Extension Study of NT-501 Ciliary Neurotrophic Factor (CNTF) Implant for Macular Telangiectasia (MacTel)
Phase: PHASE2
Conditions: MacTel (Macular Telangiectasia) Type 2
Sponsor: Neurotech Pharmaceuticals

MacTel NTMT-01/02E 
Version 2.0 October 4, 2016 
Confidential: This document contains confidential information that is the property of Neurotech 
Pharmaceuticals, Inc., and must not be disclosed to anyone other than the recipient clinical 
investigator(s) and their designees and members of the Institutional Review Board. This 
information must not be used for any purpose other than the evaluation or conduct of the clinical 
investigation without the prior written consent of Neurotech Pharmaceuticals, Inc. 
Extension Study of NT-501 Ciliary Neurotrophic Factor (CNTF) Implant 
for Macular Telangiectasia (MacTel) 
Neurotech Pharmaceuticals, Inc. 
Protocol Designation: NTMT-01/02E 
IND – 10,931 
Date of Issue: October 4, 2016 
Version: 2.0
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MacTel NTMT-01/02E 
Version 2.0 October 4, 2016 
Statement of Compliance 
This study will be conducted in compliance with the protocol, International Conference on 
Harmonization (ICH) guideline E6: Good Clinical Practice (GCP): Consolidated Guideline, and 
the applicable regulatory requirements from the United States Code of Federal Regulations 
(CFR), including but not limited to 45 CFR 46 (Human Subjects Protection, 21 CFR 312 
(Investigational New Drug [IND]), and 21 CFR 56 (Institutional Review Board [IRB]). 
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MacTel NTMT-01/02E 
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SITE PRINCIPAL INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and the investigator brochure, and I agree 
that it contains all necessary details for my staff and me to conduct this study as described. I will 
personally oversee the conduct of this study as outlined herein and will make a reasonable 
effort to complete the study within the time designated. I agree to make all reasonable efforts to 
adhere to the attached protocol. I understand and am aware of my responsibilities as an 
investigator as described in the applicable GCP regulations. 
I will provide all study personnel under my supervision with copies of the protocol and access to 
all information provided by the sponsor or the sponsor’s representative. I will discuss this 
material with study personnel to ensure that they are fully informed about the efficacy and safety 
parameters and the conduct of the study in general. I am aware that, before beginning this 
study, the IRB responsible for such matters must approve this protocol in the clinical facility 
where it will be conducted. 
I agree to provide all participants with informed consent forms, as required by government and 
ICH regulations. I further agree to report to the sponsor or its representative any adverse events 
in accordance with the terms of this protocol and the U.S. Code of Federal Regulations, Title 21, 
Part 312.64. 
 
 
 
Principal Investigator Name (Print) 
 
 
 
 
 
 
Principal Investigator Signature 
 
Date 
 
 
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MacTel NTMT-01/02E 
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Study Summary 
Protocol Number: 
NTMT-01/02E 
Title: 
Extension Study of NT-501 Ciliary Neurotrophic Factor (CNTF) Implant 
for Macular Telangiectasia (MacTel) 
Short Title:  
MacTel NTMT-01/02 Extension Study 
Sponsor: 
Neurotech Pharmaceuticals, Inc. 
 
900 Highland Corporate Drive 
 
Cumberland, RI 02864 
 
Tel: 401-333-3880 
Study Phase: 
2 
Objectives: 
• 
To investigate long term safety and efficacy of the NT-501 implant in participants 
previously enrolled in the NTMT-01 and NTMT-02 protocols. 
• 
To investigate the change in the ellipsoid zone (area of [inner/outer segment] IS/OS 
loss) in participants previously enrolled in the NTMT-01 and NTMT-02 protocols, as 
measured by en face imaging by spectral domain optical coherence tomography  
(SD-OCT) in study eye(s). 
Study Design: Two participant cohorts will be enrolled in this study: 
Cohort 1 - Prospective, multi-center, open label safety and tolerability study. All participants will 
have been enrolled (undergone a NT-501 implant) in the Protocol for Extended Follow-up of a 
Phase 1 Multicenter Open Label Safety and Tolerability Clinical Trial of Ciliary Neurotrophic 
Factor (CNTF) in Patients with Macular Telangiectasia Type 2 (MacTel NTMT-01) protocol and 
have agreed to continue in this follow-up study. 
Participant visits will occur at Months 72, 84, 96 and 108 (+/- 1 month) following the date of the 
surgical procedure for NTMT-01. 
Cohort 2 - Prospective, multi-center, single-masked sham-controlled study. All participants will 
have been enrolled (undergone a NT-501 implant and/or sham procedure) in the A Phase 2 
Multicenter Randomized Clinical Trial of Ciliary Neurotrophic Factor (CNTF) for Macular 
Telangiectasia Type 2 (MacTel NTMT-02) protocol and have agreed to continue in this follow-up 
study. 
In the event that the NTMT-02 study is positive, Cohort 2 participants who received sham only 
may be eligible for active treatment in the control/non-treated eye. 
Participant visits will occur at Months 36, 48, 60 and 72 (+/- 1 month) following the date of the 
surgical procedure for NTMT-02. 
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MacTel NTMT-01/02E 
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Sample Size: 
Cohort 1 - 7 participants (7 study eyes) – previously enrolled in NTMT-01 protocol 
Cohort 2 – 66 participants (98 study eyes) – previously enrolled in NTMT-02 protocol 
Diagnosis and Key Eligibility Criteria: Previously enrolled in NTMT-01 or NTMT-02 protocols 
Investigational Product: NT-501 implant 
Duration of Treatment: 
Cohort 1 - Visits to continue until Month 108 from date of study procedure, with annual analyses 
at Months 72, 84, 96, and 108. 
Cohort 2 - Visits to continue until Month 72 from date of study procedure, with annual analyses 
at Months 36, 48, 60, and 72. 
Number of Centers: 8 sites in the United States and 3 sites in Australia 
Study Outcomes: 
Cohort 1: The following efficacy outcomes as outlined in the NTMT-01 Protocol will continue to 
be analyzed to investigate the efficacy of Ciliary Neurotrophic Factor (CNTF) produced by NT-
501 (all changes relative to NTMT-01 baseline measurements): 
• 
Change in the ellipsoid zone (area of IS/OS loss) from baseline to Months 72, 84, 96 
and 108. 
• 
Change in retinal sensitivity (dB) as measured by microperimetry from baseline to 
Months 72, 84, 96 and 108. 
• 
Proportion of study eyes with a 35% or more increase from baseline in the ellipsoid 
zone (area of IS/OS loss) at Months 72, 84, 96 and 108. 
• 
Change in best corrected visual acuity (BCVA) from baseline to Months 72, 84, 96 
and 108. 
• 
Proportion of study eyes with 15 or more letter loss from baseline in BCVA at Months 
72, 84, 96 and 108. 
• 
Proportion of study eyes with 10 or more letter loss from baseline in BCVA at Months 
72, 84, 96 and 108. 
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MacTel NTMT-01/02E 
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Cohort 2: The following efficacy outcomes as outlined in the NTMT-02 Protocol will continue to 
be analyzed to investigate the efficacy of Ciliary Neurotrophic Factor (CNTF) produced by NT-
501 (all changes relative to NTMT-02 baseline measurements): 
• 
Change in the ellipsoid zone (area of IS/OS loss) from baseline to Months 36, 48, 60 
and 72. 
• 
Change in retinal sensitivity (dB) as measured by microperimetry from baseline to 
Months 36, 48, 60 and 72. 
• 
Proportion of study eyes with a 35% or more increase from baseline in the ellipsoid 
zone (area of IS/OS loss) at Months 36, 48, 60 and 72. 
• 
Change in BCVA from baseline to Months 36, 48, 60 and 72. 
• 
Proportion of study eyes with 15 or more letter loss from baseline in BCVA at Months 
36, 48, 60 and 72. 
• 
Proportion of study eyes with 10 or more letter loss from baseline in BCVA at Months 
36, 48, 60 and 72. 
• 
Change in reading speed from baseline to Months 36, 48, 60 and 72. 
 
 
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Assessment/Examination Schedule 
VISITS ARE SCHEDULED FROM THE DATE OF THE 
NTMT-01 OR NTMT-02 SURGERY 
VISIT  1 (+/- 1 month) 
VISIT  2 (+/- 1 month) 
VISIT  3 (+/- 1 month) 
VISIT  4 (+/- 1 month) 
GENERAL ASSESSMENTS 
 
 
 
 
NTMT-01/02 Extension Study Consent 
X 
 
 
 
Review Eligibility Criteria  
X 
 
 
 
Review Demographics and Participant Contact Information 
X 
 
 
 
Update Medical & Ophthalmic History from NTMT-01 and NTMT-02 
 -This will include AEs collected during NTMT-01 and NTMT-02 and up to Visit 1 of 
the Extension Study as applicable. Any events between the last NTMT-01 or 
NTMT-02 visit will be recorded here. 
X 
 
 
 
AE Assessment – starting from date of NTMT-01/02E Consent 
 
X 
X 
X 
Concomitant Medications – continue from NTMT-01 and NTMT-02 
X 
X 
X 
X 
Reading Speed*  
*Completed for NTMT-02 (Cohort 2) participants only 
X* 
X* 
X* 
X* 
VISUAL SYSTEM EXAMS: UN-DILATED 
 
 
 
 
Manifest Refraction 
X 
X 
X 
X 
Best Corrected Visual Acuity 
X 
X 
X 
X 
Applanation Tonometry (Goldmann applanation tonometer) 
X 
X 
X 
X 
Microperimetry 
X 
X 
X 
X 
VISUAL SYSTEM EXAMS: DILATED 
 
 
 
 
Slit lamp Biomicroscopy 
X 
X 
X 
X 
Dilated Fundus Examination 
X 
X 
X 
X 
Implant Site Clinical Examination  
X 
X 
X 
X 
SD-OCT 
X 
X 
X 
X 
Fundus Autofluorescence Imaging 
X 
X 
X 
X 
Digital Color Fundus Photographs 
X 
X 
X 
X 
**AOSLO (for participants enrolled at NTMT-02 baseline ) 
**Requires separate consent at AOSLO Center 
X** 
X** 
X** 
X** 
 
 
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MacTel NTMT-01/02E 
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Table of Contents 
1 
Précis ................................................................................................................................... 1 
2 
Background and Rationale ................................................................................................... 2 
3 
Scientific Rationale ............................................................................................................... 5 
3.1 
Encapsulated Cell Technology (ECT) .......................................................................... 5 
4 
Study Objectives .................................................................................................................. 6 
5 
Study Design and Methods .................................................................................................. 7 
6 
Study Conduct ...................................................................................................................... 7 
6.1 
Efficacy Outcomes ....................................................................................................... 7 
6.1.1 
Cohort 1 Efficacy Outcomes ............................................................................. 7 
6.1.2 
Cohort 2 Efficacy Outcomes ............................................................................. 8 
6.1.3 
Safety Outcomes ............................................................................................. 8 
6.2 
Inclusion Criteria .......................................................................................................... 9 
6.3 
Exclusion Criteria ......................................................................................................... 9 
6.4 
Study Procedures ........................................................................................................ 9 
6.5 
Concomitant Medications and Procedures ..................................................................10 
6.6 
Prohibited Medications ...............................................................................................10 
6.7 
Masking ......................................................................................................................10 
6.8 
Exam Requirements ...................................................................................................11 
6.9 
Study Visit Procedures ...............................................................................................12 
7 
Monitoring Participants and Criteria for Withdrawal .............................................................13 
7.1 
Safety Plan .................................................................................................................13 
7.2 
Adverse Experience Reporting ...................................................................................13 
7.3 
Definitions ...................................................................................................................14 
7.4 
Obligations of Investigators.........................................................................................16 
7.5 
Terminology for Adverse Event Descriptions ..............................................................17 
7.6 
Reporting of Pregnancy ..............................................................................................17 
7.7 
Notifying the Sponsor .................................................................................................18 
7.8 
Notifying FDA / Regulatory Authorities and the Data and Safety Monitoring Committee
 
18 
7.9 
Reporting SAEs to the DSMC .....................................................................................19 
7.10 Early Termination or Participant Discontinuation .........................................................19 
7.11 Safety Monitoring ........................................................................................................20 
8 
Statistical Considerations ....................................................................................................20 
8.1 
Efficacy Outcomes ......................................................................................................20 
8.2 
Analyses in Support of the Efficacy Outcomes ...........................................................21 
8.3 
Sample Size ...............................................................................................................22 
8.4 
Safety Analysis ...........................................................................................................22 
8.5 
Adverse Events ..........................................................................................................22 
8.6 
Data Quality Assurance ..............................................................................................23 
9 
Human Participant Protection ..............................................................................................23 
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10 Study Risks .........................................................................................................................24 
11 Investigator Requirements...................................................................................................25 
11.1 Informed Consent Form ..............................................................................................25 
11.2 Communication with the Institutional Review Board or Independent Ethics Committee
 
26 
11.3 Study Monitoring Requirements ..................................................................................27 
11.4 Electronic Case Report Forms ....................................................................................27 
11.5 Source Data Documentation .......................................................................................27 
11.6 Use of Computerized Systems ...................................................................................28 
11.7 Disclosure of Data ......................................................................................................28 
11.8 Retention of Records ..................................................................................................29 
12 References ..........................................................................................................................30 
13 Appendix 1 ..........................................................................................................................33 
List of Tables 
Table 1: Animal Studies using CNTF for various neurodegenerative diseases ........................... 4 
Table 2: Ex vivo production rates and vitreous CNTF concentrations at the time of NT-501 
explantation ............................................................................................................................... 6 
 
 
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List of Abbreviations and Definition of Terms 
Abbreviation  
Term 
AE 
 
 
Adverse event 
AOSLO 
 
Adaptive optics scanning laser ophthalmoscope 
BCVA  
 
Best corrected visual acuity 
CFR 
 
 
Code of Federal Regulations 
CNTF  
 
Ciliary neurotrophic factor 
CRF 
 
 
Case report form 
CTCAE 
 
Common Terminology Criteria for Adverse Events 
DSMC  
 
Data Safety and Monitoring Committee 
eCRF  
 
Electronic case report form 
ECT 
 
 
Encapsulated cell technology 
EDC 
 
 
Electronic data capture 
ERG 
 
 
Electroretinogram 
FDA 
 
 
Food and Drug Administration 
GCP 
 
 
Good Clinical Practice 
IEC 
 
 
Independent Ethics Committee 
ICH 
 
 
International Conference on Harmonization 
IDE 
 
 
Investigational Device Exemption 
IND 
 
 
Investigational New Drug 
IRB 
 
 
Institutional Review Board 
IS 
 
 
Inner segment 
MacTel 
 
Macular Telangiectasia Type 2 
MOP  
 
Manual of Procedures 
MedDRA 
 
Medical Dictionary for Regulatory Activities 
OCT 
 
 
Optical coherence Tomography 
SD-OCT 
 
Spectral Domain-Optical Coherence Tomography 
ONL 
 
 
Outer nuclear layer 
OS 
 
 
Outer segment 
RP 
 
 
Retinitis pigmentosa 
SAE 
 
 
Serious adverse event 
VEGF  
 
Vascular endothelial growth factor 
 
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MacTel NTMT-01/02E 
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1 Précis 
Macular telangiectasia type 2 (MacTel), a bilateral degenerative condition of the macula that 
may cause progressive loss of vision, is estimated to have an incidence of 1:22,000 (Lamoureux 
et al. 2011). A recent study (Chew 2015) correlating visual field defects detected by 
microperimetry with optical coherence tomography shows that the defects are closely 
associated with cavitation of the outer retina with gaps in the inner-/-outer-segment junction, 
indicating that loss of vision in MacTel is caused by loss of photoreceptors. Current evidence 
implies that photoreceptor cell loss is intrinsic to the disorder rather than being consequent upon 
blood vessel changes. Photoreceptor abnormality occurs early in the disorder and progression 
of photoreceptor cell loss is not influenced by modulation of blood vessel changes using anti-
VEGF treatment. To date, there is no effective treatment for MacTel. 
The class of molecules called “neurotrophic factors” has been demonstrated to reduce the rate 
of photoreceptor cell loss during retinal degeneration. One of these, ciliary neurotrophic factor 
(CNTF), was found to be effective in slowing vision loss from photoreceptor cell death in 12 
animal models of outer retinal degeneration (e.g., rd/rd, rds/rds, 334ter-3 rats, 334ter-4 rats, 
P23H-1 rats, Rdy cats, rcd1 dogs, etc.). Similarly, delivery of a neurotrophic factor to the outer 
retina in a mouse model that shares many phenotypic MacTel characteristics has shown 
profound functional and anatomic photoreceptor cell rescue without correcting associated 
vascular abnormalities (Dorrell 2009). In addition, there is evidence that CNTF can cause 
regeneration of cone outer segment in rats with mutations in the rhodopsin gene (McGill 2007). 
Further, encapsulated cell delivery of CNTF has been tested in three human Phase 2 safety 
studies in the treatment of retinal dystrophies and atrophic age-related macular disease. 
Specifically, CNTF did not cause neovascularization in either disorder, both of which are 
recognized as being associated with the development of abnormal blood vessels. In these 
studies, there is some evidence of therapeutic benefit (Sieving 2005 and Talcott, 2010). The 
combined evidence from animal and human studies suggests that use of neurotrophic 
molecules may provide therapeutic benefit to patients with MacTel. 
One major challenge is the delivery of this potential therapeutic CNTF agent to the back of the 
eye, and in particular, to the retina. The blood-retinal barrier prevents the penetration of a 
variety of molecules to the neurosensory retina from plasma in a manner similar to the action of 
the blood-brain barrier, which exists between the central nervous system and systemic 
circulation. To overcome this challenge, Neurotech Pharmaceuticals (Neurotech) developed 
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encapsulated cell technology (ECT), and specifically the NT-501 implant, to enable controlled, 
sustained delivery of therapeutic agents directly into the vitreous humor, thus providing direct 
access to the retina while restricting exposure of the growth factor outside the eye. ECT utilizes 
cells encapsulated within a semi-permeable polymer membrane that secretes therapeutic 
factors directly into the vitreous. Further, ECT devices can be surgically retrieved, providing an 
added level of safety. 
Histopathologic studies of multiple forms of retinal neurodegenerative diseases have 
demonstrated the efficacy of CNTF as an effective treatment to reduce photoreceptor cell loss. 
Consequently, the use of the implanted NT-501 device, which secretes CNTF into the vitreous, 
may be beneficial in people with MacTel. A Phase 1 study is completed although we continue to 
follow these participants to accumulate further data on the effect of the intraocular NT-501 
implant in 7 participants with bilateral MacTel. The primary outcome was the safety of the NT-
501 implant and the associated surgical procedure. We found the implanting of the NT-501 was 
safe as demonstrated by the ERG findings and visual function results as measured by visual 
acuity and microperimetry (Chew 2015). 
2 Background and Rationale 
In 1982, Gass et al. published the seminal paper on macular telangiectasis (then called 
juxtafoveal or parafoveal telangiectasia). In further work, Gass et al. (Gass 1987 and Gass 
1993) subdivided macular telangiectasia into three groups: Type 1: the telangiectasia is usually 
unilateral and associated with dilated retinal capillaries, leakage on fluorescein angiography and 
retinal thickening in mostly male patients. Type 2: Macular Telangiectasia (MacTel), leakage 
occurs during fluorescein angiography with manifest retinal capillary dilatation but without retinal 
thickening, and Type 3: 3 Macular Telangiectasis, capillary occlusion is suspected to cause 
telangiectasia. Mac Tel Type 2, the most common form of macular telangiectasia, is the disease 
evaluated in this study. This condition is typically diagnosed in the fifth or sixth decade of life in 
both sexes. This disorder is characterized by minimal exudation, superficial retinal crystalline 
deposits, retinal opacification and right-angle venules. As the disease progresses, intraretinal 
pigment plaques and intraretinal/subretinal neovascularization may develop. 
In 2005, a prospective natural history study was initiated to define the clinical aspects of 
macular telangiectasia type 2 and to evaluate its progression. Several new features have now 
been described that alter our concept of the disorder’s pathogenesis. One of the earliest signs is 
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loss of luteal pigment centrally as manifested by fundus autofluorescence imaging using a 
confocal laser ophthalmoscope. Optical coherence tomography has shown abnormalities in 
photoreceptors early in the disease which is associated with significant loss of scotopic and 
photopic function beginning nasal to fixation (Charbel-Issa 2010). This gives rise to pre-
fixational blindness. With adaptive optics imaging it has become evident that cone loss is an 
early characteristic of the disease (Ooto 2011). Thus, this photoreceptor loss is intrinsic to the 
disorder, occurs early in the evolution of disease and may precede vascular change. In addition, 
it has been shown that (1) anti-VEGF treatment causes reversal of the blood vessel changes 
but does not influence progression of photoreceptor cell loss or functional loss; (2) the retina is 
thinner than normal in MacTel, unlike other macular conditions such as diabetic retinopathy in 
which edema can lead to retinal thickening; and (3) there is leakage of dye during fluorescein 
angiography similar to the leakage around the perifoveal area found in the deeper retinal 
circulation associated with retinal degeneration. It is also evident that opacification of the retina 
occurs very early in disease that is not due to retinal edema. Histopathological examination of a 
single post mortem eye taken from a patient with long-standing MacTel shows an abnormality of 
Mueller cells that might explain the retinal opacification if they act normally as light guides, as 
has recently been suggested (Reichenbach 2010), and a second pair of post-mortem eyes also 
show similar results (data not published). The role of the Mueller dysfunction in this condition 
requires further clarification. 
The promise of growth factors, neurotrophic factors and cytokines as therapy for neuro-
degenerative retinal diseases has been demonstrated in many animal models. The results of 
these studies using CNTF are summarized in Table 1. CNTF may have the potential for the 
treatment of Mac Tel type 2. 
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Table 1: Animal Studies using CNTF for various neurodegenerative diseases 
Animal Studies using CNTF for various neurodegenerative diseases 
Animal Models of Retinal Degeneration 
 
 
CNTF protect from 
retinal 
degeneration 
Increased ERG 
response 
 
 
LaVail 1992 
12 animal 
models 
+ 
 
 
 
Chong 1999 
334ter-3 rats, 
334ter-4 rats 
P23H-1 rats, 
Rdy cats 
+ 
 
 
 
LaVail 1998 
rds/rds mice 
+ 
 
 
 
Cayouette 
1998 
rds/rds/mice 
+ 
+ 
 
 
Tao 2002 
rcd1 dog 
model 
+ 
 
 
 
Bush 2002 
rcd1 dog 
model 
+ 
No effect on ERG 
 
 
 
 
 
 
 
 
Studies of animal models of Amyotropic Lateral Sclerosis (ALS) 
 
Animal 
models 
Increased survival 
time 
Improved 
behavioral 
studies 
Improved 
Motor 
function 
Histology: 
Reduction in 
motor neuron 
loss 
Lindsay 1994 
Several 
Increased by 40% 
 
 
 
Sagot 1995 
mouse 
 
+ 
+ 
+ 
Aebischer 1995 
mouse 
 
+ 
+ 
+ 
 
 
 
 
 
 
 
Studies of animal models of Huntington’s Disease 
 
Animal model 
Neuroprotective 
effect 
Cognitive and 
motor function 
improvement 
 
 
de Almeida 
2001 
Rat 
+ 
 
 
 
Reguilier 2002 
Rat 
+ 
 
 
 
Mittoux 2000 
Rat 
+ 
+ 
 
 
Emerich 1996 
Rat 
+ 
+ 
 
 
Emerich 1997 
Primate 
+ 
+ 
 
 
Using the rapid retinal degeneration rat RP model (S334ter-3 rat), one eye was selected and 
given an intra-vitreal injection of either NTC-201 cells (which express CNTF) or NTC-200 cells 
(the parent line for NTC-201 that do not express CNTF). The contralateral eye served as a 
same-animal control. At the end of this study, eyes injected with NTC-201 cells had 5-6 layers of 
photoreceptors in the outer nuclear layer (ONL) while eyes injected with NTC-200 cells and 
untreated eyes had only 1-2 layers of photoreceptors in the ONL. These data suggested that 
CNTF delivered intra-ocularly from genetically engineered NTC-201 cells had a protective effect 
on the photoreceptors present in the ONL in this model. 
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Histopathologic studies in naturally occurring and genetically engineered animal models of 
photoreceptor dysfunction and death, phenotypically modeling retinitis pigmentosa (RP), have 
indicated the promise of ciliary neurotrophic factor (CNTF) as an effective therapeutic agent for 
reducing photoreceptor loss associated with degeneration of the cells of the outer retina. CNTF 
is one of several neurotrophic factors that are produced endogenously by neurons or Mueller 
cells. CNTF has been demonstrated to be highly effective in retarding photoreceptor neuron 
loss in 12 animal models of retinal degeneration of various forms, including environmental light 
stress. Neurotech has demonstrated in two preclinical animal studies that CNTF-producing cells 
have a protective effect on the photoreceptors in the ONL. A rat model of RP suggested that 
CNTF-producing cells delivered as an intravitreal injection had a protective effect on the 
photoreceptors in the ONL. The treated eyes in the rat study had 5-6 layers of photoreceptors in 
the ONL compared to 1-2 layers in the untreated eyes. In a dog model of RP, the NT-501 device 
was also observed to have a protective effect on the photoreceptors. The treated eyes in the 
dog study had 5-6 layers in the ONL compared to 2-3 layers in the untreated eyes. 
3 Scientific Rationale 
3.1 Encapsulated Cell Technology (ECT) 
This study is designed to provide long term observation of the ongoing effect of CNTF as 
delivered continuously via the NT-501 implant in patients with MacTel type 2. MacTel type 2 is a 
slowly progressive condition which may take many years to develop clinical symptoms and 
signs. 
The Phase II NTMT-02 trial was limited to 24 months of controlled observation. While it is 
anticipated that two years of controlled observation should be sufficient to determine efficacy, it 
is possible that a longer period is necessary to observe a meaningful separation between the 
groups. This extension study provides the opportunity for that continued observation. 
Previous experience with the NT-501 implant in studies of participants with geographic atrophy 
or retinitis pigmentosa suggests that the implant is capable of delivering detectable CNTF for up 
to 66 months. Output of CNTF from explanted devices, along with vitreous levels of CNTF, is 
consistent with the histologic findings at these various time points; the cells remain healthy and 
productive within the membranes (capsules), and continue to produce and deliver CNTF. These 
data support the hypothesis that NT-501 will continue to provide similar levels of CNTF to the 
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study eyes during this prolonged follow up period. Mean duration of implantations together with 
explant and vitreous CNTF levels are shown in Table 2. 
Table 2: Ex vivo production rates and vitreous CNTF concentrations at the time of NT-501 
explantation 
Implant 
Duration 
Explant 
(ng/ day) 
# 
Vitreous 
(pg/mL) 
# 
6 months 
1.54 ± 0.54 
(5) 
58 ± 0 
(1) 
12-13 months 
2.09 ± 0.59 
(11) 
64 ± 0 
(2) 
18-20 months 
1.78 ± 0.86 
(7) 
57 ± 0 
(1) 
24 months 
1.08 ± 0.48 
(11) 
46 ± 0 
(1) 
30-33 months 
1.10 ± 0.73 
(6) 
17 ± 0 
(1) 
45 months 
1.25 ± 0.00 
(1) 
55 ± 0 
(1) 
54 months 
0.70 ± 0.04 
(2) 
--- 
66 months 
1.16 ± 0.00 
(1) 
36 ± 0 
(1) 
The Phase I NTMT-01 trial designed to assess the safety and tolerability of the NT-501 implant 
in patients diagnosed with MacTel type 2 has completed enrollment (N=7) and follow-up 
continues. No serious adverse reactions have been reported to date. Preliminary data confirm 
that the progression of visual impairment is slow in MacTel type 2. This is consistent with the 
findings of Heeren et al (2015) who suggested that patients with MacTel type 2 require 
prolonged follow up for appropriate evaluation of functional loss. 
4 Study Objectives 
• 
To investigate long term safety and efficacy of the NT-501 implant in participants 
previously enrolled in the NTMT-01 and NTMT-02 protocols. 
• 
To investigate the change in the ellipsoid zone (area of [inner/outer segment] IS/OS 
loss) in participants previously enrolled in the NTMT-01 and NTMT-02 protocols, as 
measured by en face imaging by spectral domain optical coherence tomography  
(SD-OCT) in study eye(s). 
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5 Study Design and Methods 
This is a prospective, multi-center, single-masked, sham-controlled follow-up study of the 7 
participants that have completed 60 months of follow up in the open label NTMT-01 study 
(Cohort 1) and the 66 participants who completed 24 months of follow up in the NTMT-02 study 
(Cohort 2). All participants will be followed for an additional 48 months. Appendix 1 presents the 
scheduled examinations during the extended 48 month follow up period. 
In the event that the NTMT-02 study is positive, Cohort 2 participants who received sham only 
may be eligible for active treatment in the control/non-treated eye. 
6 Study Conduct 
6.1 Efficacy Outcomes 
Measures of efficacy have been determined on the principle that treatment will modulate 
deterioration of function or delay the increase in physical abnormalities. Analyses will be 
conducted separately for each cohort. 
6.1.1 
Cohort 1 Efficacy Outcomes 
Efficacy outcomes to investigate the efficacy of CNTF produced by NT-501 include (all changes 
relative to NTMT-01 baseline measurements): 
• 
Change in the ellipsoid zone (area of IS/OS loss) from baseline to Months 72, 84, 96 
and 108. 
• 
Change in retinal sensitivity (dB) as measured by microperimetry from baseline to 
Months 72, 84, 96 and 108. 
• 
Proportion of study eyes with a 35% or more increase from baseline in the ellipsoid 
zone (area of IS/OS loss) at Months 72, 84, 96 and 108. 
• 
Change in BCVA from baseline to Months 72, 84, 96 and 108. 
• 
Proportion of study eyes with 15 or more letter loss from baseline in BCVA at Months 
72, 84, 96 and 108. 
• 
Proportion of study eyes with 10 or more letter loss from baseline in BCVA at Months 
72, 84, 96 and 108. 
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6.1.2 
Cohort 2 Efficacy Outcomes 
Efficacy outcomes to investigate the efficacy of CNTF produced by NT-501 include (all changes 
relative to NTMT-02 baseline measurements): 
• 
Change in the ellipsoid zone (area of IS/OS loss) from baseline to Months 36, 48, 60 
and 72. 
• 
Change in retinal sensitivity (dB) as measured by microperimetry from baseline to 
Months 36, 48, 60 and 72. 
• 
Proportion of study eyes with a 35% or more increase from baseline in the ellipsoid 
zone (area of IS/OS loss) at Months 36, 48, 60 and 72. 
• 
Change in BCVA from baseline to Months 36, 48, 60 and 72. 
• 
Proportion of study eyes with 15 or more letter loss from baseline in BCVA at Months 
36, 48, 60 and 72. 
• 
Proportion of study eyes with 10 or more letter loss from baseline in BCVA at Months 
36, 48, 60 and 72. 
• 
Change in reading speed from baseline to Months 36, 48, 60 and 72. 
6.1.3 
Safety Outcomes 
The following ocular events (regardless of attribution) will be considered safety outcomes for 
both Cohorts if they occur: 
• 
Rejection or extrusion of the NT-501 device. 
• 
Development of peri-implant fibrosis, which either blocks the visual axis of the 
implanted eye or affects the lens or retina (minor/moderate fibrosis around the 
implant and/or the attachment point is an expected possibility and will be considered 
safe on ocular function). Attention should focus on fibrosis that may detach the 
retina. 
• 
Development of choroidal or retinal neovascularization in the study eye. 
• 
Adverse events affecting ocular function, which are different from those expected in 
the normal course of MacTel, which are potentially related to the surgical procedure, 
implant or CNTF including: 
− Endophthalmitis 
− Vitreal inflammation 
− Tractional retinal detachment 
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− Sectorial lens opacification 
− Intraocular hemorrhage 
− High or low Intraocular pressures 
− Dry eye 
− Self-reported change in dark adaptation 
− Miosis 
− Persistent chemosis 
− Scleral leak 
All adverse events (AEs) will be captured from the date of the Extension Study Consent whether 
or not considered to be related to the surgical procedure, NT-501 device, or CNTF. All adverse 
events occurring between the final NTMT-01 or NTMT-02 study visit will be considered part of 
the participants’ Medical and/or Ophthalmic History. 
An attempt will be made to differentiate between treatment-related AEs and AEs considered to 
be part of the normal progression of the disease. In addition, for treatment-related AEs, an 
attempt will be made to differentiate those the Investigator believes are due to the procedure, 
NT-501 device, or CNTF. 
Analysis of safety events will be conducted separately for each Cohort. 
6.2 Inclusion Criteria 
To participate in this study, the potential participant must meet all of the following criteria: 
1. Previously enrolled in the NTMT-01 or NTMT-02 protocol and received the NT-501 implant 
and/or underwent a Sham procedure. 
2. Participant must be offered sufficient opportunity to review and to understand the informed 
consent form, agree to the form’s contents and provide written informed consent. 
6.3 Exclusion Criteria 
There are no Exclusion Criteria. 
6.4 Study Procedures 
All study procedures will be carried out for both eyes at each visit. This will include both the 
study eye(s) and the fellow eye as applicable. 
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6.5 Concomitant Medications and Procedures 
Any concomitant medications a participant is receiving at the start of the study or given for any 
reason during the study must be recorded in the source document, including start and stop 
dates and indication information. Recording of concomitant medications on the Case Report 
Forms (CRFs) must be done according to the instructions provided in the study Manual of 
Procedures (MOP). In addition, all ocular and non-ocular procedures must also be recorded in 
the Concurrent Procedures source document. 
6.6 Prohibited Medications 
Anti-herpetic nucleoside analogs (such as Acyclovir, Valaciclovir, Penciclovir and Famciclovir) 
or anti-cytomegaloviral nucleoside analogs (such as Ganciclovir or Foscarnet) are prohibited 
unless required for the safety of the participant and the infection is not expected to be self-
limited without treatment. If used, these agents should only be used for the shortest possible 
duration. When possible, the sponsor, Neurotech, should be consulted prior to initiating 
treatment. Anti-influenza neuraminidase inhibitors (such as Zanamivir, Oseltamyvir) or other 
anti-influenza medications (such as Arbidol, Amantadine, Rimantadine) are permissible, if 
clinically indicated. 
6.7 Masking 
For participants in Cohort 2 there are different levels of masking within the study. The site staff 
refractionist, visual acuity examiner and photographers/imagers must remain masked to 
treatment assignment (NT-501 implant or sham procedure) for all visits. The Ophthalmologist, 
Surgeon and Clinic Coordinator will be unmasked to treatment assignment. 
To ensure that the refractionist, visual acuity examiner and photographers/imagers remain 
masked to the randomized assignment, the Ophthalmologist, Surgeon and Clinic Coordinator 
are not to discuss the treatment received with the refractionist, visual acuity examiner and 
photographers/imagers. 
All personnel in the Central Image Reading Center will be masked to whether the participant 
received the NT-501 implant or sham in a study eye(s). 
Masking will remain as described above until all 66 participants in the NTMT-02 protocol have 
completed their original NTMT-02 Protocol Month 24 visit and data analysis has been 
completed. At that time, the Principal Investigators will be informed by the Sponsor that they 
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may unmask the participants. They may choose to do this at the participants’ next scheduled 
visit or in a personalized communication to the participant. The sites will notify the Coordinating 
Center of the unmasking as outlined in the Manual of Procedures. 
6.8 Exam Requirements 
The following are examinations to be performed at the times indicated in Appendix 1. 
1. Informed Consent and Eligibility Criteria Review 
2. Demographics and Participant Contact Information Review 
3. Medical/Ophthalmic History Review (carried over from NTMT-01 or NTMT-02) 
• 
Adverse events noted during the NTMT-02 and NTMT-01 study period and up to the 
first Extension Study visit will be added as Medical/Ophthalmic History as applicable. 
4. Adverse Event Assessment (from the date of the NTMT-01/02 Extension Study consent) 
5. Concomitant Medications 
6. Complete Ophthalmic Examination including: 
• 
Manifest refraction 
• 
BCVA (This test will be performed by a masked certified technician) 
• 
Goldmann applanation tonometry 
• 
Slit lamp biomicroscopy 
• 
Dilated fundus examination 
• 
Implant site clinical examination  
7. Ophthalmic Assessments including: 
• 
Microperimetry  
• 
Spectral Domain Optical Coherence Tomography (SD-OCT) 
• 
Fundus Autofluorescence imaging 
• 
Digital Color Fundus photographs 
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• 
Adaptive Optics Scanning Laser Ophthalmoscopy (AOSLO), in selected participants 
o Participants who underwent AOSLO for NTMT-02 will undergo a 
separate consent process at the AOSLO Center if they agree to continue 
participating. 
8. Reading Speed –NTMT-02 (Cohort 2) participants only 
• 
Monocular and binocular reading speed will be assessed using IReST cards. 
Reading speed will be used to document the participant’s functional status with an 
important everyday visual task. 
6.9  Study Visit Procedures 
Visits will occur annually for a total of 4 years following the below schedule with visit windows of 
+/- 1 month. 
 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Cohort 1 
72 Months 
84 Months 
96 Months 
108 Months 
Cohort 2 
36 Months 
48 Months 
60 Months 
72 Months 
The following study procedures will be completed only at Visit 1: 
• 
If the participant agrees to continue in the Extension study, the Principal Investigator 
or appropriate designee will obtain the participant’s consent 
• 
Eligibility Criteria Review 
• 
Demographics and Participant Contact Information Review 
• 
Medical/Ophthalmic History Review (carried over from NTMT-01 or NTMT-02 study, 
including any AE’s that have occurred since the last participant visit) 
The following study procedures will be completed bilaterally at all visits for all participants unless 
otherwise noted: 
• 
Adverse Event Assessment (only at Visits 2, 3, and 4) 
• 
Concomitant Medications 
• 
Manifest refraction 
• 
Best Corrected Visual Acuity 
• 
Goldmann applanation tonometry 
• 
Microperimetry 
• 
Slit lamp biomicroscopy 
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• 
Dilated fundus examination 
• 
Implant site clinical examination 
• 
SD-OCT 
• 
Fundus Autofluorescence imaging 
• 
Digital Color Fundus photographs 
• 
Reading Speed – (Cohort 2 participants only) 
• 
Adaptive Optics Scanning Laser Ophthalmoscopy (AOSLO), in selected participants 
Participants who underwent AOSLO for NTMT-02 will undergo a separate 
consent process at the AOSLO Center if they agree to continue participating 
7  Monitoring Participants and Criteria for Withdrawal 
7.1 Safety Plan 
A Safety Plan will describe roles and responsibilities, adverse event reporting methods and 
requirements, communication and interaction with the Data and Safety Monitoring Committee 
(DSMC), grading the severity of adverse events and other safety monitoring processes. The 
plan will be based on the safety reporting requirements for investigational new drug applications 
(INDs) found in 21 CFR part 312 and other applicable regulatory authorities’ regulations. 
7.2 Adverse Experience Reporting 
All adverse events (AEs) either observed by the Investigator or one of his/her medical 
collaborators, or reported by the participant spontaneously or in response to direct questioning, 
will be reported. Any adverse event regardless of severity or potential association with the 
device or CNTF or study procedures must be documented in study records by the Investigator 
and appropriately reported. 
AEs will be reported within the participant’s records and in the AdvantageEDCSM system. All 
AEs should be entered into the data system within 5 business days of identification by the site 
personnel. All AEs will be recorded from the date of obtaining informed consent until the last 
study visit. 
Serious adverse events (SAEs) will be followed until resolution or until stability is reached. In 
rare instances, this may include following the participant after completion of the study. 
All serious adverse events should be entered into the data system within 24 hours of 
identification. If there are technical difficulties when entering the event into the EDC system, the 
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SAE will be reported to the Coordinating Center by fax communication, and these numbers will 
be provided in the Manual of Operations. All information reported by fax will need to be entered 
in the data system when it is available. All SAEs should be reported to local Institutional Review 
Boards/Ethic Committees (IRBs/IEs) per local IRB/IEC requirements. 
7.3 Definitions 
An adverse event is any untoward medical occurrence in humans, whether or not considered 
treatment- or procedure-related, which occurs during the conduct of a clinical trial. Any change 
in clinical status, routine labs, ophthalmological assessments etc., that is considered clinically 
significant by the Study Investigator or designee and requires intervention is considered an AE. 
Medical conditions or diseases present before a participant starts study treatment are only 
considered adverse events if they worsen after the participant starts study treatment (temporal 
association). 
Suspected adverse reaction (Related Adverse Event) is any adverse event for which there is 
a reasonable possibility that the treatment caused the adverse event. A reasonable possibility 
implies that there is evidence that the treatment caused the event. 
Serious Adverse Events 
A serious adverse event (SAE) as determined by the Investigator or the Sponsor is any event 
that results in any of the following outcomes: 
1. Death 
2. Life-threatening AE (Life-threatening means that the study participant was, in the opinion of 
the Investigator or Sponsor, at immediate risk of death from the event as it occurred.) 
3. Persistent or significant incapacity or substantial disruption of the ability to conduct normal 
life functions. 
4. Inpatient hospitalization or prolongation of existing hospitalization. 
5. Congenital abnormality or birth defect. 
6. Important medical event that may not result in one of the above outcomes, but may 
jeopardize the health of the study participant or require medical or surgical intervention to 
prevent one of the outcomes listed in the above definition of serious event. 
Note that the term “serious” is not a measure of severity, but speaks to a very specific definition 
as noted in 1-6 above. 
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A hospitalization for an elective or cosmetic procedure, scheduled prior to enrollment or during 
the course of the study, unrelated to the medical condition under study, is excluded from this 
definition of a serious adverse event. 
Unexpected Adverse Event 
An unexpected adverse event is an event where the specificity or severity of which is not 
consistent with the current approved product labeling (package insert) for the test article or the 
Investigator’s Brochure. This includes an increase in the frequency or severity of a previously 
reported adverse event that is significantly above the rates known from previous experience 
with the test article. 
Guidelines for Determining when Changes in Pre-Existing Conditions are Considered 
Adverse Events 
Adverse events include illnesses with onset during the study or exacerbations of pre-existing 
illnesses. Exacerbation of pre-existing illness is defined as a clinically relevant increase in the 
severity of the illness as compared to the start of the study and should be considered when a 
participant requires new or additional treatment for that illness. Investigators should use the 
following guidelines to assess when an adverse event needs to be reported for a condition 
which results in a change to an ongoing medication and/or addition of a new medication: 
• 
Addition of a new medication and/or change in ongoing medication due to an untoward 
(unfavorable and unintended) change in a participant's medical health for a 
disease/condition documented as ongoing at baseline. 
• 
Addition of a new medication due to an untoward (unfavorable and unintended) change in a 
participant's medical health for a disease/condition not present at baseline. 
Guidelines for Assessing Intensity of an Adverse Event 
The Investigator should use the following definitions when assessing Intensity of an Adverse 
Event: 
• 
MILD: Transient (< 48 hours) or mild discomforts, no or minimal medical therapy or 
intervention required, hospitalization not necessary, no or little limitation in normal activities. 
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• 
MODERATE: Mild to moderate limitation in activity, some assistance may be needed; 
possibly none but usually minimal intervention/therapy required; hospitalization possible. 
• 
SEVERE: Marked limitation in activity, some assistance usually required; medical 
intervention/therapy required; hospitalization possible or likely. 
• 
LIFE THREATENING: Extreme limitation in activity, significant and immediate assistance 
required; significant medical/therapy intervention required to prevent loss of life; 
hospitalization, emergency treatment or hospice care probable. 
• 
FATAL: Death 
Guidelines for Determining Causality of an Adverse Event 
The Investigator will answer the following question when assessing causality of an adverse 
event to study treatment: “Is there a reasonable possibility that the treatment caused the event?” 
A reasonable possibility implies there is evidence that the specific event was caused by the 
study treatment. An affirmative answer designates the event as a suspected adverse reaction, 
and the AE is therefore considered “related.” If the answer is no, then the AE is considered 
“unrelated.” For every related adverse event, the Investigator will determine the causality in 
relation to the surgical procedure - those related to the device itself, and the CNTF. 
7.4 Obligations of Investigators 
The Investigator is obligated to promptly report all adverse events. When submitting adverse 
event information, the Investigator may not delegate to someone other than a listed study 
physician the responsibility for reviewing the accuracy of the contents of an adverse event 
report. When reporting an adverse event, the Investigator must assign a severity grade to each 
event and also declare an opinion on the causality of the event relative to the study test article 
or procedure. 
For any serious adverse event, the Coordinating Center and Sponsor must be notified within 24 
hours of when the Investigator first learns of the occurrence of the event. Adequate information 
must be collected with supporting documentation to complete the standard electronic form set. 
If the participant reaches the final scheduled follow-up visit, any new adverse events, as well as 
follow-up information for ongoing adverse events, must be recorded. For participants who 
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withdraw prematurely, adverse events should be followed until 30 days after last study visit. In 
any case, every attempt must be made by the Investigator to follow serious adverse events that 
are not resolved or medically stable within 30 days of the last study visit until they become 
resolved or medically stable. 
7.5 Terminology for Adverse Event Descriptions 
When reporting an adverse event, the event description should use the best matching 
terminology describing the event as found in the “Common Terminology Criteria for Adverse 
Events” (CTCAE, v 4.0). If an available CTCAE term fits the event well, no additional descriptors 
may be needed. However, any necessary descriptions should be used in order to clarify the 
event or to place it in an appropriate context. If an appropriate term matching the adverse event 
cannot be found in the CTCAE, the adverse event description should include a diagnosis, sign 
or symptom with additional information to facilitate subsequent categorization into MedDRA 
coding terms. Each reported event will be a single term or concept. 
7.6 Reporting of Pregnancy 
Pregnancy, in and of itself, is not regarded as an adverse event. A confirmed pregnancy in a 
participant (by urine or blood test) should be reported to the Coordinating Sponsor as soon as 
the Investigator has been made aware of the pregnancy. The decision on whether to remove 
the implant and terminate the participant from the study will be made by the Investigator and the 
participant following consultation with the Sponsor. The Investigator will use his/her expert 
judgment, based on an assessment of the potential benefit/risk to the participant, to determine if 
it is in the participant’s best interest to continue participation in the study. 
A pregnancy in the partner of a participant should also be reported to the Investigator who will in 
turn notify the Coordinating Center as soon as possible. 
The pregnancy should be followed until birth. The outcome of all such pregnancies  
(i.e., spontaneous miscarriage, elective termination, normal birth or congenital abnormality) 
must be documented and followed-up on a form that will be provided by the Coordinating 
Center. The pregnancy will be followed to term and the outcome, including any premature 
termination, must be reported to the Coordinating Center. All live births must be followed for a 
minimum of 30 days or to the first well-baby visit. All reports of congenital abnormalities/birth 
defects and spontaneous abortions/miscarriages should be reported as an SAE for this study. 
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Elective abortion procedures, without complications, should not be considered as adverse 
events. 
7.7 Notifying the Sponsor 
The Investigators will provide the Coordinating Center with data of all SAEs as defined per the 
protocol on an ongoing basis. The Coordinating Center’s Medical Monitor is responsible for 
notifying the Sponsor and will do so simultaneously with the reporting to the clinical database. 
As noted above, this should be within 24 hours of site awareness of the event. The Medical 
Monitor will review each SAE report and will determine whether the SAE must be reported to 
FDA/regulatory authorities on an expedited basis. The final decision for disposition regarding 
reporting to the FDA/regulatory authorities rests with the Sponsor or their designee. The IND 
Sponsor or their designee is responsible for submitting the SAE reports to FDA/regulatory 
authorities. The Coordinating Center will provide the DSMC with any safety reports submitted to 
FDA/regulatory authorities. The Coordinating Center will maintain copies of any SAE reports 
submitted to FDA/regulatory authorities by the Sponsor. 
The Coordinating Center will provide these expedited reports to the individual site Investigators 
to submit to their respective IRB. Events that are serious, related to therapy and unexpected will 
be reported to FDA/regulatory authorities in 15 days or, for deaths and life threatening events, in 
7 days (per 21 CFR 312.32). 
7.8 Notifying FDA / Regulatory Authorities and the Data and Safety Monitoring 
Committee  
After the SAE has been reported by the Principal Investigator and assessed by the IND 
Sponsor, the IND Sponsor or their designee must report the event to the appropriate regulatory 
authorities using one of these two options: 
• 
Standard reporting (report in the annual report). This option applies if the AE is classified as 
one of the following: 
1. Serious, expected, suspected adverse reaction (serious, expected and related) 
2. Serious and not a suspected adverse reaction (serious and not related) 
• 
Expedited reporting is required. This option applies if the AE is classified serious and 
unexpected suspected adverse reaction (serious, unexpected and related). 
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The Sponsor must report an adverse event as a suspected adverse reaction (related AE) only if 
there is evidence to suggest a causal relationship between the test article and the adverse 
event, such as: 
• 
A single occurrence of an event that is uncommon and known to be strongly associated with 
test article. 
• 
One or more occurrences of an event that is not commonly associated with the test article 
exposure, but is otherwise uncommon in the population exposed to the test article. 
• 
Aggregate analysis of specific serious adverse events observed in a clinical trial (such as 
known consequences of the underlying disease or condition under investigation or other 
events that commonly occur in the study population independent of the test article therapy) 
that indicates those events occur more frequently in the test article treatment group than in a 
concurrent or historical control group. 
• 
Any findings from clinical or epidemiological studies, analysis of data pooled across multiple 
studies, published or unpublished scientific papers or from animal or in vitro testing that 
would result in a safety-related change in the protocol, informed consent, General 
Investigational Plan section of the IND or other aspects of the overall conduct of the trial. 
7.9 Reporting SAEs to the DSMC 
The Coordinating Center will provide the DSMC with safety reports submitted to FDA/regulatory 
authorities as well as data on all SAEs on an ongoing basis. 
The Investigator will ensure the timely dissemination of all AE information, including expedited 
reports and DSMC safety reviews, to the IRB and IEC in accordance with applicable local 
regulations and guidelines. 
7.10 Early Termination or Participant Discontinuation 
Participants may choose to withdraw from this study for any reason at any time without penalty 
or prohibition from enrolling in other clinical protocols. 
The Investigator may discontinue a participant from the study if warranted. The Investigator and 
the Sponsor may also request the withdrawal of a participant because of non-compliance (e.g., 
missed visits), administrative reasons or any other valid and ethical reasons. 
Reasons for participant discontinuation may include, but are not limited to, the following: 
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• 
Investigator determination that it is not in the best interest of the participant to continue 
participation 
• 
Intercurrent illness 
• 
Adverse event 
• 
Worsening condition 
• 
Any other safety concerns 
If a participant withdraws or is discontinued from the study, they should return for an exit visit. 
The schedule of assessments for this visit is the same as that for the final visit. 
The Sponsor may terminate the study earlier than planned for any reason. In the event of early 
termination, the Sponsor will notify the Investigators and IRBs of the decision and will provide all 
relevant information. 
7.11 Safety Monitoring 
A medical monitor will be assigned to review safety information throughout the study. An 
independent Data and Safety Monitoring Committee (DSMC) will operate according to the 
DSMC Charter that will specify operations, roles and responsibilities and communication with 
the Sponsor. 
8 Statistical Considerations 
All analyses will be conducted separately for each Cohort. 
8.1 Efficacy Outcomes 
Cohort 1 
Efficacy outcomes to investigate the efficacy of CNTF produced by NT-501 include (all changes 
relative to NTMT-01 baseline measurements): 
• 
Change in the ellipsoid zone (area of IS/OS loss) from baseline to Months 72, 84, 96 and 
108. 
• 
Change in retinal sensitivity (dB) as measured by microperimetry from baseline to Months 
72, 84, 96 and 108. 
• 
Proportion of study eyes with a 35% or more increase from baseline in the ellipsoid zone 
(area of IS/OS loss) at Months 72, 84, 96 and 108. 
• 
Change in BCVA from baseline to 72, 84, 96 and 108. 
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• 
Proportion of study eyes with 15 or more letter loss from baseline in BCVA at 72, 84, 96 and 
108. 
• 
Proportion of study eyes with 10 or more letter loss from baseline in BCVA at 72, 84, 96 and 
108. 
Cohort 2 
The outcomes to investigate long term efficacy of CNTF or NT-501 include (all change relative 
to NTMT-02 baseline measurements): 
• 
Change in ellipsoid zone (area of IS/OS loss) from baseline to Months 36, 48, 60 and 72. 
• 
Change in retinal sensitivity (dB) as measured by microperimetry from baseline to Months 
36, 48, 60 and 72. 
• 
Proportion of study eyes with a 35% or more increase from baseline in the ellipsoid zone 
(area of IS/OS loss) at Months 36, 48, 60 and 72. 
• 
Change in BCVA from baseline to Months 36, 48, 60 and 72. 
• 
Proportion of study eyes with 15 or more letter loss from baseline in BCVA at Months 36, 48, 
60 and 72. 
• 
Proportion of study eyes with 10 or more letter loss from baseline in BCVA at Months 36, 48, 
60 and 72. 
• 
Change in reading speed from baseline to Months 36, 48, 60 and 72. 
8.2 Analyses in Support of the Efficacy Outcomes 
Cohort 1 
For continuous measures mean, median and distribution of change from baseline in BCVA, and 
enlargement of inner/outer segment discontinuity as measured by SD-OCT will be computed 
separately for study eyes and fellow eyes. For dichotomous outcomes proportions along with 
95% confidence intervals will be computed separately for study eyes and fellow eyes. 
Cohort 2 
Continuous efficacy measures will be assessed using mixed effects models with an overall Type 
I error rate of 0.05 (no adjustments of the type I error rate will be made). Due to clustered data 
(data from two eyes for a percentage of the participants), the variability associated with the 
estimates of effect (mean difference) from a fixed effects model is likely to be biased, leading to 
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incorrect test statistics and confidence intervals. For example, if the correlation from paired eyes 
is ignored, the standard error for the treatment effect is likely to be overestimated when paired 
eyes from the same participant are in different treatment groups. For this reason, the unpaired t-
test for the comparison of means between two treatment groups is not appropriate as it 
assumes that observations from the same cluster are independent. The appropriate statistical 
analysis of clustered data should take such correlation into consideration which can be 
accomplished for continuous outcome measures using a mixed effects model. The mixed 
effects model will incorporate both random (accounting for the correlation between eyes) and 
fixed effects (treatment) into the model and will be estimated with accompanying 95% 
confidence intervals and compared between treatment groups. For dichotomous outcomes, 
logistic regression incorporating the generalized estimation equation (GEE) methodology with 
accompanying 95% confidence intervals will be performed to determine if there are significant 
differences in the odds between the two treatment groups. 
The efficacy analyses will be repeated to investigate the strength of potential predictors using  
multivariable mixed effects models or multiple logistic regression models. Examples of potential 
predictors include the following: baseline visual acuity, clinical site, participant’s age at 
enrollment and gender. 
8.3 Sample Size 
A sample size of 66 participants, the number of participants enrolled in the NTMT-02 study and 
7, the number of participants enrolled in the NTMT-01 study, will be eligible for enrollment. 
8.4 Safety Analysis 
Long term safety will be assessed through the summary of ocular and non-ocular adverse 
events, serious adverse events and pre-specified safety outcome as defined in Section 6.1.3 
and will include frequency and descriptive tabulation. No formal statistical analysis will be 
employed. Safety analyses will include all participants who received the implant or sham. 
8.5  Adverse Events 
Adverse events will be tabulated by body system, high-level term and preferred term separately 
for each Cohort. Summaries of adverse events by severity will be provided. Separate 
summaries will be prepared for non-ocular and ocular adverse events, with events in the study 
eye(s) and fellow eye summarized separately for Cohort 1 and 2. Separate summaries of non-
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ocular and ocular adverse events reported as related to the implant or the implant surgery will 
be prepared. Serious adverse events will be summarized similarly. Adverse events leading to 
discontinuation from the study will be listed and tabulated. 
8.6  Data Quality Assurance 
A Coordinating Center will have the primary responsibility for assuring that the quality of the 
data collected and reported in the study are of consistently high quality. Many factors contribute 
to the quality of the data, from the design and procedures of the trial to the analytic methods 
employed. The Coordinating Center works with the Reading Center on the design and 
implementation of a quality assurance program for grading images collected as part of the 
study. 
The major quality assurance features of the study are: 
• 
Standard data collection forms and procedures; 
• 
Common protocol for eligibility, examination and follow-up of all participants in all clinical 
centers; 
• 
MASKED assessment of the primary outcome measure and secondary outcome measures; 
• 
Central masked grading of study images; 
• 
Data entry into the study database and the Clinical Centers; 
• 
Central, computer driven data editing for missing, invalid and suspect responses; 
• 
Regular reporting of performance of all Clinical Centers; 
• 
Monitoring visits to all Clinical Centers; and 
• 
Certification of clinic staff and of imaging equipment. 
9 Human Participant Protection 
All participants will receive a verbal explanation from the Principal Investigator or his/her 
appropriate designee in terms suited to their comprehension of the purposes, procedures and 
potential risks of the study. In the opinion of the Principal Investigator or designee, the 
participants must be capable of comprehending the contents of the informed consent and able 
to sign an informed consent form, which must be obtained prior to enrollment. The participants 
will have an opportunity to review the consent form carefully and ask questions regarding this 
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study prior to signing, and they will be informed that they may withdraw from the study at any 
time without prejudice to themselves. 
The participants’ names will not appear on any of the data forms reported to the Coordinating 
Center. Participants will be identified by a study number. The date of birth of each participant 
will be collected in the data system. The information collected will remain confidential. 
10 Study Risks 
There are risks associated with the diagnostic procedures required for participants in this study. 
However, these are all standard procedures that are performed as part of a normal eye and 
medical exam. Some of the discomforts associated with the ocular exam include the following: 
1. Dilating drops or anesthetic drops may sting. They can cause an allergic reaction, or if 
contaminated, can cause an infection, but neither of these problems is very likely to occur. 
2. Dilating drops can also cause a sudden increase of pressure (acute glaucoma) in eyes that 
are already predisposed to develop this condition. There is little risk of glaucoma being 
triggered in this way, but if it is, treatment is available. 
3. In rare instances, the cornea may be abraded during measurement of intra-ocular pressure 
or use of a contact lens (used for examination purpose only and not a contact lens used to 
correct a participants' refractive error). 
There are risks to the procedures required for participants in this study. 
Optical Coherence Tomography is an FDA-approved imaging technique, which is not 
associated with any adverse events. 
Fundus photography and autofluorescence are not associated with any adverse events, 
although some participants may experience mild discomfort due to the bright lights. 
There are also risks associated with the operations performed during the NTMT-01 and NTMT-
02 surgical visit to implant the device and/or perform the sham procedure. These risks will 
remain in the extension protocol in case any new procedure related adverse experiences are 
recorded. In general, the risks of intraocular surgery are very small. Some side effects could 
occur locally in the eye and could affect the participant’s vision. There may be pain or infection, 
a small amount of bleeding, miosis, retinal detachment, cataract, vitritis and/or mild astigmatism. 
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In many cases, topical antibiotics and topical steroids can treat minor degrees of inflammation 
or infection. More serious infection or inflammation may require further surgery on the eye, likely 
with removal of the implant. The sham procedure of subconjunctival injection of lidocaine and 
inserting a final suture in the conjunctiva may be accompanied by subconjunctival bleeding, pain 
or infection which all can be readily treated without any functional changes or any other 
permanent structural changes. 
A possible complication of the explant surgery, if necessary, to remove the NT-501 device is a 
retinal detachment. The probability of retinal detachment in the normal population is less than 
1%. These other side effects are also possible (a probability of less than 1%): 
• 
Bleeding in the eye 
• 
Cataract 
• 
Infection 
• 
Inflammation inside the eye 
Surgery to remove the device may result in pain, loss of vision or blindness in rare cases. Some 
of these side effects can be treated with medication either by mouth or injections in or around 
the eye. Some side effects may require laser or surgery on the eye to treat. 
A small sample (about 0.1 mL) of the vitreous along with the device may be collected and 
shipped back to Neurotech for analysis. 
If the participants have the NT-501 device removed, they will be invited to continue to participate 
in the Extension Study visits and assessments until the final Extension Study visit. 
11 Investigator Requirements 
This study will be conducted in accordance with Good Clinical Practice (GCP), using the 
guidance documents and practices offered by ICH and FDA, and in accordance with the 
Declaration of Helsinki. This study will also comply with the regulations 21 CFR Parts 50, 54, 56 
and 312 under an IND application authorized by FDA. 
11.1 Informed Consent Form 
A template Informed Consent Form will be provided to each site. The Sponsor, or their 
designee, must review and approve any proposed deviations from the provided Informed 
Consent template or any alternate consent forms proposed by the site (collectively, the 
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“Consent Forms”) before IRB/IEC submission. The final IRB/IEC-approved Consent Forms must 
be provided to the Sponsor for regulatory purposes. 
The Consent Forms must be dated and signed by the participant before his or her participation 
in the study. The case history for each participant shall document the informed consent process 
and that written informed consent was obtained prior to participation in the study. A copy of 
each signed Consent Form must be provided to the participant. 
All signed and dated Consent Forms must remain in each participant’s study file and must be 
available for verification by protocol monitors at any time. 
The Informed Consent Form should be revised whenever there are changes to the procedures 
outlined in the informed consent or when new information becomes available that may affect the 
willingness of the participant to participate. Participants must be re-consented with the most 
current (updated) version of the respective Consent Form during their participation in the study if 
deemed required by the Sponsor due to updated risks or new information becomes available 
that may affect the willingness of the participant to participate. This consent process must be 
documented in the case history. 
11.2 Communication with the Institutional Review Board or Independent Ethics 
Committee 
This protocol, the Informed Consent Forms, any information to be given to the participant and 
relevant supporting information must be submitted to the IRB/IEC by the Principal Investigator of 
each site for review and approval before the study is initiated. In addition, any participant 
recruitment materials must be approved by the IRB/IEC. 
The Principal Investigator is responsible for providing written summaries of the status of the 
study to the IRB/IEC annually or more frequently in accordance with the regulatory requirements 
and policies and procedures established by the IRB/IEC. Investigators are also responsible for 
promptly informing the IRB/IEC of any protocol changes or amendments and of any 
unanticipated problems involving risk to human participants or others. 
In addition to the requirements to report protocol-defined AEs to the Sponsor, Investigators are 
required to promptly report to their respective IRB/IEC all unanticipated problems involving risk 
to human participants. Some IRBs/IECs may want prompt notification of all SAEs, whereas 
others require notification only about events that are serious, assessed to be related to study 
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treatments and are unexpected. Investigators may receive written IDE safety reports or other 
safety-related communications from the Sponsor. Investigators are responsible for ensuring that 
such reports are reviewed and processed in accordance with regulatory requirements and with 
the policies and procedures established by their IRB/IEC and archived in the site’s Study File. 
11.3 Study Monitoring Requirements 
To ensure compliance with GCP and all applicable regulatory requirements, the Sponsor or their 
representative may conduct a quality assurance audit of the site records, and the regulatory 
agencies may conduct a regulatory inspection at any time during or after completion of the 
study. In the event of an audit or inspection, the Principal Investigator (and institution) must 
agree to grant the monitor(s) and inspector(s) direct access to all relevant documents and to 
allocate their time and the time of their staff to discuss any findings/relevant issues. The 
Principal Investigator will permit the monitors, Sponsor representatives, US FDA, other 
regulatory agencies, Institutional Review Boards and the respective national or local health 
authorities to inspect facilities and records relevant to this study. 
11.4 Electronic Case Report Forms 
Sites will receive training and a user’s guide appropriate for electronic case report form (eCRF) 
completion. The eCRFs will be submitted electronically to the Coordinating Center and should 
be handled in accordance with instructions from the Coordinating Center. 
All eCRFs should be completed by designated, trained examining personnel or the study 
coordinator as appropriate. 
In addition, at the end of the study, the Investigator will receive participant data for his or her site 
in a readable format that must be kept with the study records. 
11.5 Source Data Documentation 
Protocol monitors will perform ongoing site visits to confirm that critical protocol data (i.e., 
source data) entered into the eCRFs by authorized site personnel are accurate, complete and 
verifiable from source documents. 
Source documents are where participant data are recorded and documented for the first time. 
They include, but are not limited to, hospital records, clinical and office charts, memoranda, 
evaluation checklists, recorded data from automated instruments, copies of transcriptions that 
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are certified after verification as being accurate and complete, photographic negatives, magnetic 
media and medico-technical departments involved in the clinical trial. 
To facilitate monitoring, the Investigator(s) and institution(s) must provide the Sponsor direct 
access to applicable source documents and reports for trial-related monitoring, Sponsor audits 
and IRB/IEC review. The investigational site must also allow inspection by applicable regulatory 
authorities. 
11.6 Use of Computerized Systems 
When clinical observations are entered directly into an investigational site’s computerized 
medical record system (i.e., in lieu of original hardcopy records), the electronic record can serve 
as the source document if the system has been validated in accordance with FDA requirements 
pertaining to computerized systems used in clinical research. An acceptable computerized data 
collection system (for clinical research purposes) would be one that (1) allows data entry only by 
authorized individuals, (2) prevents the deletion or alteration of previously entered data and 
provides an audit trail for such data changes (e.g., modifications of file), (3) protects the 
database from tampering and (4) ensures data preservation. 
If a site’s computerized medical record system is not adequately validated for the purposes of 
clinical research (as opposed to general clinical practice), applicable hardcopy source 
documents must be maintained to ensure that critical protocol data entered into the eCRFs can 
be verified. 
11.7 Disclosure of Data 
Participant medical information obtained by this study is confidential and may only be disclosed 
to third parties as permitted by the Informed Consent Form (or separate authorization to use 
and disclose personal health information) signed by the participant, or unless permitted or 
required by law. 
Medical information may be given to a participant’s physician or other appropriate medical 
personnel responsible for the participant’s welfare for treatment purposes. 
Data generated by this study must be available for inspection upon request by representatives 
of the US FDA and other regulatory agencies, national and local health authorities, Sponsor 
representatives and the IRB/IEC for each study site, if appropriate. 
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11.8 Retention of Records 
US FDA regulations (21 CFR §312.62[c]) and ICH Guideline for GCP (see Section 4.9 of the 
guideline) require that records and documents pertaining to the conduct of this study, including 
eCRFs and consent forms, must be retained by the Principal Investigator for 2 years after the 
last marketing application approval in an ICH region or after at least 2 years have elapsed since 
formal discontinuation of clinical development of the investigational product. All state and local 
laws for retention of records also apply. 
No records should be disposed of without the written approval of the Sponsor. Written 
notification should be provided to the Sponsor for transfer of any records to another party or 
moving them to another location. 
For studies conducted outside the United States under a US IND/IDE, the Principal Investigator 
must comply with the record retention requirements set forth in the US FDA IND/IDE regulations 
and the relevant national and local health authorities. 
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12 References 
Aebischer, P. & Kato, A.C. Treatment of amyotrophic lateral sclerosis using a gene therapy  
approach. Eur Neurol 1995;35: 65-8. 
Bush, R.A., Lei, B., Tao, W., Raz, D., Chan, C-C., Cox, T.A., Santos-Muffley, M., and Sieving, 
P.A. (2004) Encapsulated cell-based intraocular delivery of ciliary neurotrophic factor (CNTF) in 
normal rabbit: dose dependent effects on ERG and retinal histology. IOVS. 45(7):2420-30. 
Cayouette, M., Behn, D., Sendtner, M., Lachapelle, P. & Gravel, C. Intraocular gene transfer of 
ciliary neurotrophic factor prevents death and increases responsiveness of rod photoreceptors 
in the retinal degeneration slow mouse. J Neurosci 1998;18: 9282-93. 
Charbel Issa P, Troeger E, Finger R, Holz FG, Wilke R, Scholl HP. Structure-function correlation 
of the human central retina. PLoS One. 2010 Sep 22;5(9):e12864. 
Chew EY, Clemons, Peto T, Sallo FB, Ingermann A, Tao W, Singerman L, Schwartz SD, 
Peachey NS, Bird AC. Ciliary Neurotrophic Factor for Macular Telangiectasia Type 2: Results 
From a Phase 1 Safety Trial. 2015. 159 (4):659-666 
Chong, N.H. et al. Repeated injections of a ciliary neurotrophic factor analogue leading to long 
term photoreceptor survival in hereditary retinal degeneration. Invest Ophthalmol Vis Sci 
1999;40: 1298-305. 
de Almeida, L.P., Zala, D., Aebischer, P. & Deglon, N. Neuroprotective effect of a CNTF-
expressing lentiviral vector in the quinolinic acid rat model of Huntington's disease. Neurobiol 
Dis 2001;8: 433-46. 
Department of Health and Human Services, Food and Drug Administration. Human cells, 
tissues, and cellular and tissue-based; donor screening and testing; and related labeling. Fed. 
Register. 70, 29949-29952. 
Dorrell MI, Aguilar E, Jacobson R, Yanes O, Gariano R, Heckenlively J, Banin E, Ramirez GA, 
Gasmi M, Bird A, Siuzdak G, Friedlander M. (2009). Antioxidant or neurotrophic factor treatment 
preserves function in a mouse model of neovascularization-associated oxidative stress. Journal 
of Clinical Investigations Mar;119(3):611-23. 
Emerich, D.F. et al. Implants of encapsulated human CNTF-producing fibroblasts prevent 
behavioral deficits and striatal degeneration in a rodent model of Huntington's disease. J 
Neurosci 1996;16: 5168-81. 
Emerich, D.F. et al. Protective effect of encapsulated cells producing neurotrophic factor CNTF 
in a monkey model of Huntington's disease. Nature 1997;386: 395-9. 
Gass, J.D.M. Stereoscopic atlas of macular disease: diagnosis and treatment. 1987. Mosby; St. 
Louis 
Gass, J.D., Oyakawa, R,T. Idiopathic juxtafoveolar retinal telangiectasis, Arch Ophthalmol 
1982;100:769-780. 
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Gass, J.D.M. & Blodi, B.A. Idiopathic juxtafoveolar retinal telangiectasis: update of classification 
and follow-up study. Ophthalmology 1993;1536-1546. 
Heeren et al (2015) Invest Ophthalmol Vis Sci. 2015;56:3905–3912). 
International Conference of Harmonization Tripartite Guideline, 'Viral Safety Evaluation of 
Biotechnology Products Derived from Cell Lines of Human or Animal Origin'. 
International Congress of Harmonization; Guidance on Quality of Biotechnological/Biological 
Products: Derivation and Characterization of Cell Substrates Used for Production of 
Biotechnological/Biological Products. 
Investigational New Drug Application BB-IND-10931; NT-501; Allogeneic Retinal Pigment 
Epithelial Cells Transfected with DNA Plasmid Vector (pNUT-IgSP-hCNTF), Expressing Ciliary 
Neurotrophic Factor (CNTF), Encapsulated in a Hollow Fiber Membrane, Original Submission 
(000). 
Lamoureux E, Maxwell R, Marella M, Dirani M, Fenwick E, Guymer R. The longitudinal impact 
of Macular Telangiectasia (MacTel) Type 2 on vision-related quality of life. Invest Ophthalmol 
Vis Sci. 2011 Jan 7. [Epub ahead of print]. 
LaVail, M.M. et al. Multiple growth factors, cytokines, and neurotrophins rescue photoreceptors 
from the damaging effects of constant light. Proc Natl Acad Sci U S A 1992;89: 11249-53. 
LaVail, M.M. et al. Protection of mouse photoreceptors by survival factors in retinal 
degenerations. Invest Ophthalmol Vis Sci 1998;39: 592-602. 
Lindsay, R.M. Neurotrophic growth factors and neurodegenerative diseases: therapeutic 
potential of the neurotrophins and ciliary neurotrophic factor. Neurobiol Aging 1994;15: 249-51. 
McGill, T.J. et al. Intraocular CNTF reduces vision in normal rats in a dose-dependent manner. 
IOVS 2007;48:5756-66. 
Mittoux, V. et al. Restoration of cognitive and motor functions by ciliary neurotrophic factor in a 
primate model of Huntington's disease. Hum Gene Ther 2000;11: 1177-87. 
Ooto, S., Hangai, M., Takayama, K., Arakawa N., Tsujkawa, A., Hideka, K., Susumu, O. & 
Yoshimura, N. High-resolutation photoreceptor imaging in idiopathic macular telangiectasia type 
2 using adaptive optics scanning laser ophthalmoscopy. Invest Ophthalmol Vis Sci 
2011;52:5541-5550. 
Pre-Clinical Evaluation of NT-501-X.02 in the Rabbit Eye: CNTF Vitreous Levels and Pre-
Implant and Post-Explant CNTF Device Output Rates (Neurotech Study P0068). 
Regulier, E., Pereira de Almeida, L., Sommer, B., Aebischer, P. & Deglon, N. Dose-dependent 
neuroprotective effect of ciliary neurotrophic factor delivered via tetracycline-regulated lentiviral 
vectors in the quinolinic acid rat model of Huntington's disease. Hum Gene Ther 2002;13: 1981-
90. 
Reichenbach A. & Bringmann A. Mueller cells in the healthy and diseased retina. 2010. 
Springer; New York. 
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Sagot, Y. et al. Polymer encapsulated cell lines genetically engineered to release ciliary 
neurotrophic factor can slow down progressive motor neuronopathy in the mouse. Eur J 
Neurosci 1995;7: 1313-22. 
Sieving, P.A. et al. Phase I study of ciliary neurotrophic factor (CNF) delivered by intravitreal 
implant of encapsulated cell technology (ECT) device in patients with retinitis pigmentosa. 
Invest Ophthalmol Vis Sci 2005;46:E-Abstract 531. 
Talcott, K.E, et al. Longitudinal study of cone photoreceptors during retinal degeneration and in 
response to ciliary neurotrophic factor treatment. IOVS 2010 [Epub ahead of print]. 
Tao, W. et al. Encapsulated cell-based delivery of CNTF reduces photoreceptor degeneration in 
animal models of retinitis pigmentosa. Invest Ophthalmol Vis Sci 2002;43: 3292-8. 
Toxicology Assessments for Intraocular Implantation of NT-501 (Neurotech Study P0008). 
 
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13 Appendix 1 
Assessment / Examination Schedule 
VISITS ARE SCHEDULED FROM THE DATE OF THE 
NTMT-01 OR NTMT-02 SURGERY  
 
VISIT  1 (+/- 1 month) 
VISIT  2 (+/- 1 month) 
VISIT  3 (+/- 1 month) 
VISIT  4 (+/- 1 month) 
GENERAL ASSESSMENTS 
 
 
 
 
NTMT-01/02 Extension Study Consent 
X 
 
 
 
Review Eligibility Criteria  
X 
 
 
 
Review Demographics and Participant Contact Information 
X 
 
 
 
Update Medical & Ophthalmic History from NTMT-01 and NTMT-02 
 -This will include AEs collected during NTMT-01 and NTMT-02 and up to Visit 1 of 
the Extension Study as applicable. Any events between the last NTMT-01 or 
NTMT-02 visit will be recorded here. 
X 
 
 
 
AE Assessment – starting from date of NTMT-01/02E Consent 
 
X 
X 
X 
Concomitant Medications – continue from NTMT-01 and NTMT-02 
X 
X 
X 
X 
Reading Speed*  
*Completed for NTMT-02 (Cohort 2) participants only 
X* 
X* 
X* 
X* 
VISUAL SYSTEM EXAMS: UN-DILATED 
 
 
 
 
Manifest Refraction 
X 
X 
X 
X 
Best Corrected Visual Acuity 
X 
X 
X 
X 
Applanation Tonometry (Goldmann applanation tonometer) 
X 
X 
X 
X 
Microperimetry 
X 
X 
X 
X 
VISUAL SYSTEM EXAMS: DILATED 
 
 
 
 
Slit lamp Biomicroscopy 
X 
X 
X 
X 
Dilated Fundus Examination 
X 
X 
X 
X 
Implant Site Clinical Examination  
X 
X 
X 
X 
SD-OCT 
X 
X 
X 
X 
Fundus Autofluorescence Imaging 
X 
X 
X 
X 
Digital Color Fundus Photographs 
X 
X 
X 
X 
**AOSLO (for participants enrolled at NTMT-02 baseline ) 
**Requires separate consent at AOSLO Center 
X** 
X** 
X** 
X** 
 
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