A Phase 1, Open-label, Single-dose, Parallel-group Study to Evaluate the Effects of Renal Impairment on the Pharmacokinetics of ELX-02
Phase: PHASE1
Conditions: Impaired Renal Function
Sponsor: Eloxx Pharmaceuticals, Inc.

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PROTOCOL 182023 
Eloxx Pharmaceuticals Study Number: EL-008 
 
IND Number: 137391 
 
 
 
A PHASE 1, OPEN-LABEL, SINGLE-DOSE, PARALLEL-GROUP STUDY TO 
EVALUATE THE EFFECTS OF RENAL IMPAIRMENT ON THE 
PHARMACOKINETICS OF ELX-02 
 
 
 
 
Contract Research Organization: 
inVentiv Health Clinical Research 
Services LLC (« inVentiv »), 
a Syneos Health company 
1951 NW 7th Avenue, Suite 450 
Miami, FL 33136, USA 
Tel.: 1-305-547-5800 
 
Sponsor: 
Eloxx Pharmaceuticals 
950 Winter Street 
Waltham, MA 02451-1208 
USA  
Tel.: +1-781-577-5300 
 
 
 
 
CONFIDENTIAL 
 
 
This document contains confidential information belonging to Eloxx Pharmaceuticals. Except as otherwise agreed to 
in writing, by accepting or reviewing this document, you agree to hold this information in confidence and not copy 
or disclose it to others (except where required by applicable law, provided prompt written notice is provided to 
Eloxx Pharmaceuticals and an opportunity to accord confidential treatment to the requested disclosable information) 
or use it for unauthorized purposes. In the event of any actual or suspected breach of this obligation, Eloxx 
Pharmaceuticals must be promptly notified.  

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Final 2.0 
Protocol Historical File 
Version 
number 
Brief description/summary of changes 
Date 
Final 2.0 
Version submitted to the IEC. 
06-NOV-2018 

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1. 
Facilities and Responsible Staff 
1.1 
Contract Research Organization 
 
 
 
 
 
1.2 
Clinical Research Facilities 
This study will be conducted at the following facilities: 
Site 01: 
 
 
 
 
 
 
 
 
 
 
Site 02: 
 
 
 
 
 
 
 
 
1.3 
Biomedical Laboratory Facilities 
Biomedical laboratory testing will be performed by the following laboratories: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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If another biomedical laboratory is used, this will be documented and annexed to the protocol. 
1.4 
Clinical Pharmacology 
 
 
 
 
Data Management, Pharmacokinetics and Statistical Analyses: 
 
 
Protocol Writing: 
 
  
1.5 
Bioanalytical Facility 
 
 
 
 
 
 

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Table of Contents 
1. 
FACILITIES AND RESPONSIBLE STAFF ................................................................................. 6 
1.1 
CONTRACT RESEARCH ORGANIZATION ....................................................................................................................................................... 6 
1.2 
CLINICAL RESEARCH FACILITIES ................................................................................................................................................................. 6 
1.3 
BIOMEDICAL LABORATORY FACILITIES ....................................................................................................................................................... 6 
1.4 
CLINICAL PHARMACOLOGY ......................................................................................................................................................................... 7 
1.5 
BIOANALYTICAL FACILITY .......................................................................................................................................................................... 7 
2. 
SYNOPSIS OF PROTOCOL ........................................................................................................ 10 
3. 
LIST OF ABBREVIATIONS ........................................................................................................ 20 
4. 
SCHEDULE OF EVENTS ............................................................................................................. 23 
5. 
INTRODUCTION .......................................................................................................................... 25 
5.1 
BACKGROUND INFORMATION ON ELX-021 ................................................................................................................................................ 25 
5.1.1 
Pre-Clinical Data ........................................................................................................................................................................... 25 
5.1.2 
Clinical Data .................................................................................................................................................................................. 26 
 
 
5.2 
STUDY RATIONALES .................................................................................................................................................................................. 29 
5.2.1 
Rationale for Study Design ............................................................................................................................................................. 29 
5.2.2 
Rationale for Dose Selection........................................................................................................................................................... 30 
5.2.3 
Safety Measures to be Utilized during the Present Study ................................................................................................................ 31 
5.2.4 
Rationale for the Study Population ................................................................................................................................................. 31 
6. 
OBJECTIVES ................................................................................................................................. 33 
7. 
STUDY DESIGN ............................................................................................................................ 33 
8. 
STUDY POPULATION ................................................................................................................. 34 
8.1 
SAMPLE SIZE ............................................................................................................................................................................................. 34 
8.2 
SUBJECTS WITH RENAL IMPAIRMENT (GROUPS 1 TO 3) ............................................................................................................................. 34 
8.2.1 
Inclusion Criteria for Subjects with Renal Impairment (Groups 1 to 3) ......................................................................................... 34 
8.2.2 
Exclusion Criteria for Subjects Renal Impairment (Groups 1 to 3) ................................................................................................ 35 
8.3 
SUBJECTS WITH NORMAL RENAL FUNCTION (GROUP 4) ............................................................................................................................ 37 
8.3.1 
Inclusion Criteria for Subjects with Normal Renal Function (Group 4) ......................................................................................... 37 
8.3.2 
Exclusion Criteria for Subjects with Normal Renal Function (Group 4) ........................................................................................ 38 
9. 
CLINICAL PROCEDURES .......................................................................................................... 40 
9.1 
SCREENING PROCEDURES .......................................................................................................................................................................... 40 
9.2 
ASSESSMENT OF RENAL FUNCTION FOR ELIGIBILITY AND CATEGORIZATION ........................................................................................... 40 
9.3 
IN-PATIENT STAY AND VISIT ..................................................................................................................................................................... 41 
9.3.1 
Outings ........................................................................................................................................................................................... 41 
9.4 
RANDOMIZATION, BLINDING, AND MATCHING .......................................................................................................................................... 41 
9.5 
STUDY MEDICATION .................................................................................................................................................................................. 42 
9.6 
DRUG SUPPLIES AND ACCOUNTABILITY .................................................................................................................................................... 42 
9.7 
DRUG ADMINISTRATION ............................................................................................................................................................................ 42 
9.8 
STUDY RESTRICTIONS................................................................................................................................................................................ 43 
9.8.1 
Food and Fluids .............................................................................................................................................................................. 43 
9.8.2 
Tobacco, Alcohol, and Illicit Drugs ................................................................................................................................................ 44 
9.8.3 
Concomitant Medications ............................................................................................................................................................... 44 
9.8.4 
Posture and Physical Activity ......................................................................................................................................................... 44 
9.8.5 
Contraception ................................................................................................................................................................................. 45 
9.9 
SAMPLE COLLECTION FOR PHARMACOKINETIC EVALUATION ................................................................................................................... 45 
9.9.1 
Blood Sample Collection and Processing ....................................................................................................................................... 45 
9.9.2 
Urine Sample Collection and Processing ....................................................................................................................................... 46 
9.10 
SUBJECT MONITORING............................................................................................................................................................................... 47 
9.10.1 
Vital Signs ....................................................................................................................................................................................... 47 
9.10.2 
ECG ................................................................................................................................................................................................ 47 
9.10.3 
Physical Examination and Body Measurements ............................................................................................................................. 48 
9.10.4 
Injection Site Evaluation ................................................................................................................................................................. 48 
9.10.5 
Drug, Alcohol and Cotinine Screen ................................................................................................................................................ 48 
9.10.6 
Pregnancy Test ............................................................................................................................................................................... 48 
9.10.7 
Laboratory Assessments ................................................................................................................................................................. 48 
9.10.8 
Determination of Creatinine Clearance .......................................................................................................................................... 49 
9.10.9 
Renal Injury Biomarkers ................................................................................................................................................................. 50 
9.11 
STUDY EXIT / EARLY TERMINATION PROCEDURES .................................................................................................................................... 50 
9.12 
DATA COLLECTION AND EVALUATION ...................................................................................................................................................... 50 

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9.13 
SUBJECT WITHDRAWAL AND REPLACEMENT ............................................................................................................................................ 50 
9.14 
ADVERSE EVENTS ...................................................................................................................................................................................... 51 
9.14.1 
Recording of Adverse Events .......................................................................................................................................................... 51 
9.14.2 
Assessment of Severity .................................................................................................................................................................... 51 
9.14.3 
Assessment of Relationship to the Study Drug ................................................................................................................................ 51 
9.14.4 
Serious Adverse Events ................................................................................................................................................................... 52 
9.15 
ON-STUDY PREGNANCY ............................................................................................................................................................................ 54 
9.16 
REPORTABLE DISEASE ............................................................................................................................................................................... 54 
10. 
STUDY TERMINATION .............................................................................................................. 54 
11. 
ANALYTICAL METHODOLOGY ............................................................................................. 55 
12. 
PHARMACOKINETIC AND STATISTICAL ANALYSES ..................................................... 55 
12.1 
PHARMACOKINETICS ................................................................................................................................................................................. 55 
12.1.1 
Plasma Pharmacokinetic Parameters ............................................................................................................................................. 55 
12.1.2 
Urine Pharmacokinetic Parameters................................................................................................................................................ 56 
12.2 
ANALYSIS POPULATIONS ........................................................................................................................................................................... 56 
12.2.1 
Safety Population ............................................................................................................................................................................ 56 
12.2.2 
Pharmacokinetic Population........................................................................................................................................................... 56 
12.3 
STATISTICAL ANALYSES ............................................................................................................................................................................ 57 
12.3.1 
Statistical Analyses of Pharmacokinetic Parameters ...................................................................................................................... 57 
12.3.2 
Safety and Tolerability Parameters and Analyses ........................................................................................................................... 57 
13. 
FINAL REPORT ............................................................................................................................ 58 
14. 
REGULATORY CONSIDERATIONS AND QUALITY ASSURANCE .................................. 58 
14.1 
INDEPENDENT ETHICS COMMITTEE APPROVAL OF PROTOCOL AND OTHER STUDY DOCUMENTS .............................................................. 58 
14.2 
COMPLIANCE ............................................................................................................................................................................................. 58 
14.3 
LIABILITY .................................................................................................................................................................................................. 59 
14.4 
QUALITY ASSURANCE PROGRAM .............................................................................................................................................................. 59 
14.5 
AUDITS, INSPECTIONS AND MONITORING .................................................................................................................................................. 59 
15. 
CONFIDENTIALITY AND RETENTION OF ESSENTIAL DOCUMENTATION .............. 59 
16. 
REFERENCES ............................................................................................................................... 59 
17. 
APPENDIX 1 ................................................................................................................................... 61 
 
 
 
List of Tables 
Table 1. 
Schedule of Events for Study Groups 1 to 4 ................................................................... 23 
Table 2. 
Classification of Subjects in Groups According to Renal Function ............................... 41 
Table 3. 
Blood Volume for Laboratory Analyses ......................................................................... 46 
Table 4. 
Assessment of AE Severity ............................................................................................ 51 
Table 5. 
Site Reactions to Injections and Infusions DAIDS Grading Table................................. 61 
 
 
 

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2. 
Synopsis of Protocol 
Project No.: 
182023 
Eloxx Pharmaceuticals study number: EL-008 
Study Title: 
A PHASE 1, OPEN-LABEL, SINGLE-DOSE, PARALLEL-GROUP STUDY 
TO EVALUATE THE EFFECTS OF RENAL IMPAIRMENT ON THE 
PHARMACOKINETICS OF ELX-02 
Study Drug: 
ELX-02 [6'-(R)-Methyl-5-O-(5-amino-5,6-dideoxy-α-L-talofuranosyl)-
paromamine sulfate] 
Study Phase and Type: 
Phase 1 – Pharmacokinetics in Patients with Impaired Renal Function 
Objectives: 
Primary objective: 
To determine the effect of various severities of renal impairment on the 
pharmacokinetics (PK) of ELX-02 following a single subcutaneous (SC) dose 
in subjects with normal renal function, mild, moderate, or severe renal 
impairment. 
Secondary objective: 
To assess the safety and tolerability of a single SC dose of ELX-02 in subjects 
with normal renal function, mild, moderate, or severe renal impairment. 
Study Design: 
The study is a two-center, Phase 1, open-label, single-dose, one-period, four-
parallel-group, PK study in subjects with various severities of renal dysfunction 
and healthy volunteers. 
Subjects will be categorized in 4 groups: 
Group 1: subjects with mild renal impairment 
Group 2: subjects with moderate renal impairment 
Group 3: subjects with severe renal impairment 
Group 4 (control group): subjects with normal renal function 
The mild (Group 1) and moderate (Group 2) patients with renal disease will be 
dosed first, in a parallel fashion. At this point, interim PK analyses will be 
performed and a safety committee composed of Sponsor and Contract Research 
Organization (CRO) members will jointly review the PK data before dosing the 
patients with severe renal disease (Group 3). Control subjects (Group 4) will be 
recruited after the recruitment of Groups 1 to 3. 
Subjects: 
It is targeted to enroll approximately 24 to 26 adult male or female subjects, 
≥ 18 and ≤ 80 years of age. Subjects with normal renal function will be non-
smoker while renally impaired (RI) subjects may be light smoker (no more than 
5 cigarettes/day or equivalent) or non-smoker. 
An effort will be made to carefully match the healthy subjects in the control 
group with the RI subjects by age (± 10 years), body mass index [BMI] (±15%), 
and gender, to the extent possible. Attempts will be made to enroll at least two 
subjects of each gender in each group and subjects with various BMIs. A mean 
matching procedure will be performed. Six (6) subjects completing the study 
are targeted for each group of RI subjects (Groups 1 to 3) and 6 to 8 subjects 
will be included in the control group (Group 4). 
Subjects who withdraw or are withdrawn from the study after dosing, for 
reasons other than safety and tolerability, may be replaced in order to ensure a 
minimum of 6 completed subjects per group. The total number of subjects 
dosed (including potential replacement subjects) will remain within a maximum 
of 8 subjects per group and within a maximum of 32 subjects for the whole 

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study. 
Inclusion and Exclusion 
Criteria for Subjects With 
Renal Impairment (Groups 1 
to 3): 
Inclusion Criteria: 
1) Male or female, non-smoker and/or light smoker (up to 5 cigarettes or 
equivalent/day), ≥ 18 and ≤ 80 years of age, with BMI ≥ 18.0 and 
≤ 40.0 kg/m2 and body weight ≥ 50.0 kg for males and ≥ 45.0 kg for 
females.  
2) Have a diagnosis of renal impairment that has been stable, without any 
significant change in overall disease status in the last 3 months prior to 
screening as determined by the Principal Investigator (PI). 
3) Have an estimated glomerular filtration rate (eGFR) expressed in 
mL/min/1.73 m2 (Modification of Diet in Renal Disease 4-variable 
[MDRD4] equation) at screening within the range of: 
a) Group 1 - Mild Group: 60 - 89 mL/min/1.73 m2; 
b) Group 2 - Moderate Group: 30 - 59 mL/min/1.73 m2; 
c) Group 3 - Severe Group: < 30 mL/min/1.73 m2 not requiring dialysis. 
eGFR results that are deemed inconsistent with the usual stage of renal 
impairment may be repeated. Subjects are categorized into severity group 
at screening. If the eGFR scores change on Day-1 or other visit due to a 
non-clinically significant change in clinical status or laboratory result, the 
subject keeps the original severity group. 
4) Subject may have stable treated medical illnesses and underlying diseases 
producing the renal impairment such as diabetes, hypertension, or 
cardiovascular disease, providing that, in the opinion of the PI, the disease 
is stable.  
5) Have normal or non-clinically significant findings at physical examination, 
vital signs and electrocardiogram (ECG) and normal limits or non-
clinically significant deviations in clinical laboratory evaluations at 
screening, with the exception of findings that in the opinion of the PI are 
consistent with subject’s renal impairment or due to other stable diseases. 
Clinical data, ECG and laboratory tests may be repeated at the discretion of 
the Investigator. 
6) Other than renal impairment, have no other conditions which may 
significantly impact study drug absorption or metabolism, as determined by 
the PI. 
7) Stable medical regimen, deemed not to interact with study drug PK, for 
14 days prior to dosing, except for routine daily management of 
electrolytes (e.g. potassium), acid-base, or other associated disorders 
expected in patients with renal impairment. The approval of the 
medications for the management of renal impairment and the treatment of 
concomitant stable medical conditions (e.g. diabetes, hypertension, 
associated stable cardiovascular disease, stable psychiatric conditions) is at 
the discretion of the PI. 
8) Females of childbearing potential who are sexually active with a non-
sterile male partner (sterile male partners are defined as men vasectomized 
since at least 6 months) must be willing to use one of the following 
acceptable contraceptive method throughout the study and for 30 days after 
study drug administration: 
a) simultaneous use of intra-uterine contraceptive device, without 
hormone release system, placed at least 4 weeks prior to study drug 
administration, and condom for the male partner; 

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b) simultaneous use of diaphragm with intravaginally applied spermicide 
and male condom for the male partner, starting at least 21 days prior to 
study drug administration. 
9) Male subjects who are not vasectomized for at least 6 months, and who are 
sexually active with a non-sterile female partner (sterile female partners 
include post-menopausal females and surgically sterile females) must be 
willing to use one of the following acceptable contraceptive method from 
dosing until at least 90 days after study drug administration: 
a) simultaneous use of a male condom and, for the female partner, 
hormonal contraceptives (used since at least 4 weeks) or intra-uterine 
contraceptive device (placed since at least 4 weeks); 
b) simultaneous use of a male condom and, for the female partner, a 
diaphragm with intravaginally applied spermicide. 
10) Male subjects (including men who have had vasectomy) with a pregnant 
partner must agree to use a condom from dosing until at least 90 days after 
study drug administration. 
11) Male subjects must be willing not to donate sperm until 90 days following 
study drug administration. 
12) Able to understand and willing to sign the Informed Consent Form (ICF) 
and comply with the study restrictions. 
Exclusion Criteria: 
1) Unstable renal function or acute exacerbation of renal disease within 
14 days of study drug administration, as indicated by recent history or 
worsening of clinical and/or laboratory signs of renal impairment as judged 
by the PI. For inclusion and for categorization by MDRD4 or other 
equations, laboratory results that are deemed inconsistent with the usual 
stage of renal impairment may be repeated. 
2) Has a functioning renal transplant. 
3) Major illness or surgery within 4 weeks prior to dosing. 
4) Clinically significant unstable medical condition or history of any illness 
that may increase the risk associated with study participation or 
investigational drug administration or may interfere with the interpretation 
of study results and, in the judgment of the PI, would make the subject 
inappropriate for entry into this study. Subjects who do not qualify based 
on a reversible medical condition or mild inter-current illness may be re-
evaluated after further testing/examination or re-screened after the 
condition is resolved. 
5) Positive test for hepatitis B, hepatitis C, or human immunodeficiency virus 
(HIV) at screening.  
6) History of allergic reactions, hypersensitivity or toxic reactions to 
aminoglycosides. 
7) History of anaphylaxis. 
8) Supine 12-lead ECG abnormalities at screening considered clinically 
significant by the PI. 
9) Clinically significant vital sign abnormalities (systolic blood pressure 
lower than 90 or over 160 mmHg, diastolic blood pressure lower than 40 or 
over 100 mmHg, or heart rate less than 45 or over 100 bpm) at screening. 
10) History of significant drug or alcohol abuse within six months prior to 
screening. 
11) Participation in a clinical research study involving the administration of an 

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investigational or marketed drug or device within 30 days (or 5 half-lives, 
whichever is longer) prior to dosing, administration of a biological product 
in the context of a clinical research study within 90 days prior to dosing, or 
concomitant participation in an investigational study involving no drug or 
device administration. 
12) Positive urine drug screen or alcohol test at screening, unless the positive 
drug screen is due to prescription drug use that is documented and 
approved by the PI. 
13) Female subject with positive pregnancy test at screening. 
14) Breast-feeding or pregnant subject within 6 months prior to study drug 
administration. 
15) Use of any drugs known as strong inducer or inhibitor of hepatic drug 
metabolism within 30 days prior to study drug administration. 
16) Use of medication other than stable medications approved by the PI and 
topical products without significant systemic absorption:  
a) any new prescription medication within 14 days prior to dosing; 
b) over-the-counter (OTC) products or natural health products (including 
herbal remedies such as St. John’s wort, homeopathic and traditional 
medicines, probiotics, food supplements such as vitamins, minerals, 
amino acids, essential fatty acids, and protein supplements used in 
sports) within 7 days prior to dosing, with the exception of the 
occasional use of acetaminophen (that is allowed up to 2 g daily), 
unless the products are used by RI subjects as part of their routine 
care; 
c) a depot injection or an implant of any drug within 3 months prior to 
dosing. 
17) The following medications are prohibited during the study: neuromuscular 
blocking agents (e.g. succinylcholine, tubocurarine), neurotoxic and/or 
nephrotoxic drugs (e.g. other aminoglycosides, cisplatin, cephaloridine, 
polymyxin B, vancomycin, viomycin). At the discretion of the PI, a 
suitable substitute medication may be prescribed to replace the prohibited 
medication. 
18) Donation of plasma within 7 days prior to dosing. Donation or loss of 
blood (excluding volume drawn at screening) of 50 mL to 499 mL of blood 
within 30 days, or more than 499 mL within 56 days prior to the first 
dosing. 
19) Any reason which, in the opinion of the PI, would prevent the subject from 
participating in the study. 
20) Inability to be venipunctured and/or tolerate catheter venous access. 
21) Presence of mitochondrial mutation(s) making the subject susceptible to 
aminoglycoside toxicity. 
22) Presence of signs of dehydration, recent history of neuromuscular blockade 
or clinically significant history of vestibular impairment. 
Inclusion and Exclusion 
Criteria for Subjects with 
Normal Renal Function 
(Group 4): 
Inclusion Criteria: 
1) Male or female, non-smoker (no use of tobacco or nicotine products within 
3 months prior to screening), ≥ 18 and ≤ 80 years of age, with BMI ≥ 18.0 
and ≤ 40.0 kg/m2 and body weight ≥ 50.0 kg for males and ≥ 45.0 kg for 
females.  
2) Have an eGFR ≥ 90 mL/min/1.73 m2 (MDRD4 equation). 

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3) Healthy as defined by: 
a) the absence of clinically significant illness and surgery within 4 weeks 
prior to dosing. Subjects vomiting within 24 hours pre-dose will be 
carefully evaluated for upcoming illness/disease. Inclusion pre-dosing 
is at the discretion of the PI. 
b) the absence of clinically significant history of hematological, renal, 
endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, 
psychiatric, neurologic, and immunologic disease. 
4) Matched to subjects with RI (mild, moderate or severe) according to 
gender, age (± 10 years), and BMI (± 15%). 
5) Females of childbearing potential who are sexually active with a non-
sterile male partner (sterile male partners are defined as men vasectomized 
since at least 6 months) must be willing to use one of the following 
acceptable contraceptive method throughout the study and for 30 days after 
study drug administration: 
a) simultaneous use of intra-uterine contraceptive device, without 
hormone release system, placed at least 4 weeks prior to study drug 
administration, and condom for the male partner; 
b) simultaneous use of diaphragm with intravaginally applied spermicide 
and male condom for the male partner, starting at least 21 days prior to 
study drug administration. 
6) Male subjects who are not vasectomized for at least 6 months, and who are 
sexually active with a non-sterile female partner (sterile female partners 
include post-menopausal females and surgically sterile females) must be 
willing to use one of the following acceptable contraceptive method from 
dosing until at least 90 days after study drug administration: 
a) simultaneous use of a male condom and, for the female partner, 
hormonal contraceptives (used since at least 4 weeks) or intra-uterine 
contraceptive device (placed since at least 4 weeks); 
b) simultaneous use of a male condom and, for the female partner, a 
diaphragm with intravaginally applied spermicide. 
7) Male subjects (including men who have had vasectomy) with a pregnant 
partner must agree to use a condom from the first dosing until at least 
90 days after study drug administration. 
8) Male subjects must be willing not to donate sperm until 90 days following 
study drug administration. 
9) Able to understand and willing to sign the ICF and comply with the study 
restrictions. 
Exclusion Criteria 
1) Any clinically significant abnormality at physical examination or clinically 
significant abnormal laboratory test results at screening. 
2) Positive test for hepatitis B, hepatitis C, or HIV at screening.  
3) History of allergic reactions, hypersensitivity or toxic reactions to 
aminoglycosides. 
4) Evidence or history of clinically relevant hematological, renal, endocrine, 
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, 
neurologic, immunologic, or allergic disease. This includes any acute or 
chronic medical or psychiatric condition or laboratory abnormality that 
may increase the risk associated with study participation or investigational 
drug administration or may interfere with the interpretation of study results 

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and, in the judgment of the PI, would make the subject inappropriate for 
entry into this study. 
5) History of anaphylaxis. 
6) Clinically significant supine 12-lead ECG abnormalities at screening, e.g., 
QTcF >450 msec for men and >470 msec for women, or a QRS interval 
>120 msec. 
7) Clinically significant vital sign abnormalities (systolic blood pressure 
lower than 90 or over 140 mmHg, diastolic blood pressure lower than 50 or 
over 90 mmHg, or heart rate less than 50 or over 100 bpm) at screening. 
8) History of significant alcohol abuse within one year prior to screening or 
regular use of alcohol within six months prior to the screening visit (more 
than fourteen units of alcohol per week [1 unit = 150 mL of wine, 360 mL 
of beer, or 45 mL of 40% alcohol]).  
9) History of significant drug abuse within one year prior to screening or use 
of soft drugs (such as marijuana) within 3 months prior to the screening 
visit or hard drugs (such as cocaine, phencyclidine [PCP], crack, opioid 
derivatives including heroin, and amphetamine derivatives) within 1 year 
prior to screening. 
10) Participation in a clinical research study involving the administration of an 
investigational or marketed drug or device within 30 days (or 5 half-lives, 
whichever is longer) prior to dosing, administration of a biological product 
in the context of a clinical research study within 90 days prior to dosing, or 
concomitant participation in an investigational study involving no drug or 
device administration. 
11) Positive urine drug screen, alcohol test, or urine cotinine test at screening. 
12) Female subject with positive pregnancy test at screening. 
13) Breast-feeding or pregnant subject within 6 months prior to study drug 
administration. 
14) Use of any drugs known to induce or inhibit hepatic drug metabolism 
within 30 days prior to study drug administration. 
15) Use of medication other than topical products without significant systemic 
absorption:  
a) prescription medication within 14 days prior to dosing; 
b) OTC products and natural health products (including herbal remedies 
such as St. John’s wort, homeopathic and traditional medicines, 
probiotics, food supplements such as vitamins, minerals, amino acids, 
essential fatty acids, and protein supplements used in sports) within 
7 days prior to dosing, with the exception of the occasional use of 
acetaminophen (that is allowed up to 2 g daily); 
c) a depot injection or an implant of any drug within 3 months prior to 
dosing. 
16) Donation of plasma within 7 days prior to dosing. Donation or loss of 
blood (excluding volume drawn at screening) of 50 mL to 499 mL of blood 
within 30 days, or more than 499 mL within 56 days prior to dosing. 
17) Hemoglobin < 12.8 g/dL (males) and < 11.5 g/dL (females) and hematocrit 
< 37% (males) and < 32% (females) at screening. 
18) Any reason which, in the opinion of the PI, would prevent the subject from 
participating in the study. 
19) Inability to be venipunctured and/or tolerate catheter venous access. 

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Study Restrictions: 
Subjects will be asked to refrain from using products that may potentially affect 
their safety and/or the pharmacokinetic profile of the study drug. Main study 
restrictions include: 
- 
prescription medication (other than stable medications approved by the PI 
for Groups 1-3) from 14 days prior to dosing until study exit; 
- 
OTC products from 7 days prior to dosing until study exit, with the 
exception of the occasional use of acetaminophen (that is allowed up to 2 g 
daily) and products used by RI subjects as part of their routine care; 
- 
natural health products from 7 days pre-dose until study exit, except for 
products used by RI subjects as part of their routine care; 
- 
food containing poppy seeds within 24 hours prior to admission; 
- 
food or beverages containing xanthine derivatives or xanthine-related 
compounds or energy drinks from 48 hours pre-dose until after the 72-hour 
blood sample collection; 
- 
food or beverages containing grapefruit, Seville orange, starfruit, 
pomegranate, pineapple, or pomelo from 7 days pre-dose until after the 
72-hour blood sample collection; 
- 
alcohol-based products from 24 hours prior to admission until after the 
72-hour blood sample collection; 
- 
for light smoking subjects in Groups 1 to 3, smoking will be prohibited 
from at least 2 hours pre-dose until 2 hours post-dose and a maximum of 
5 cigarettes per day will be allowed while subjects are in-patients in the 
clinic. 
Subjects will be allowed to engage in normal activity but will avoid lying down 
or sleeping, unless medically necessary or procedurally required, for 4 hours 
after drug administration. 
For subjects in Groups 1 to 3: Short outings will be permitted during the in-
patient period for smoking subjects. Non-smokers could also go out for 
supervised outings at the discretion of the site staff. Outings will be supervised 
at all times by the clinical staff to ensure compliance with protocol and will be 
limited to the grounds surrounding the site, as per the clinical site specific 
procedures for supervised outings. 
Blood Sample Collection for 
PK Analysis: 
A total of 13 blood samples will be collected for PK analysis for each subject of 
Groups 1 to 4: 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 36, 48, 72, and 
168 (Day 8) hours post-dose. 
Urine Sample Collection for 
PK Analysis: 
Urine samples for PK analysis will be collected for each subject at the 
following time or time intervals: pre-dose (first void in the morning of Day 1), 
0-3, 3-6, 6-9, 9-12, 12-18, 18-24, 24-36, 36-48, and 48-72 hours post-dose. 
Urine Sample Collection for 
Creatinine Analysis: 
Urine samples collected for PK assessment from dosing to 24 hours post-dose 
will also be used for analysis of creatinine to calculate creatinine clearance 
(ClCr). 
Urine sample for creatinine analysis will be collected along with samples for 
renal injury biomarkers: prior to dosing and at approximately 12, 24, 36, and 
48 hours post-dose, and on Day 8. 
Renal Injury Biomarkers: 
Urine samples for early markers of renal injury (KIM-1 and clusterin) will be 
collected prior to dosing and at approximately 12, 24, 36, and 48 hours post-
dose, and on Day 8.  
 

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On-Study Safety Procedures: 
Physical examination and body measurements: 
Brief physical examination: on Day -1 and at check-out on Day 4. 
Body weight measurement: on Day -1. 
Laboratory tests: 
Serum pregnancy test, alcohol test (breath or urine), urine cotinine test (for 
Group 4 only), and urine drug screen: on Day -1. 
Biochemistry, hematology, and coagulation (all clinical laboratory tests 
following a fasting period of at least 8 hours): on Day -1. 
Urinalysis: on Day -1 and at approximately 24 and 72 hours post-dose. 
Serum creatinine: approximately 24 hours post-dose. 
Vital signs: 
BP, HR and OT: before dosing and approximately 2, 4, 24, and 48 hours post-
dose. 
BP, HR, RR and OT: at check-out on Day 4. 
ECG: 
12-lead ECG: before dosing, approximately 2 hours post-dose and at check-out 
on Day 4. 
Injection site evaluation: 
Injection site evaluation: before dosing and approximately 0.75, 2, 6, 12, 24, 36, 
48, and 72 hours post-dose. 
Medical surveillance and AE monitoring: 
Medical surveillance: Subjects will be monitored throughout the study by the 
site staff for adverse events (AEs). A physician will be on site/campus for drug 
administration and until 4 hours post-dose, and available on call for the 
remainder of the study. 
Study Exit / Early 
Termination Procedures: 
Study exit procedures are scheduled to be performed at the follow-up visit on 
Day 8 (±1 day) or within 14 days after the last participation of the subject in the 
study in case of early termination. 
The study exit procedures include: brief physical examination, hematology, 
biochemistry, coagulation, urinalysis, vital signs, 12-lead ECG, urine pregnancy 
test, injection site evaluation, and AE monitoring.  
Analytical Methods: 
QPS will analyze ELX-02 in plasma and urine samples using validated 
methods.   
Pharmacokinetics: 
Parameters calculated with plasma concentrations of ELX-02: AUC0-72, AUC0-t, 
AUC0-inf, Cmax, Residual area, Tmax, T½ el, Kel, CL/F, and Vd/F. 
Parameters calculated with urine concentrations of ELX-02: Aeinterval, Ae0-t, 
Rmax, TRmax, Fe0-t, and CLR. 
Statistical Analyses: 
Pharmacokinetics: 
For plasma PK parameters, using GLM procedures in SAS, ANOVA will be 
performed on untransformed Tmax, Kel and T½ el and on ln-transformed AUC0-72, 
AUC0-t, AUC0-inf, and Cmax at the alpha level of 0.05. The ratio of geometric 
means (Mild/Control, Moderate/Control, Severe/Control) and 90% confidence 
interval (CI) for the ratio of geometric means, based on least-squares means 
from the ANOVA of the ln-transformed data, will be calculated for AUC0-72, 
AUC0-t, AUC0-inf, and Cmax. Tmax will be analyzed nonparametrically with point 
estimates and 90% CIs for the median differences of Tmax between treatments 

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(Mild-Control, Moderate-Control, Severe-Control).  
For urine PK parameters, using GLM procedures in SAS, ANOVA will be 
performed on ln-transformed Ae0-t and Rmax at the alpha level of 0.05 to 
compare groups (Mild, Moderate, Severe and Control). The ratio of geometric 
means (Mild/Control, Moderate/Control, Severe/Control) and 90% CI for the 
ratio of geometric means, based on least-squares means from the ANOVA of 
the ln-transformed data, will be calculated for Ae0-t and Rmax. 
Safety and tolerability: 
Treatment-emergent AEs (TEAEs) will be tabulated by study group. Changes 
from baseline values in vital signs, ECG, and clinical laboratory parameters will 
be evaluated. Safety and tolerability data will be reported using descriptive 
statistics. 
Details of statistical analyses will be developed in a Statistical Analysis Plan 
(SAP). 

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3. 
List of Abbreviations 
AE 
Adverse Event 
Ae 
Cumulative Urinary Excretion 
AIDS 
Acquired Immune Deficiency Syndrome 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
AUC 
Area Under the Curve 
BMI 
Body Mass Index 
BP 
Blood Pressure 
BSA 
Body Surface Area 
BUN 
Blood Urea Nitrogen 
CI 
Confidence Interval 
CF 
Cystic Fibrosis 
CFR 
Code of Federal Regulations 
CFTR 
Cystic Fibrosis Transmembrane Regulator  
CLR 
Renal Clearance 
CL/F 
Total Body Clearance 
ClCr 
Creatinine Clearance 
Cmax 
Maximum Plasma Concentration 
CPK 
Creatine Phosphokinase 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CV 
Coefficient of Variation 
DAIDS 
Division of AIDS 
DMD 
Duchenne Muscular Dystrophy 
ECG 
Electrocardiogram 
eGFR 
Estimated Glomerular Filtration Rate 
ERSG 
Eukaryotic Ribosomal Specific Glycoside 
FDA 
Food and Drug Administration 
Fe 
Fraction of Drug Excreted Unchanged 
GCP 
Good Clinical Practices 
GFR 
Glomerular Filtration Rate 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
HBsAg 
Hepatitis B 
HCV 
Hepatitis C 
HEENT 
Head, Eyes, Ears, Nose, and Throat 
HIV 
Human Immunodeficiency Virus 
HR 
Heart Rate 
IB 
Investigator’s Brochure 

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ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
IV 
Intravenous 
Kel 
Elimination Rate Constant 
kg 
Kilogram 
L 
Liters 
MDMA 
3,4-Methylenedioxymethamphetamine 
MDRD4 
Modification of Diet in Renal Disease 4-variable Equation 
mg 
Milligram 
mL 
Milliliter 
mmHg 
Millimeters of Mercury 
MPS I 
Mucopolysaccharidosis Type I 
NOAEL 
No Observed Adverse Event Level 
OT 
Oral Temperature 
OTC 
Over-the-Counter 
PCP 
Phencyclidine 
PI 
Principal Investigator 
PK 
Pharmacokinetic 
aPTT 
Activated Partial Thromboplastin Time 
PT 
Prothrombin Time 
QA 
Quality Assurance 
QC 
Quality Control 
QRS 
QRS Complex 
QT 
QT Interval 
QTcF 
Fridericia’s Corrected QT interval 
RI 
Renally Impaired 
Rmax 
Maximum Rate of Urinary Excretion 
RR 
Respiratory Rate 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SARS 
Severe Acute Respiratory Syndrome 
SC 
Subcutaneous 
SD 
Standard Deviation 
SOP 
Standard Operation Procedure 
SPVG 
Syneos Health Safety and Pharmacovigilance 
TEAE 
Treatment-Emergent Adverse Event 
T1/2 
Half-Life 
T½ el 
Elimination Half-Life 

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Tmax 
Time of Maximum Concentration 
Vd/F 
Apparent Volume of Distribution 
 
 
 

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4. 
Schedule of Events 
Table 1. 
Schedule of Events for Study Groups 1 to 4 
PROCEDURE 
Screening 
Groups 1 to 4 
Study Exit (Follow-
Up Visit on 
Day 8 ± 1) or Early 
Termination 
D-1 
D1 
D2 
D3 
D4 
Demographic Data 
X 
 
 
 
 
 
 
Medical and Medication Histories 
X 
 
 
 
 
 
 
Review and Monitoring of AEs 
and Concomitant Medications 
 
X 
X 
X 
X 
X 
X 
Physical Examination1 
X 
X 
 
 
 
X 
X 
Body Measurements 
X 
X2 
 
 
 
 
 
Vital Signs (BP, HR, RR, OT) 
X 
 
X3 
X3 
X3 
X3 
X 
ECG 
X 
 
X4 
 
 
X4 
X 
Hematology 
X 
X5 
 
 
 
 
X 
Biochemistry 
X 
X5 
 
X6 
 
 
X 
Serum Cystatin C Measurement7 
X 
 
 
 
 
 
 
Coagulation 
X 
X5 
 
 
 
 
X 
Urinalysis 
X 
X5 
 
X 
 
X 
X 
HIV and Hepatitis 
X 
 
 
 
 
 
 
Genetic Testing for Mitochondrial 
Mutations 
X 
 
 
 
 
 
 
Urine Drug Screen 
X 
X 
 
 
 
 
 
Urine Cotinine Test (for Group 4 
only) 
X 
X 
 
 
 
 
 
Alcohol Test (Breath or Urine 
Test) 
X 
X 
 
 
 
 
 
Serum Pregnancy Test 
 
X 
 
 
 
 
 
Urine Pregnancy Test 
X 
 
 
 
 
 
X 
Injection Site Evaluation 
 
 
X8 
X8 
X8 
X8 
X 
In-Patient Stay 
 
X 
X 
X 
X 
 
 
Study Drug Administration 
 
 
X 
 
 
 
 
PK Blood Samples9 
 
 
X 
X 
X 
X 
X 
PK Urine Sample10 
 
 
X 
X 
X 
X 
 
Urine Sample for Creatinine11 
 
 
X 
X 
X 
 
X 
Renal Injury Biomarkers12 
 
 
X 
X 
X 
 
X 
1 A complete physical examination will be performed at screening. A brief physical examination will be performed 
on Day -1, at check-out on Day 4 and at study exit. 
2 Body weight only on Day -1. 
3 BP, HR and OT: before dosing and approximately 2, 4, 24, and 48 hours post-dose. BP, HR, RR and OT: at 
check-out on Day 4. 
4 ECG: pre-dose, approximately 2 hours post-dose and at check-out on Day 4. 
5 Laboratory assessments (i.e., biochemistry, hematology, coagulation, and urinalysis) will be done in the morning 
of Day -1 following a fasting period of at least 8 hours. 
6 Serum creatinine only: approximately 24 hours post-dose. 

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7 Cystatin C will be measured at screening and cystatin GFR will be estimated for additional data analysis, only if 
needed. These values will have no impact on subject’s eligibility and categorization. 
8 Injection site evaluation: before dosing and approximately 0.75, 2, 6, 12, 24, 36, 48, and 72 hours post-dose. 
9 PK blood samples: 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 36, 48, 72, and 168 (Day 8) hours post-dose. 
10 Urine samples for PK analysis: pre-dose (first void in the morning of Day 1), 0-3, 3-6, 6-9, 9-12, 12-18, 18-24, 
24-36, 36-48, and 48-72 hours. 
11 Urine samples collected for PK assessment from 0 to 24 hours post-dose will also be used for analysis of 
creatinine to calculate ClCr. Spot urine sample for creatinine analysis will be collected prior to dosing and at 
approximately 12, 24, 36, and 48 hours post-dose, and on Day 8. 
12 Renal Injury Biomarkers (KIM-1 and clusterin): pre-dose, at approximately 12, 24, 36, and 48 hours post-dose 
and on Day 8. 

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5. 
Introduction 
5.1 
Background Information on ELX-021 
Eloxx Pharmaceuticals is developing ELX-02 [6'-(R)-Methyl-5-O-(5-amino-5,6-dideoxy-α-L-
talofuranosyl)- paromamine sulfate], a small molecule, new chemical entity for SC 
administration. The target indication for ELX-02 is the treatment of genetic diseases caused by 
nonsense mutations. 
ELX-02 is a 
 
 
 eukaryotic ribosomal specific glycoside (ERSG) 
optimized as a translational read-through drug. Chemically, ELX-02 can be synthesized from 
standard precursor blocks. Biologically, ELX-02 exhibits high selectivity towards the eukaryotic 
ribosome and decreased binding to mitochondrial and prokaryotic ribosomes. ELX-02 induces 
high read-through activity leading to the synthesis of functional proteins in models carrying 
nonsense mutations in cystic fibrosis transmembrane regulator (CFTR) (cystic fibrosis [CF]). 
5.1.1 
Pre-Clinical Data 
In a large number of pharmacology studies, the translational read-through capabilities of ELX-02 
have been tested in in vitro cell models and in in vivo animal models. ELX-02 induced 
expression of functional proteins with pharmacodynamic and behavioral effects with a 
satisfactory window of safety in several cellular and animal models of genetic disease caused by 
nonsense mutations, including, CF, cystinosis, Duchenne muscular dystrophy (DMD), 
mucopolysaccharidosis type I (MPS I), and Rett syndrome. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Further preclinical data on ELX-02 are available in the Investigator’s Brochure (IB).1 

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5.1.2 
Clinical Data 
Eloxx Pharmaceuticals has completed two Phase 1a, first-in-human, randomized, double-blinded 
placebo-controlled single dose-escalating studies in healthy human subjects. These studies 
(combined) evaluated single doses of ELX-02 between 0.3 mg/kg and 7.5 mg/kg in 60 healthy 
subjects and characterized general and specialized safety parameters, and PK. In these studies, 
ELX-02 was generally well tolerated, showed typical PK parameters for an aminoglycoside, and 
showed an acceptable safety profile without severe or serious drug-related AEs. A Phase 1b, 
randomized, double-blinded placebo-controlled multiple dose-escalating study in healthy human 
subjects is ongoing. 
In total, 25/40 (62.5%) subjects experienced at least 1 TEAE after administration of ELX-02 and 
9/20 (45.0%) subjects after administration of placebo. The most frequently observed TEAEs 
were: injection site reaction, observed in 4/40 (10%) subjects after administration of ELX-02 and 
2/20 (10%) subjects after administration of placebo, and headache, observed in 4/40 (10%) 
subjects after administration of ELX-02 and 1/20 (5%) subjects after administration of placebo. 
Ototoxicity is a known complication associated with aminoglycoside use. Auditory function and 
vestibular function were assessed in the Phase 1a studies using a battery of tests. An abnormal 
audiogram was reported in 1 out of 7 subjects, 7 days after administration of ELX-02 0.3 mg/kg 
IV. The AE was considered mild and not related to study drug by the Investigator and resolved 
on Day 106 after the administration of study drug. One out of 8 subjects, at a dose level of 
5 mg/kg showed a high frequency threshold shift on audiometry, and it remained unresolved on 
post-dose Day 58. There was no clinical impact, as there were no symptoms, and pure tone 
audiometry (normal speech frequencies) remained normal. This event was considered probably 
related to the study drug by the Investigator, the Sponsor did not consider it related to the study 
drug based on the opinion of the audiometry expert. This event was considered to be an SAE by 
the Investigator. There were no abnormal auditory findings noted at a dose level of 7.5 mg/kg. In 
addition to these events, ear discomfort was reported in 3 subjects and ear pain was reported in 
3 subjects (7.1%, each): 5 of the 6 subjects with ear symptoms received ELX-02 while 1 subject 
received placebo. 
The Phase 1a studies assessed the impact of ELX-02 dosing on clusterin and KIM-1, biomarkers 
of early proximal renal tubular injury. Although nephrotoxicity is a known complication of 
aminoglycoside use, there was no evidence in the completed single-dose studies that injection of 
ELX-02 affects renal function. 
ELX-02 demonstrated linear dose PK in plasma with a short plasma half-life and parameters 
characteristic of an aminoglycoside. After single SC administrations, ELX-02 was rapidly 
absorbed with a median Tmax of 0.5 hours for the lowest dose of 0.3 mg/kg and of 1 hour for the 
other doses. The elimination was rapid with mean terminal half-life (T1/2) ranging between 2 to 
4 hours for lower doses (0.3 to 5.0 mg/kg) whereas mean T1/2 was longer for the highest dose 
(about 8 hours for 7.5 mg/kg) as expected with the use of a non-compartmental model in a 
situation of multiple exponential elimination. The decline of plasma concentrations was 
monophasic at lowest doses whereas it was biphasic for doses of 2.5 and 5.0 mg/kg and 
multiphasic for dose of 7.5 mg/kg with concentrations longer quantifiable at higher doses. Mean 
residence time was about 3 to 4 hours and mean apparent body clearance about 6 L/h for all 
doses. Mean apparent volume of distribution was dose-dependent with values of about 

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16.9-70.5 L for doses of 0.3 to 7.5 mg/kg. These data suggest a larger distribution with higher 
doses, not only restricted to extracellular fluids. The inter-subject variability on main plasma PK 
parameters (Cmax, AUC0-inf, partial AUCs) was low with CV% ranging from 6.54 to 18.6% for 
Cmax and 7.64 to 18.2% for AUCs. 
Renal excretion accounted for a large part of the eliminated drug. Mean percent of ELX-02 
recovered in urine over the 48 hours post-dose of collection was 85.2% for IV treatment and 
ranged from 81.1 to 99.2% for SC doses. For all SC doses, more than 78% of the administered 
drug was excreted within the 12 hours post-dosing. Mean renal clearance was about 4.8 L/h for 
IV treatment and ranged between 4.6 to 6.1 L/h for SC treatments. 
Further clinical data on ELX-02 from single dose studies are available in the IB.1 
Presently, there is one ongoing clinical study with ELX-02 (study EL-002). It is a Phase 1, 
randomized, double-blinded, placebo-controlled, third party open, multiple-dose escalation, 
single center study to evaluate the safety, tolerability, and PK of subcutaneously administered 
ELX-02 in independent consecutive cohorts of healthy subjects. 
The study includes at least 5 cohorts of 9 subjects each (both males and females need to be 
enrolled in each cohort, a significant number of female subjects need to be enrolled). Subjects 
will be randomized to receive multiple doses of ELX-02 or placebo at a ratio of 2:1 in each 
cohort. Six subjects in each cohort will receive ELX-02 and three will receive placebo. The 
cohorts are as follows: 
Cohort 1 – ELX-02, 0.1 mg/kg or placebo SC twice a week for a total of nine doses; 
Cohort 2 - ELX-02, 0.3 mg/kg or placebo SC twice a week for a total of nine doses; 
Cohort 3 - ELX-02, 1.0 mg/kg or placebo SC twice a week for a total of nine doses; 
Cohort 4 – ELX-02, 2.5 mg/kg (100 mg/mL) or placebo SC twice a week for a total of nine 
doses; 
Cohort 5 - ELX-02, up to 2.5 mg/kg (50 mg/mL per injection) or placebo SC twice a week for a 
total of nine doses; 
Cohort 6 - ELX-02, 2.5 to 5.0 mg/kg ELX-02 or placebo SC twice a week for a total of nine 
doses;  
Cohort 7 - ELX-02, up to 5.0 mg/kg or placebo SC twice a week for a total of nine doses. 
Dose escalation to the next cohort will not proceed until after the 14-day observation period for 
the previous cohort in order to allow for the detection of unanticipated delayed AEs. Changes to 
the planned dose may be made in any cohort, depending on available safety and PK data. The 
dose will not exceed 5.0 mg/kg. Additional cohorts of subjects may be considered to further 
establish the safety of ELX-02. 
As of the date of this protocol, the first 4 dosing cohorts have been completed. The study remains 
blinded (except for one subject with AE of abnormal audiometry that was unblinded by the 
Sponsor) and the available data are preliminary. 
 
 
 
 
 
 
 
 

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5.1.3.2 
Benefits 
ELX-02 is being developed for patients with genetic disorders caused by nonsense mutations, 
and this study will help in the development of the drug. There are no direct benefits for the 
subjects participating in this study. 
5.2 
Study Rationales 
5.2.1 
Rationale for Study Design 
Aminoglycosides are known to produce nephrotoxicity in experimental animals and man at high 
doses and after repeated doses, and the risk of nephrotoxicity is generally greater in patients with 
impaired renal function and in those who receive high dosage of prolonged therapy.1,2 ELX-02 is 
a synthetic aminoglycoside that is eliminated primarily through renal excretory mechanisms.1 
The clinical development program of ELX-02 includes Phase 2, proof-of-principle, dose finding 
studies in patients with CF and cystinosis.1 Before starting the first Phase 2 study involving the 
administration of ELX-02 doses from 1 mg/kg up to 5 mg/kg over 4 weeks in patients with mild 
to moderate nephropathic cystinosis with at least 1 nonsense mutation in the cystinosin gene, the 
influence of renal impairment in relation to the PK of the drug will be evaluated. This is because 
when there is a risk of clinically relevant increases in exposure to a drug or active metabolite in 
patients with renal impairment, the FDA Draft Guidance for Industry, Pharmacokinetics in 
Patients with Impaired Renal Function - Study Design, Data Analysis, and Impact on Dosing 
and Labeling3 and the EMA Guideline on the evaluation of the pharmacokinetics of medicinal 
products in patients with decreased renal function4 recommend the conduct of a PK study in 
subjects with decreased renal function in order to obtain adequate treatment recommendations. 

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This Phase 1 study is designed to determine the effect of various severities of renal impairment 
(i.e., mild, moderate, and severe renal impairment, as compared to a control group with normal 
renal function) on the PK of ELX-02 after a single dose of 1 mg/kg. The study will also gather 
additional data on the safety and tolerability of ELX-02 in subjects with normal renal function, 
and preliminary safety and tolerability in RI subjects, by evaluating AEs, local reactions at the 
injection site, physical examination, vital signs, ECG, and clinical laboratory parameters. This 
study should allow the development of specific dosing recommendations across the entire 
spectrum of renal impairment. 
5.2.2 
Rationale for Dose Selection 
A single-dose study to evaluate the effects of renal impairment is appropriate if the drug and its 
active metabolites (if any) are expected to exhibit dose-linear and time-independent PK in RI 
individuals, and steady state PK can be predicted from single-dose data.4 ELX-02 showed dose-
exposure linearity in the range of 0.3 mg/kg to 7.5 mg/kg following single-dose administration. 
Based on pre-clinical data, the anticipated clinically efficacious doses range from 2.5 mg/kg to 
5.0 mg/kg, which are within the dose proportionality range. At pharmacological doses, ELX-02 
shows no accumulation in plasma and a relatively low accumulation in the kidney and cochlear 
tissues.1 Based on these properties, a single-dose design is judged appropriate to assess the 
influence of renal impairment on the PK of ELX-02. 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 

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5.2.2.2 
Anticipated Exposure 
ELX-02 is primarily eliminated via the kidney similar to what has been observed for other 
aminoglycosides. The main processes are glomerular filtration and subsequent reabsorption in 
the kidney. Aminoglycosides are reabsorbed in the proximal tubules in the kidney via megalin, a 
transmembrane endocytic receptor expressed in epithelial membrane in the kidney as well as 
other tissues. In addition to megalin, other transporters expressed in the kidney (OCT2 and 
SGLT2) play a role in the reabsorption of aminoglycosides in the kidney. 
A dose of 1 mg/kg of ELX-02 has been selected for the present study as it has been shown to 
allow for a good characterization of ELX-02 PK profile. In the Phase 1 SAD study noted above, 
following a single 1 mg/kg SC dose, the mean (N=6) Cmax was 3576 (± 502) ng/mL, the median 
Tmax was 1.0 (range 1.0-1.0) hours, and the mean AUC0-12 was 13,131 (± 1729) ng*h/mL. The 
half-life was 2.14 (± 2.14) hours, and clearance (CL/F) was 5.50 (± 0.349) L/h.1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5.2.3 
Safety Measures to be Utilized during the Present Study 
 
 
The mild (Group 1) and moderate (Group 2) patients with renal disease will be dosed first, 
in a parallel fashion. At this point, a safety committee composed of Sponsor and CRO members 
will jointly review the PK data before dosing the patients with severe renal disease (Group 3). 
For the control group (Group 4) a mean matching procedure will be performed in order to match 
the healthy subjects in the control group with the RI subjects. 
5.2.4 
Rationale for the Study Population 
This study will be conducted in patients with mild, moderate, or severe renal impairment, as well 
as in age and BMI matched healthy controls. Most drugs are cleared by elimination of unchanged 
drug by the kidney and/or metabolism in the liver and/or small intestine. In patients with 
impaired renal function, the PK of a drug that is eliminated primarily by the kidney may be 
altered to an extent that the dosing regimen may need to be changed. The primary change 

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resulting from renal impairment is a decrease in renal excretion of the drug or its metabolites, but 
changes in renal excretion of a drug may also occur. Renal impairment may also be associated 
with changes in absorption, plasma protein binding, transport and tissue distribution. Therefore, 
the FDA recommends that PK be assessed in patients with renal impairment in order to provide 
proper dosing recommendations.  
 

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6. 
Objectives 
Primary objective: 
To determine the effect of various severities of renal impairment on the PK of ELX-02 following 
a single SC dose in subjects with normal renal function, mild, moderate, or severe renal 
impairment. 
Secondary objective: 
To assess the safety and tolerability of a single SC dose of ELX-02 in subjects with normal renal 
function, mild, moderate, or severe renal impairment. 
7. 
Study Design 
The study is a two-center, Phase 1, open-label, single-dose, one-period, four-parallel-group, PK 
study in subjects with various severities of renal dysfunction and healthy volunteers. 
The subjects enrolled in the study will be categorized in 4 groups according to their renal 
function (eGFR value calculated using the MDRD4 equation – refer to section 9.2): 
Group 1: subjects with mild renal impairment 
Group 2: subjects with moderate renal impairment 
Group 3: subjects with severe renal impairment 
Group 4 (control group): subjects with normal renal function 
The mild (Group 1) and moderate (Group 2) patients with renal disease will be dosed first, in a 
parallel fashion. At this point, interim PK analyses will be performed and a safety committee 
composed of Sponsor and CRO members will jointly review the PK data. 
 
 
 
 
The safety committee will then authorize dosing in patients with severe renal disease (Group 3). 
Control subjects (Group 4) will be recruited after the recruitment of Groups 1 to 3 to facilitate 
subjects' matching between the healthy subjects in the control group with the RI subjects. 
Each subject will receive a single SC dose of ELX-02 1 mg/kg on Day 1. They will remain as 
in-patients at the clinical site under close surveillance by the site staff for 72 hours post-dose and 
they will come back for a follow-up visit on Day 8 (±1 day). 
Serial blood and urine samples will be collected to quantify ELX-02, in order to evaluate the 
effect of the various severities of renal impairment (i.e., mild, moderate, and severe renal 
impairment, as compared to a control group with normal renal function) on the PK of study drug. 
The study will also evaluate the safety and tolerability of ELX-02 in subjects with normal renal 
function and in RI subjects, by evaluating AEs, local reactions at the injection site, physical 
examination, vital signs, ECG, early markers of renal injury, and clinical laboratory parameters. 
This study is intended for filing under FDA regulations. 

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8. 
Study Population 
8.1 
Sample Size 
It is targeted to enroll approximately 24 to 26 healthy adult male or female volunteers. 
Subjects will be assigned to one of the 4 study groups. Six (6) subjects completing the study are 
targeted for each group of RI subjects (Groups 1 to 3) and 6 to 8 subjects will be included in the 
control group (Group 4). Attempts will be made to enroll at least two subjects of each gender in 
each group and subjects with various BMIs. 
Subjects who withdraw or are withdrawn from the study after dosing, for reasons other than 
safety and tolerability, may be replaced in order to ensure a minimum of 6 completed subjects 
per group. The total number of subjects dosed (including potential replacement subjects) will 
remain within a maximum of 8 subjects per group and within a maximum of 32 subjects for the 
whole study. 
8.2 
Subjects with Renal Impairment (Groups 1 to 3) 
Subjects enrolled in Groups 1, 2, and 3 will be members of the community at large. The 
recruitment advertisements may use various media types (e.g. radio, newspaper, Web site or 
volunteer database of the University of Miami). 
8.2.1 
Inclusion Criteria for Subjects with Renal Impairment (Groups 1 to 3) 
Subjects must meet all of the following criteria to be included in the study Groups 1 to 3: 
1) Male or female, non-smoker and/or light smoker (up to 5 cigarettes or equivalent/day), ≥ 18 
and ≤ 80 years of age, with BMI ≥ 18.0 and ≤ 40.0 kg/m2 and body weight ≥ 50.0 kg for 
males and ≥ 45.0 kg for females.  
2) Have a diagnosis of renal impairment that has been stable, without any significant change in 
overall disease status in the last 3 months prior to screening as determined by the PI. 
3) Have an eGFR expressed in mL/min/1.73 m2 (MDRD4 equation) at screening within the 
range of: 
a) Group 1 - Mild Group: 60 - 89 mL/min/1.73 m2; 
b) Group 2 - Moderate Group: 30 - 59 mL/min/1.73 m2; 
c) Group 3 - Severe Group: < 30 mL/min/1.73 m2 not requiring dialysis. 
eGFR results that are deemed inconsistent with the usual stage of renal impairment may be 
repeated. Subjects are categorized into severity group at screening. If the eGFR scores 
change on Day-1 or other visit due to a non-clinically significant change in clinical status or 
laboratory result, the subject keeps the original severity group. 
4) Subject may have stable treated medical illnesses and underlying diseases producing the 
renal impairment such as diabetes, hypertension, or cardiovascular disease, providing that, in 
the opinion of the PI, the disease is stable.  
5) Have normal or non-clinically significant findings at physical examination, vital signs and 
ECG and normal limits or non-clinically significant deviations in clinical laboratory 

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evaluations at screening, with the exception of findings that in the opinion of the PI are 
consistent with subject’s renal impairment or due to other stable diseases. Clinical data, ECG 
and laboratory tests may be repeated at the discretion of the Investigator. 
6) Other than renal impairment, have no other conditions which may significantly impact study 
drug absorption or metabolism, as determined by the PI. 
7) Stable medical regimen, deemed not to interact with study drug PK, for 14 days prior to 
dosing, except for routine daily management of electrolytes (e.g. potassium), acid-base, or 
other associated disorders expected in patients with renal impairment. The approval of the 
medications for the management of renal impairment and the treatment of concomitant stable 
medical conditions (e.g. diabetes, hypertension, associated stable cardiovascular disease, 
stable psychiatric conditions) is at the discretion of the PI. 
8) Females of childbearing potential who are sexually active with a non-sterile male partner 
(sterile male partners are defined as men vasectomized since at least 6 months) must be 
willing to use one of the following acceptable contraceptive method throughout the study and 
for 30 days after study drug administration: 
a) simultaneous use of intra-uterine contraceptive device, without hormone release system, 
placed at least 4 weeks prior to study drug administration, and condom for the male 
partner; 
b) simultaneous use of diaphragm with intravaginally applied spermicide and male condom 
for the male partner, starting at least 21 days prior to study drug administration. 
9) Male subjects who are not vasectomized for at least 6 months, and who are sexually active 
with a non-sterile female partner (sterile female partners include post-menopausal females 
and surgically sterile females) must be willing to use one of the following acceptable 
contraceptive method from dosing until at least 90 days after study drug administration: 
a) simultaneous use of a male condom and, for the female partner, hormonal contraceptives 
(used since at least 4 weeks) or intra-uterine contraceptive device (placed since at least 
4 weeks); 
b) simultaneous use of a male condom and, for the female partner, a diaphragm with 
intravaginally applied spermicide. 
10) Male subjects (including men who have had vasectomy) with a pregnant partner must agree 
to use a condom from dosing until at least 90 days after study drug administration. 
11) Male subjects must be willing not to donate sperm until 90 days following study drug 
administration. 
12) Able to understand and willing to sign the ICF and comply with the study restrictions. 
8.2.2 
Exclusion Criteria for Subjects Renal Impairment (Groups 1 to 3) 
Subjects to whom any of the following applies will be excluded from the study: 
1) Unstable renal function or acute exacerbation of renal disease within 14 days of study drug 
administration, as indicated by recent history or worsening of clinical and/or laboratory signs 
of renal impairment as judged by the PI. For inclusion and for categorization by MDRD4 or 

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other equations, laboratory results that are deemed inconsistent with the usual stage of renal 
impairment may be repeated. 
2) Has a functioning renal transplant. 
3) Major illness or surgery within 4 weeks prior to dosing. 
4) Clinically significant unstable medical condition or history of any illness that may increase 
the risk associated with study participation or investigational drug administration or may 
interfere with the interpretation of study results and, in the judgment of the PI, would make 
the subject inappropriate for entry into this study. Subjects who do not qualify based on a 
reversible medical condition or mild inter-current illness may be re-evaluated after further 
testing/examination or re-screened after the condition is resolved. 
5) Positive test for hepatitis B, hepatitis C, or HIV at screening.  
6) History of allergic reactions, hypersensitivity or toxic reactions to aminoglycosides. 
7) History of anaphylaxis. 
8) Supine 12-lead ECG abnormalities at screening considered clinically significant by the PI. 
9) Clinically significant vital sign abnormalities (systolic blood pressure lower than 90 or over 
160 mmHg, diastolic blood pressure lower than 40 or over 100 mmHg, or heart rate less than 
45 or over 100 bpm) at screening. 
10) History of significant drug or alcohol abuse within six months prior to screening. 
11) Participation in a clinical research study involving the administration of an investigational or 
marketed drug or device within 30 days (or 5 half-lives, whichever is longer) prior to dosing, 
administration of a biological product in the context of a clinical research study within 
90 days prior to dosing, or concomitant participation in an investigational study involving no 
drug or device administration. 
12) Positive urine drug screen or alcohol test at screening, unless the positive drug screen is due 
to prescription drug use that is documented and approved by the PI. 
13) Female subject with positive pregnancy test at screening. 
14) Breast-feeding or pregnant subject within 6 months prior to study drug administration. 
15) Use of any drugs known as strong inducer or inhibitor of hepatic drug metabolism within 
30 days prior to study drug administration. 
16) Use of medication other than stable medications approved by the PI and topical products 
without significant systemic absorption:  
a) any new prescription medication within 14 days prior to dosing; 
b) OTC products or natural health products (including herbal remedies such as St. John’s 
wort, homeopathic and traditional medicines, probiotics, food supplements such as 
vitamins, minerals, amino acids, essential fatty acids, and protein supplements used in 
sports) within 7 days prior to dosing, with the exception of the occasional use of 
acetaminophen (that is allowed up to 2 g daily), unless the products are used by RI 
subjects as part of their routine care; 
c) a depot injection or an implant of any drug within 3 months prior to dosing. 

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17) The following medications are prohibited during the study: neuromuscular blocking agents 
(e.g. succinylcholine, tubocurarine), neurotoxic and/or nephrotoxic drugs (e.g. other 
aminoglycosides, cisplatin, cephaloridine, polymyxin B, vancomycin, viomycin). At the 
discretion of the PI, a suitable substitute medication may be prescribed to replace the 
prohibited medication. 
18) Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding 
volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than 
499 mL within 56 days prior to the first dosing. 
19) Any reason which, in the opinion of the PI, would prevent the subject from participating in 
the study. 
20) Inability to be venipunctured and/or tolerate catheter venous access. 
21) Presence of mitochondrial mutation(s) making the subject susceptible to aminoglycoside 
toxicity. 
22) Presence of signs of dehydration, recent history of neuromuscular blockade or clinically 
significant history of vestibular impairment. 
8.3 
Subjects with Normal Renal Function (Group 4) 
An effort will be made to carefully match the healthy subjects in the control group with the RI 
subjects by age (± 10 years), BMI (±15%), and gender, to the extent possible. A mean matching 
procedure will be performed. Subjects enrolled in this group of study will be members of the 
community at large. The recruitment advertisements may use various media types (e.g. radio, 
newspaper, inVentiv Web site, inVentiv volunteer database). 
8.3.1 
Inclusion Criteria for Subjects with Normal Renal Function (Group 4) 
Subjects must meet all of the following criteria to be included in the study Group 4: 
1) Male or female, non-smoker (no use of tobacco or nicotine products within 3 months prior to 
screening), ≥ 18 and ≤ 80 years of age, with BMI ≥ 18.0 and ≤ 40.0 kg/m2 and body weight 
≥ 50.0 kg for males and ≥ 45.0 kg for females.  
2) Have an eGFR ≥ 90 mL/min/1.73 m2 (MDRD4 equation). 
3) Healthy as defined by: 
a) the absence of clinically significant illness and surgery within 4 weeks prior to dosing. 
Subjects vomiting within 24 hours pre-dose will be carefully evaluated for upcoming 
illness/disease. Inclusion pre-dosing is at the discretion of the PI. 
b) the absence of clinically significant history of hematological, renal, endocrine, 
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, and 
immunologic disease. 
4) Matched to subjects with RI (mild, moderate or severe) according to gender, age 
(± 10 years), and BMI (± 15%). 
5) Females of childbearing potential who are sexually active with a non-sterile male partner 
(sterile male partners are defined as men vasectomized since at least 6 months) must be 

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willing to use one of the following acceptable contraceptive method throughout the study and 
for 30 days after study drug administration: 
a) simultaneous use of intra-uterine contraceptive device, without hormone release system, 
placed at least 4 weeks prior to study drug administration, and condom for the male 
partner; 
b) simultaneous use of diaphragm with intravaginally applied spermicide and male condom 
for the male partner, starting at least 21 days prior to study drug administration. 
6) Male subjects who are not vasectomized for at least 6 months, and who are sexually active 
with a non-sterile female partner (sterile female partners include post-menopausal females 
and surgically sterile females) must be willing to use one of the following acceptable 
contraceptive method from dosing until at least 90 days after study drug administration: 
a) simultaneous use of a male condom and, for the female partner, hormonal contraceptives 
(used since at least 4 weeks) or intra-uterine contraceptive device (placed since at least 
4 weeks); 
b) simultaneous use of a male condom and, for the female partner, a diaphragm with 
intravaginally applied spermicide. 
7) Male subjects (including men who have had vasectomy) with a pregnant partner must agree 
to use a condom from the first dosing until at least 90 days after study drug administration. 
8) Male subjects must be willing not to donate sperm until 90 days following study drug 
administration. 
9) Able to understand and willing to sign the ICF and comply with the study restrictions. 
8.3.2 
Exclusion Criteria for Subjects with Normal Renal Function (Group 4) 
Subjects to whom any of the following applies will be excluded from the study: 
1) Any clinically significant abnormality at physical examination or clinically significant 
abnormal laboratory test results at screening. 
2) Positive test for hepatitis B, hepatitis C, or HIV at screening.  
3) History of allergic reactions, hypersensitivity or toxic reactions to aminoglycosides. 
4) Evidence or history of clinically relevant hematological, renal, endocrine, pulmonary, 
gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, immunologic, or allergic 
disease. This includes any acute or chronic medical or psychiatric condition or laboratory 
abnormality that may increase the risk associated with study participation or investigational 
drug administration or may interfere with the interpretation of study results and, in the 
judgment of the PI, would make the subject inappropriate for entry into this study. 
5) History of anaphylaxis. 
6) Clinically significant supine 12-lead ECG abnormalities at screening, e.g., QTcF >450 msec 
for men and >470 msec for women, or a QRS interval >120 msec. 

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7) Clinically significant vital sign abnormalities (systolic blood pressure lower than 90 or over 
140 mmHg, diastolic blood pressure lower than 50 or over 90 mmHg, or heart rate less than 
50 or over 100 bpm) at screening. 
8) History of significant alcohol abuse within one year prior to screening or regular use of 
alcohol within six months prior to the screening visit (more than fourteen units of alcohol per 
week [1 unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol]).  
9) History of significant drug abuse within one year prior to screening or use of soft drugs (such 
as marijuana) within 3 months prior to the screening visit or hard drugs (such as cocaine, 
PCP, crack, opioid derivatives including heroin, and amphetamine derivatives) within 1 year 
prior to screening. 
10) Participation in a clinical research study involving the administration of an investigational or 
marketed drug or device within 30 days (or 5 half-lives, whichever is longer) prior to dosing, 
administration of a biological product in the context of a clinical research study within 
90 days prior to dosing, or concomitant participation in an investigational study involving no 
drug or device administration. 
11) Positive urine drug screen, alcohol test, or urine cotinine test at screening. 
12) Female subject with positive pregnancy test at screening. 
13) Breast-feeding or pregnant subject within 6 months prior to study drug administration. 
14) Use of any drugs known to induce or inhibit hepatic drug metabolism within 30 days prior to 
study drug administration. 
15) Use of medication other than topical products without significant systemic absorption:  
a) prescription medication within 14 days prior to dosing; 
b) OTC products and natural health products (including herbal remedies such as St. John’s 
wort, homeopathic and traditional medicines, probiotics, food supplements such as 
vitamins, minerals, amino acids, essential fatty acids, and protein supplements used in 
sports) within 7 days prior to dosing, with the exception of the occasional use of 
acetaminophen (that is allowed up to 2 g daily); 
c) a depot injection or an implant of any drug within 3 months prior to dosing. 
16) Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding 
volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than 
499 mL within 56 days prior to dosing. 
17) Hemoglobin < 12.8 g/dL (males) and < 11.5 g/dL (females) and hematocrit < 37% (males) 
and < 32% (females) at screening. 
18) Any reason which, in the opinion of the PI, would prevent the subject from participating in 
the study. 
19) Inability to be venipunctured and/or tolerate catheter venous access. 
20) Presence of mitochondrial mutation(s) making the subject susceptible to aminoglycoside 
toxicity. 

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21) Presence of signs of dehydration, recent history of neuromuscular blockade or clinically 
significant history of vestibular impairment. 
9. 
Clinical Procedures 
The study will be conducted jointly at inVentiv and the Division of Clinical Pharmacology of the 
University of Miami. Groups 1 to 3 study procedures will be conducted at the Division of 
Clinical Pharmacology of the University of Miami (identified as Site 01) and Group 4 study 
procedures will be conducted at inVentiv (identified as Site 02). Clinical procedures, data 
collection and evaluation will be performed as per applicable SOPs of the Division of Clinical 
Pharmacology of the University of Miami and inVentiv, as appropriate, unless specified 
otherwise. 
9.1 
Screening Procedures 
Subject screening procedures will be performed within 35 days preceding administration of study 
medication. Subjects must provide written informed consent prior to initiation of any screening 
procedures. The consent to perform some general screening procedures may be obtained on a 
consent document other than the ICF specific to this study, and therefore, some screening test 
results could be obtained before signature of the ICF specific to this study. The study-specific 
ICF must be signed and dated by the subject before participation to study-specific procedures. 
Screening procedures will include: demographic data, medical and medication histories, 
complete physical examination, body measurements, ECG (12-lead), vital signs (BP, HR, RR, 
OT), hematology, biochemistry, coagulation, HIV, hepatitis B and C tests, urinalysis, genetic 
testing for mitochondrial mutations, urine drug screen, alcohol test (breath or urine), urine 
pregnancy test, and urine cotinine test (for Group 4 only). 
Serum cystatin C will be measured at screening and cystatin GFR will be estimated for 
additional data analysis, only if needed. These values will have no impact on subject’s eligibility 
and categorization. 
For eligibility purposes, abnormal laboratory or vital signs results may be repeated once (subjects 
of Groups 1 to 3 may need more repeats to confirm stability) if abnormal result is observed at the 
initial reading. Moreover, abnormalities found in the ECG may need to be confirmed by repeated 
measurements. In the event that the participation of a subject in the study is delayed and some 
screening procedures had been performed outside the prescribed screening window, outdated 
screening procedures can be repeated. 
Subjects from Groups 1 to 3 (mild, moderate, and severe RI subjects) should be recruited prior to 
recruiting control group subjects in order to facilitate subjects' matching. 
Subjects of Groups 1 to 3 who do not qualify based on a reversible condition or mild inter-
current illness may be re-evaluated after further testing/examination or re-screened after the 
condition is resolved. 
9.2 
Assessment of Renal Function for Eligibility and Categorization 
Renal function will be assessed at screening. Subjects will be classified in one of the 4 study 
groups according to their eGFR obtained from the MDRD4 study equation (Table 2) based on 

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Subjects will be assigned to one of the 4 study groups (Group 1, 2, 3, or 4) according to their 
eGFR value, as per Table 2. 
Subjects with normal renal function (Group 4) will be matched with RI subjects by age 
(± 10 years), gender, and BMI (± 15%). A mean matching procedure will be performed. 
Approximately 6 subjects completing the study are targeted for each of the RI groups (Groups 1 
to 3) and 6 to 8 subjects will be included in the control group (Group 4). 
9.5 
Study Medication 
Treatment: 
ELX-02 ready-to-use, sterile, solution for injection 
 
 
 
 
 
 
 
 
 
 
Dose: 
Single SC dose of 1 mg/kg ELX-02 
9.6 
Drug Supplies and Accountability 
It is the responsibility of the Sponsor to ensure that study medication provided for this study are 
manufactured under Good Manufacturing Practices (GMP) and are suitable for human use. It is 
the responsibility of the Sponsor to ship a sufficient amount of dosage units to allow the clinical 
sites to conduct the study. Study medication will be stored by the clinical sites as per the labeled 
storage conditions and the pharmacy manual. 
The medications will be stored in a locked, environmentally-controlled medication room with 
restricted access. Container(s) will bear a label containing at least the name of the study drug, lot 
and/or batch number, and expiry/retest date. One single-use vial per subject will be identified 
with at least the project number and the subject number/spare number. The medications will be 
dispensed according to the clinical site SOP and prepared according to the pharmacy manual. 
All study drug received at the site will be inventoried and accounted for throughout the study and 
the result recorded in the drug accountability/retention record according to the clinical site 
appropriate SOP. Upon completion of the study, the remaining drug products will be maintained 
at the clinical sites, destroyed or returned to the Sponsor, as per Sponsor’s request. 
9.7 
Drug Administration 
Subjects will receive a single dose of 1 mg/kg ELX-02 on Day 1. The body weight of each 
subject will be measured on Day -1 (check-in) and this value will be used to calculate the exact 
individual dose of ELX-02 required on a mg/kg basis. 

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SC injection of ELX-02 will be done in the abdominal region around the umbilicus, by an 
appropriately qualified, GCP-trained, and experienced member of the study staff, as allowed by 
local, state, and institutional guidance. A study physician must be present during any ELX-02 
administration. 
9.8 
Study Restrictions 
9.8.1 
Food and Fluids 
For standardization purpose, ELX-02 will be administered at least 30 minutes after subjects have 
been served a light breakfast. No food will be allowed until at least 1 hour after dosing. 
Standardized meals will be served at appropriate times thereafter. 
To keep subjects well hydrated, they will be asked to consume 240 mL of fluids within 
120 minutes prior to ELX-02 dosing (including fluids served as part of the breakfast). The fluids 
will be water or a fruit beverage should the PI or designee judges that such beverage is more 
appropriate to prevent dizziness and fainting. Water will be provided ad libitum at all other 
times, however the study staff will encourage subjects to drink at least 200 mL of fluids at the 
beginning of each 12-hour post-dose period.  
In addition, subjects will be required to abstain from: 
 food containing poppy seeds within 24 hours prior to admission; 
 food or beverages containing xanthine derivatives or xanthine-related compounds (coffee, 
black/green tea, chocolate) or energy drinks from 48 hours prior to dosing until after the 
72-hour blood sample collection; 
 natural health products (including herbal remedies such as St. John’s wort, homeopathic 
and traditional medicines, probiotics, food supplements such as vitamins, minerals, amino 
acids, essential fatty acids, and protein supplements used in sports) from 7 days prior to 
dosing until study exit; 

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 food or beverages containing grapefruit, Seville orange, starfruit, pomegranate, 
pineapple, or pomelo from 7 days prior to dosing until after the 72-hour blood sample 
collection. 
9.8.2 
Tobacco, Alcohol, and Illicit Drugs 
For Groups 1 to 3, subjects will be required to abstain from using soft or hard drugs from 
screening and throughout the study. For light smoking subjects, smoking will be prohibited from 
at least 2 hours pre-dose until 2 hours post-dose and a maximum of 5 cigarettes or equivalent per 
day will be allowed while subjects are in-patients in the clinic. 
For Group 4, subjects will be required to abstain from using soft or hard drugs and from smoking 
from screening and throughout the study. 
Consumption of alcohol-based products will be prohibited from 24 hours prior to admission until 
after the 72-hour blood sample collection. 
9.8.3 
Concomitant Medications 
Stable concomitant medical treatment is allowed for subjects of Groups 1 to 3, provided that 
a) no changes in their dosing regimen occurred for at least 14 days prior to dosing, and no 
changes are expected throughout the study, other than for routine daily management of 
electrolytes (e.g. potassium), acid-base, or other associated disorders expected in patients with 
renal impairment; b) the medications are deemed not to interact with study drug PK; and c) the 
medications have been approved by the PI before the subject inclusion. The following 
medications are prohibited during the study: neuromuscular blocking agents (e.g. 
succinylcholine, tubocurarine), neurotoxic and/or nephrotoxic drugs (e.g. other aminoglycosides, 
cisplatin, cephaloridine, polymyxin B, vancomycin, viomycin). If a subject is taking an excluded 
medication, the PI can switch the subject to an alternate medication that is allowed and the 
subject can be screened for the study after appropriate stabilization on the new medication. This 
will be done after the subject signs the ICF. 
No other concomitant drug therapy (new prescription or OTC medications) will be allowed for 
subjects of Groups 1 to 3, except one(s) required for the medical management of an AE or a new 
medical condition. 
For subjects of Group 4, prescription and OTC medications will be prohibited throughout the 
study. No concomitant drug therapy will be allowed during the study except one(s) required for 
the medical management of an AE. 
Any concomitant medication use (in Groups 1 to 4) other than the occasional use of 
acetaminophen will be evaluated on a case-by-case basis by the PI or a Sub-Investigator. All 
concomitant medication use will be documented from screening through study exit / early 
termination.  
9.8.4 
Posture and Physical Activity 
Subjects will be allowed to engage in normal activity but will avoid lying down or sleeping, 
unless medically necessary or procedurally required, for 4 hours after drug administration. 
Vigorous activity will be prohibited at all times during the in-house portion of the study. Because 

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excessive physical activity may increase the level of CPK above the upper normal limit value, 
subjects will be advised to avoid performing such activity (e.g., high-intensity running, biking, 
weightlifting) at all times during the study duration.  
9.8.5 
Contraception 
In the reproduction phase of toxicology studies conducted in juvenile rats, there were no adverse 
ELX-02-related effects noted on sexual maturation, reproductive and fertility indices, maternal 
uterine examinations, or sperm evaluations.1 However, since there are no adequate and well-
controlled studies with pregnant women, it is uncertain whether there is human fetal risk 
associated with the use of ELX-02. However, aminoglycosides are known to be associated with 
fetal deformities, therefore, non-pregnant, non-lactating females will be included in the study. 
Female subject of childbearing potential will be included only if they use appropriate methods of 
contraception. 
Male subjects who are not vasectomized will also be required to use appropriate methods of 
contraception during the study to avoid pregnancies in their female partners. Male subjects 
(including men who have had vasectomy) with a pregnant partner must agree to use a condom to 
prevent in utero drug exposure. 
9.9 
Sample Collection for Pharmacokinetic Evaluation 
9.9.1 
Blood Sample Collection and Processing 
A total of 13 blood samples will be drawn from each subject of Groups 1 to 4 for PK analyses. 
Blood samples will be collected 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 36, 48, 72, and 
168 (Day 8) hours post-dose (up to 6 mL for each sampling time). 
The time tolerance window for blood samples will be ±1 minute for timepoints up to 2 hours 
post-dose; ±5 minutes from 4 hours to 12 hours; ± 10 minutes from 24 hours to 72 hours; and 
± 24 hours for the 168-hour sample. Sample collections done outside the pre-defined time 
windows will not be considered as protocol deviations since actual post-dose sampling times will 
be used for PK and statistical analyses. Unless otherwise specified or for subject safety, when 
blood draws and other procedures coincide, blood draws will have precedence. A saline 
intravenous catheter may be used for blood collection to avoid multiple skin punctures, when 
appropriate. Otherwise, blood samples will be collected by direct venipuncture. 
The total volume of blood including that collected for eligibility and safety purposes should not 
exceed 196 mL for the whole study (refer to Table 3 for details). Deviations related to the 
volume of blood collected will be reported only when the total volume collected from a subject 
for the whole study is exceeded. 

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Table 3. 
Blood Volume for Laboratory Analyses 
Analysis 
Approximate 
Amount of 
Blood per 
Sample (mL) 
Number of 
Timepoints 
Total Amount of 
Blood (mL) 
Hematology 
4 
3 
12 
Biochemistry 
8.5 
4 
34 
Coagulation 
2.7 
3 
8.1 
Serology 
8.5 
1 
8.5 
Genetic testing for 
mitochondrial mutations 
5.4 
1 
5.4 
PK 
6 
13 
78 
Extra volume for potential 
repeat draws or additional 
safety tests 
- 
- 
50 
Total Volume 
196 
 
Samples will be collected and processed as per the instructions given in the laboratory manual. 
9.9.2 
Urine Sample Collection and Processing 
Urine samples will be collected for quantitation of unchanged ELX-02 at the following time or 
time intervals: pre-dose (first void in the morning of Day 1), 0-3, 3-6, 6-9, 9-12, 12-18, 18-24, 
24-36, 36-48, and 48-72 hours post-dose. Urine samples will be collected as follows: 
 At each void, all urine will be collected into a collection cup. The weight of each sample 
will be recorded and the volume of urine calculated assuming specific gravity of 1. 
 Subjects will be asked to void their bladder within 10 minutes before the end of each 
collection interval, so that each new interval begins with an empty bladder.  
 When a urine aliquot is needed at a specific timepoint for renal injury biomarkers and 
creatinine (pre-dose and at 12, 24, 36, and 48 hours post-dose), the aliquot will be 
withdrawn from the urine collection cup. If a subject is unable to void at the specified 
timepoint, it will be duly recorded and renal injury biomarkers and creatinine will be 
analyzed in the subsequent urine sample. Residual urine will be used for pooling with 
other voids of the same collection interval. 
 All voids collected during a defined time interval will be pooled into one urine collection 
container. The sum of individual samples’ weights will be recorded. Any urine voided by 
subjects at the intersection (within 10 minutes) of two intervals will be included in the 
earlier sample. Two aliquots will be taken in each pooled time interval container for PK 
analysis. 
 Thereafter, all urine collected in the intervals 0-3, 3-6, 6-9, 9-12, 12-18, 18-24 will be 
pooled together to withdraw a sample for the calculation of creatinine clearance. The sum 
of all samples’ weights will be recorded. Refer to section 9.10.8. 

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 At approximately 24 and 72 hours post-dose, a mid-stream safety sample will also be 
collected for urinalysis. 
 Any urine voided by subjects but not collected will be documented. 
Urine samples will be collected and processed as per the instructions given in the laboratory 
manual. 
9.10 Subject Monitoring 
Subjects will be monitored throughout the study by the clinical sites staff for AEs. The PI or a 
Sub-Investigator will be on site/campus for drug administration and until 4 hours after 
administration of the study medication to the last subject. The PI or a Sub-Investigator will also 
be on call for the remainder of the study. If necessary, a physician, either at the clinical site or in 
a nearby hospital will administer treatment for any AE(s). A crash cart or emergency bag 
containing the necessary rescue material and appropriate medications will be available in the 
clinic to allow rapid intervention in case of emergency. 
Safety parameters, including laboratory results and ECG, will be assessed by the PI or delegate, 
using the clinical site criteria for biomedical laboratory and ECG acceptance ranges as suggested 
guidelines in making the medical assessment. 
Scheduled safety measurements will be repeated according to appropriate clinical site SOPs or 
upon request from a physician. Any abnormal repeated measurement will be evaluated by a 
physician and repeated if judged necessary. Further action may be taken upon physician's 
request. 
Subjects will be advised to notify their health care professional(s) (e.g., physician, dentist, and/or 
pharmacist) that they are participating in a clinical research study on an experimental drug called 
ELX-02 being developed for the treatment of genetic diseases before taking any medicines or 
undergoing any medical procedure. 
9.10.1 Vital Signs 
Blood pressure, respiratory rate, heart rate, and oral temperature will be measured after at least 
5 minutes of sitting (except for safety reasons) at screening, at check-out on Day 4 and at study 
exit. Blood pressure, heart rate and oral temperature will also be measured prior to dosing and 
approximately 2, 4, 24, and 48 hours post-dose. When vital signs measurements coincide with a 
blood draw, they should preferably be performed before the blood collection whenever possible. 
A time window of 15-20 minutes for vital signs will be allowed if there are multiple procedures 
at the same time point. 
9.10.2 ECG 
12-lead ECG will be performed at screening, prior to dosing, approximately 2 hours post-dose, at 
check-out on Day 4 and at study exit. ECG will be performed after a resting time of at least 5 
minutes in supine position. When ECG coincides with a blood draw, it should preferably be 
performed before the blood collection whenever possible. A time window of 15-20 minutes for 
ECG will be allowed if there are multiple procedures at the same time point. 

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9.10.3 Physical Examination and Body Measurements 
A complete physical examination will be performed at screening. A complete physical 
examination includes assessments of at least the following: head, eyes, ears, nose, throat 
(HEENT), neck, chest, lungs, abdomen, musculoskeletal, dermatological, 
cardiovascular/peripheral vascular, and general neurological examination. 
A brief physical examination will be done on Day -1, at check-out on Day 4 and at study exit. A 
brief physical examination includes assessments of the following: HEENT, chest, lungs, 
abdomen, dermatological, cardiovascular/peripheral vascular, and areas of note elicited from the 
subject. 
Body weight and height will be measured at screening and the BMI calculated. Body weight 
measurement will be done again on Day -1 and this value will be used to calculate the exact 
individual dose of ELX-02 required on a mg/kg basis. 
9.10.4 Injection Site Evaluation 
Local reactions at the injection site will be evaluated by a trained observer and recorded: prior to 
study drug injection, approximately 0.75, 2, 6, 12, 24, 36, 48, and 72 hours hours post-dose, and 
at study exit. The extent of local reaction at the injection site will be graded according to the 
Division of AIDS (DAIDS) criteria5 presented in APPENDIX 1. 
9.10.5 Drug, Alcohol and Cotinine Screen 
A urine drug screen (amphetamines, methamphetamines, barbiturates, benzodiazepines, 
tetrahydrocannabinol, cocaine, opiates, PCP, MDMA, methadone) and an alcohol test (breath or 
urine) will be performed at screening and on Day -1. For Group 4 only, a urine cotinine test will 
also be performed at screening and on Day -1. 
9.10.6 Pregnancy Test 
A urine pregnancy test will be performed at screening and at study exit, and a serum pregnancy 
test will be performed on Day -1. 
9.10.7 Laboratory Assessments 
Procedures of processing and storing clinical laboratory samples will be detailed in the 
laboratory manual. 
9.10.7.1 
Biochemistry 
Biochemistry will be performed at screening, on Day -1 and at study exit, following a fasting 
period of at least 8 hours. The following will be assessed: albumin, alkaline phosphatase, AST, 
ALT, urea, calcium, chloride, glucose, phosphorus, potassium, creatinine, sodium, total bilirubin, 
CPK, and total protein. 
Serum creatinine will also be measured approximately 24 hours post-dose (Day 2). 

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9.10.7.2 
Cystatin C Measurement 
Serum cystatin C will be measured at screening in order to allow, if required, additional analyses 
based on this endogenous glomerular filtration marker. Only if requested, cystatin GFR will be 
estimated (eGFR) using the eGFR equation for serum cystatin C. The values obtained will be 
used for additional data analysis and will have no impact on subjects’ eligibility and 
categorization. 
9.10.7.3 
Serology 
Hepatitis B (HBs Ag), Hepatitis C (HCV) antibody, and HIV antigen and antibody detection will 
be performed at screening. 
9.10.7.4 
Genetic Testing 
Genetic testing for mitochondrial mutations will be performed at screening. 
9.10.7.5 
Hematology 
Hematology will be performed at screening, on Day -1 and at study exit. The following will be 
assessed: complete blood count with differential, hemoglobin, and hematocrit. 
9.10.7.6 
Coagulation 
Coagulation tests will be performed at screening, on Day -1 and at study exit. The following will 
be assessed: prothrombin time (PT), activated partial thromboplastin time (aPTT), and 
international normalized ratio (INR). 
9.10.7.7 
Urinalysis 
Urinalysis will be performed at screening, on Day -1, at approximately 24 and 72 hours post-
dose, and at study exit. The following will be assessed: macroscopic examination, pH, specific 
gravity, protein, glucose, ketones, bilirubin, occult blood, nitrite, urobilinogen, and leukocytes. 
Unless otherwise specified, microscopic examination will be performed on abnormal findings. 
9.10.8 Determination of Creatinine Clearance 
Urine samples collected for PK assessment from dosing to 24 hours post-dose will also be used 
for analysis of creatinine, in order to calculate creatinine clearance (corrected for BSA), along 
with the serum creatinine value measured 24 hours post-dose. The total amount of creatinine 
excreted over 24 hours (addition of the 0-3, 3-6, 6-9, 9-12, 12-18, 18-24-hour post-dose time 
intervals) and the total volume of urine excreted over this 24-hour period will allow calculating 
creatinine clearance over 24 hours using the following formula: 
Corrected CrCl =  Ucr  x  Uvol  x   1.73 
Scr 
Time 
BSA    where: 
Corrected CrCl is expressed as mL/min/1.73 m2 of BSA 
Ucr is urine creatinine expressed in mg/dL 
Uvol is the volume of urine expressed in mL 
Scr is serum creatinine expressed in mg/dL 
Time is expressed in minutes 

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BSA is calculated based on the height measured at screening and body 
weight measured on Day -1, and expressed in m2. 
The corrected CrCl values obtained may be used for additional data analysis. 
9.10.9 Renal Injury Biomarkers 
Urine samples for early markers of renal injury (KIM-1 and clusterin) and for creatinine will be 
collected prior to dosing, at approximately 12, 24, 36, and 48 hours post-dose, as well as on 
Day 8. 
9.11 Study Exit / Early Termination Procedures 
Study exit procedures are scheduled to be performed at the follow-up visit on Day 8 (±1 day). If 
not possible, or in case of early termination, all efforts will be made to complete study exit / early 
termination procedures within 14 days after the last participation of the subject in the study. 
The study exit procedures include a brief physical examination, hematology, biochemistry, 
coagulation, urinalysis, vital signs (BP, HR, RR and OT), 12-lead ECG, urine pregnancy test, 
injection site evaluation, and AE monitoring. 
9.12 Data Collection and Evaluation 
All clinical raw data will be recorded promptly, accurately, legibly, and indelibly by the clinical 
staff on raw data sheets and/or recorded electronically using validated and Code of Federal 
Regulations (CFR) part 11 compliant software(s) and transcribed into Case Report Forms 
(CRFs). All raw data will be conserved in order to maintain data integrity. A physician and/or the 
clinical staff will assume the responsibility of ensuring the completeness and accuracy of the 
clinical data. Please refer to Section 15 for record retention requirements. 
9.13 Subject Withdrawal and Replacement 
Subjects will be advised that they are free to withdraw from the study at any time. Over the 
course of the study, the Sponsor and the PI or a delegate may withdraw any subject from the 
study for one of the reasons described below; subject withdrawal will be done in accordance with 
the clinical site SOP: 
○ 
safety reason; 
○ 
non-compliance with protocol requirements; 
○ 
significant protocol deviation; 
○ 
positive alcohol test, cotinine test (Group 4 only), drug screen, or pregnancy test. 
For RI subjects (Groups 1 to 3) taking medications allowed by the PI, a positive result to 
opiate/benzodiazepine/THC screen (drug screen) may derive from the use of the concomitant 
medications. The subjects will not be automatically withdrawn from the study but will be 
evaluated on a case-by-case basis by the PI. 
Hematology, biochemistry, urinalysis, and coagulation results will be reviewed by the PI or a 
Sub-Investigator prior to dosing; subjects will be withdrawn from the study if it is deemed that 
the subject’s safety may be at risk on the basis of these test results. 

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Subjects who withdraw or are withdrawn from the study after dosing, for reasons other than 
safety and tolerability, may be replaced in order to ensure a minimum of 6 completed subjects 
per group. The total number of subjects dosed (including potential replacement subjects) will 
remain within a maximum of 8 subjects per group and within a maximum of 32 subjects for the 
whole study. Additional replacement resulting in dosing more subjects than planned in this 
protocol would be documented in a protocol amendment. 
Subjects who withdraw or are withdrawn will be asked to remain at the clinic until the PI or a 
delegate agrees that the subject is fine and can be discharged. As soon as subject withdrawal is 
confirmed, blood sampling will be stopped. A PK blood draw may be collected at the time of 
withdrawal if deemed required by the PI. Study exit procedures will be performed at the time of 
withdrawal from the study or as soon as possible thereafter.  
9.14 Adverse Events 
9.14.1 Recording of Adverse Events 
AEs will be recorded and evaluated for their seriousness, severity, and relationship to the study 
medication. AEs will be collected and documented during the course of the study, from 
screening up to study exit. AEs will be followed-up until complete resolution, or until a Sub-
Investigator judges safe to discontinue follow-up. For events considered related to study drug, 
follow-up by the Investigator may be required until the event or its sequelae resolve or stabilize at a 
level acceptable to the Investigator, and Eloxx Pharmaceuticals concurs with that assessment. The 
relationship to the study medication will be classified according to section 9.14.3. 
9.14.2 Assessment of Severity 
The severity of AEs will be described and documented using the following definitions: 
Table 4. 
Assessment of AE Severity 
Severity 
Description 
Mild 
Awareness of signs and symptoms, but are easily tolerated; are of minor irritant 
type; causing no limitations of usual activities. Signs or symptoms may require 
minor action. 
Moderate 
Discomfort severe enough to cause some limitations of usual activities and may 
require action. 
Severe 
Incapacitating with inability to carry out usual activities or significantly affects 
clinical status, and requires specific action and/or medical attention. 
9.14.3 Assessment of Relationship to the Study Drug 
Each AE must be classified based on medical judgment and according to the following 
categories: certain, probable/likely, possible, unlikely, or unrelated. 

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The definitions for the causality assessments according to the WHO-Uppsala Monitoring Center 
(UMC) system for standardized case causality assessment are as follows: 
Note: all of the assessment criteria per causality should be reasonably complied with. 
Certain: 
 Event or laboratory test abnormality with plausible time relationship to drug intake; 
 Cannot be explained by disease or other drugs;  
 Response to withdrawal plausible (pharmacologically, pathologically);  
 Event definitive pharmacologically or phenomenologically (i.e., an objective and specific 
medical disorder or a recognized pharmacological phenomenon); 
 Rechallenge satisfactory, if necessary. 
Probable/Likely 
 Event or laboratory test abnormality with reasonable time relationship to drug intake;  
 Unlikely to be attributable to disease or other drugs;  
 Response to withdrawal clinically reasonable; 
 Rechallenge not required. 
Possible 
 Event or laboratory test abnormality with reasonable time relationship to drug intake; 
 Could also be explained by disease or other drugs; 
 Information on drug withdrawal may be lacking or is unclear. 
Unlikely 
 Event or laboratory test abnormality with a time to drug intake that makes a relationship 
improbable (but not impossible); 
 Disease or other drugs provide plausible explanations. 
Unrelated 
 It does not follow a reasonable temporal sequence from the administration of the test 
drug; 
 It could readily have been produced by the subject’s clinical state, environmental or toxic 
factors, or other modes of therapy administered to the subject; 
 It does not follow a known pattern of response to the test drug. 
9.14.4 Serious Adverse Events 
9.14.4.1 
Definition of Serious Adverse Event 
A SAE is any event that meets any of the following criteria: 
 Death 
 Life-threatening 
 Inpatient hospitalization or prolongation of existing hospitalization 
 Persistent or significant disability/incapacity 

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 Congenital anomaly/birth defect in the offspring of a subject who received rimegepant 
 Other: Important medical events that may not result in death, be life-threatening, or require 
hospitalization, may be considered an SAE when, based upon appropriate medical judgment, 
they may jeopardize the subject and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. Examples of such events are: 
 Intensive treatment in an emergency room or at home for allergic bronchospasm 
 Blood dyscrasias or convulsions that do not result in inpatient hospitalization 
 Development of drug dependency or drug abuse 
9.14.4.2 
Serious Adverse Event Reporting to the Sponsor 
The Investigator or designee must report all serious adverse events (SAEs) 
 
 immediately, or within 24 hours of knowledge by the 
Investigator or his staff, regardless of the presumed relationship to the study drug. The 
notification must be directed to: 
 
 
 
 will work with the clinical site to obtain complete information on the 
event. When further information becomes available, the SAE should be updated with the new 
information and reported via the same 
 contact information. 
Any SAE will be reported to the Sponsor by 
 via telephone and by fax or 
e-mail, within 24 hours of 
 becoming aware of the event, and then in 
writing as soon as possible, but no later than 7 calendar days after first knowledge of the SAE. 
The notification must be directed to: 
 
 
 
 
 
Must be copied on all notifications: 
 
  
9.14.4.3 
Serious Adverse Event Reporting to Regulatory Agency(ies) 
The Sponsor is responsible for notifying the FDA of suspected, unexpected, serious adverse drug 
reactions observed during conduct of studies in which the investigational drug is administered.  
FDA notification of fatal or life-threatening suspected, unexpected, serious adverse drug reaction 
must be made as soon as possible, but no later than 7 calendar days after becoming aware of the 
information. FDA notification of all other suspected, unexpected, serious adverse drug reactions 

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that are neither fatal nor life-threatening must be made as soon as possible, but no later than 
15 calendar days after becoming aware of the information. 
The Sponsor is responsible to comply with any other applicable regulatory requirement(s) related 
to the reporting of SAE to other regulatory authority(ies). 
9.14.4.4 
Serious Adverse Event Reporting to the Independent Ethics Committee 
It is the responsibility of each clinical site to report as soon as possible, but no later than 
7 calendar days after first knowledge by the Investigator, fatal or life-threatening suspected, 
unexpected, serious adverse drug reactions occurring at its site to the Independent Ethics 
Committee (IEC) responsible for the study. 
It is the responsibility of each clinical site to report to the IEC all other suspected, unexpected, 
serious adverse drug reactions that are neither fatal nor life-threatening, as soon as possible, but 
no later than 14 calendar days after first knowledge by the Investigator. 
9.15 On-Study Pregnancy 
If a subject or partner of a subject participating in the study becomes pregnant during the study, 
the Investigator should report the pregnancy to 
 within 24 hours of being 
notified (see contact information in section 9.14.4.2). 
A subject becoming pregnant while on study drug will immediately be withdrawn from the study 
and early termination study procedures will be performed. 
The subject or partner should be followed by the Investigator until completion of the pregnancy. 
If the pregnancy ends for any reason before the anticipated date, the Investigator should notify 
 At the completion of the pregnancy, the Investigator will document the 
outcome of the pregnancy. 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 SAE reporting. 
 will report the information related to on-study pregnancies to the Sponsor 
as per established safety management procedures. 
9.16 Reportable Disease 
In the case a subject has or manifested any clinical signs characteristic of a reportable disease or 
condition (e.g., HIV, tuberculosis, SARS), it is the responsibility of the PI to notify the public 
health department of the 
 within 72 hours after becoming aware of the 
information. 
10. Study Termination 
The study may be terminated by the PI following consultation with the Sponsor, by the Sponsor 
or by the regulatory authorities. Following a decision to discontinue the trial, the PI will 
immediately inform the active study subjects and the IEC responsible for this trial, stating the 
reasons for discontinuation of the study and, furthermore, advise them in writing of any potential 
risks to the health of study subjects or other persons. It is the Sponsor’s responsibility to report 

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the premature termination of the study to the regulatory authority(ies), when required by the 
applicable regulatory requirement(s).  
11. Analytical Methodology 
Samples will be transported to the bioanalytical facility in at least two separate shipments, with 
each set of aliquots in separate shipments. Once the bioanalytical laboratory confirms receipt of 
the first shipment, the second set of aliquots may be sent. The samples should be packed on 
sufficient dry ice to keep them frozen for at least 72 hours. 
All shipments will be accompanied by an inventory list and delivered to the following address:  
 
Attn: Sample Coordination 
 
 
 
 
 
 
Clinic personnel will notify the analytical laboratory prior to shipment by phone, fax or e-mail. 
 will analyze ELX-02 in plasma and urine samples using validated methods.  
The bioanalytical work in support to the study will be conducted in compliance with the GCP 
using the SOPs in place in the bioanalytical laboratory and as per applicable regulations. 
Samples from subjects included in the PK population (see section 12.2.2) and from subjects who 
were withdrawn from the study due to AEs will be analyzed. 
12. Pharmacokinetic and Statistical Analyses 
Pharmacokinetic analysis will be performed using Phoenix® WinNonlin®, which is validated for 
bioequivalence/bioavailability studies by inVentiv. Inferential statistical analyses will be 
performed using SAS® according to FDA guidelines. 
Interim PK analyses will be performed after completion of dosing in the mild (Group 1) and 
moderate (Group 2) RI patients. 
12.1 Pharmacokinetics 
12.1.1 Plasma Pharmacokinetic Parameters 
The following PK parameters will be calculated by standard non-compartmental methods with 
ELX-02 plasma concentrations:  

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1) 
AUC0-72: area under the concentration-time curve from time zero to 72 hours post-dose. 
Whenever concentration data is missing for the 72-hour post-dose sample for a subject, 
calculation of the AUC0-72 must not be done. 
2) 
AUC0-t: area under the concentration-time curve from time zero to the last non-zero 
concentration 
3) 
AUC0-inf: area under the concentration-time curve from time zero to infinity (extrapolated) 
4) 
Cmax: maximum observed concentration  
5) 
Residual area: calculated as 100*(1- AUC0-t / AUC0-inf) 
6) 
Tmax: time of observed Cmax 
7) 
T½ el: elimination half-life 
8) 
Kel: elimination rate constant 
9) 
CL/F: apparent total clearance (L/hr) estimated from dose/AUC0-inf 
10) Vd/F: apparent volume of distribution (L) estimated from CL/Kel (β) 
12.1.2 Urine Pharmacokinetic Parameters 
The following PK parameters will be calculated by standard non-compartmental methods with 
ELX-02 urine concentrations: 
1) 
Aeinterval: Amount of drug excreted in urine for each time interval, calculated as the urine 
concentration multiplied by the urine volume. 
2) 
Ae0-t: Cumulative urinary excretion from time zero to time t, calculated as the sum of the 
amounts excreted over each collection interval. 
3) 
Rmax: Maximum rate of urinary excretion, calculated by dividing the amount of drug 
excreted in each collection interval by the time over which it was collected. 
4) 
TRmax: Time of maximal urinary excretion, calculated as the midpoint of the collection 
interval during which Rmax occurred. 
5) 
Fe0-t: Fraction (% dose) excreted unchanged 
6) 
CLR: Renal clearance, calculated as Ae0-72 / AUC0-72 
Additional pharmacokinetic analysis may be performed. 
12.2 Analysis Populations 
12.2.1 Safety Population 
The safety population is defined as all subjects who received at least one dose of the study 
medication. 
12.2.2 Pharmacokinetic Population 
The pharmacokinetic population will include all subjects completing the study and for whom the 
PK profile can be adequately characterized. 
Data (concentrations and PK parameters) from subjects withdrawn due to AEs will be presented 
but excluded from descriptive statistics. 

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12.3 Statistical Analyses 
12.3.1 Statistical Analyses of Pharmacokinetic Parameters 
GFR estimated with serum creatinine concentrations and the MDRD4 equation will be used to 
classify subjects and this classification will serve for primary analyses. If applicable, GFR, PK, 
and statistical analyses estimated with serum cystatin C concentrations will be presented for 
supportive purposes. 
Individual and mean plasma concentration versus time curves will be presented for both linear 
and semi-log scales. Descriptive statistics (arithmetic and geometric means, standard deviation 
[SD], coefficient of variation [CV%], minimum [Min], maximum [Max], and median) of the 
plasma concentrations versus time will be presented as well for the PK parameters according to 
renal function groups included in the study (Mild, Moderate, Severe renal impairment, and 
Control). A graphical description of the relationship between renal function measures and PK 
will be presented. 
For plasma PK parameters, using GLM procedures in SAS, ANOVA will be performed on 
untransformed Tmax, Kel and T½ el and on ln-transformed AUC0-72, AUC0-t, AUC0-inf, and Cmax at 
the alpha level of 0.05 to compare groups (Mild, Moderate, Severe and Control). Factor 
incorporated in the model will include Group as a fixed effect. Inter-subject coefficient of 
variation will be estimated. The ratio of geometric means (Mild/Control, Moderate/Control, 
Severe/Control) and 90% CI for the ratio of geometric means, based on least-squares means from 
the ANOVA of the ln-transformed data, will be calculated for AUC0-72, AUC0-t, AUC0-inf, and 
Cmax. Tmax will be analyzed nonparametrically with point estimates and 90% CIs for the median 
differences of Tmax between study groups (Mild-Control, Moderate-Control, Severe-Control). 
For urine PK parameters, using GLM procedures in SAS, ANOVA will be performed on ln-
transformed Ae0-t and Rmax at the alpha level of 0.05 to compare groups (Mild, Moderate, Severe 
and Control). Factor incorporated in the model will include Group as a fixed effect. Inter-subject 
coefficient of variation will be estimated. The ratio of geometric means (Mild/Control, 
Moderate/Control, Severe/Control) and 90% CI for the ratio of geometric means, based on least-
squares means from the ANOVA of the ln-transformed data, will be calculated for Ae0-t and 
Rmax. 
Additional statistical analysis may be performed. 
In the event that renal impairment has a clinically relevant effect on ELX-02 PK, the relationship 
between renal function and appropriate PK parameters for ELX-02 (e.g., CL/F, AUC0-t, AUC0-inf, 
and Cmax) will be determined by a linear or non-linear regression. 
12.3.2 Safety and Tolerability Parameters and Analyses 
Demographic parameters will be summarized descriptively. 
Safety and tolerability to ELX-02 will be evaluated through the assessment of AEs (i.e., 
seriousness, severity, relationship to the study drug, outcome, duration, and management), local 
reactions at the injection site, physical examination, vital signs, ECG, early markers of renal 
injury, and clinical laboratory parameters. TEAEs will be summarized descriptively by renal 
function group (Mild, Moderate, Severe renal impairment, and Control) for all subjects who were 

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dosed (safety population). Changes from baseline values in vital signs, ECG, and clinical 
laboratory parameters will be evaluated. Safety and tolerability data will be reported using 
descriptive statistics. No inferential statistical analysis of safety data is planned. 
Details of statistical analyses will be developed in a Statistical Analysis Plan (SAP). 
13. Final Report 
Clinical and statistical sections of the report will be the responsibility of inVentiv. The 
bioanalytical section of the report will be the responsibility of QPS. 
In the event that the study is prematurely terminated, inVentiv will produce an abbreviated safety 
report. In such an event, raw data will not be submitted with the abbreviated report but will be 
archived at each site, unless requested by the Sponsor. 
14. Regulatory Considerations and Quality Assurance 
14.1 Independent Ethics Committee Approval of Protocol and Other Study Documents 
The Investigators agree to provide the IEC with all appropriate documents, including a copy of 
the protocol/amendments, ICFs, advertising text (if any), Investigator’s Brochure (if any) and 
any other written information provided to study subjects. The trial will not begin until the 
Investigators have obtained the IEC favourable written approvals for the above-mentioned study 
documents. A properly executed written ICF shall be read, signed, and dated by each subject 
prior to entering the trial or prior to performing any study procedure. The original signed and 
dated ICF will be kept at the clinical site and a copy will be given to the subject.  
In the event that the protocol is amended, the revised protocol must be approved by the IEC prior 
to its implementation, unless the changes involve only logistical or administrative aspects of the 
trial. If a revised ICF is introduced during the study, each subject’s further consent must be 
obtained. The new version of the ICF must be approved by the IEC, prior to subsequently 
obtaining each subject’s consent. 
The PI and the Sponsor’s representative must sign the protocol and its amendments (if any) 
before initiating the study. 
It is the Sponsor’s responsibility to submit the protocol and its amendments (if any), and the 
ICFs to regulatory authorities when necessary. 
14.2 Compliance 
This study will be conducted in compliance with the protocol, GCP, and all applicable 
regulations, including the Federal Food, Drug and Cosmetic Act, U.S. applicable Code of 
Federal Regulations (title 21), and any IEC requirements relative to clinical studies. The study 
will also be conducted in compliance with the recommendations laid down in the most recent 
version of the Declaration of Helsinki, with the exception that registration of such Phase 1 trials 
in a publicly accessible database is not mandatory. 

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14.3 Liability 
If a bodily injury is sustained, resulting directly from the use of the study drug, the Sponsor will 
reimburse for reasonable physician fees and medical expenses necessary for diagnosis and 
treatment of only the bodily injury, provided that the injury is not due to a negligent or wrongful 
act or omission by the study doctor and his/her staff, in which case the clinical site would cover 
associated fees. 
14.4 Quality Assurance Program 
The clinical sites have established Quality Control (QC) and Quality Assurance (QA) systems 
with written SOPs to ensure that the study will be conducted and data will be generated, 
recorded, and reported in compliance with the protocol, GCP, and applicable regulatory 
requirements. A rigorous QC program is applied to ensure accuracy of all data and reports. 
14.5 Audits, Inspections and Monitoring 
In accordance with the principles of GCP and GLP, the study may be inspected by the QA unit 
of the clinical sites, regulatory authorities, and the Sponsor. The Sponsor is entitled to access 
information about the status of the study and to review the original documents of the study. 
15. Confidentiality and Retention of Essential Documentation 
This document contains trade secrets and commercial information that is confidential and may 
not be disclosed to third parties. Persons to whom this study protocol is disclosed must be 
informed that all the information herein is confidential and may not be further divulged. These 
restrictions will apply as well to all future communications if deemed privileged or confidential. 
Publication of the study results may only be allowed with written permission from the Sponsor. 
Study documents should be retained for a minimum of 2 years after the last approval of a 
marketing application in an International Conference on Harmonization (ICH) region and until 
there are no pending or contemplated marketing applications in an ICH region or until at least 
2 years have elapsed since the formal discontinuation of clinical development of the study 
intervention. These documents should be retained for a longer period, however, if required by 
local regulations. No records will be destroyed without the written consent of the sponsor, if 
applicable. It is the responsibility of the sponsor to inform the investigator when these documents 
no longer need to be retained. 
16. References 
1 
ELX-02 Investigator’s Brochure. Eloxx Pharmaceuticals. Edition no. 3.2, released on 
26 June 2018. 
2 
Gentamicin Injection, USP (Fresenius Kabi USA, LLC), Prescribing Information. 
Version revised on October 2013. Available online at: 
http://www.accessdata.fda.gov/scripts/cder/daf/ 
3 
CDER. U.S. FDA, Draft Guidance for Industry: Pharmacokinetics in Patients with 
Impaired Renal Function - Study Design, Data Analysis, and Impact on Dosing and 
Labeling. March 2010. Available at: https://www.fda.gov/downloads/Drugs/ 
Guidances/UCM204959.pdf 

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4 
EMA, Guideline on the evaluation of the pharmacokinetics of medicinal products in 
patients with decreased renal function. EMA/CHMP/83874/2014. December 2015. 
Available at: https://www.ema.europa.eu/documents/scientific-guideline/guideline-
evaluation-pharmacokinetics-medicinal-products-patients-decreased-renal-
function_en.pdf 
5 
Division of AIDS, National Institute of Allergy and Infectious Diseases, NIH. Division of 
AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, 
Version 2.1. March 2017. Available at: https://rsc.niaid.nih.gov/clinical-research-
sites/daids-adverse-event-grading-tables 
 

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17. APPENDIX 1 
Table 5. 
Site Reactions to Injections and Infusions DAIDS Grading Table 
PARAMETER  
GRADE 1 MILD  
GRADE 2 MODERATE  
GRADE 3 SEVERE  
GRADE 4 
POTENTIALLY LIFE-
THREATENING  
Injection Site Pain or 
Tenderness  
Report only 1  
Pain or tenderness causing 
no or minimal limitation of 
use of limb  
Pain or tenderness causing 
greater than minimal 
limitation of use of limb  
Pain or tenderness causing 
inability to perform usual 
social and functional 
activities  
Pain or tenderness causing 
inability to perform basic 
self-care function OR 
hospitalization indicated  
Injection Site Erythema or 
Redness* 
Report only 1 
(> 15 years of age) 
2.5 to <5 cm in diameter OR 
6.25 to <25 cm2 surface area 
AND symptoms causing no 
or minimal interference with 
usual social and functional 
activities  
≥5 to <10 cm in diameter OR 
≥25 to <100 cm2 surface area 
OR Symptoms causing 
greater than minimal 
interference with usual social 
and functional activities  
≥10 cm in diameter OR ≥100 
cm2 surface area OR 
ulceration OR secondary 
infection OR phlebitis OR 
sterile abscess OR drainage 
OR symptoms causing 
inability to perform usual 
social and functional 
activities  
Potentially life-threatening 
consequences (eg, abscess, 
exfoliative dermatitis, 
necrosis involving dermis or 
deeper tissue)  
Injection Site Induration 
or Swelling  
Report only 1 
(> 15 years of age) 
2.5 to <5 cm in diameter OR 
6.25 to <25 cm2 surface area 
AND symptoms causing no 
or minimal interference with 
usual social and functional 
activities  
≥5 to <10 cm in diameter OR 
≥25 to <100 cm2 surface area 
OR Symptoms causing 
greater than minimal 
interference with usual social 
and functional activities  
≥10 cm in diameter OR ≥100 
cm2 surface area OR 
ulceration OR secondary 
infection OR phlebitis OR 
sterile abscess OR drainage 
OR symptoms causing 
inability to perform usual 
social and functional 
activities  
Potentially life-threatening 
consequences (eg, abscess, 
exfoliative dermatitis, 
necrosis involving dermis or 
deeper tissue)  
Injection Site Pruritus  
Itching localized to the 
injection site that is relieved 
spontaneously or in <48 
hours of treatment  
Itching beyond the injection 
site that is not generalized 
OR itching localized to the 
injection site requiring ≥48 
hours treatment  
Generalized itching causing 
inability to perform usual 
social and functional 
activities  
NA  
* Injection Site Erythema or Redness should be evaluated and graded using the greatest single diameter or measured surface area.