Conditions: ICU Acquired Weakness
Keywords: ICU acquired weakness, PICS, SIRS Muscle wasting and weakness muscle function quality of life
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 8
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics (PK) of FDY-5301 compared to placebo in major trauma ICU patients at risk of intensive care unit acquired weakness (ICUAW)

Detailed description:
The purpose of the trial is to evaluate the efficacy, safety, and PK of FDY-5301 compared to placebo in trauma ICU patients at risk of ICUAW.

Muscle wasting occurs rapidly after major trauma and is often associated with multi-organ failure lasting from a few weeks to a long term disability. It is believed that FDY-5301 may help prevent or treat muscle weakness and organ dysfunction in major trauma patients.

Approximately 252 subjects will be randomized (1:1:1) to receive up to 7 daily bolus IV doses of FDY-5301 at 1 mg/kg or 2 mg/kg, or volume-matched placebo. To ensure equal representation in each group, the randomization will be stratified by the presence or absence of any pelvic or lower limb fractures.

All subjects who satisfy the eligibility criteria will be randomly allocated to one of three treatment groups (FDY-5301 low dose, FDY-5301 high dose, or placebo).

All subjects will be followed for 6 months.

This study will be conducted globally.

Arms:
arm 1: FDY-5301 will be administered intravenously once daily for up to 7 days. Dosage will be determined on a body weight basis, according to treatment assignment and using the subject's body weight (estimated or actual) determined at screening. arm 2: FDY-5301 will be administered intravenously once daily for up to 7 days. Dosage will be determined on a body weight basis, according to treatment assignment and using the subject's body weight (estimated or actual) determined at screening. arm 3: Placebo will be administered intravenously once daily for up to 7 days. Dosage will be determined on a body weight basis, according to treatment assignment and using the subject's body weight (estimated or actual) determined at screening.

Other Names:

Saline

Interventions: intervention 1: FDY-5301 intervention 2: Placebo
Intervention descriptions: intervention 1: FDY-5301 is Sodium Iodide administered as an isotonic solution for intravenous injection with a concentration of 7.2 mg/ml. intervention 2: Placebo is delivered as a single dose, non-reserved liquid parenteral consisting of a formulation matched compendial saline.

Protocol document:
Prot_SAP_001.pdf: 
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Clinical Study Protocol FDY-5301-203 
 
Amendment 2: 21 OCT 2020 
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CLINICAL STUDY PROTOCOL 
 
Study Title: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled 
Study of Intravenous FDY-5301 for the Prevention and 
Treatment of ICU Acquired Weakness in Major Trauma 
Patients 
Investigational Product: 
FDY-5301 
Protocol Number: 
IND Number: 
EudraCT Number: 
FDY-5301-203 
142828 
2019-003429-66 
Sponsor: 
Faraday Pharmaceuticals, Inc. 
1616 Eastlake Ave E, Suite 560 
Seattle, WA 98102 
United States 
Protocol Version / Date: 
Original / 07 NOV 2019 
Amendment 1 / 21 JAN 2020 
Amendment 1.1 (UK) / 25 MAR 2020 
Amendment 2 / 21 OCT 2020 
 
 
 
 
   
 
Confidentiality Statement 
This document contains confidential information of Faraday Pharmaceuticals, Inc. that must not 
be disclosed to anyone other than the recipient study staff and members of the study site or their 
IRB/IEC. This information cannot be used for any purpose other than the evaluation or conduct 
of the clinical investigation without the prior written consent of Faraday Pharmaceuticals, Inc.  


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INVESTIGATOR’S AGREEMENT 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of Intravenous FDY-
5301 for the Prevention and Treatment of ICU Acquired Weakness in Major Trauma 
Patients 
Protocol Version / Date: 
Amendment 2 / 21 OCT 2020 
I have read the attached protocol and agree to comply with the International Council for 
Harmonization Tripartite Guideline on Good Clinical Practice, the ethical principles stated in the 
latest version of the Declaration of Helsinki, and the applicable local and international 
regulations, whichever provide the greater protection of the individual. 
I agree to ensure that the confidential information contained in this document will not be used for 
any purpose other than the evaluation or conduct of the clinical investigation without the prior 
written consent of Faraday Pharmaceuticals, Inc. 
 
 
 
Signature 
 
 
 
 
 
Principal Investigator 
 
Date (DD MON YYYY) 
 


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SPONSOR STATEMENT 
I have read this protocol and agree that it contains all necessary information required to conduct 
the study. 
 
 
 
Signature 
 
 
Simon J. Tulloch, MA(Oxon), BM BCh 
 
 
Chief Medical Officer  
 
Date (MM/DD/YYYY) 
DocuSign Envelope ID: FB63DAB7-A6AC-499C-A42B-6DFD84395FD7
10/22/2020


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SYNOPSIS 
Sponsor: 
Faraday Pharmaceuticals, Inc. 
1616 Eastlake Ave E, Suite 560 
Seattle, WA 98102 
Investigational Product: 
FDY-5301 
Active Ingredient: 
Sodium Iodide (NaI) 
Study Title:  
A Phase 2, Randomized, Double-Blind, Placebo-Controlled 
Study of Intravenous FDY-5301 for the Prevention and 
Treatment of ICU Acquired Weakness in Major Trauma 
Patients 
Study Number: 
IND Number: 
EudraCT Number: 
FDY-5301-203 
142828 
2019-003429-66 
Phase:  
2 
Purpose: 
To evaluate the efficacy, safety, and pharmacokinetics (PK) 
of FDY-5301 compared to placebo in major trauma ICU 
patients at risk of intensive care unit acquired weakness 
(ICUAW) 
Primary Objective: 
To assess the effect of FDY-5301 on muscle function and 
organ dysfunction in the major trauma intensive care unit 
(ICU) population 
Secondary Objectives: 
To assess the effect of FDY-5301 on other clinical 
outcomes in the major trauma ICU population 
Coprimary Endpoints: 
• Chelsea Critical Care Physical Assessment Tool (CPAx) 
total score at Day 10, or hospital discharge, whichever 
occurs first 
• Organ dysfunction total time to recovery (TTR) until 
Day 28 
Secondary Endpoints: 
The secondary endpoints will be analyzed in the following 
sequence: 
• Medical Research Council Sum Score (MRC-SS) at Day 
28 or hospital discharge, whichever occurs first  
• Worst Sequential Organ Failure Assessment (SOFA) 
score during ICU stay 


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• Overall survival at Day 28 
Safety Endpoints: 
Safety will be evaluated based on occurrence of or changes 
throughout the study in the following parameters: 
• Adverse events (AEs), treatment-emergent adverse 
events (TEAEs), and serious adverse events (SAEs) 
• Clinical laboratory assessments (hematology, clinical 
chemistry, and thyroid function tests) 
• 12-lead electrocardiogram (ECG) assessments 
Exploratory Endpoints: 
• Overall survival at Month 3 and Month 6 from date of 
injury 
• Time to successful ventilator extubation from time of 
first dose 
• Time to hospital discharge from first hospital arrival 
time and time of first dose, and discharge disposition 
(e.g., home, home with community support, 
rehabilitation unit, or nursing home) 
• Incidence of sepsis through Day 28 
• SOFA score and sub score components at Days 1, 3, 7,  
14, 21, and Day 28 or ICU discharge, whichever occurs 
first 
• CPAx total score and sub score components at Days 1, 
3, 7, 10 (sub score components only), 14, 21, and Day 
28 or hospital discharge, whichever occurs first 
• Medical Outcomes Study Questionnaire Short Form 
36v2 Health Survey (SF-36v2) and activities of daily 
living questionnaire (Barthel Index) at Day 28 or 
hospital discharge (whichever occurs first), Month 3, 
and Month 6  
• Proportion of subjects who can complete any sit-to-stand 
maneuver and the number of sit-to-stand maneuvers 
completed in 30 seconds at Days 10, 14, 21, and Day 28 
or hospital discharge, whichever occurs first 
• Individual organ dysfunction TTR until Day 28 
In a subset of subjects: 
• Blood metabolic, inflammatory, and biochemical 
markers of muscle damage analysis at Days 1, 3, and 7  
• Plasma iodide concentrations evaluated at up to 4 hours 
(hrs) pre- and post-dose on Days 1, 3, and 7 
• Leukocyte gene expression analysis at Days 1 and 7 
• Percent change from baseline in the level of the 3rd 
lumbar (L3) vertebra Skeletal Muscle Index (SMI) and 


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other muscle volume measures based on Computerized 
Tomography (CT) scan at Day 10 
Methodology:  
Randomized subjects will be dosed as soon as possible and 
within 48 hours of their first hospital arrival time and will 
receive up to 7 daily bolus intravenous (IV) doses of 
FDY-5301 (1 mg/kg or 2 mg/kg) or volume-matched 
placebo. All subjects will be followed for 6 months.  
Number of Subjects: 
Approximately 252 subjects randomized in a 1:1:1 ratio 
Inclusion Criteria:  
1. Age 18-75 years 
2. Major trauma defined as:  
a. thoracic and/or abdominal and/or pelvic injury 
b. necessitating admission to ICU with ventilation 
anticipated for at least 24 hrs 
c. hemorrhagic shock defined as systolic blood 
pressure (SBP) <90 mmHG requiring blood 
transfusion or base deficit of at least 6mEq/L pre-
hospital arrival or within one hour after hospital 
arrival 
3. IRB/IEC-approved consent obtained within 48 hours of 
first hospital arrival time (i.e., in case of transfers, use 
time of arrival to first hospital immediately post injury) 
Exclusion Criteria: 
1. Likely to die within 48 hrs from time of screening  
2. Any neurological condition that is perceived at the time 
of hospital admission as an immediate threat to life or 
incompatible with good functional recovery and where 
early limitation or withdrawal of therapy is being 
considered. For example: 
• Computed tomography imaging showing evidence of 
traumatic brain injury (TBI), combined with best 
representative Glasgow Coma Score (GCS) Motor 
Score of ≤4 at approximately 24 hrs post injury 
3. Evidence of nonreversible spinal cord injury  
4. Bilateral femoral fractures 
5. Women who are pregnant or breastfeeding. Women of 
reproductive potential must have a negative serum 
pregnancy test prior to randomization. 
6. Known thyroid disease or thyroid disorder, including 
subjects on thyroid hormone replacement therapy at the 
time of randomization 
7. Known allergy to iodine 
8. Chronic renal disease requiring dialysis 
9. Body mass index (BMI) >40 kg/m2 or <16 kg/m2 


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10. Body weight (BW) >140 kg (or >309 lb) 
11. History or presence of debilitating neurologic or other 
neuromuscular disease (e.g., spina bifida, amyotrophic 
lateral sclerosis, multiple sclerosis) at time of 
randomization 
12. Current metastatic cancer 
13. Solid organ transplant recipient 
14. Evidence of pre-existing sarcopenia defined as having a 
pre-trauma Clinical Frailty Score (CFS) of ≥5 or based 
on clinical judgement (e.g. frail by appearance, cachexia, 
etc.) 
15. Use of systemic corticosteroids, immunomodulators, or 
oncologic chemotherapy within 6 months of 
randomization (inhaled and topical steroids are allowed) 
16. Use of investigational drugs or devices within 30 days of 
randomization  
17. Any clinically significant abnormality identified prior to 
randomization that in the judgment of the Investigator or 
Sponsor would preclude safe completion of the study, or 
confound the anticipated benefit of FDY-5301 
Test Product, Dosage and 
Mode of Administration:  
FDY-5301 (dose of 1 mg/kg or 2 mg/kg) will be 
administered IV by bolus injection daily for up to 7 
injections. 
Control Product, Dosage and 
Mode of Administration:  
Placebo (normal saline) will be administered IV by bolus 
injection daily for up to 7 injections. Placebo will be 
volume-matched and indistinguishable from FDY-5301. 
Duration of Study: 
Each subject’s participation will be approximately 6 months 
from the time of screening to study exit.  
Statistical Methods: 
A stratified randomization scheme will be employed in this 
study, with presence of pelvic or lower limb fractures as the 
stratification factor. 
Subjects will be stratified into two groups: 
• subjects with pelvic or lower limb fractures 
• subjects without pelvic or lower limb fractures 
Safety Analyses: 
All safety measures will be summarized descriptively. AEs 
will be summarized by Medical Dictionary for Regulatory 
Activities (MedDRA) system organ class and preferred 
term. 


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Efficacy Analyses: 
For comparisons between groups, the primary analysis will 
be the combined FDY-5301 treated groups compared to 
placebo. If the difference between the means of pooled 
treatment group compared to the placebo group is 
statistically significant, a step-down procedure will be 
followed to test the individual FDY-5301 doses compared to 
placebo. The following testing order of doses will be 
employed:  
1) FDY-5301 2 mg/kg versus placebo 
2) FDY-5301 1 mg/kg versus placebo 
The first primary efficacy endpoint is the CPAx total score 
at Day 10 (or at hospital discharge, whichever occurs first). 
As the primary analysis, the treatment comparison of the 
CPAx total score will be performed using an analysis of 
covariance (ANCOVA). The model will include CPAx total 
score at Day 10 (or at hospital discharge, whichever occurs 
first) as a dependent variable, treatment and stratification 
category (with or without presence of pelvic or lower limb 
fractures) as factors, and “baseline” CPAx (the first 
available datapoint) as a continuous covariate. 
The p-values, least-squares means, standard errors, and the 
2-tailed 95% confidence intervals for the treatment groups 
and placebo group will be presented. 
The second primary efficacy endpoint, organ dysfunction 
total  TTR until Day 28, will be estimated using Kaplan-
Meier estimator and compared using log-rank test at a 
significance level 0.05. 
Sample size determination: 
Approximately 252 subjects will be randomized to receive 
FDY-5301 1 mg/kg, 2 mg/kg, or placebo, in a 1:1:1 ratio. 
This sample size was established based on a 15% drop-out 
rate. This sample size provides greater than 90% power to 
detect an improvement of 6 in the CPAx total score for 
pooled FDY-5301 (1 mg/kg or 2 mg/kg) compared with 
placebo (e.g. 36 in pooled FDY-5301 group vs. 30 in 
Placebo group), assuming a standard deviation of 12 
(Corner 2015 and Raymond 2020).  
Given the assumption that the median expected organ 
dysfunction recovery time is 7 days for the placebo group 
and the median expected organ dysfunction recovery time is 
4.9 days for the pooled treatment group (Xiao 2011) (i.e. an 


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expected relative risk reduction of 30% and a 2-sided log-
rank test at a significance level of 0.05), the study would 
have approximately 70% power if at least 213 events are 
observed (based on no subject being censored until Day 28).  
The sample size calculations were based on the coprimary 
endpoints achieving a p-value of <0.05 each. 
For secondary endpoints, a sequential analysis will be 
performed. The continuous secondary efficacy endpoints of 
MRC-SS and worst SOFA score will be analyzed with an 
ANCOVA model similar to the one described for the 
primary endpoint of CPAx total score. The secondary 
endpoint of overall survival at Day 28 will be analyzed 
using a Kaplan-Meier approach and a log-rank test, similar 
to the methodology described for the primary endpoint of 
organ dysfunction total TTR until Day 28. 
Data Safety Monitoring Committee (DSMC): 
An independent DSMC will be established prior to the 
initiation of the study to monitor and assess safety at 
intervals. 


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TABLE OF CONTENTS  
SYNOPSIS ..................................................................................................................................... 4 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ............................................ 14 
1 
INTRODUCTION...................................................................................................... 17 
1.1 
Disease Setting ............................................................................................................. 17 
1.2 
FDY-5301 Background ................................................................................................ 17 
1.2.1 
Product Description ..................................................................................................... 17 
1.2.2 
Preclinical Data ............................................................................................................ 17 
1.2.3 
Clinical Experience ...................................................................................................... 18 
1.2.4 
Theoretical Risks and Benefits .................................................................................... 19 
1.3 
Rationale for Disease Indication .................................................................................. 19 
1.4 
Rationale for Study Design .......................................................................................... 20 
1.5 
Justification for Dose ................................................................................................... 21 
2 
TRIAL OBJECTIVES AND ENDPOINTS............................................................. 22 
3 
INVESTIGATIONAL PLAN ................................................................................... 24 
3.1 
Overall Study Design ................................................................................................... 24 
3.2 
Number of Centers/Subjects ........................................................................................ 25 
3.3 
Estimated Study Duration ............................................................................................ 25 
3.4 
Assignment to Study .................................................................................................... 25 
4 
SELECTION AND WITHDRAWAL OF SUBJECTS .......................................... 26 
4.1 
Inclusion Criteria ......................................................................................................... 26 
4.2 
Exclusion Criteria ........................................................................................................ 26 
4.3 
Screen Failures ............................................................................................................. 27 
4.4 
Subject Discontinuation of Investigational Product Administration ........................... 27 
4.4.1 
Renal Failure ................................................................................................................ 27 
4.5 
Subject Withdrawal from the Study ............................................................................. 28 
4.6 
Subjects Lost to Follow Up.......................................................................................... 28 
5 
STUDY SCHEDULE ................................................................................................. 29 
6 
STUDY ASSESSMENTS .......................................................................................... 32 
6.1 
Efficacy Assessments................................................................................................... 32 
6.1.1 
CT Scan of Abdomen (CT Subset of Subjects Only) .................................................. 32 
6.1.2 
Sit-to-Stand Assessment .............................................................................................. 32 
6.1.3 
Organ Dysfunction Time to Recovery (TTR) .............................................................. 32 
6.1.4 
Sequential Organ Failure Assessment Score (SOFA) ................................................. 32 
6.1.5 
Chelsea Critical Care Physical Assessment (CPAx) ................................................... 33 
6.1.6 
Medical Research Council Sum Score (MRC-SS) ...................................................... 33 
6.1.7 
Barthel Index ................................................................................................................ 34 
6.1.8 
Medical Outcomes Study Questionnaire Short Form 36v2 (SF-36v2) Health Survey 34 
6.1.9 
Time of Extubation ...................................................................................................... 35 
6.1.10 
Occurrence of Sepsis.................................................................................................... 35 
6.1.11 
Discharge and Disposition ........................................................................................... 35 
6.1.12 
General Health Inquiry ................................................................................................ 35 


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6.1.13 
Overall Survival ........................................................................................................... 35 
6.1.14 
Research Blood Samples (US Sites Only) ................................................................... 35 
6.2 
Demographics and Safety Assessments ....................................................................... 36 
6.2.1 
Demographics .............................................................................................................. 36 
6.2.2 
Medical History ........................................................................................................... 36 
6.2.3 
Physical Examination................................................................................................... 36 
6.2.4 
Estimated Height and Weight ...................................................................................... 36 
6.2.5 
Serum Pregnancy Test ................................................................................................. 36 
6.2.6 
Concomitant Medications ............................................................................................ 36 
6.2.7 
Safety Laboratory Tests ............................................................................................... 36 
6.2.8 
12-Lead Electrocardiogram ......................................................................................... 36 
6.2.9 
Trauma Related Injury Severity Score (TRISS) .......................................................... 37 
7 
STUDY TREATMENTS ........................................................................................... 38 
7.1 
Description of Investigational Product ........................................................................ 38 
7.2 
Randomization, Stratification and Blinding ................................................................ 38 
7.3 
Procedure for Unblinding ............................................................................................ 38 
7.4 
Prohibited Concomitant Medications .......................................................................... 38 
8 
INVESTIGATIONAL PRODUCT MATERIALS AND MANAGEMENT ........ 39 
8.1 
Investigational Product ................................................................................................ 39 
8.2 
Packaging and Labeling ............................................................................................... 39 
8.3 
Shipment and Storage .................................................................................................. 39 
8.4 
Preparation and Administration ................................................................................... 39 
8.5 
Investigational Product Accountability and Disposal .................................................. 40 
9 
SAFETY: ADVERSE EVENTS ............................................................................... 41 
9.1 
Definitions.................................................................................................................... 41 
9.2 
Recording Diagnosis Versus Signs and Symptoms ..................................................... 41 
9.3 
Laboratory Abnormalities or Other Abnormal Assessments ....................................... 41 
9.4 
Relationship to Investigational Product ....................................................................... 41 
9.5 
Severity of Adverse Events .......................................................................................... 42 
9.6 
Reporting Serious Adverse Events .............................................................................. 42 
9.7 
Pregnancy Reporting .................................................................................................... 44 
9.8 
Expedited Reporting Requirements ............................................................................. 45 
9.8.1 
Suspected Unexpected Serious Adverse Reaction ....................................................... 45 
10 
STATISTICS .............................................................................................................. 46 
10.1 
Analysis Populations .................................................................................................... 46 
10.2 
Statistical Methods ....................................................................................................... 46 
10.2.1 
Demographic and Baseline Characteristics ................................................................. 46 
10.2.2 
Handling of Missing Data ............................................................................................ 46 
10.2.3 
Safety Analyses ............................................................................................................ 46 
10.2.4 
Efficacy Analyses ........................................................................................................ 47 
10.2.5 
Pharmacokinetics Analyses ......................................................................................... 49 
10.2.6 
Interim Analysis ........................................................................................................... 49 
10.2.7 
Sample Size Determination and Power Calculations................................................... 49 
11 
DATA MONITORING COMMITTEES ................................................................. 50 


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11.1 
Data Safety Monitoring Committee ............................................................................. 50 
11.2 
Imaging Central Review .............................................................................................. 50 
12 
STUDY GOVERNANCE .......................................................................................... 51 
12.1 
Regulatory and Ethical Conduct of the Study.............................................................. 51 
12.2 
Financial Disclosure..................................................................................................... 51 
12.3 
Informed Consent......................................................................................................... 51 
12.4 
Data Protection............................................................................................................. 52 
12.5 
Publication Policy ........................................................................................................ 52 
12.6 
Dissemination of Clinical Study Data.......................................................................... 52 
12.7 
Data Quality Assurance ............................................................................................... 52 
12.8 
Study and Site Closure ................................................................................................. 54 
13 
REFERENCES ........................................................................................................... 55 
APPENDIX 1: STUDY ADMINISTRATIVE INFORMATION ........................................... 57 
APPENDIX 2: CLINICAL LABORATORY TESTS ............................................................. 58 
APPENDIX 3: TRISS METHOD .............................................................................................. 59 
APPENDIX 4: ORGAN DYSFUNCTION TTR ...................................................................... 61 
APPENDIX 5: SOFA CRITERIA ............................................................................................. 62 
APPENDIX 6: BARTHEL INDEX ........................................................................................... 63 
APPENDIX 7: CLINICAL FRAILTY SCORE ....................................................................... 64 
 
 
 


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List of Tables 
Table 1: Schedule of Assessments ............................................................................................. 30 
Table 2: Additional Schedule of Assessments ........................................................................... 31 
Table 3: Relationship of Adverse Events to IP .......................................................................... 42 
Table 4: CTCAE General Categories ......................................................................................... 42 
 
LIST OF FIGURES 
Figure 1: 
Study Schema .......................................................................................................... 24 
 


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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation or Specialist Term Explanation 
A-aDO2 
alveolar-arterial oxygen gradient 
ADL 
activities of daily living 
AE 
adverse event 
ANCOVA 
analysis of covariance 
AUC 
area under the curve 
AUCinf 
area under the plasma concentration-time curve from time 
zero to infinity 
BMI 
body mass index 
BW 
body weight 
CFS 
Clinical Frailty Score 
Cmax 
maximal concentration  
CNS 
central nervous system 
CPAx 
Chelsea Critical Care Physical Assessment Tool 
CRF 
case report form 
CRO 
clinical research organization 
CT 
computerized tomography 
DLT 
dose-limiting toxicity 
DSMC 
Data Safety Monitoring Committee 
ECG 
electrocardiogram 
EDC 
electronic data capture 
FiO2 
fraction of inspired oxygen 
GCP 
Good Clinical Practice 
GCS 
Glasgow Coma Score 
GLP 
Good Laboratory Practice 
hrs 
hours 
IB 
Investigator Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonization 
ICU 
intensive care unit 
ICUAW 
intensive care unit acquired weakness 
IEC 
Independent Ethics Committee 


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Abbreviation or Specialist Term Explanation 
INDSR 
Investigational New Drug safety report 
IP 
investigational product 
IRB 
Institutional Review Board 
IRT 
interactive response technology 
ISS 
Injury Severity Score 
ITT 
intent to treat 
IV 
intravenous  
L3 
level of third lumbar vertebrae 
MedDRA 
Medical Dictionary for Regulatory Activities 
µg/kg/min 
microgram per kilogram per minute 
µL 
microliter(s) 
µmol/L 
micromolar per liter 
mEq/L 
milliequivalents per liter 
mg/dL 
milligram per deciliter 
mL 
milliliter(s) 
mmHg 
millimeters of mercury 
MRC 
Medical Research Council 
MRC-SS 
Medical Research Council Sum Scores 
NaI 
sodium iodide 
NOAEL 
no-observed-adverse-effect level 
PaO2 
partial pressure of arterial oxygen 
PCI 
percutaneous coronary intervention 
PICS 
post intensive care syndrome 
PK 
pharmacokinetics 
PP 
per protocol 
ROS 
reactive oxygen species 
RR 
respiratory rate 
RTS 
Revised Trauma Score 
S2S 
sit-to-stand 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SBP 
systolic blood pressure 


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Abbreviation or Specialist Term Explanation 
SF-36v2 
Short Form 36v2 
SMI 
skeletal muscle index 
SOFA 
Sequential Organ Failure Assessment 
STEMI 
ST-elevation myocardial infarction 
SUSAR 
suspected unexpected serious adverse reaction 
T1/2 
terminal half-life 
TBI 
traumatic brain injury 
TEAE 
treatment-emergent adverse event 
Tmax 
time when the maximal concentration is achieved 
TMF 
trial master file 
TRISS 
Trauma Related Injury Severity Score 
TTR 
time to recovery 
 


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1 
INTRODUCTION 
1.1 
Disease Setting 
ICU-acquired weakness (ICUAW) is characterized by peripheral muscle weakness and wasting 
for which no other cause can be identified besides the acute illness or its treatment (Hermans 
2015, Needham 2012, Stevens 2009, Puthucheary 2013), which has been observed to last from a 
few weeks to years. ICUAW may be a major part of a long-term, post-intensive care syndrome 
(PICS) described as physical, mental and cognitive dysfunction, which extends beyond the acute 
hospitalization and has a major impact on the quality of life of the growing population of ICU 
survivors (Needham 2012). ICUAW is associated with diminished life expectancy 12 months 
post-discharge (Hermans 2015).  
The profound inflammation and oxidative stress that occurs during critical illness leads to early 
depletion of many endogenous antioxidants; for example, lower circulating concentrations of 
tocopherol and ascorbate in association with increased concentrations of oxidized glutathione in 
the plasma of critically ill patients have been documented (Friedrich 2015, Goode 1995, 
Marshall 2007, Bertrand 1989, Metnitz 1999, Borrelli, 1996). De-iodination of thyroid hormones 
to release free iodide may be a beneficial endogenous reaction to injury, however the reducing 
capacity of that free iodide will be exceeded by anything beyond a modest injury. 
FDY-5301 is designed to provide immediate and bioavailable supra-physiological concentrations 
of iodide, which is a potent reducing agent. In particular, it acts to catalytically degrade hydrogen 
peroxide; this differs from other agents which themselves are oxidized in the reaction with 
peroxide. The hypothesis, supported by clinical and preclinical data, is that FDY-5301 will 
therefore ameliorate the systemic inflammatory response and consequent tissue damage and 
immune dysfunction that follow major trauma, with benefits to tissues, including muscle, that are 
injured downstream of the initial traumatic injury.  
1.2 
FDY-5301 Background 
1.2.1 
Product Description 
The active pharmaceutical ingredient in FDY-5301 Injection is sodium iodide. FDY-5301 is 
formulated as an isotonic solution in single-use vials for intravenous (IV) administration. The 
solution has a pH between 7.0 and 9.5. The chemical formula of sodium iodide is NaI.  
1.2.2 
Preclinical Data 
Pharmacology studies have shown that iodide catalytically disproportionates hydrogen peroxide 
in vitro and reduced myocardial injury in several species with experimentally induced ischemia-
reperfusion models. In a hind limb ischemia-reperfusion rodent model, iodide was seen to reduce 
muscle damage, and reduce systemic and muscle markers of inflammation. 
The studies conducted for nonclinical safety assessment of FDY-5301 include pilot and Good 
Laboratory Practice (GLP) 7- and 14-day IV repeat-dose toxicity studies, fertility and 
teratogenicity studies, pharmacokinetic studies, local tolerability studies, a series of in vitro and 


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in vivo safety pharmacology, in vitro hemocompatibility, in vitro cytochrome P450 induction 
and inhibition, in vitro protein binding, and genotoxicity studies conducted in accordance with 
International Council for Harmonization (ICH) guidelines. 
In rats, no signs of toxicity were observed at doses up to 74 mg/kg given daily IV for 14 days. In 
beagle dogs, the no-observed-adverse-effect level (NOAEL) was established at 20 mg/kg for 
7 days of dosing. The observed dose-limiting toxicity (DLT) at 40 mg/kg was reversible 
gastrointestinal inflammation.  
Safety pharmacology studies included an in vitro hERG K+ ion channel assay, a central nervous 
system (CNS) safety pharmacology study (general signs and behavior) in rats, a pulmonary 
safety pharmacology study in rats, and a cardiovascular safety pharmacology study in dogs. 
Overall, the results of these studies show that at the dosing regimen and at expected systemic 
exposures of FDY-5301 to be achieved in humans, no adverse effects are anticipated to occur in 
any of the major organ systems tested.  
FDY-5301 was found not to be mutagenic in the bacterial reverse mutation assay.  
Other studies with FDY-5301 show that the formulation to be used for clinical trials is not 
expected to cause local perivenous irritation. In addition, it does not exhibit protein binding, nor 
does it inhibit or induce cytochrome P450 enzymatic activity. Other nonclinical assessments 
confirmed that FDY-5301 is not genotoxic in in vitro and in vivo micronucleus studies, does not 
cause irritation at injection sites, does not cause hemolysis, and is compatible with human serum 
and plasma. 
1.2.3 
Clinical Experience 
Faraday has completed recruitment into three clinical trials of FDY-5301:  
1. Study FDY-5301-101: A phase 1 trial evaluating the safety and pharmacokinetics (PK) of 
FDY-5301, which included single ascending doses in 40 healthy volunteer subjects at IV 
doses of 0.1, 0.3, 1.0, 3.0, 10.0 mg/kg and placebo, was conducted. No significant 
adverse events were detected, including biochemical measures of thyroid function, and 
no clinically significant effects on vital signs or electrocardiograms (ECGs) were 
observed.  
2. Study FDY-5301-201: A phase 2 trial in 120 subjects with acute ST-elevation myocardial 
infarction (STEMI) undergoing percutaneous coronary intervention (PCI) was conducted. 
Subjects were randomized to receive IV doses of FDY-5301 (0.5, 1, and 2 mg/kg) or 
volume-matched placebo within an hour prior to myocardial reperfusion for STEMI. 
FDY-5301 did not provoke undesirable arrhythmias based on 14-day continuous 
monitoring. There was a slight excess of nonsustained ventricular tachycardias (<30 
seconds) in the first 48 hours in the 2 mg/kg group. At 3 months, the data suggest the 
subjects on FDY-5301 had smaller infarcts measured by cardiovascular magnetic 
resonance and better cardiac function. The adverse event profile, biochemistry testing, 
including thyroid function, and other safety parameters have identified no safety issues of 
concern. 


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3. Study FDY-5301-202: A phase 2 trial in 34 subjects undergoing unilateral total knee 
replacement was conducted to measure the effect of FDY-5301 at a dose of 1mg/kg on 
quadriceps wasting after the use of a tourniquet. The pattern of TEAEs and SAEs were 
consistent with those normally expected in this adult population and there appears to be 
no relationship between any of these events and study drug when looking at the aggregate 
data. No significant difference was seen between the treatment groups for any of the main 
efficacy parameters. Outliers in both groups lead to wide and unequal variances. The data 
showed that the control group had no impairment in functionality at 6 weeks compared to 
baseline, showed no evidence of muscle wasting, and had a minimal impairment in 
strength. It is conceivable that tourniquet induced ischemia reperfusion injury is not a 
particularly conspicuous contributor to recovery after total knee replacement. 
1.2.4 
Theoretical Risks and Benefits 
There is a theoretical risk of thyroid dysfunction because the active ingredient is sodium iodide. 
Gastrointestinal irritation and bleeding were seen at 40mg/kg per day in 7-day dosing toxicology 
studies in dogs. The dose at which no adverse effects were seen was at 20mg/kg per day in 7-day 
dosing (the intended clinical doses are 1 or 2 mg/kg per day). Faraday continues to actively 
assess and closely monitor these potential risks in clinical trial subjects. 
Trauma patients in ICU are at high risk of developing muscle weakness and other organ failures 
consequent at least in part to a systemic inflammatory response. This leads to short and long-
term morbidity and poor outcomes and has in part been characterized as a “post ICU syndrome.”  
This represents a very high unmet medical need for which effective and safe interventions would 
be of huge benefit. Subjects randomized to FDY-5301 are anticipated to have potential benefits 
such as improvement in muscle wasting or other organ dysfunction consequent on serious injury. 
Subjects randomized to placebo are not anticipated to have any adverse effects related to the 
administration of intravenous sterile saline. In addition, FDY-5301 or placebo will be 
administrated in addition to standard of care, so no subject in FDY-5301 clinical studies will 
have any approved treatment withheld. Subjects randomized to FDY-5301 will have the prospect 
of benefit from this adjunctive experimental medication. 
1.3 
Rationale for Disease Indication 
The precise mechanism by which intensive care unit acquired weakness (ICUAW) occurs is 
unclear; however, there is mounting evidence to suggest that organ and muscle tissue injury are 
mediated at least in part by reactive oxygen species (ROS) (Abrigo 2018, Dodd 2010, Li 2008) 
and systemic inflammation (Friedrich 2015). Faraday has demonstrated, through a series of 
nonclinical mechanistic and pharmacologic studies, the ability of FDY-5301 to catalytically 
disproportionate hydrogen peroxide, reduce inflammation, improve survival, attenuate tissue 
injury, and, in particular, reduce muscle injury in trauma and cancer animal models.  
The hypothesis, therefore, is that damage consequent to the systemic inflammatory response 
from a major injury will be attenuated by the administration of an exogenous reducing agent 
(iodide). This will be measurable as diminished tissue injury, including skeletal muscle, in ICU 
survivors.  


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Importantly, iodide is a catalytic disproportionator of peroxide, which differentiates it from 
vitamins C and E, and other “antioxidants” which, unlike iodide, are oxidized in such reactions 
into pro-oxidant metabolites. In addition, iodide, as FDY-5301, can be quickly, easily and safely 
introduced into patients at doses that are potently catalytic of ROS, and are thousands of fold 
higher than physiological levels of endogenous iodide. 
Given the apparent roles that oxidative stress and oxidant-mediated tissue injury may play in the 
development of multiple organ failure, including muscle wasting, immediate supplementation 
with a potent reducing agent such as iodide may augment patients’ endogenous defenses and 
serve to prevent the development of organ dysfunction (Schorah 1996, Hemila 1997, Maderazo 
1991).  
This hypothesis is supported by recent data from a phase 2 STEMI study in ST elevation 
myocardial infarction patients, which suggests that FDY-5301 may have an effect in reducing 
myocardial ischemia-reperfusion injury after a single IV bolus dose. The improvement of infarct 
size and cardiac function seen, in particular at the 2.0 mg/kg dose, suggests that FDY-5301 might 
be expected to confer benefit in the oxidative damage due to the prolonged inflammatory 
response to major injury.  
The cumulative human and preclinical experience to date suggest that FDY-5301 has an 
acceptable safety profile, and a broad therapeutic margin. 
1.4 
Rationale for Study Design 
The study is designed as a randomized double-blind parallel-group comparison of FDY-5301 and 
placebo. This construct is regarded as the gold standard assay for assessing drug efficacy and 
safety, in that it mitigates observer and reporter bias, has a control group, and should allocate 
similar populations to each group. Given the potential heterogeneity of the major trauma ICU 
population, inclusion and exclusion criteria have been designed to ensure a degree of 
homogeneity, especially in terms of conditions that could compromise efficacy measures, e.g., 
head injury and bilateral lower limb fractures. To ensure equal representation in each group, the 
randomization will be stratified by the presence or absence of any pelvic or lower limb fracture. 
Outcome measures have been selected to collect information on the anatomical, biochemical, and 
functional effects on muscle and on multiple organ failures. In addition, composite rating scales 
are employed to identify effects on specific domains of musculoskeletal and organ function. 
The co-primary outcomes are the Chelsea Critical Care Physical Assessment Tool (CPAx) and 
organ dysfunction total time to recovery (TTR). CPAx is a tool used to measure functional status 
relevant to ICU patients and is dependent on muscle strength and coordination. CPAx will 
provide useful information as to whether muscle wasting and its consequences on muscle 
function can be mitigated by FDY-5301. Organ dysfunction total TTR will provide important 
data on the clinical progress of patients with respect to the cluster of organ failures often seen in 
these patients as a consequence of their injuries and systemic inflammatory responses.   


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1.5 
Justification for Dose 
The selected dosing regimen for FDY-5301 is 1 or 2 mg/kg daily for 7 days and is based on the 
available safety, efficacy and PK modeling data for FDY-5301.  
FDY-5301 is expected to provide clinically significant exogenous reducing capacity when 
administered to major trauma ICU patients. The systemic inflammatory response which triggers 
a catabolic state occurs very early following major trauma, but is postulated to last for longer 
than a day, and perhaps weeks following trauma (Pedroso 2012). For this reason, and given the 
poor outcomes expected in the ICUAW population, 7-day dosing is proposed to provide reducing 
capacity for a period long enough to potentially confer clinical benefit. Daily dosing is based on 
the half-life of FDY-5301 in healthy volunteers of 6 to 8 hours, implying a return to baseline 
levels after 24 hours. 
Up to 10 mg/kg IV of FDY-5301 has been given to healthy volunteers in a phase 1 study without 
adverse effects, and a single IV bolus dose of 2 mg/kg was well tolerated in the phase 2 AMI 
reperfusion study in acutely ill subjects. Specifically, thyroid function tests showed similar group 
means across all groups, with no suggestion of a drug effect. In a published study of healthy 
volunteers, cumulative doses of 14 mg/kg of sodium iodide (given as daily oral doses of 1 mg/kg 
for 14 days) were well tolerated. (Robison 1998). 
In nonclinical safety testing, the NOAEL in a rat 14-day repeat dose GLP toxicity study was 
74 mg/kg/day and the NOAEL in a GLP dog 7-day repeat dose study was 20 mg/kg/day. These 
data support daily dosing in subjects at the high dose in this study of 2 mg/kg for up to 7 days. 
The PK profile of FDY-5301 has been well characterized in humans. Following IV 
administration, a rapid maximal concentration (Cmax) occurs, followed by rapid initial clearance 
from plasma, a terminal half-life of 6 to 8 hours, and trough levels approaching zero at 24 hours. 
Exposure will be adequate for daily administration without accumulation, even in subjects with 
renal impairment. 


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2 
TRIAL OBJECTIVES AND ENDPOINTS 
The purpose of the trial is to evaluate the efficacy, safety, and PK of FDY-5301 compared to 
placebo in major trauma ICU patients at risk of ICUAW.  
Objectives 
Endpoints 
Primary 
To assess the effect of FDY-
5301 on muscle function and 
organ dysfunction in the major 
trauma ICU population 
Coprimary 
• Chelsea Critical Care Physical Assessment Tool (CPAx) 
total score at Day 10, or hospital discharge, whichever 
occurs first  
• Organ dysfunction total time to recovery (TTR) until 
Day 28 
Secondary 
 
To assess the effects of FDY-
5301 on other clinical outcomes 
in the major trauma ICU 
population  
Secondary 
The secondary endpoints will be analyzed in the following 
sequence: 
• Medical Research Council Sum Score (MRC-SS) at Day 
28 or hospital discharge, whichever occurs first  
• Worst Sequential Organ Failure Assessment (SOFA) 
score during ICU stay 
• Overall Survival at Day 28 
Safety 
 
To investigate the safety and 
tolerability of up to 7 daily bolus 
IV doses of FDY-5301 in the 
major trauma ICU population 
Safety 
Safety will be evaluated based on occurrence of or changes 
throughout the study in the following parameters: 
• Adverse events (AEs), treatment-emergent adverse 
events (TEAEs) and serious adverse events (SAEs) 
• Clinical laboratory assessments (hematology, clinical 
chemistry, and thyroid function tests) 
• 12-lead electrocardiogram (ECG) assessments 
Exploratory 
 
To assess the effects of FDY-
5301 on skeletal muscle, muscle 
function, and other clinical 
outcomes and to investigate the 
PK of up to 7 daily bolus IV 
doses in the major trauma ICU 
population  
 
Exploratory 
• Overall survival at Month 3 and Month 6 from date of 
injury 
• Time to successful ventilator extubation from time of 
first dose 
• Time to hospital discharge from first hospital arrival 
time and time of first dose, and discharge disposition 
(e.g., home, home with community support, 
rehabilitation unit, or nursing home) 


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• Incidence of sepsis through Day 28 
• SOFA score and sub score components at Days 1, 3, 7, 
14, 21, and Day 28 or ICU discharge, whichever occurs 
first 
• CPAx total score and sub score components at Days 1, 
3, 7, 10 (sub score components only), 14, 21, and Day 
28 or hospital discharge, whichever occurs first 
• Medical Outcomes Study Questionnaire Short Form 
36v2 Health Survey (SF-36v2) and activities of daily 
living questionnaire (Barthel Index) at Day 28 or 
hospital discharge (whichever occurs first), Month 3, 
and Month 6 
• Proportion of subjects who can complete any sit-to-
stand maneuver and the number of sit-to-stand 
maneuvers completed in 30 seconds at Days 10, 14, 21, 
and Day 28 or hospital discharge, whichever occurs first 
• Individual organ dysfunction TTR until Day 28 
In a subset of subjects: 
• Blood metabolic, inflammatory, and biochemical 
markers of muscle damage analysis at Days 1, 3, and 7 
• Plasma iodide concentrations evaluated up to 4 hrs 
pre- and post-dose on Days 1, 3, and 7 
• Leukocyte gene expression analysis at Days 1 and 7 
• Percent change from baseline in the level of the 3rd 
lumbar (L3) vertebra Skeletal Muscle Index (SMI) and 
other muscle volume measures based on Computerized 
Tomography (CT) scan at Day 10 
 




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3.2 
Number of Centers/Subjects 
This study will be conducted at approximately 12 centers globally. Approximately 252 subjects 
are planned for enrollment in this study. 
3.3 
Estimated Study Duration 
Each subject’s participation will be approximately 6 months from the time of screening to study 
exit.  
3.4 
Assignment to Study  
All subjects with documented consent will be assigned a unique subject number. 
All subjects who satisfy the eligibility criteria will be randomly allocated to one of three 
treatment groups (FDY-5301 at 1 mg/kg or 2 mg/kg, or volume-matched placebo). 


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4 
SELECTION AND WITHDRAWAL OF SUBJECTS 
4.1 
Inclusion Criteria 
Subjects who meet all of the following criteria will be eligible to participate in the study: 
1. Age 18-75 years 
2. Major trauma defined as:  
a. thoracic and/or abdominal and/or pelvic injury 
b. necessitating admission to ICU with ventilation anticipated for at least 24 hrs 
c. hemorrhagic shock defined as systolic blood pressure (SBP) <90 mmHG requiring 
blood transfusion or base deficit of at least 6 mEq/L pre-hospital arrival or within one 
hour after hospital arrival 
3. IRB/IEC-approved consent obtained within 48 hours of first hospital arrival time (i.e., in 
case of transfers, use time of arrival to first hospital immediately post injury) 
4.2 
Exclusion Criteria 
Subjects who meet any of the following criteria will be excluded from participation in the study: 
1. Likely to die within 48 hrs from time of screening 
2. Any neurological condition that is perceived at the time of hospital admission as an 
immediate threat to life or incompatible with good functional recovery and where early 
limitation or withdrawal of therapy is being considered. For example: 
• Computed tomography imaging showing evidence of traumatic brain injury (TBI), 
combined with best representative Glasgow Coma Score (GCS) Motor Score ≤4 at 
approximately 24 hrs post injury 
3. Evidence of nonreversible spinal cord injury  
4. Bilateral femoral fractures 
5. Women who are pregnant or breastfeeding. Women of reproductive potential must have a 
negative serum pregnancy test prior to randomization. 
6. Known thyroid disease or thyroid disorder, including subjects on thyroid hormone 
replacement therapy at the time of randomization 
7. Known allergy to iodine 
8. Chronic renal disease requiring dialysis 
9. Body mass index (BMI) >40 kg/m2 or <16 kg/m2 
10. Body weight (BW) >140 kg (or >309 lb) 
11. History or presence of debilitating neurologic or other neuromuscular disease (e.g., spina 
bifida, amyotrophic lateral sclerosis, multiple sclerosis) at time of randomization 


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12. Current metastatic cancer 
13. Solid organ transplant recipient 
14. Evidence of pre-existing sarcopenia defined as having a pre-trauma Clinical Frailty Score 
(CFS) of ≥5 (see Appendix 7: Clinical Frailty Score) or based on clinical judgement (e.g. 
frail by appearance, cachexia, etc.) 
15. Use of systemic corticosteroids, immunomodulators, or oncologic chemotherapy within 
6  months of randomization (inhaled and topical steroids are allowed) 
16. Use of investigational drugs or devices within 30 days of randomization 
17. Any clinically significant abnormality identified prior to randomization that in the 
judgment of the Investigator or Sponsor would preclude safe completion of the study, or 
confound the anticipated benefit of FDY-5301 
4.3 
Screen Failures 
Screen failures are defined as subjects for whom consent to participate in the clinical study is 
obtained but who are not subsequently randomized. A minimal set of screen failure information 
is required and will be captured on study case report forms (CRFs).  
Individuals who are consented but do not meet the criteria for participation in this study (screen 
failure) may not be rescreened. 
4.4 
Subject Discontinuation of Investigational Product Administration 
Subjects who receive at least 1 dose of IP and are subsequently discontinued from further IP 
administration (e.g., due to toxicity) will not be withdrawn from the study.  
Subjects will remain on study and continue to have all scheduled evaluations through the Month 
6 visit per Section 5, Study Schedule. 
Administration of the IP to a subject may be discontinued for any of the following reasons: 
• Adverse event 
• Investigator decision 
• Sponsor decision 
• Subject or subject’s representative decision 
• Hospital discharge prior to Day 7 
Subjects who discontinue IP will not be replaced. 
4.4.1 
Renal Failure 
Subjects who develop acute renal failure, whether or not they begin dialysis treatment, do not 
require discontinuation of IP administration.  
If a subject requires dialysis, unscheduled plasma PK samples (US sites only) will be collected 
pre- and post-dose of each IP administration while on dialysis.  


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4.5 
Subject Withdrawal from the Study 
All randomized subjects should remain on study and continue to have all scheduled evaluations 
through the Month 6 visit per Section 5. A subject may be withdrawn from the study for any of 
the following reasons: 
• Withdrawal of consent 
• Study termination by Sponsor 
• Lost to follow-up 
Whenever possible, subjects withdrawing from the study should undergo a final visit, to include 
those assessments noted for the Day 28 visit (or Month 6 visit if Day 28 visit was completed).  
The term “withdrawal of consent” should be used only when the subject (or the subject’s legally 
authorized representative) no longer wishes to participate in the trial and no longer authorizes the 
Investigators to follow the subject. 
Withdrawal of consent for follow-up should be accompanied by documentation of the reason for 
withdrawal. Withdrawal of consent for treatment should be distinguished from withdrawal of 
consent for follow-up visits and from withdrawal of consent for non-subject contact follow-up, 
e.g., medical records checks. When consent is withdrawn, subjects should be explicitly asked 
about the contribution of possible adverse events to the decision to withdraw consent, and any 
adverse event information elicited should be documented. Preferably, the subject should 
withdraw consent in writing and, if the subject (or the subject’s legally authorized representative) 
refuses or is physically unavailable, the site should document the reason for the subject’s failure 
to withdraw consent in writing. In the event that consent is withdrawn, the study site may consult 
public records, such as those establishing survival status of the subject. 
Subjects who withdraw from the study will not be replaced. 
4.6 
Subjects Lost to Follow Up 
If the subject fails to respond to requests for follow-up, the clinical trial site will send a registered 
letter or equivalent, at a minimum, to the subject requesting contact with the clinic. All attempts 
to resume contact (including copies of written correspondence) will be included in the source 
documentation. Subjects who do not respond to requests for follow-up after all reasonable 
attempts to establish contact will be considered “lost to follow-up”.  
Subjects who are lost to follow-up will not be replaced. 


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5 
STUDY SCHEDULE 
The schedule of assessments for all clinical trial sites is listed in Table 1. The additional schedule 
of assessments for US clinical trial sites only is listed in Table 2. 
All study visits will be calculated from time of first IP dose (Day 1). Month 3 and Month 6 visits 
will be calculated based on the calendar month (e.g., if Day 1 is February 15th, Month 3 would be 
May 15th and Month 6 would be August 15th).






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6 
STUDY ASSESSMENTS  
6.1 
Efficacy Assessments 
6.1.1 
CT Scan of Abdomen (CT Subset of Subjects Only) 
Subjects with standard of care CT scans (with or without contrast) that include the abdomen 
conducted at admission (within 48 hours of first hospital arrival and up to 24 hours after first IP 
dose) will have a follow-up CT scan (without contrast) of the abdomen (conducted per 
institutional guidelines) at the timepoint specified in the Schedule of Assessments if the subject 
is still in the hospital. The purpose is to assess changes in muscle volumes in a standardized way. 
When available, follow-up standard of care CT scans (with or without contrast) including the 
abdomen may be used if collected at the timepoint specified in the Schedule of Assessments. 
Subjects that do not have a CT scan (with or without contrast) including the abdomen conducted 
as standard of care upon admission (within 48 hours of first hospital arrival and up to 24 hours 
after first IP dose) will not have a follow-up CT scan conducted or collected for the study and 
will not be a part of the CT subset. 
For subjects in the CT Subset, the admission and follow-up CT scans of the abdomen will be 
collected and uploaded for central interpretation per the study specific Imaging Acquisition 
Manual. 
6.1.2 
Sit-to-Stand Assessment 
Trained site personnel will conduct the sit-to-stand physical assessment per the study-specific 
Functional Assessments Manual.  
The number of sit-to-stand maneuvers a subject completes over a period of 30 seconds will be 
recorded.  
6.1.3 
Organ Dysfunction Time to Recovery (TTR) 
Organ dysfunction time to recovery (TTR) will be assessed based on the criteria presented in 
Appendix 4: Organ Dysfunction TTR. The definition of time to recovery is the first day meeting 
the organ failure recovery criteria in cardiovascular, hematologic, hepatic, renal, and respiratory 
systems without any subsequent days with further organ system failure. 
6.1.4 
Sequential Organ Failure Assessment Score (SOFA) 
The Sequential Organ Failure Assessment (SOFA) is a scoring system that assesses the 
performance of several organ systems in the body (e.g., neurologic, blood, liver, kidney, and 
blood pressure/hemodynamics) and assigns a score based on the data obtained in each category 
(see Appendix 5: SOFA Criteria).  
The SOFA score will be calculated using 6 common points of data: 
• Respirations (partial pressure of arterial oxygen [PaO2] and FiO2) 


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• Coagulation (platelets) 
• Liver (bilirubin) 
• Cardiovascular (hypotension) 
• Central nervous system (Glasgow Coma Score [GCS]) 
• Renal (creatinine or urine output) 
The full-length SOFA score ranges from 0 to 24. Worst values of the day should be used to 
calculate SOFA score. See the Study Reference Manual for details. 
6.1.5 
Chelsea Critical Care Physical Assessment (CPAx) 
Trained site personnel will conduct the Chelsea Critical Care Physical Assessment (CPAx) per 
the study-specific Functional Assessments Manual. The CPAx is designed to measure functional 
recovery from critical illness. The CPAx includes the following 10 components: 
• Respiratory function 
• Cough 
• Moving within bed 
• Supine to sitting on the edge of bed 
• Dynamic sitting 
• Standing balance 
• Sit to stand 
• Transferring from bed to chair 
• Stepping 
• Grip strength 
The CPAx components will be graded on a 6-point scale from dependent to independent (0 to 5). 
The individual values will be collated giving a total score out of 50.  
6.1.6 
Medical Research Council Sum Score (MRC-SS) 
Trained site personnel will conduct the Medical Research Council Sum Score (MRC-SS) 
physical assessment per the study-specific Functional Assessments Manual.  
The MRC-SS measures global peripheral muscle strength which ranges from 0 (complete 
paralysis) to 60 (normal strength). The MRC-SS includes 6 muscle strength tests: 
• Shoulder abduction 
• Elbow flexion 
• Wrist extension 
• Hip flexion 
• Knee extension 
• Ankle dorsiflexion 


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6.1.7 
Barthel Index 
The Barthel Index will be administered by asking the subject, friends/relatives/caregivers, and/or 
nurses/doctors about the subject’s performance either in person or via telephone. Use direct 
observation if obtainable, but direct testing is not required for administration. Each subject’s 
performance should be established using the best available evidence (see Study Reference 
Manual). 
The Barthel Index is an ordinal scale used to measure performance of activities of daily living 
(ADL) (see Appendix 6: Barthel Index). It uses 10 variables describing ADL and mobility: 
• 
Presence or absence of fecal incontinence 
• 
Presence or absence of urinary incontinence 
• 
Help needed with grooming 
• 
Help needed with toilet use 
• 
Help needed with feeding 
• 
Help needed with transfers (e.g., from chair to bed) 
• 
Help needed with walking 
• 
Help needed with dressing 
• 
Help needed with climbing stairs 
• 
Help needed with bathing 
Each performance variable is rated on a scale with a given number of points assigned to each 
level or ranking. Scores range from 0 to 100 with a higher number associated with a greater 
likelihood of being able to live at home with a degree of independences following discharge 
from the hospital.  
6.1.8 
Medical Outcomes Study Questionnaire Short Form 36v2 (SF-36v2) Health Survey   
Each subject will complete the Short Form 36v2 (SF-36v2) Health Survey by self-reporting 
electronically (e.g., using smartphone or tablet).  
The SF-36v2 Health Survey is an indicator of overall health status. The SF-36v2 Health Survey 
uses 8 scaled scores and the scores will be weighted sums of the questions in each of the 
following sections:  
• Vitality 
• Physical functioning 
• Bodily pain 
• General health perceptions 
• Physical role functioning 
• Emotional role functioning 
• Social role functioning 
• Mental health 


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Scores range from 0 to 100 with lower scores indicating more disability and higher scores 
indicating less disability. 
6.1.9 
Time of Extubation 
Time of intubation(s) and successful extubation(s) will be recorded. Extubation will be 
considered successful if subject remains extubated for at least 24 hours.  
6.1.10 
Occurrence of Sepsis 
Time and occurrence of sepsis and septic shock will be recorded. Sepsis is defined as an acute 
change in total SOFA score ≥2 points consequent to infection. Septic shock is defined as sepsis 
with persisting hypotension requiring vasopressors to maintain Mean Arterial Pressure 
≥65 mmHg. 
6.1.11 
Discharge and Disposition 
Time of hospital discharge and disposition type (e.g., step-down unit, rehabilitation facility, 
home) will be recorded. Time of hospital discharge will be defined as the date the subject is 
cleared for discharge from the hospital.  
6.1.12 
General Health Inquiry 
A general health inquiry, including documentation of any new significant medical diagnoses 
and/or hospitalizations, will be conducted by telephone. 
6.1.13 
Overall Survival 
Confirmation of survival status will be obtained by speaking directly with subject, via medical 
records, or public health records. 
6.1.14 
Research Blood Samples (US Sites Only)  
Research blood samples will be collected from subjects and shipped to a central laboratory, 
stored, and batched for analysis. Research samples will be stored no longer than 2 years after the 
completion of the study and include: 
• Leukocyte Gene Expression: gene expression analysis for blood leukocyte gene 
transcription changes in response to trauma 
• Plasma PK: pharmacokinetic analysis measuring the concentration of FDY-5301 in 
plasma 
• Blood Biomarkers: analysis of metabolic, inflammatory, and biochemical markers of 
muscle damage in blood 


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6.2 
Demographics and Safety Assessments 
6.2.1 
Demographics 
Demographic information, including gender, birth date, race, and ethnicity will be recorded 
following consent.  
6.2.2 
Medical History 
Significant historic and current medical conditions or illnesses, allergies to medications, and 
prior surgical interventions will be recorded. 
6.2.3 
Physical Examination 
Physical examinations will be performed per institutional guidelines.  
6.2.4 
Estimated Height and Weight 
Height and weight will be recorded. Estimated values are acceptable per institutional guidelines. 
6.2.5 
Serum Pregnancy Test  
A serum pregnancy test will be performed only for female subjects of reproductive potential. A 
woman is considered of reproductive potential following menarche and until becoming post-
menopausal unless permanently sterile (i.e., both ovaries have been removed, fallopian ducts 
tied, womb removed, or completed menopause). 
6.2.6 
Concomitant Medications 
For all medications ongoing at time of consent (prescription, nonprescription, and supplements), 
the medication name, dose, route, frequency, start and stop dates, and indication will be recorded 
in the subject’s medical record and in the CRF. Imaging contrast agents and any parenteral or 
enteral feeding, including amount of energy and protein, will also be recorded. 
6.2.7 
Safety Laboratory Tests 
Clinical laboratory evaluations will be performed by each site’s clinical laboratory per 
institutional guidelines. See Appendix 2: Clinical Laboratory Tests for a list of required analytes. 
Additional assessments may be performed between scheduled study visits as clinically required 
to diagnose and monitor AEs/SAEs.  
6.2.8 
12-Lead Electrocardiogram 
Standard 12-lead ECGs will be performed as single recordings and read at the clinical site. 


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6.2.9 
Trauma Related Injury Severity Score (TRISS)  
A Trauma Related Injury Severity Score (TRISS) will be recorded (see Appendix 3: TRISS 
Method). See the Study Reference Manual for details. 
The TRISS is a scoring system that assesses probability of survival by looking at the following: 
• Injury Severity Score (ISS) looks at head and neck, face, chest, abdomen and pelvic 
contents, extremity and pelvic girdle, and external injuries and each body region is 
given a score based on the Abbreviated Injury Score Code (AIS) 
• Revised Trauma Score (RTS) also looks at Systolic blood pressure (SBP), 
Respiratory rate (RR), and GCS 
• Age 
 


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7 
STUDY TREATMENTS 
7.1 
Description of Investigational Product 
FDY-5301 is sodium iodide (chemical formula NaI) administered as an isotonic solution for 
intravenous injection with a concentration of 7.2 mg/mL. The dosage form of FDY-5301 is a 
small-volume parenteral solution. The solution has a pH between 7.0 and 9.5. Normal saline will 
be used as placebo. 
7.2 
Randomization, Stratification and Blinding 
Study treatment will consist of FDY-5301 or placebo.  
All subjects who fulfill all study eligibility criteria will be randomized to receive one of the 
treatment kits allocated by a computer-generated randomization code (FDY-5301 at 1 mg/kg, or 
2 mg/kg, or volume-matched placebo). Randomization will be stratified by whether the subject 
has pelvic or lower limb fractures.  
The clinical trial site will remain blinded to treatment allocation of active or placebo, as placebo 
and active vials will be identical in appearance.  
7.3 
Procedure for Unblinding 
The randomization code may be broken by the Investigator to manage an urgent medical event 
provided that knowledge of the IP (i.e., active or placebo) will alter the subject’s management. If 
possible, the Medical Monitor should be contacted to discuss the case before the code is broken. 
For each subject, the treatment group can be unblinded using the interactive response technology 
(IRT) system and the site’s Emergency Unblinding Code, provided with the site’s study start-up 
materials. Using the Emergency Unblinding Code, the Investigator or designee will be able to 
unblind a subject by following instructions on the IRT Quick Reference Guide.  
Unblinding must be clearly justified and explained in source documentation, along with the date 
on which the code was broken and identity of the person who authorized unblinding. 
7.4 
Prohibited Concomitant Medications 
The following medications and supplements are prohibited until Day 28 as they may confound 
efficacy and safety measures in the study: 
• High-dose Selenium (>55µg per day) 
• High-dose vitamins or nutritional supplements (> recommended daily allowance) 
• Use of any investigational drug or device that may confound efficacy or safety measures 
in this study 


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8 
INVESTIGATIONAL PRODUCT MATERIALS AND MANAGEMENT  
8.1 
Investigational Product 
FDY-5301 is delivered as a single dose, non-preserved liquid parenteral solubilized in water for 
injection and balanced with sodium chloride. Each vial is formulated to contain 20 mL of a 
7.2 mg/mL concentration of sodium iodide to support clinical dosing by IV injection. 
Placebo is delivered as a single dose, non-preserved liquid parenteral consisting of a formulation 
matched compendial saline. Each vial is formulated to contain 20 mL of saline to support clinical 
dosing by IV injection. 
8.2 
Packaging and Labeling 
IP will be manufactured, packaged, and labeled by contract manufacturing organizations on 
behalf of the Sponsor in accordance with Good Manufacturing Practice.  
IP will be supplied in cartons containing 7 kits. One carton will be assigned to a single subject 
upon randomization. A single kit within that carton will be used each day for the assigned 
subject’s daily dose. Each kit will contain 2 x 20 mL vials to ensure sufficient dose volume for 
anyone with a body weight of ≤140 kg (or ≤309 lbs). 
Refer to the Study Pharmacy Manual for details of the packaging and description of the label. 
8.3 
Shipment and Storage 
IP will be shipped to sites following the completion of study initiation and receipt of IEC/IRB 
approval. IP will be stored as supplied (20°C to 25°C) in a secured location at the clinical trial 
site. IP should not be stored frozen and direct exposure to sunlight and heat should be avoided. If 
storage conditions are found to be outside of the specified storage requirements, immediately 
contact the sponsor. Contact details are provided in the Study Pharmacy Manual. 
8.4 
Preparation and Administration 
The formulation has no preservative and is intended for single use only. Injection solutions will 
be prepared using aseptic technique and inspected prior to administration. The solution for 
injection is a clear, colorless solution with no particulate matter.  
Preparation of the administered dose will be achieved by adjusting the volume of undiluted 
solution (calculation is based on IP concentration of 7.2 mg/mL) according to treatment 
assignment. Dosage is based on the subject’s body weight (estimated or actual) at screening.  
IP will be administered intravenously by a healthcare professional by bolus injection over no 
more than 10 minutes. Use of an infusion pump is acceptable provided it can administer the total 
volume in less than 10 minutes. IP may be administered through a central line as long as the line 
is flushed prior to and following injection. IP must be administered without mixing with any 
other IV drugs. 


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The first IP administration must occur as soon as possible and within 48 hours of first hospital 
arrival time (i.e. in case of transfers, use time of arrival to first hospital immediately post injury) 
and then daily for up to 7 days at approximately the same time each day (±4 hours using the time 
of day of the first IP administration). 
8.5 
Investigational Product Accountability and Disposal 
IP will only be used for purposes of this study. The clinical site staff will be responsible for IP 
accountability, reconciliation, and record maintenance in accordance with all applicable 
regulatory requirements.  
An IP accountability record must be kept current and will contain an accurate and current 
accounting of study drug receipt, storage, administration, and destruction. 
At the end of the study, any remaining IP will be disposed of as per Sponsor instructions (e.g., at 
the site by using approved drug destruction methods) and a final IP reconciliation statement must 
be completed and provided to the Sponsor.  
Accountability records must be made available to the study monitor for verification throughout 
the course of the study. 


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9 
SAFETY: ADVERSE EVENTS 
9.1 
Definitions 
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical 
investigation subject administered an investigational product (pharmaceutical) and which does 
not necessarily have a causal relationship with the treatment. An AE can therefore be any 
unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or 
disease temporally associated with the use of a medicinal (investigational) product, whether or 
not related to the investigational product. A relationship to the investigational product is not 
necessarily proven or implied.  
All adverse events occurring from the time of consent until Day 28, observed by the Investigator 
or reported by the subject (whether or not attributed to IP), will be recorded. The following 
attributes must be recorded in subject’s medical records and in the CRF: description, start and 
stop dates, seriousness, outcome, severity, relationship to IP, and action taken with IP.  
Any medical condition already present at the time of consent should not be reported as an AE 
unless the medical condition (or signs or symptoms) present at consent changes in severity or 
seriousness at any time during the study. In this case, it should be reported as an AE. 
9.2 
Recording Diagnosis Versus Signs and Symptoms 
Wherever possible, a specific disease or syndrome rather than individual associated signs and 
symptoms should be identified by the Investigator and recorded in the CRF. However, if an 
observed or reported sign or symptom is not considered a component of a specific disease or 
syndrome by the Investigator, it should be recorded as a separate AE in the CRF. Additionally, a 
condition that leads to a medical or surgical procedure should be recorded as an AE rather than 
the procedure (e.g. record appendicitis instead of appendectomy). 
9.3 
Laboratory Abnormalities or Other Abnormal Assessments 
The following laboratory or other assessment abnormalities will be considered AEs and recorded 
in the subject’s medical record and in the CRF: 
• Any result deemed clinically significant by the Investigator and that is not part of another 
reported clinical diagnosis 
• Any result leading to discontinuation or interruption of IP 
• Any result that requires therapeutic intervention or a change in subject management 
Abnormalities that do not meet one of the above conditions will not be recorded on the CRF. 
9.4 
Relationship to Investigational Product 
The Investigator will classify every AE according to its relationship to IP. Investigators should 
pay particular attention to etiology of subject’s symptoms that are anticipated in the ICU setting.  
The relationship categories are listed in Table 3. 


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Table 3: Relationship of Adverse Events to IP  
Classification 
            Definition 
Related 
The AE follows a reasonable temporal sequence from 
administration of IP and cannot readily have been 
produced by the subject’s clinical state, other modes of 
therapy, or concomitant medications administered to the 
subject  
 
Not Related 
The AE is clearly related to other factors, such as the 
subject’s clinical state, other modes of therapy, or 
concomitant medications administered to the subject 
 
9.5 
Severity of Adverse Events 
The severity of AEs will be graded from 1 to 5 according to NCI Common Terminology Criteria 
for Adverse Events (CTCAE) version 5.0 general guidelines (see Table 4). An AE that is 
assessed as severe should not be confused with an SAE. Severity is a category utilized for rating 
the intensity of an event; both AEs and SAEs can be assessed as severe. 
Table 4: CTCAE General Categories 
Grade Clinical Description 
1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated 
2 
Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living 
3 
Severe or medically significant but not immediately life-threatening; hospitalization 
or prolongation of hospitalization indicated; disabling; limiting self-care activities of 
daily living 
4 
Life-threatening consequences; urgent intervention indicated 
5 
Death related to AE 
9.6 
Reporting Serious Adverse Events 
A serious adverse event (SAE) is any untoward medical occurrence that at any dose: 
• Results in death 
• Is life-threatening (NOTE: The term "life-threatening" in the definition of "serious" refers 
to an event/reaction in which the subject was at risk of death at the time of the 
event/reaction; it does not refer to an event/reaction which hypothetically might have 
caused death if it were more severe) 
• Requires inpatient hospitalization or results in prolongation of existing hospitalization 


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NOTE: Prolongation of existing hospitalizations for social or situational reasons will not 
be considered an SAE (e.g., waiting for placement or availability in a step-down unit or 
rehabilitation facility, no place to stay, etc.). 
• Results in persistent or significant disability/incapacity 
• Is a congenital anomaly/birth defect 
• Is a medically important event or reaction 
Medical and scientific judgment should be exercised in deciding whether reporting is appropriate 
in other situations, such as important medical events that may not be immediately life threatening 
or result in death or hospitalization but may jeopardize the subject or may require medical or 
surgical intervention to prevent one of the other outcomes listed in the above definition. These 
should also usually be considered serious. Examples of such medical events include cancer, 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in hospitalizations, or the development of drug 
dependency or drug abuse. 
Initial Reports 
All SAEs occurring from the time of informed consent until Day 28, regardless of causality or 
relationship to treatment, must be reported to Medpace Clinical Safety within 24 hours of the 
knowledge of the occurrence. After Day 28, any SAE that the Investigator considers related to IP 
must be reported to Medpace Clinical Safety or the Sponsor/designee.  
To report the SAE, the Investigator/designee completes the SAE form electronically in the 
electronic data capture (EDC) system for the study. When the form is completed, Medpace 
Safety personnel will be notified electronically by the EDC system and will retrieve the form. 
If the event meets serious criteria and access to the EDC system is not possible, send an e-mail to 
Medpace Safety at medpace-safetynotification@medpace.com or call the Medpace SAE 
reporting line (phone number listed below), and fax or e-mail the completed back-up paper SAE 
reporting form to Medpace (fax number listed below) within 24 hours of awareness. When the 
EDC system becomes available, the SAE information must be entered within 24 hours of the 
system becoming available. 
Company: 
Medpace 
Attention: 
Medpace Clinical Safety 
Email: 
Medpace-SafetyNotification@medpace.com 
Phone: 
North America: (800) 730-5779, dial 3 or +1 (513) 579-9911, dial 3 
Europe: +49 89 89 55 718 44 
Fax: 
North America: +1 (866) 336-5320 or +1 513-570-5196 
 
Europe: +49 89 89 55 718 104 
 


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The initial notification will include at least a description of the event and the subject 
identification number. This information should be supported as needed with written copies of 
hospital case reports, autopsy reports, and other documents when applicable. 
Follow-up Reports  
The Investigator must continue to follow the subject until the SAE has subsided or until the 
condition becomes chronic in nature, stabilizes (in the case of persistent impairment), or the 
subject dies. 
Within 24 hours of receipt of follow-up information, the Investigator must update the SAE form 
electronically in the EDC system for the study and submit any supporting documentation (e.g., 
patient discharge summary or autopsy reports) to Medpace Clinical Safety via fax or e-mail. If 
access to the EDC system is not possible, refer to the procedures outlined above for initial 
reporting of SAEs. 
IEC/IRB and Regulatory Reporting  
The Investigator should notify the IEC/IRB of SAEs occurring at the site in accordance with 
local procedures. 
The Sponsor has a legal responsibility to notify the appropriate regulatory authorities about the 
safety of any test drug. Accordingly, prompt notification of any adverse events by Investigators 
to the Sponsor is required. The reporting of SAEs will be conducted in accordance with ICH, 
Good Clinical Practice (GCP), and local regulatory guidelines. 
9.7 
Pregnancy Reporting 
If a subject becomes pregnant before Day 28, the subject will be followed per the schedule of 
assessments for the full study follow-up period (6 months; see Table 1), and in addition, the 
pregnancy should be followed by the Investigator until completion.  
A pregnancy is not considered to be an AE or SAE; however, it must be reported to Medpace 
Clinical Safety within 24 hours of knowledge of the event. Medpace Clinical Safety will then 
provide the Investigator/site the Exposure In Utero (EIU) form for completion. The 
Investigator/site must complete the EIU form and fax or email it to Medpace Clinical Safety.  
If the female partner of a male subject becomes pregnant before Day 28, the Investigator should 
notify Medpace Clinical Safety as described above.  
The pregnancy should be followed until the outcome of the pregnancy, whenever possible. Once 
the outcome of the pregnancy is known, the follow-up EIU form should be completed and faxed 
or emailed to Medpace Clinical Safety. If the outcome of the pregnancy meets the criteria for 
immediate classification as an SAE (i.e., postpartum complication, spontaneous abortion, 
stillbirth, neonatal death, or congenital anomaly), the Investigator should follow the procedures 
for reporting an SAE. 


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9.8 
Expedited Reporting Requirements 
9.8.1 
Suspected Unexpected Serious Adverse Reaction  
A suspected unexpected serious adverse reaction (SUSAR) is considered any SAE for which 
there is a reasonable possibility that the IP caused the SAE and is considered "unexpected" i.e., 
not listed in the Reference Safety Information section of the Investigator’s Brochure, or is not 
listed at the specificity or severity that has been observed in an adverse reaction, the nature or 
severity of which is not consistent with the applicable product information. 
The Sponsor or designee will report all relevant information about fatal or life-threatening 
SUSARs or IND safety reports (INDSRs) as soon as possible to the FDA and applicable 
competent authorities, and in any case no later than 7 calendar days after knowledge by the 
Sponsor or designee of such a case. Relevant follow-up information will subsequently be 
communicated as soon as the information is available but no later than 15 calendar days after the 
Sponsor or designee receives the information. 
All other SUSARs or INDSRs will be reported to the FDA and applicable competent authorities 
as soon as possible but within a maximum of 15 days of first knowledge by the Sponsor or 
designee. The Sponsor or designee will also inform all Investigators of SUSARs or INDSRs as 
required. 


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10 
STATISTICS 
A separate Statistical Analysis Plan (SAP) will provide additional details for statistical analyses 
and data displays.  
10.1 
Analysis Populations 
The Safety Population will include all subjects who are randomized and receive at least 1 dose of 
IP (FDY-5301 or placebo). 
The Intent-to-Treat (ITT) Population will include all randomized subjects. 
The Per-Protocol (PP) Population will include all subjects in the ITT Population who meet the 
following criteria: 
• have met all inclusion and no exclusion criteria 
• receive at least 1 dose of IP (FDY-5301 or placebo) 
• have CPAx total score at Day 10 or hospital discharge, whichever occurs first 
• have interpretable organ dysfunction total TTR data 
• do not have any major protocol deviations that may impact the efficacy endpoints 
The PK Population will include all subjects who are enrolled and receive at least 1 dose of IP and 
have at least 1 evaluable PK sample. 
10.2 
Statistical Methods 
10.2.1 
Demographic and Baseline Characteristics 
Demographic and baseline characteristics will be summarized using descriptive statistics by 
treatment group. Subject disposition will be summarized by treatment group. All subjects 
enrolled will be included in a summary of subject disposition.  
10.2.2 
Handling of Missing Data 
CPAx total scores will be analyzed using ANCOVA on observed data. To assess the impact of 
missing data, multiple imputation will used as supplementary analysis. Tipping-point analysis 
will also be performed. Details will be described in the SAP. 
For organ dysfunction total TTR, no imputation will be performed. For all other endpoints, 
missing observations will be excluded from analysis. 
Descriptive summaries of efficacy and safety measures will be based on observed data. 
10.2.3 
Safety Analyses 
The Safety Population will be used for all safety analyses.  


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All adverse events reported in this study will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA). 
Safety analysis includes summary for AEs, TEAEs, SAEs, clinical laboratory assessments, and 
12-lead ECGs. No statistical testing will be conducted for safety endpoints.  
All clinical safety and tolerability data will be listed for each subject. Hematology, clinical 
chemistry, and thyroid function will be analyzed by group mean and outlier analyses.  
AEs, TEAEs, and SAEs will be summarized by group, severity, and relationship to the IP. Other 
safety measures will be summarized descriptively by treatment and visit.  
10.2.4 
Efficacy Analyses 
The ITT Population will be used for all efficacy analyses. The PP Population will be used as a 
sensitivity analysis to assess robustness of the efficacy results. 
10.2.4.1 Primary Efficacy Analyses 
There are two co-primary efficacy endpoints defined in this study: 
• CPAx total score at Day 10 (or at hospital discharge, whichever occurs first) 
• Organ dysfunction total TTR until Day 28 
Both primary endpoints will be compared across treatment groups and tested at the 0.05 level of 
significance and, by convention, both endpoints must demonstrate statistical significance (i.e., 
p ≤ 0.05) to conclude treatment superiority for regulatory purposes. 
For the first primary efficacy endpoint, CPAx total score at Day 10 (or at hospital discharge, 
whichever occurs first), the following hypothesis will be tested: 
𝐻𝐻0: 𝜇𝜇𝑇𝑇𝑇𝑇= 𝜇𝜇𝑝𝑝 𝑣𝑣.𝑠𝑠.𝐻𝐻𝑎𝑎:𝜇𝜇𝑇𝑇𝑇𝑇≠𝜇𝜇𝑝𝑝   
Where 𝜇𝜇𝑇𝑇𝑇𝑇, 𝜇𝜇𝑝𝑝 denote the CPAx total score at Day 10 (or at hospital discharge, whichever occurs 
first) in the pooled treatment group (FDY-5301 1 mg/kg and FDY-5301 2 mg/kg combined) and 
placebo groups, respectively. As the primary analysis, the treatment comparison of the CPAx 
total scores will be performed using analysis of covariance (ANCOVA). The model will include 
CPAx total score at Day 10 (or at hospital discharge, whichever occurs first) as dependent 
variable treatment and stratification category (with or without presence of pelvic or lower limb 
fractures) as factors; and “baseline” CPAx (the first available datapoint) as a continuous 
covariate.  
The p-values, least-squares means, standard errors, and the 2-tailed 95% confidence intervals for 
the treatment groups and placebo group will be presented. 


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If the difference between the means of the pooled treatment group compared to the placebo 
group is statistically significant, a step-down procedure will be followed to test the individual 
FDY-5301 doses compared to placebo. The following testing order of doses will be used:  
1) FDY-5301 2 mg/kg versus placebo 
2) FDY-5301 1 mg/kg versus placebo 
The same statistical method as for the comparison between the pooled treatment group and 
placebo will be used. 
For the second primary efficacy endpoint, organ dysfunction total TTR, the time will be 
calculated as date of recovery minus date of treatment start plus 1 day. The time to recovery will 
be estimated using Kaplan-Meier methodology. The Kaplan-Meier curves will be plotted and the 
time to recovery will be compared using log-rank test at significance level 0.05. The pooled 
versus placebo and then step-down analysis procedure will be used. 
10.2.4.2  Secondary Efficacy Analysis 
For secondary endpoints, a sequential analysis will be performed. The continuous secondary 
efficacy endpoints of MRC-SS and worst SOFA score will be analyzed with an ANCOVA model 
similar to the one described for the primary endpoint of CPAx total score. The secondary 
endpoint of overall survival at Day 28 will be analyzed using a Kaplan-Meier approach and a 
log-rank test, similar to the methodology described for the primary endpoint of organ 
dysfunction total TTR until Day 28. 
The pooled treatment groups versus placebo will be analyzed first, followed by a step-down 
analysis.  
The p-values, least-squares means, standard errors, and the 2-tailed 95% confidence intervals for 
the treatment groups and placebo group will be presented, where appropriate. 
10.2.4.3 Exploratory Efficacy Analyses 
Continuous variables will be summarized by descriptive statistics (n, mean, median, standard 
deviation, minimum, and maximum) by treatment group. Continuous variables will also be 
analyzed using analysis of covariance or analysis of variance. The least-squares means, standard 
errors, and the 2-tailed 95% confidence intervals for the treatment group and placebo group will 
be presented. 
Categorical variables will be summarized by frequency and percentage by treatment groups. 
Categorical variables will be analyzed using a Pearson’s Chi-square test or Cochran-Mantel-
Haenszel test. 
Time to event data will be analyzed using Kaplan-Meier lifetables and a log-rank test to compare 
time to efficacy between treatment groups and placebo groups. 


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10.2.4.4 Subgroup Analyses 
To assess the heterogeneity of treatment effects among subgroups, the primary and secondary 
endpoints will be summarized descriptively and analyzed by stratification group (with or without 
presence of pelvic or lower limb fractures).  
In addition, forest plots displaying effect estimates and 95% CIs for subgroups and the entire ITT 
population will be provided for the primary and secondary endpoints. 
10.2.5 
Pharmacokinetics Analyses 
The PK Population will be used for all pharmacokinetics analyses. 
The concentration of iodide in plasma (at different time points and doses) will be derived and 
summarized for each group. The pharmacokinetic analysis will include collections of a 
concentration-time profile in subjects following dosing with IP. Mean, standard deviation, and 
coefficient of variation will be calculated at each time point. The pharmacokinetic behavior of 
plasma iodide will be described for both samples from days 1, 3, and 7 as area under the 
concentration versus time curve (AUC, AUCinf) the maximal concentration (Cmax), trough 
concentration (Cmin), the time when the maximal concentration is achieved (Tmax), and terminal 
half-life (T1/2) for each subject.  
In subjects, at US sites only, who develop acute renal failure and require dialysis during their 
first 7 days on this study, pre- and post-dose samples will be obtained each day of IP 
administration while on dialysis as well. This data will be analyzed descriptively in terms of peak 
and trough concentrations observed and modelled based on sampling times, where possible. 
10.2.6 
Interim Analysis 
No interim analysis is planned for this study. 
10.2.7 
Sample Size Determination and Power Calculations 
Approximately 252 subjects will be randomized in a 1:1:1 ratio to receive either FDY-5301 1 
mg/kg, FDY-5301 2 mg/kg, or placebo (i.e. 84 subjects per group). 
With 252 subjects (with a drop-out rate of 15%, corresponding to 213 evaluable subjects), using a 
2-sided significance level of 0.05 and placebo group mean in CPAx total score at Day 10 of 30, 
assuming a standard deviation of 12 (Corner 2015 and Raymond 2020), this would provide >90% 
power if there exists an improvement of 6 points in the CPAx total score in the pooled treatment 
group (either FDY-5301 1mg/kg or 2 mg/kg) compared with placebo group, (i.e. scores of 36 for 
FDY-5301 vs. 30 Placebo). 
Given the assumption that median expected organ dysfunction recovery time is 7 days for the 
placebo group and the median expected organ dysfunction recovery time is 4.9 days for the 
pooled treatment group (Xiao 2011), i.e. an expected relative risk reduction of 30% and a 2-sided 
log-rank test at a significance level of 0.05, the study would have approximately 70% power if at 
least 213 events are observed (based on no subject being censored until Day 28). 


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11 
DATA MONITORING COMMITTEES 
11.1 
Data Safety Monitoring Committee 
An independent Data Safety Monitoring Committee (DSMC) will be convened for this study. 
The DSMC is an expert advisory group responsible for safeguarding the interests of trial 
participants and assessing the safety of the interventions during the trial. The DSMC will meet at 
intervals as specified in the DSMC charter and may convene for ad hoc meetings if there are 
immediate safety concerns identified during the study. Subject safety will be evaluated as 
specified in the DSMC charter. The DSMC will provide advice to the Sponsor and study 
Investigators as specified in the DSMC charter. The Sponsor will provide DSMC 
recommendations to the study Investigators for submission to the IRB/IEC per institutional 
policies, upon request. 
11.2 
Imaging Central Review 
A blinded Imaging Central Review of the L3 vertebra Skeletal Muscle Index (SMI) and other 
muscle volume measures based on CT scans will be performed as specified in the Imaging 
Review Charter. 


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12 
STUDY GOVERNANCE 
12.1 
Regulatory and Ethical Conduct of the Study 
This study will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
International Ethical Guidelines. 
• Applicable ICH GCP Guidelines.  
• Applicable local, federal or country-specific regulations and laws. 
Prior to the onset of the study, the protocol, informed consent, and any other information to be 
provided to the subject must be approved by the IRB/IEC. Any amendments to the protocol, 
informed consent, or subject materials will require review and approval by the IRB/IEC before 
the changes are implemented to the study. 
The Investigator will be responsible for: 
• Obtaining continued review of the clinical research at intervals not exceeding 1 year or as 
otherwise specified by the IRB/IEC 
• Notifying the IRB/IEC of SAEs or other significant safety findings as specified by the 
IRB/IEC procedures 
• Providing oversight of the conduct of the study at the site and adherence to applicable 
guidelines and regulations 
• Notifying the Sponsor in advance of an impending regulatory inspection. The 
Investigator may request that the Sponsor provide support for preparation, if necessary, 
and is required to provide updates on the ongoing activities during the inspection and 
submit any citations/objectionable findings (i.e., FDA 483) and is required to share any 
follow up responses to the outcome. 
12.2 
Financial Disclosure 
Investigators, including sub-investigators, will provide the Sponsor with sufficient, accurate 
financial information as requested to allow the Sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the course of 
the study and for 1 year after completion of the study. 
12.3 
Informed Consent 
The informed consent form (ICF) and any changes made to the ICF during the course of the 
study must be agreed to by the Sponsor or designee and the IRB/IEC prior to its use and must be 
in compliance with all ICH GCP, local regulatory requirements, and legal requirements. 


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The Investigator or his/her representative will explain the nature of the study to the subject or 
his/her legally authorized representative (personal or professional, as applicable per local 
regulations) and answer all questions regarding the study.  
Subjects must be informed that their participation is voluntary. Subjects or their legally 
authorized representative (personal or professional, as applicable per local regulations) will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 50, local 
regulations, ICH guidelines, Health Insurance Portability and Accountability Act requirements, 
where applicable, and the IRB/IEC or study center.  
The medical record must include a statement that consent was obtained prior to the initiation of 
any study procedures and the date the consent was obtained. The Investigator or his/her 
representative obtaining consent must also sign the ICF. 
A copy of the fully signed ICF(s) must be provided to the subject or the subject’s legally 
authorized representative (personal or professional, as applicable per local regulations). 
12.4 
Data Protection 
Each subject will be assigned a unique subject identification number by the Sponsor or designee 
that should be used on all forms associated with the subject’s samples or documents that will be 
supplied to the Sponsor or designee or to any party processing the subject’s samples or 
information on behalf of the Sponsor (e.g., samples for central laboratory analyses). Data privacy 
will be maintained according to applicable local, federal or country-specific regulations, laws or 
requirements and will not be released without the written permission of the subject (or the 
subject’s legally authorized representative), except as necessary for monitoring and auditing by 
the Sponsor, its designee, the FDA or other applicable regulatory authority, or the IRB/IEC. 
12.5 
Publication Policy 
The results of this study may be published or presented at scientific meetings in accordance with 
the provisions contained in the clinical trial agreement.  
12.6 
Dissemination of Clinical Study Data 
The Sponsor will be responsible for ensuring the study information is appropriately listed and 
updated on the ClinicalTrials.gov website throughout the course of the study. 
12.7 
Data Quality Assurance 
All subject data relating to the study will be recorded on the CRF unless transmitted to the 
Sponsor or designee electronically (e.g., central laboratory data). The Investigator is responsible 
for verifying that data entries are accurate and correct by signing the CRF.  
The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. Source documents provide evidence for the existence of the 
subject and substantiate the integrity of the data recorded. The Investigator may need to request 
previous medical records or transfer records. Also, current medical records must be available. 


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Source documents are filed at the Investigator’s site. Data entered in the CRF that are transcribed 
from source documents must be consistent with the source documents or the discrepancies must 
be explained. 
The Investigator must maintain site files containing the protocol with all amendments and 
protocol signature pages, copies of all other required regulatory documentation, and all 
correspondence between the clinical trial site and the IRB and Sponsor or its designee. 
The Investigator must maintain drug accountability files containing a complete account of the 
receipt and disposition of all study treatments. 
The Investigator must maintain a subject identification list (subject and treatment numbers with 
the corresponding subject names) to enable records to be identified. 
The Sponsor or designee is responsible for the data management of this study including quality 
checking of the data. Data will be processed using a validated computer system conforming to 
regulatory requirements. Data quality checks programmed within the EDC system, as well as 
supplemental data quality checks performed by review of the downloaded data, will be applied to 
ensure accurate, consistent, and reliable data. Data identified as potentially inaccurate or 
incomplete will be referred to the clinical trial site for resolution through data queries. 
The Investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents and inform the Sponsor 
of any such inspection immediately. 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of subjects are being protected; and that the study is being 
conducted in accordance with the currently approved protocol and any other study agreements, 
ICH GCP, and all applicable regulatory requirements. The Investigator will permit the Sponsor 
or their designee to monitor the study as frequently as deemed necessary to determine that data 
recording and protocol adherence are satisfactory. During the monitoring visits, information 
recorded on the CRFs will be verified against source documents and requests for clarification or 
correction may be made. The monitor will review the data for safety information, completeness, 
accuracy, and logical consistency.  
The Sponsor or their designee may arrange a visit to the clinical trial site to audit the 
performance of the study and the study documents originating at the site. The Investigator will be 
informed of the outcome of the audit.  
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the Investigator for 2 years following marketing application approval or investigation 
is discontinued by the Sponsor and regulatory authorities are notified unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of the Sponsor. No records may be transferred to 
another location or party without written notification to the Sponsor. Prior to transfer or 
destruction of these records, the Sponsor must be notified in writing and be given the opportunity 


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to further store such records. If the Investigator relocates, retires, or for any reason withdraws 
from the study, the Sponsor should be prospectively notified. The study records must be 
transferred to an acceptable designee, such as another Investigator, another institution, or to the 
Sponsor. 
12.8 
Study and Site Closure 
The Sponsor or designee reserves the right to close the clinical trial site or terminate the study at 
any time for any reason at the sole discretion of the Sponsor. In the event of such action, written 
notification documenting the reason for study termination will be provided to each Investigator. 
Additionally, the Sponsor or its designee will inform the appropriate regulatory authorities of the 
termination of the study and the reasons for termination, and the Investigator will inform the 
IRB/EC of the same. In terminating the study, the Sponsor and the Investigator will assure that 
adequate consideration is given to the protection of the subjects’ interests. Circumstances that 
may warrant early termination include, but are not limited to: 
• Discovery of an unexpected, serious or unacceptable risk to subjects enrolled in the study 
• Evidence suggesting that safety risks associated with FDY-5301 outweigh the possible 
benefit for the subject or at recommendation of the DSMC 
• Decision on the part of the Sponsor to suspend or discontinue testing of the study drug 
Clinical trial sites will be closed upon study completion. A clinical trial site is considered closed 
when all required documents and study supplies have been collected and a study-site closure visit 
has been performed. 
The Investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a clinical trial site by the Sponsor or Investigator may include 
but are not limited to: 
• Failure of the Investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the Sponsor's procedures, or GCP guidelines 
• Inadequate recruitment of subjects by the Investigator 
 


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13 
REFERENCES 
Abrigo J, et al. Role of oxidative stress as key regulator of muscle wasting during cachexia, 
Oxidative Medicine and Cellular Longevity, vol. 2018; Article ID 2063179, 17 pages.  
Bertrand Y, et al. Differences in tocopherol-lipid ratios in ARDS and non-ARDS patients. 
Intensive Care Med 1989; 15:87–93. 
Borrelli E, et al. Plasma concentrations of cytokines, their soluble receptors, and antioxidant 
vitamins can predict the development of multiple organ failure in patients at risk. Crit Care Med 
1996; 24:392–397. 
Corner, Evelyn J., et al. "The responsiveness of the Chelsea Critical Care Physical Assessment 
tool in measuring functional recovery in the burns critical care population: An observational 
study." Burns 41.2 (2015): 241-247. 
Cuschieri J, et al. Benchmarking outcomes in the critically injured trauma patient and the effect 
of implementing standard operating procedures. Annals of surgery 2012 May:255.(5): 993-999. 
Dodd SL, et al. ROS-mediated activation of NF-κB and Foxo during muscle disuse. Muscle 
Nerve. 2010 January; 41(1): 110–113. 
Friedrich O, et al. The sick and the weak: Neuropathies/myopathies in the critically ill. 
Physiological Reviews 2015; 95:3, 1025-1109. 
Goode HF, et al. Decreased antioxidant status and increased lipid peroxidation in patients with 
septic shock and secondary organ dysfunction. Crit Care Med 1995; 23:646–651. 
Hemila H. Vitamin C intake and susceptibility to pneumonia. Pediatr Infect Dis J 1997; 16:836–
837. 
Hermans G and Van den Berghe G. Clinical review: intensive care unit acquired weakness. 
Critical Care 2015. 19:274.  
Li H, et al. Nuclear factor-kappa B signaling in skeletal muscle atrophy Mol Med (Berl). 2008 
October; 86(10): 1113–1126.  
Maderazo EG, et al. A randomized trial of replacement antioxidant vitamin therapy for 
neutrophil loco-motory dysfunction in blunt trauma. J Trauma 1991; 31:1142–1150. 
Marshall B and R Thomas. Trace element and vitamin supplementation in critical illness. Journal 
of the Intensive Care Society 2007; Vol.8, number 3: 24-26. 
Metnitz PG, et al. Antioxidant status in patients with acute respiratory distress syndrome. 
Intensive Care Med 1999; 25:180–185. 
Needham DM, et al. Improving long-term outcomes after discharge from intensive care unit: 
report from a stakeholders’ conference. Crit Care Med. 2012;40:502–9. 


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Puthucheary ZA, et al. Acute skeletal muscle wasting in critical illness. JAMA. 
2013;310(15):1591-1600.  
Raymond, Steven L., et al. "Prospective validation of a transcriptomic metric in severe trauma." 
Annals of Surgery 271.5 (2020): 802-810.  
Robison LM, et al. Comparison of the effects of iodine and iodide on thyroid function in 
humans. Journal of Toxicology and Environmental Health, Part A, 1998 55:93–106. 
Rockwood K, Song X, MacKnight C, Bergman H, Hogan DB, McDowell I, Mitnitski A. A 
global clinical measure of fitness and frailty in elderly people. CMAJ. 2005 Aug 30;173(5):489-
95. 
Schorah CJ, et al. Total vitamin C, ascorbic acid, and dehydroascorbic acid concentrations in 
plasma of critically ill patients. Am J Clin Nutr 1996; 63:760–765. 
Stevens RD, et al. A framework for diagnosing and classifying intensive care unit-acquired 
weakness. Crit Care Med. 2009;37:S299–S308.  
Vincent JL, et al. Working group on sepsis-related problems of the European Society of 
Intensive Care Medicine. The SOFA (sepsis-related organ failure assessment) score to describe 
organ dysfunction/failure. Intensive Care Med. 1996;22 (7):707-710. 
Xiao, Wenzhong, et al. "A genomic storm in critically injured humans." Journal of Experimental 
Medicine 208.13 (2011): 2581-2590. 
 




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APPENDIX 2: CLINICAL LABORATORY TESTS 
Biochemistry 
Alanine aminotransferase 
Glucose 
Albumin 
Inorganic phosphorus 
Alkaline phosphatase 
Lactate dehydrogenase 
Aspartate aminotransferase transaminase 
Potassium 
Bicarbonate 
Sodium 
Blood urea nitrogen 
Total and conjugated bilirubin 
Chloride  
Total protein 
Total calcium 
Uric acid 
Creatinine 
*TSH, free T3, and free T4 
Gamma-glutamyl transferase  
 
*TSH = thyroid stimulating hormone; T3 = triiodothyronine; T4 = thyroxine 
Hematology 
Hematocrit 
Mean corpuscular volume  
Hemoglobin 
Platelets 
Mean corpuscular hemoglobin 
Red blood cell count 
Mean corpuscular hemoglobin concentration 
White blood cell count and differential (absolute 
neutrophils, lymphocytes, monocytes, eosinophils, and 
basophils)  
 






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APPENDIX 4: ORGAN DYSFUNCTION TTR  
Time to recovery (TTR) is defined as the first day of meeting the criteria for organ failure 
recovery in all systems listed below, without any subsequent days with further organ system 
failure.  
Cardiovascular recovery 
Mean arterial pressure >60 mmHg and no inotropic/vasopressor support (dopamine, 
dobutamine, epinephrine, norepinephrine, phenylephrine, or vasopressin) 
Hematologic recovery 
Platelet count >120,000/mL 
Hepatic recovery 
Serum bilirubin <3 mg/dL 
Renal recovery 
No dialysis and creatinine <1.3 mg/dL 
Respiratory recovery 
No mechanical ventilation or PaO2/FiO2 >300 
 FiO2 = fraction of inspired oxygen; PaO2 = partial pressure of arterial oxygen. 
Source: Raymond SL, Hawkins RB, Wang Z, et al. Prospective Validation of a Transcriptomic 
Metric in Severe Trauma. Ann Surg. 2019 Jan 24. doi: 10.1097/SLA.0000000000003204. (Epub 
ahead of print) 


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APPENDIX 5: SOFA CRITERIA 
SOFA Score 
0 
1 
2 
3 
4 
Respiration  
PaO2/FiO2 
>400 
301 - 400 
201 - 300 
101 - 200 
With 
respiratory 
support 
≤100 
With 
respiratory 
support 
Coagulation 
Platelets, 
x103/mm3 
>150 
101 - 150 
51 - 100 
21-50 
≤20 
Liver  
Bilirubin, mg/dL 
(µmol/L) 
 
<1.2 
(<20) 
 
1.2 - 1.0 
(20 - 32) 
 
2.0 - 5.9 
(33 - 101) 
 
6.0 - 11.0 
(102 - 204) 
 
>12.0 
(>204) 
Cardiovascular 
Hypotension 
MAP ≥70 
mmHg 
MAP<70 
mmHg 
Dopamine 
≤ 5 or 
dobutamine 
(any dose)* 
Dopamine>5 
or epinephrine 
≤0.1 or 
norepinephrine 
≤0.1* 
Dopamine>15 
or 
epinephrine>0.1 
or 
norepinephrine 
>0.1* 
CNS 
Glasgow Coma 
Score 
15 
13 - 14 
10 - 12 
6 - 9 
<6 
Renal 
Creatinine, 
mg/dL 
(µmol/L) 
Or urine output 
 
<1.2 
(<110) 
 
1.2 - 1.9 
(110 - 170) 
 
2.0 - 3.4 
(171 - 299) 
 
3.5 - 4.9 
(300 - 440) 
Or <550mL/d 
 
>5.0 
(>440) 
Or <200mL/d 
CNS = central nervous system; d = day; FiO2, fractional inspired oxygen; MAP, mean arterial pressure; PaO2, partial 
arterial oxygen pressure. 
a 
Adrenergic agents administered for at least 1 hour (doses are given in µg/kg/min). 
Source: Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, 
et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ 
dysfunction/failure. Working Group on “sepsis-related problems” of the European Society of 
Intensive Care Medicine. Intensive Care Med 1996;22:707-710. 
 
 




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APPENDIX 7: CLINICAL FRAILTY SCORE 
The Clinical Frailty Scale (CFS) is an optional tool that may be used to calculate a pre-trauma 
frailty score to determine if a subject has pre-existing sarcopenia based on a 4-week pre-trauma 
social and/or medical history review. 
 
Source: Rockwood K, Song X, MacKnight C, Bergman H, Hogan DB, McDowell I, Mitnitski 
A. A global clinical measure of fitness and frailty in elderly people. CMAJ. 2005 Aug 
30;173(5):489-95