Clinical trial NCT04895293
Conditions: Age Related Macular Degeneration
Sponsor: Maturi, Raj K., M.D., P.C.
Start date: 2021-06-15; Completion date: 2022-03-04
Enrollment: 5 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study is a single-center, open label, 4-month study, designed to evaluate the safety and treatment efficacy of RBM-007 in patients with intraretinal or subretinal edema due to previously untreated neovascular AMD. Up to 5 subjects will be randomized to receive study medication. Study treatment will be administered by intravitreal injections.

Detailed description:

Arms: arm 1: Single intravitreal injection in study eye
Interventions: intervention 1: RBM-007 Injectable Solution
Intervention descriptions: intervention 1: Sterile solution

Protocol documents:
Prot_SAP_000.pdf: 
Cover Page for Protocol 
NCT04895293 
Title: Evaluation of RBM-007 in subjects with treatment naïve exudative age-related macular 
degeneration (TEMPURA Study) 
Study: RKM-011 
Date: 11 April 2021 
Statistical plans contained within protocol 


Raj J. Maturi, M.D., P.C. 
Clinical Study Protocol 
Confidential 
rkm-011_protocol.docx/11 April 2021/page 1 
 
 
 
 
 
Clinical Study Protocol 
RKM-011 
 
Evaluation of RBM-007 in subjects with treatment naïve exudative age-
related macular degeneration 
 
Protocol Number: 
RKM-011 
Investigational Product: 
RBM-007 Injectable Solution 
Indication: 
Treatment of exudative age-related macular 
degeneration 
Phase: 
Phase 2 
Sponsor: 
Raj K. Maturi, M.D., P.C. 
 
 
Phone 
 
Medical Monitor 
Raj K. Maturi, M.D., P.C. 
Protocol Date: 
11 April 2021  
Protocol Version: 
Initial 
Replaces: 
N/A/ 
 
 
 
 
 
 


Raj J. Maturi, M.D., P.C. 
Clinical Study Protocol 
Confidential 
rkm-011_protocol.docx/11 April 2021/page 2 
 
Contact Information and Protocol Authorization 
 
Clinical Study Protocol 
RKM-011  
Phase 2 
 
 
Protocol Title: 
Evaluation of RBM-007 in subjects with treatment naïve exudative 
age-related macular degeneration 
Protocol Number: 
RKM-011 
This study will be conducted in compliance with the clinical study protocol (and 
amendments), International Conference on Harmonisation (ICH) guidelines for current 
Good Clinical Practice (GCP) and applicable regulatory requirements. 
Sponsor Signatory: 
Raj K. Maturi, M.D., P.C. 
Date: 
 
 
 


Raj J. Maturi, M.D., P.C. 
Clinical Study Protocol 
Confidential 
rkm-011_protocol.docx/11 April 2021/page 3 
 
 
 
 
TABLE OF CONTENTS 
 
1 
PROTOCOL SUMMARY ........................................................................................................................... 4 
2 
BACKGROUND AND CLINICAL RATIONALE ................................................................................... 6 
3 
STUDY OBJECTIVES ................................................................................................................................ 6 
4 
STUDY DESIGN .......................................................................................................................................... 6 
5 
STUDY POPULATION AND ENTRY CRITERIA ................................................................................. 6 
5.1 
Number of Subjects: ................................................................................................................................ 6 
5.2 
Inclusion Criteria: ................................................................................................................................... 7 
5.3 
Exclusion Criteria: .................................................................................................................................. 7 
5.4 
Permissible Medications/Treatments: ................................................................................................... 7 
5.5 
Prohibited Medications/Treatments: ..................................................................................................... 8 
6 
ESCAPE CRITERIA/ MEDICATIONS .................................................................................................... 9 
6.1 
Escape Criteria: ....................................................................................................................................... 9 
6.2 
Escape Medications: ................................................................................................................................ 9 
7 
STUDY TREATMENT ............................................................................................................................... 9 
7.1 
Randomization: ....................................................................................................................................... 9 
7.2 
Administration ......................................................................................................................................... 9 
7.3 
Investigational drug: RBM-007: .......................................................................................................... 10 
8 
SAFETY MEASURES ............................................................................................................................... 10 
9 
ADVERSE EVENTS .................................................................................................................................. 10 
10 
METHOD OF ANALYSIS ........................................................................................................................ 11 
10.1 
General Data Summaries ................................................................................................................. 11 
10.2 
Efficacy evaluation ........................................................................................................................... 11 
11 
STUDY VISIT SCHEDULE AND PROCEDURES ............................................................................... 11 
12 
ADMINISTRATIVE ITEMS .................................................................................................................... 13 
13 
REFERENCES ........................................................................................................................................... 13 
 
APPENDIX A: INJECTION PROCEDURE FOR ALL SUBJECTS ............................................................. 15 
 
List of tables 
TABLE 1: SCHEDULE OF VISITS AND EVENTS ................................................................................. 17 
 
 
 


Raj J. Maturi, M.D., P.C. 
Clinical Study Protocol 
Confidential 
rkm-011_protocol.docx/11 April 2021/page 4 
 
 
 
1 Protocol Summary 
 
Study Compound:  RBM-007 
 
Phase:  2 
 
Study Objective:  To determine safety and efficacy of intravitreal injections of RBM-007 in 
subjects with treatment naïve exudative AMD in the study eye. 
 
Clinical Hypothesis:  RBM-007, as used in previous trials of neovascular AMD, has shown an 
improvement in vision as well as an improvement in subretinal fibrosis in a cohort of subjects with 
chronic wet AMD.  The mechanism of action of RBM-007 is distinct from that of Anti-VEGF 
treatments. RBM-007 has a powerful fibroblast growth factor-2 inhibition which serves to reduce 
both VEGF expression as well as inhibit FGF based neovascular response and fibroblast-
proliferation.  Having both mechanisms of action active early in the disease process will reduce 
the development of fibrosis in naïve wet-AMD subjects and potentially provide an improved and 
sustained visual function and favorable anatomic change. 
 
Structure:  Single site, open label study 
 
Duration:  4 months 
 
Study Treatment group: 
• RBM-007 treatment at baseline, month 1and month 2.  Safety evaluations at week 2, 
months 3 and 4.  
 
 
Randomization: all study subjects will receive study drug and those non-responsive to study drug 
will be treated with rescue anti-VEGF drug, in addition to continuing RBM-007 
 
Visit Schedule: 
 
There will be 6 scheduled visits during the study.  These include baseline (Day 0), week 2, and 
months 1, 2,3, 4/exit. 
 
Primary endpoint one month after the last RBM-007 injection (month 3) 
 
Study Population Characteristics 
 
Number of subjects: Up to 5 subjects will be enrolled 
 


Raj J. Maturi, M.D., P.C. 
Clinical Study Protocol 
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Condition/Disease:  Naïve exudative Age-Related Macular Degeneration with associated visual 
loss. 
 
Key Inclusion Criteria:   
• Aged 50 or older, diagnosed with exudative AMD.  
• BCVA 5-73, inclusive, in study eye  
• Presence of choroidal neovascularization (CNV) secondary to AMD, in study eye 
 
Key Exclusion Criteria: 
• History of major ophthalmic surgery in the past 3 months, and any ophthalmic surgery in 
study eye in the last 30 days 
• History of significant ocular disease other than exudative AMD that many confound results 
• Hypersensitivity to components of study medication 
 
Response Measures 
Efficacy: 
 
• Change in BCVA from baseline to month 3 
• Change in intraretinal and subretinal fluid from baseline to month 3, as measured by  
 
CST on Heidelberg OCT 
• Change in OCT-angiography in study eye from baseline to month 3 
• Number of subjects escaping to standard of care  
• Change in measured area of intraretinal/subretinal fibrosis  
 
Safety: adverse events, BCVA, complete ophthalmic examination, physical examination and vital 
signs. 
 
All adverse events and serious adverse events will be continually assessed throughout the study. 
The investigator will assess safety throughout the study to determine appropriateness of continuing 
dosing and enrollment. 
 
General Statistical methods and Types of Analyses: 
 
The primary efficacy endpoint is: 
• Change in edema from baseline to month 3 (one month after the last injection) as measured 
by CST on Heidelberg OCT 
 
Secondary endpoints include the following: 
• Change in BCVA from baseline to month 3 
• Change in intraretinal and subretinal edema from baseline to month 3  
• CNV lesions components: subretinal hyper-reflective material (SRHM), PED thickness  
• Number of subjects escaping to standard of care treatment  
• Change in size of OCT-angiography leakage from baseline to month 3 


Raj J. Maturi, M.D., P.C. 
Clinical Study Protocol 
Confidential 
rkm-011_protocol.docx/11 April 2021/page 6 
2 Background and Clinical Rationale 
Age-related macular degeneration (AMD) is the leading cause of severe vision loss in people over 
the age of 65 in the United States.1  The majority of severe vision loss due to advanced AMD is 
related to the onset of choroidal neovascularization (CNV). 2,3  Neovascular AMD is characterized 
by the growth of choroidal vessels into the subretinal space.  These vessels have a tendency to 
leak fluid and blood, causing retinal edema and central vision loss.   
 
The CATT study data demonstrates that it is difficult to achieve anatomic flattening of the macula 
in patients with neovascular AMD.4  After one year of required monthly treatment in both the 
bevacizumab and ranibizumab groups, approximately 50% of subjects continued to have 
intraretinal and/or subretinal fluid on optical coherence tomography.4  When fluid is present in 
these structures, retreatment is generally necessary to stabilize vision – and subjects with persistent 
fluid generally have poorer visual gain.  RBM-007 has shown, in a previous clinical trial (see 
attached SUSHI Study CSR) evidence of bioactivity, reducing macular edema associated with 
choroidal neovascularization in wet AMD.  Additionally, the mechanism of action of RBM-007 
is more expansive than that of Anti-VEGF treatment alone as RBM-007, a novel oligonucleotide-
based aptamer, has potent anti-FGF2 activity, which leads to reduced VEGF expression.5,6 In the 
rat and mouse models of laser-induced choroidal neovascularization, RBM-007 showed activity 
after intravitreal injection at doses as low as 5 μg/eye7. In the laser-induced choroidal 
neovascularization fibrosis model in rats, it showed activity after intravitreal injection at doses as 
low as 15 μg/eye7 (see Ribomic Investigator Brochure for RBM-007, 2020).  
 
3 Study Objectives 
To determine safety and efficacy of intravitreal injections of RBM-007 in subjects with naïve 
exudative AMD. 
 
4 Study Design 
This study is a single-center, open label, 4-month study, designed to evaluate the safety and 
treatment efficacy of RBM-007 in patients with intraretinal or subretinal edema due to previously 
untreated neovascular AMD.  Up to 5 subjects will be randomized to receive study medication.  
Study treatment will be administered by intravitreal injections.   
 
There will be 5 scheduled visits during the study.  See table 1.   
 
5 Study Population and Entry Criteria 
5.1 
Number of Subjects:   
5 
 
Study Population Characteristics:  If both eyes meet all of the inclusion/exclusion criteria the eye 
with the worse BCVA at baseline will be selected as the study eye.  If both eyes meet all of the 


Raj J. Maturi, M.D., P.C. 
Clinical Study Protocol 
Confidential 
rkm-011_protocol.docx/11 April 2021/page 7 
inclusion/exclusion criteria and BCVA values are identical for both eyes, the right eye will be 
selected as the study eye. 
 
5.2 
Inclusion Criteria: 
• General Inclusion Criteria: 
1. Male or female patients, 50 years of age or older at baseline 
2. Patient has completed/signed an informed consent prior to any study-related procedures 
and is able to follow study instructions and likely to complete all required visits. 
 
• Ocular Inclusion Criteria: 
3. BCVA 5 – 73 ETDRS letters (20/800-20/40 Snellen equivalent), inclusive, in study eye  
4. Presence of choroidal neovascularization secondary to AMD 
5. Clear ocular media and adequate pupil dilation to permit good quality photographic 
imaging. 
 
5.3 
Exclusion Criteria: 
• General Exclusion Criteria: 
1. Females who are pregnant, nursing, planning a pregnancy or who are of childbearing 
potential not using a reliable method of contraception. 
2. History or current evidence of hypersensitivity to any components of the study 
medication or fluorescein, as assessed by the investigator. 
3. Participation in any investigational drug or device study within 30 days prior to 
baseline 
4. History or current evidence of a medical condition that may, in the opinion of the 
investigator, preclude the safe administration of study medication or affect the results 
of the study. 
 
• Ocular Exclusion Criteria: 
5. Active ocular or periocular infections, malignancy 
6. Aphakia  
7. History of pars plana vitrectomy in the study eye 
8. History of major ophthalmic surgery in the past 3 months in the study eye, or minor 
surgery in the past 30 days 
9. History of significant ocular disease other than exudative AMD that may confound 
results 
10. Uncontrolled glaucoma (defined as intraocular pressure >21mm Hg despite treatment 
with ocular hypotensive medications at baseline). 
 
5.4 
Permissible Medications/Treatments: 
• Therapy considered necessary for the patient's welfare may be given at the discretion of 
the investigator.  Therapies for the non-study eye are permissible at any time. 
 


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Clinical Study Protocol 
Confidential 
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5.5 
Prohibited Medications/Treatments: 
Systemic anti-VEGF medications, or systemic anti-fibroblast growth factor mediations. 


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Clinical Study Protocol 
Confidential 
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6 Escape Criteria/ Medications 
6.1 
Escape Criteria: 
• Subjects with a 10 letter decrease at two consecutive visits or a 15 letter decrease at any 
visit may be escaped to standard of care.  
• Central retinal thickness increase by 50 µm or more associated with at least a 5-letter 
decrease may be escaped to standard of care 
• Presence of new hemorrhage, worsening hemorrhage, new extra foveal fluid, or at the 
discretion of the investigator. 
• Note: Subjects that escape to standard of care will continue to be followed for safety 
through the four-month study period. 
 
6.2 
Escape Medications: 
• Subjects that escape to standard of care may receive treatment with medications at the 
investigator's discretion, which in most cases would be an intravitreal Anti-VEGF drug 
(Eylea, or another drug as determined by the investigator). 
 
7 Study Treatment 
RBM-007 injectable solutions (20 mg/mL) are filled (0.5 mL fill) in 2-mL Type 1 Glass 
(borosilicate) clear vials, capped with 13 mm Gray Butyl stoppers with B2-40 coating (on top) and 
FluroTec coating 
(on bottom), and sealed. Three single use vials will be placed in a carton, and the labeling will 
include protocol number, kit number, drug concentration and storage conditions.  RBM-007 
injectable solutions will be provided by RIBOMIC/Representative and will be stored in an 
appropriate secure area at the investigational site. RBM-007 vials should be protected from light, 
stored upright, and kept at -20°C. 
 
7.1 
Randomization:   
Not applicable for this open-label, single-treatment study. 
 
7.2 
Administration 
Once investigational drug kit numbers have been assigned to the subject, the vial of 
investigational drug with the assigned kit number will be removed from the freezer. The contents 
should be thawed by rotating the vials between the palms of the hands, or by setting the vial at 
room temperature. Care should be taken to protect the product from light. 
Investigational drug should be used for intravitreal injection in the study subject within 1 hour 
after removing the vial from the freezer. 
 
Study drug preparation should be performed by the designated physician. 
 
Each vial contains enough RBM-007 to inject one subject. Each vial will be used one time only. 


Raj J. Maturi, M.D., P.C. 
Clinical Study Protocol 
Confidential 
rkm-011_protocol.docx/11 April 2021/page 10 
Write the subject number on the carton label. After injection, vials should be placed in the plastic 
bag provided by the sponsor, write the subject number and kit number clearly and robustly using 
a permanent marker, seal and store the bag in a secure area. 
 
7.3 
Investigational drug: RBM-007:  
Loading the syringe 
1. A sterile, single-use 250 μL syringe with several custom marking including 0.1 mL (100 μL) 
will be provided separately for IVT injection of RBM-007. Instructions for filling the syringe 
are as follows: 
2. Remove the sterile, single-use 250 μL syringe from the packaging. 
3. Attach a 19-gauge x 1 ½ inch filter needle to the syringe. RBM-007 is dispensed in a 0.5 mL 
fill in a 2 mL vial.  
4. Using sterile technique, carefully draw up approximately 200 μL of RBM-007 into the syringe. 
(Sufficiently larger volume than 100 μL is needed to allow for dead space in syringe and 
needles prior to IVT injection). 
5. Remove the 19-gauge x 1½ inch filter needle from the syringe and replace with a 30-gauge x 
0.5-inch needle for the IVT injection. 
6. Ensure that the 30-gauge x 0.5-inch needle is affixed tightly to the syringe. 
7. Align the top edge of the red O-ring of the plunger with the 100 μL black mark on the syringe, 
expelling the excess fluid drawn up. 
8. Ensure there are no air bubbles within the syringe or the needle hub prior to injection, and prior 
to expelling the excess fluid drawn up. 
 
8 Safety Measures 
 
Safety measures include the following: 
• adverse events recording 
• BCVA 
• complete ophthalmic exam (consisting of an external examination of the eye, routine 
screening for eyelid/pupil responsiveness, confrontation visual field, slit-lamp 
biomicroscopy, dilated fundus exam and IOP measurement) 
• vital signs (blood pressure and pulse rate) and general physical examination 
• optical coherence tomography (OCT), with OCT-A determination 
• Fluorescein angiography 
• Fundus autofluorescence 
9 Adverse Events 
All adverse events throughout the course of the study will be monitored and reported on the adverse 
event form including seriousness, severity, action taken and relationship to study drug.  If adverse 
events occur, the first concern will be the safety of the study participants.  For serious adverse 
events, the participant will be followed until the event has been resolved or deemed medically 
stable by the investigator.   
 


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Clinical Study Protocol 
Confidential 
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If a female of childbearing potential becomes pregnant during the study, the subject will be exited 
from the study.  The investigator will notify the subject's physician that the subject has been 
treated with RBM-007 and will follow the progress of the pregnancy.  The investigator will 
document the outcome of the pregnancy. 
 
10 Method of Analysis   
The analysis of data from the study will be performed when all subjects have either completed the 
visit at Month 4 or discontinued early from the study. Once all of data through Month 4 have been 
cleaned, verified, and placed in the database, it will be transferred to the personnel performing the 
analysis. 
 
10.1 General Data Summaries 
Continuous variables will be summarized with means and standard deviations and medians with 
min and max values and categorical variables with frequencies and percentages.  Standard 
parameters and statistical tests will be performed to evaluate for the primary and secondary end 
points.  Specifically, mean change in the CST, manual determination for the presence of 
subretinal fluid and intraretinal fluid at month three (and at other time points), change in BCVA 
between baseline and month three, and the number of anti-VEGF injections needed will be 
measured. Based on the results of these tests, additional testing, as outlined below, may be 
performed.   
 
10.2 Efficacy evaluation 
Descriptive statistics will be performed on all subjects with special care taken to carefully analyze 
the change in OCT-A, OCT determined macular thickness, visual acuity (BCVA), fundus 
autofluorescence and fluorescein angiography.  All subjects randomized (ITT population) will be 
included in the analysis, and subjects will be grouped according to the number of study treatments 
received (if less than 3). Safety parameters will be evaluated in the patient population. 
 
11 Study Visit Schedule and Procedures 
Please see Table 1 for a schematic of the schedule of visits and procedures.  The visit schedule 
includes 5 scheduled visits: baseline, month 1, 2, 3, and 4.   
 
Baseline visit: 
• obtain informed consent and authorization 
• collect demographic information and medical and ophthalmic history 
• collect information about concomitant medication and procedures 
• physical examination 
• vital signs (blood pressure and pulse rate) 
• Pregnancy Test (if indicated) 
Perform the following procedures in both eyes: 
• standard BCVA, using ETDRS method following refraction 


Raj J. Maturi, M.D., P.C. 
Clinical Study Protocol 
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rkm-011_protocol.docx/11 April 2021/page 12 
• complete ophthalmic examination: slit-lamp biomicroscopy, indirect ophthalmoscopy and 
IOP 
• Heidelberg OCT imaging 
• Angiovue OCT-A imaging 
• dilated fundus photography (Heidelberg) 
• fluorescein angiography (Heidelberg) 
• autofluorescence fundus photography (Heidelberg)  
• confirm eligibility  
• perform intravitreal injection in study eye (treat fellow eye as standard of care, as indicated) 
• query for adverse evets 
 
 
Week 2 Safety Assessment Visit 
• query for adverse events 
• query for medication changes and medical procedures 
• if rescue criteria met, treat with anti-VEGF at this visit. 
Perform the following procedures in both eyes: 
• standard BCVA, using ETDRS method following refraction 
• complete ophthalmic examination: slit-lamp biomicroscopy, indirect ophthalmoscopy and 
IOP 
• Heidelberg OCT imaging 
• Angiovue OCT-A imaging 
 
Month 1, and 2 visits 
• query for adverse events 
• query for medication changes and medical procedures 
• if rescue criteria met, treat with RBM-007 then, standard of care anti-VEGF at that visit.  
An anterior chamber paracentesis will be performed at the visit as well for intraocular 
pressure control.  Treatment with RBM-007 may be withheld per investigator discretion.   
Perform the following procedures in both eyes: 
• standard BCVA, using ETDRS method following refraction 
• complete ophthalmic examination: slit-lamp biomicroscopy, indirect ophthalmoscopy and 
IOP 
• Heidelberg OCT imaging 
• Angiovue OCT-A imaging 
• dilated fundus photography (Heidelberg) 
• Perform assigned intravitreal injection per protocol in study eye 
 
Month 3 visit: (primary endpoint) 
• query for adverse events 
• query for medication changes and medical procedures 
Perform the following procedures in both eyes 
• standard BCVA, using ETDRS method following refraction 
• complete ophthalmic examination: slit-lamp biomicroscopy, indirect ophthalmoscopy and 
IOP 


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Clinical Study Protocol 
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rkm-011_protocol.docx/11 April 2021/page 13 
• Heidelberg OCT imaging 
• Angiovue OCT-A imaging  
• dilated fundus photography (Heidelberg) 
• autofluorescence fundus photography (Heidelberg)  
 
Month 4 (exit): 
• query for adverse events 
• query for medication changes and medical procedures 
• vital signs (blood pressure and pulse rate) 
• physical examination 
• Pregnancy Test (if indicated) 
Perform the following procedures in both eyes: 
• standard BCVA, using ETDRS method following refraction 
• complete ophthalmic examination: slit-lamp biomicroscopy, indirect ophthalmoscopy and 
IOP 
• Heidelberg OCT imaging 
• Angiovue OCT-A imaging 
• fluorescein angiography (Heidelberg) 
• dilated fundus photography (Heidelberg) 
• autofluorescence fundus photography (Heidelberg) 
 
 
Unscheduled visits: 
Additional examinations may be performed at the investigator’s discretion to ensure the safety and 
well-being of the subject during the study.   
 
12 Administrative Items 
This protocol is to be conducted in accordance with the applicable Good Clinical Practice (GCP) 
regulations and guidelines. 
 
Written informed consent is to be obtained from each patient prior to any study-related activities 
or procedures in the study. 
 
This study is to be conducted in accordance with IRB regulations.  The investigator will obtain 
approval from a properly constituted IRB prior to initiating the study and re-approval or review at 
least annually.   
 
13 References 
 
1. Rein DB, Wittenborn JS, Zhang X, Honeyutt AA, Lesesne SB, Saaddine J, et al. 
Forecasting age-related macular degeneration through the year 2050: the potential impact 
of new treatments. Arch ophthalmol. 2009;127;533-540. 


Raj J. Maturi, M.D., P.C. 
Clinical Study Protocol 
Confidential 
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2. Ferris FL 3rd.  Senile macular degeneration: review of epidemiologic features. Am J 
Epidemiol. 1983;118(2)132-151. 
3. Sommer A, Tielsch JM, Katz J, Quigley HA, Gottsch JD, Javitt JC et al. Racial differences 
in the cause-specific prevalence of blindness in East Baltimore. N Engl J Med. 
1991;14(20):1412-1417. 
4. Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research 
Group. 5-Year Outcomes with Anti-VEGF Treatment of Neovascular Age-related Macular 
Degeneration (AMD): The Comparison of AMD Treatments Trials. Ophthalmology. 2016 
August; 123(8): 1751–1761. 
5. Jin L, Nonaka Y, Miyakawa S, Fujiwara M, Nakamura Y. Dual Therapeutic Action of a 
Neutralizing Anti-FGF2 Aptamer in Bone Disease and Bone Cancer Pain. Mol Ther 2016; 
24:1974-86. 
6. Belgore F, Lip GYH, Blann AD. Basic fibroblast growth factor induces the secretion of 
vascular endothelial growth factor by human aortic smooth muscle cells but not by 
endothelial cells. European Journal of Clinical Investigation 2003; 33:833-839. 
7. Matsuda Y, Nonaka Y, Satoshi Futakawa, et al. Anti-Angiogenic and Anti-Scarring Dual 
Action of an Anti-Fibroblast Growth Factor 2 Aptamer in Animal Models of Retinal 
Disease. Mol Ther 2019; 17: 819-832. 
 
Investigator Brochure for RBM-007 Injectable Solution (Ribomic USA, Version 3.0, 9 September 
2020). 
 
 


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Clinical Study Protocol 
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Appendix A: Injection Procedure for All Subjects 
 
The following procedures will be implemented to minimize the risk of potential adverse events 
associated with serial intravitreal injections.  Aseptic technique will be observed by clinic staff 
involved in the anesthetic preparation, study drug preparation and administration.   
Assemble the supplies.  Supplies include gloves, eyelid speculum, 0.5% proparacaine 
hydrochloride, 5% povidone iodine ophthalmic solution, ophthalmic antimicrobial solution and 
injection supplies. 
 
Instill at least 2 drops of 0.5% proparacaine into the study eye. 
 
The investigator will glove.  Optional: place a speculum underneath the eyelids of the study eye. 
 
Instill 2 drops of 5% povidone iodine ophthalmic solution in the study eye, making sure the drops 
cover the planned injection site on the conjunctiva.  Wait 15-30 seconds. 
 
Investigator performs intravitreal injection of RBM-007 into study eye.   
 
Remove lid speculum (if placed) and irrigate eye with eyewash solution. 
 
Instruct subject verbally on post injection instructions including signs of infection. 
 
Confirm vision is at least hand motions before subject leaves the clinic. 
 
 
Study Drug Storage 
 
RBM-007 will be received frozen. RBM-007 must be stored and should remain frozen in a secure, 
locked, dark, temperature-controlled freezer at -20 ºC with restricted access.   
 
Study Drug Preparation 
 
The vial of study drug will be removed from the freezer and thawed by rotating the vial between 
the palms of the hands, or by setting the vial at room temperature. Care should be taken to protect 
the product from light.  
A sterile, single-use 250 μL syringe custom marked at 100 µL will be provided separately for 
intravitreal injection use. Study drug should be drawn into the provided single-use plastic syringe. 
Use separate needles for drawing and injecting the study drug. Study drug should be used for 
intravitreal injection in the study subject within 1 hour after removing the vial from the freezer.  
Each vial contains enough study drug to inject one subject.  Each vial will be used one time only. 
 
Method of administration 
 
Pre-injection antibiotic eye drops may be administered at the discretion of the treating doctor. 
 


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Clinical Study Protocol 
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Proper aseptic injection techniques must always be used when administering RBM-007. which 
includes the use of surgical hand disinfection, sterile gloves, a sterile drape, a sterile eyelid 
speculum (or equivalent).  The periocular skin, eyelid and ocular surface should be disinfected 
and adequately anesthetized, and a broad-spectrum topical microbicide should be administered 
prior to the injection according to standard medical practice. 
 
Inferior temporal injection site is recommended. The intravitreal injection site may be modified at 
the physician’s discretion.  The injection needle should be inserted 3.5-4.0 mm posterior to the 
limbus aiming towards the center of the globe, avoiding the horizontal meridian. Care should be 
taken to avoid injecting RBM-007 into the visual axis. The injection volume of 0.1 mL is then 
delivered.  A different scleral site should be used with each subsequent injection. 
 
Post-injection antibiotic eye drops may be administered at the discretion of the treating doctor 
 
Both intraocular pressure and the perfusion of the optic nerve head must be monitored and 
managed appropriately after injection.  In addition, patients should be monitored during the week 
following the injection to permit early treatment if an infection occurs. 
 
 
 
 


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Clinical Study Protocol 
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Table 1: Schedule of Visits and Events 
 
Procedure 
Baseline Week 2 
(± 7days) 
Month 1 
(± 7days) 
Month 2 
(± 7days) 
Month 3 
(± 7days) 
Month 4 
(± 7days) 
Informed consent 
X 
 
 
 
 
 
Inclusion/exclusion 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Pregnancy Test1  
X 
 
 
 
 
X 
Vital signs 
X 
 
 
 
 
X 
Med/Ophthalmic History 
X 
 
 
 
 
 
AE query 
X 
X 
X 
X 
X 
X 
Con meds/proc 
X 
X 
X 
X 
X 
X 
BCVA & IOP 
X 
X 
X 
X 
X 
X 
Biomicroscopy w/lens grading 
X  
X 
X 
X 
X 
X 
Indirect Ophthalmoscopy 
X 
X 
X 
X 
X 
X 
Heidelberg-OCT 
X 
X 
X 
X 
X 
X 
Optovue OCT-A 
X 
X 
X 
X 
X 
X 
Fluorescein Angiography 
X 
 
 
 
 
X 
Fundus Photos 
X 
 
X 
X 
X 
X 
Autofluorescence Fundus Photography 
X 
 
 
 
X 
X 
Physical Examination 
X 
 
 
 
 
X 
RBM-007 injection 
X 
 
X 
X 
 
 
Injection of Anti-VEGF agent (SOC +
Anterior chamber paracentesis) 1 
 
X 
X 
X 
X 
X 
 
 
 
                                                 
1 If indicated