Clinical trial NCT05425719
Conditions: Chronic Kidney Disease
Keywords: Glomerular Filtration Rate Transdermal fluorescence detection Relmapirazin
Sponsor: MediBeacon
Start date: 2022-06-14; Completion date: 2023-02-15
Enrollment: 249 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The goal of this clinical trial was to compare transdermal glomerular filtration rate (tGFR) to plasma-derived indexed (to body surface area; BSA) GFR (nGFR) using MB-102 (relmapirazin) as the fluorescent compound. Adults with kidney function ranging from normal to Stage 4 chronic kidney disease (CKD) and participants spanning the entire range of human skin colors as defined by the Fitzpatrick Skin Scale (FSS) were included in the study.

The main questions that the study aimed to answer were:

* To establish that the MB-102 transdermal fluorescence measured GFR using the MediBeacon Transdermal GFR Measurement System is comparable to the measured MB-102 plasma GFR
* To evaluate the safety and tolerability of a single dose of MB-102 in study participants
* To evaluate the safety and effectiveness of the MediBeacon Transdermal GFR Measurement System (TGFR) for the non-invasive transdermal fluorescence detection of MB-102 in participants

Participants had a transdermal sensor placed on their upper chest, and the TGFR collected background fluorescence. Participants then received a single dose of MB-102. Blood samples were collected and fluorescent measurements were taken over a 12- to 24-hour period. Following completion of the treatment period, participants returned to the study center approximately 1 week later for a safety follow-up visit. Researchers compared the results to see if the transdermal GFR measurements were comparable to the measured plasma GFR in those with and without normal kidney function and different skin coloration.

Detailed description:

Arms: arm 1: Participants with eGFR ≥ 70 mL/min/1.73 m\^2 received one 130 mg dose of MB-102 and a transdermal sensor was placed on their chest. Blood samples and fluorescent measurements were collected over 12 hours. arm 2: Participants with eGFR \< 70 mL/min/1.73 m\^2 received one 130 mg dose of MB-102 and a transdermal sensor was placed on their chest. Blood samples and fluorescent measurements were collected over 24 hours.
Interventions: intervention 1: MB-102 intervention 2: MediBeacon Transdermal Glomerular Filtration Rate Measurement System (TGFR)
Intervention descriptions: intervention 1: 18.6 mg/mL in a 7.0 mL volume administered by intravenous injection over 30 - 60 seconds, followed by a 10 mL normal saline flush administered intravenously over 30 - 60 seconds intervention 2: On treatment day, participants had a transdermal sensor placed on their upper chest, and the MediBeacon Transdermal GFR Measurement System was initiated to collect background fluorescence. After collection of background fluorescence, participants received a single dose of MB-102.

Protocol documents:
Prot_SAP_001.pdf: 
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   MediBeacon® Transdermal GFR Measurement System 
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NCT05425719 
CLINICAL STUDY PROTOCOL 
A Pivotal, Open Label, Multi-Center, Safety and Pharmacokinetic Study of MB-102 
(Relmapirazin) and the Use of the MediBeacon® Transdermal GFR Measurement System 
in Normal and Renal Compromised Subjects for the Evaluation of Kidney Function 
 
 
Statement of Compliance 
The study will be conducted in compliance with the protocol, International Conference on Harmonization Good 
Clinical Practice E6 R2 (ICH-GCP), and the applicable regulatory requirements including the National Medical 
Products Administration Good Clinical Practice (NMPA GCP), The Code of Federal Regulations Title 21 CFR Parts 
812, 11, 50, 54 and 56 and ISO 14155: 2020 (3rd Edition) Clinical Investigation of Medical Devices for Human 
Subjects – Good Clinical Practice 
 
Protocol Number: 
100-003 
Investigational Product: 
MB-102 (Relmapirazin) / MediBeacon® Transdermal GFR 
Measurement System 
Phase: 
Pivotal 
Sponsor: 
MediBeacon Inc. 
425 N. New Ballas Road 
St. Louis, MO 63141 
USA 
Date of Protocol 
20 September 2022  
Version of Protocol: 
Version 4.0 
CONFIDENTIAL 
This protocol may not be reproduced or communicated to a third party without the 
written permission of MediBeacon Inc. 


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1 
Synopsis 
Protocol Number: 
100-003 
Title: 
A Pivotal, Open Label, Multi-Center, Safety and Pharmacokinetic Study of MB-
102 (Relmapirazin) and the Use of the MediBeacon® Transdermal GFR 
Measurement System in Normal and Renal Compromised Subjects for the 
Evaluation of Kidney Function 
Investigational 
Products: 
MB-102 (Relmapirazin) 
MediBeacon® Transdermal GFR Measurement System (TGFR) 
Number of Study 
Sites: 
This study will take place at up to 10 investigational sites in the US and China  
Phase: 
Pivotal 
Objectives: 
• To establish that the MB-102 transdermal fluorescence measured GFR 
using the MediBeacon® Transdermal GFR Measurement System is 
comparable to the measured MB-102 plasma GFR   
• To evaluate the safety and tolerability of a single dose of MB-102 in 
subjects   
• To evaluate the safety and effectiveness of the MediBeacon® Transdermal 
GFR Measurement System for the non-invasive transdermal fluorescence 
detection of MB-102 in subjects 
Study Design: 
Multi-center, pivotal open-label pharmacokinetic study comparing transdermal 
measured GFR (tGFR) to plasma-derived indexed GFR (nGFR).  
Number of Treated 
Subjects:  
Up to 250 subjects are planned for enrollment. The US sites will plan to enroll at 
least 140 evaluable subjects; Chinese sites will plan to enroll at least 48 
evaluable subjects.  The population will be split into stratums in accordance with 
screening eGFR measured by the CKD-EPI equation: 
• 
Stratum 1: 50% of evaluable subjects with an eGFR ≥ 70 mL/min/1.73 m2 
• 
Stratum 2: 50% of evaluable subjects with an eGFR < 70 mL/min/1.73 m2 
Approximately 50% of subjects within each Stratum enrolled in the US will be 
Fitzpatrick skin scale (FSS) I-III and 50% of subjects will have FSS IV-VI. 
Subjects in the US will be enrolled across a spectrum of both eGFR (<120 - >15  
mL/min/1.73 m2) and FSS.  
 
Subjects enrolled in China will also be represented across the same spectrum of 
eGFR (<120 - >15 mL/min/1.73 m2) however the FSS will not apply. This is 
because the Chinese subject demographic is unlikely to represent the full FSS 
spectrum.  
Subjects with incomplete assessments or major protocol deviations may be 
replaced. Thus, a maximum of 250 subjects may be enrolled.  
Treatment: 
Eligible subjects in stratums 1 and 2 will receive a single 130 mg dose of MB-
102.  
Blood draws will be taken at pre-defined timepoints and the MediBeacon® 
Transdermal GFR Measurement System fluorescent measurements will be 
collected over a 12 hour - 24 hour period. 


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Study Duration per 
Subject: 
Screening period: up to 21 days prior to dosing; dosing day, and a follow-up visit 
within 7+/-3 days of dosing.   
Study Population: 
Main Criteria for Inclusion: 
1. Age > 18 years – male or female  
a. Eligible female non-pregnant subjects who are either not of 
child-bearing potential or willing to use adequate 
contraception during the trial 
b. Males must be willing to practice abstinence or utilize 
adequate contraception from dosing day to at least 7 days 
post-dose 
c. For women of child-bearing potential, the subject should 
have a negative serum pregnancy test at screening, and agrees 
to one of the following acceptable contraceptive methods 
used consistently and correctly i.e. abstinence, oral 
contraceptive either combined or progesterone alone; 
injectable progesterone, implants of levonorgestrel, 
estrogenic vaginal ring, percutaneous contraceptive patches, 
IUD device or system or male partner sterilization 
d. Men will not donate sperm during the study and for 1 month 
following the last dose of study drug  
2. Subjects who are capable of directly providing informed consent and 
who can comply with the requirements and restrictions required by 
the protocol 
3. Adequate venous access sufficient to allow blood sampling per 
protocol requirements 
Main Criteria for Exclusion: 
1. Subjects positive via PCR testing for COVID-19 
a. Vaccinated subjects without symptoms of COVID-19 are not 
required to undergo PCR testing but may be tested at the 
discretion of the study site 
2. Recent donation or loss of blood or plasma: 100 mL to 499 mL 
within 30 days prior to the initial dose of the study medication; or 
more than 499 mL within 56 days prior to the initial dose of study 
medication  
3. Non-steroidal anti-inflammatory (NSAID) use within 3 days of MB-
102 dosing 
4. The subject has participated in a clinical trial and has received an 
investigational product within the following time ranges: prior to the 
first dosing day in the current study:  either 30 days or 5 half-lives of 
the investigational product (whichever duration is longer). 
5. History of skin sensitivity to adhesives (e.g. Band-Aids, surgical 
tape) 
6. History of severe allergic hypersensitivity reactions (unacceptable 
adverse events) or anaphylactoid reaction to any allergen including 
drugs, MB-102 or other related products (intolerance to a drug is not 
considered a drug allergy).  
7.  Any characteristics such as acute or chronic medical condition or 
cardiac or laboratory or physical examination abnormality that may 
increase the risk associated with study participation or investigational 
product administration or may interfere with the interpretation of the 


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study results in the judgement of the investigator and would make the 
subject inappropriate for entry into this study.  
8. Significant scaring, tattoos or alterations in pigmentation on the 
sternum or other sensor location testing areas that would alter sensor 
readings versus other areas of the skin 
9. Any serious or uncontrolled medical disorder, active infection, 
physical exam finding, laboratory finding, or psychiatric condition 
that in the opinion of the investigator would limit the subjects’ ability 
to complete study requirements or may put the subject at increased 
risk or compromise the interpretability of study results.  
10. Currently receiving dialysis 
11. Currently anuric 
12. Subjects with positive serum pregnancy test 
13. Subjects with an eGFR > 120 mL/min/1.73m2 
Primary Endpoint: 
The primary endpoint is the performance measure of P30 for transdermal-
derived GFR with respect to the plasma-derived indexed GFR, with a 95% 
confidence interval. The performance goal is 85%. Success for the study will be 
that the lower limit of the 95% CI is greater than 85%. 
Safety Evaluation 
• Safety of MB-102 will be evaluated through treatment emergent adverse 
events (TEAEs), where treatment emergence is defined with respect to the 
first administration of MB-102. 
• Safety of the MediBeacon® Transdermal GFR Measurement System will be 
evaluated through TEAEs, where treatment emergence is defined with respect 
to the start time of device use. 
Statistical Analyses   The primary endpoint is the performance measure of P30 for transdermal-
derived GFR with respect to the plasma-derived indexed GFR, with a 95% 
confidence interval. The performance goal is 85%. Success for the study will be 
that the lower limit of the 95% CI is greater than 85%. 
 
Safety of MB-102 will be evaluated through treatment emergent adverse events 
(TEAEs), where treatment emergence is defined with respect to the 
administration of MB-102. 
 
Safety of the MediBeacon® Transdermal GFR Measurement System will be 
evaluated through TEAEs, where treatment emergence is defined with respect 
to the start time of Transdermal GFR Measurement System use. 
 
Additional safety variables include physical examinations, vital sign 
measurements, ECGs, clinical laboratory assessments, and medication use. 
Sample Size 
Determination 
For a P30 true value of 0.95, alpha of 0.025, performance goal of 85%, power 
of 90%, the one-sided exact binomial test yields a sample size of 102. 
 
Time Schedule: 
Planned Start of Study:  Q2 2022 
Planned End of Study:  Q4 2022 
 
 
 


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DOCUMENT APPROVALS 
 
 
 
____________________________________ 
 
_________ 
Richard Dorshow, PhD 
 
 
 
 
Date 
President & Chief Scientific Officer 
 
 
 
 
____________________________________ 
 
_________ 
Joseph Pierro, MD 
 
 
 
 
 
Date 
Acting Head: Medical Affairs 
 
 
 
 
____________________________________ 
 
_________ 
Nancy Morrison 
 
 
 
 
 
Date 
Acting Head: Regulatory Affairs 
 
 
 
 
____________________________________ 
 
_________ 
Elizabeth LaPointe, MA 
 
 
 
 
Date 
Acting Head: Clinical Operations 
 
 


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Table of Contents 
1 
Synopsis ............................................................................................................................................ 2 
2 
List of Abbreviations and Definition of Terms .................................................................... 9 
3 
Introduction .................................................................................................................................. 11 
3.1 
Background ........................................................................................................................... 11 
3.2 
Nonclinical Data ................................................................................................................... 12 
3.3 
Clinical Data .......................................................................................................................... 12 
3.4 
Study Rationale .................................................................................................................... 13 
4 
Study Objectives .......................................................................................................................... 13 
5 
Investigational Plan.................................................................................................................... 14 
5.1 
Overall Study Design and Plan........................................................................................ 14 
5.2 
Overview of Study Procedures ....................................................................................... 14 
5.3 
Discussion of Study Design .............................................................................................. 15 
5.4 
Selection of Study Population ......................................................................................... 15 
5.4.1 
Number of Planned Evaluable Subjects .......................................................................... 15 
5.4.2 
Inclusion Criteria ..................................................................................................................... 16 
5.4.3 
Exclusion Criteria ..................................................................................................................... 16 
5.4.4 
Removal of Subjects from Therapy or Assessments .................................................. 17 
5.4.5 
Replacement of Subjects ....................................................................................................... 17 
5.5 
Investigational Device ....................................................................................................... 18 
5.5.1 
Premature Dislodgment of a TGFR Sensor from the Skin ........................................ 18 
5.5.2 
Sensor Detachment from the TGFR Monitor ................................................................. 18 
5.5.3 
Identity of Investigational Device ...................................................................................... 18 
5.5.4 
Labeling ....................................................................................................................................... 19 
5.5.5 
Storage, Supply and Return/Destruction ....................................................................... 19 
5.5.6 
Device Accountability ............................................................................................................. 19 
5.6 
Investigational Drug ........................................................................................................... 19 
5.6.1 
Stability of Drug Product ...................................................................................................... 20 
5.6.2 
Identity of Investigational Drug ......................................................................................... 21 
5.6.3 
Investigational Drug Labeling ............................................................................................. 21 
5.6.4 
Investigational Drug Storage, Supply, Return/Destruction .................................... 22 
5.6.5 
Investigational Drug Accountability ................................................................................. 22 
5.7 
Contact Procedures for Medical Issues Requiring Immediate Attention ........ 22 
5.8 
Prior and Concomitant Therapy .................................................................................... 23 
5.8.1 
Prohibited Concomitant Medications .............................................................................. 23 
5.8.2 
Stable Use of Immunosuppressive Medications .......................................................... 23 
6 
Study Procedures ........................................................................................................................ 23 
6.1 
Schedule of Assessments and Procedures .................................................................. 24 
6.2 
Pre-screening ....................................................................................................................... 27 
6.3 
Screening ................................................................................................................................ 27 
6.4 
Night before Dosing Day ................................................................................................... 27 
6.5 
Dosing Day: Baseline Assessments ............................................................................... 28 
6.6 
MB-102 Dosing ..................................................................................................................... 29 


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6.7 
Post-dose Study Procedures ............................................................................................ 30 
6.7.1 
Stratum 1 (12 hour follow-up) ........................................................................................... 30 
6.8 
Stratum 2 (24 hour follow-up) ....................................................................................... 31 
6.9 
Follow-up Visit ..................................................................................................................... 32 
6.10 
Early Withdrawal / Unscheduled Visits .................................................................. 32 
6.11 
Repeat Subjects ................................................................................................................ 33 
7 
Efficacy and Safety Variables .................................................................................................. 33 
7.1 
Efficacy and Safety Measurements Assessed and Flow Chart .............................. 33 
7.1.1 
Efficacy Assessments .............................................................................................................. 33 
7.1.2 
Safety Assessments ................................................................................................................. 33 
7.2 
Safety Review Committee ................................................................................................. 40 
8 
Information for the Investigator: Potential Risks of the Device ................................. 41 
8.1 
Investigational Drug ........................................................................................................... 41 
8.2 
MediBeacon® Transdermal GFR Measurement System ........................................ 42 
8.2.1 
Adhesive Clip ............................................................................................................................. 42 
8.3 
Trial Procedures .................................................................................................................. 42 
8.3.1 
Dose Extravasations ............................................................................................................... 43 
9 
Statistical Methods...................................................................................................................... 43 
9.1 
Overview ................................................................................................................................ 43 
9.2 
Analysis Populations .......................................................................................................... 43 
9.3 
Subject Disposition ............................................................................................................. 43 
9.4 
Plasma Pharmacokinetic Analyses ............................................................................... 43 
9.5 
Primary Endpoint Analysis .............................................................................................. 44 
9.6 
Safety Analyses ..................................................................................................................... 44 
9.6.1 
Treatment-Emergent Adverse Events ............................................................................. 45 
9.6.2 
Physical Examinations/Limited Physical Assessments ............................................ 45 
9.6.3 
Clinical Laboratory Assessments ....................................................................................... 45 
9.6.4 
ECGs .............................................................................................................................................. 45 
9.6.5 
Prior and Concomitant Therapies ..................................................................................... 45 
9.7 
Determination of Sample Size ......................................................................................... 45 
9.8 
Missing Data .......................................................................................................................... 46 
9.9 
Analysis Phases .................................................................................................................... 46 
10 
Quality Assurance and Quality Control ........................................................................... 46 
10.1 
Training .............................................................................................................................. 46 
10.2 
Audit and Inspection ...................................................................................................... 46 
10.3 
Monitoring ......................................................................................................................... 46 
10.4 
Data Management and Coding .................................................................................... 47 
10.5 
Protocol Deviations ........................................................................................................ 47 
10.6 
Direct Data Collection .................................................................................................... 48 
11 
Records / Retention ............................................................................................................... 48 
12 
Ethics ........................................................................................................................................... 49 
12.1 
Independent Ethics Committee (IEC) ....................................................................... 49 
12.2 
Ethical Conduct of the Study ........................................................................................ 50 


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12.3 
Subject Information and Consent .............................................................................. 50 
12.4 
Financing and Insurance .............................................................................................. 50 
12.5 
Subject Confidentiality .................................................................................................. 50 
12.6 
Reporting and Publication, Including Archiving .................................................. 51 
13 
References ................................................................................................................................. 52 
14 
Appendix A Fitzpatrick Scale .............................................................................................. 53 
15 
Appendix B Clinical Research Sites ................................................................................... 54 
Investigator Signature Page ............................................................................................................ 55 
16 
Signature of the Sponsor’s Responsible Officers .......................................................... 56 
16.1 
Chief Scientific Officer ................................................................................................... 56 
16.2 
Medical Officer ................................................................................................................. 56 
Appendix I  Protocol 100-003 Supplemental Justifications ................................................. 57 
 
 
 


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2 
List of Abbreviations and Definition of Terms 
AE 
Adverse event 
AKI 
Acute kidney injury 
ALP 
Alkaline phosphatase 
ALT 
Alanine transaminase 
AST 
Aspartate aminotransferase 
BMI 
Body Mass Index 
BP 
Blood pressure 
BUN 
Blood urea nitrogen 
CFR 
Code of Federal Regulations 
CKD 
Chronic kidney disease 
CKD-EPI 
Chronic kidney disease – epidemiology collaboration 
CO2 
Carbon dioxide 
COVID-19 
Coronavirus disease 2019 
CRF 
Case report form 
Cl 
Chloride 
Cr 
Creatinine 
CV 
Coefficient of variation 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
eGFR 
Estimated glomerular filtration rate 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
GMP 
Good Manufacturing Practice 
HCG 
Human chorionic gonadotropin 
HCT 
Hematocrit 
HEENT 
Head, Ears, Eyes, Neck, Throat 
I 
Iodine 
IB 
Investigator’s Brochure 
ICF 
informed Consent Form 
ICH 
International Council on Harmonisation 
ICU 
Intensive Care Unit 
IDE 
Investigational Device Exemption 
IEC 
Independent Ethics Committee 
INR 
International normalized ratio 
IP 
Investigational Product 
ISO 
International Organization for Standardization 
K 
Potassium 
K2EDTA 
Potassium ethylenediaminetetraacetic acid 
MedDRA 
Medical Dictionary for Regulatory Activities 
nGFR 
NIH 
Indexed plasma glomerular filtration rate 
National Institute of Health 
NSAID 
Non-steroidal anti-inflammatory drug 
OM 
Operational Manual 
ORFM 
Optical Renal Function Monitor 
OTC 
Over the counter 
PA 
Physical Assessment (limited) 
PE 
Physical exam (full) 
PI 
Principal Investigator  


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PK 
Pharmacokinetic 
POC 
Point of care 
PP 
Per Protocol 
RBC 
Red blood cell 
SAE 
Serious Adverse Event 
SAF 
Safety Analysis Set 
SAP 
Statistical Analysis Plan 
SCr 
Serum creatinine 
SNR 
Signal to Noise Ratio 
Tc-DTPA 
Technetium diethylene triamine - pentaacetate 
TEAE 
Treatment-emergent adverse event  
tGFR 
Transdermal Glomerular Filtration Rate 
TGFR 
UADE 
MediBeacon® Transdermal GFR Measurement System 
Unanticipated Adverse Device Effect 
Vd 
Volume of Distribution 
WBC 
White blood cell 
WHO 
World Health Organization 
WOCBP 
Women of Child-Bearing Potential 


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3 
Introduction 
3.1 
Background 
Therapeutic interventions for acute kidney injury (AKI) patients are delayed due to current 
clinical practice of reliance on a serum creatinine blood test (SCr) for an estimation of 
glomerular filtration rate (GFR). Typically, 24-72 hours elapse from onset of a kidney injury 
event to a SCr indicating a non-normal level (Stevens et al, 2006). Since AKI affects upwards of 
20% of hospitalized patients and 70% of critically ill patients in the intensive care unit (ICU), 
this contributes to high mortality rates (approaching 60% for those requiring renal replacement 
therapy [Endre at al., 2011]), development of chronic kidney disease (affecting an estimated 27 
million Americans, accounting for ~ 24% of Medicare costs [NIH 2008]), and consequent 
progression to end stage renal disease (with an estimated 400,000 Americans on dialysis [Kidney 
Disease Statistics for the US]). 
 
Glomerular filtration rate (GFR) is widely accepted as the best indicator of kidney function and 
is a key component of the diagnosis and management of renal impairment. A simple, accurate, 
and point-of-care (POC) method for determining GFR is needed, as current methods for 
determining GFR are either: 1) practical but lack accuracy, or 2) accurate but prohibitively 
complex, especially for frequent and recurrent measurements. 
 
Current medical practice for general renal function assessment relies on estimated GFR 
(eGFR).  This involves estimation using equations based on a single serum creatinine (SCr) 
measurement, or a measurement of creatinine clearance (CrCl) based on a 24-hour collection 
of urine plus measurement of a single SCr concentration.  Although readily available and 
convenient, measurement of SCr as an indicator of renal function is problematic because it is a 
lagging indicator of current renal function, lacks sensitivity, and may be misleading because it 
is affected by age, state of hydration, renal perfusion, muscle mass, dietary intake, and many 
other anthropometric and clinical variables (Agarwal, 2003 and Verhave et al., 2005).  CrCl 
estimation using timed urine collections can be more accurate, but problems with 
completeness of 24-hour urine collection often result in under or over estimation of CrCl. 
Measuring GFR using urinary or plasma clearance of exogenous filtration markers is the 
accepted standard for evaluation of kidney function.  In the past three decades, renally filtered 
exogenous agents such as inulin, iohexol, 125Iodine-iothalamate (125I-iothalamate), and 
technetium-99m-diethylene triamine - pentaacetate (99mTc-DTPA) have all been used to 
determine GFR (Stevens et al., 2006).  From both a safety and effectiveness standpoint, these 
agents are acceptable, although they contain iodine, which can cause anaphylactoid reactions, 
and they can be nephrotoxic when very high volumes are used.  However, they are not used 
routinely to determine GFR because the protocols are time-consuming, complex, and expensive, 
which make their repeated use impractical in many clinical settings, and they may require 
imaging equipment and administration of radioactive agents (Stevens and Levey, 2009).  
Accurate measurement of GFR at the patient’s bedside is highly desirable in order to assess the 
patient’s renal function.  There is a significant need to develop a simple, accurate, and POC 
method for measuring GFR (Erley et al., 2001). 
 


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To address this unmet clinical need, MediBeacon is developing a combination product that 
requires the administration of a fluorescent tracer agent designated relmapirazin (also known as 
MB-102 and formerly known as MP-3180) that will be detected transdermally by a sensor which 
is attached to a device monitor (called the MediBeacon® Transdermal GFR Measurement System 
[TGFR]).   
 
MB-102 has been engineered to be excreted from the body by the renal system, and specifically 
by the GFR mechanism. Normal functioning kidneys will remove this agent from the body with 
an approximate 2 hour half-life. Impaired functioning kidneys will take longer to excrete the 
agent and hence result in a longer half-life.  
 
An initial algorithm had been developed from the Pilot 2 study Group 1 data to convert measured 
fluorescence half-life data to GFR. Pilot 2 study Groups 2 and 3 refined this algorithm for 
efficacy and robustness, as well as adding to the algorithm database. 
 
The sensor contains the light source for excitation of the tracer agent, the agent having a peak 
absorption wavelength of 440 nm. The detector is able to acquire the emission of the tracer 
agent, the agent having a peak emission wavelength of 560 nm. The sensor for the TGFR device 
is small and limited to the materials necessary for excitation and acquisition, and collection and 
processing of the data is conducted within the monitor.  The device monitor displays the TGFR 
data.    
 
3.2 
Nonclinical Data 
Available nonclinical study data on MB-102 support that the chemistry of the drug 
substance/drug product, and the manufacturing of the drug substance/drug product does not 
present a risk to human subjects. Additional information on the 24 nonclinical studies performed 
on MB-102 is found in the Investigator’s Brochure.  
 
3.3 
Clinical Data 
A total of 266 subjects have been treated with an IV administration of MB-102 across the three 
pilot studies (Pilot 1A, Pilot 1B and Pilot 2 Groups 1, 2 and 3). The Pilot 1 studies enrolled 
subjects with an eGFR indicating normal renal function. The Pilot 2 study enrolled subjects with 
normal renal function and those with renal function in the CKD stage 1-5 range. In addition, a 
total of 22 subjects (11 healthy volunteers and 11 Crohn’s patients) have received a 4 or 8 
µmol/kg oral dose of MB-102 in a study evaluating the use of MB-102 in the evaluation of gut 
permeability (MediBeacon Protocol 300-01). The total population exposure to MB-102 as of this 
protocol is 288 subjects. A total of 52 subjects (18.1% of the total population across 4 studies) 
were reported to have adverse events (AE). All reported events were mild or moderate in 
severity. No severe events have been reported, nor have any serious adverse events been reported 
or unanticipated adverse device effects. 
 
There have been no clinically significant findings with regard to vital signs, physical exams or 
ECGs.  Overall MB-102 administered intravenously at a dose of 4 µmol/kg whether or not 
followed by a 5 mL (milliliter) dose of iohexol (Omnipaque™ 300), or at a fixed dose of 130 mg 


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/ 7 mL (n=44) or consumed orally at a dose of 4 µmol/kg (n=8) or 8 µmol/kg (n=14) was well 
tolerated in the populations studied to date. 
 
Adverse events related to the device itself were due to the adhesive materials used to hold the 
ORFM (Optical Renal Function Monitor) sensor in place.  All device related events were 
considered mild or moderate in severity. For more information, please see the Investigator’s 
Brochure.  
 
MB-102 equilibrates between the vasculature and tissues post IV administration. The plasma 
pharmacokinetics show a peak concentration at the first sample time point. In Pilot 1A and Pilot 
2, the first sample time point taken was approximately 5 minutes post administration; in Pilot 1B 
the first sample time point taken was approximately 30 minutes post administration. The 
fluorescence pharmacokinetics, reflecting the agent concentration in the tissue, has a peak 
fluorescence intensity in the range of 30 - 90 minutes, depending on the subject.  MB-102 
concentration equilibration between the vasculature and the tissue occurs approximately 30 – 60 
minutes after the peak. 
 
In the Pilot 2 Groups 1 and 2, the first blood draw was taken at 5 minutes post administration of 
MB-102, and the last at 12 hours post administration. The transdermal fluorescence was 
measured at the sternum and one other location for each subject using the prototype device 
QuantumLeap and Radiance. For all 120 subjects over the wide range of GFR values, the 
following were observed: 
 
• A two-compartment plasma pharmacokinetic profile 
• A high correlation between the MB-102 and iohexol plasma derived GFR values 
• A high correlation between the MB-102 plasma and transdermal fluorescence 
pharmacokinetics 
 
More information is available in the Investigator’s Brochure and in Appendix I.  
 
3.4 
Study Rationale 
This clinical study will evaluate the use of MB-102 and the MediBeacon® Transdermal GFR 
Measurement System for the purpose of marketing application with the final device design.   
 
4 
Study Objectives 
The objectives of this pivotal study are:  
• To establish that the MB-102 transdermal fluorescence measured GFR using the 
MediBeacon® Transdermal GFR Measurement System is comparable to the measured MB-
102 plasma GFR   
• To evaluate the safety and tolerability of a single dose of MB-102 in subjects   
• To evaluate the safety and effectiveness of the MediBeacon® Transdermal GFR 
Measurement System for the non-invasive transdermal fluorescence detection of MB-102 
in subjects 
 


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5 
Investigational Plan 
5.1 
Overall Study Design and Plan 
Protocol 100-003 is a multi-center, open-label, pivotal trial studying the safety and 
pharmacokinetics of MB-102 and the use of the MediBeacon® Transdermal GFR Measurement 
System in normal and compromised renal function subjects with different skin color types 
comparing tGFR to plasma derived indexed GFR (nGFR).  
 
Approximately 250 subjects are planned for enrollment. The US sites will plan to enroll 140 
evaluable subjects; China sites will enroll 48 evaluable subjects.  The population will be split 
into stratums in accordance with eGFR by the CKD-EPI equation. 
 
Subjects will be screened and if deemed eligible, will be enrolled. On treatment day, subjects 
will have a transdermal sensor placed on their chest, and the MediBeacon® Transdermal GFR 
Measurement System will be initiated to collect background fluorescence. When this is 
completed, subjects will then receive a single dose of MB-102. Serial PK draws will be collected 
over a 12 to 24 hour period.  Fluorescent measurements will also be collected during this period. 
For subjects with significant renal compromise, fluorescent measurements will continue until the 
sensor no longer detects MB-102 in the body. Following completion of the treatment period, 
subjects will return to the study center approximately 1 week later for a safety follow-up visit.  
 
Subjects who do not complete the study or who have major protocol deviations may be replaced. 
Up to 250 subjects may be enrolled.  
 
The global study will include 188 evaluable subjects. The US enrolment will have 140 evaluable 
subjects. Once the US sites have enrolled the targeted number of evaluable subjects, the US 
clinical sites will be closed. The US data alone may be used to support the market authorization 
and approval in the US.  The completed OUS dataset, if available will be included in the US 
application.  
 
 
5.2 
Overview of Study Procedures 
Potential subjects will be screened for eligibility within 21 days prior to planned dosing. Based 
on their screening eGFR (measured using the CKD-EPI equation), they will be assigned to 
Stratum 1 or Stratum 2:  
• Stratum 1: eGFR ≥ 70 mL/min/1.73 m2 (50% of subjects) 
• Stratum 2:  eGFR < 70 mL/min/1.73 m2 (50% of subjects) 
 
Following pre-dose procedures to ensure eligibility, one sensor will be affixed to the subject on 
the upper chest in the area between the shoulders (including the pectoralis and sternum area).  
The subject will then receive the MB-102 injection.  MB-102 will be administered by IV 
injection over 30 – 60 seconds, followed by a saline flush IV over 30 - 60 seconds. 
 
Stratum 1:  PK sampling will be collected pre-dose and at 5, 15, 30, 60, 90, 120, 180, 240, 300, 


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360, 480, 600 and 720 minutes post-dose (12 hour collection period).  
 
Stratum 2:  PK sampling will be collected pre-dose and at 5, 15, 30, 60, 90, 120, 180, 240, 300, 
360, 480, 600, 720 960, 1200, and 1440, minutes post-dose (24 hour collection period).  
 
Safety assessments in the form of vital signs, safety labs, ECGs, and adverse event collection 
will occur during the dosing day.  
 
Within 7 +/- 3 days of dosing, subjects will return to the study center for additional safety 
follow-up assessments.  
 
5.3 
Discussion of Study Design 
The study is designed to validate the performance of the TGFR Measurement System.  
5.4 
Selection of Study Population 
5.4.1 Number of Planned Evaluable Subjects  
A total of 188 evaluable subjects are planned for enrollment. The population will be split into 
stratums accordance with eGFR by the CKD-EPI equation and location of enrollment: 
• Stratum 1: 50% of subjects with an eGFR ≥ 70 mL/min/1.73 m2 
• Stratum 2: 50% of subjects with an eGFR < 70 mL/min/1.73 m2 
 
Subjects will be targeted across the spectrum of eGFR from normal through Stage 4 CKD. 
Subjects with an eGFR greater than 120 mL/min/1.73 m2 or less than 15 mL/min/1.73 m2 will be 
excluded. Efforts will be made to balance enrollment across the following eGFR levels such that 
each subcategory has minimum of 10 subjects:  
• > 90 mL/min/1.73 m2  
• 60 – 89 mL/min/1.73 m2  
• 45 – 59 mL/min/1.73 m2  
• 30 – 44 mL/min/1.73 m2  
• 15 – 29 mL/min/1.73 m2  
 
Of the evaluable subjects, 140 will plan to be enrolled in the United States and 48 will plan to be 
enrolled at sites in China.  
 
Approximately 50% of subjects within each stratum enrolled in the US will be Fitzpatrick skin 
scale (FSS) I-III and 50% of subjects will have FSS IV-VI. In the US, subjects will be targeted 
across the full spectrum of FSS (I – VI) such that FSS cohorts I-II, III-IV and V-VI will each 
enroll no less than 20 subjects.   
 
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unlikely to support the full FSS spectrum.  
 
If subjects are not considered evaluable, they will be replaced in the study with a total potential 
enrollment up to 250 subjects.  
 
 
5.4.2 Inclusion Criteria 
To be eligible for study entry, all subjects must satisfy all of the following criteria: 
Main Criteria for Inclusion: 
1. Age > 18 years – male or female  
a. Eligible female non-pregnant subjects who are either not of child-bearing 
potential or willing to use adequate contraception during the trial 
b. Males must be willing to practice abstinence or utilize adequate contraception 
from dosing day to at least 7 days post-dose 
c. For women of child-bearing potential, the subject should have a negative serum 
pregnancy test at screening, and agrees to one of the following acceptable 
contraceptive methods used consistently and correctly i.e. abstinence, oral 
contraceptive either combined or progesterone alone; injectable progesterone, 
implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive 
patches, IUD device or system or male partner sterilization 
d. Men will not donate sperm during the study and for 1 month following the last 
dose of study drug  
2. Subjects who are capable of directly providing informed consent and who can comply 
with the requirements and restrictions required by the protocol 
3. Adequate venous access sufficient to allow blood sampling per protocol requirements 
 
5.4.3 Exclusion Criteria 
To be eligible for the study, subjects must not meet any of the criteria noted below:  
1. Subjects positive via PCR testing for COVID-19 
a. Note: Vaccinated subjects without symptoms of COVID-19 are not required to 
undergo PCR testing but may be tested at the discretion of the study site 
2. Recent donation or loss of blood or plasma: 100 mL to 499 mL within 30 days prior to 
the initial dose of the study medication; or more than 499 mL within 56 days prior to the 
initial dose of study medication  
3. Non-steroidal anti-inflammatory (NSAID) use within 3 days of MB-102 dosing 
4. The subject has participated in a clinical trial and has received an investigational product 
within the following time ranges: prior to the first dosing day in the current study:  either 
30 days or 5 half-lives of the investigational product (whichever duration is longer). 
5. History of skin sensitivity to adhesives (e.g. Band-Aids, surgical tape) 
6. History of severe allergic hypersensitivity reactions (unacceptable adverse events) or 
anaphylactoid reaction to any allergen including drugs, MB-102 or other related products 
(intolerance to a drug is not considered a drug allergy). 


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7. Any characteristics which, in the opinion of the investigator, makes the subject a poor 
candidate for participation in the clinical trial 
8. Significant scaring, tattoos or alterations in pigmentation on the sternum or other sensor 
location testing areas that would alter sensor readings versus other areas of the skin 
9. Any serious or uncontrolled medical disorder, active infection, physical exam finding, 
laboratory finding, or psychiatric condition that in the opinion of the investigator would 
limit the subjects’ ability to complete study requirements or may put the subject at 
increased risk or compromise the interpretability of study results.  
10. Currently receiving dialysis 
11. Currently anuric 
12. Positive serum pregnancy test 
13. Subjects with an eGFR > 120 mL/min/1.73m2 
 
5.4.4 Removal of Subjects from Therapy or Assessments 
In accordance with applicable regulations, a subject has the right to withdraw from the study at 
any time and for any reason without prejudice to his or her future medical care by the 
investigator or at the institution where the subject’s care is provided.   
Reasons for withdrawal from the study may include one or more of the following:  
• Withdrawal of consent  
• Administrative decision by the PI or MediBeacon  
• Adverse event requiring removal from the study 
• Physician prescribes a treatment that would conflict with the subject’s continued 
participation in the study  
Subjects withdrawing from the study will be encouraged to complete the follow-up study visit 
including all safety evaluations.  The reason(s) for withdrawal will be documented. 
Reasonable efforts will be made to contact subjects who are lost to follow-up.  All attempts and 
contacts must be documented in the subject’s file.   
The sponsor has the right to terminate the study at any time due to a safety issue or if special 
circumstances arise making further treatment of subjects impossible.  In this event, the 
investigator(s) will be informed of the reason for study termination.  
5.4.5 Replacement of Subjects 
Should a subject meet eligibility, but is unable to be scheduled for dosing, that subject will be 
considered a screen failure. In addition, subjects who are unable to have a tGFR measured by the 
MediBeacon® TGFR Measurement System (due to premature sensor removal, for example) or a 
major protocol deviation (such as a dosing extravasation) may be replaced to ensure the 
minimum evaluable sample size is enrolled.  All subjects with exposure to MB-102 will be 
included in the safety analysis.  


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5.5 
Investigational Device 
MediBeacon® Transdermal GFR Measurement System (TGFR) is an investigational device that 
is intended to measure the Glomerular Filtration Rate (GFR) in patients with normal or impaired 
renal function by noninvasively monitoring fluorescent light emission from an exogenous tracer 
agent (MB-102) over time.  
 
Site staff will place and affix the sensors for all enrolled subjects. One sensor will be attached via 
adhesive pad to the upper chest. An adhesive clip, surgical tape or other means may also be used 
to alleviate tension on the sensor cord. Additional instructions for sensor placement will be 
provided in the Study Procedure Manual.  
 
The only parts of the MediBeacon® TGFR that come into contact with the subject are the single-
use adhesive pad, and the optical window.  The optical window protrudes very slightly from the 
adhesive, ensuring consistent contact with the subject’s skin.  The sensors remain in contact with 
the skin and are held in place by means of a self-adhesive pad, typical of those used for 
disposable ECG patches.  The sensor remains affixed to the subject for at least 12.5 hours for 
Stratum 1 and up to 24 hours for Stratum 2.  
 
5.5.1 Premature Dislodgment of a TGFR Sensor from the Skin 
Should a sensor be prematurely dislodged from the subject’s skin during the measurement period 
and after injection with MB-102, it will not be replaced and the subject will be discontinued from 
the measurement period of the study (but will remain in the trial to be followed for safety).  End 
of treatment assessments should be collected (safety labs, vitals, and ECG). If a sensor dislodges 
from the skin during the baseline period (prior to MB-102 injection), a new sensor may be used 
and the study re-started.  
The TGFR is designed to require a clean baseline (pre-injection of MB-102) in order to 
accurately measure GFR. If MB-102 is in the body at the time a sensor is attached, it will not 
allow measurement.  
5.5.2 Sensor Detachment from the TGFR Monitor 
If a sensor becomes detached even temporarily from the TGFR monitor, the data will be 
compromised and may not be used in the final analysis. However, the sensor should be re-
plugged into the monitor and the prompts on the screen should be followed so that fluorescent 
measurements can continue. This occurrence should be recorded as a major protocol deviation if 
the tGFR is NOT reported, and a minor deviation if the monitor displays the tGFR.  
5.5.3 Identity of Investigational Device 
The MediBeacon® Transdermal GFR Measurement System is manufactured by MediBeacon Inc. 
(St. Louis, MO, USA).  All packaging and labeling operations will be performed according to 
current Good Manufacturing Practice (GMP), ISO 13485 and the relevant regulatory 
requirements. 


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5.5.4 Labeling  
Each MediBeacon® Transdermal GFR Measurement System monitor and each sensor will be 
clearly labelled with a Serial Number and REF MDB (Rev).  
Each device will be labelled with the following information:   
CAUTION 
Investigational Device.  
Limited by United States 
Law to Investigational Use.  
 
Additional labels will include the following information: 
REF MDB ####### Rev 0# 
LOT MDBNNNNNN-## 
SN. ######## 
Non Sterile 
 
 
5.5.5 Storage, Supply and Return/Destruction  
Multiple investigational devices (monitors and sensors) will be provided to the clinical sites. 
Disposable items (sensors and any adhesive material) will be single-subject use only. Devices 
and disposable materials must be stored in a secure location and are only for use during the 
clinical trial. All devices (including any unused single use sensors) will be returned to the 
Sponsor at the conclusion of the trial. Instructions for return will be included in the Study 
Procedure Manual.  
5.5.6 Device Accountability  
All inventory received for clinical trial use will be tracked. All inventory will be returned to 
MediBeacon or disposed of following instructions from the Sponsor. An investigational device 
accountability record will be kept current and will contain:  
• Subject ID (screening number) 
• Device(s) monitor serial number  
• Sensor serial number 
• Date of dosing 
• Any observations noted during the use of the device 
 
5.6 
Investigational Drug 
MB-102 (relmapirazin) is a bis-serine aminopyrazine that will be used as an exogenous 
fluorescent Glomerular Filtration Rate (GFR) agent.  This agent is excited by blue light and 


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emits green light.   
 
MB-102 has the following characteristics: 
 
• Produces fluorescence in vivo when excited by blue light, which can be reliably detected 
by transdermal measurement when MB-102 is injected intravenously 
• Has elimination kinetics that allows determination of GFR from fluorescence 
measurement within a clinically useful timeframe 
• Is filtered by the kidney 
• Is not protein bound 
• Is not expected to undergo secretion or tubular reabsorption  
• Is not expected to be metabolized by the liver or other organs 
• Is not expected to affect kidney function 
• Has been shown to be safe in animal models, in therapeutic dose range 
• Is photostable in its administration form and during sample handling and analysis 
• Has been shown to be a GFR tracer agent in nonclinical animal models and early clinical 
studies 
 
5.6.1 Stability of Drug Product 
5.6.1.1 Active Pharmaceutical Ingredient (API) 
A sixty (60) month stability-testing program conducted under Good Manufacturing Practices 
(GMP) for the Active Pharmaceutical Ingredient (API) Lot # 07-130227-02/02-43-01 (140 grams 
manufactured April 2013 by Cambrex Inc., formerly PharmaCore) used in the Pilot 1 and 2 
studies was completed. Stability conditions was 25°C ± 2°C, 60% ± 5% R.H. Results at 60 
months show negligible degradation in active ingredient purity and essentially no change in the 
total impurity amount with respect to the zero time parameters. 
 
A sixty (60) month stability-testing program conducted under GMP for a second API lot (1 kg 
manufactured in August 2017 by Cambrex), API Lot # 2337-1706-00256 is on-going. Stability 
conditions was 25°C ± 2°C, 60% ± 5% R.H. Results show negligible degradation in active 
ingredient purity and essentially no change in the total impurity amount with respect to the zero 
time parameters at the four year time point.  
 
A third GMP API lot of 1 kg was manufactured in June 2020 by Cambrex, Lot # 2337-2004-
00667. A sixty (60) month stability-testing program has been initiated and is ongoing at 
conditions of 25°C ± 2°C, 60% ± 5% R.H. Results show negligible degradation in active 
ingredient purity and essentially no change in the total impurity amount with respect to the zero 
time parameters at the one year time point. 
 
5.6.1.2 Formulated Product 
A 12 month stability-testing program for the GMP formulated product Batch P02213 (~1500 
mL), manufactured in April 2013 by AMRI (formerly Aptuit) from API Lot # 07-130227-02/02-
43-01, which was used for the Pilot 1A and 1B studies, has been completed. Results show 


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negligible degradation in active ingredient purity and essentially no change in the total impurity 
amount with respect to the zero time parameters for the 2 - 8°C condition. 
 
A 24 month stability-testing program for the GMP formulated product Batch P03915 (~3200 
mL), manufactured in May 2015 by AMRI from API Lot # 07-130227-02/02-43-01, and which 
was used for Groups 1 and 2 in Protocol ORFM Pilot 2 study, has been completed. Stability 
condition was 2 - 8°C. Results show negligible degradation in active ingredient purity and 
essentially no change in the total impurity amount with respect to the zero time parameters.  
 
Formulated product with designation Batch P04517 (~9000 mL) was manufactured under GMP 
conditions by AMRI using API Lot # 2337-1706-00256. This batch was placed on stability at 2 - 
8°C for a three year period. At the 36 month time point, there was negligible degradation in 
active ingredient purity and essentially no change in the total impurity amount. This batch was 
used in Group 3 of Protocol Pilot 2 ORFM. 
 
Clinical lots of drug product for use in Protocol 100-003 are in the process of being 
manufactured.  Stability studies will be conducted on these lots.  
 
5.6.2 Identity of Investigational Drug 
MB-102 is packaged in amber vials at a concentration of 18.6 mg/mL in a 7.4 mL volume.  MB-
102 in formulation includes the following: sodium dihydrogen phosphate monohydrate, sodium 
hydroxide, sodium chloride, water for injection. Instructions for preparation of MB-102 will be 
included in the Study Procedure Manual.  
 
5.6.3 Investigational Drug Labeling 
MB-102 drug labels for US distribution include the following information:  
Relmapirazin 
7 mL of MB-102 Solution for injection only  
18.6 mg/mL 
BMR No: MDBP05  
Lot No: P03322/1 
Mfg. Date: 03/10/2022 
Store at 2°C - 8°C 
Caution: New Drug – Limited by Federal (United States) law to Investigational use.  
Manufactured for MediBeacon 
 
 
 
 


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MB-102 drug labels for China distribution includes the following information: 
English 
China Distribution 
Protocol Number: 100-003 
 
MB-102 (Relmapirazin) 
18.6 mg/mL solution for injection 
Each single use vial contains 7.4 mL MB-102 
RELMAPIRAZIN in formulation 
Product for IV use only. Please refer to the 
protocol. 
Store at 2°C- 8°C  
Lot No: xxxxx 
Expiration date: TBD 
 
For clinical trial use only 
 
Sponsor: MediBeacon Inc. 
Manufacturer: Curia (Scotland) Ltd. 
研究方案号: 100-003 
  
MB-102 (Relmapirazin) 注射液 
18.6 mg/mL 溶液 
每瓶含7.4 mL MB-102 (Relmapirazin)注射液 
本品仅供静脉注射使用，按照研究方案使用 
2 - 8°C储存 
批号: XXXXX 
使用期限：TBD 
  
仅用于临床试验 
  
申请人：MediBeacon Inc. 
生产商：Curia (Scotland) Ltd. 
 
 
5.6.4 Investigational Drug Storage, Supply, Return/Destruction 
Relmapirazin vials should be stored at 2°C – 8°C in a secure location. Temperature records will 
be maintained by the clinical site.  
 
All study medications will be stored, reconciled and either returned to the sponsor or destroyed 
according to applicable regulations following authorization by MediBeacon. 
 
5.6.5 Investigational Drug Accountability 
Drug accountability will be maintained by the clinical site and will be reviewed during the study 
and 100% reconciled at the conclusion of the trial.  
Drug accountability documentation may include, but may not be limited to, the following 
information: 
• Receipt date 
• Lot 
• Expiry and/or manufacture date 
• Dispensing information 
 
5.7 
Contact Procedures for Medical Issues Requiring Immediate Attention 
Any medical-related issues or questions requiring immediate resolution or direction should be 
directed to the Sponsor medical monitor using the contact information listed below: 
Joseph Pierro, MD (United States) 
Cell: +1 636-484-3168 
 
 


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Email: jpierro@medibeacon.com 
 
For China, the following individual should be contacted:  
 
Dr. Huimin Ma (Beijing, China) 
Phone: +86 10 57323067 
Email:  huimin.ma@labcorp.com 
 
For submission of Serious Adverse Event information or Unanticipated Adverse Device Effects, 
the following email maybe used:  
• Email: Safety@medibeacon.com 
 
5.8 
Prior and Concomitant Therapy 
Throughout the study, investigators may prescribe concomitant medications or treatments 
deemed necessary to provide adequate care, with the exception of other investigational agents or 
drugs that may alter renal function.  All attempts should be made to maintain the subjects on a 
stable dosing regimen of medications from screening through the duration of the study.   
Concomitant medication information will be collected for all subjects within 3 days of dosing 
through the follow-up visit.  Additionally, use of any non-drug procedural therapies will be 
recorded for each subject including the nature of the therapy, the date/time of the procedure, and 
the reason for the therapy.  Concomitant medication information taken at the time of an SAE will 
also be collected during the safety data follow-up.  
5.8.1 Prohibited Concomitant Medications 
The use of NSAIDs are prohibited 3 days prior to dosing for all subjects. 
5.8.2 Stable Use of Immunosuppressive Medications 
The protocol currently allows for subjects on immunosuppressant medications.  Those 
medications that fall into this category are found in Table 1. This table also outlines timelines 
around stability of those medications required at the time of enrolment.  
 
Table 1 Dose Stability Timelines for Subjects on Immunosuppressive Agents 
Immunosuppressive Agent 
Dose Stability Timeframe 
Antithymocyte Globulin (rabbit) 
No changes within 90 days 
Basiliximab 
No changes within 90 days 
Infliximab 
No changes within 90 days 
Antithymocyte Globulin (equine) 
No changes within 90 days 
Rituximab 
No changes within 90 days 
Cyclosporine 
No changes within 30 days 
Tacrolimus 
No changes within 30 days 
 
 
6 
Study Procedures 


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6.1 
Schedule of Assessments and Procedures 
The schedule of planned study assessments is shown in Table 2.


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Table 2 Study Schedule of Events 
Period 
Pre-Screen 
(optional) 
Screening 
Dosing Day 
Dosing Day 
Dosing Day 
Dosing Day 
Follow-up Visit 
 
 
21 days to day -2 
prior to Dosing 
Pre-dose 
Dosing  
(time 0) 
 
During 12 – 24 
hours post IP 
injection 
Completion of 12 hours 
or up to 24 hours post 
IP injection 
7 days +/- 3 days 
Informed Consenta 
X 
X 
 
 
 
 
 
Inclusion / Exclusion 
 
X 
X 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
Medical History 
 
X 
X 
 
 
 
 
Pregnancy Test for WOCBPb 
 
X 
X 
 
 
 
 
PE or Limited PAc 
 
X 
X 
 
 
 
X 
Vital Signsd  
 
X 
X 
 
X 
X 
X 
Height and Weighte 
 
X 
X 
 
 
 
 
Clinical Labsf   
 
X 
X 
 
 
X 
X 
Mexameter measurements 
 
 
X 
 
 
 
 
Transdermal Data Collectiong 
 
 
X 
X 
X 
X 
 
Drink water h 
 
 
X 
X 
 
 
 
Administration of MB-102i 
 
 
 
X 
 
 
 
PK blood collectionj 
 
 
X 
 
X 
X 
 
ECGk 
 
X 
X 
 
 
X 
 
Concomitant Therapiesl 
 
X 
X 
 
X 
X 
X 
Adverse Eventsm 
 
 
X 
X 
X 
X 
X 
Document Fitzpatrick Skin 
Color Typen 
X 
X 
 
 
 
 
 


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Table 2 Legend 
 
a. Pre-screening consent may be used to evaluate skin color only.  Full informed consent is required prior to any study related procedures being 
conducted. 
b. Negative pregnancy serum human chorionic gonadotropin (hCG) test at screening for women of childbearing potential (WOCBP) is required 
for eligibility. On dosing day, a urine pregnancy test will be conducted for WOCBP who agree to use an acceptable method of birth control  
c. A full physical examination (PE) is required at the screening visit.  A full PE or limited physical assessment (PA) may be conducted prior to 
dosing. (Limited PA includes assessments of HEENT, respiratory, cardiovascular, abdominal systems). A full or limited exam may be 
conducted at the follow-up visit.  
d. Vital signs include blood pressure, respiration rate, heart rate and temperature.   Note: temperature is collected at screening, pre-dose, at 
approximately 12 hours post-dose and at the follow-up visit (and not during multiple timepoints on dosing day). Whenever possible, the 
subject should be resting for approximately 5 minutes prior to all measurements.   Vital signs will be collected at screening, pre-dose and at the 
following post-dose timepoints: 90, 250 and 500, 710 minutes (±5 min). For subjects followed for 24 hours, an additional measurement will be 
taken at 1450 minutes.  
e. Height and Weight should be measured at screening; weight will also be measured on the day of dosing.  
f. Clinical laboratory assessments will be analyzed by a central laboratory and consist of standard chemistry, hematology and urinalysis 
parameters per Table 3. Coagulation panel will be conducted at Screening only.  
g. MediBeacon® Transdermal GFR Measurement System data collection will commence prior to dose administration. At least 15 minutes prior 
to dosing, sensors should be placed on the subject and the MediBeacon® Transdermal GFR Measurement System started. Data collection will 
continue through 12 - 24 hours of PK sampling. Once an tGFR is measured, sensors may be removed while PK sampling continues.  
h. The subject should be given 240 mL of ambient water to drink the night prior (if brought in the night before dosing), the morning of dosing, 
and just prior to MB-102 dose administration 
i. 
MB-102 will be administered as a dose of 130 mg (7 mL) via IV injection over a 30 - 60 second injection period. This will be followed by a 
saline flush over 30 - 60 seconds. Time of administration will be recorded. 
j. 
Stratum 1:  PK sampling will be collected pre-dose and at 5, 15, 30, 60, 90 (±2 min), 120, 180, 240, 300, 360, 480, 600 (±5 min) and 720 
minutes post-dose (12 hour collection period). Stratum 2:  PK sampling will be collected pre-dose and at 5, 15, 30, 60, 90 (±2 min), 120, 180, 
240, 300, 360, 480, 600, 720, 960, 1200, and 1440 (±5 min) minutes post-dose (24 hour collection period). Blood draws should be via a 
venous catheter and will be processed in accordance with instructions available in the Study Procedure Manual.  
k. A 12 lead ECG will be performed at Screening, prior to dosing, and at 700 minutes post dosing (±5 min). Subjects should be resting quietly 
for 10-15 minutes prior to the ECG collection. 
l. 
Concomitant medications administered within 3 days prior to baseline through the final follow-up visit will be recorded.   
m. Adverse events are collected from the time of sensor placement (for baseline measurement) through the follow-up visit. 
n. Fitzpatrick Skin Scale will be assessed by evaluating the skin on the upper chest (where sensors will be placed). 


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6.2 
Pre-screening 
US sites will have the option to pre-screen study subjects to evaluate them directly for skin color 
in order to meet Fitzpatrick Skin Scale stratification recruitment requirements.   
6.3 
Screening  
Screening will occur within 21 days (but at least 2 days prior to) the baseline / dosing day and 
will comprise of the following: 
• Obtain written informed consent before any study-specific assessments are performed 
• Assess eligibility against the inclusion and exclusion criteria 
• Collect demographic data and medical history; review concomitant medications 
• Obtain screening non-fasting laboratory tests including chemistry, hematology, and 
coagulation profile (See Section 7.1.2.6 and Table 3). Perform serum pregnancy test in 
women of child-bearing potential and collect a urine sample for urinalysis. 
• Perform COVID-19 testing for unvaccinated subjects or per study center requirements 
o Vaccinated subjects without COVID-19 symptoms are not required to have a 
COVID-19 test performed 
• Collect height and weight measurements  
• Perform a full physical exam and collect vital signs including temperature (Sections 
7.1.2.7 and 7.1.2.8) 
• Perform a 12 lead ECG (Section 7.1.2.9) 
• Document Fitzpatrick Skin Scale Color Type by examining the upper chest (locations for 
possible sensor placement) (see Appendix A) 
6.4 
Night before Dosing Day 
For institutions that prefer to bring study subjects to the institution the night before dosing day, 
the following procedures may be performed:  
• Review subject eligibility 
• Update medical history with any new information or issues since screening 
• Perform a limited physical assessment 
• Record concomitant medications taken within 3 days prior to dosing day 


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• Perform a urine pregnancy test for WOCBP 
• Have the subject consume 240 mL of ambient water 
6.5 
Dosing Day: Baseline Assessments 
Baseline assessments will be performed prior to dosing (with the exception of those procedures 
noted in Section 6.3 that were performed the night before for those sites that bring subjects in the 
night prior to dosing).  
• Update medical history with any new information or issues occurring since the initial 
screening visit (if not performed the night before).  
• Collect the subject weight (BSA and BMI will be calculated based on screening height 
and baseline weight measurements) 
• Review subject eligibility 
• Confirm that the subject has consumed 240 mL of ambient temperature water at least 1 
hour prior to dosing time.  
• Perform a limited physical assessment and collect vital signs (including temperature) 
(Sections 7.1.2.7 and 7.1.2.8).  
• Perform a baseline ECG (Section 7.1.2.9). 
• Record concomitant medications taken within 3 days of the dosing visit 
• For WOCBP, a urine pregnancy test will be performed 
• Clean and prepare the body areas for sensor attachment using an alcohol pad. Excess hair 
should be clipped (not shaved) from the area for sensor.  
• Obtain melanin (only) measurements with the Mexameter (Section 7.1.2.11) 
• A venous catheter should be placed in one arm for PK blood draws.  A pre-dose baseline 
draw should be collected.  
• Obtain baseline laboratory tests including chemistry, hematology, and urinalysis (See 
Section 7.1.2.6 and Table 3).  
• Prior to dosing, the device sensor should be attached to the subject and the MediBeacon® 
Transdermal GFR Measurement System data acquisition initiated. During this data 
acquisition period, no other study procedures should be performed.  
• Adverse event collection begins 


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• Prior to dosing, have the subject consume an additional 240 mL of ambient water 
• Place a venous catheter for the purpose of MB-102 dosing in the opposite arm. An 
appropriately sized angio-catheter should be selected based on study subject (22 – 24 
gauge).  
6.6 
MB-102 Dosing 
The dose of 130 mg MB-102 (7.0 mL injection) should be prepared based on instructions 
provided in the Study Procedure Manual. Final dose calculation should be based on weight and 
not volume, therefore dosing syringes will be weighed prior to administration.   The prepared 
syringe should be maintained at ambient temperature. MB-102 dosing will be performed in the 
opposite arm from PK draws whenever feasible.  
Administration of MB-102 will be via direct intravenous (IV) injection following angio-catheter 
placement. Care should be taken to prevent extravasations during dosing.   Ideally, a 22 – 24 
gauge angio-catheter and 10 mL syringe should be used for administration. Catheter size will be 
collected.  
• Ensure Universal Standard precautions are taken with handwashing and gloving 
procedures; maintain aseptic technique when handling the prepared syringe 
• Check the patency of the placed catheter by injecting a small volume of saline prior to 
MB-102 dosing 
• Administration of MB-102 should be via a steady IV injection (without hard pressure) 
over 30 - 60 seconds (smaller bore catheters [24 gauge] may require a slower injection) 
• Following MB-102, a 10 mL saline flush should be administered over 30 - 60 seconds 
• The injection site should be observed for swelling or induration or yellow discoloration 
indicative of a drug infiltration. Drug infiltration may also cause discomfort or pain to the 
study subject.  
• The dosing catheter will be removed after the saline flush is completed. 
 
To avoid extravasation/infiltration: 
• Ensure no dislodgement of the needle cannula during venepuncture 
• Ensure the back vein wall is not punctured during placement 
• Avoid strong pressure on the syringe plunger during saline or MB-102 administration 
• Perform a slow injection over the full 30 - 60 seconds.  
 
If an extravasation occurs, record it as both an adverse event and a protocol deviation. Subjects 
with evidence of MB-102 or saline extravasations will be discontinued from PK collection and 
fluorescent measurements but followed for safety. Subjects may be replaced at the discretion of 
the Sponsor.  
 
The time noted at the completion of MB-102 injection (but prior to the saline flush) is the start-
time for the timing of the PK draws.  
Following dosing, the syringe will be weighed in order to calculate an accurate dose of MB-102.  


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6.7 
Post-dose Study Procedures 
6.7.1 Stratum 1 (12 hour follow-up) 
During the course of the study day, it is particularly important for site teams to check the patency 
of PK catheters. If a catheter is determined to be compromised in anyway, another catheter may 
be placed in the same arm as the original catheter utilizing a different vein.  
PK draws will be drawn via the venous catheter at the following timepoints: 
• PK draw in K2 EDTA tube at 5 minutes (±2 minute) 
• PK draw in K2 EDTA tube at 15 minutes (±2 minute) 
• PK draw in K2 EDTA tube at 30 minutes (±2 minutes) 
• PK draw in K2 EDTA tube at 60 minutes (±2 minutes) 
• PK draw in K2 EDTA tube at 90 minutes (±2 minute) 
• Vital sign collection at 90 minutes (±5 minutes) 
• PK draw in K2 EDTA tube at 120 minutes (±5 minutes) 
• PK draw in K2 EDTA tube at 180 minutes (±5 minutes) 
• PK draw in K2 EDTA tube at 240 minutes (±5 minutes) 
• Vital sign collection at 250 minutes (±5 minutes) 
• PK draw in K2 EDTA tube at 300 minutes (±5 minutes) 
• PK draw in K2 EDTA tube at 360 minutes (±5 minutes) 
• PK draw in K2 EDTA tube at 480 minutes (±5 minutes) 
• Vital sign collection at 500 minutes (±5 minutes) 
• PK draw in K2 EDTA tube at 600 minutes (±5 minutes) 
• Perform a 12 lead ECG at 700 minutes (±5 minutes) 
• Vital sign collection (includes temperature) at 710 minutes (±5 minutes) 
• PK draw in K2 EDTA tube at 720 minutes (±5 minutes) 


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• Obtain laboratory tests including chemistry, hematology, and urinalysis (See Section 
7.1.2.6 and Table 3) at 725 minutes (±5 minutes) 
• At the conclusion of TGFR measurements (when tGFR is reported on the monitor), the 
sensor may be removed 
• Adverse events will be collected based on subject reports and medical team observations 
6.8 
Stratum 2 (24 hour follow-up) 
PK draws will be drawn via the venous catheter at the following timepoints: 
• PK draw in K2 EDTA tube at 5 minutes (±2 minute) 
• PK draw in K2 EDTA tube at 15 minutes (±2 minutes) 
• PK draw in K2 EDTA tube at 30 minutes (±2 minutes) 
• PK draw in K2 EDTA tube at 60 minutes (±2 minutes) 
• PK draw in K2 EDTA tube at 90 minutes (±2 minute) 
• Vital sign collection at 90 minutes (±5 minutes) 
• PK draw in K2 EDTA tube at 120 minutes (±5 minutes) 
• PK draw in K2 EDTA tube at 180 minutes (±5 minutes) 
• PK draw in K2 EDTA tube at 240 minutes (±5 minutes) 
• Vital sign collection at 250 minutes (±5 minutes) 
• PK draw in K2 EDTA tube at 300 minutes (±5 minutes) 
• PK draw in K2 EDTA tube at 360 minutes (±5 minutes) 
• PK draw in K2 EDTA tube at 480 minutes (±5 minutes) 
• Vital sign collection at 500 minutes (±5 minutes) 
• PK draw in K2 EDTA tube at 600 minutes (±5 minutes) 
• Perform a 12 lead ECG at 700 minutes (±5 minutes) 
• Vital sign collection (includes temperature) at 710 minutes (±5 minutes) 
• PK draw in K2 EDTA tube at 720 minutes (±5 minutes) 


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• Obtain laboratory tests including chemistry, hematology, and urinalysis (See Section 
7.1.2.6 and Table 3) at 725 minutes (±5 minutes) 
• PK draw in K2 EDTA tube at 960 minutes (±5 minutes) 
• PK draw in K2 EDTA tube at 1200 minutes (±5 minute) 
• PK draw in K2 EDTA tube at 1440 minutes (±5 minutes) 
• Vital sign collection at 1450 minutes (±5 minutes) 
• At the conclusion of TGFR measurements (when an tGFR is reported on the monitor), 
the sensor may be removed.  
• Adverse events will be collected based on subject reports and medical team observations 
• Subjects may be discharged from the study center 
6.9 
Follow-up Visit 
Subjects will return for a safety follow-up visit approximately 7 +/-3 days after the dosing visit. 
The following assessments will be performed 
• Perform a full or limited physical exam and collect vital signs including temperature 
(Sections 7.1.2.7 and 7.1.2.8) 
• Obtain laboratory tests including chemistry, hematology, and urinalysis (Section 7.1.2.6 
and Table 3).   
• Record concomitant medications  
• Collect adverse events; review ongoing AEs and document resolution (when applicable)  
6.10 Early Withdrawal / Unscheduled Visits 
Any subject that withdraws from the study early for any reason, or who needs to have an 
unscheduled visit performed to assess a safety issue, will have the following assessments 
performed:  
• Obtain laboratory tests including chemistry, hematology, and urinalysis profile (Section 
7.1.2.6 and Table 3). 
•  Perform a full or limited physical exam and collect vital signs (Sections 7.1.2.7 and 
7.1.2.8) 
• Record concomitant medications  


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• Collect adverse events; review ongoing AEs and document resolution (when applicable)  
• Record withdrawal date and reason for withdrawal, if appropriate 
6.11 Repeat Subjects 
Subjects may be re-enrolled in the protocol in the following situations (and if no documented 
safety concerns regarding exposure to the investigational device or drug):  
• When a dose extravasation has occurred 
• When there is a device malfunction (sensor falling off during the monitoring period and 
before a tGFR has been reported) 
• Back-up subjects who were not dosed 
Stratum 1 subjects must have a minimum of a 3-day wash-out from prior exposure of MB-102 
before receiving another dose. Stratum 2 subjects must have a minimum of a 7-day wash-out 
from prior exposure of MB-102 before receiving another dose  
In some cases, the screening visit (if outside the 21-day window) may need to be repeated.  
Repeat subjects will maintain the same subject ID.  
Subjects can be in the study a maximum of two times and only when the above situations have 
occurred.  
7 
Efficacy and Safety Variables  
7.1 
Efficacy and Safety Measurements Assessed and Flow Chart  
Table 2 shows the planned study assessments.   
7.1.1 Efficacy Assessments 
This pivotal study is not designed to address treatment efficacy rather it is to evaluate the use of 
MB-102 and the MediBeacon® Transdermal GFR Measurement System to provide a point of 
care (POC) means to collect GFR data. The specific endpoints related to calculation of GFR are 
discussed in Section 9. 
7.1.2 Safety Assessments 
Safety will be monitored by the assessments described below as well as the collection of AEs at 
every visit after screening. Planned safety assessments are detailed in the MediBeacon® 
Transdermal GFR Measurement System Study Schedule (Table 2). The investigators or site staff 
will be responsible for monitoring the safety of subjects who have entered this study and will be 
responsible for detecting, documenting and reporting events that meet the definition of an 
adverse event (AE) or serious adverse event (SAE).  Significant findings that were noted to be 


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present at or prior to dosing must be included in the relevant medical history page of the eCRF. 
Significant new findings that begin or worsen after dosing must be recorded on the AE page of 
the eCRF. Subjects should be followed until the event is resolved or stabilized. AEs are collected 
from the time of initial sensor placement until the completion of the follow-up visit.   
7.1.2.1 Adverse Events 
Adverse Event Definition 
An adverse event is defined as any untoward medical occurrence, unintended disease or injury, 
or untoward clinical signs (including abnormal laboratory findings) in subjects, temporally 
associated with the use of a medicinal product, whether or not related to the investigational 
medical device or drug. 
An unanticipated adverse device effect (UADE) is any serious adverse effect on health or safety, 
any life-threatening problem or death caused by, or associated with a device, if that effect, 
problem, or death was not previously identified in nature, severity, or degree of incidence in the 
application; or any other unanticipated serious problem associated with a device that relates to 
the rights, safety, or welfare of subjects. For the purposes of this trial, the device is the 
MediBeacon® Transdermal GFR Measurement System and the sensor system including the 
adhesive pads for the attachment of the optical sensors to the body.  
Documentation and Reporting of Adverse Events 
AEs should be reported and documented in accordance with the procedures outlined below. The 
following data should be documented for each AE: 
• Description/term of the symptom event (underlying diagnosis) 
• Date of first occurrence and date of resolution (if applicable) 
• Classification of “serious” or “not serious” (Section 7.1.2.2) 
• Severity 
• Causal relationship  
• Action taken 
• Outcome of event  
For abnormal clinically significant laboratory findings, the clinical manifestation (diagnosis) 
should be noted as an adverse event (e.g. anemia instead of low hemoglobin). Should a clinically 
significant lab abnormality occur that is not part of a diagnosis, the abnormality itself may be 
reported as an AE. Laboratory abnormalities that meet the criteria for an AE should be followed 
until they have returned to normal or an adequate explanation of the abnormality is determined. 
When an abnormal laboratory result corresponds to a sign/symptom of an already reported AE it 
is not necessary to separately record the lab result as an additional AE.   


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Assessment of Severity 
Each AE will be assigned a category by the investigator as follows: 
• Mild: results in minimal transient impairment of a body function or damage to a body 
structure and/or does not require any intervention other than monitoring or OTC 
medication.  
 
• Moderate: Results in moderate transient impairment of a body function or transient 
damage to a body structure and/or requires intervention, such as administration of 
medication or transfusion or laparoscopic or endoscopic procedure to prevent permanent 
impairment of a body function or damage to a body structure.  
 
Severe: An event which is life threatening, results in permanent impairment of a body 
function or permanent damage to a body structure or necessitates significant intervention, 
such as major surgery, to prevent permanent impairment of a body function or permanent 
damage to a body structure. The term severe is often used to describe the intensity 
(severity) of a specific event (as in mild, moderate, or severe myocardial infarction); the 
event itself, however, may be of relatively minor medical significance (such as severe 
headache). This is not the same as serious, which is based on patient/event outcome or 
action criteria usually associated with events that pose a threat to a patient‘s life or 
functioning. Seriousness (not severity) serves as a guide for defining regulatory reporting 
obligations. An event that changes in severity (gets worse or gets better) should be noted 
as its worst severity.  
 
Assessment of Causality 
Every effort will be made by the investigator to assess the relationship of the AE, if any, to the 
study device (and components), investigational drug.  Causality should be assessed using the 
categories presented below: 
Unrelated 
Clinical event with an incompatible time relationship to study device or 
study drug, and that could be explained by underlying disease or other 
drugs or is incontrovertibly not related to the study device. 
Unlikely 
Clinical event whose time relationship to study device investigational 
drug makes a causal connection improbable, but that could plausibly be 
explained by underlying disease or other drugs. 
Possible 
Clinical event with a reasonable time relationship to study device or 
investigational drug, but that could also be explained by concurrent 
disease or other drugs. 
Probable 
Clinical event with a reasonable time relationship to study device or 
investigational drug and is unlikely to be attributed to concurrent disease 
or other drugs. 


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Very Likely/Certain 
Clinical event with plausible time relationship to study device or 
investigational drug, and that cannot be explained by concurrent disease 
or other drugs. 
AEs that are deemed related should be further assessed to determine if a relationship to the 
investigational drug, or device can be elucidated.  
Action Taken 
The investigator will describe the action taken in the appropriate section of the eCRF, as follows: 
• None 
• Concomitant interventional treatment(s) administered (includes medications or 
procedures) 
• Other, specify 
Outcome of the Event 
The investigator will describe the outcome of the event in the appropriate section of the eCRF, as 
follows: 
• Unknown 
• Resolved 
• Ongoing 
• Resolved with sequelae 
• Death (with date and cause reported) 
 
Follow-up of Adverse Events 
Subjects with AEs should be followed until the event is resolved or until, in the opinion of the 
investigator and medical monitor, the event is stabilized or determined to be chronic. 
7.1.2.2 Serious Adverse Events 
Serious Adverse Event Definition 
An SAE is any AE from this study that results in one of the following outcomes: 
 
An adverse event that:  
a) led to death;  
b) led to serious deterioration in the health or the subject, that either resulted in: 
  
1) a life threatening illness or injury or  
2) a permanent impairment of a body structure or a body function, or 
3) in-patient or prolonged hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body function; 
 
c) led to fetal distress, fetal death or a congenital abnormality or birth defect 


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Reporting requirements for all SAEs is detailed in Section 7.1.2.3.  
Note: Planned hospitalization for a pre-existing condition, or a procedure required by the 
protocol without serious deterioration in health, is not considered a serious adverse event. 
 
7.1.2.3 Reporting of Serious Adverse Events  
Any SAE must be reported by the investigator if it occurs during the clinical study whether or 
not the event is considered to be related to the MediBeacon® Transdermal GFR Measurement 
System, or the investigational drug.  All serious adverse events must be reported by the 
Investigator (or designee) by submitting the Serious Adverse Event Report Form (via the 
electronic data capture (EDC) system) or via email to MediBeacon within 24 hours of learning of 
the adverse event.   
The Sponsor safety team, in cooperation with the Investigator, will assess all serious adverse 
events considered drug or device-related for potential reportability to regulatory authorities and 
ethical committees as an Unanticipated Adverse Device Effect (UADE) or as an expedited 
serious adverse event.  
Note: It is also the responsibility of the Investigator to inform their Independent Ethics 
Committee (IEC) of other serious adverse events (i.e. non-UADEs) as required by their IEC 
procedures and in conformance with regulations. 
 
SAEs must be reported within 24 hours of knowledge.  
For submission of Serious Adverse Event information or Unanticipated Adverse Device Effects, 
the following email maybe used:  
Email: Safety@medibeacon.com 
 
The investigator should not wait to receive additional information to document fully the event 
before notification to the Sponsor of an SAE, though additional information may be requested.  
Where applicable, information from relevant laboratory results, hospital case records, and 
autopsy reports should be obtained. 
Instances of death, congenital abnormality, or an event that is of such clinical concern as to 
influence the overall assessment of safety, if brought to the attention of the investigator at any 
time and linked by the investigator to this study, should be reported to MediBeacon.   
The sponsor or designee will promptly notify all relevant investigators and the regulatory 
authorities of findings that could adversely affect the safety of subjects, impact on the conduct of 
the study or alter the IEC approval/favorable opinion of the study.  In addition, the sponsor, will 
expedite the reporting to all concerned investigators, to the IECs, and to the regulatory 
authorities of all adverse device reactions that are both serious and unanticipated.   


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7.1.2.4 Pregnancies 
Testing for pregnancy for a female study subject with childbearing potential must be conducted 
at screening (or within 7 days of dosing).  In addition, a urine pregnancy test will be performed 
prior to dosing on treatment day. Subjects who are pregnant or intend to become pregnant during 
the study will be excluded. Should a pregnancy occur with a study subject, the pregnancy should 
be reported to MediBeacon within 24 hours of the site’s knowledge. All pregnancies will be 
followed to term, delivery or premature termination.  
7.1.2.5 Device Observations / Malfunctions  
All device observations, malfunctions or failures of the MediBeacon® Transdermal GFR 
Measurement System will be documented in the eCRF. In addition, failures of the sensor 
adhesive will be specifically documented.  
 
7.1.2.5.1 Sensor Displacement 
Prior dosing with MB-102: 
Should a sensor be accidently removed (or significantly bumped) prior to receipt of MB-102, it 
should be removed from the subject, a new sensor placed on the subject, and baseline 
measurements re-started.  
 
After dosing with MB-102: 
If a sensor is accidently removed (or significantly bumped) following receipt of MB-102 but 
before a tGFR is calculated, the subject will remain in the study for safety follow-ups only for 
the full duration required by their stratum (12 hours or 24 hours). PK sample collection and 
fluorescent measurements will be terminated, however safety assessments (vital signs, ECGs and 
clinical safety labs) will be performed.  
 
7.1.2.6 Clinical Laboratory Evaluation 
Clinical laboratory assessments (Table 3) will be performed by a central lab in the US. A central 
lab will be used in China, if available. If the central lab is unavailable due to COVID-19, Chinese 
sites may utilize their local hospital laboratory if appropriately accredited.  Reference ranges will 
be used by the investigator to assess the laboratory data for clinical significance and changes 
relative to baseline measurements.  Clinically significant changes in laboratory values will be 
documented as adverse events.  
 
 


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Table 3 Clinical Laboratory Analytes 
Chemistry Panel                                   
Hematology       
Other required lab tests 
• 
Alkaline Phosphatase  
• 
Alanine Aminotransferase (ALT) 
• 
Albumin 
• 
Aspartate Aminotransferase (AST) 
• 
Bilirubin (total and direct) 
• 
Blood Urea Nitrogen (BUN) 
• 
Calcium (Ca) 
• 
Carbon dioxide (CO2) 
• 
Chloride (C) 
• 
Creatinine (SCr) 
• 
Glucose 
• 
Phosphorus 
• 
Potassium  
• 
Sodium 
• 
Total Protein 
• 
Uric acid 
• 
BUN/Creatinine ratio 
 
 
 
All lab tests are non-fasting 
• 
Hematocrit 
• 
Hemoglobin 
• 
WBC 
• 
RBC 
• 
Platelets 
Differentials 
• 
Neutrophils 
• 
Lymphocytes 
• 
Monocytes 
• 
Eosinophils 
• 
Basophils 
 
 
For WOCBP 
• 
Serum pregnancy test 
(screening and a urine 
dipstick on day of 
dosing  
• 
Urinalysis  
• 
Protein 
• 
Glucose 
• 
Ketones 
• 
Hemoglobin 
• 
Bilirubin 
• 
Urobilinogen 
• 
Acetone 
• 
Nitrite 
• 
Leucocytes 
• 
pH 
• 
Specific gravity 
• 
Color 
• 
Bacteria 
If abnormalities are seen, 
then microscopic 
examination will be 
performed 
Coagulation 
Parameters 
Only performed 
at screening  
• 
PT 
• 
INR 
• 
aPTT 
 
COVID-19 Test: nasopharyngeal swab (only performed at screening for unvaccinated 
subjects or per study center requirements) 
 
7.1.2.7 Vital Signs 
Vital signs (including blood pressure, heart rate, respiration, and temperature) will be measured 
at screening, at multiple timepoints on dosing day(s), and at the follow-up visit. Vital signs 
should be collected while the subject is in a seated position and after resting for approximately 5 
minutes for all measurements.  Temperature is only collected at screening, pre-dose, and the 
completion of the dosing day, and at the follow-up visit.  
7.1.2.8 Physical Examinations or Limited Physical Assessments 
Physical examinations (when conducted by a physician, or other medically qualified 
investigator) or limited physical assessments (when performed by a nurse or other qualified 
individual) should include at a minimum an assessment of the head, ears, eyes, nose, throat 
(HEENT), respiratory, cardiovascular, and gastrointestinal systems. It is preferred that the same 
medical professional perform the baseline and post dosing assessments. Significant findings that 
were present prior to dosing must be included in the Medical History eCRF page. Significant 
new findings that begin or worsen after dosing must be recorded on the AE page of the eCRF. 


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Clinically significant abnormalities occurring post-dose should be evaluated by a physician and 
noted as AEs.   
The study investigator will assess the subject for the occurrence of clinically significant new 
findings that begin or worsen after dosing which must be recorded as an AE on the eCRF page. 
A full physical exam should be conducted at screening and limited physical assessments may be 
conducted at other time points and must also be inclusive of the relevant organ or body system of 
interest for assessing the AE 
7.1.2.9 ECGs 
Standard 12 lead ECGs will be collected at screening, prior to dosing and at 700 minutes (±5 
min). The following parameters will be assessed: interpretation, ventricular rate, PR interval, 
QRS duration, QT, and QTcF.  
 
Subjects should be allowed to rest quietly approximately 10-15 minutes prior to their ECG.  
Additional ECGs may be collected if an issue or safety concern is noted.  
 
An appropriately trained and experienced investigator will interpret the ECGs.  A subject with an 
abnormal clinically significant ECG during screening does not qualify for the study.  A subject 
with an abnormal not clinically significant ECG does not qualify for dosing without investigator 
comment on the ECG source document/eCRF.  
 
7.1.2.10 PK Sample Collection 
PK samples will be collected at the timepoints noted in Table 2. Recommendations for venous 
access and sample processing information are available in the Study Procedure Manual. PK 
samples should be collected in a manner to prevent haemolysis and placed on ice until processed 
and aliquoted into cryovials. PK samples must be stored frozen at   -70 to -80ºC until shipped for 
PK analysis.  
 
7.1.2.11 Mexameter® Measurements 
A commercially available Mexameter® device will be provided to the sites for the measurement 
of skin pigment (melanin) and erythema.  The device should be used in accordance with the 
instructions provided in the Study Procedure Manual (including pre-use calibration). 
Measurements should be performed on subjects when they are not in close proximity to a 
window and should be made on the approximate location of sensor placement. It is advisable, 
when required, to clip excess hair as early in the dosing day as possible to allow transient redness 
due to the clipping process to fade. The site should note any skin irritation due to clipping as 
medical history. Mexameter® measurements of melanin will be collected prior to sensor 
placement.  
7.2 
Safety Review Committee  
A Safety Review Committee (SRC) will be convened and will include the medical monitor, the 
safety manager(s), clinical monitor(s) and clinical manager.  The SRC will oversee safety data 


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(AEs, vitals, clinical labs, ECG data, etc.) generated by enrolled study subjects on the trial. In 
addition, they will review all SAEs and UADEs and clinically significant safety observations 
noted during the study. Oversight work and study related decisions will be performed in 
accordance with a written Safety Review Committee Plan. 
8 
Information for the Investigator: Potential Risks of the Device 
Adverse events that may be anticipated in this clinical study are outlined for the investigational 
drug and the MediBeacon® Transdermal GFR Measurement System. 
 
8.1 
Investigational Drug 
Clinical data from the Pilot 1A and 1B studies (total n = 32 subjects) included the following 
adverse events:  
• Pilot 1A (n = 16) 
o Vasovagal reaction (1 subject) 
o Dizziness (1 subject, 2 events) 
 
These events occurred in fasting subjects shortly after dosing and resolved on that day.  No other 
AEs, injection site reactions, clinically significant laboratory values or significant changes in 
vital signs were noted during this study.  
 
• Pilot 1B (n = 16) 
o Headaches (56.3% of subjects) 
o Erythema (at the site of the adhesive) (100% of subjects) 
o Diarrhoea (1 subject) 
o Dizziness (occurring in 1 subject following release from the study center) 
 
Erythema was thought to be related to the adhesive used to adhere the sensor to the skin. 
Headaches were deemed related to the head strap required to hold the forehead sensor in place. 
Sensor placement on forehead was discontinued post Pilot 1B.  
 
MB-102 is excreted in the urine. Therefore, urine discoloration (chromaturia) is expected but has 
not been considered an adverse event in prior studies.  
 
In the Pilot 2 study, a total of 234 subjects with normal to compromised renal function have been 
exposed to MB-102. A total of 120 subjects received a dose of 4 µmol/kg followed by a 5 mL 
injection of iohexol. Seventy (70) subjects received a single dose only (no iohexol) of 4 µmol/kg 
of MB-102) and 44 have received a fixed dose of 130 mg (7 mL). All reported AEs were mild or 
moderate in severity and resolved without sequalae.  Overall, MB-102 given in conjunction with 
or without iohexol was well tolerated in this subject population.  
 
A total of 40 adverse events were reported in 28 treated subjects in Groups 1, 2 and 3 for an AE 
rate of 12.0% in the treated population. A total of 31 events were considered mild and 9 
moderate events occurred in 5 subjects (2.5% of the population). There were no severe events 


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reported. There were no Serious Adverse Events (SAEs) reported during the study. There were 
no Unanticipated Adverse Device Effects (UADEs) reported during the study.  
 
Four AEs, dyspepsia, chromaturia, hot flush and (facial) rash were considered related to 
investigational product (MB-102); all events resolved by study completion. Dyspepsia and 
chromaturia were also considered to be related to iohexol. Of note, chromaturia is an expected 
effect of MB-102 (noted in the Investigator’s Brochure) and expected in all subjects as the 
excretion of MB-102 will color the urine of subjects receiving the product. It is not a 
documented effect of iohexol (per the label).   
 
Seven (7) AEs occurring in 7 subjects were considered related to the device (sensor attachment); 
these included application site erythema, dermatitis, and pruritus and were considered related to 
the adhesive material used to hold the sensor in place. Two events of application site 
discoloration (melanin spot at the sensor location) were noted in 2 subjects in the SOG cohort 
which resolved within 24 hours of removal of the sensor.  Other reported AEs (conjunctivitis, 
nausea, vomiting, cardiac murmur, headache, anxiety, micturition urgency, pollakiuria, urine 
odor abnormal, peripheral oedema, fatigue, and a pruritis event [not at the sensor location] were 
considered not related to MB-102, the sensor device or iohexol.  Injection site reactions 
(bruising, erythema, extravasation) were also not considered related to MB-102.   
 
There may also be other risks that are unforeseen at this time. For additional information on the 
risk profile, please reference the current Investigator’s Brochure.  
 
8.2 
MediBeacon® Transdermal GFR Measurement System  
There are no direct risks associated with the MediBeacon® Transdermal GFR Measurement 
System (monitor portion) as it does not contact the study subject.  Adverse events observed from 
the sensors are with regard to the methods used to affix it to the study subject.   Risks may 
include a reaction to the sensor or adhesive material or the adhesive used on the skin clip.  
8.2.1 Adhesive Clip 
As with the adhesive used on the sensors, there is the chance of reaction to the adhesive used to 
attach the clip to the skin.  Reactions could include redness, itchiness or other localized skin 
reactions. Clips will be provided, however other means (surgical tape, tegaderm, etc.) to secure 
the sensor cord may be used.  
8.3 
Trial Procedures 
Blood collection may lead to light-headedness and dizziness in some study subjects. It is 
recommended to ensure subjects continue to hydrate and eat during the dosing day to mitigate 
the effect of blood loss.  
Bruising and pain at the site of the venous catheters may also be expected.  
 


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8.3.1 Dose Extravasations 
Should a dosing extravasation occur, a subject may report pain or burning during the injection. 
Subjects should be queried during the injection regarding any sensation. Subjects with MB-102 
or saline extravasations will be discontinued from PK collection and fluorescent measurements 
but continued in the study for safety. All extravasations will be collected as adverse events and 
protocol deviations.  
9 
Statistical Methods 
9.1 
Overview  
The transdermal-derived GFR data (tGFR) is obtained directly from the MediBeacon® 
Transdermal GFR Measurement System (TGFR) for each subject. This tGFR value is compared 
to the subject's nGFRBSA for the study endpoint determination. 
 
9.2 
Analysis Populations 
The following analysis populations will be defined for the study: 
➢ Intent-to-Measure (ITM) Population – The ITM population will consist of all subjects 
who are enrolled in the study in Stratum 1 & 2 and for whom an end of session tGFR has 
been calculated, and who have not had any major protocol deviations. 
➢ Modified Intent-to-Measure (mITM) Population – The mITM population will consist 
of all subjects in the ITM population with no outlier PK parameters. 
➢ Safety Population – The safety population will consist of all subjects who are enrolled in 
the study and have been dosed with MB-102.   
➢ Pharmacokinetic (PK) Population – The pharmacokinetic population will consist of all 
subjects who are enrolled in the study and have any PK data. 
The mITM population will be the primary analysis set for all effectiveness analyses.  The 
Safety Population will be used for the analysis of all safety variables and baseline 
characteristics. The PK Population will be used for the analyses of PK data.  
 
9.3 
Subject Disposition 
The number and percentage of subjects who complete the study or who terminate early from the 
study and the reasons for early termination will be collected and reported.  Subjects will be 
considered to have completed the study if they complete the dosing day.  
The number and percentage of subjects in each analysis population will be presented.  
Percentages will be based on the number of subjects enrolled. 
9.4 
Plasma Pharmacokinetic Analyses 
The pharmacokinetic objective is to characterize the single dose pharmacokinetics of MB-102 


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following IV bolus dosing, specifically, to obtain the clearance and total volume of distribution 
of MB-102 using compartmental methods in Phoenix WinNonlin (Certara, Version 8.1 or 
higher). 
 
Based on prior data, it is expected that a two-compartment model will adequately describe the 
pharmacokinetic profiles of MB-102. The following two-compartmental pharmacokinetic 
parameters will be determined: 
 
➢ Cmax: The maximum plasma concentration. 
➢ AUC: Area under the plasma concentration-time curve 
➢ t1/2α: Half-life associated with distribution phase 
➢ t1/2β: Half-life associated with elimination phase 
➢ t1/2: elimination half-life from central compartment.   
➢ V: Total volume of distribution 
➢ CL: Systemic clearance 
➢ V1: Volume of distribution for central compartment 
➢ V2: Volume of distribution for peripheral compartment 
 
The two key PK parameters from compartmental analysis are CL and V. The clearance (CL) 
derived from the two-compartment model is the plasma-derived GFR used to calculate the BSA 
indexed nGFR that is the comparison to the tGFR for the P30 calculations. V is used in the 
calculation of GFR indexed to volume of distribution.  
 
All PK concentrations and parameters will be listed. As each subject will have a unique GFR 
measurement, summary statistics are not applicable in this analysis. 
Individual figures will be provided for plasma PK concentrations. All figures will be produced 
on both linear-linear and logarithmic- linear scales with data and the two-compartment fit. 
 
9.5 
Primary Endpoint Analysis 
The primary endpoint is the performance measure of P30 for transdermal-derived GFR with 
respect to the plasma-derived indexed GFR, with a 95% confidence interval. The performance 
goal is 85%. Success for the study will be that the lower limit of the 95% CI is greater than 85%. 
 
9.6 
Safety Analyses 
Safety of MB-102 will be evaluated through treatment emergent adverse events (TEAEs), where 
treatment emergence is defined with respect to the first dose of MB-102. 
 
Safety of the MediBeacon® Transdermal GFR Measurement System will be evaluated through 
TEAEs, where treatment emergence is defined with respect to the start time of Transdermal GFR 
Measurement System use (placement of the sensor on the skin). 
 


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Additional safety variables include physical examinations, clinical laboratory assessments, 
ECGs, and concomitant medication use. 
 
All safety analyses will be done for subjects receiving a single dose of MB-102. 
 
9.6.1 Treatment-Emergent Adverse Events 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). The 
system organ class and preferred term for each AE will be available, along with the verbatim 
reported term, event start and stop dates/times, seriousness, severity, relationship to 
treatment/device, action taken, and event outcome. SAEs will also be documented in a case 
narrative format.  
The overall numbers and percentages of subjects who experienced any treatment-emergent AEs 
(TEAEs) will be presented.  TEAEs will also be summarized at the subject level by system organ 
class and preferred term, and at the event level by system organ class/preferred term and severity 
and by system organ class/ preferred term and relationship to treatment. 
9.6.2 Physical Examinations/Limited Physical Assessments 
The results of physical examinations will be collected as adverse events if clinically significant 
or as medical history (if observations are noted prior to TGFR start).  Physical exam data will not 
be listed.  
9.6.3 Clinical Laboratory Assessments  
Clinical laboratory tests include clinical chemistry, hematology, urinalysis and coagulation 
parameters. Each parameter will be summarized using the descriptive statistics.  Details will be 
specified in the Statistical Analysis Plan (SAP).  Also, individual subject results will be assessed 
against an appropriate reference range if available.  The manifestation of any clinically 
significant abnormality that develops during the study will be reported as an AE. 
9.6.4 ECGs 
ECG data will be listed. Clinically significant findings will be noted as adverse events.  
9.6.5 Prior and Concomitant Therapies 
Concomitant medications administered within 3 days prior to MB-102 dose administration and 
through the follow-up study visit will be listed. Medications will be coded using the World 
Health Organization (WHO) drug dictionary. Data will be provided in one or more subject data 
listings. Concomitant non-drug therapies will be listed. 
9.7 
Determination of Sample Size 
For a P30 true value of 0.95, alpha of 0.025, performance goal of 85%, power of 90%, the one-
sided exact binomial test yields a sample size of 102. 


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9.8 
Missing Data 
Missing values will not be imputed.  
9.9 
Analysis Phases 
The global study will include 188 evaluable subjects. The US enrolment will have 140 evaluable 
subjects. Once the US sites have enrolled the targeted number of evaluable subjects, the US 
clinical sites will be closed. The US data alone may be used to support the market authorization 
and approval in the US.  The completed OUS dataset, if available will be included in the US 
application.  
 
10 Quality Assurance and Quality Control 
10.1 Training 
The clinical site will be trained on the protocol and study procedures. In addition, Sponsor 
representatives may be onsite during dosing procedures for the initial subjects at each site to 
assist sites with the operation of the MediBeacon® Transdermal GFR Measurement System.  
 
10.2 Audit and Inspection 
The study site and study documentation may be subject to quality assurance audits during the 
course of the study by the sponsor, or its nominated representative.  In addition, inspections may 
be conducted by regulatory authorities at their discretion. 
10.3 Monitoring 
Data for each subject will be recorded in an electronic data capture (EDC) system.   Data 
collection must be completed for each subject enrolled in the study.   
In accordance with GCP and International Conference on Harmonization (ICH) guidelines, the 
study monitor will conduct monitoring visits at regular intervals.  During the visits, the study 
monitor will perform the source document verification and verification that investigator’s 
obligations and all applicable regulatory requirements are being fulfilled.  The frequency of 
monitoring visits will be determined by the rate of subject recruitment.  
The investigator must permit the monitor, the IEC, the sponsor’s internal auditors and 
representatives from regulatory authorities direct access to all study-related documents and 
pertinent hospital or medical records, including direct access to electronic medical records for 
confirmation of data contained within the EDC system.  Subject confidentiality will be protected 
at all times. 


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10.4 Data Management and Coding 
MediBeacon or designee will be responsible for activities associated with the data management 
of this study.  This will include setting up a relevant database and data transfer mechanisms, 
along with appropriate validation of data and resolution of queries.  Data generated within this 
clinical study will be handled according to the relevant SOPs at MediBeacon or their designee. 
Study sites will enter data into a 21 CFR Part 11 compliant electronic data capture (EDC) system 
via a secure internet connection.  Data entered into the EDC system must be verifiable against 
source documents at the study site. Any changes to the data entered into EDC system will be 
recorded in the audit trail. 
Missing or inconsistent data will be queried via the EDC system to the investigator for 
clarification.  Subsequent modifications to the database will be documented. 
Fluorescent data from the TGFR System will be downloaded to hard media then transferred 
electronically to the Data Management designee via a secure data transfer process per the Study 
Procedure Manual.  
All medical terms (medical history, concomitant medications and adverse events) will be coded.  
10.5 Protocol Deviations 
The Investigator will not deviate from the clinical protocol without the prior written approval of 
MediBeacon except in medical emergencies or in unforeseen, isolated instances where minor 
changes are made that will not increase the subject’s risk or affect the validity of the study.  In 
medical emergencies, prior written approval for protocol deviations will not be required, but 
MediBeacon or their designee must be notified via telephone within 24 hours of occurrence. 
Prospective approval of protocol deviations to recruitment and enrolment criteria (also known as 
protocol waivers or exemptions) are not permitted.  
 
Major Protocol Deviation is a significant deviation from the protocol that may impact subject 
safety and/or affect the integrity of clinical trial data.  These may include, but are not limited to 
the following: 
 
• Improper or inadequate informed consent procedures 
• Subject did not meet eligibility criteria 
• Subject received prohibited concomitant medication(s) at any time during the trial with 
the exception of low dose aspirin (which would be considered a minor deviation) 
• A significant protocol required assessment or procedure was not performed per protocol 
requirements 
• Subject received incorrect study medications at any time during the trial  
• Significant departure from protocol-required dosing (dosing extravasation) 
• Subject developed criteria that required withdrawal from study protocol but was not 
withdrawn 
• The sensor was removed prior to measurement of a tGFR 


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A Minor Protocol Deviation is a deviation that does not impact subject safety and/or compromise 
the integrity of the clinical trial data.  
 
Subjects who experience a sensor dislodgement, a dosing or device issue or an extravasation 
(which would be considered a major deviation) will have PK sample collection discontinued and 
the sensor removed, but will be asked to remain in the study for safety follow-up (including dosing 
day safety assessments and the follow-up visit). The event that triggered the discontinuation of PK 
/ fluorescent data collection will be considered the protocol deviation, however missing PK sample 
collections will not need to be documented as individual protocol deviations.  
 
Deviations will be documented at the site and submitted to the IEC (as required) and the sponsor.  
 
10.6 Direct Data Collection 
Fluorescent measurements will be collected directly by the MediBeacon® Transdermal GFR 
Measurement System and will not appear on any available source documentation with the 
exception of the tGFR which will be recorded onto the site source document and transcribed into 
the EDC. The MediBeacon® Transdermal GFR Measurement System will be a closed system. 
11 Records / Retention 
Essential documents are those documents that individually and collectively permit evaluation of 
the study and quality of the data produced.  After completion of the study, all documents and 
data relating to the study will be kept in an orderly manner by the investigator in a secure study 
file. All study records will be available for inspection by the sponsor or its representatives, or a 
regulatory agency.  
 
Investigator files containing all records and reports of the investigation should be retained for a 
minimum of two (2) years (US) and 5 years (China) after the completion/ termination of the 
investigational study or the date that the records are no longer required for purposed of 
supporting a premarket approval application.  The Sponsor will determine with the 
investigational site as to this exact date so that the minimum two-year record retention can be 
accomplished.  Records may be discarded upon written notification by the Sponsor.  To avoid 
error, the Principal Investigator should contact MediBeacon, before the destruction of any 
records and reports pertaining to the study to ensure they no longer need to be retained. 
 
In addition, in accordance with the Clinical Trial Agreement, the Sponsor should be contacted if 
the Principal Investigator plans to leave the investigational site so that appropriate arrangements 
for file custodianship can be made. 
 
The following records must be maintained in designated study administrative files:  
• Clinical protocol and all amendments  
• Signed Investigator Agreement  
• Independent Ethics Committee Approval Letter(s)documenting review and approval of 
all protocols, amendments, IBs, ICFs, subject materials, etc.  


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• IEC-approved informed consent(s) (including any revisions)  
• Current CV for all Investigators and subinvestigators including evidence of current 
medical licensure  
• Financial Disclosure Form for all Investigators 
• Site Delegation of Authority Log 
• Correspondence relating to this study  
• Correspondence with the IEC  
• IEC membership list and/or assurance  
• Investigational site authorized study personnel signature list and delegation of authority 
• Device Instructions for Use  
• Lab certification, including a set of the lab’s normal range for tests performed  
• EDC Completion Guidelines  
• Subject Screening & Enrolment Log  
• Site Visit Log (e.g. for Monitor sign-in)  
• Site Training records  
• Investigational Device and Drug Accountability Logs  
• Reports (includes Adverse Event reports and final reports from Investigator and Sponsor) 
• Copy of all EC approved subject-related materials and/or study advertising materials  
 
The following records must be maintained for each subject enrolled in the study:  
• Signed subject consent forms  
• Electronic copy of final completed case reports (to be provided by the sponsor at the end 
of the study) 
• Jump drive with subject’s fluorescent data from the TGFR system 
• All lab work and testing results  
• Record of any complications, adverse events, device problems and/or malfunctions, with 
supporting documentation  
• Procedure reports, progress notes, physician and/or nursing notes, and subject office files 
• Records pertaining to subject deaths  
 
12 Ethics 
12.1 Independent Ethics Committee (IEC) 
Before initiation of the study at each study site, the protocol, all protocol amendments, 
Investigators Brochure, the ICF, the subject information sheet and any other relevant study 
documentation will be submitted to the appropriate IEC.  Written approval of the study and all 
relevant study information must be obtained before the study site can be initiated or the study 
device is released to the investigator.  Any necessary extensions or renewals of IEC approval 
must be obtained, in particular, for changes to the study such as modification of the protocol, the 
ICF, the written information provided to subjects, and/or other procedures. 
The investigator will report promptly to the IEC any new information that may adversely affect 
the safety of the subjects or the conduct of the study.  The investigator will submit written 


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summaries of the study status to the IEC annually, or more frequently if requested by the IEC.  
On completion of the study, the site will notify the IEC that the study has ended. 
12.2 Ethical Conduct of the Study 
The ICH guidelines for current GCP (ICH R2, 2016), the National Medical Products 
Administration Good Clinical Practice (NMPA GCP), the Code of Federal Regulations Title 21 
CFR Parts 812, 11, 50, 54 and 56 and ISO 14155: 2020(E) Clinical Investigation of Medical 
Devices for Human Subjects – Good Clinical Practice, as well as the ethical principles defined 
by the World Medical Association Declaration of Helsinki, and the requirements of national 
device and data protection laws and other applicable regulatory requirements will be followed. 
  
12.3 Subject Information and Consent 
The investigator is responsible for ensuring that no subject undergoes any study related 
examination or activity before that subject has given written informed consent to participate in 
the study.  The written consent must be given by the subject, after detailed information about the 
study has been given and in accordance with any national provisions on the protection of clinical 
study subjects.  The verbal explanation will cover all the elements specified in the written 
information provided for the subject. 
The investigator or designated personnel will inform the subject of the objectives, methods, 
anticipated benefits, and potential risks and inconveniences of the study.  The subject should be 
given every opportunity to ask for clarification of any points he/she does not understand and, if 
necessary, ask for more information.  At the end of the interview, the subject will be given time 
to consider the study, if this is required, or if the subject requests more time.  Subjects and/or 
legally authorized representatives will be required to sign and date the ICF.  After signatures are 
obtained, a copy will be provided to the subject, and a signed ICF will be kept and archived by 
the investigator in the investigator’s study file for possible inspection by regulatory authorities, 
the IEC, or sponsor. 
It should be emphasized to the subject that he/she is at liberty to withdraw from the study at any 
time, without penalty or loss of benefits to which the subject is otherwise entitled.  Subjects who 
refuse to give or who withdraw written informed consent should not be included or continue in 
the study. 
12.4 Financing and Insurance 
This clinical trial will be sponsored by MediBeacon and its conduct will be governed under an 
executed Clinical Trial Agreement that will define the coverage of costs associated with study 
implementation by the trial site. MediBeacon will maintain appropriate clinical trial insurance at 
limits agreed upon in the agreement.  
12.5 Subject Confidentiality  
All personal data collected and processed for the purposes of this study should be managed by 
the investigator and his/her staff with adequate precautions to ensure confidentiality of those 


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data, in accordance with applicable national and/or local laws and regulations on personal data 
protection. 
Monitors, auditors, and other authorized agents of the sponsor and/or its designee, the ethics 
committees approving this research, and any other applicable regulatory agency(ies), will be 
granted direct access to the study subjects’ original medical records (including electronic medical 
records) for verification of clinical study procedures and/or data, without violating the 
confidentiality of the subjects to the extent permitted by the law and regulations.  In any 
presentations of the results of this study or in publications, the subjects’ identity will remain 
confidential. 
12.6 Reporting and Publication, Including Archiving 
Publication of all study results in the form of abstracts, manuscripts, presentations, posters, etc. 
will be developed in accordance with the Clinical Trial Agreement.  
 
 


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13 References 
Agarwal R. Ambulatory GFR measurement with cold iothalamate in adults with chronic kidney 
disease. Am J Kidney Dis. 2003 Apr; 41(4): 752-9. 
 
Endre ZH, Pickering JW, Walker RJ.  Clearance and beyond: the complementary roles of GFR 
measurement and injury biomarkers in acute kidney injury (AKI). Am J Physiol Renal Physiol 
2011 301: F697-F707. 
 
Erley CM, Bader BD, Berger ED, et al. Plasma clearance of iodine contrast media as a measure 
of glomerular filtration rate in critically ill patients. Crit Care Med. 2001 Aug; 29(8):1544-50. 
 
Fitzpatrick TB. Soleil et peau [Sun and skin]. Journal de Médecine Esthétique. 1975; 2:33-34 
 
Kidney Disease Statistics for the United States. 
http://kidney.niddk.nih.gov/kudiseases/pubs/kustats/index.aspx#13 
 
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers 
P, Van Lente F, Greene T, Coresh J; CKD-EPI (Chronic Kidney Disease Epidemiology 
Collaboration). A New Equation to Estimate Glomerular Filtration Rate. Ann Intern Med. 2009 
May 5;150(9):604-12. 
 
National Institutes of Health Web Site (Bethesda MD, 08 October 2008), “Annual report targets 
chronic kidney disease in the United States,” http://www.nih.gov/news/health/oct2008/niddk-
08.htm 
 
Stevens, LA and Levey, AS. Measured GFR as a Confirmatory Test for Estimated GFR. 2009. J. 
Am Soc Nephrol 20: 2305-2313.  
 
Stevens LA, Coresh J, Greene T, Levey AS. Assessing kidney function--measured and estimated 
glomerular filtration rate. N Engl J Med. 2006 Jun 8;354 (23):2473-83. 
 
Verhave JC, Fesler P, Ribstein J, du Cailar G, Mimran A. Estimation of renal function in 
subjects with normal serum creatinine levels: influence of age and body mass index. Am J 
Kidney Dis. 2005 Aug; 46(2): 233-41. 
 


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14 Appendix A Fitzpatrick Scale  
The Fitzpatrick Scale should be used against the skin on the upper chest (on areas considered for 
sensor placement).  
 
 
Source: Fitzpatrick, 1975 
 
 
 


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MediBeacon® Transdermal GFR Measurement System 
Protocol No.  100-003 
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15 Appendix B Clinical Research Sites 
 
Site 
Number 
Institution 
PI Name 
Address 
Country 
401 
Nucleus Network 
George C. Canas, MD 
(Internal medicine / 
nephrology) 
 
1000 Westgate Dr. Suite 149, St. 
Paul, MN 55114 
 
USA 
402 
Research by 
Design, LLC 
 
Paul W. Crawford, 
MD, FACP, FASN 
(Internal medicine / 
nephrology) 
 
1080 South Western Avenue, Suite 
201, Chicago, IL 60643 
 
USA 
403 
Carolina Phase I 
Research 
Matthew Hong, MD 
(Family medicine) 
 
3100 Duraleigh Road, Suite 303 & 
304, Raleigh, NC 27612 
 
USA 
404 
Velocity Clinical 
Research 
 
Margaret Chang, MD 
(Family medicine) 
 
1410 S. Ridgewood Ave., 
Edgewater, FL 32132 
 
USA 
406 
Endeavor Clinical 
Trials, LLC 
 
Hernan Alfonso 
Salazar, DO 
(Family medicine) 
 
9150 Huebner Road, Ste. 345, San 
Antonio, Tx 78240 
 
USA 
412 
Peking University 
First Hospital 
Ming-hui Zhao, MD 
(nephrology) 
Yimin Cui 
(Pharmacist) 
 
No. 8 Xi Shi Ku Street, Xicheng 
District, Beijing, 100034 
 
China 
413 
Affiliated Hospital 
of Xuzhou 
Medical 
University 
Dong Sun, MD 
(nephrology) 
 
No. 99, Huaihai West Road, Xuzhou 
City, Jiangsu Province, 2210029 
 
China 
414 
Huashan Hospital 
Affiliated to 
Fudan University 
 
Jun Xue, MD 
(nephrology) 
Jing Zhang 
 
No. 12, Wulumugi Middle Road, 
Shanghai, 200040 
 
China 
 
Site Undergoing Qualification 
 
Site 
Number 
Institution 
PI Name 
Address 
Country 
415 
West China 
Hospital of 
Sichuan 
University 
Ping Feng MD 
(nephrology) 
 
#37 Guoxue Alley, Wuhou District, 
Chengdu, Sichuan Province 
 
China 
 
 


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MediBeacon® Transdermal GFR Measurement System 
Protocol No.  100-003 
V 4.0 
 
 
20 Sep 2022 
CONFIDENTIAL INFORMATION  
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Investigator Signature Page 
 
Protocol Title: 
A Pivotal, Open Label, Multi-Center, Safety and Pharmacokinetic 
Study of MB-102 and the Use of the MediBeacon® Transdermal 
GFR Measurement System in Normal and Renal Compromised 
Subjects for the Evaluation of Kidney Function 
Protocol Number: 
100-003  
Confidentiality and cGCP Compliance Statement 
I, the undersigned, have reviewed this protocol, including appendices and other documents that 
may be considered part of the investigational plan, and I will conduct the study as described in 
compliance with this protocol, GCP, the ethical principles defined by the World Medical 
Association Declaration of Helsinki (2013), applicable regional regulations and relevant ICH 
guidelines. 
Once the protocol has been approved by the IEC, I will not modify this protocol without 
obtaining prior approval of the MediBeacon Inc. and of the IEC.  I will submit the protocol 
modifications and/or any ICF modifications to MediBeacon Inc. and IEC, and approval will be 
obtained before any modifications are implemented. 
I understand that all information obtained during the conduct of the study with regard to the 
subjects’ state of health will be regarded as confidential.  No subjects’ names will be disclosed.  
All subjects will be identified by assigned numbers on all eCRFs, laboratory samples or source 
documents forwarded to the sponsor.  Clinical information may be reviewed by the sponsor or its 
agents or regulatory agencies.  Agreement must be obtained from the subject before disclosure of 
subject information to a third party. 
I will oversee all aspects of study conduct and will only appropriately delegate responsibilities to 
adequately qualified and trained staff. I will oversee the completion of source data collection 
such that all data collected for the study may be substantiated against accurate source medical 
records.  
Information developed in this clinical study may be disclosed by MediBeacon Inc. to other 
clinical investigators, regulatory agencies, or other health authority or government agencies as 
required. 
Investigator Signature 
Date 
 
 
 


MediBeacon Inc. 
MediBeacon® Transdermal GFR Measurement System 
Protocol No.  100-003 
V 4.0 
 
 
20 Sep 2022 
CONFIDENTIAL INFORMATION  
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16 Signature of the Sponsor’s Responsible Officers 
 
 
16.1 Chief Scientific Officer 
 
 
__________________________________________  
 
__________ 
Richard Dorshow, PhD 
 
 
 
 
 
Date 
 
MediBeacon Inc.  
USA 
 
 
16.2 Medical Officer 
 
 
__________________________________________  
 
__________ 
Dr. Joseph Pierro 
 
 
 
 
 
 
Date 
 
MediBeacon Inc.  
USA 
 
Phone:  +1 636-484-3168 (Central Time; United States) 
 
 
425 N. New Ballas Road 
St. Louis, MO 63141 
425 N. New Ballas Road 
St. Louis, MO 63141 


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MediBeacon® Transdermal GFR Measurement System 
Protocol No.  100-003 
V 4.0 
 
 
20 Sep 2022 
CONFIDENTIAL INFORMATION  
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Appendix I  Protocol 100-003 Supplemental Justifications