A Phase 1b Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of EQ001 in Subjects With Moderate-to-Severe Uncontrolled Asthma
Phase: PHASE1
Conditions: Asthma
Sponsor: Equillium

 
 
 
Study Title: 
A Phase 1b Randomized, Double-blind, Placebo-
controlled Study to Evaluate the Safety, Tolerability, 
Pharmacokinetics, Pharmacodynamics, and Clinical 
Activity of EQ001 in Subjects with Moderate-to-Severe 
Uncontrolled Asthma 
Protocol Number: 
EQ001-19-001 
 
Investigational Product(s): 
EQ001 
 
Sponsor: 
Equillium AUS Pty Ltd 
 
Development Phase: 
Phase 1b 
 
NCT Number: 
NCT04007198 
Document Version Date: 
03 February 2021 
 
 
 
 
CONFIDENTIAL 
 
Information contained in this protocol is proprietary and confidential in nature and may not be used, divulged, published, or 
otherwise disclosed to others except to the extent necessary to obtain approval of the Institutional Review Board/Independent 
Ethics Committee, or as required by law. Persons to whom this information is disclosed should be informed that this information 
is confidential and may not be further disclosed without the express permission of Equillium AUS Pty Ltd. 

 
 
 
 
Clinical Study Protocol 
Study Title: 
A Phase 1b Randomized, Double-blind, Placebo-
controlled Study to Evaluate the Safety, Tolerability, 
Pharmacokinetics, Pharmacodynamics, and Clinical 
Activity of EQ001 in Subjects with Moderate-to-Severe 
Uncontrolled Asthma 
Protocol Number: 
EQ001-19-001 
 
Investigational Product(s): 
EQ001 
 
Sponsor: 
Equillium AUS Pty Ltd 
 
 
 
Development Phase: 
Phase 1b 
 
Sponsor's Responsible 
Medical Officer: 
 
 
 
 
  
 
 
 
 
 
 
 
CONFIDENTIAL 
 
Information contained in this protocol is proprietary and confidential in nature and may not be used, divulged, published, or 
otherwise disclosed to others except to the extent necessary to obtain approval of the Institutional Review Board/Independent 
Ethics Committee, or as required by law. Persons to whom this information is disclosed should be informed that this information 
is confidential and may not be further disclosed without the express permission of Equillium AUS Pty Ltd. 
 
 

 
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TABLE OF CONTENTS 
 
 
TABLE OF CONTENTS ........................................................................................................4 
2 
Synopsis and Schedule of Events ...........................................................................9 
2.1 
Synopsis .......................................................................................................9 
 
 
3 
List of Abbreviations and Definitions of Terms .................................................19 
4 
Introduction ...........................................................................................................22 
4.1 
Background ................................................................................................22 
4.2 
Itolizumab ..................................................................................................22 
 
 
 
 
 
 
 
 
 
 
4.5 
Rationale for Evaluating EQ001 for the Treatment of Patients with 
Moderate-to-Severe Uncontrolled Asthma ................................................26 
4.6 
Rationale for Selection for Starting Dose of EQ001 .................................26 
5 
Study Objectives ....................................................................................................28 
5.1 
Primary Objective ......................................................................................28 
5.2 
Secondary Objectives.................................................................................28 
6 
Study EnDPOINTS ...............................................................................................29 
6.1 
Primary Endpoints .....................................................................................29 
6.2 
Secondary Endpoints .................................................................................29 
7 
Investigational Plan ...............................................................................................30 
7.1 
Overall Study Design and Plan ..................................................................30 
7.2 
Data Review Committee, Dose-Limiting Toxicity, and Stopping 
Criteria .......................................................................................................31 
7.2.1 
Dose-Limiting Toxicities .............................................................32 

 
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7.2.2 
Study Drug Dosing Discontinuation ............................................32 
7.2.3 
Study Discontinuation ..................................................................33 
7.3 
Rationale for Study Design ........................................................................33 
7.4 
Study Duration ...........................................................................................34 
8 
Study Population ...................................................................................................35 
8.1 
Study Population ........................................................................................35 
 
 
8.3 
Inclusion Criteria .......................................................................................35 
8.4 
Exclusion Criteria ......................................................................................36 
9 
Study Treatments ..................................................................................................38 
 
 
 
 
9.3 
Treatments Administered ...........................................................................39 
 
 
 
 
 
9.4 
Prior and Concomitant Medications ..........................................................41 
9.4.1 
Permitted Therapies ......................................................................41 
9.4.2 
Prohibited Therapies .....................................................................41 
9.5 
Treatment Compliance ...............................................................................42 
 
 
9.7 
Enrollment or Randomization and Blinding ..............................................42 
 
 
10 
Study Procedures ...................................................................................................44 
10.1 
Screening and Informed Consent ...............................................................44 
10.2 
Demographics and Medical/Surgical History ............................................44 
10.2.1 Demographics ...............................................................................44 
10.2.2 Medical and Surgical Histories ....................................................45 
10.3 
Physical Examination.................................................................................45 
10.4 
Vital Signs ..................................................................................................46 

 
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10.5 
Asthma Clinical Status Assessment ...........................................................46 
10.6 
Pulmonary Function Assessment ...............................................................46 
10.7 
FeNO Assessment ......................................................................................47 
10.8 
Home Peak Flow Testing ...........................................................................48 
10.9 
Measurement of Patient-reported Outcomes .............................................48 
10.9.1 Asthma Daily Diary ......................................................................48 
10.9.2 Asthma Control Questionnaire-6 ..................................................48 
10.10 
12-Lead Electrocardiography .....................................................................48 
10.11 
Clinical Laboratory Tests ...........................................................................49 
10.11.1 Safety Laboratory Tests ................................................................49 
10.11.2 Central Laboratory Tests ..............................................................50 
 
 
 
11 
Adverse Events ......................................................................................................53 
11.1 
Severity ......................................................................................................53 
11.2 
Causality Assessment.................................................................................54 
11.3 
Clinical Laboratory Adverse Events ..........................................................54 
11.4 
Serious Adverse Events .............................................................................55 
11.5 
Reporting Adverse Events .........................................................................55 
11.5.1 Reporting Procedures for Nonserious Adverse Events ................55 
11.5.2 Reporting Procedures for Serious Adverse Events ......................56 
 
 
12 
Study Activities ......................................................................................................58 
12.1 
Screening Visit ...........................................................................................58 
12.2 
Study Day 1 (Baseline) ..............................................................................58 
12.3 
Study Day 4 (± 1 Day) ...............................................................................60 
12.4 
Study Day 8 (± 1 Day) ...............................................................................60 
12.5 
Study Day 15 (± 2 Days) ...........................................................................61 
12.6 
Study Day 29 (± 2 Days) ...........................................................................62 
12.7 
Study Day 43 (± 2 Days) ...........................................................................63 

 
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12.8 
Study Day 57 (± 2 Days) ...........................................................................64 
12.9 
Study Day 85 (± 2 Days), ET, or Unscheduled Visits ...............................65 
13 
Planned Statistical Methods .................................................................................67 
13.1 
General Considerations ..............................................................................67 
 
 
13.3 
Analysis Populations ..................................................................................67 
13.3.1 Safety Population .........................................................................67 
13.3.2 Pharmacokinetic Analysis Population ..........................................67 
 
 
13.3.4 Efficacy Population ......................................................................67 
13.4 
Subject Disposition ....................................................................................68 
13.5 
Demographics and Baseline Characteristics ..............................................68 
 
 
13.7 
Safety Analyses ..........................................................................................68 
 
 
13.9 
Efficacy Analyses ......................................................................................69 
14 
Administrative Considerations ............................................................................70 
14.1 
Investigator Responsibilities ......................................................................70 
14.2 
Independent Ethics Committee Approval ..................................................71 
14.3 
Ethical Conduct of Study ...........................................................................71 
14.4 
Subject Information and Consent...............................................................72 
14.5 
Confidentiality ...........................................................................................72 
14.6 
Study Initiation...........................................................................................73 
14.7 
Case Report Forms and Other Study Records ...........................................73 
14.8 
Study Monitoring .......................................................................................74 
14.9 
Access to Source Documentation ..............................................................74 
14.10 
Study or Study Site Termination................................................................75 
 
 
 
 
14.13 
Quality Assurance ......................................................................................76 

 
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2 
SYNOPSIS AND SCHEDULE OF EVENTS 
2.1 
Synopsis 
Title of Study Protocol:  A Phase 1b Randomized, Double-blind, Placebo-controlled Study to Evaluate the 
Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of EQ001 in Subjects with 
Moderate-to-Severe Uncontrolled Asthma 
Protocol Number: EQ001-19-001 
Name of Sponsor Company: 
Equillium AUS Pty Ltd 
 
 
Name of Finished Product:  EQ001 (itolizumab; Bmab 600) 
Phase of Development:  Phase 1b 
Objectives: 
Primary Objective 
Characterize the safety and tolerability of EQ001 (itolizumab) 
Secondary Objectives 
1. Characterize the pharmacokinetics (PK) of EQ001 
 
 
 
 
4. Characterize the clinical activity of EQ001 
Endpoints: 
Primary Endpoints 
Safety and tolerability of EQ001, as assessed by treatment-emergent adverse events (TEAEs), treatment 
emergent serious adverse events (TESAEs), clinical laboratory values, ECGs, vital signs and physical 
examinations 
 
Secondary Endpoints 
1. Pharmacokinetics of EQ001 will be assessed 
 
 
 
 
 
 
 
 
 
  
4. Clinical activity of EQ001, as assessed by the following variables: 
a. Change from baseline in prebronchodilator FEV1  
b. Change from baseline in fractional exhaled nitric oxide (FeNO) 
c. Change in peak expiratory flow rate 
d. Change from baseline in Asthma Control Questionnaire (ACQ-6) score 
e. Time to first exacerbation (any severity) 

 
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f. Asthma symptoms, peak expiratory flow rate measurements, use of controller and rescue medication, 
nighttime awakening due to asthma and asthma-related activity limitations (as recorded on an eDiary) 
g. Annualized rate of asthma exacerbations (of any severity) 
Study Design: 
This is a phase 1b, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, PK, 
 clinical activity of EQ001, a humanized immunoglobulin G1 (IgG1) monoclonal antibody that 
selectively targets CD6 on Teff cells, in subjects with moderate-to-severe uncontrolled asthma. The study will 
initially enroll up to 32 subjects in up to 4 successive dose cohorts of 8 adult subjects each (up to 10 subjects may 
be enrolled to achieve 8 DLT evaluable subjects). Doses of 0.8, 1.6, 2.4, and 3.2 mg/kg EQ001, or an equivalent 
volume of placebo, will be administered subcutaneously (SC) every 2 weeks (Q2W) for a total of 5 doses. 
Subjects will be randomized in a 3:1 ratio (active:placebo) to characterize the safety, tolerability, PK, PD, and 
clinical activity of ascending SC doses of EQ001 and to determine the maximum tolerated dose (MTD). After 
determination of the MTD, and at the Sponsor’s discretion, the MTD cohort may be repeated to increase the 
number of subjects receiving the MTD to 12 and subjects in the pooled placebo cohort to 10; therefore, the total 
number of subjects enrolled in the study may be up to 40. 
Written informed consent for study participation will be obtained before any study-related procedures or 
assessments are performed. All potential subjects will be screened for potential participation, and those meeting 
all eligibility criteria will be offered participation in the study. 
The study will be conducted in the following 3 defined periods: 
1. Screening Period: Will begin when the informed consent form (ICF) is signed. During this period, the 
subject will undergo baseline assessments to determine eligibility for study participation. The subject 
will complete an electronic diary (eDiary) to record asthma symptoms, AM and PM peak expiratory 
flow rate measurements, use of controller and rescue medication, nighttime awakening due to asthma 
and asthma-related activity limitations. The Screening Period duration will be up to 4 weeks; it will end 
after at least 2 weeks of baseline assessments have been conducted and all studies required to meet 
eligibility have been completed. If a subject meets all eligibility criteria (including documented 
compliance with eDiary completion, peak flow monitoring and adherence to their standard-of-care 
[SoC] meds), they will be enrolled into the study.  
2. Treatment Period: Will begin on Day 1 with the first study drug dose and have a duration of 8 weeks. 
During the Treatment Period, 5 doses of study drug will be administered SC, 1 dose each on Study 
Days 1, 15, 29, 43, and 57. Subjects will return to the study site for follow-up evaluations according to 
the Schedule of Events (SOE). Following the last dose of study drug, subjects will enter the Safety 
Follow-up Period. 
3. Safety Follow-up Period: Will have a 4-week duration and conclude 4 weeks after the final study drug 
dose with the End-of-Study (EOS) Visit on Day 85. 
Successive cohorts that are randomized in a 3:1 ratio (active:placebo) will be enrolled. Subjects will be treated 
Q2W for 8 weeks and followed for a total of 12 weeks after the initial study drug dose on Day 1. 
 
 
 Randomization in the next dose cohort will not begin until the Data Review Committee 
(DRC) review of all available safety data from all subjects supports escalation to the next dose level. The MTD of 
EQ001 in subjects with moderate-to-severe uncontrolled asthma will be determined based on all available data, 
including safety, tolerability, PK, PD, and clinical activity data. 
 
 
 

 
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Study drug should be administered so that there are at least 12 days between doses. 
Data Review Committee, Dose-Limiting Toxicity, and Stopping Criteria: 
The DRC will periodically review all available clinical and laboratory safety data during the study. When the last 
subject in a cohort completes the Day 29 assessments, the DRC will convene and make recommendations 
regarding cohort advancement and study continuation, discontinuation, or modification. 
Dose-limiting toxicity is defined as any study drug-related adverse event (AE) of National Cancer Institute (NCI) 
Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 ≥ Grade 3 severity (including 
≥ Grade 3 injection-related reaction or other clinical finding associated with hypersensitivity related to study 
drug) and not related to underlying asthma. The occurrence of Grade 3 lymphopenia will be classified as a DLT 
only if present with concomitant infection at least possibly related to the underlying lymphopenia; Grade 4 or 
higher severity of lymphopenia will be classified as a DLT. If 2 subjects experience DLTs in a single cohort (in 
the DLT assessment period; Study Days 1-29), the DRC will convene to review all available, unblinded safety, 
PK, PD, and clinical activity data. After its evaluation, the DRC may recommend study continuation (with or 
without modification) or termination of dose escalation. If dose escalation is terminated, the next-lower dose may 
be declared the MTD. Alternatively, an additional cohort at an intermediate dose may be added to better define 
the MTD. 
Subject Stopping Criteria: 
Dosing of EQ001 will be permanently discontinued in a subject if any of the following occurs: 
• Any DLT (see definition above) 
• Subject’s consent withdrawn 
• Investigator or Sponsor decides that the subject will not benefit from further investigational product (IP) 
• Pregnancy 
• Subject is unable to comply with the study requirements 
• Sponsor terminates the study 
• A regulatory authority mandates a study dosing cessation 
• Subject experiences a DLT anytime during the treatment period 
Number of Subjects Planned:  
Up to 40 subjects with moderate-to-severe uncontrolled asthma are planned to be enrolled in the study. 
Inclusion Criteria: 
 
Subjects will be required to meet all of the following inclusion criteria in order to be eligible for study 
enrollment: 
 
1. Is male or female, age ≥ 18 and ≤ 75 years 
2. Has a documented clinical diagnosis of moderate-to-severe uncontrolled asthma requiring moderate- or high-
dose inhaled CS (ICS; ≥ 250 mcg of fluticasone propionate twice daily or equipotent ICS daily dosage to a 
maximum of 2000 mcg/day of fluticasone propionate or equivalent) and one or more additional controller 
medications (inhaled LABA or anticholinergic or LTA) for ≥ 3 months, with a stable dose ≥1 month prior to 
the initial Screening Visit 

 
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3. Has a prebronchodilator forced expiratory volume in 1 second (FEV1) ≥ 40% and ≤ 90% of predicted value 
during the Screening Period, despite use of a moderate- or high-dose ICS and one or more additional 
controller medications (inhaled LABA or anticholinergic or LTA) 
4. Has a history of clinically diagnosed asthma, which could include a history of FEV1 reversibility and/or 
positive bronchial challenge test 
5. Has a history of ≥ 1 clinically significant asthma exacerbation (see definition in Section 10.2.2) prior to the 
initial Screening Visit, despite use of a moderate- or high-dose ICS and one or more additional controller 
medications at the time the exacerbation(s) occurred 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
Exclusion Criteria: 
Subjects will be ineligible for enrollment in the study if they meet any of the following criteria: 
1. Is a current or former smoker with a smoking history of ≥10 pack-years (number of pack-years = number of 
cigarettes per day/20 × number of years smoked; a former smoker is defined as a subject who stopped 
smoking ≥ 6 months prior to the Screening Visit) 
2. Has a body mass index > 36 kg/m2 
3. Has a documented history or radiological evidence of a clinically important lung condition other than asthma 
(eg, α1-antitrypsin deficiency, bronchiectasis, cystic fibrosis, primary ciliary dyskinesia, pulmonary fibrosis, 
allergic bronchopulmonary mycosis, or lung cancer) 
4. Has a respiratory tract infection (RTI) within 4 weeks before the initial Screening Visit, or during the 
Screening Period (these subjects may be re-screened following complete resolution of their RTI) 
5. Has an asthma exacerbation within 4 weeks before the initial Screening Visit, or during the Screening Period 
(these subjects may be re-screened following complete resolution of their exacerbation) 
6. Has a diagnosis of currently active malignancy; subjects with a medical history of basal cell carcinoma, 
localized squamous cell carcinoma of the skin, or in situ carcinoma of the uterine cervix are eligible; subjects 
with a medical history of other malignancies are eligible if the subject is in remission and curative therapy 
was completed ≥ 2 years prior to the initial Screening Visit 
7. Has a history or presence of clinically concerning cardiac arrythmias, atrial fibrillation, New York Heart 
Association Class III or IV heart failure, or prolonged QT or corrected QT interval > 500 milliseconds (ms) 
at the Screening Visit 
8. Has any disorder (including, but not limited to, cardiovascular [CV], gastrointestinal [GI], hepatic, renal, 
neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical 
impairment) that is not stable in the opinion of the investigator and/or could: 
a. 
Affect the subject’s safety  
b. Influence the findings of the study or data interpretation 
c. 
Impede the subject’s ability to complete the study 
9. Has undergone bronchial thermoplasty 

 
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10. Has a history of substance abuse (including alcohol) that may, in the investigator’s judgment, increase the 
risk to the subject of participation in the study 
11. Has used monoclonal antibody (mAb) therapy for the management of asthma or any other condition within 
3 months prior to the initial Screening Visit (these subjects may be re-screened following the 3 month 
period) 
12. Has required an oral corticosteroid burst within 1 month prior to the initial Screening Visit or during the 
Screening Period (these subjects may be re-screened following the 1 month period); maintenance oral 
corticosteroids ≤ 10 mg/d prednisone or equivalent is permitted 
 
 
 
 
 
 
 
 
 
 
  
Investigational Products, Dosage, and Mode of Administration: 
The investigational product (IP) is EQ001 (itolizumab [Bmab 600]), a humanized recombinant immunoglobulin 
G1 (IgG1) monoclonal antibody (mAb) that selectively targets the extracellular scavenger receptor cysteine-rich 
(Sc) membrane-distal domain 1 of human CD6.
 
. 
The placebo is comprised of the same excipients at the same concentrations as in the active drug. It will be 
provided as a preservative-free sterile, clear, colorless solution in a single-use vial for SC administration. 
Study drug and placebo will be administered by SC injection. 
 
 
Criteria for Evaluation: 
Safety: 
Safety will be assessed by physical examinations, vital signs, 12-lead ECGs, laboratory tests 
 
 and AE monitoring. 
 
 
 
Pharmacokinetics: 
Serum for PK sampling will be collected at specified time points, as outlined in the Schedule of Events and will 
be descriptively summarized by the nominal assessment time point for each dose. 
 
 
 
 

 
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Efficacy: 
Clinical activity of EQ001 will be assessed in subjects with moderate-to-severe uncontrolled asthma using the 
change from baseline in prebronchodilator FEV1, FeNO, peak flow rate, ACQ-6 scores, time to first exacerbation 
(of any severity), rescue medication use, and annualized rates of asthma exacerbations (of any severity). 
Statistical Methods: 
All safety, 
 and efficacy endpoints will be tabulated using descriptive statistics; data from all placebo 
subjects will be pooled. Data from EQ001-treated subjects will be presented by dose and combined (a total of up 
to 30 subjects). If data permits, differences between the treatment groups and 95% confidence intervals for the 
difference will be presented. 
Analysis Populations: 
The study consists of the following analysis populations: 
Safety Population: Consists of all subjects who receive any study drug. 
 
. 
Efficacy Population: Consists of those subjects in the safety population who have at least 1 post-treatment clinical 
activity assessment. 
The primary analyses of safety and efficacy endpoints will be based on the actual administered treatment if the 
administered treatment differs from the randomized treatment. 
 
 
 
 
 
Safety Analyses: 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) v 20.1, or the 
current version for the purposes of summarization. Incidence of treatment-emergent AEs (TEAEs), treatment-
emergent serious AEs (TESAEs), TEAEs leading to study drug discontinuation, and TEAEs with an outcome of 
death will be summarized by MedDRA system organ class (SOC) and preferred term (PT). Adverse events will 
also be summarized by worst severity grade and causality relationship to study drug. 
 
 
Clinical laboratory data will be descriptively summarized, including observed values at collection time points and 
change from baseline. All laboratory parameters that can be graded using CTCAE v5.0 will be graded. For 
selected parameters, the following summaries may be produced: 
• Worst post-baseline severity grade 
• Shift summary of baseline grade to worst post-baseline severity grade 
Safety evaluations may also include changes in the subject’s physical examination findings, vital signs, and ECG 
results. The incidence of treatment-emergent anti-EQ001 binding and neutralization antibody will be reported. 
 

 
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PK Analyses: 
PK data resulting from SC administration of EQ001 in this study will be compared with those of intravenous (IV) 
administration in healthy volunteers and subjects with other medical conditions in other clinical studies to the 
extent possible. 
 
 
 

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3 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
ACQ 
Asthma Control Questionnaire 
ADA 
anti-drug antibody 
ADD 
Asthma Daily Diary 
AE 
adverse event 
AESI 
adverse event of special interest 
ALC 
absolute lymphocyte count 
ALCAM 
activated leukocyte cell adhesion molecule  
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
AST 
aspartate aminotransferase 
ATS 
American Thoracic Society 
BD 
bronchodilator 
Bmab 600 
itolizumab; EQ001 
BMI 
body mass index 
BUN 
blood urea nitrogen 
CBC 
complete blood count 
CFR 
Code of Federal Regulations 
Cl 
Clearance 
Cmax 
maximum serum drug concentration 
CS 
corticosteroid 
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
DBP 
diastolic blood pressure 
DLT 
dose-limiting toxicity 
DNA 
deoxyribonucleic acid 
DRC 
Data Review Committee 
EAE 
experimental autoimmune encephalomyelitis 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
eDiary 
electronic diary 
EOS 
End of Study, or End-of-Study (adj) 
ERS 
European Respiratory Society 
ET 
early termination 
FDA 
Food and Drug Administration 
FeNO 
fractional exhaled nitric oxide 
FEV1 
forced expiratory volume in 1 second 
FVC 
forced vital capacity 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl transferase 
GI 
gastrointestinal(ly) 

 
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GINA 
Global Initiative for Asthma 
HBV 
hepatitis B virus 
Hct 
Hematocrit 
HCV 
hepatitis C virus 
Hgb 
Hemoglobin 
HIV 
human immunodeficiency virus 
HBsAg 
hepatitis B virus surface antigen 
IB 
investigator’s brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
ICS 
inhaled corticosteroids 
IEC 
Independent Ethics Committee 
IgE 
immunoglobulin E 
IgG1 
immunoglobulin G1  
IL- 
interleukin- 
IM 
investigators meeting 
INF 
Interferon 
IP 
investigational product 
IV 
intravenous(ly) 
IWRS 
Interactive Web Response System 
LABA 
long-acting beta agonist 
LDH 
lactate dehydrogenase 
LTA 
leukotriene antagonist 
mAb 
monoclonal antibody 
MedDRA 
Medical Dictionary for Regulatory Activities 
MTD 
maximum tolerated dose 
NAB 
neutralizing anti-drug antibody 
NCI 
National Cancer Institute 
OVA 
Ovalbumin 
PBMC 
peripheral blood mononuclear cell 
PC20 
provocative concentration causing a 20% decrease 
PD 
pharmacodynamic(s) 
PEFR 
peak expiratory flow rate 
PFT 
pulmonary function test 
Ph.Eur. 
European Pharmacopoeia 
PK 
pharmacokinetic(s) 
PT 
preferred term 
Q2W 
every 2 weeks 
RBC 
red blood cell 
RNA 
ribonucleic acid 

 
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RTI 
respiratory tract infection 
SABA 
short-acting beta agonist 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SC 
subcutaneous(ly) 
Sc 
scavenger receptor cysteine-rich 
SIV 
site initiation visit 
SOC 
system organ class 
SoC 
standard-of-care 
SOE 
Schedule of Events 
SSDL 
site signature and delegation log 
SWFI 
sterile water for injection 
t½ 
half-life 
TCR 
T-cell receptor 
TEAE 
treatment-emergent adverse event 
Teff 
effector T cell 
TESAE 
treatment-emergent serious adverse event 
Th 
T helper  
Tmax 
time to maximum concentration 
TNF 
tumor necrosis factor 
USP 
United States Pharmacopeia 
US 
United States 
Vd 
volume of distribution 
WBC 
white blood cell 
WOCBP 
women of childbearing potential 

 
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4 
INTRODUCTION 
4.1 
Background 
Asthma is a chronic inflammatory disease of the airways characterized by airway 
hyperresponsiveness, acute and chronic bronchoconstriction, airway edema, and mucus plugging. 
The inflammatory component of asthma involves many cell types, including mast cells, 
eosinophils, T-lymphocytes, neutrophils, and epithelial cells and their biological products. For 
most asthma patients, a regimen of controller therapy and reliever therapy provides adequate 
long-term control. However, 10% to 15% of asthma patients have symptomatic disease despite 
maximum recommended treatment. These patients account for approximately 60% of the total 
health care costs for patients who have asthma
 
Asthma had long been considered a single disease characterized by airway inflammation and 
predominantly attributed to Type 2 inflammatory processes. More recent analyses of large cohorts 
have resulted in the identification of several asthma phenotypes and endotypes, including 
subgroups of patients for whom disease is driven predominantly by non-Type 2 mechanisms 
 
 
 
 
 
 
 
 
 
 
 
 
 
4.2 
Itolizumab 
Itolizumab (Bmab 600; EQ001) is a humanized recombinant immunoglobulin G1 (IgG1) 
monoclonal antibody (mAb) that selectively targets the extracellular scavenger receptor cysteine-
rich (Sc) membrane-distal domain 1 of human CD6 
 
 a co-stimulatory membrane glycoprotein associated with T cell modulation and implicated 
in several autoimmune and inflammatory diseases, including psoriasis, multiple sclerosis, 
rheumatoid arthritis, and Sjogren’s disease 
 

 
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EQ001 binds to domain-1 of human CD6 and is believed to sterically hinder the optimal 
engagement of activated leukocyte cell adhesion molecule (ALCAM) with domain-3, modulating 
both co-stimulation and trafficking without causing T cell depletion. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 

 
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4.5 
Rationale for Evaluating EQ001 for the Treatment of Patients with Moderate-to-
Severe Uncontrolled Asthma 
Patients with severe asthma make up only 10% to 15% of the population of adults with asthma, 
but account for 60% of the healthcare costs attributable to asthma 
 Currently 
available therapeutics for asthma include corticosteroids, beta agonists, anticholinergics, 
leukotriene antagonists, cromones, theophylline, and a variety of targeted biologics 
 
 
 
 
 
 
 
 
4.6 
Rationale for Selection for Starting Dose of EQ001 
 
 
 
 

 
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 Clinical experience with itolizumab in patients with 
psoriasis and rheumatoid arthritis has demonstrated the safety and tolerability of IV doses ranging 
from 0.1 mg/kg to 1.6 mg/kg, administered chronically as a bimonthly infusion. A Phase 1 study 
in healthy volunteers with EQ001 administered SC demonstrated safety at single doses as high as 
3.2 mg/kg, with a half-life that supports a dosing interval of 2 weeks. The present study is 
designed to assure adequate trough levels while assessing the potential for accumulation in this 
short-term study, the first to evaluate multiple SC dosing of EQ001. These clinical data support 
the proposed clinical study design with a starting SC dose of 0.8 mg/kg itolizumab. 

 
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5 
STUDY OBJECTIVES 
5.1 
Primary Objective 
Characterize the safety and tolerability of EQ001 (itolizumab) 
5.2 
Secondary Objectives 
1. Characterize the pharmacokinetics (PK) of EQ001 
 
 
 
 
4. Characterize the clinical activity of EQ001  

 
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6 
STUDY ENDPOINTS 
6.1 
Primary Endpoints 
Safety and tolerability of EQ001, as assessed by treatment-emergent adverse events 
(TEAEs), treatment-emergent serious adverse events (TESAEs), clinical laboratory 
values, ECGs, vital signs, and physical examinations 
 
6.2 
Secondary Endpoints 
1. Pharmacokinetics of EQ001 will be assessed by descriptively summarizing the PK 
 
 
 
 
 
 
 
 
 
 
 
4. Clinical activity of EQ001, as assessed by the following variables: 
a. Change from baseline in prebronchodilator FEV1  
b. Change from baseline in fractional exhaled nitric oxide (FeNO) 
c. Change in peak expiratory flow rate 
d. Change from baseline in Asthma Control Questionnaire (ACQ-6) score 
e. Time to first exacerbation (any severity) 
f. Asthma symptoms, peak expiratory flow rate measurements, use of controller and rescue 
medication, nighttime awakening due to asthma and asthma-related activity limitations 
(as recorded on an eDiary) 
g. Annualized rate of asthma exacerbations (of any severity) 

 
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7 
INVESTIGATIONAL PLAN 
7.1 
Overall Study Design and Plan 
This is a phase 1b randomized, double-blind, placebo-controlled study to evaluate the safety, 
tolerability, PK, PD, and clinical activity of EQ001 in subjects with moderate-to-severe 
uncontrolled asthma.  
The study will initially enroll up to 32 subjects in up to 4 successive dose cohorts of 8 adult 
subjects each (up to 10 subjects may be enrolled in order to achieve 8 DLT evaluable subjects). 
Doses of 0.8, 1.6, 2.4, and 3.2 mg/kg EQ001, or an equivalent volume of placebo, will be 
administered SC every 2 weeks (Q2W) for a total of 5 doses. Subjects will be randomized in a 3:1 
ratio (active:placebo) to characterize the safety, tolerability, 
 and clinical activity of 
ascending SC doses of EQ001 and to determine the maximum tolerated dose (MTD). After 
determination of the MTD, and at the Sponsor’s discretion, the MTD cohort may be repeated to 
increase the number of subjects receiving the MTD to 12 and to increase the number of subjects 
in the pooled placebo cohort to 10; therefore, the study may enroll as many as 40 total subjects. 
Written informed consent for study participation will be obtained before any study-related 
procedures or assessments are performed. All potential subjects will be screened for potential 
participation, and those meeting all eligibility criteria will be offered participation in the study. 
The study will be conducted in the following 3 defined periods : 
1. Screening Period: Will begin when the informed consent form (ICF) is signed. During this 
period, the subject will undergo baseline assessments to determine eligibility for study 
participation. The subject will complete an electronic diary (eDiary) to record symptoms 
of asthma, AM and PM peak expiratory flow rates, and use of controller and rescue 
medications, nighttime awakening due to asthma and asthma-related activity limitations. 
The Screening Period duration will be up to 4 weeks; it will end after at least 2 weeks of 
baseline assessments have been conducted and all studies required to meet eligibility have 
been completed. If a subject provides written informed consent and meets all eligibility 
criteria (including documented compliance with eDiary completion, peak flow monitoring 
and adherence to their standard-of-care [SoC] medications), they will be enrolled into the 
study.  
2. Treatment Period: Will begin on Day 1 with the first study drug dose and have a duration of 
8 weeks. During the Treatment Period, 5 doses of study drug will be administered SC, 
1 dose each on Study Days 1, 15, 29, 43, and 57. Subjects will return to the study site for 

 
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follow-up evaluations according to the Schedule of Events (SOE, Section 2.2). Following 
the last dose of study drug, subjects will enter the Safety Follow-up Period. 
3. Safety Follow-up Period: Will have a 4-week duration and conclude 4 weeks after the final 
study drug dose with the End-of-Study (EOS) Visit on Study Day 85. 
Successive cohorts that are randomized in a 3:1 ratio (active:placebo) will be enrolled. Subjects 
will be treated Q2W for 8 weeks and followed for a total of 12 weeks after the initial study drug 
dose on Day 1. 
 
 
 
 The MTD of EQ001 in 
subjects with moderate-to-severe uncontrolled asthma will be determined based on all available 
data, including safety, tolerability, PK, PD, and clinical activity data. 
 
 
 
If subjects do not complete the required study visits or discontinue from the study for any reason, 
they will be asked to return to their clinical study site for an Early Termination (ET) Visit, as 
described in the SOE (Section 2.2). 
Dose-limiting toxicity is defined in Section 7.2.1. If 2 subjects experience dose-limiting toxicities 
(DLTs) in a single cohort in the DLT assessment period, the DRC will convene to review all 
available, unblinded safety, 
 clinical activity data. After its evaluation, the DRC may 
recommend continuation of the study (with or without modification) or termination of dose 
escalation. If dose escalation is terminated, the next-lower dose may be declared the MTD. 
Alternatively, an additional cohort at an intermediate dose may be added to better define the 
MTD. 
The study will enroll subjects with an initial clinical diagnosis of moderate-to-severe uncontrolled 
asthma. 
7.2 
Data Review Committee, Dose-Limiting Toxicity, and Stopping Criteria 
The DRC, comprised of the independent statistician, DRC coordinator, Equillium representatives 
and 3 independent asthma clinicians, will provide periodic review of the safety data generated by 
the clinical study. The DRC will be unblinded. A Sponsor representative will also serve as a 
non-voting member of the DRC to facilitate Sponsor internal planning. Minutes of all DRC 
meetings will be archived for inclusion in the Trial Master File. 

 
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The DRC Chair will be informed by the Sponsor of the potential need for ad hoc meetings and 
will coordinate such meetings. A formal DRC Charter will be prepared. 
The DRC will review all available clinical and laboratory safety data at defined intervals during 
the study. It will make recommendations regarding cohort advancement and continuation, 
discontinuation, or modification of the study. 
Additional subjects may be enrolled in a cohort if considered necessary by the DRC to further 
characterize drug safety, tolerability, or efficacy. Also, the DRC may recommend modification of 
the doses to be evaluated, to not initiate specific dose cohorts, to initiate additional dose cohorts, 
or to terminate the study if it is deemed necessary. Appropriate regulatory approvals will be 
obtained prior to initiation of any recommended changes by the DRC, as required. 
7.2.1 
Dose-Limiting Toxicities 
 
 
 
 
 
 
 
 
 
 
 
 
If 2 subjects experience DLTs in the DLT assessment period in a single cohort, the DRC will 
convene to review all available, unblinded safety, 
 and clinical activity data. After its 
evaluation, the DRC may recommend continuation of the study (with or without modification) or 
termination of dose escalation. If dose escalation is terminated, the next-lower dose may be 
declared the MTD. Alternatively, an additional cohort at an intermediate dose may be added to 
better define the MTD. 
 
 
 
 
 
 
 

 
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7.3 
Rationale for Study Design 
This study has a double-blinded, placebo-controlled design. Patients and investigators will remain 
blinded for the duration of the study. Site staff will remain blinded, with the exception of the 
unblinded pharmacist. The Sponsor will be unblinded, including the Sponsor representatives to 
the DRC. Subjects will be randomized in a 3:1 ratio (active:placebo) to characterize the safety, 
tolerability, 
 and clinical activity of ascending SC doses of EQ001 and determine the 
MTD.  
After the MTD determination and at the Sponsor’s discretion, the MTD cohort may be repeated to 
increase to 12 the number of subjects receiving the MTD and increase to 10 the number of 
subjects in the pooled placebo cohort. 

 
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7.4 
Study Duration 
Each subject who completes the study will undergo up to 4 weeks for Screening, 8 weeks of 
treatment and 4 weeks of follow-up, for a total of up to 16 weeks on study. 

 
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8 
STUDY POPULATION 
8.1 
Study Population 
Each cohort will enroll unique subjects who may not be treated in more than 1 cohort. Subjects 
will have moderate-to-severe uncontrolled asthma. 
 
 
 
 
 
8.3 
Inclusion Criteria 
Potential subjects will be required to meet all of these inclusion criteria in order to be eligible for 
study enrollment: 
1. Is male or female, age ≥18 and ≤ 75 years 
2. Has a documented clinical diagnosis of moderate-to-severe uncontrolled asthma 
requiring moderate- or high-dose inhaled CS (ICS; ≥ 250 mcg of fluticasone 
propionate twice daily, or equipotent ICS daily dosage, to a maximum of 
2000 mcg/day of fluticasone propionate or equivalent) and one or more additional 
controller medications (inhaled long-acting beta agonist [LABA] or anticholinergic or 
LTA) for ≥ 3 months, with a stable dose ≥ 1 month prior to the initial Screening Visit 
3. Has a prebronchodilator forced expiratory volume in 1 second (FEV1) ≥ 40% and ≤ 
90% of predicted value during the Screening Period, despite use of a moderate- or 
high-dose ICS and one or more additional controller medications (inhaled LABA or 
anticholinergic or LTA) 
4. Has a history of clinically diagnosed asthma, which could include a history of FEV1 
reversibility and/or positive bronchial challenge test 
5. Has a history of ≥ 1 clinically significant asthma exacerbation prior to the initial 
Screening Visit, despite use of a moderate- or high-dose ICS and one or more 
additional controller medications at the time the exacerbation(s) occurred 
 
 
 
 
 
 
 
 
 
 
 

 
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8.4 
Exclusion Criteria 
Potential subjects will be ineligible for enrollment in the study if they meet any of the following 
criteria:  
1. Is a current or former smoker with a smoking history of ≥10 pack-years (number of 
pack-years = number of cigarettes per day/20 × number of years smoked; a former 
smoker is defined as a subject who stopped smoking ≥ 6 months prior to the Screening 
Visit) 
2. Has a body mass index (BMI) > 36 kg/m2 
3. Has a documented history or radiological evidence of a clinically important lung 
condition other than asthma (eg, α1-antitrypsin deficiency, bronchiectasis, cystic 
fibrosis, primary ciliary dyskinesia, pulmonary fibrosis, allergic bronchopulmonary 
mycosis, or lung cancer) 
4. Has a respiratory tract infection (RTI) within 4 weeks before the initial Screening 
Visit, or during the Screening Period (these subjects may be re-screened following 
complete resolution of their RTI) 
5. Has an asthma exacerbation within 4 weeks before the initial Screening Visit, or 
during the Screening Period (these subjects may be re-screened following complete 
resolution of their exacerbation) 
6. Has a diagnosis of currently active malignancy; subjects with a medical history of 
basal cell carcinoma, localized squamous cell carcinoma of the skin, or in situ 
carcinoma of the uterine cervix are eligible; subjects with a medical history of other 
malignancies are eligible if the subject is in remission and curative therapy was 
completed ≥ 2 years prior to the initial Screening Visit 
7. Has a history or presence of clinically concerning cardiac arrythmias, atrial fibrillation, 
New York Heart Association Class III or IV heart failure, or prolonged QT or 
corrected QT interval > 500 milliseconds (ms) at the Screening Visit 
8. Has any disorder (including, but not limited to, cardiovascular [CV], gastrointestinal 
[GI], hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, 
hematological, psychiatric, or major physical impairment) that is not stable in the 
opinion of the investigator and/or could: 
a. Affect the subject’s safety  
b. Influence the findings of the study or data interpretation 

 
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c. Impede the subject’s ability to complete the study  
9. Has undergone bronchial thermoplasty 
10. Has a history of substance abuse (including alcohol) that may, in the investigator’s 
judgment, increase the risk to the subject of participation in the study 
11. Has used monoclonal antibody (mAb) therapy for the management of asthma or any 
other condition within 3 months prior to the initial Screening Visit (these subjects may 
be re-screened following the 3 month period) 
12. Has required an oral corticosteroid burst within 1 month prior to the initial Screening 
Visit or during the Screening Period (these subjects may be re-screened following the 
1 month period); maintenance oral corticosteroids ≤ 10 mg/d prednisone or equivalent 
is permitted 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 

 
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9.3 
Treatments Administered 
All subjects will take their standard medications for their moderate-to-severe asthma as prescribed 
by the study physician, consisting of a moderate- or high-dose inhaled corticosteroid (CS) and one 
or more additional controller medications (eg, inhaled LABA or anticholinergic). Leukotriene 
antagonists (LTAs) may also be used as controller medications. Allergen immunotherapy at a 
stable dose is permitted; however, use of monoclonal antibody (mAb) therapeutics is prohibited. 
Doses of all controller medications must be stable for 4 weeks including the duration of the 
Screening Period. EQ001 will be administered Q2W for 8 weeks (a total of 5 doses) at the 
following dose levels: 
• Cohort 1: 0.8 mg/kg 
• Cohort 2: 1.6 mg/kg  
• Cohort 3: 2.4 mg/kg  
• Cohort 4: 3.2 mg/kg 
EQ001 or placebo doses will be administered in the clinic; subjects will be observed for a 
minimum of 30 minutes after administration. 
 
 
 
 
 

 
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9.3.1 
Study Drug Dosage Preparation and Administration 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 

 
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9.4 
Prior and Concomitant Medications 
Prior and concomitant medications and treatments will be collected from Screening and 
throughout the study. 
9.4.1 
Permitted Therapies 
All subjects will take standard medications for their moderate-to-severe asthma, consisting of a 
moderate- or high-dose inhaled CS and one or more additional controller medications (eg, inhaled 
LABA or anticholinergic). Leukotriene antagonists may also be used as controller medications. 
Allergen immunotherapy at a stable dose is permitted. 
9.4.2 
Prohibited Therapies 
Treatment with mAb therapeutics other than EQ001 is prohibited. 
If a determination is made to treat a subject with any prohibited therapies or medications during 
the study, the Medical Monitor should be informed. Subjects will be asked to remain in the study 
and complete all study visits through Study Day 85, but no additional study drug will be 
administered. 
Caffeine and other xanthines (coffee, tea, etc.) should be avoided beginning the night prior to each 
study visit. 
Donation of blood products or sperm is not permitted while on study treatment and for 3 months 
after the last dose of study drug. 

 
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9.5 
Treatment Compliance 
The study drug will be administered in a blinded fashion at the clinic/facility by a qualified staff 
member. The time of the SC injection at each administration will be recorded. 
9.6 
Packaging and Labeling 
 
 
Placebo is provided in a single-use vial for SC injection. 
 
 
 
9.7 
Enrollment or Randomization and Blinding 
It is the investigator’s responsibility to ensure that subjects are eligible to participate in the study 
prior to enrollment and continue to remain eligible throughout the study. An IWRS will be used to 
ensure study drug inventory, accountability, and appropriate cohort allocation and blinded 
treatment assignment. The site’s unblinded pharmacist or designee will have access to the IWRS 
and all treatment assignments. 
The study will be randomized, double blinded, and placebo controlled. Subjects will be 
randomized in a 3:1 ratio (active:placebo). 
After informed consent has been obtained, all Screening procedures have been assessed, and 
study eligibility has been confirmed, subjects will be randomized to receive either EQ001 or 
placebo on Study Day 1. The unblinded study pharmacist or designee will access the IWRS to 
randomize the subject into the study, receive the blinded treatment assignment and dose, record 
drug accountability, and request resupply. 
Investigators, site staff, and subjects will be blinded to treatment assignment. The Sponsor will be 
unblinded to treatment assignment. The unblinded pharmacist or designee will be instructed not to 
divulge the treatment administered to any subject with the blinded site personnel, study subject or 
blinded study monitor and any other blinded CRO/vendor team members. 
The blind should be broken only if knowledge of the subject’s treatment allocation would 
facilitate specific emergency treatment. Unblinding procedures are provided in the Pharmacy 
Manual. The investigator must contact the Sponsor and/or designee prior to unblinding a subject’s 
treatment assignment. In the event of an emergency when unblinding is necessary and the 
Sponsor and/or designee could not be contacted, the investigator should contact the Sponsor 

 
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and/or designee as soon as possible after the unblinding. Treatment assignment may be provided 
to the study sites/subjects after database lock. 
9.8 
Storage and Accountability 
 
 
 
The Sponsor or designee will supply the study drug. The site will maintain the following records: 
receipt of shipments, dispensation to subjects, and return of partially used, or unused study drug. 
Upon completion or early termination of the study, all unused and partially used IP must be 
returned to the Sponsor (or designated agent), unless the Sponsor authorizes the study site to 
destroy the IP. 
If the Sponsor authorizes the study site to destroy IP, the investigator is responsible to ensure that 
arrangements are made for proper disposal. Written authorization should be issued by the Sponsor 
or designee; procedures for proper disposal should be established according to applicable 
regulations and guidelines; appropriate records of the disposal should be documented and 
forwarded to the Sponsor or designee. 
If the study site is unable to destroy the IP, the unblinded study monitor will facilitate the return 
of unused and/or partially used IP, if required prior to database lock. After database lock, the 
study monitor will close out the site and may complete any returns as needed. 

 
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10 
STUDY PROCEDURES 
The following assessments will be conducted during Screening and at the time points specified in 
the SOE (Section 2.2) and protocol Section 12. Additional procedures deemed necessary as part 
of standard of care may be performed at the investigator’s discretion. All missed visits and any 
performed procedures that are not protocol-specified activities must be documented in the 
subject’s medical record and the appropriate eCRF. 
10.1 
Screening and Informed Consent 
Each subject must sign and date the ICF before participating in any study-specific activities, 
including washout periods to screen for the study. 
After the ICF is signed, the subject enters the Screening Period. Each subject will be assigned a 
unique subject identification number by IWRS at Screening.  
The subject number, assigned at the time of Screening, will be used to identify the subject during 
the study and must be used on all study documentation related to that subject. The subject 
identification number will remain constant throughout the entire study and must not be changed 
after initial assignment. Each study site will maintain a list identifying all subjects by subject 
identification number and subject initials. 
After completing the Screening Period, the subject will be evaluated by the investigator to 
confirm eligibility. A subject is considered enrolled when the investigator decides that all of the 
eligibility criteria are met. The investigator will document this decision and date in the subject’s 
medical record. Screen failure subjects will be entered into the eCRF. Investigators will maintain 
a Screening log of all potential study subjects that includes limited information about each 
candidate, including dates of Screening and procedures, and the outcome of Screening process 
(eg, enrolled into the study, reason for ineligibility, or withdrawal of consent). 
At Baseline and before any study drug is administered, potential subjects will be reviewed by the 
site to reconfirm their eligibility. If appropriate, repeat assessments can be performed within the 
Screening Period with approval from the Medical Monitor, as needed. 
10.2 
Demographics and Medical/Surgical History 
10.2.1 
Demographics 
Demographic data will be collected, including each subject’s sex, age, race, and ethnicity. 

 
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10.2.2 
Medical and Surgical Histories 
The investigator or designee will collect the subject’s medical and surgical histories, including 
information on the subject’s concurrent medical conditions. All findings will be recorded on the 
medical history eCRF. 
A complete medical history at the Screening Visit will include, but will not be limited to, the 
following information: 
• Date of diagnosis of asthma 
• Current medications 
• Past medications 
• History of hospitalization and intubations for asthma 
• History of allergies 
• History of asthma exacerbations 
The subject’s interval history of asthma exacerbations is to be obtained at every scheduled study 
visit (except Day 4); clinically significant asthma exacerbation is defined as a > 20% decrease in 
AM or PM peak flow measurements sustained for 2 days, a doubling of the inhaled corticosteroid 
dose, initiation of an oral corticosteroid burst for asthma or an emergency department 
visit/hospitalization for asthma. 
A complete surgical history at the Screening Visit will include, but not be limited to, any history 
of upper or lower airway surgeries, such as sinus or laryngeal surgery. An interval surgical 
history is to be obtained at every scheduled study visit (except Day 4 and any unscheduled visits). 
10.3 
Physical Examination 
The investigator or designee will conduct a complete physical examination at Screening and a 
targeted physical examination at selected time points thereafter. 
Physical examination findings prior to the first dose of study drug administration will be recorded 
on the medical history eCRF; clinically significant findings after the first study drug dose will be 
recorded as AEs. 
At a minimum, the complete physical examination should include assessments of the skin, head and 
neck, lungs, cardiovascular (CV) system, abdomen, thyroid, and extremities. A targeted physical 
examination will include assessment of the lungs and any new subject complaints or changes 
from baseline. 

 
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10.4 
Vital Signs 
The following vital sign measurements will be performed: systolic (SBP) and diastolic blood 
pressure (DBP), pulse, respiration rate, and temperature. On dosing days, vital signs will be taken 
pre-dose. Vital signs (except for temperature) will also be periodically monitored for a minimum 
of 30 minutes following the SC administration of study drug. The subject must be seated or in a 
semi-recumbent position in a rested, calm state for at least 3 minutes before vital signs are 
collected. The position selected for a subject should be the same throughout the study and 
documented on the vital signs eCRF. 
Height will be measured without shoes at Screening. 
Weight without shoes will be obtained at Screening. On dosing days, weight will be obtained 
before dosing. The weight at Screening will be used to calculate all study drug doses, unless there 
has been a weight change of ≥ 20% from Screening. 
10.5 
Asthma Clinical Status Assessment 
The investigator and/or designee will conduct an asthma clinical status assessment at specific time 
points, as specified in the SOE. These clinical status assessments will include:   
• Pulmonary function test  
• FeNO level measurement 
• PRO assessment, ACQ-6  
A history of clinically significant asthma exacerbations (defined as a > 20% decrease in AM or 
PM peak flow measurements sustained for 2 days, a doubling of the inhaled corticosteroid dose, 
initiation of an oral corticosteroid burst for asthma or an emergency department 
visit/hospitalization for asthma) will be obtained at each scheduled study visit (other than Day 4) 
and any unscheduled visits. Diary entries that meet the criteria for a clinically significant 
exacerbation should also be recorded in the eCRF. 
10.6 
Pulmonary Function Assessment 
Spirometry will be performed at every visit by the investigator or qualified designee according to 
ATS/European Respiratory Society (ERS) guidelines 
 Spirometry testing should be 
started each day between 6 AM and 12 PM; every effort should be made to conduct spirometry 
testing at the same time at every study visit. Spirometry should be performed before study drug or 
placebo administration. Subjects should refrain from strenuous exercise for a minimum of 
30 minutes prior to spirometry testing and must not use short-acting bronchodilator medication 
within 6 hours, and long-acting bronchodilator medications within 12-24 hours (as determined by 

 
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the regular dosing interval for the specific long-acting bronchodilator medication), prior to 
spirometry testing. If the subject takes these medications within the prohibited timeframe, 
spirometry testing should be rescheduled. 
The subject should rest for at least 15 minutes prior to the test. The subject should be sitting 
during spirometry testing; however, if the subject is unable to sit, then standing is acceptable. 
Spirometry testing should be completed in the same manner (ie, sitting or standing) at every study 
visit. Multiple forced expiratory efforts (at least 3, but no more than 8) will be performed for each 
spirometry session, and the 2 best efforts that meet ATS/ERS acceptability and reproducibility 
criteria will be recorded. The best efforts will be based on the highest FEV1. The maximum 
FEV1 of the 2 best efforts will be used for the analysis. Both the absolute measurement (for FEV1 
and forced vital capacity [FVC]) and the percentage of predicted normal value will be recorded 
using appropriate reference values. The highest FVC will also be reported, regardless of the effort 
in which it occurred (even if the effort did not result in the highest FEV1). Nose clips may be 
used for spirometry; however, if nose clips are used, they should be used consistently for all 
spirometry. 
Post-bronchodilation (BD) spirometry testing, when performed, will be assessed after the subject 
has induced maximal BD using a short-acting beta agonist (SABA), such as albuterol (90 μg 
metered dose) or salbutamol (100 μg metered dose) or equivalent, with a spacer device for a 
maximum of 8 total puffs 
 according to ATS/ERS guidelines (Miller 2005), a 
dose of 400 µg salbutamol/albuterol or lower is recommended for the reversibility test. The same 
number of puffs (ie, 4, 6, or 8 puffs) and post-BD maneuvers should be used each time post-BD 
spirometry testing is performed. 
10.7 
FeNO Assessment 
The level of FeNO will be measured in each subject at every study visit (other than Day 4) using a 
standardized single-breath FeNO (American Thoracic Society; ATS, 2005) test. FeNO testing 
must be completed before spirometry is performed. In addition, subjects should not eat or drink 
within ≤ 1 hour prior to FeNO measurement. 
The subject should be sitting during FeNO testing; however, if the subject is unable to sit, then 
standing is acceptable. FeNO testing should be completed in the same manner (ie, sitting or 
standing) at every study visit using the same equipment. Subjects are to inhale to total lung 
capacity through the NIOX VERO® Airway Inflammation Monitor, then exhale for 10 seconds at 
50 mL/sec (assisted by visual and auditory cues). The obtained value will be recorded and the 
process repeated, for a total of 2 measurements. The 2 measurements will be printed to serve as a 
source document.  

 
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10.8 
Home Peak Flow Testing 
Home peak flow testing for peak expiratory flow rate (PEFR) will be performed twice daily, in 
the morning upon awakening and in the evening before bedtime, using a peak flow meter. PEFR 
will be recorded during the Screening, Treatment, and Safety Follow-up Periods in the eDiary. 
PEFR measurements should be taken at least 6 hours after the last dose of SABA rescue 
medication. Subjects should perform 3 successive peak flow maneuvers while the subject is 
sitting or standing, but the subject should be in the same position at every testing. The highest of 
the 3 values should be captured for each time point. At each study visit, the investigator or 
authorized delegate will check the subject’s compliance with the peak flow measurements and 
confirm that the subject is using the peak flow meter correctly. 
10.9 
Measurement of Patient-reported Outcomes 
10.9.1 
Asthma Daily Diary 
The subject’s Asthma Daily Diary (eDiary) will be provided at Screening and includes the 
following daily assessments: asthma symptoms; peak expiratory flow rate measurements; use of 
controller and rescue medication; nighttime awakening due to asthma; and asthma-related activity 
limitations. The eDiary will be completed each morning and evening. Triggers will alert subjects 
to signs of worsening of asthma, and they will be instructed to contact their investigator. 
10.9.2 
Asthma Control Questionnaire-6 
The ACQ-6 is a patient-reported questionnaire that assesses asthma symptoms (ie, nighttime 
waking, symptoms on waking, activity limitation, shortness of breath, and/or wheezing) and daily 
rescue bronchodilator use during the past week 
 Questions are equally weighted 
and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score is the 
mean of the responses. Mean scores of ≤ 0.75 indicate well-controlled asthma, scores between 
0.75 and ≤ 1.5 indicate partly controlled asthma, and a score > 1.5 indicates uncontrolled asthma 
 individual changes of at least 0.5 are considered clinically meaningful. The 
subject’s ACQ-6 score will be assessed at every study visit prior to pulmonary function and FeNO 
assessments.  
10.10 12-Lead Electrocardiography 
The subject must be in a seated, semi-recumbent, or supine position in a rested, calm state for at 
least 10 minutes before ECG assessment is performed. Each 12-lead ECG should be performed 
prior to blood draws, dosing (if applicable), or other invasive procedures. 

 
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A single ECG will be recorded using the equipment provided by the Sponsor designee. The 
investigator or designated study site physician will review, sign, and date all ECGs.  
Any clinically significant abnormal ECG findings will be recorded as an AE. 
10.11 Clinical Laboratory Tests 
10.11.1 
Safety Laboratory Tests 
Blood samples will be collected according to the SOE (Section 2.2), protocol Section 12, and 
below. All safety laboratory tests will be performed at the central laboratory. Samples will be 
collected pre-dose on study dosing days. Repeat laboratory testing will not be required if a test 
was already performed within the specified time window for collection. Samples may be analyzed 
for the tests outlined in this protocol and for any additional tests necessary to ensure each 
subject’s safety. These may include, but are not limited to, investigation of unexpected results. 
Subjects will be in a seated, semi-recumbent, or supine position during blood collection.  
During the Treatment Period, ALC must be monitored by the investigator within 7 days prior to 
dosing (Section 9.3.2). 

 
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10.11.2 
Central Laboratory Tests 
Validated assays will be used for analysis of serum samples for determination of EQ001 and 
treatment-emergent anti-EQ001 antibodies (anti-drug antibody [ADA]) concentrations. Collection 
procedures are described in the study Laboratory Manual. 
10.11.2.1 Pharmacokinetics 
Serum will be assayed for EQ001 concentrations using a validated assay. The PK samples will be 
collected at time points specified in the SOE; the PK samples should be obtained after the ECG is 
recorded. 
10.11.2.2 Anti-Drug Antibody and Neutralizing ADA 
Serum samples will be obtained for detection of ADA against EQ001 at the time points specified 
in the SOE, and, if required, a neutralizing ADA (NAB) assay will be performed on the same 
samples. Samples will be taken on Study Days 1, 29, and 57 (pre-dose), and on Study Day 85 or 
ET. 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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11 
ADVERSE EVENTS 
An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease or any worsening of a pre-existing condition temporally 
associated with the use of a study drug, whether or not related to study drug. The AEs that occur 
after the first dose of EQ001 or during the study treatment and safety follow-up periods will be 
documented on the AE eCRF. The investigator will assess AE severity and the causality 
relationship of the AE to study drug. The investigator will treat the subject as medically required 
to ensure the subject’s safety.  
Laboratory values that are outside the laboratory reference range should be reported as AEs only 
if the investigator considered those AEs to be clinically significant. 
From the time of signing the ICF through the first study drug administration, all SAEs and 
nonserious AEs related to protocol-mandated procedures will be recorded on the SAE/AE eCRF. 
All other untoward medical occurrences observed during Screening, including exacerbation or 
changes in the medical and surgical history, will be captured on the medical and surgical history 
eCRF. Details on recording and reporting AEs are provided below. All AEs will be captured 
through Study Day 85 or the ET Visit. 
Investigators should use their clinical judgment to determine whether a subject is to be withdrawn 
due to an AE. In the event the subject requests to withdraw from study-related treatment or the 
study due to an AE, the subject should be asked to return for all remaining study visits through 
Study Day 85. In the event a subject is withdrawn from study, an ET Visit should be completed. 
All subjects experiencing AEs, including clinically significant abnormal laboratory values, 
whether or not associated with use of the study drug, must be monitored until the condition 
(1) returns to normal, (2) returns to the subject’s baseline, (3) the investigator determines the AE 
has reached a stable outcome and is no longer clinically significant, or (4) the subject is 
considered lost to follow-up. 
11.1 
Severity 
All AEs, both serious and nonserious, will be assessed for severity using the NCI CTCAE v 5.0. 
The CTCAE scale includes unique clinical descriptions of AEs categorized by anatomy and/or 
pathophysiology. Reference the following website: 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Re
ference_8.5x11.pdf 

 
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The CTCAE scale displays Grades 1 through 5 with unique clinical descriptions of severity for 
each AE (including abnormal laboratory values), based on this general guideline provided in the 
scale. For AEs not covered by CTCAE, the conventional definition of severity will be used, as 
follows:  
• Grade 1 (mild) AE: Minor; no specific medical intervention; marginal clinical relevance.  
• Grade 2 (moderate) AE: Minimal intervention; local intervention; noninvasive intervention. 
• Grade 3 (severe) AE: Significant symptoms requiring hospitalization or invasive intervention. 
• Grade 4 (life-threatening or disabling) AE: Complicated by acute, life-threatening 
complications; need for intensive care or emergent invasive procedure. 
• Grade 5: Fatal AE. 
11.2 
Causality Assessment 
The investigator or qualified subinvestigator is responsible for assessing and assigning the 
causality relationship of the event to study drug using clinical judgment and the following 
categories of relatedness: 
• Related: There is at least some possibility that the AE could be related to study drug 
administration. 
• Not related: There is a high degree of certainty that the AE is NOT related to study drug 
administration. 
The investigator or qualified subinvestigator is also responsible for assessing and assigning the 
causality relationship of the event to study-related procedures (eg, invasive procedures, such as 
venipuncture) using clinical judgment and the following categories of relatedness: 
• Related: There is at least some possibility that the AE could be related to study drug 
administration. 
• Not related: There is a high degree of certainty that the AE is NOT related to study drug 
administration.  
In making a causality assessment of an AE, it should be considered as to whether or not the AE is 
expected to occur due to the underlying disease, based on the investigator’s clinical experience in 
managing moderate-to-severe uncontrolled asthma (Section 10.5). 
11.3 
Clinical Laboratory Adverse Events 
The investigator is responsible for reviewing the results of all laboratory tests as they become 
available and determining whether an abnormal value in an individual subject is a clinically 
significant change from the subject’s baseline value(s). The investigator may repeat the laboratory 

 
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test or request additional tests to verify the results of the original laboratory tests. In general, 
abnormal laboratory findings without clinical significance (based on the investigator's judgment) 
are not to be recorded as AEs. However, laboratory value changes that require treatment or 
adjustment in current therapy are to be considered AEs. When applicable, clinical sequelae (not 
the laboratory abnormality) are to be recorded as the AE. 
11.4 
Serious Adverse Events 
A serious adverse event (SAE) is defined as any AE occurring at any dose that results in any of 
the following outcomes: 
• Death 
• Life-threatening AE (Note: A life-threatening AE is one that, in the view of the investigator 
places the subject at immediate risk of death from the reaction as it occurred) 
• Hospitalization or prolongation of existing hospitalization 
• A persistent or significant disability/incapacity 
• A congenital anomaly/birth defect. 
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 medical events include blood dyscrasias or 
convulsions that do not result in subject hospitalization, or the development of drug dependency 
or drug abuse. 
An unexpected AE is defined as any adverse event for which the specificity or severity is not 
consistent with the AE profile in the current EQ001 Investigator’s Brochure. 
All SAEs, regardless of cause(s) or causal relationship to study drug, must be reported within 
24 hours to the study Sponsor and/or designee. 
11.5 
Reporting Adverse Events 
11.5.1 
Reporting Procedures for Nonserious Adverse Events 
The investigator is responsible for ensuring that all AEs observed by the investigator or designee 
or reported by the subject are reported using the AE eCRF. 
The investigator will assign the following AE attributes: 
• AE diagnosis or syndrome(s), if known (if not known, signs or symptoms) 
• Dates of onset and resolution (if resolved) 

 
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• Severity 
• Causality relationship to study drug or study-related procedures  
• Action taken 
• Outcome 
Follow-up of nonserious AEs will continue through the last day on the study and/or until a 
definitive outcome (eg, resolved, resolved with sequelae, lost to follow-up) is achieved. 
When a subject is withdrawn from the study because of a nonserious AE, the Sponsor and/or 
designee must be notified by email or phone within 48 hours. 
11.5.2 
Reporting Procedures for Serious Adverse Events 
The investigator is responsible for ensuring that all SAEs observed by the investigator or reported 
by the subject are promptly assessed and reported to the Sponsor and/or designee. The 
investigator must assess the causality relationship of the SAE to study drug or any study-related 
procedure. 
The procedures for reporting SAEs are as follows: 
• Record the SAE on the AE eCRF and complete the Serious Adverse Event Report form. 
• Within 24 hours of the investigator’s knowledge of the event, enter via the eCRF the SAE 
Report form to the attention of the Sponsor and/or designee. Additional contact numbers and 
AE/SAE reporting instructions will be provided in the Study Manual. 
• For fatal or life-threatening events, also email and/or fax redacted copies of hospital case 
reports, autopsy reports, and other documents, when requested and applicable. Transmission 
of such documents should occur with personal subject details de-identified, without losing the 
traceability of a document to the subject identifiers. Transmission of the initial report of the 
event should not be delayed in order to include these additional documents. 
• The Sponsor or/or designee may request additional information from the investigator to 
ensure the timely completion of accurate safety reports. 
The investigator must take all necessary therapeutic measures for resolution of the SAE. Any 
medications or therapies necessary for treatment of the SAE must be recorded in the event 
description section of the SAE form and the concomitant medication eCRF. 
Follow-up of SAEs will continue through the last day on the study and/or until a definitive 
outcome (eg, resolved, resolved with sequelae, lost to follow-up, fatal) is achieved. 
While pregnancy is not considered an AE, all cases of fetal drug exposure via a maternal parent as 
study subject or pregnancy of a partner of a male study subject will be reported immediately to 

 
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the Sponsor or its designee. Information related to the pregnancy must be documented on a 
Pregnancy Confirmation and Outcome Form, provided by the Sponsor or its designee, and the 
pregnancy should be followed until a definitive outcome has been determined. 
The Sponsor or its designee will report SAEs as required to regulatory authorities and 
investigators in compliance with all reporting requirements, according to local regulations and 
International Council for Harmonisation (ICH) Good Clinical Practice (GCP). 
The investigator will notify the appropriate Independent Ethics Committee (IEC) of SAEs 
occurring at the study site and other AE reports received from the Sponsor, in accordance with 
local requirements. The investigator or designee at each study site is responsible for submitting 
safety reports (initial and follow-up) and other safety information (eg, in the revised EQ001 
Investigator’s Brochure) to the IEC and/or other applicable regulatory authorities for retaining a 
copy in the study files. 
 
 
 
 
 
 
 

 
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13 
PLANNED STATISTICAL METHODS 
A detailed description of data analysis and statistical methods to be used will be outlined 
separately in the SAP. 
13.1 
General Considerations 
Data will be summarized using descriptive statistics (n, mean, median, standard deviation, 
minimum, maximum) for continuous variables and frequencies and percentages for discrete 
variables. All data summaries will be displayed by cohort and by treatment group (EQ001 or 
placebo). A total column for treated cohorts separated by treatment group will also be included. 
Baseline values of variables are considered the last available non-missing value prior to receiving 
any study drug. By-subject listings of the data will also be provided. All data summaries and 
listings will be produced using the SAS® software, version 9.3 or higher. 
 
 
 
 
 
 
13.3 
Analysis Populations 
13.3.1 
Safety Population 
The safety population consists of all subjects who receive any study drug.  
13.3.2 
Pharmacokinetic Analysis Population 
The pharmacokinetics population consists of those subjects in the safety population who have at 
least 1 measurable post-EQ001 exposure concentration. 
 
 
 
 
13.3.4 
Efficacy Population 
The efficacy population consists of those subjects in the safety population who have at least 1 
post-treatment clinical activity assessment. 

 
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13.4 
Subject Disposition 
Subject disposition data will be summarized and will include the number and percent of enrolled 
subjects; number and percent of subjects initiating and completing treatment; and number and 
percent of subjects discontinuing treatment and discontinuing the study, further broken down by 
the reasons for discontinuation. Subject enrollment will also be summarized by study site. A 
summary of major protocol deviations will be tabulated for each cohort and cohorts combined by 
treatment group. 
13.5 
Demographics and Baseline Characteristics 
Demographics and other baseline characteristics will be summarized for the subjects in the safety 
population. Demographic data will include age, gender, race, and ethnicity. Baseline 
characteristics data will include (but not be limited to) total serum IgE, FeNO, ACQ-6, and PFT 
(FEV1 absolute, FVC, FEV1/FVC ratio, and FEV1 %) with bronchodilator reversibility. Medical 
history data will include (but not be limited to) time from diagnosis of asthma to Screening, prior 
and current medications used for asthma control, history of biologic therapy use for asthma 
control, hospitalizations, and intubations. 
 
 
 
 
 
 
 
 
13.7 
Safety Analyses 
All safety data summaries will use the safety population. 
The number and percent of subjects experiencing any DLTs will be presented by cohort. A listing 
of DLTs will also be provided. 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA, 
v 20.1, or the current version) and will be graded by the investigator using the CTCAE v 5.0 or 
the current version. Subject incidence of TEAEs, treatment-emergent serious AEs (TESAEs), 
TEAEs leading to treatment discontinuation and TEAEs with an outcome of death will be 
summarized by SOC and preferred term (PT). Adverse events will also be further summarized by 

 
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worst severity grade and relationship to study drug. 
 
  
Clinical laboratory data will be summarized descriptively, these summaries will include observed 
values at collection time points and their changes from baseline. All laboratory parameters that 
can be graded using the CTCAE will be graded. For selected parameters, following summaries 
may be produced: 
• Worst post-baseline severity grade 
• Shift summary of baseline grade to worst post-baseline severity grade. 
Safety evaluations may also include changes in the subject’s physical examination findings, vital 
signs, and 12-lead ECG findings. 
 
 
 
 
 
13.9 
Efficacy Analyses 
All efficacy analyses will use the Efficacy population. Following efficacy data summaries will be 
produced by cohort. 
Change from baseline in FeNO, serum total IgE, PFT (FEV1) and ACQ-6 will be assessed at 
specific data collection time points, as described in the SOE (Section 2.2). Number and percent of 
subjects showing an improvement of ≥ 0.5 points (a minimally important difference) in ACQ-6 
score will also be tabulated. Percent changes will be assessed over time in AM and PM peak flow 
measures and changes in diurnal variation of peak flow. Use of concomitant medications will also 
be assessed, specifically the number and percent of subjects with a need for rescue medications 
prior to each assessment time point will be tabulated. If data permit, the time to first exacerbation 
(of any severity) will be summarized and plotted using the Kaplan-Meier method, and further, 
annualized rates of asthma exacerbations (of any severity) will be calculated by study drug dose 
to inform future study designs. All efficacy data will be provided in a data listing. 
 

 
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14 
ADMINISTRATIVE CONSIDERATIONS 
14.1 
Investigator Responsibilities 
The investigator is responsible for complying with all regulatory requirements relating to 
performing clinical research with an IP. The investigator is responsible for ensuring that the 
investigation is conducted according to the signed investigator Agreement (FDA Form 1572, or 
equivalent), the approved protocol, and applicable regulations for protecting the rights, safety, and 
welfare of study subject under the investigator's care. The investigator is additionally responsible 
for the control of IP and for providing accurate and verifiable data to the Sponsor. 
The investigator must obtain the written informed consent of each subject before participation in 
the study. The investigator must assure initial and continuing review of the study by an IEC that 
complies with applicable national and local regulations.  
The investigator will ensure adequate documentation of the training of research study personnel 
for conduct of the study, including qualifications, experience, and study role. 
The investigator will be given a copy of the most current version of the EQ001 IB and appropriate 
study process manuals and plans. The investigator is obligated to become familiar with these 
documents prior to initiation of the study. 
Other investigator responsibilities relative to the IEC include, but are not limited to, the 
following: 
• Submit to the IEC for review any advertisements that will be used to recruit subjects, as 
applicable 
• Submit all protocol amendments, revisions of the Investigator’s Brochure, or revisions of the 
Informed Consent to the IEC for review 
• If Sponsor notifies the investigator about SAEs reported in other studies associated with this 
IP, report that information to the IEC if required per local regulations 
• Provide the IEC with any other information it requests before or during the conduct of the 
study 
• Report to the IEC all adverse drug reactions that are serious, unexpected, and related to IP as 
per local regulations 
• Maintain a file of study-related information 
• Update the IEC on a minimum of a yearly basis as per local regulations 

 
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14.2 
Independent Ethics Committee Approval 
Before initiation of the study at a study site, the protocol, including the final version of the ICF, 
the subject information sheet (if applicable), and any other applicable/relevant study 
documentation will be submitted to the appropriate IEC. In addition, the IEC must approve all 
advertising used to recruit subjects for the study prior to use. Written approval of the study 
documentation must be obtained and sent to the Sponsor or its designee before the study drug can 
be released to the investigator.  
The investigator is responsible for informing the IEC of any amendments to the protocol, ICF, 
written information provided to subjects, and/or other procedures in accordance with local 
requirements. The protocol must be re-approved by the IEC upon receipt of amendments, in 
accordance with applicable law. The investigator must send a copy of the approval letter from the 
IEC to the Sponsor or its designee. 
The investigator will report promptly to the IEC and the Sponsor any new information that may 
adversely affect the health or safety of past or current subjects or the conduct of the study, 
including deviations from the protocol or reports of any reportable SAEs, during and for 
one (1) year after study completion.  
The investigator should submit written reports of clinical study status to their IEC annually or 
more frequently if required. A final study notification will also be forwarded to the IEC after the 
study is completed or in the event of premature termination of the study in accordance with the 
applicable regulations. After completion of the study, the investigator will provide the IEC with a 
report of the outcome of the study. Copies of all contacts with the IEC should be maintained in 
the study file. Copies of clinical study status reports (including termination) should be provided to 
the Sponsor. 
14.3 
Ethical Conduct of Study 
The investigator(s) and all parties involved in this study should conduct the study in adherence to 
the ethical principles based on the Declaration of Helsinki, GCP, ICH Guidelines, and the 
applicable national and local laws and regulatory requirements (referred to herein as “applicable 
law”). 
Investigators and all sub-investigators will comply with 21 Code of Federal Regulations (CFR), 
Part 54, 1998 and similar conflicts of interest laws requiring documentation of financial interests 
or arrangements with the Sponsor, or proprietary interests in the drug under study and any other 
local regulatory requirements as applicable. Any required documentation must be provided prior 
to the investigator’s (and any subinvestigator’s) participation in the study. The investigator and 

 
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subinvestigator(s) will notify the Sponsor or its designee of any change in reportable interests 
during the study and for 1 year following completion of the study. Study completion is defined as 
the date when the last subject completes all protocol-defined activities. 
14.4 
Subject Information and Consent 
Prior to conducting any study-related procedures, the investigator must obtain written informed 
consent from each subject, in accordance with applicable law. Consent will be documented on a 
written ICF. The ICF must be approved both by the Sponsor and by the reviewing IEC prior to 
presenting it to a subject. Each ICF must comply with the ICH GCP Guidelines and applicable 
regulatory requirements.  
Investigators may discuss study availability and the possibility for entry with a potential subject 
without first obtaining consent. However, informed consent must be obtained and documented 
prior to initiation of any procedures that are performed solely for the purpose of determining 
eligibility for research, including withdrawal from current medication(s). The informed consent 
process should take place under conditions where the subject has adequate time to consider the 
risks and benefits associated with his/her participation in the study. The investigator or qualified 
designee must explain to each subject the aims, methods, reasonably anticipated benefits, and 
potential hazards of the study. 
Once appropriate essential information has been provided and fully explained in layman’s 
language to the subject by the investigator (or a qualified designee), the approved ICF will be 
signed and dated by both the subject and the person obtaining consent (investigator or designee), 
as well as by any other parties required by the IEC. The subject will receive a copy of the signed 
ICF; the original will be retained in the study files. The investigator must document the consent 
interview and place the record in the study files. The investigator shall also maintain a log of all 
subjects who sign the ICF and indicate if the subject was enrolled into the study or reason for 
non-enrollment. 
14.5 
Confidentiality 
The investigator must assure that subjects’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties. Only subject initials, age, another unique 
identifier (as allowed by local law) and an identification code will be recorded on any form or 
biological sample submitted to the Sponsor, IEC, or laboratory. Laboratory specimens must be 
labeled in such a way as to protect subject identity while allowing the results to be recorded to the 
proper subject. Refer to specific laboratory instructions (or in accordance with local regulations). 
NOTE: The investigator must keep a Screening log showing codes, names, and addresses for all 

 
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subjects screened and for all subjects enrolled in the study. Subject data will be processed in 
accordance with all applicable regulations. (Some studies may require double-coding of samples). 
The investigator agrees that all information received from the Sponsor, including but not limited 
to the Investigator’s Brochure, this protocol, CRF/eCRF, the study drug, and any other study 
information, remain the sole and exclusive property of the Sponsor during the conduct of the 
study and thereafter. This information is not to be disclosed to any third party (except employees 
or agents directly involved in the conduct of the study or as required by law) without prior written 
consent from the Sponsor. The investigator further agrees to take all reasonable precautions to 
prevent the disclosure by any employee or agent of the study site to any third party or otherwise 
into the public domain. In compliance with applicable law and/or ICH GCP Guidelines, the 
investigator will permit the Sponsor’s representatives and, when necessary, representatives of the 
regulatory authorities, direct access to any medical records relevant to the study for verification of 
study-related procedures and data. Direct access includes examining, analyzing, verifying, and 
reproducing any records and reports that are important to the evaluation of the study. 
Investigators will obtain authorization from the subject to permit access to study-related records, 
including personal information.  
Authorization is required from each subject (ie, specific permission granted by such individual to 
a covered entity for the use or disclosure of an individual's protected health information). The 
investigator and institution must obtain such waiver/authorization in writing from the subject. 
Valid authorization must meet the implementation specifications under the applicable privacy 
laws. Authorization may be combined in the ICF (approved by the IEC), or it may be a separate 
document (approved by the IEC) or provided by the investigator or Sponsor (without IEC 
approval). 
14.6 
Study Initiation 
Before the study drug can be shipped to the study site and before enrollment can begin, all 
applicable documentation and approvals as per local regulations must be in place. 
The Sponsor or designee will notify the site when they are activated.  
14.7 
Case Report Forms and Other Study Records 
The investigator will comply with the requirements for all assessments and data collection for 
each subject, as specified in the protocol. 

 
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During each subject’s visit to the clinic, the investigator or qualified designee will record progress 
notes in the subject’s medical record to document all significant observations. At a minimum, 
these notes will contain the following: 
• Documentation of the informed consent process, including any revised consents. 
• The date of the visit and the corresponding visit or day in the study schedule. 
• General subject status remarks, including any significant medical findings. The severity, 
frequency, and duration of any AEs and the investigator's assessment of relationship to study 
drug must also be recorded. 
• Any changes in concomitant medications. 
• A general reference to the procedures completed. 
In addition, any contact with the subject via telephone or other means that provides significant 
clinical information will also be documented in the progress notes, as described above.   
Data for this study will be captured in electronic eCRFs. Study auditing, data entry, verification 
and validation, and subsequent analysis will be performed by the Sponsor, or its designees, in 
accordance with GCPs and established Standard Operating Procedures. 
Clinical data (including AEs, concomitant medications, and applicable clinical laboratory data) 
will be entered into a database. The creation and validation of the database, data entry, validation, 
and verification will be performed according to 21 CFR and other applicable local regulations. 
The data system includes password protection and internal quality checks, such as automatic 
range checks, to identify data that appear inconsistent, incomplete, or inaccurate. 
14.8 
Study Monitoring 
The Sponsor or designee will assign monitors who will perform on-site monitoring as frequently 
as necessary and in accordance with ICH GCP. 
Source documents and eCRFs will be reviewed at monitoring visits and any findings will be 
discussed with the investigational staff. The Sponsor expects that at monitoring visits study 
documents and staff will be available and a suitable space will be provided for review of the study 
documents. The monitor will meet with the investigator on a regular basis to provide feedback on 
the conduct of the study. 
14.9 
Access to Source Documentation 
The study may be subject to audit by the Sponsor, its designee, or by regulatory authorities. If 
such an audit occurs, the investigator must agree to allow access to required subject records. The 

 
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investigator should notify the Sponsor promptly of regulatory authority audits that are scheduled 
and must forward copies of any findings or audit reports to the Sponsor promptly. 
By signing this protocol, the investigator grants permission to personnel from the Sponsor, its 
representatives, and appropriate regulatory authorities for on-site monitoring and review of all 
appropriate study documentation, as well as on-site review of the procedures employed in data 
collection, where clinically appropriate. 
14.10 Study or Study Site Termination 
The Sponsor may suspend or stop the study at all centers or at specific study centers due to (but 
not limited to) the discovery of an unexpected, serious, or unacceptable risk to the subjects 
enrolled in the study, a decision on the part of the Sponsor to suspend or discontinue development 
of the product, failure of the investigator to enroll subjects into the study at an acceptable rate, 
failure of the investigator to comply with regulatory authority or ICH Guidelines, or submission 
of knowingly false information. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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14.13 Quality Assurance 
Authorized representatives of the Sponsor, a regulatory authority, or IEC may visit the study site 
to perform audits or inspections, including source data verification. The purpose of any such audit 
or inspection is to systematically and independently examine all study-related activities and 
documents to determine whether these activities were conducted, and data were recorded, 
analyzed, and accurately reported according to the protocol, ICH GCP Guidelines, and any other 
applicable regulatory requirements. 
The investigator should contact the Sponsor immediately if contacted by a regulatory agency 
about an inspection. 
It is important that the investigator and relevant personnel are available during the possible audits 
or inspections and that sufficient time is devoted to the process. 
14.14 Retention of Data 
When the study is completed, the investigator must retain the essential documents for as long as 
needed (up to 25 years) to comply with regulatory guidelines and Sponsor requirements. The 
investigator will notify the Sponsor prior to moving or destroying any of the study documents. It 
is the responsibility of the Sponsor to inform the investigator/institution as to when these 
documents no longer need to be retained. The investigator should take measures to prevent any 
accidental or premature destruction of these documents. 
14.15 Study Report and Publications 
A clinical study report (CSR) will be prepared and submitted to the appropriate regulatory agency 
or agencies. The Sponsor will ensure that the report meets the standards set out in the ICH 
Guideline for Structure and Content of Clinical Study Reports (ICH E3). Note that an abbreviated 
report may be prepared in certain cases. 
Investigators in this study may communicate, orally present, or publish in scientific journals or 
other scholarly media only after written consent has been obtained from the Sponsor. 
The investigator will submit to the Sponsor any proposed publication or presentation along with 
the respective scientific journal or presentation forum at least 60 days before submission of the 
publication or presentation.  
No such communication, presentation, or publication will include the Sponsor’s confidential 
information (see Section 14.5). 

 
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The investigator will comply with the Sponsor’s request to delete references to its confidential 
information (other than the study results) in any paper or presentation and agrees to withhold 
publication or presentation for an additional 60 days in order to obtain patent protection if deemed 
necessary.