rechallenge information is not required 
to fulfill this definition. 
• Potentially Related – There is some evidence to suggest a causal relationship (e.g., the 
event occurred within a reasonable time after administration of the trial medication). 
However, other factors may have contributed to the event (e.g., the participant’s clinical 
condition, other concomitant events). Although an AE may rate only as “possibly related” 
soon after discovery, it can be flagged as requiring more information and later be upgraded 
to “probably related” or “definitely related”, as appropriate. 
• Unlikely to be related – A clinical event, including an abnormal laboratory test result, 
whose temporal relationship to study intervention administration makes a causal 
relationship improbable (e.g., the event did not occur within a reasonable time after 
administration of the study intervention) and in which other drugs or chemicals or 
underlying disease provides plausible explanations (e.g., the participant’s clinical 
condition, other concomitant treatments). 
• Not Related – The AE is completely independent of study intervention administration, 
and/or evidence exists that the event is definitely related to another etiology. There must 
be an alternative, definitive etiology documented by the clinician. 
8.4.3.3 Expectedness 
The Principal Investigator or designated study team member will be responsible for 
determining whether an adverse event (AE) is expected or unexpected. An AE will be considered 
unexpected if the nature, severity, or frequency of the event is not consistent with the risk 
information previously described for the study intervention. 

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8.4.4 Time Period and Frequency for Event Assessment and Follow-Up 
The occurrence of an adverse event (AE) or serious adverse event (SAE) may come to the 
attention of study personnel during study visits and interviews of a study participant presenting for 
medical care, or upon review by a study monitor. 
All AEs including local and systemic reactions not meeting the criteria for SAEs will be 
captured on the appropriate case report form (CRF). Information to be collected includes event 
description, time of onset, clinician’s assessment of severity, relationship to study product 
(assessed only by those with the training and authority to make a diagnosis), and time of 
resolution/stabilization of the event. All AEs occurring while on study must be documented 
appropriately regardless of relationship. All AEs will be followed to adequate resolution. 
Any medical condition that is present at the time that the participant is screened will be 
considered as baseline and not reported as an AE. As CLN3 is a neurodegenerative, multisystemic 
disease, progression or new onset of symptoms may be part of the disease process and unrelated 
to the intervention. Problems listed in Table 2 will not be reported to the IRB as adverse events 
unless increase in frequency is noted. 
Changes in the severity of an AE will be documented to allow an assessment of the duration 
of the event at each level of severity to be performed. AEs characterized as intermittent require 
documentation of onset and duration of each episode. 
A designated study team member will record all reportable events with start dates occurring 
any time after informed consent is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) 
after the last day of study participation. At each study visit, the investigator will inquire about the 
occurrence of AE/SAEs since the last visit. Events will be followed for outcome information until 
resolution or stabilization. 
8.4.5 Adverse Event Reporting 
The Principal Investigator and designated study team members are responsible for detecting, 
documenting, and reporting unanticipated problems, adverse events (AEs), including serious 
adverse events (SAEs), and deviations in accordance with NIH policy, and IRB requirements. 
Relatedness to the research of all serious adverse events will be determined by the PI in 
consultation with the CD. 
Serious unanticipated problems and serious protocol deviations will be reported to the IRB and 
CD as soon as possible and in writing not more than 7 days after the PI first learns of the event. 
Deaths will be reported to the Clinical Director within 7 days after the PI first learns of the 
event. 
All adverse events, deviations, and unanticipated problems will be summarized and reported 
at the time of Continuing Review. 
 
Table 2. Adverse events associated with CLN3 
Category 
Adverse Event 
HEENT 
Eyes 
Low vision/blindness; abnormal movements 
(nystagmus); photophobia; visual hallucination 
Ears 
Auditory hallucination; abnormalities in Behavioral 
Hearing and ABR tests 
Oromotor/ 
Speech 
Dysphagia; drooling; dysarthria 

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Cardiovascular 
Sinus arrythmias; prolonged ECG intervals; elevated 
BNP 
Hematology 
Decreased serum iron, % saturation 
Endocrinology 
Abnormal TSH; low vitamin D 
Musculoskeletal 
Abnormal gait; falls; scoliosis; in-toeing; abnormal 
muscle tone; tremors 
Neurological 
Brain atrophy; seizures; cognitive impairment; 
memory impairment; sleep disruption; fatigue 
Psychiatric/Behavioral 
Irritability; aggression; perseveration; anxiety; mood 
instability 
ABR: auditory brainstem response. BNP: pro-brain natriuretic peptide. ECG: electrocardiogram. 
HEENT: head, eyes, ears, nose, throat. TSH: thyroid stimulating hormone 
 
8.4.6 Serious Adverse Event Reporting 
The study investigator shall report the event to the reviewing Institutional Review Board (IRB) 
IC’s designee and as soon as possible, but in no event later than 7 calendar days after the 
investigator first learns of the effect. 
8.4.7 Events of Special Interest 
Not applicable. 
 
8.4.8 Reporting of Pregnancy 
Not applicable. 
8.5 
UNANTICIPATED PROBLEMS 
 
8.5.1 Definition of Unanticipated Problems (UP) 
Any incident, experience, or outcome that meets all of the following criteria: 
• Unexpected in terms of nature, severity, or frequency given (a) the research procedures 
that are described in the protocol-related documents, such as the Institutional Review 
Board (IRB)-approved research protocol and informed consent document; and (b) the 
characteristics of the participant population being studied; and 
• Related or possibly related to participation in the research (“possibly related” means 
there is a reasonable possibility that the incident, experience, or outcome may have 
been caused by the procedures involved in the research); and 
• Suggests that the research places participants or others (which many include research 
staff, family members or other individuals not directly participating in the research) at 
a greater risk of harm (including physical, psychological, economic, or social harm) 
than was previously known or expected. 
 
8.5.2 
Unanticipated Problem Reporting 
The investigator will report unanticipated problems (UPs) to the NIH Institutional Review 
Board (IRB) as per Policy 801. 

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8.5.3 NIH Intramural IRB Reporting of IND Safety Reports 
Not applicable. 
9 
STATISTICAL CONSIDERATIONS 
9.1 
STATISTICAL HYPOTHESIS 
• Primary Endpoint(s): The primary endpoint of this study is to assess the safety and 
feasibility of using the OrCam device pediatric individuals with low vision. Assessment of 
safety will be made by evaluating summary statistics of Adverse events/ Unanticipated 
problems, Feasibility test, Feasibility questionnaire, and Device use diary in all 30 enrolled 
participants. We hypothesize that use of the device will be safe and feasible in pediatric 
individuals with CLN3. 
• Secondary Endpoint(s): We hypothesize that the use of OrCam MyEye 2 will enhance the 
participants’ function on visual related tasks as measured by performance on the Function 
Test, and the Ability and Applicability questionnaires. 
9.2 
SAMPLE SIZE DETERMINATION 
Since no prior research or data are available and these measures are developed specifically for 
this pediatric population with multiple disabilities, power calculation is not able to be determined. 
The study in 12 neurologically intact adults reported a mean improvement of 70% in performance 
over baseline on the Function Test. We anticipate that the improvement will be lower given the 
age and comorbidities in the CLN3 cohort, thus propose a total enrolment of 30 pediatric 
participants. As outlined in Section 4.2 Scientific Rationale for Study Design, we anticipate 
being able to recruit 5 CLN3 and 5 non-CLN3 participants with low vision in one year. 
A major purpose of this trial is to obtain pilot data on feasibility and potential functional 
outcome measures that appears to improve with device use. The pilot data will inform power 
calculations for a subsequent trial focused on establishing device intervention efficacy. 
9.3 
POPULATIONS FOR ANALYSES 
 
9.3.1 Evaluable for toxicity 
All participants will be evaluable for adverse events from the time of their first use of the 
OrCam. 
 
9.3.2 Evaluable for objective response 
Only those participants who have used the device for at least 3 days and have completed the 
Feasibility and Efficacy evaluations both before and after device use will be considered evaluable 
for response. 
 
9.3.3 Evaluable Non-Target Disease Response 
Not applicable. 

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9.4 
STATISTICAL ANALYSES 
 
9.4.1 General Approach 
For comparisons of before and after device intervention in the same participant and correlation 
calculations, statistical significance will be determined by corresponding parametric (e.g., paired 
t-test and Pearson correlation) or non-parametric (Wilcoxon Rank sum test and Spearman 
correlation) methods. A p value < 0.05 will be considered significant and between 0.05 and 0.10 
will be considered a trend. Multiple comparisons will be corrected by appropriate post-hoc 
analysis. 
 
9.4.2 Analysis of the Primary Endpoints 
Adverse events and Device use diary data will be provided using descriptive statistics. 
Feasibility Test 
Data analysis. Participants’ scores will be the sum of items 1 to 5 and will range from 0 
to 5. Analysis will consist of summary descriptive statistics (mean, standard deviation, 
median, proportion of participants at each score level). No formal statistical tests will be 
conducted. Interpretation of results will be rule-based. 
Rules for data interpretation. Device use is feasible if at baseline, 1-week, or 1-month 50% 
or more of total number of participants score 3 or greater out of 5. 
Feasibility Questionnaire 
Data analysis. Participants’ scores will be the sum of items 1 to 11 and will range from 0 
to 11. Analysis will consist of summary descriptive statistics (mean, standard deviation, 
median, proportion of participants at each score level). No formal statistical tests will be 
conducted. Interpretation of results will be rule-based. 
Rules for data interpretation. Device use is feasible if at 1-week or 1-month 50% or more 
of total number of participants score 6 or greater out of 11. 
 
9.4.3 Analysis of the Secondary Endpoint(s) 
Function Test – Efficacy Scores 
Data analysis. Participants’ scores will be the sum of items 1 to 7 combining levels a & b 
and will range from 0 to 14, and the mean duration to complete each task. Analysis will 
consist of change in scores and mean duration to complete each task from baseline to 1 
week and 1 month). No formal statistical tests will be conducted. Interpretation of results 
will be rule-based. 
Rules for data interpretation. Device use is efficacious if at 1-week or 1-month compared 
to baseline: 
● 25% or more of total number of participants increased score by at least 30% 
● 25% or more of total number of participants decreased time by at least 30% 
Below are some simulations of the power of a paired-sample test for change from baseline, 
using a sample size of 10 participants. This provides a sense of the possible characteristics 
of the data and for justifying the sample size. 
Simulations for tasks-completed scores 
Each simulation study used 1000 replications with N = 10. For each replication, 
baseline and post-baseline sets of scores were randomly generated. Means, standard 
deviations, and paired-samples t-tests of difference scores (Post-baseline – Baseline) 

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were computed. Power was computed by the percent of replications (out of 1000) with 
t-test p-values less than or equal to 0.05. Baselines were generated by randomly 
selecting, with replication, scores from 0 to 5 with equal probability, 1/6. The baseline 
range matched the baseline values reported in the adult study. Post-baseline scores 
included a specified number of baseline cases randomly selected without replacement 
to improve by 30% (Baseline x 1.30). Cases with baseline values = 0 were excluded 
from random selection since percentage change from 0 is undefined. 
Simulation 1. Based on the decision rule of 25% of total participants, 3 cases 
(rounded up since 25% of N= 10 is 2.5) were randomly selected to improve 30% 
from baseline and the other 7 cases did not improve. Results: power = proportion 
of 1000 p-values <= 0.05 = 0.37. 
Simulation 2. 3 cases randomly selected to improve 30% and 7 cases improved by 
1 point. Results: power = proportion of 1000 p-values <= 0.05 = 1.0. 
Simulation 3. 4 cases randomly selected to improve 30% and 6 cases did not 
improve. Results: power = proportion of 1000 p-values <= 0.05 = 0.95. 
Simulation 4. 4 cases randomly selected to improve 30%, 6 cases improved by 1. 
Results: power = proportion of 1000 p-values <= 0.05 = 1.0. 
Simulation 5. 2 cases randomly selected to improve 30% and 8 cases did not 
improve. Results: power = proportion of 1000 p-values <= 0.05 = 0.00. 
Simulation 6. 2 cases randomly selected to improve 30%, 8 cases improved by 1. 
Results: power = proportion of 1000 p-values <= 0.05 = 1.0. 
 
Simulations with baseline values 1 to 5, # cases improving 30%: 2 to 5; # cases 
improving by 1: 0 to 3; # cases no improvement: 4 to 8. (For any simulation run, # 
cases improving 30% + #cases improving by 1 + # cases not improving = 10). 
Results: These simulations correct for the problem that percentage improvement is 
undefined when baseline = 0. When stipulating that percentage improvement is 
30% for as few as 2 or 3 cases, power is greater than .99 when only 1 to 3 other 
randomly selected cases improve by 1 from baseline. Power will be higher if 
participants’ scores improve more than 1 over baseline. 
Based on these simulations, a test of efficacy using a paired-samples t-test with N = 10 
would be adequately powered provided that post-baseline scores are likely to improve 
from baseline. Whether or not a sample of 10 is large enough to make conclusions about 
different characteristics of the sample group is not addressed. 
Ability Questionnaire 
Data analysis. Proportions of participants with scores 3 or greater in all items from 1-12. 
No formal statistical tests will be conducted. Interpretation of results will be rule-based. 
Rules for data interpretation. Device use is efficacious if there is a 25% increase in the 
proportion of participants scoring 3 or greater in all items at 1-week or 1-month as 
compared to baseline. 
 
9.4.4 Safety Analyses 
As described in Section 9.4.2. 

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9.4.5 Baseline Descriptive Statistics 
Baseline demographics, ophthalmic, neurodevelopmental and auditory data will be 
summarized using descriptive statistics or qualitatively as applicable. 
 
9.4.6 Planned Interim Analyses 
No interim analysis is planned for this pilot study. However, the Principal Investigator and 
designated study team members will be continually monitoring the feasibility and safety of the use 
of the OrCam and may terminate this study at any time for safety or administrative reasons. 
 
9.4.7 Sub-Group Analyses 
Analyses of the sub-groups will be as described in Sections 9.4.2 and 9.4.3. 
 
9.4.8 Tabulation of individual Participant Data 
Not applicable. 
 
9.4.9 Exploratory Analyses 
We will compare the feasibility and efficacy of the OrCam use in the CLN3 versus non-CLN3 
groups. We will evaluate data collected on unanticipated use (uses identified by participants and 
not an advertised feature) of OrCam MyEye 2 and correlation of use feasibility and ability to 
measures of disease status (e.g., disease severity, neuropsychologic ability, etc.) using summary 
statistics. Exploratory analyses of clinical and biochemical markers may be done under protocol 
18-CH-0002. 
10 REGULATORY AND OPERATIONAL CONSIDERATIONS 
10.1 INFORMED CONSENT PROCESS 
 
10.1.1 Consent/Assent Procedures and Documentation 
The informed consent document will be provided as a physical or electronic document to the 
participant or consent designee as applicable for review prior to consenting. A designated study 
investigator will carefully explain in terms suited to their comprehension the purposes, procedures, 
and tests involved in this study, and the associated risks, discomfort, and benefits. To minimize 
potential coercion, as much time as is needed to review the document will be given, including an 
opportunity to discuss it with friends, family members and/or other advisors, and to ask questions 
of any designated study investigator prior to signing. A signed informed consent document will be 
obtained prior to any research activities taking place. 
The initial consent process as well as re-consent, when required, may take place in person or 
remotely (e.g., via telephone or other NIH approved remote platforms used in compliance with 
policy, including HRPP Policy 303) per discretion of the designated study investigator and with 
the agreement of the participant/consent designee(s). Whether in person or remotely, the privacy 
of the subject will be maintained. Consenting investigators (and participant/consent designee, 
when in person) will be located in a private area (e.g., clinic consult room). When consent is 
conducted remotely, the participant/consent designee will be informed of the private nature of the 
discussion and will be encouraged to relocate to a more private setting if needed. If the consent 
process is occurring remotely, participants and investigators will view individual copies of the 
approved consent document either on paper or on screens at their respective locations; the same 
screen or paper document may be used when both the investigator and the participant are co-
located but this is not required. When required, the witness signature will be obtained similarly as 

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described for the investigator and participant below. 
Consent will be documented with required signatures on the physical document (which 
includes the printout of an electronic document sent to the participant) or on the electronic 
document and made part of the participant’s NIH record. The process for documenting signatures 
on an electronic document is described below. 
When a hand signature on an electronic document is used for the documentation of consent, 
this study will use the following electronic platforms to obtain the required signatures: 
 
• Adobe Acrobat platform (which is 21 CFR Part 11 compliant); or 
• iMedConsent platform (which is 21 CFR Part 11 compliant) 
 
Both the investigator and the participant will sign the electronic document using a finger, 
stylus, or mouse. Electronic signatures (i.e., the “signature” is digitally generated) will not be used. 
We will obtain written informed consent from the parents /guardian(s) who accompany the 
child to the NIH Clinical Center (CC). If the parents are divorced and share custody, we will obtain 
consent from both parents. If the second parent is unable to attend the visit, the second parent will 
be consented via telephone or other NIH approved remote platforms as described above An 
individual who is not associated with the protocol must witness the signature of the absent 
parent/guardian on the consent form. According to 45 CFR 
46.408 when one parent is deceased, unknown, incompetent, or not reasonably available, or 
when only one parent has legal responsibility for the care and custody of the child, the permission 
of one parent suffices. Where deemed appropriate by the clinician and the child’s parent(s) or 
guardian, the child will also be included in all discussions about the trial and age-appropriate 
language will be used to describe the procedures and tests involved in this study, along with the 
risks, discomforts, and benefits of participation. Verbal assent will be obtained as appropriate for 
children ages 6-10. Children under the age of 18, but who are age > 10 years will be asked to sign 
an age-appropriate assent form. Children under the age of 6 years are not eligible for enrolment. 
The consent/assent process will be documented in the child’s medical record, including the 
assessment of the child’s ability to provide assent (verbal versus written) as applicable. If 
applicable, children will be contacted after they have reached the age of 18 to determine whether 
they wish to continue on the trial and informed consent will be obtained from them at that time. 
 
10.1.2 Consent for minors when they reach the age of majority 
When a pediatric subject reaches age 18, continued participation (including ongoing 
interactions with the subject or continued analysis of identifiable data) will require that consent be 
obtained from the now adult with the standard protocol consent document to ensure legally 
effective informed consent has been obtained. 
If reconsent is not feasible, we request waiver of informed consent to continue to use data 
and/or specimens for those individuals who become lost to follow up or who have been taken off 
study prior to reaching the age of majority. 
Requirements for Waiver of Consent consistent with 45 CFR 46.116 (d): 
(1) The research involves no more than minimal risk to the subjects. 
a. Analysis of samples and data from this study involves no additional risks to 
subjects. 
(2) The research could not practicably be carried out without the waiver or alteration. 

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a. Considering the length of time between the minor’s last contact with the 
research team and their age of majority, it will likely be very difficult to locate 
them again. A significant reduction in the number of samples analyzed is likely 
to impact the quality of the research. 
(3) As the research involves using identifiable private information or identifiable 
biospecimens, the research could not practicably be carried out without using such 
information or biospecimens in an identifiable format. 
a. Though the purpose of future studies cannot yet be known, they often involve 
the correlation of clinical outcomes and clinical interventions with laboratory 
studies. Such information would be unavailable if access to medical record 
numbers was unavailable. 
(4) The waiver or alteration will not adversely affect the rights and welfare of the subjects. 
a. Retention of these samples or data does not affect the welfare of subjects. 
(5) Whenever appropriate, the subjects will be provided with additional pertinent 
information after participation. 
10.1.3 We only request a waiver of consent for those subjects who have been lost to follow-up 
or who have been taken off study prior to reaching the age of majority. Considerations 
for Consent of NIH staff, or family members of study team members 
Consent for NIH staff or family members of study team members will be obtained as detailed 
above with following additional protections: 
Consent will be obtained by an individual independent of the staff member’s team whenever 
possible. Otherwise, the consent procedure will be independently monitored by the CC 
Department of Bioethics Consultation Service to minimize the risk of undue pressure on the staff 
member. 
10.2 STUDY DISCONTINUATION AND CLOSURE 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending, or terminating party to study participants, 
investigator, and regulatory authorities. If the study is prematurely terminated or suspended, the 
Principal Investigator (PI) will promptly inform study participants and the Institutional Review 
Board (IRB) and will provide the reason(s) for the termination or suspension. Study participants 
will be contacted, as applicable, and be informed of changes to study visit schedule. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• Determination of unexpected, significant, or unacceptable risk to participants 
• Demonstration of efficacy that would warrant stopping 
• Insufficient compliance to protocol requirements 
• Data that are not sufficiently complete and/or evaluable 
• Determination that the primary endpoint has been met 
• Determination of futility 
Study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the IRB. 
 

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10.3 CONFIDENTIALITY AND PRIVACY 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, 
their staff, and the sponsor(s). This confidentiality is extended to cover testing of biological 
samples and genetic tests in addition to the clinical information relating to participants. Therefore, 
the study protocol, documentation, data, and all other information generated will be held in strict 
confidence. No information concerning the study, or the data will be released to any unauthorized 
third party without prior written approval of the PI/study team, or responsible party. 
All research activities will be conducted in as private a setting as possible. 
The study monitor, representatives of the Institutional Review Board (IRB), and/or regulatory 
agencies may inspect all documents and records required to be maintained by the investigator, 
including but not limited to, medical records (office, clinic, or hospital) and pharmacy records for 
the participants in this study. The clinical study site will permit access to such records. 
The study participant’s contact information will be securely stored at each clinical site for 
internal use during the study. At the end of the study, all records will continue to be kept in a secure 
location for as long a period as dictated by the reviewing IRB or Institutional policies requirement. 
To further protect the privacy of study participants, a Certificate of Confidentiality has been issued 
by the National Institutes of Health (NIH). This certificate protects identifiable research 
information from forced disclosure. It allows the investigator and others who have access to 
research records to refuse to disclose identifying information on research participation in any civil, 
criminal, administrative, legislative, or other proceeding, whether at the federal, state, or local 
level. By protecting researchers and institutions from being compelled to disclose information that 
would identify research participants, Certificates of Confidentiality help achieve the research 
objectives and promote participation in studies by helping assure confidentiality and privacy to 
participants. 
10.4 FUTURE USE OF STORED SPECIMENS AND DATA 
See Sections 8.3.14, Safety and Other Assessments, Future Research; 10.3, 
Confidentiality and Privacy; and 10.8, Data Handling and Record Keeping, for further 
information on future use of study records and specimens. 
10.5 SAFETY OVERSIGHT 
The research team will be responsible for monitoring adverse events, participant safety, and 
participant tolerability. Regular, typically weekly, meetings will be held by the research staff to 
review status of all participants, potential issues, and possible adverse events. The study is not 
blinded, of relatively short duration, and involves a small number of participants that can be 
adequately assessed through simple comparison, thus a DSMC is not required. It will be monitored 
by random audits by the NICHD Office of the Clinical Director as specified in the NICHD SOP 
for Intramural Clinical Protocol Monitoring. 
10.6 CLINICAL MONITORING 
The research team and Medical Monitor will be responsible for monitoring for participant 
safety. This protocol will be monitored by random audits by the NICHD Office of the Clinical 
Director as specified in the NICHD SOP (5.25.12). 
10.7 QUALITY ASSURANCE AND QUALITY CONTROL 
The NICHD Quality Assurance Program will perform random audits annually on at least 10% 

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of 
actively 
accruing 
NICHD 
protocols 
(policy: 
https://science.nichd.nih.gov/confluence/display/ocd/Protocol+Navigation). Study procedures 
will be subject to audits to ensure compliance with the protocol and applicable regulatory 
requirements consistent with the NICHD quality assurance program plan. Audit visits results will 
be reported to the Principal Investigator for further reporting as appropriate. 
10.8 DATA HANDLING AND RECORD KEEPING 
 
10.8.1 Data Collection and Management Responsibilities 
Data collection is the responsibility of the clinical trial staff under the supervision of PI. The 
investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of 
the data reported. 
All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data. Hardcopies of the study visit worksheets will be provided for use as source 
document worksheets for recording data for each participant enrolled in the study. Data recorded 
in the electronic case report form (eCRF) derived from source documents should be consistent 
with the data recorded on the source documents. Participants may enter responses directly in a 
web-based format such as the NICHD CTDB Clinical Trial Survey System (CTSS), which allows 
participants to respond either remotely or at the Clinical Center to their assigned self-reported 
questionnaires/eCRFs. These eCRFs are considered as the source documents. 
Clinical data (including adverse events (AEs), concomitant medications, and expected adverse 
reactions data) and clinical laboratory data will be entered into CTDB, a 21 CFR Part 11-compliant 
data capture system provided by NICHD. The data system includes password protection and 
internal quality checks, such as automatic range checks, to identify data that appear inconsistent, 
incomplete, or inaccurate. Clinical data will be entered directly from the source documents. 
 
10.8.2 Study Records Retention 
Study documents should be retained for a minimum of 2 years after the formal discontinuation 
of clinical development of the study intervention, and as per the NIH Intramural Records Retention 
Schedule. 
10.9 PROTOCOL DEVIATIONS AND NON-COMPLIANCE 
It is the responsibility of the investigator to use continuous vigilance to identify and report 
deviations and/or non-compliance to the NIH Institutional Review Board as per Policy 801. All 
deviations must be addressed in study source documents, reported to NICHD Program Official. 
The investigator is responsible for knowing and adhering to the reviewing IRB requirements. 
 
10.9.1 NIH Definition of Protocol Deviation 
A protocol deviation is any changed, divergence, or departure from the IRB-approved research 
protocol. 
• Major deviations: Deviations from the IRB approved protocol that have, or may have the 
potential to, negatively impact the rights, welfare, or safety of the subject, or to substantially 
negatively impact the scientific integrity or validity of the study. 
• Minor deviations: Deviations that do not have the potential to negatively impact the rights, 
safety or welfare of subjects or others, or the scientific integrity or validity of the study. 
 

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10.10 PUBLICATION AND DATA SHARING POLICY 
 
10.10.1 
Human Data Sharing Plan 
This study will be conducted in accordance with the following publication and data sharing 
policies and regulations: 
National Institutes of Health (NIH) Public Access Policy, which ensures that the public has 
access to the published results of NIH funded research. It requires scientists to submit final peer- 
reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed Central 
upon acceptance for publication. This study will comply with the NIH Data Sharing Policy and 
Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials 
Registration and Results Information Submission rule. As such, this trial will be registered at 
ClinicalTrials.gov, and results information from this trial will be submitted to ClinicalTrials.gov. 
In addition, every attempt will be made to publish results in peer-reviewed journals. Data from this 
study may be requested from other researchers 5 years after the completion of the primary endpoint 
by contacting the PI or NICHD. 
 
10.10.2 
Genomic Data Sharing Plan 
Not applicable. 
10.11 COLLABORATIVE AGREEMENTS 
Not applicable. 
 
10.11.1 
Agreement Type 
Not applicable. 
10.12 CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence, such as by the device 
manufacturer, is critical. Therefore, any actual conflict of interest of persons who have a role in 
the design, conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. 
Furthermore, persons who have a perceived conflict of interest will be required to have such 
conflicts managed in a way that is appropriate to their participation in the design and conduct of 
this trial. The study leadership in conjunction with the NICHD has established policies and 
procedures for all study group members to disclose all conflicts of interest and will establish a 
mechanism for the management of all reported dualities of interest. 
 
 
 
 
 
 
 
 
 
 

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11 ABBREVIATIONS 
 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
CFR 
Code of Federal Regulations 
CLIA 
Clinical Laboratory Improvement Amendments 
CMP 
Clinical Monitoring Plan 
COC 
Certificate of Confidentiality 
CONSORT Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data Safety Monitoring Board 
DRE 
Disease-Related Event 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Forms 
 
ERG 
Electroretinogram 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
FFR 
Federal Financial Report 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GWAS 
Genome-Wide Association Studies 
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation 
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
ISO 
International Organization for Standardization 
ITT 
Intention-To-Treat 
LVQOL 
Low Vision Quality-Of-Life Questionnaire 
LSMEANS Least-squares Means 
MedDRA 
Medical Dictionary for Regulatory Activities 
MOP 
Manual of Procedures 
MSDS 
Material Safety Data Sheet 
NCT 
National Clinical Trial 
NIH 
National Institutes of Health 
NIH IC 
NIH Institute or Center 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 

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SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMC 
Safety Monitoring Committee 
SOA 
Schedule of Activities 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
UBDRS 
Unified Batten Disease Rating Scale 
UP 
Unanticipated Problem 
US 
United States 
 
 
 

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APPENDICES 
Appendix A. Feasibility Test 
Appendix B. Feasibility Questionnaire 
Appendix C. Function Test 
Appendix D. Ability Questionnaire 
Appendix E. Applicability Questionnaire 
Appendix F. Device Use Diary 
Appendix G. PedEyeQ Questionnaire 
Appendix H. PROMIS QoL Questionnaires 
Appendix I. LVQOL Questionnaire 
Appendix J. OrCam MyEye 2 User Guide 
Appendix K. Pediatric User Pictures 
Appendix L. Device Determination Information