Clinical trial NCT05777174
Conditions: Kidney Diseases Kidney Injury Kidney Failure
Keywords: Glomerular Filtration Rate Relmapirazin Iohexol Pharmacokinetics Transdermal fluorescence detection MB-102
Sponsor: MediBeacon
Start date: 2023-03-20; Completion date: 2024-04-15
Enrollment: 149 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 GFR (nGFR) using MB-102 (relmapirazin) as the fluorescent compound. Adults with kidney function ranging from estimated glomerular filtration rate (eGFR) \<120 to \>15 mL/min/1.73 m2 and 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 assessed GFR using the MediBeacon Transdermal GFR System with the TGFR reusable sensor with disposable adhesive ring was comparable to the measured MB-102 plasma GFR.
* To evaluate the safety and effectiveness of the MediBeacon Transdermal GFR System and the TGFR reusable sensor with disposable adhesive ring for the non-invasive transdermal fluorescence detection of MB-102 in participants

On dosing day, participants had the TGFR reusable sensor with disposable adhesive ring placed on their chest, and the MediBeacon Transdermal GFR System initiated to collect background fluorescence. When this was completed, participants then received a single dose of MB-102. Blood samples were collected and fluorescent measurements were taken over a 12- or 24-hour (or longer) period, depending upon enrollment group. For those with significant renal compromise, fluorescent measurements were continued until the sensor no longer detected MB-102 in the body. 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.

Detailed description:

Arms: arm 1: A TGFR Reusable Sensor with Disposable Adhesive Ring was placed on participants' chests at least 15 minutes prior to dosing on treatment day, and the MediBeacon Transdermal GFR System was initiated to collect background fluorescence. After the collection of background fluorescence, a single dose of MB-102 (130 mg) was administered intravenously to participants with estimated glomerular filtration rate (eGFR) eGFR ≥ 70 mL/min/1.73 m\^2. Approximately half of the participants had Fitzpatrick Scale Type I, II or III, and half had Type IV, V and VI skin color type. Blood samples and fluorescent measurements were collected over 12 hours. arm 2: A TGFR Reusable Sensor with Disposable Adhesive Ring was placed on participants' chests at least 15 minutes prior to dosing on treatment day, and the MediBeacon Transdermal GFR System was initiated to collect background fluorescence. After the collection of background fluorescence, a single dose of MB-102 (130 mg) was administered intravenously to participants with estimated glomerular filtration rate eGFR \< 70 mL/min/1.73 m\^2. Approximately half of the participants had Fitzpatrick Scale Type I, II or III, and half had Type IV, V and VI skin color type. 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 the TGFR reusable sensor with disposable adhesive ring placed on their chest, and the MediBeacon® Transdermal GFR Measurement System was initiated to collect background fluorescence. When this was completed, participants received a single dose of MB-102. Fluorescent measurements were collected for 12-24 hours. For those with significant renal compromise, fluorescent measurements were continued until the sensor no longer detected MB-102 in the body.

Protocol documents:
Prot_000.pdf: 
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   MediBeacon® Transdermal GFR Measurement System 
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NCT05777174 
 
CLINICAL STUDY PROTOCOL 
An Open Label, Multi-Center, Safety and Pharmacokinetic Bridging Study of MB-102 
(Relmapirazin) and the Use of the MediBeacon® Transdermal GFR Measurement System 
using the TGFR Reusable Sensor with Disposable Adhesive Ring 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), 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: 
100-201 
Investigational Product: 
MB-102 (Relmapirazin) / MediBeacon® Transdermal GFR 
Measurement System 
Phase: 
Bridging 
Sponsor: 
MediBeacon Inc. 
425 N. New Ballas Road 
St. Louis, MO 63141 
USA 
Date of Protocol 
2 April 2024  
Version of Protocol: 
Version 5.1 
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: 
100-201 
Title: 
An Open Label, Multi-Center, Safety and Pharmacokinetic Bridging Study of 
MB-102 (Relmapirazin) and the Use of the MediBeacon® Transdermal GFR 
Measurement System using the TGFR Reusable Sensor with Disposable 
Adhesive Ring 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 5 investigational sites in the US.  
Phase: 
Bridging 
Objectives: 
• To establish that the MB-102 transdermal fluorescence measured GFR 
using the MediBeacon® Transdermal GFR Measurement System with the 
TGFR reusable sensor with disposable adhesive ring is comparable to the 
measured MB-102 plasma GFR   
• To evaluate the safety and effectiveness of the MediBeacon® Transdermal 
GFR Measurement System and the TGFR reusable sensor with disposable 
adhesive ring for the non-invasive transdermal fluorescence detection of 
MB-102 in subjects 
Study Design: 
Multi-center, bridging, adaptive open-label pharmacokinetic study comparing 
transdermal measured GFR (tGFR) to plasma-derived indexed GFR (nGFR).  
 
As the reusable sensor is new, an adaptive trial design will be employed.  
1. Run-in cohort of up to 30 evaluable subjects will commence the 
study. Additional Run-in subjects may be enrolled at new clinical 
sites to ensure protocol compliance. Run-in subject data will be 
considered tuning data.  
2. Validation Cohort 1 (approximately 20 evaluable subjects) will be 
used to confirm final algorithm selection. Validation Cohort 1 subject 
data will be considered tuning data.  
3. Validation Cohort 2 (approximately 75 evaluable subjects) will be 
analyzed in an interim analysis to compare results against the primary 
endpoint specification. If the primary endpoint has been achieved, the 
study will be terminated. If not, the trial will be continued.  
4. Validation Cohort 3 (approximately 65 evaluable subjects) will be 
enrolled in the event the interim analysis did not meet the primary 
outcome measure. Final analysis will be of the 140 evaluable 
subjects.  
Number of Treated 
Subjects:  
Up to 240 subjects are planned for enrollment. The population will be split into 
stratums in accordance with screening eGFR measured by the CKD-EPI 
equation (pre-2021): 
• 
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 will be Fitzpatrick 
skin scale (FSS) I-III and 50% of subjects will have FSS IV-VI. Subjects will be 


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enrolled across a spectrum of both eGFR (<120 - >15 mL/min/1.73 m2) and FSS. 
An adaptive trial design will be employed. A Run-in cohort of 30 evaluable 
subjects and Validation Cohort 1 of up to 20 evaluable subjects with a mixture of 
eGFR and FSS will enroll to provide tuning data and allow algorithm 
finalization. This will be followed by up to 140 additional evaluable subjects 
enrolled: after 75 evaluable subjects in Validation 2 Cohort have been 
completed, an interim analysis will be conducted to compare results against the 
primary endpoint specification. If the primary endpoint has been achieved, the 
study will be terminated. If not, the trial will be continued with Validation Cohort 3 
until 140 evaluable subjects are enrolled. 
 
Subjects with incomplete assessments or major protocol deviations may be 
replaced. Thus, a maximum of 240 subjects may be enrolled.  
Treatment: 
Eligible subjects in stratums 1 and 2 will receive a single 130 mg dose of MB-
102. Subjects who enroll in the Run-in and/or Validation 1 Cohort may repeat 
the study.  
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 or longer period. 
Study Duration per 
Subject: 
Screening period: up to 28 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 for COVID-19 at the time of dosing 
2. Recent donation or loss of blood or plasma: 100 mL to 499 mL 


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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 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. Use of tanning sprays, tanning products etc. on the upper chest within 
2 weeks of dosing day 
10. Use make-up, lotions, Vaseline or other products on the area of the 
upper chest on the day prior to or the day of dosing 
11. 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.  
12. Currently receiving dialysis 
13. Currently anuric 
14. Subjects with positive serum pregnancy test 
15. 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. 


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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 
Prior data demonstrated 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:  Q1 2023 
Planned End of Study:  Q2 2024 
 
 
 
 


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


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Table of Contents 
1 
Synopsis ............................................................................................................................................ 2 
2 
List of Abbreviations and Definition of Terms .................................................................. 10 
3 
Introduction .................................................................................................................................. 12 
3.1 
Background ........................................................................................................................... 12 
3.2 
Nonclinical Data ................................................................................................................... 13 
3.3 
Clinical Data .......................................................................................................................... 13 
3.4 
Study Rationale .................................................................................................................... 14 
4 
Study Objectives .......................................................................................................................... 15 
5 
Investigational Plan.................................................................................................................... 15 
5.1 
Overall Study Design and Plan........................................................................................ 15 
5.2 
Overview of Study Procedures ....................................................................................... 16 
5.3 
Discussion of Study Design .............................................................................................. 17 
5.4 
Selection of Study Population ......................................................................................... 17 
5.4.1 
Number of Planned Evaluable Subjects .......................................................................... 17 
5.4.2 
Inclusion Criteria ..................................................................................................................... 18 
5.4.3 
Exclusion Criteria ..................................................................................................................... 18 
5.4.4 
Removal of Subjects from Therapy or Assessments .................................................. 19 
5.4.5 
Replacement of Subjects ....................................................................................................... 19 
5.5 
Investigational Device ....................................................................................................... 20 
5.5.1 
Premature Dislodgment of a TGFR Sensor from the Skin ........................................ 20 
5.5.2 
Sensor Detachment from the TGFR Monitor ................................................................. 21 
5.5.3 
Identity of Investigational Device ...................................................................................... 21 
5.5.4 
Labeling ....................................................................................................................................... 21 
5.5.5 
Storage, Supply and Return/Destruction ....................................................................... 21 
5.5.6 
Device Accountability ............................................................................................................. 22 
5.6 
Investigational Drug ........................................................................................................... 22 
5.6.1 
Stability of Drug Product ...................................................................................................... 22 
5.6.2 
Identity of Investigational Drug ......................................................................................... 24 
5.6.3 
Investigational Drug Labeling ............................................................................................. 24 
5.6.4 
Investigational Drug Storage, Supply, Return/Destruction .................................... 24 
5.6.5 
Investigational Drug Accountability ................................................................................. 24 
5.7 
Contact Procedures for Medical Issues Requiring Immediate Attention ........ 24 
5.8 
Prior and Concomitant Therapy .................................................................................... 25 
5.8.1 
Prohibited Concomitant Medications .............................................................................. 25 
5.8.2 
Stable Use of Immunosuppressive Medications .......................................................... 25 
6 
Study Procedures ........................................................................................................................ 26 
6.1 
Schedule of Assessments and Procedures .................................................................. 26 
6.2 
Pre-screening ....................................................................................................................... 29 
6.3 
Screening ................................................................................................................................ 29 
6.4 
Night before Dosing Day ................................................................................................... 29 
6.5 
Dosing Day: Baseline Assessments ............................................................................... 30 
6.6 
MB-102 Dosing ..................................................................................................................... 31 


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6.7 
Post-dose Study Procedures ............................................................................................ 32 
6.7.1 
Stratum 1 (12 hour follow-up) ........................................................................................... 32 
6.8 
Stratum 2 (24 hour follow-up) ....................................................................................... 33 
6.9 
Sensor Cleaning and Disinfection .................................................................................. 35 
6.9.1 
Sensor Cleaning ........................................................................................................................ 35 
6.9.2 
Sensor Disinfection ................................................................................................................. 35 
6.10 
Follow-up Visit ................................................................................................................. 35 
6.11 
Early Withdrawal / Unscheduled Visits .................................................................. 36 
6.12 
Repeat Subjects ................................................................................................................ 36 
7 
Efficacy and Safety Variables .................................................................................................. 37 
7.1 
Efficacy and Safety Measurements Assessed and Flow Chart .............................. 37 
7.1.1 
Efficacy Assessments .............................................................................................................. 37 
7.1.2 
Safety Assessments ................................................................................................................. 37 
7.2 
Safety Review Committee ................................................................................................. 44 
8 
Information for the Investigator: Potential Risks of the Device ................................. 44 
8.1 
Investigational Drug ........................................................................................................... 44 
8.2 
MediBeacon® Transdermal GFR Measurement System ........................................ 46 
8.2.1 
Adhesive Clip ............................................................................................................................. 46 
8.3 
Trial Procedures .................................................................................................................. 46 
8.3.1 
Dose Extravasations ............................................................................................................... 46 
9 
Statistical Methods...................................................................................................................... 46 
9.1 
Overview ................................................................................................................................ 46 
9.2 
Analysis Populations .......................................................................................................... 46 
9.3 
Subject Disposition ............................................................................................................. 47 
9.4 
Plasma Pharmacokinetic Analyses ............................................................................... 47 
9.5 
Primary Endpoint Analysis .............................................................................................. 48 
9.6 
Safety Analyses ..................................................................................................................... 49 
9.6.1 
Treatment-Emergent Adverse Events ............................................................................. 49 
9.6.2 
Physical Examinations/Limited Physical Assessments ............................................ 49 
9.6.3 
Clinical Laboratory Assessments ....................................................................................... 49 
9.6.4 
ECGs .............................................................................................................................................. 50 
9.6.5 
Prior and Concomitant Therapies ..................................................................................... 50 
9.7 
Determination of Sample Size ......................................................................................... 50 
9.8 
Missing Data .......................................................................................................................... 50 
10 
Quality Assurance and Quality Control ........................................................................... 50 
10.1 
Training .............................................................................................................................. 50 
10.2 
Audit and Inspection ...................................................................................................... 50 
10.3 
Monitoring ......................................................................................................................... 50 
10.4 
Data Management and Coding .................................................................................... 51 
10.5 
Protocol Deviations ........................................................................................................ 51 
10.6 
Direct Data Collection .................................................................................................... 52 
11 
Records / Retention ............................................................................................................... 52 
12 
Ethics ........................................................................................................................................... 54 


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12.1 
Independent Ethics Committee (IEC) ....................................................................... 54 
12.2 
Ethical Conduct of the Study ........................................................................................ 54 
12.3 
Subject Information and Consent .............................................................................. 54 
12.4 
Financing and Insurance .............................................................................................. 55 
12.5 
Subject Confidentiality .................................................................................................. 55 
12.6 
Reporting and Publication, Including Archiving .................................................. 55 
13 
References ................................................................................................................................. 56 
14 
Appendix A Fitzpatrick Scale .............................................................................................. 57 
Investigator Signature Page ............................................................................................................ 58 
15 
Signature of the Sponsor’s Responsible Officers .......................................................... 59 
15.1 
Chief Scientific Officer ................................................................................................... 59 
15.2 
Medical Officer ................................................................................................................. 59 
 
 
 


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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 
CrCl 
Creatinine clearance 
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 
GFR 
Glomerular filtration rate 
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 
IV 
Intravenous 
K 
Potassium 
K2EDTA 
Potassium ethylenediaminetetraacetic acid 
MedDRA 
Medical Dictionary for Regulatory Activities 
mL 
Milliliter 
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 (now TGFR) 


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OTC 
Over the counter 
PA 
Physical Assessment (limited) 
PE 
Physical exam (full) 
PI 
Principal Investigator  
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 
MediBeacon® Transdermal GFR Measurement System 
UADE 
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.  
 
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.  Collection and 
processing of the data is performed within the monitor.  The device monitor displays the TGFR 
data.    
 
An initial algorithm had been developed from the Pilot 2 study data to convert measured 
fluorescence half-life data to GFR. Additional Pilot 2 study groups refined this algorithm for 
efficacy and robustness, as well as adding to the algorithm database. This algorithm was further 
tested in the Pivotal Trial 100-003 using the single use Brilliance sensor.  
 
The TGFR reusable sensor with disposable adhesive ring is based off of the single use Brilliance 
sensor tested in protocol 100-003. This sensor is revised for serviceability by the end user for 
reuse of up to 100 times.  The sensor base can be released by a clipping mechanism, facilitating 
easy reapplication of a new disposable adhesive ring. The sensor itself can be cleaned and 
disinfected between uses.  
 
This sensor has the same light source, detector, and senses tracer and endogenous 
autofluorescence in the same way as the Brilliance sensor. The sensor interfaces and operates 
with the Brilliance monitor in the same manner as the original single use Brilliance sensor.  
 
 
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 29 nonclinical studies performed 
on MB-102 is found in the Investigator’s Brochure.  
 
3.3 
Clinical Data 
A total of 586 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) and a completed Pivotal trial and 
including subjects enrolled in this trial as of the date of this protocol amendment. The Pilot 1 


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studies enrolled subjects with an eGFR indicating normal renal function. The Pilot 2 study and 
pivotal trial 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 608 subjects. A total of 95 subjects (16.0% 
of the total population across 6 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, clinical laboratory 
results, 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 / 7 mL (n=282) 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 
MediBeacon® Transdermal GFR Measurement System (TGFR) 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 140 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.  
 
3.4 
Study Rationale 
This clinical study will evaluate the use of MB-102 and the MediBeacon® Transdermal GFR 


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Measurement System using the TGFR reusable sensor with disposable adhesive ring for the 
purpose of bridging the marketing application with a more useable sensor.   
 
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 with the TGFR reusable sensor with 
disposable adhesive ring is comparable to the measured MB-102 plasma GFR   
• To evaluate the safety and effectiveness of the MediBeacon® Transdermal GFR 
Measurement System with the TGFR reusable sensor with disposable adhesive ring for the 
non-invasive transdermal fluorescence detection of MB-102 in subjects 
 
5 
Investigational Plan 
5.1 
Overall Study Design and Plan 
Protocol 100-201 is a multi-center, open-label, adaptive bridging investigation studying the 
safety and pharmacokinetics of MB-102 and the use of the MediBeacon® Transdermal GFR 
Measurement System with the TGFR reusable sensor with disposable adhesive ring in normal 
and compromised renal function subjects with different skin color types comparing tGFR to 
plasma derived indexed GFR (nGFR).  
 
Up to 240 subjects are planned to be dosed.  The population will be split into stratums in 
accordance with eGFR by the CKD-EPI equation (pre- 2021) (Levey et al., 2009). The study will 
enroll into 4 consecutive cohorts:  
 
1. A Run-in Cohort of up to 30 evaluable subjects will be enrolled to test monitor algorithm 
settings with the TGFR reusable sensor with disposable adhesive ring. Additional Run-in 
subjects may be enrolled at new clinical sites to ensure protocol compliance. Run-in subject 
data will be considered tuning data.  
 
The following will be enrolled into the Run-in cohort: 
• At least 5 subjects will be enrolled in Stratum 2 
• At least 4 subjects in each of the FSS I-II; III-IV and V-VI 
 
Clinical sites not yet active on the trial may also be required to participate in the Run-in Cohort 
in order to demonstrate protocol compliance prior to participating in the Validation 2 Cohort or 
Validation 3 Cohort.  
 
2. Validation Cohort 1 (approximately 20 evaluable subjects) will be used to confirm final 
algorithm selection. Validation Cohort 1 subject data will be considered tuning data.  
 
3. Validation Cohort 2 (approximately 75 evaluable subjects) will be analysed in an interim 
analysis to compare results against the primary endpoint specification. If the primary 
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4. Validation Cohort 3 (approximately 65 evaluable subjects) will be enrolled in the event the 
interim analysis did not meet the primary outcome measure. Final analysis will be of the 140 
evaluable subjects. 
 
Subjects will be screened, FSS determined by Mexameter, and if deemed eligible, will be 
enrolled. On treatment day, subjects will have the TGFR reusable sensor with disposable 
adhesive ring 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 or 24 
hour (or longer) period (depending upon enrolment strata).  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 monitoring 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 considered not evaluable  (major protocol deviations, 
extravasations, etc.) may be replaced. Up to 240 total subjects may be enrolled.  
 
 
5.2 
Overview of Study Procedures 
Potential subjects will be screened for eligibility within 28 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, 
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.  
 


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5.3 
Discussion of Study Design 
The study is designed to validate the performance of the TGFR Measurement System using the 
TGFR reusable sensor with disposable adhesive ring.  
5.4 
Selection of Study Population 
5.4.1 Number of Planned Evaluable Subjects  
The study may enroll up to 240 subjects across 4 consecutive cohorts in order to obtain 140 
evaluable subjects.  Unevaluable subjects are those with major protocol deviations that impact 
efficacy (such as no reported average session tGFR, premature sensor removal, extravasations, 
etc.). The cohorts include:  
 
1. Run-in Cohort (approximately 30 subjects) 
2. Validation Cohort 1 (approximately 20 subjects) 
3. Validation Cohort 2 (approximately 75 evaluable subjects) 
4. Validation Cohort 3 (approximately 65 evaluable subjects) 
 
After 75 evaluable subjects in the Validation 2 Cohort have been completed, an interim analysis 
will be conducted to compare results against the primary endpoint specification. If the primary 
endpoint has been achieved, the study will be terminated. If not, the trial will continue with 
enrolment into Validation Cohort 3 until 140 evaluable subjects are enrolled. 
 
The population will be split into stratums in accordance with eGFR by the CKD-EPI equation 
(pre-2021): 
• 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 > 120 mL/min/1.73 m2 or < 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 at least 6 subjects enrolled:  
• > 90 - <120 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  
 
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 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 6 subjects.   


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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 for COVID-19 at the time of dosing 
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 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 


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9. Use of tanning sprays, tanning products etc. on the upper chest within 2 weeks of 
dosing day 
10. Use make-up, lotions, Vaseline or other products on the area of the upper chest on the 
day prior to or the day of dosing 
11. 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.  
12. Currently receiving dialysis 
13. Currently anuric 
14. Positive serum pregnancy test 
15. 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 TGFR reusable sensor and disposable adhesive ring 
for all enrolled subjects. One sensor will be attached 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 TGFR reusable sensor and disposable adhesive ring is revised for serviceability by the end 
user for reuse of up to 100 times. The sensor base can be released by a clipping mechanism, 
facilitating easy reapplication of a new disposable adhesive ring.  
 
The sensor itself must be cleaned and sanitized between uses. To clean, the sensor is wiped with 
a damp cloth wetted with a mild detergent mixed with a 20:1 ratio of water to detergent. To 
sanitize, the sensor should be wiped with a 70% alcohol wipe or an equivalent lint free wipe 
wetted with a 70% isopropyl alcohol solution. This sensor has the same light source, detector, 
and senses tracer and endogenous autofluorescence in the same way as the Brilliance sensor. The 
sensor interfaces and operates with the Brilliance monitor in the same manner as the Brilliance 
sensor.  
 
The only parts of the MediBeacon® TGFR reusable sensor and disposable adhesive ring 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 self-adhesive pad is similar to 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 or exceeding 
24 hours for Stratum 2 subjects.  
 
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.  
 
 


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5.5.2 Sensor Detachment from the TGFR Monitor 
If a sensor becomes detached even temporarily from the TGFR monitor, there will be loss of data 
for the period of time until the sensor is reattached.  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. 
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 (disposable sensor ring and adhesive materials) 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 will be returned to the Sponsor at the conclusion of the trial. 
Instructions for return will be included in the Study Procedure Manual.  
 
 


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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 
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. 
 


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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 five year (and final) 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 three year time point. 
 
Three batches of API have been manufactured at the commercial manufacturing facility (Regis 
Technologies) and stability has been initiated and is on-going.  Results for all three lots 
(including Lot M20213-980-11) show negligible degradation in active ingredient purity and 
essentially no change in the total purity amount with respect to the zero-time parameters at the 
twelve-month time point. 
  
The samples for long term stability testing of registration Lots M24213-980-11, M24218-975-9, 
and M24241-978-6 were stored at 25°C ± 2°C, 60% R.H. ± 5%, relative humidity and 
accelerated stability stored at 40°C ± 2°C, 75% R.H. ± 5%.  
 
 
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 
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.  
 
Stability testing of the GMP formulated product Batch MLF001 (registration batch manufactured 
by Curia in Albuquerque, New Mexico) from drug substance batch M24213-980-11 evaluated 
physical, chemical, and microbiological attributes at designated time points. At the nine month 


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time point, all samples (upright and inverted) stored at the 5⁰C ± 3⁰C storage conditions have met 
specifications.  
 
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 
Lot No: MLF001 
Mfg. Date: 06/15/2022 
Store at 2°C - 8°C 
Caution: New Drug – Limited by Federal (United States) law to Investigational use.  
Manufactured for MediBeacon 
 
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: 
 


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Joseph Pierro, MD (United States) 
Cell: +1 636-484-3168 
 
 
Email: jpierro@medibeacon.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 with the exception of 
low-dose (81 mg or less) aspirin. 
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 dosing.  
 
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 
 
 
 
 


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6 
Study Procedures 
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 
 
 
28 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 
X 
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 using the Mexameter device.  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) will be conducted prior to 
dosing. (Limited PA includes assessments of HEENT, respiratory, cardiovascular, abdominal systems). A full or limited exam will be 
conducted at the follow-up visit.  
d. Vital signs include blood pressure, respiration rate, pulse 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; height and 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 baseline 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 and 720 (±5 min) 
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) using the Mexameter 
measurement. 


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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.  The Mexameter 
will be used to determine FSS type.  
6.3 
Screening  
Screening will occur within 28 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  
• Collect height and weight measurements; ensure subjects are not wearing shoes 
• 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 (FSS) Color Type by examining the upper chest 
(locations for possible sensor placement)) and perform Mexameter measurements to 
determine the FSS.  Collect 3 melanin and erythema measurements to obtain an average 
value and use the following to determine the FSS value:  
o FSS type I:  
Mexameter melanin range:                   0 - 100  
o FSS type II:  Mexameter melanin range: 
 
100 - 150  
o FSS type III:  Mexameter melanin range: 
 
150 - 250  
o FSS type IV:  Mexameter melanin range: 
 
250 - 350  
o FSS type V:  Mexameter melanin range: 
 
350- 450  
o FSS type VI:  Mexameter melanin range:              450 – 999 
 
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:  


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• Perform COVID testing  
• 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 
• 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 and height (BSA and BMI will be calculated based on dosing 
day height and baseline weight measurements). Ensure subjects are not wearing shoes 
and only light clothing.   
• 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.  
• Calibrate the Mexameter prior to use in accordance with instructions in the Study 
Procedure Manual. Record calibration results.  


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• Obtain melanin and erythema measurements with the Mexameter at the location of sensor 
placement (Section 7.1.2.11). Measurements should be reviewed, and the values should 
be within range of each other.  Measurements with significantly disparate values should 
be repeated as it is likely the probe position was on different locations on the body.   
• 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, confirm the sensor has been cleaned and disinfected (see Section 6.9).  
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 and the subject should be asked to remain 
very still. This period requires approximately 20 – 30 minutes.  
• Adverse event collection begins 
• 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 is strongly recommended).  
o NOTE:  The Sponsor may request that the placement of the dosing catheter occur 
BEFORE the sensor is attached to the subject. In these cases, the dosing catheter 
will be in place during the baseline data acquisition.  The subject should be 
instructed to keep the arm with the dosing catheter very still, and the site should 
dose as quickly as possible after the “Administer Lumitrace” screen appears on 
the TGFR monitor.     
o If the catheter is placed AFTER the baseline assessment is completed, sites should 
minimize the time between catheter placement and dosing to no more than 5 
minutes.  As catheter placement can be difficult in older subjects, if this duration 
exceeds 5 minutes, it should not be considered a protocol deviation.  
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-


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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 start 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.  
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. Direct sticks may 
also be used to obtain blood.  
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) 


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• 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) 
• Obtain laboratory tests including chemistry, hematology, and urinalysis (See Section 
7.1.2.6 and Table 3) at 725 minutes (-245 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) 


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• 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) 
• Obtain laboratory tests including chemistry, hematology, and urinalysis (See Section 
7.1.2.6 and Table 3) at 725 minutes (-245 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 


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• Subjects may be discharged from the study center 
6.9 
Sensor Cleaning and Disinfection 
Following removal of the sensor of the subject, the sensor must be cleaned and disinfected prior 
to use on subsequent subjects. A cleaning kit will be provided to the sites which will include a 
mild dish soap (detergent) and lint free cloths.  
6.9.1 Sensor Cleaning 
Sites will make a solution of 20:1 ratio of water to detergent. This mixture should not exceed 
55°C (130°F).  
 
Clean the surfaces of the TGFR Reusable Sensor with a damp cloth using 20:1 detergent 
mixture, removing all visible soil.  Ensure all excess fluid is squeezed from the cloth before 
cleaning. If the cloth is excessively wet, the detergent and water solution may penetrate the 
sensor and affect functionality.  After cleaning the TGFR Reusable Sensor, wipe the TGFR 
Reusable Sensor with a clean lint free damp cloth to remove the mild detergent mixture.  Dry the 
TGFR Reusable Sensor with a clean lint free cloth.  Never use an abrasive pad or abrasive 
cleaner on the monitor. 
 
6.9.2 Sensor Disinfection 
The TGFR Reusable Sensor will be disinfected by wiping the surface with a 70% isopropyl 
alcohol wipe, or an equivalent lint free wipe wetted with 70% isopropyl alcohol. Wipe the TGFR 
Reusable Sensor as necessary to maintain visual wetness for a minimum duration of 2 minutes. 
After disinfecting the TGFR Reusable Sensor, allow each to air dry completely.  
 
Sensor cleaning and disinfection will be documented on a log and maintained with the 
Investigator Site Files.  
 
Caution: The use of other cleaners and disinfectants may cause significant damage to the TGFR 
Reusable Sensor and may impair its future use.  Never use an abrasive pad on any surface of the 
TGFR sensor. Do not use Bleach or other solutions aside from what is described above. The 
TGFR Reusable Sensor is not designed to be immersed, soaked, rinsed, or sprayed with water. 
Do not immerse, soak, rinse, or spray the TGFR Reusable Sensor in water or other cleaning 
solutions. Failure to follow the cleaning procedures described herein could result in hazards to 
users, patients, and clinicians. As with any medical electrical equipment, care must be taken to 
prevent liquid from entering the TGFR Reusable Sensor to avoid electrical shock hazard, fire 
hazard, or damage to the electrical components.  
 
6.10 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 


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• 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)  
6.11 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  
• Collect adverse events; review ongoing AEs and document resolution (when applicable)  
• Record withdrawal date and reason for withdrawal, if appropriate 
6.12 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):  
• If they were part of the Run-in Cohort and/or Validation Cohort 1 
• 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) 
• If no tGFR is reported due to another issue 
• 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 5-day wash-out 
from prior exposure of MB-102 before receiving another dose.  


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In some cases, the screening visit (if outside the 28-day window) may need to be repeated.  
Repeat subjects enrolled into Validation Cohort 2 or 3 will be provided with a new subject ID, 
however the original subject ID will be cross-referenced in the database.  
Subjects can be in the study a maximum of four times and only when the above situations have 
occurred. Subjects who successfully complete Validation Cohort 2 with full PK and an average 
session TGFR cannot repeat the study.  
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 bridging 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 using the TGFR 
resusable sensor and disposable adhesive ring 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 
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 


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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 
disposable adhesive ring 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.   
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 


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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. 
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 


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• 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 
 
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.  


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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.   
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 administration of MB-
102, it should be removed from the subject, the disposable ring removed and a new ring put on 


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the sensor and re-attached after re-cleaning the area with an ethanol wipe.  Baseline 
measurements may then be re-started.  
 
After dosing with MB-102: 
If a sensor is accidently removed (or significantly bumped) following administration 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 continue to be performed.  
 
7.1.2.6 Clinical Laboratory Evaluation 
Clinical laboratory assessments (Table 3) will be performed by a central lab. 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.  
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 at screening and prior to dosing (local testing) 
 
 
 


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7.1.2.7 Vital Signs 
Vital signs (including blood pressure, pulse, 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. 
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.  


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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 and erythema 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 
(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) 
 


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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 
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.   
 
A pivotal trial (protocol 100-003) enrolled 249 subjects.  There were 31 adverse events reported 
in 26 subjects (10.4%). All reported events are mild or moderate in severity. Only 1 event 
(moderate nausea) was considered related to MB-102. No severe or serious events have been 
reported.  
 
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.  
 


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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.  
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 average session tGFR or 


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an average snapshot tGFR* has been calculated, and who have not had any major 
protocol deviations that would impact TGFR system performance.  
➢ 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. 
* Note: this includes short gaps in data that are less than 30 minutes due to a resumption of 
the monitoring session where an “average snapshot GFR” is reported instead of a “average 
session GFR”.  
 
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.  
Note: Data from the Run-in Cohort and Validation Cohort 1 will be considered Tuning Data 
and will not be used in the final analyses.   
 
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 
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.   


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➢ 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%. 
 
Prior data demonstrated 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.  As the reusable 
sensor is new, an adaptive trial design will be employed.  
 
A Run-in Cohort of up to 30 evaluable subjects will be enrolled to test monitor algorithm settings 
with the TGFR reusable sensor with disposable adhesive ring. Additional run-in subjects may be 
enrolled at new clinical sites to ensure protocol compliance. Run-in subject data will be 
considered tuning data. The following will be enrolled into the run-in cohort: 
o At least 5 subjects will be enrolled in Stratum 2 
o At least 4 subjects in each of the FSS I-II; III-IV and V-VI 
 
• Validation Cohort 1 (approximately 20 evaluable subjects) will be used to confirm final 
algorithm selection. Validation Cohort 1 subject data will be considered tuning data.  
• Validation Cohort 2 (approximately 75 evaluable subjects) will be analysed in an interim 
analysis to compare results against the primary endpoint specification. At that time, the 
primary endpoint null hypothesis will be tested using an exact binomial test at a one-
sided nominal alpha level of 0.0150 using the method of Pocock for a two-stage design 
with the interim analysis performed based on the first 53.57% of the planned number of 
subjects. At the final analysis, the primary endpoint null hypothesis will also be tested at 
a one-sided nominal alpha level of 0.0150. This will control the overall Type I error rate 
at the one-sided 0.025 level. 


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• If the primary endpoint has been achieved, the study will be terminated. If not, the trial 
will be continued.  
• Validation Cohort 3 (approximately 65 evaluable subjects) will be enrolled in the event 
the interim analysis did not meet the primary outcome measure. Final analysis will be of 
the 140 evaluable subjects. 
 
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). 
 
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. 


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9.6.4 ECGs 
ECG data will be listed. Clinically significant findings noted after dosing 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. 
 
9.8 
Missing Data 
Missing values will not be imputed.  
 
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 Council 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.  


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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. 
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  
• A significant protocol required assessment or procedure was not performed per protocol 
requirements 


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• 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 
• An Average Session GFR or an Average Snapshot GFR was not obtained 
• Sensors that are not cleaned and disinfected between study subjects 
 
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) 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 


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2 April 2024 
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Page 53 of 59 
 
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.  
• 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  
 


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Protocol No.  100-201 
V 5.1 
 
 
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12 Ethics 
12.1 Independent Ethics Committee (IEC) 
Before initiation of the study at each study site, the protocol, all protocol amendments, 
Investigator’s 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 
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 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 


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MediBeacon® Transdermal GFR Measurement System 
Protocol No.  100-201 
V 5.1 
 
 
2 April 2024 
CONFIDENTIAL INFORMATION  
Page 55 of 59 
 
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 
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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V 5.1 
 
 
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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 (shown below) will be determined via measurements of melanin using the 
Mexameter on the upper chest area where the sensor is anticipated to be placed.  As a general 
reference, the subjective skin color scale is show below.  
 
 
Source: Fitzpatrick, 1975 
 
Mexameter melanin measurements correspond to FSS scores as noted below:  
 
o FSS type I:  
Mexameter melanin range:                   0 - 100  
o FSS type II:  Mexameter melanin range: 
 
100 - 150  
o FSS type III:  Mexameter melanin range: 
 
150 - 250  
o FSS type IV:  Mexameter melanin range: 
 
250 - 350  
o FSS type V:  Mexameter melanin range: 
 
350- 450  
o FSS type VI:  Mexameter melanin range:              450 – 999 
 
 
 
 


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Investigator Signature Page 
 
Protocol Title: 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using the 
TGFR Reusable Sensor with Disposable Adhesive Ring in Normal 
and Renal Compromised Subjects for the Evaluation of Kidney 
Function 
Protocol Number: 
100-201  
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. 
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Protocol No.  100-201 
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2 April 2024 
CONFIDENTIAL INFORMATION  
Page 59 of 59 
 
15 Signature of the Sponsor’s Responsible Officers 
 
 
15.1 Chief Scientific Officer 
 
 
Richard Dorshow, PhD 
 
 
 
 
 
 
 
MediBeacon Inc.  
USA 
 
 
15.2 Medical Officer 
 
 
 
Dr. Joseph Pierro 
 
 
 
 
 
 
 
 
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 

SAP_001.pdf: 
 
 
Statistical Analysis Plan 
Page 1 of 29 
MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
NCT05777174 
    
 
 
MediBeacon Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic Bridging Study of MB-102 
(Relmapirazin) and the Use of the MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in Normal and Renal Compromised 
Subjects for the Evaluation of Kidney Function  
Protocol No. 100-201, Version 4.0 
 
 
 
 
Statistical Analysis Plan 
Version 4.0 
   18 September 2024 
 
 
 


 
 
Statistical Analysis Plan 
Page 2 of 29 
MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
Version History 
Version
Version Date 
Author/Title 
Summary of Key Changes 
1.0 
5 January 2023 
Nancy 
Morrison/Regulatory 
Consultant 
Initial Release 
1.1 
20 April 2023 
E. LaPointe 
Clinical Operations 
Consultant 
Updated run-in cohort size (from 20 evaluable to 30 
evaluable); clarified run-in cohort data as Tuning Data 
and not to be included in final analysis 
2.0 
23 August 2023 
E. LaPointe 
Clinical Operations 
Consultant 
Aligned SAP to Protocol version 3.0 (definition of study 
cohorts) and revised the definition of the ITM 
population 
3.0 
15 Nov 2023 
E. LaPointe 
Clinical Operations 
Consultant 
Revised the definition of the ITM population; added 
language regarding type I error during the interim 
analysis; removed geographic poolability analysis 
because use of Chinese sites was removed in an earlier 
version of the protocol  
4.0 
18 Sep 2024 
E. LaPointe 
Clinical Operations 
Consultant 
Updated the protocol version to the most up to date 
version of the protocol (version 3 to version 5.1); added 
language to sections 4: Primary Endpoint and 8.1 
Analysis Sets to clarify that ITM and the mITM analysis 
would be based on Validation 2 and Validation 3 (if 
applicable) cohorts only.  The Run-in cohort and the 
Validation 1 cohort contributed to tuning data on the 
study only as outlined in the protocol.  
 
 
 


 
 
Statistical Analysis Plan 
Page 3 of 29 
MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
 
Document Approval 
 
 
Approval 
Approved By
Liyang Xie, PhD
Signature 
Role
Biostatistician, LLX Solutions, LLC
 
 
Approval 
Approved By
Richard Dorshow, PhD
Signature 
      
Role
President and Chief Scientific Officer, MediBeacon
 


 
 
Statistical Analysis Plan 
Page 4 of 29 
MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
TABLE OF CONTENTS 
1 
INTRODUCTION ................................................................................................................... 6  
2 
STUDY DESIGN ..................................................................................................................... 6  
2.1 
Overview ...................................................................................................................................................... 6 
2.2 
Number of Planned Sites and Subjects ........................................................................................................ 6 
2.3 
Replacement of Subjects .............................................................................................................................. 7 
2.4 
Study Schedule ............................................................................................................................................. 7 
2.5 
Randomization ........................................................................................................................................... 10 
3 
STUDY OBJECTIVE AND ENDPOINTS .................................................................................... 10  
3.1 
Primary Objective and Endpoint ................................................................................................................ 10 
3.2 
Pharmacokinetic Objective and Parameters .............................................................................................. 10 
3.3 
Safety Evaluation ........................................................................................................................................ 11 
4 
ANALYSIS OF PRIMARY ENDPOINT ...................................................................................... 12 
4.1 
Subgroup and Stratified Analysis ............................................................................................................... 12 
5 
PHARMACOKINETIC ANALYSIS ............................................................................................ 13  
5.1 
Compartmental Pharmacokinetic Data Analysis ........................................................................................ 13 
5.2 
Calculation of nGFR .................................................................................................................................... 13 
5.3 
Criteria for Handling Concentration Below the Limit of Quantification or Missing Concentrations for 
Pharmacokinetic Analysis ........................................................................................................................................ 15 
5.4 
Treatment of Outliers in Pharmacokinetic Analysis ................................................................................... 15 
5.4.1 
Exclusion and Remedy for Plasma Concentration at each Time Point ....................................................... 15 
5.4.2 
Exclusion Based on Subject Dosing Errors .................................................................................................. 17 
5.4.3 
Exclusion Based on Small Dosing Errors and/or Extravasations................................................................. 19 
5.4.4 
Exclusion Based on Body Size ..................................................................................................................... 21 
5.5 
Presentation of Pharmacokinetic Data ...................................................................................................... 21 
6 
TRANSDERMAL DERIVED GFR DATA .................................................................................... 21  


 
 
Statistical Analysis Plan 
Page 5 of 29 
MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
7 
ANALYSIS OF SAFETY .......................................................................................................... 22  
7.1 
Safety Review Committee .......................................................................................................................... 23 
7.2 
Assessment of Causality ............................................................................................................................. 23 
7.3 
Assessment of Severity .............................................................................................................................. 23 
7.4 
Action Taken .............................................................................................................................................. 24 
7.5 
Outcome of the Event ................................................................................................................................ 24 
7.6 
Evaluation of Device Malfunctions ............................................................................................................. 24 
8 
GENERAL STATISTICAL CONSIDERATIONS ............................................................................ 25 
8.1 
Analysis Sets ............................................................................................................................................... 25 
8.2 
Sample Size Determination ........................................................................................................................ 25 
8.3 
Pooling Data Across Sites ........................................................................................................................... 26 
8.4 
Handling of Missing Data ........................................................................................................................... 27 
8.5 
Statistical Software .................................................................................................................................... 27 
8.6 
Descriptive Statistics .................................................................................................................................. 27 
8.7 
Statistical Significance ................................................................................................................................ 27 
8.8 
Subject Disposition ..................................................................................................................................... 27 
8.9 
Analysis ...................................................................................................................................................... 28 
9 
CHANGES FROM PLANNED ANALYSES ................................................................................. 28 
10 SUBJECT LISTINGS ............................................................................................................... 28  
11 TABLES ............................................................................................................................... 29  
 
 


 
 
Statistical Analysis Plan 
Page 6 of 29 
MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
1 Introduction 
 
This statistical analysis plan (SAP) describes the planned statistical methods to be used during the 
reporting and analysis of data collected under the Clinical Investigation Protocol, “An Open Label, Multi-
Center, Safety and Pharmacokinetic Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using the TGFR Reusable Sensor with 
Disposable Adhesive Ring in Normal and Renal Compromised Subjects for the Evaluation of Kidney 
Function”. This SAP should be read in conjunction with the study Clinical Investigation Plan and 
associated case report forms (CRFs). This version of the analysis plan has been developed with respect to 
the Study Protocol Version 5.1. Any revisions to the protocol or CRFs that impact the planned analyses 
may require updates to the SAP. If there are any discrepancies between the SAP and the protocol, the 
SAP will prevail. 
2 Study Design 
 
2.1 
Overview 
MediBeacon is expanding the MediBeacon® Transdermal GFR (TGFR) Measurement System with the 
addition of a reusable sensor for use in the system. The TGFR Measurement System is a combination 
product that requires the administration of a fluorescent tracer agent designated relmapirazin (MB-102) 
that will be detected transdermally by a sensor which is attached to the device console.  The study is a 
bridging trial investigating effectiveness of the TGFR reusable sensor in the MediBeacon® Transdermal 
GFR Measurement System in normal and compromised renal function subjects with different skin color 
types. The drug portion of the combination product is unchanged from prior investigations.  
The objectives of this study are:  
 To establish that the MB-102 transdermal fluorescence measured GFR using the MediBeacon® 
Transdermal GFR Measurement System with the TGFR reusable sensor with disposable 
adhesive ring is comparable to the measured MB-102 plasma GFR  
 To evaluate the safety and effectiveness of the MediBeacon® Transdermal GFR Measurement 
System and the TGFR reusable sensor with disposable adhesive ring for the non-invasive 
transdermal fluorescence detection of MB-102 in subjects 
2.2 
Number of Planned Sites and Subjects 
This study will take place at up to 5 investigational sites in the US.  


 
 
Statistical Analysis Plan 
Page 7 of 29 
MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
Up to 240 subjects are planned for enrollment. The population will be split into stratums in accordance 
with screening eGFR measured by the CKD-EPI equation (pre-2021): 
 
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 will be Fitzpatrick skin scale (FSS) I-III and 50% of 
subjects will have FSS IV-VI. Subjects will be enrolled across a spectrum of both eGFR (15 
mL/min/1.73 m2 ) and FSS.  
Subjects will be screened and if deemed eligible, will be enrolled. Subjects will be considered enrolled in 
the study after  
 
Signing the study specific informed consent form 
 
Receiving the sensor, and  
 
Receiving the MB-102 injection  
 
2.3 
Replacement of Subjects 
Should a subject not meet eligibility, or is unable to be scheduled for dosing, that subject will be 
considered a screen failure. In addition, subjects who are unable to have an “average session GFR” 
measured by the TGFR Measurement System (due to premature sensor removal, for example), a major 
protocol deviation (such as a dosing extravasation), or meet the agreed upon post-PK outlier exclusion 
criteria (defined in Section 5.4) may be replaced to ensure the minimum sample size is enrolled.  If 
subjects are not considered evaluable, they will be replaced in the study with a total potential enrollment 
up to 240 subjects. All subjects with exposure to MB-102 will be included in the safety analysis. 
 
2.4 
Study Schedule 
The study will consist of screening time period within 28 days (but at least 2 days prior to) the baseline / 
dosing day. Subjects will be screened and if deemed eligible, will be enrolled. Screening will compromise 
of the following: 
 
Obtain written informed consent form 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 (Table 1). Perform serum pregnancy test in women of child-bearing potential; and collect 
a urine sample for urinalysis 


 
 
Statistical Analysis Plan 
Page 8 of 29 
MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
 
Perform COVID-19 testing for unvaccinated subjects or per study center requirements. 
Vaccinated subjects without COVID-19 symptoms are not required to have COVID-19 test 
performed 
 
Collect height and weight measurements 
 
Perform a full physical exam (by a physician) and collect vital signs. The full physical 
examination includes at a minimum an assessment of the head, ears, eyes, nose, throat (HEENT), 
respiratory, cardiovascular, and gastrointestinal systems. The vital signs include blood pressure, 
heart rate, respiration and temperature. 
 
Perform a 12 lead ECG. In addition to the interpretation, ventricular rate, PR interval, QRS 
duration, QT, and QTcF will be collected. Additional ECGs may be collected if an issue or safety 
concern is noted. 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. 
 
Document Fitzpatrick Skin Scale Color Type by examining the upper chest (locations for possible 
sensor placement) and collecting Mexameter data on possible sensor locations 
For sites who elect to bring subjects into the clinic the night before the 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 (performed by a nurse or other qualified personnel) 
 
Record concomitant medications taken within 3 days prior to dosing day 
 
Perform a urine pregnancy test for WOCBP 
 
Have the subject consume 240 mL of ambient water 
On dosing day, subjects will have baseline assessments performed (with the exception of those 
procedures noted above if they were performed the night before): 
 
Review subject eligibility 
 
Update medical history with any new information or issues occurring since the initial screening 
visit 
 
Collect the subject weight; BSA (and BMI) will be calculated based on the Screening height and 
the day of dosing weight 
 
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) 


 
 
Statistical Analysis Plan 
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MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
 
Perform a baseline ECG 
 
Record concomitant medications taken within 3 days of the dosing visit 
 
Urine pregnancy test for WOCBP 
 
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 Mexameter 
 
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 (Table 1) 
 
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 
 
Prior to dosing, have the subject consume an additional 240 mL 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). Note: the venous 
catheter may also be placed PRIOR to sensor attachment and baseline acquisition upon Sponsor 
direction.  
When this is completed, subjects will then receive a single dose of 130 mg MB-102. Serial PK draws will 
be collected over a 12-hour or 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.  
The population will be split into stratums accordance with baseline eGFR by the CKD-EPI equation and 
location of enrollment: 
 Stratum 1: In this stratum, there will be 50% of subjects with an eGFR ≥ 70 mL/min/1.73 m2. Eligible 
subjects will receive a single 130 mg dose of MB-102 and 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: In this stratum, there will be 50% of subjects with an eGFR <70 mL/min/1.73 m2. Eligible 
subjects will receive a single 130 mg dose of MB-102 and 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). 


 
 
Statistical Analysis Plan 
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MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
 Subjects will return for a safety follow-up visit approximately 7 ± 3 days after the dosing visit. The 
following assessments will be performed: 
 
Full or limited physical exam will be performed and vital signs (including temperature) will be 
collected 
 
Laboratory tests including chemistry, hematology, and urinalysis will be obtained (Table 1) 
 
Concomitant medications will be recorded 
 
Adverse events will be recorded. 
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: 
 
Full or limited physical exam will be performed and vital signs (including temperature) will be 
collected 
 
Laboratory tests including chemistry, hematology, and urinalysis will be obtained (Table 1) 
 
Concomitant medications will be recorded 
 
Adverse events will be recorded 
 
Withdrawal date and reason will be recorded (if applicable) 
2.5 
Randomization 
This is a single-arm, multicenter, prospective clinical study where all eligible subjects will use the 
investigational device and be injected with MB-102. Subjects will not be randomized. 
3 Study Objective and Endpoints 
 
3.1 
Primary Objective and Endpoint 
The primary objective is to establish that MB-102 transdermal fluorescence measured GFR using the 
MediBeacon® Transdermal GFR Measurement System is comparable to the measured MB-102 indexed 
plasma GFR.  
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%. 
3.2 
Pharmacokinetic Objective and Parameters 
The pharmacokinetic objective is to characterize the single dose pharmacokinetics of MB-102 following 
IV bolus dosing, specifically, to obtain the clearance and total volume of distribution of MB-102 using 


 
 
Statistical Analysis Plan 
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MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
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. 
 
3.3 
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. Additional safety 
variables include physical examinations, clinical laboratory assessments, ECGs, and concomitant 
medication use. All clinically significant findings in physical examinations, clinical laboratory 
assessments and ECGs will be reported as an AE or as medical history (if observations are noted prior to 
dose administration). 


 
 
Statistical Analysis Plan 
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MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
4 Analysis of 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%.   
The primary endpoint will be calculated for subjects enrolled into the Validation 2 and 3 (if applicable) 
cohorts only.  The Run-in cohort and Validation 1 cohort enrollment were performed to provide final 
tuning data and used for software updates.  
 
4.1 
Subgroup and Stratified Analysis 
For the primary effectiveness endpoints, all data will be included in the primary analysis. To examine the 
consistent device performance, two sub-group analyses will be performed. The first sub-group analysis 
will be nGFR vs tGFR for eGFR > 70 mL/min/1.73 m2, and then for eGFR < 70 mL/min/1.73 m2. The 
second sub-group analysis will be nGFR vs tGFR for FSS I-III, and then for FSS IV-VI.  
FSS will be generated based on Mexameter melanin measurements collected on the dosing day instead of 
using the subjective screening categorization. The mean of the melanin will be calculated and the FSS 
applied per the Mexameter manual (below):  
 
FSS I: Nordic/Celtic skin: extremely white skin, often red hair and freckles, never tan, always 
sunburns, average melanin content: 0 - 100  
 
FSS II: Light Caucasians: very light skin, often blond, tans with difficulty and sunburns 
quickly, average melanin content: 100 - 150  
 
FSS III: European mixed type/ very fair Asian skin: light skin, dark blond to brown hair, tans 
sometimes, sunburns sometimes, average melanin content: 150 - 250  
 
FSS IV: Mediterranean/fair Asian skin: dark hair, tans well and sunburns rarely, average 
melanin content: 250 - 350  
 
FSS V: Dark skin: e.g. dark Asians, tans very well and sunburns almost never, average melanin 
content: 350- 450  
 
FSS VI: Black skin: Immediately tans and never sunburns, average melanin content: 450 – 999 
 
Note that the 30 evaluable subjects used for the run-in cohort and the 20 subjects enrolled into Validation 
Cohort 1 will not be included in the primary endpoint analysis as these data are considered Tuning Data.  


 
 
Statistical Analysis Plan 
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MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
5 Pharmacokinetic Analysis 
 
Pharmacokinetic blood samples will be collected at the time points noted in Section 2.4. Single-dose 
pharmacokinetic parameters for MB-102 will be calculated using compartmental analysis methods.   
5.1 
Compartmental Pharmacokinetic Data Analysis 
A compartmental pharmacokinetic analysis will be performed separately using each subject’s plasma 
concentration-time profile.  Based on prior data, it is expected that a two compartmental model will 
provide an adequate fit using Phoenix WinNonlin (Certara, Version 8.1 or higher). Model PK parameters 
for each subject will be reported.  
 
Parameter 
Unitsa 
Definition 
AUC 
h*ng/mL 
area under the plasma concentration-time curve, calculated as 
AUC=A/α + B/β 
Cmax 
ng/mL 
maximum plasma concentration, calculated as Dose/V 
t1/2α 
h 
half-life associated with distribution phase 
t1/2β 
h 
half-life associated with elimination phase 
t1/2 
h 
elimination half-life from central compartment 
CL 
L/h 
systemic clearance 
V 
L 
total volume of distribution 
V1 
L 
volume of distribution for central compartment 
V2 
L 
volume of distribution for peripheral compartment 
 
5.2 
Calculation of nGFR  
𝒏𝑮𝑭𝑹𝑩𝑺𝑨 – calculation of indexing to body surface area (BSA): 
 
The GFR for each subject is obtained from the two-compartment pharmacokinetic model. 


 
 
Statistical Analysis Plan 
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MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
BSA in units of m2 is calculated for each subject from their height and weight using the formula1: 
 
BSA=0.007184 * heightcm0.725 * weightkg0.425 
 
 
𝑛𝐺𝐹𝑅஻ௌ஺=
ீிோ (௠௅/௠௜௡)
ಳೄಲ (೘మ)
భ.ళయ
= 
ீிோ (௠௅/௠௜௡)
஻ௌ஺ (௠మ)
∗1.73   (Eqn. 1) 
 
Note that in clinical practice GFR indexed to BSA (nGFRBSA) is reported as “mL/min/1.73 m2”. 
 
𝒏𝑮𝑭𝑹𝑽𝒅 – calculation of indexing to volume of distribution (Vd): 
 
The GFR and volume of distribution (Vd) for each subject is obtained from the two-compartment 
pharmacokinetic model. 
 
𝑛𝐺𝐹𝑅௏ௗ=
ீிோ (௠௅/௠௜௡)
ೇ೏ (ಽ)
భయ.య
=
ீிோ (௠௅/௠௜௡)
௏೏ (௅)
∗13.3 
     (Eqn. 2) 
 
 
The standard value of 13.3 L for Vd was derived from our earlier clinical studies by computing the mean 
BSA across all subjects and computing the ratio of 1.73 m2 to the mean BSA.  This ratio was then 
multiplied by the mean Vd across all subjects to obtain the standard value of 13.3 L.    
 
Note: Dosing day height and dosing day weight will be used for BSA / BMI calculations, however in the 
event dosing day weight or height is unavailable, screening day weight or height may be used.  
 
 
1 DuBois D, DuBois EF. A formula to estimate the approximate surface area if height and weight be known. Arch Intern Medicine. 
1916; 17:863-71. 
 


 
 
Statistical Analysis Plan 
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MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
5.3 
Criteria for Handling Concentration Below the Limit of Quantification or Missing 
Concentrations for Pharmacokinetic Analysis 
Plasma concentrations below the limit of quantification (BLQ) will be assigned a value of 0 before the 
first measurable concentration and thereafter BLQ concentrations will be treated as missing. The 
following rules apply to the specific situations defined below: 
● If an entire concentration-time profile is BLQ, it will be excluded from PK analysis. 
● Where 2 or more consecutive concentrations are BLQ at the end of a profile, the profile will be 
deemed to have terminated and any further quantifiable concentrations will be set to missing for the 
calculation of the PK parameters, unless they are considered to be a true characteristic of the profile 
of the drug. 
● If a predose plasma concentration is missing, it will be set to 0 by default within Phoenix 
WinNonlin. 
5.4 
Treatment of Outliers in Pharmacokinetic Analysis 
Four outlier exclusion criteria which will be identified following PK analysis are addressed below. 
5.4.1 Exclusion and Remedy for Plasma Concentration at each Time Point 
MediBeacon developed the analytical methodology for MB-102 concentration determination in plasma. 
This method was shown to be very robust and much simpler than the usual analytical methods employed 
for iohexol determination in plasma samples. In the Pilot 2 Group 1 study, a rigorous method transfer and 
technician training program resulted in exceptional agreement between agent concentration in plasma 
samples measured at the sponsor lab and the third-party bioanalytical lab. The data was published in the 
peer-reviewed journal “Analytical Methods” (Shieh et. al. 20182). However, when processing the Pilot 2 
Group 2 samples, obvious errors in sample concentration were randomly observed. All indications 
pointed to lack of carefulness on the technician doing the work at the third-party bioanalytical lab. 
Thus to ensure accuracy, it is necessary to implement a check on the bioanalytical lab that is performing 
the plasma agent concentration measurements. The plasma concentration vs time data generated by the 
third party bioanalytical lab is crucial to the clinical study endpoint. We have instituted further training on 
 
2 J. J. Shieh, I.R. Riley, R.B. Dorshow, Clinical analysis and quantitation of MB-102, a novel fluorescence tracer 
agent, in human plasma Royal Society of Chemistry, Anal. Methods, 2018, 10, 2376 


 
 
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MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
our analytical technique at the bioanalytical laboratory and have instituted written protocols covering the 
entire analysis procedure. 
A review of all plots of such data both in linear space and semi-log space will be performed prior to the 
GFR calculation. An example of data in semi-log space is in Figure 1;  red circles are the measured 
concentrations from a subject with normal kidney function, the blue line is the two-compartment 
pharmacokinetic fit. 
 
Figure 1 Plasma concentration as a function of time for a subject with normal renal function 
Should a data point be observed that is 20% off the fit line, this may be an indication of an issue with the 
sample or with sample preparation. Thus, for any plasma sample value that is greater than 20% off the fit 
line, a re-analysis of agent concentration will be performed in that sample. The request will be for re-
analysis in triplicate (3 new PK analyses of the timepoint), and the average value for concentration from 
the triplicate run will be used for that time point in the calculation of plasma GFR. If WinNonLin default 
parameters are not able to provide a pharmacokinetic result, then the full set of PK timepoints for that 
subject will be re-analyzed in triplicate and the means used in the final analysis.  


 
 
Statistical Analysis Plan 
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MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
Any quantifiable pre-dose concentration value will be considered anomalous and set to missing for the 
PK analysis, which will then be subsequently set to 0 by default in Phoenix WinNonlin. 
It is anticipated that this exclusion criteria will seldom need to be employed due to our training 
program and written protocols at the third-party bioanalytical lab. 
5.4.2 Exclusion Based on Subject Dosing Errors 
In the initial implementation of the Pilot 2 Group 1, the site staff was not properly determining the 
amount dosed due to weighing errors of the agent-filled dosing syringe. The error in measured dose 
translated to error in GFR since: 
GFR = Dose / AUC 
where AUC is the area under the curve in the plasma concentration of MB-102 vs time plot. We 
subsequently implemented a strict weighing protocol to accurately determine the amount of administered 
dose, which has been followed for all subsequent studies, with the weighing protocol monitored by 
company staff at each study to prevent weighing errors of the dose.  
In the 100-201 clinical study, which will be performed at up to 5 clinical sites, the clinical site staff will 
be expected to perform subject dosing error-free.. Written protocols will be provided to minimize dosing 
errors. However, as a check on dosing at the clinical sites, exclusion criteria based on the calculation of 
GFR from the standard two-compartment pharmacokinetic model and the indexed GFR will be 
implemented.  
MB-102 plasma GFR is deduced using the MB-102 concentration vs time data and dose in the standard 
two-compartment pharmacokinetic model. We will use the most current version of WinNonlin for this 
task. The derived GFR is directly dependent on the input dose amount.  This pharmacokinetic model also 
outputs many other parameters including the volume of distribution Vd.  The derived Vd is also directly 
dependent on the input dose amount.  
In the clinical setting, GFR is indexed to body surface area (BSA) using one of several formulas, all of 
which use the subject’s height and weight. In fact, GFR indexed by BSA is how nephrologists stage 
kidney disease. The symbol nGFRBSA will be used for this indexing. Like non-indexed GFR, the GFRBSA 
determination is also directly dependent on dose.  
GFR can also be indexed by Vd. The symbol nGFRVd will be used for this indexing. Because both the 
derived GFR and Vd are directly dependent on the input dose amount, indexing makes nGFRVd 
independent of dose.  


 
 
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MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
Due to the dependence of nGFRBSA on dose amount and independence of nGFRVd on dose amount, 
comparison of these two values reveals errors in dosing.  An example is in Figure 2 shown below from 
some of our clinical data obtained in the device optimization studies. 
 
Figure 2: Plasma GFR indexing comparison 
The y-axis is nGFRBSA and the x-axis is nGFRVd. Two of the 67 subjects are seen to be obvious outliers in 
a plot of nGFRBSA vs. nGFRVd. The conclusion is that a major dosing error has occurred for these two 
subjects.  
It is anticipated that this exclusion criteria will seldom need to be employed due to our training 
program and written protocols at the clinical sites. 
0
50
100
150
200
250
300
0
20
40
60
80
100
120
140
160
nGFRBSA
nGFRVd


 
 
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MediBeacon 
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An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
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5.4.3 Exclusion Based on Small Dosing Errors and/or Extravasations 
MediBeacon have found that plasma determined nGFR may also be affected by more subtle issues. These 
include small dosing errors and/or small extravasations of the MB-102 dose.  
For example, after deleting the two extreme outliers in Figure 2, and correcting for a small linear trend in 
the absolute difference between nGFRBSA and nGFRVd for the remaining subjects, the root mean square 
(RMS) percent error of the difference of the two indices was computed in 20 mL/min wide nGFRVd 
subject bins, as shown in the Figure 3: 
 
Figure 3: RMS percent error of nGFRBSA - nGFRVd as a function of nGFRVd.  
Subjects were grouped into 20 mL/min wide bins according to nGFRVd. Error bars represent ± the 
standard error within each binned group of subjects. 
0%
5%
10%
15%
20%
25%
30%
0
20
40
60
80
100
120
140
160
RMS % Error: nGFRBSA -nGFRVd, Lin. Corr.
nGFRVd
13% RMS Error


 
 
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MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
The resulting RMS percent error is seen to be independent of nGFRVd with a combined value of 13% 
across all subjects.  
Choosing two times the RMS percent error as a threshold limit for outlier detection (since it is similar to 
the standard deviation) results in identification of four additional outlier subjects, as shown in the Figure 
4 below. 
 
Figure 4: RMS percent error for nGFRBSA - nGFRVd as a function of nGFRVd. Dashed lines are 
outlier thresholds 
Summary: Two nGFR indexing calculations, nGFRBSA and nGFRVd, will be performed for all subjects in 
the 100-201 study. Any subject nGFR data that is an obvious outlier as described in section 2 above, and 
-40%
-30%
-20%
-10%
0%
10%
20%
30%
40%
50%
0
20
40
60
80
100
120
% Err, nGFRBSA - nGFRVd, Lin. Corr.
nGFRVd


 
 
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MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
any subject nGFR that is outside the threshold boundary as described in Figure 4 will be eliminated 
before applying the remaining nGFR data to the evaluation of the tGFR endpoint criteria. 
It is anticipated that this exclusion criteria will need to be seldom employed due to implementation of a 
rigorous training program and written protocols at the clinical sites. However, MediBeacon has 
historically seen evidence of these minor deviations and need to ensure this is not occurring in our 
100-201 clinical study data set. 
5.4.4 Exclusion Based on Body Size 
Body surface area calculation for subjects at the extremes of body size are problematic. This issue has 
been widely discussed and a good summary is in Redlarski et al 20163. Thus, any subjects with nGFRBSA 
> 120 mL/min/1.73m2 will be excluded from the tGFR vs nGFRBSA dataset comparison. Note that 
clinically this is not relevant as these are highly normal subjects with respect to kidney function.  
It is anticipated that this exclusion criteria will seldom be employed due to the enrollment exclusion 
criteria that excludes subjects with an eGFR > 120 mL/min/1.73m2 per the CKD-EPI equation. 
 
5.5 
Presentation of Pharmacokinetic Data 
 
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. 
6 Transdermal Derived GFR Data 
 
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. 
 
3 G. Redlarski, A. Palkowski, M. Krawczuk, Body surface area formulae: an alarming ambiguity, Nature Scientific 
Reports 21Jun2016 


 
 
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MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
7 Analysis of Safety 
 
All TEAEs reported during the study will be reviewed and adequately reported to comply with applicable 
regulations. All reportable TEAEs will be assessed by the investigator who will determine whether the 
event is related to MB-102 or related to the study device, and whether the event meets any of the criteria 
for seriousness. A serious adverse event (SAE) is any AE from this study that results in one of the 
following outcomes: 
 
led to death; 
 
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; 
 
led to fetal distress, fetal death or congenital abnormality or birth defect. 
Significant findings that were noted to be 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.   
 All reported TEAEs, including unanticipated adverse device effects (UADE), and serious adverse events 
(SAE) will be summarized for all enrolled subjects. The overall numbers and percentages of subjects who 
experienced any TEAEs will be presented.  In addition to the TEAEs, description of all TEAEs, including 
description/term of the symptom event (underlying diagnosis), the date of first occurrence and date of 
resolution (if applicable), classification of serious or not serious, severity, causal relationship, action 
taken, and event outcome will be listed. 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.  
In addition to the events reported as AEs, the parameters of clinical laboratory tests including clinical 
chemistry, hematology, urinalysis and coagulation parameters will be summarized using the descriptive 


 
 
Statistical Analysis Plan 
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MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
statistics.  Clinical laboratory analytes are presented in Table 1. More information on descriptive statistics 
is presented in Section 8.6. 
ECG data will be listed. Concomitant medications, coded using the World Health Organization (WHO) 
drug dictionary, administered within 3 days prior to MB-102 dose administration and through the follow-
up study visit will be also listed. Furthermore, concomitant non-drug therapies will be listed. 
7.1 
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 (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 will be performed in accordance with a written Safety Review Committee Plan. 
7.2 
Assessment of Causality 
The casual relationship to the study procedures and the investigational device for each adverse event will 
be related as follows: 
 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. 
 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. 
7.3 
Assessment of Severity 
The severity of the adverse events will be rated based upon the following grades: 
 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 


 
 
Statistical Analysis Plan 
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29 
MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
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.  
7.4 
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 
 
7.5 
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) 
 
7.6 
Evaluation of Device Malfunctions  
Device malfunctions will be tabulated and listed in a manner similar to the methods described for adverse 
events. Any device malfunction leading to an adverse event or study termination will be listed separately. 
 
 


 
 
Statistical Analysis Plan 
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29 
MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
8 General Statistical Considerations 
 
8.1 
Analysis Sets 
 
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 average session tGFR or an average 
snapshot tGFR* has been calculated, and who have not had any major protocol deviations that 
would impact TGFR system performance.   
 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. 
* Note: this includes short gaps in data that are less than 30 minutes due to a resumption of the 
monitoring session where an “average snapshot GFR” is reported instead of an “average session 
GFR”.  
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.  
The ITM and mITM populations will be analyzed from subjects enrolled in the Validation 2 and 
Validation 3 (if applicable) cohorts only.  
8.2 
Sample Size Determination 
 
The One-Sample Proportion Test is used to calculate the sample size. The required sample size was 
calculated assuming the true proportion is 0.95, the test is one-sided exact binomial, 𝛼= 0.025, and the 
power is 1 −𝛽= 0.90. The P30 sample size calculation yields 102 subjects. However, to remain 
consistent with the previous sample size from the pivotal study (protocol 100-003) for the TGFR, the 
study will enroll 140 evaluable subjects. 


 
 
Statistical Analysis Plan 
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29 
MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
An adaptive trial design will be employed for the reusable sensor as follows:   
1. Run-in cohort of up to 30 evaluable subjects will commence the study. Additional Run-in 
subjects may be enrolled at new clinical sites to ensure protocol compliance. Run-in subject 
data will be considered tuning data.  
2. Validation Cohort 1 (approximately 20 evaluable subjects) will be used to confirm final 
algorithm selection. Validation Cohort 1 subject data will be considered tuning data.  
3. Validation Cohort 2 (approximately 75 evaluable subjects) will be analyzed in an interim 
analysis to compare results against the primary endpoint specification. At that time, the 
primary endpoint null hypothesis will be tested using an exact binomial test at a one-sided 
nominal alpha level of 0.0150 using the method of Pocock for a two-stage design with the 
interim analysis performed based on the first 53.57% of the planned number of subjects. At 
the final analysis, the primary endpoint null hypothesis will also be tested at a one-sided 
nominal alpha level of 0.0150. This will control the overall Type I error rate at the one-sided 
0.025 level. 
4. If the primary endpoint has been achieved, the study will be terminated. If not, the trial will 
be continued.  
5. Validation Cohort 3 (approximately 65 evaluable subjects) will be enrolled in the event the 
interim analysis did not meet the primary outcome measure. Final analysis will be of the 140 
evaluable subjects. 
The subjects will be chosen to span the range of renal function from normal to Stage 4 CKD impaired.  
The protocol will target enrolling 50% of subjects in the Fitzpatrick Skin Scale range of I-III and 50% 
within Fitzpatrick Skin Scale range of IV-VI.  
8.3 
Pooling Data Across Sites 
 
Up to five US investigational sites will enroll subjects into the study. All investigational sites will follow 
the requirements of a common protocol and standardized data collection and validation procedures and 
forms. The sponsor will also adequately monitor the study to assure protocol compliance. The primary 
effectiveness and safety endpoints will be presented separately for each site using descriptive statistics. 
Poolability of the primary efficacy endpoint across investigational sites will be evaluated using a logistic 
regression model with a fixed effect for site at the 15% level of significance. If there is a significant effect 
of site (i.e., p<0.15 for the fixed effect for site), analysis will be repeated using site as a random effect. 
Sites enrolling fewer than 5 subjects will be combined to form one quasi site.  Additional exploratory 
analyses may be performed to understand any variations in outcome by site.  
 


 
 
Statistical Analysis Plan 
Page 27 of 
29 
MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
8.4 
Handling of Missing Data 
All attempts will be made to limit the amount of missing data. No imputation will be utilized. If a data 
point is missing, that data point will not contribute to that portion of the analysis. The number of 
evaluable observations will be reported in the analysis so that extent of missing data can be assessed. 
8.5 
Statistical Software 
All statistical analysis will be conducted using SAS version 9.4 or later (SAS Institute Inc., Cary, NC) or 
other widely accepted statistical or graphical software as required. The pharmacokinetic assessments will 
be performed using Phoenix WinNonlin (and possibly Phoenix NLME) Build 8.1 or higher. 
 
8.6 
Descriptive Statistics 
Continuous data will be summarized with the number of evaluable observations, mean, standard 
deviation, median, minimum, and maximum. Categorical variables will be summarized with frequency 
counts and percentages. Summaries will be based on observed data (i.e., no missing data will be imputed). 
Confidence intervals may be presented, where appropriate, using the t-distribution for continuous data 
and Clopper-Pearson Exact method for categorical variables. 
 
8.7 
Statistical Significance 
Unless otherwise specified, hypothesis testing will be performed at the two-sided 0.05 significance level 
and one-sided 0.025 significance level. Nominal p-values will be rounded to four decimal places. If a 
nominal p-value is less than 0.0001 it will be reported as “<0.0001”. In the event of multiple testing the 
overall type I error becomes inflated. There are several strategies to correct the alpha level when 
performing multiple tests.  In this study, to control the inflation of overall type I error, the Benjamini-
Hochberg method will be applied.  
 
8.8 
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. 


 
 
Statistical Analysis Plan 
Page 28 of 
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MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
8.9 
Analysis  
After the run-in cohort, the study will include up to 140 evaluable subjects. After 75 evaluable subjects 
have completed the study, an interim analysis will be conducted.  If the primary endpoint has been 
reached, the study will be terminated.  If the primary endpoint has not been completed, the study will 
continue until 140 evaluable subjects have completed the study.  
 
9 Changes from Planned Analyses 
 
Any changes to planned statistical analyses determined necessary prior to performing the analyses will be 
documented in an amended Statistical Analysis Plan and approved prior to the analysis when possible. 
Any other deviations or changes from the planned analyses deemed necessary due to violation of critical 
underlying statistical assumptions, data characteristics, or missing data will be clearly described in the 
clinical study report with justification and rationale. 
 
10 Subject Listings 
 
Subject listings will be provided for the primary endpoint. Listings will also be provided for adverse 
events. 
All plasma concentrations will be provided in listings by subject and time point. Any blood measurements 
obtained outside of a ±2 minute window around the scheduled time point for up through 90 minutes, and 
a ±5 minute window for the remaining sampled collected will be identified as protocol deviations. 
Additionally, pharmacokinetic parameters will be provided in listings sorted by subject. 
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. ECG data will be listed. 
 
 


 
 
Statistical Analysis Plan 
Page 29 of 
29 
MediBeacon 
Inc. 
An Open Label, Multi-Center, Safety and Pharmacokinetic 
Bridging Study of MB-102 (Relmapirazin) and the Use of the 
MediBeacon® Transdermal GFR Measurement System using 
the TGFR Reusable Sensor with Disposable Adhesive Ring in 
Normal and Renal Compromised Subjects for the Evaluation of 
Kidney Function 
Ver 4.0 
 
 
Confidential 
 
11 Tables 
 
Table 1 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