A Phase IIa, Double-Blind, Single Dose, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Potential Efficacy of LT3001 Drug Product in Subjects With Acute Ischemic Stroke (AIS)
Phase: PHASE2
Conditions: Acute Ischemic Stroke
Sponsor: Lumosa Therapeutics Co., Ltd.

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1 
FINAL CLINICAL STUDY PROTOCOL 
Lumosa Therapeutics Co, Ltd 
Protocol Title: A Phase IIa, Double-Blind, Single Dose, Randomized, Placebo-Controlled Study 
to Evaluate the Safety, Tolerability, and Potential Efficacy of LT3001 Drug Product in 
Subjects with Acute Ischemic Stroke (AIS) 
Protocol Number: LT3001-201 
 
 
 
 
Name of Investigational Product: 
LT3001 drug product 
Phase of Development: 
IIa 
Indication: 
Acute Ischemic Stroke (AIS) 
Sponsor: 
Lumosa Therapeutics 
4th Floor, No. 3-2, Park Street, 
Nangang District, Taipei,  
11503, Taiwan 
Tel: 
+886-2-26557918 
Fax: 
+886-2-26557919 
Protocol Version: 
Version 2.1 
Protocol Date: 
Final 17 February 2020 
-CONFIDENTIAL- 
This document and its contents are the property of and confidential to Lumosa Therapeutics. Any 
unauthorized copying or use of this document is prohibited. 

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INVESTIGATOR SIGNATURE PAGE 
Protocol Title: 
A Phase IIa, Double-Blind, Single Dose, Randomized, Placebo-
Controlled Study to Evaluate the Safety, Tolerability, and Potential 
Efficacy of LT3001 Drug Product in Subjects with Acute Ischemic 
Stroke (AIS) 
Protocol Number: 
LT3001-201 
Confidentiality and Current Good Clinical Practice (GCP)/E6(R2) Compliance 
Statement 
•
I, the undersigned, have reviewed this protocol, including appendices, and I will conduct
the study as described in compliance with this protocol (and amendments), GCP, and
relevant International Council for Harmonisation (ICH) guidelines.
•
I am thoroughly familiar with the appropriate use of the investigational product, as
described in this protocol and any other information provided by Lumosa Therapeutics
including, but not limited to, the current investigator’s brochure (IB).
•
Once the protocol has been approved by the independent ethics committee
(IEC)/institutional review board (IRB), I will not modify this protocol without obtaining
prior approval of Lumosa Therapeutics and of the IEC/IRB. I will submit the protocol
amendments and/or any informed consent form modifications to Lumosa Therapeutics
and the IEC/IRB, and approval will be obtained before any amendments are
implemented.
•
I ensure that all persons or party assisting me with the study are adequately qualified and
informed about the Lumosa Therapeutics investigational product and of their delegated
study-related duties and functions as described in the protocol.
•
I ensure that source documents and trial records that include all pertinent observations on
each of the site’s trial subjects will be attributable, legible, contemporaneous, original,
accurate, and complete.
•
I understand that all information obtained during the conduct of the study with regard to
the subjects’ state of health will be regarded as confidential. No subjects’ names will be
disclosed. All subjects will be identified by assigned numbers on all case report forms,
laboratory samples, or source documents forwarded to the Sponsor. Clinical information
may be reviewed by the Sponsor or its agents or regulatory agencies. Agreement must be
obtained from the subject before disclosure of /subject information to a third party.
•
Information developed in this clinical study may be disclosed by Lumosa Therapeutics to
other clinical Investigators, regulatory agencies, or other health authority or government
agencies as required.

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3 
TABLE OF CONTENTS 
1 
FINAL CLINICAL STUDY PROTOCOL .......................................................................1 
2 
SYNOPSIS ........................................................................................................................1 
3 
TABLE OF CONTENTS ..................................................................................................5 
3.1 
List of In-text Tables ....................................................................................................9 
3.2 
List of In-text Figures ...................................................................................................9 
4 
LIST OF ABBREVIATIONS .........................................................................................10 
5 
INTRODUCTION ...........................................................................................................12 
5.1 
General Information on Acute Ischemic Stroke .........................................................12 
5.2 
Background on LT3001 ..............................................................................................13 
 
Nonclinical Studies ............................................................................................13 
5.2.1
 
Clinical Studies ..................................................................................................16 
5.2.2
5.3 
Clinical Risks/Benefits of LT3001 .............................................................................16 
5.4 
Study Rationale ..........................................................................................................17 
6 
STUDY OBJECTIVES AND ENDPOINTS ..................................................................18 
6.1 
Study Objectives .........................................................................................................18 
 
Primary Objective ..............................................................................................18 
6.1.1
 
Secondary Objectives .........................................................................................18 
6.1.2
6.2 
Study Endpoints..........................................................................................................18 
 
Primary Endpoint ...............................................................................................18 
6.2.1
 
Secondary Endpoints ..........................................................................................18 
6.2.2
6.2.2.1 
Safety and Efficacy Endpoints .....................................................................18 
 
 
7 
INVESTIGATIONAL PLAN .........................................................................................20 
7.1 
Description of Overall Study Design and Plan...........................................................20 
7.2 
Discussion of Study Design........................................................................................20 
7.3 
End of Study ...............................................................................................................21 
8 
SELECTION OF STUDY POPULATION .....................................................................22 
8.1 
Inclusion Criteria ........................................................................................................22 
8.2 
Exclusion Criteria .......................................................................................................23 
8.3 
Rescreening ................................................................................................................24 
8.4 
Study Withdrawal, Removal, and Replacement of Subjects ......................................24 
9 
TREATMENTS ...............................................................................................................26 

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14.6 Interim Analysis .........................................................................................................50 
 
15 
STUDY MANAGEMENT ..............................................................................................52 
15.1 Approval and Consent ................................................................................................52 
 
Regulatory Guidelines ........................................................................................52 
15.1.1
 
Institutional Review Board/Independent Ethics Committee ..............................52 
15.1.2
 
Informed Consent ...............................................................................................52 
15.1.3
15.2 Data Handling .............................................................................................................52 
15.3 Source Documents ......................................................................................................53 
15.4 Record Retention ........................................................................................................53 
15.5 Monitoring ..................................................................................................................54 
15.6 Quality Control and Quality Assurance .....................................................................54 
15.7 Protocol Amendment and Protocol Deviation ............................................................54 
 
Protocol Amendment .........................................................................................54 
15.7.1
 
Protocol Deviations ............................................................................................55 
15.7.2
15.8 Ethical Considerations ................................................................................................55 
15.9 Financing and Insurance .............................................................................................55 
15.10 Publication Policy/Disclosure of Data........................................................................55 
16 
REFERENCES ................................................................................................................56 
17 
APPENDICES .................................................................................................................58 
APPENDIX 1. Contraception Guidelines .............................................................................59 
APPENDIX 2. Institute of Health Stroke Scale (Sample) ....................................................61 
APPENDIX 3. Modified Rankin Scale (Sample) .................................................................65 
 

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3.1 
List of In-text Tables 
Table 10-1.Schedule of Assessments .......................................................................................30 
Table 12-1.Laboratory Assessments ........................................................................................40 
Table 12-2.Classification of Adverse Events by Intensity .......................................................41 
Table 12-3.Classification of Adverse Events by Relationship to Investigational Product ......42 
 
3.2 
List of In-text Figures 
Figure 1. Study Design ...........................................................................................................20 
 
 

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4 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
AE 
adverse event 
AIS 
acute ischemic stroke 
aPTT 
activated partial thromboplastin time 
 
 
 
 
 
 
CI 
confidence interval 
 
 
 
 
 
  
 
 
ECG 
electrocardiogram 
EDC 
electronic data capture 
eCRF 
electronic case report form 
FDA 
Food and Drug Administration 
FIH 
first-in-human 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
 
  
HIPAA 
Health Insurance Portability Accountability Act 
 
 
IB 
investigator’s brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation OR 
intracranial hemorrhage 
 
 
IEC 
independent ethics committee 
INR 
International Normalized Ratio 
IRB 
institutional review board 
ITT 
intent-to-treat 
IV 
intravenous 
 
 
mRS 
modified Rankin Scale 
 
 
NIHSS 
National Institute of Health Stroke Scale 
PK 
pharmacokinetic 
PP 
Per-Protocol 
PT 
prothrombin time 

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Abbreviation 
Definition 
rtPA 
recombinant tissue-type plasminogen activator 
 
 
SAE 
serious adverse event 
sICH 
symptomatic intracranial hemorrhage 
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 
 
 
 
 
 
 
 
 
WOCBP 
women of childbearing potential 
US 
United States 

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5 
INTRODUCTION 
5.1 
General Information on Acute Ischemic Stroke 
Stroke is classically characterized as a neurological deficit attributed to an acute focal injury of 
the central nervous system by a vascular cause.1 Ischemic strokes account for about 87% of all 
strokes; 10% are intracerebral hemorrhage strokes, whereas 3% are subarachnoid hemorrhage 
strokes.2 Annually, 15 million people worldwide suffer a stroke; in the United States (US), on 
average, someone experiences stroke every 40 seconds.2,3 Globally, stroke is the second leading 
cause of death above the age of 60 years and is the leading cause of disability.4,5  
The ultimate result of ischemic cascade initiated by acute stroke is neuronal death along with an 
irreversible loss of neuronal function via direct starvation from lack of glucose, failure of 
adenosine triphosphate production, membrane depolarization, rise in intracellular calcium, and 
free radical production.5,6 Furthermore, free radicals directly damage cells and also initiate other 
reactions that lead to cerebral edema.7 Based on the pathogenesis of ischemic stroke, the 2 main 
aims of the treatment strategies in ischemic stroke are restoration of cerebral blood flow and 
reduction of the harmful effects of ischemia on neurons.5 
Alteplase (Activase®), a recombinant tissue-type plasminogen activator (rtPA), was the first 
medication approved for the treatment of ischemic stroke by the US Food and Drug 
Administration (FDA) in 1996 (BLA 103172/S-1055). Although alteplase has been shown to 
improve the outcome of subjects with acute ischemic stroke (AIS), its use has been limited due 
to the low eligibility rate for this medication. The most common exclusion for alteplase is the 
delay in seeking medical attention; only 22% to 31% of patients with ischemic stroke present to 
an emergency department within the time window approved for rtPA administration, which is 3 
or 4.5 hours after symptom onset.8 In addition, symptomatic intracerebral hemorrhage is the most 
feared complication after intravenous (IV) alteplase; with nearly 5-fold risk even when alteplase 
was given within 3 hours, as shown in a recent meta-analysis of 1779 subjects.8 The time 
window allowed for rtPA treatment varies among countries; for example, FDA did not approve 
the change from 3 hours to 4.5 hours after their review of the trial results and unpublished data 
from alteplase manufacturer.8 Administration later than 4.5 hours is associated with an increased 
risk of mortality, and the risk-benefit ratio has not been established (SIGN 2008).9  
Restoration of the blood supply is essential to minimize the damage caused by the ischemic 
condition, but reperfusion by thrombolytic drugs such as alteplase and angioplasty techniques 
often lead to an increase in the extent of brain injury. This reperfusion injury is thought to be 
caused by the activity of free radicals.10 Although the benefit of alteplase is well established, its 
adverse effects remain the major concerns for the use of the thrombolytic agent. Additionally, 
rtPA also has potential for direct neurotoxicity that is not related to its thrombolytic activity.11 
Due to the abovementioned reasons, the usage rate of alteplase is low, with only approximately 
5% of stroke patients being administered alteplase.12 As such, there is a need to develop 

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treatments that can offer similar efficacy to alteplase but with a lower increase of bleeding and/or 
longer therapeutic window. 
5.2 
Background on LT3001 
LT3001 
 is a novel small molecule designed to have both 
thrombolytic and free radical scavenging activities, which were characterized in various in vitro 
and in vivo models. In vitro studies have shown that LT3001 exhibits substantial anti-oxidation 
activity. In animal studies, LT3001 can restore blood flow, reduce cerebral infarct volume, and 
improve neurological outcome in rodent and non-human primate stroke models, with an apparent 
wider therapeutic time window and a better safety profile than those reported for rtPA. Effect of 
LT3001 on the bleeding time was evaluated in male Institute of Cancer Research (ICR) mice 
using an amputation tail model. The tail bleeding time of mice treated with 
 
LT3001 was comparable to animals that received vehicle control and significantly shorter than 
those treated with rtPA (10 mg/kg). 
LT3001 appears to have both thrombolytic and free radical scavenging effects with minimal risk 
of bleeding and potentially extended treatment time window. Therefore, LT3001 is being 
developed for the treatment of AIS. 
 
Nonclinical Studies 
5.2.1
The nonclinical program for LT3001 included the following: 
• In vitro pharmacology studies to evaluate antioxidant activity, anti-platelet activity, 
 and binding to receptors and critical enzymes; 
• In vivo pharmacology studies to evaluate efficacy in mouse, rat, and monkey models of 
stroke; 
• Good Laboratory Practices (GLP) safety pharmacology studies, involving neurological 
and respiratory in rats, cardiovascular in dogs, an in vitro human Ether-a-go-go Related 
Gene (hERG) assay, and a non-GLP cardiovascular study in monkeys; 
• In vivo pharmacokinetic (PK)/toxicokinetic evaluations in rats, dogs, and mini-pigs; 
• In vitro distribution and metabolism studies using mouse, rat, dog, monkey, mini-pig, and 
human hepatocytes; 
• Acute toxicity studies in rats, dogs, monkeys, and mini-pigs; 
• 14-day repeat-dose GLP toxicity studies in rats and dogs; 
• 6-day repeat-dose GLP toxicity study in mini-pigs;  
• In vitro genotoxicity studies and in vivo genotoxicity evaluation in rats; and 
• In vitro phototoxicity study. 
A summary of noteworthy findings from these nonclinical studies is listed below: 

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• Effect of LT3001 on the bleeding time was evaluated in male ICR mice and was 
comparable to animals that received vehicle control and significantly shorter than those 
treated with rtPA (10 mg/kg). 
• LT3001 showed stronger antioxidant capacity than the known antioxidant control 
substances (Trolox®, L-ascorbic acid, and Edaravone). 
• The interaction of LT3001 and Aspirin was assessed by optical microplate-based assay. 
LT3001 
 showed no effect on Aspirin’s anti-platelet aggregation 
activity. 
• In secondary pharmacodynamic studies, LT3001, 
 had no effect on any of 
the receptors or critical enzymes evaluated. 
• In GLP safety pharmacology studies in vivo, LT3001
 
showed no biologically significant effect in either the central nervous system Irwin test or 
respiratory physiological parameters in rats. 
• In a GLP 
assay in vitro, 
inhibition of mean hERG-mediated potassium currents 
was observed at the highest concentration tested 
 No inhibition was observed  
. 
• In 2 GLP cardiovascular studies in dogs, a decrease in blood pressure and an increase in 
heart rate (with concomitant decreases in RR, PR, and uncorrected QT intervals) were 
observed at LT3001 
 
 
• In a non-GLP cardiovascular study in monkeys, a decrease in blood pressure and an 
increase in heart rate (a compensatory response to decreased blood pressure) were 
observed 
. The effects on 
cardiovascular parameters were all transient and recovered to normal range within a few 
hours. 
• PK studies of LT3001 in rats, dogs, and mini-pigs indicated that LT3001 plasma levels 
increased roughly in proportion to the IV dose
 
with no signs of accumulation after repeated doses. 
• In vitro protein binding studies showed that LT3001 does not bind significantly to human 
serum albumin (HSA) or serum acid alpha-1-glycoprotein (AGP), which are considered 
the most relevant drug carriers in human plasma. 
 
 
• In vitro metabolite identification studies with LT3001 were conducted using plasma and 
following in vitro incubation with hepatocytes from mice, rats, dogs, monkeys, mini-pigs, 
and humans.
 
 
 

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• LT3001 was not phototoxic and showed no genotoxic activity in either the Ames test or 
the chromosomal aberration assay with Chinese Hamster Ovary (CHO) cells. LT3001 did 
not induce micronuclei in rat bone marrow cells. 
• Acute toxicity studies with LT3001 were conducted in rats, dogs, monkeys, and 
mini-pigs, respectively. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• The repeat-dose toxicity of LT3001 was evaluated in a 5-day non-GLP study in dogs 
 14-day GLP repeat-dose (once daily) IV toxicity studies in rats 
 and in dogs 
 and a GLP repeat-dose 
 study in Bama mini-pigs 
. Notable 
LT3001-related findings included swelling and discoloration at the injection site on the 
tail and mild vocalization during dosing in rats; and prolonged capillary refill time, weak 
pulse, rapid respiration, recumbency, decreased activity, and skin redness in dogs. These 
clinical signs subsided or became absent with subsequent dosing. There was no mortality 
reported in either of the 14-day studies or during the dosing period in the 6-day mini-pig 
study (
prior to 
scheduled Day 14 sacrifice, due to a moribund condition). The no observed adverse effect 
levels (NOAELs) were determined 
 
 

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Clinical Studies 
5.2.2
 12 human subjects have been exposed to LT3001 drug product 
 
 in the first-in-human (FIH) Phase 1, single 
ascending dose study (LT3001-101), which was conducted at 1 clinical site in the US. The 
objectives of the study were to evaluate the safety, tolerability, and PK of a single IV infusion of 
LT3001 drug product in healthy subjects. The study is now completed, and the results are used to 
determine the doses to be assessed for a Phase 1 multiple-ascending dose study in healthy 
subjects, and to determine the Recommended Phase 2 Dose of LT3001 drug product to be tested 
in future studies in AIS patients, including this study. 
5.3 
Clinical Risks/Benefits of LT3001 
In the FIH study for LT3001 drug product 
 
involving healthy human volunteers, the LT3001 drug product was safe and well tolerated  
. There were no serious adverse events (SAEs) reported in either cohort. 
There were no adverse events (AEs) reported 
 one subject presented 
with an allergy to medical tape, one subject developed a hematoma that was acquired during IV 
needle removal, and one subject 
 developed a 
headache. All AEs occurred post dosing, were classified as mild in severity, and were resolved. 
The AE of “headache” was considered by the Investigator to be mild in intensity and possibly 
related to the investigational product; the other AEs were considered unrelated. 
Safety data collected in this study also included vital signs (heart rate, blood pressure, respiratory 
rate, and body temperature), electrocardiograms (ECGs), clinical biochemistry, hematology, and 
coagulation/clotting parameters. There were no clinically significant findings in any of the safety 
parameters measured. 
Based on the outcomes of this study and the nonclinical studies, the safety monitoring plan for 
all LT3001 clinical studies will include the following: 
1. Physical examination. 
2. Assessment of vital signs. 
3. Monitoring of injection site reactions. 
4. Clinical laboratory tests including hematology and clinical biochemistry. 
5. Coagulation/clotting parameters, including prothrombin time, activated partial thromboplastin 
time, and thrombin time. 
6. ECG monitoring (single lead). 
7. Stool occult blood assessment. 
 
8. Monitoring of AEs. 

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Overdose 
The dose level of LT3001 drug product will be calculated by the Investigator or a qualified 
designee 
. Since drug accumulation is not anticipated 
due to the short half-life of LT3001 and subjects will only receive LT3001 drug product 
administered by an Investigator or a qualified designee and under close monitoring, it is 
anticipated that the risk of overdose or medication error will be low. 
Any overdose, with or without associated AEs, should be promptly reported by the Investigators 
or designee
 
. Overdoses and medication errors will be documented as protocol deviations and 
communicated to the Study Monitor. 
No specific therapy for overdose of LT3001 drug product exists. In the event of overdose or 
medication error, appropriate standard of care therapy for the subject/patient’s symptoms and 
clinical status will be provided. 
Details regarding known or anticipated benefits and risks, as well as reasonably anticipated AEs 
for LT3001 may be found in the investigator’s brochure (IB). 
5.4 
Study Rationale 
Tissue plasminogen activator (alteplase) is the only approved drug treatment for stroke in the US 
and, per the labeling, must be administered within 3 hours of stroke symptom onset. The 
approved window of administration in some other countries is 4.5 hours of stroke symptom 
onset.  
LT3001 is a novel chemical entity designed to have both thrombolytic and free radical 
scavenging activities, which were characterized in various in vitro and in vivo models. Its 
advantages over IV rtPA include: shorter infusion time, within 24 hours of stroke onset (as 
opposed to 3 hours), better recanalization rate, prevention of reperfusion injury by scavenging 
free radicals, no effect on bleeding time, no evidence of increase in intracranial hemorrhage (as 
seen with IV rtPA), and ease of use. 
This Phase IIa, double-blind, single-dose, randomized, placebo-controlled study is to evaluate 
the safety, tolerability, and potential efficacy of LT3001 drug product in subjects/patients with 
AIS. The safety and potential efficacy outcomes from this Phase IIa study will guide the design 
of future studies in subjects/patients with AIS.  
 

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6 
STUDY OBJECTIVES AND ENDPOINTS 
6.1 
Study Objectives 
 
Primary Objective 
6.1.1
The primary objective of the study is to determine the safety of a single dose 
 of 
LT3001 drug product administered IV in subjects with AIS. 
 
Secondary Objectives 
6.1.2
• To determine the tolerability of a single dose
 of LT3001 drug product 
administered IV in subjects with AIS. 
• To determine the potential efficacy of a single dose
 of LT3001 drug 
product administered IV in subjects with AIS. 
 
 
 
 
6.2 
Study Endpoints 
 
Primary Endpoint 
6.2.1
The primary endpoint of this study is the occurrence of symptomatic intracranial hemorrhage 
(sICH) within 36 hours after dosing -- clinical deterioration defined as an increase in the 
National Institute of Health Stroke Scale (NIHSS) of 4 points or more AND confirmed by 
computed tomography (CT)- or magnetic resonance imaging (MRI)- documented. 
 
Secondary Endpoints 
6.2.2
6.2.2.1 
Safety and Efficacy Endpoints 
The secondary efficacy and safety endpoints are as follows: 
• The occurrence of sICH 
. 
• The occurrence of asymptomatic intracranial hemorrhage (ICH) 
 
. 
• The occurrence of mortality due to intracerebral or other major bleeding complications 
. 
• The occurrence of mortality due to any reason 
 
. 
• The number and severity of AEs 
. 
• The number of subjects with AEs 
. 

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• The occurrence of recurrent stroke 
. 
• Functional outcome 
- 
The frequency and percentage of subjects with each grade on modified Rankin 
Scale (mRS) 
. 
- 
The frequency and percentage of subjects 
. 
• Neurological outcome 
- 
Absolute change in NIHSS 
. 
- 
The proportion of subjects with NIHSS ≤2 
. 
 
 
 
 
 
 
 
 
 
 
 
 
 

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7 
INVESTIGATIONAL PLAN 
7.1 
Description of Overall Study Design and Plan 
This is a multicenter, double-blind, single-dose, randomized, and placebo-controlled prospective 
Phase IIa clinical study, designed to evaluate LT3001 drug product versus placebo/control in 
subjects with AIS. 
There is only one dose of LT3001 drug product
. The dose is based on the results 
from nonclinical studies, the FIH study in healthy human volunteers (LT3001-101), and US FDA 
recommendations. Approximately 24 eligible subjects will be randomized 2:1 to LT3001 drug 
product or placebo. Each eligible subject will receive a single dose of LT3001 drug product or 
placebo within 24 hours after stroke symptoms onset. LT3001 drug product or placebo will be 
administered via a
 IV infusion. The infusion will be stopped if an SAE occurs during 
infusion.  
 
 
 
 
 
The participation for each subject is approximately 92 days from the screening visit (Visit 1) to 
the last visit. The study design is illustrated in Figure 1. The Schedule of Assessments is 
provided in Section 10. 
7.2 
Discussion of Study Design 
For this first study in subjects with AIS, a single-dose placebo-controlled design is chosen. 
Because there is no approved drug treatment for AIS for administration beyond 3 hours of stroke 
onset in the US and beyond 3 to 4.5 hours of stroke onset in Taiwan, a placebo-controlled study 

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will be ethically acceptable in order to evaluate the drug effect objectively. Preliminary efficacy 
will be evaluated by assessing the infarct volume, occurrence of recurrent stroke, functional 
outcome measured by mRS, and neurological outcome measured by the NIHSS. 
The dose and regimen chosen is based on results from the nonclinical studies, FIH healthy 
volunteer study, and US FDA recommendations. 
7.3 
End of Study  
A subject will have fulfilled the requirements for study completion when the subject has 
completed all study periods, including the last scheduled follow-up visit as indicated in the 
Schedule of Assessments (Table 10-1). 
The end of the study will be the last subject’s last visit. 

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8 
SELECTION OF STUDY POPULATION 
Section 7.1 provides information regarding number of subjects planned to be randomized. 
8.1 
Inclusion Criteria 
Individuals must meet all of the following criteria to be included in the study: 
1. Subject or subject’s legal representative consented to participation by signing the 
informed consent form (ICF) after receiving full information about the study. 
2. Subject is aged 18 to 90 years, inclusive, at the time of Screening 
. 
3. Subject has a NIHSS of 4 to 30. 
4. Subject has a clinical diagnosis of AIS within 24 hours after stroke symptoms onset. 
5. 
 
6. Subject is able to receive the investigational product within 24 hours after stroke 
symptoms onset.  
7. Subjects are women of childbearing potential (WOCBP) or men whose sexual partners 
are WOCBP, are able and willing to use at least 1 highly effective method of 
contraception during the study until 3 months after dosing of investigational product.  

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8.2 
Exclusion Criteria 
Individuals meeting any of the following criteria at Screening 
 or Baseline are ineligible 
to participate in this study: 
1. Subject has been treated with rtPA and/or endovascular thrombectomy (EVT) during the 
current AIS. 
2. Subject has a pre-stroke disability that requires help for activities of daily living 
. 
3. Subject has imaging evidence of acute intracranial hemorrhage, intraparenchymal tumor, 
arteriovenous malformations, other central nervous system lesions that could increase the 
risk of bleeding, or aneurysm requiring treatment. 
4. 
 
5. Subject has symptoms of suspected subarachnoid hemorrhage,
. 
6. Subject has generalized seizure
. 
7. Subject has current uncontrolled hypertensio
 
. 
8. Subject has International Normalized Ratio (INR) >1.7, abnormal activated partial 
thromboplastin time (aPTT) or platelet count <100,000/mm3. 
9. Subject has blood glucose concentration <50 mg/dL or >400 mg/dL. 
10. Subject is lactating, pregnant (pregnancy test required for all female subjects), or 
planning to become pregnant during the study.  
11. Subject has received anticoagulants within 48 hours prior to treatment, e.g., direct oral 
anticoagulants (e.g., dabigatran, rivaroxaban, apixaban, edoxaban), low molecular weight 
heparin (e.g., enoxaparin), fondaparinux. 
12. Subject has received oral dual antiplatelet therapy and glycoprotein (GP) IIb/IIIa 
inhibitors within 48 hours prior to treatment. 
13. Subject has had prior AIS, myocardial infarction, or serious head trauma within 90 days 
of Screening 
. 
14. Subject has history of ICH within 90 days of Screening 
. 
15. Subject has had any major surgery within 90 days of Screening 
, e.g., intracranial 
or intraspinal surgery, coronary artery bypass graft, obstetrical delivery, organ biopsy. 
16. Subject with bleeding event within 21 days of Screening
, e.g., gastrointestinal or 
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17. Subject has puncture of noncompressible vessels within 7 days of Screening 
. 
18. Subject has severe hepatic, renal, and/or active infectious disease at Screening 
. 
19. Subject has participated in another investigational study and received investigational 
product within 30 days of Screening 
 or 5 half-lives (whichever is longer). 
20. In the opinion of the Investigator, the subject is not appropriate for the study for any other 
reason. 
8.3 
Rescreening 
Individuals who sign the ICF to participate in the study but who do not subsequently meet all the 
requirements as outlined in the inclusion and exclusion criteria and therefore do not enroll 
(screen failures) may be rescreened if they have another episode of stroke ≥90 days after the 
previous one.  
8.4 
Study Withdrawal, Removal, and Replacement of Subjects 
If a subject discontinues study treatment and is withdrawn from the study for any reason, the 
study site must immediately notify the Medical Monitor (see contact details in Section 12.7.3). 
The date and the reason for study discontinuation must be recorded on the electronic case report 
form (eCRF). Subjects who discontinue early from the study will be asked to return to the study 
site within to complete Early Termination assessments as indicated in the Schedule of 
Assessments (Table 10-1). 
In the event that a subject discontinues prematurely from the study because of a 
treatment-emergent AE (TEAE) or serious TEAE, the TEAE or serious TEAE will be followed 
up until it resolves (returns to normal or baseline values) or stabilizes, or until it is judged by the 
Investigator to no longer be clinically significant. 
Once a subject is withdrawn from the study, the subject may not re-enter the study. 
A subject may voluntarily withdraw or be withdrawn from the study at any time for reasons 
including, but not limited to, the following: 
• unacceptable toxicity or AE. 
• subject withdrawal of consent: at any time, a subject's participation in the study may be 
terminated at his/her request or on the basis of the Investigator’s clinical judgment. The 
reason for subject withdrawal will be noted on the eCRF. 
• intercurrent illness: a condition, injury, or disease unrelated to the primary diagnosis that 
became apparent during treatment and necessitated the subject’s termination from the 
study. 
• general or specific changes in the subject's condition that renders him/her ineligible for 
further treatment according to the inclusion/exclusion criteria. 

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• subject fails to adhere to the protocol requirements (e.g., drug noncompliance, failure to 
return for defined number of visits).  
• lost to follow-up: the subject stopped coming for visits, and study personnel were unable 
to contact the subject 3 times. 
• pregnancy, as indicated in Section 12.7.5. 
Additionally, the Sponsor may stop the study at any time for safety, regulatory, legal, or other 
reasons aligned with Good Clinical Practice (GCP). This study may be terminated at the 
discretion of the Sponsor or any regulatory agency. An Investigator may elect to discontinue or 
stop the study at his or her study site for any reason, including safety or low enrollment. 
 

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Investigators will maintain records that adequately document that the subjects were administered 
the correct study treatment and reconcile the products received from the drug dispensing center. 
Investigational product will not be returned to the Sponsor until accountability has been fully 
monitored. 
Administration of investigational product will be supervised by study site personnel to ensure 
compliance. 
9.5 
Prior and Concomitant Therapy 
 
Prior and Concomitant Medications 
9.5.1
Restricted prior therapies are provided in Section 8.2.  
All medications and other treatments taken by the subject during the study, including those 
treatments initiated before the start of the study, must be recorded on the eCRF. 
Medications taken by or administered to the subject for the time period before Screening 
 will be recorded in the eCRF. After the dosing of investigational product, medication to 
treat minor treatment-emergent illness(es) is generally permitted. After 24 hours of completion 
of investigational product infusion, use of antiplatelet agent(s) will be at the discretion of the 
Investigator. After 24 hours, the following are allowed at the discretion of the Investigator: 
heparin, non-vitamin K antagonist oral anticoagulant such as dabigatran, rivaroxaban, apixaban, 
or other factor Xa inhibitors. Low dose heparin or low molecular weight heparin at a preventive 
dose are allowed from 24 hours after treatment completion and after no intracranial bleeding has 
been confirmed on 24 hours repeat brain imaging.  
Any medication or therapy that is taken by or administered to the subject during the course of the 
study must be recorded in the eCRF. The entry must include the dose, regimen, route, indication, 
and dates of use. 

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10 STUDY PROCEDURES 
Table 10-1 outlines the timing of procedures and assessments to be performed throughout the 
study. Section 12.6 specifies laboratory assessment samples to be obtained. See Sections 11 and 
12 for additional details regarding efficacy assessments and safety assessments, respectively. 
  

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Table 10-1. 
Schedule of Assessments 

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10.1 Informed Consent 
Before performing any study-related procedures, the Investigator or designee will obtain the 
signed ICF from the subject or his/her legally acceptable representative. 
In the event that rescreening occurs (see Section 8.3), the individual is required to sign a new 
ICF and must be assigned a new Subject Number. 
10.2 Study Procedures 
Assessments and corresponding timings are to be performed as outlined in the Schedule of 
Assessments (Table 10-1). Section 12.6 specifies laboratory assessment samples to be obtained.  
 
Efficacy assessments are described in Section 11. Efficacy endpoints include occurrences of 
recurrent stroke, neurological and functional outcomes (via NIHSS and mRS 
 
.  
Safety assessments are described in Section 12 and include bleeding assessment (occurrences of 
sICH and asymptomatic ICH), vital signs, physical and neurological examinations, ECGs, 
laboratory assessments, and AEs.  
 
The Investigator may, at his/her discretion, arrange for a subject to have an unscheduled 
assessment, especially in the case of AEs that require follow-up or are considered by the 
Investigator to be possibly related to the use of investigational product. The unscheduled visit 
page in the eCRF must be completed.  
Study discontinuation procedures are described in Section 8.4. 
Assessments will be done at each visit as detailed in the subsections below. 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 

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11 EFFICACY ASSESSMENTS 
The Schedule of Assessments (Table 10-1) outlines the efficacy assessments to be performed 
throughout the study and their timing. Efficacy endpoints include occurrences of recurrent 
stroke, neurological and functional outcomes (via NIHSS and mRS assessments) 
 
. 
11.1 National Institute of Health and Stroke Scale  
The NIHSS is a systematic assessment tool that provides a quantitative measure of stroke-related 
neurologic deficit. It consists of 11 items, each with a score range of 0 to 2-4, with higher scores 
indicating more deficit/impairment in that specific ability. The total score ranges from 0 (no 
deficit) to 42 (dead). The score and corresponding description for the NIHSS is provided in 
Appendix 2. 
 
 
.  
11.2 Modified Rankin Scale 
The mRS measures the degree of disability or dependence in the daily activities of patients who 
have suffered a stroke. The scale runs from 0 (perfect health without symptoms) to 6 (dead). 
 
 The score 
and corresponding description is provided in Appendix 3. 
 
  
 
 
 
 
 

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12 SAFETY ASSESSMENTS 
Safety assessments (bleeding assessment, vital signs, physical and neurological examinations, 
ECGs, laboratory assessments, and AEs) are to be performed at protocol-specified visits, as 
specified in the Schedule of Assessments (Table 10-1).  
12.1 Bleeding Assessment 
Bleeding assessment will be done by the Investigator or designee and categorized as sICH and 
asymptomatic ICH. The occurrence of sICH and asymptomatic ICH within 36 hours and 7 days 
after dosing will be recorded. 
 
 
 
 
 
 
12.2 Medical History 
Medical history will be recorded at Screening 
. Investigators should document the 
occurrence, signs, and symptoms of the subject’s preexisting conditions, including all prior 
significant illnesses, up to and including 1 year before Screening 
. Additional preexisting 
conditions present at the time when informed consent is given and up to the time of the initiation 
of dosing 
 are to be regarded as concomitant illnesses. Medical history will include 
alcohol consumption and smoking history, if applicable. 
Illnesses first occurring or detected during the study and/or worsening of a concomitant illness 
during the study are to be documented as AEs on the eCRF in accordance with Section 12.7. All 
changes not present at Baseline or described in the past medical history and identified as 
clinically noteworthy must be recorded as AEs. 
Additionally, demographic data will be collected for all subjects and include date of birth or age 
according to applicable regulations, gender, and race/ethnicity. 
12.3 Vital Signs 
Vital signs (body temperature, pulse rate, respiration rate, systolic blood pressure, and diastolic 
blood pressure) will be measured at the visits indicated in the Schedule of Assessments 
(Table 10-1). All vital signs will be measured after the subject has been resting in a supine 
position for at least 5 minutes. Blood pressure measurements are to be taken in the same arm for 
the duration of the study. 
Vital signs measurements will be repeated if clinically significant or machine/equipment errors 
occur. Out-of-range body temperature, pulse rate, respiratory rate, or blood pressure 

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measurements will be repeated at the Investigator’s or designee’s discretion. Any confirmed, 
clinically significant vital sign measurements must be recorded as AEs.  
Body weight (without shoes) will be recorded will be recorded at Screening 
 only. For 
subjects who cannot stand on a scale, bed weight measurement is allowed at the Investigator’s or 
designee’s discretion. 
12.4 Physical and Neurological Examination 
A complete physical examination 
 
 
 will 
be performed at Screening 
. Physical examinations will be performed by a physician. 
 
 
 
  
12.5 12-Lead Electrocardiograms 
A 12-lead, resting ECG will be obtained at the visits indicated in the Schedule of Assessments 
(Table 10-1). 
At Screening
, the Investigator will examine the ECG traces for signs of cardiac disease 
that could exclude the subject from the study. An assessment of normal or abnormal will be 
recorded; if the ECG is considered abnormal, the abnormality will be documented on the eCRF. 
Electrocardiograms will be repeated if clinically significant abnormalities are observed or 
artifacts are present at the Investigator’s or designee’s discretion. 
 
 
12.6 Laboratory Assessments 
Laboratory assessment samples (Table 12-1) are to be obtained at designated visits as detailed in 
the Schedule of Assessments (Table 10-1). 

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Table 12-1. 
Laboratory Assessments 
Blood samples will be analyzed at each site. All laboratory reports must be reviewed, signed, and 
dated by the Investigator or designee. A legible copy of all reports must be filed with both the 
subject’s eCRF and medical record (source document) for that visit. Any laboratory test result 
considered by the Investigator or designee to be clinically significant should be considered an 
AE (clinically significant AEs include those that require an intervention). Clinically significant 
abnormal values occurring during the study will be followed up until repeat test results return to 
normal, stabilize, or are no longer clinically significant. 

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12.7 Adverse Events 
 
Adverse Events 
12.7.1
An AE is any symptom, physical sign, syndrome, or disease that either emerges during the study 
or, if present at Screening 
, worsens during the study, regardless of the suspected cause 
of the event. 
 
 Changes 
in these conditions and new symptoms, physical signs, syndromes, or diseases should be noted 
on the AE eCRF during the rest of the study. Clinically significant laboratory abnormalities 
should also be recorded as AEs. Surgical procedures that were planned before the subject 
enrolled in the study are not considered AEs if the conditions were known before study 
inclusion; the medical condition should be reported in the subject’s medical history. 
Treatment-emergent AEs (TEAEs) are defined as events with onset dates on or after the start of 
the investigational product. 
Subjects will be instructed to report AEs at each study visit. All AEs are to be followed up until 
resolution or a stable clinical endpoint is reached. 
Each AE is to be documented on the eCRF with reference to date of onset, duration, frequency, 
severity, relationship to investigational product, action taken with investigational product, 
treatment of event, and outcome. Furthermore, each AE is to be classified as being serious or 
nonserious. Changes in AEs and resolution dates are to be documented on the eCRF.  
For the purposes of this study, the period of observation for collection of AEs extends from the 
time the subject gives informed consent until the last follow-up visit. Follow-up of the AE, even 
after the date of therapy discontinuation, is required if the AE persists until the event resolves or 
stabilizes at a level acceptable to the Investigator. 
When changes in the intensity of an AE occur more frequently than once a day, the maximum 
intensity for the event should be noted. If the intensity category changes over a number of days, 
then those changes should be recorded separately (with distinct onset dates). 
Specific guidelines for classifying AEs by intensity and relationship to investigational product 
are given in Table 12-2 and Table 12-3. 
Table 12-2. 
Classification of Adverse Events by Intensity 
MILD: An event that is easily tolerated by the subject, causing minimal discomfort, and not interfering with 
everyday activities. 
MODERATE: An event that is sufficiently discomforting to interfere with normal everyday activities. 
SEVERE: An event that prevents normal everyday activities. 
 

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Table 12-3. 
Classification of Adverse Events by Relationship to Investigational Product 
UNRELATED: This category applies to those AEs that are clearly and incontrovertibly due to extraneous 
causes (disease, environment, etc). 
UNLIKELY:  
This category applies to those AEs that are judged to be unrelated to the test drug/study 
procedure but for which no extraneous cause may be found. An AE may be considered unlikely to be related to 
investigational product /procedure if or when it meets 2 of the following criteria: (1) it does not follow a 
reasonable temporal sequence from administration of the test drug /study procedure; (2) it could readily have 
been produced by the subject’s clinical state, environmental or toxic factors, or other modes of therapy 
administered to the subject; (3) it does not follow a known pattern of response to the test drug/study procedure; 
or (4) it does not reappear or worsen when the drug/study procedure is readministered. 
POSSIBLY: This category applies to those AEs for which a connection with the test drug /study procedure 
administration appears unlikely but cannot be ruled out with certainty. An AE may be considered possibly 
related if or when it meets 2 of the following criteria: (1) it follows a reasonable temporal sequence from 
administration of the drug /study procedure; (2) it could not readily have been produced by the subject’s 
clinical state, environmental or toxic factors, or other modes of therapy administered to the subject; or (3) it 
follows a known pattern of response to the test drug /study procedure. 
PROBABLY: This category applies to those AEs that the Investigator feels with a high degree of certainty are 
related to the test drug /study procedure. An AE may be considered probably related if or when it meets 3 of 
the following criteria: (1) it follows a reasonable temporal sequence from administration of the drug /study 
procedure; (2) it could not be reasonably explained by the known characteristics of the subject’s clinical state, 
environmental or toxic factors, or other modes of therapy administered to the subject; (3) it disappears or 
decreases on cessation or reduction in dose (note that there are exceptions when an AE does not disappear 
upon discontinuation of the drug, yet drug-relatedness clearly exists; for example, as in bone marrow 
depression, fixed drug eruptions, or tardive dyskinesia); or (4) it follows a known pattern of response to the test 
drug/study procedure. 
DEFINITELY: This category applies to those AEs that the Investigator feels are incontrovertibly related to test 
drug/study procedure. An AE may be assigned an attribution of definitely related if or when it meets all of the 
following criteria: (1) it follows a reasonable temporal sequence from administration of the drug /study 
procedure; (2) it could not be reasonably explained by the known characteristics of the subject’s clinical state, 
environmental or toxic factors, or other modes of therapy administered to the subject; (3) it disappears or 
decreases on cessation or reduction in dose and recurs with re-exposure to drug (if rechallenge occurs); and (4) 
it follows a known pattern of response to the test drug /study procedure. 
Abbreviation: AE, adverse event. 
 
Serious Adverse Events 
12.7.2
An SAE is any untoward medical occurrence, in the view of either the Investigator or Sponsor, 
that: 
• results in death, 
• is life-threatening, 
• results in inpatient hospitalization or prolongation of existing hospitalization, 
• results in persistent or significant disability/incapacity, and/or 
• is a congenital anomaly/birth defect. 

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Other important medical events that may not be immediately life-threatening or result in death or 
hospitalization, based upon appropriate medical judgment, are considered SAEs if they are 
thought to jeopardize the subject and/or require medical or surgical intervention to prevent one of 
the outcomes defining an SAE. Serious AEs are critically important for the identification of 
significant safety problems; therefore, it is important to take into account both the Investigator’s 
and the Sponsor’s assessment. If either the Sponsor or the Investigator believes that an event is 
serious, the event must be considered serious and evaluated by the Sponsor for expedited 
reporting. 
 
Serious Adverse Event Reporting 
12.7.3
An SAE occurring from the time informed consent is obtained, during the study, or within 
3 months of stopping the treatment must be reported to the 
 Safety and 
Pharmacovigilance group and will be communicated to the Sponsor. Any such SAE due to any 
cause, whether or not related to the investigational product, must be reported within 24 hours of 
occurrence or when the Investigator becomes aware of the event. Notification can be made using 
the dedicated fax line or email 
 Safety and Pharmacovigilance group: 
 
 
 
 
 
If the Investigator contacts the 
 Safety and Pharmacovigilance group by telephone, 
then a written report must follow within 24 hours and is to include a full description of the event 
and sequelae in the format detailed in the SAE reporting form. 
The event must also be recorded on the standard AE eCRF. Preliminary reports of SAEs must be 
followed up by detailed descriptions later on, including clear and anonymized photocopies of 
hospital case reports, consultant reports, autopsy reports, and other documents when requested 
and applicable. SAE reports must be made whether or not the Investigator considers the event to 
be related to the investigational drug. 
Appropriate remedial measures should be taken to treat the SAE, and the response should be 
recorded. Clinical, laboratory, and diagnostic measures should be employed as needed in order to 
determine the etiology of the problem. The Investigator must report all additional follow-up 
evaluations to the 
 Safety and Pharmacovigilance group within 24 hours of 
becoming aware of the additional information or as soon as is practicable. All SAEs will be 
followed up until the Investigator and Sponsor agree the event is satisfactorily resolved. 

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Any SAE that is not resolved by the end of the study or upon discontinuation of the subject’s 
participation in the study is to be followed up until it either resolves, stabilizes, returns to 
baseline values (if a baseline value is available), or is shown to not be attributable to the 
investigational product or procedures. 
 
Suspected Unexpected Serious Adverse Reactions 
12.7.4
Adverse events that meet all of the following criteria will be classified as suspected unexpected 
serious adverse reactions (SUSARs) and reported to the appropriate regulatory authorities in 
accordance with applicable regulatory requirements for expedited reporting: 
• serious 
• unexpected (i.e., the event is not consistent with the safety information in the IB) 
• there is at least a reasonable possibility that there is a causal relationship between the 
event and the study treatment 
The Investigator will assess whether an event is causally related to study treatment. The Sponsor 
 will consider the Investigator’s assessment and determine whether the event 
meets the criteria for being reportable as a 7-day or 15-day safety report. Suspected unexpected 
serious adverse reactions (SUSARs) that are fatal or life-threatening must be reported to the 
regulatory authorities and the independent ethics committee (IEC)/institutional review boards 
(IRBs) (where required) within 7 days after the Sponsor 
 has first knowledge 
of them, with a follow-up report submitted within a further 8 calendar days. Other SUSARs must 
be reported to the relevant regulatory authorities and the IEC/IRBs within 15 calendar days after 
the Sponsor 
 first has knowledge of them. 
The Sponsor 
 is responsible for reporting SUSARs and any other events 
required to be reported in an expedited manner to the regulatory authorities and for informing 
Investigators of reportable events, in compliance with applicable regulatory requirements within 
specific timeframes. Investigators will notify the relevant IEC/IRBs of reportable events within 
the applicable timeframes. 
 
Pregnancy 
12.7.5
Women of childbearing potential (WOCBP) must have a negative pregnancy test at Screening 
. Following administration of investigational product, any known cases of pregnancy in 
female subjects will be reported until the subject completes or withdraws from the study. The 
pregnancy will be reported immediately by faxing/emailing a completed pregnancy report to the 
Sponsor (or designee) within 24 hours of knowledge of the event. The pregnancy will not be 
processed as an SAE; however, the Investigator will follow up with the subject until completion 
of the pregnancy and must assess the outcome in the shortest possible time but not more than 
30 days after completion of the pregnancy. The Investigator should notify the Sponsor (or 
designee) of the pregnancy outcome by submitting a follow-up pregnancy report. If the outcome 
of the pregnancy involved spontaneous or therapeutic abortion (any congenital anomaly detected 

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in an aborted fetus is to be documented), stillbirth, neonatal death, or congenital anomaly, the 
Investigator will report the event by faxing/emailing a completed pregnancy report form to the 
Sponsor (or designee) within 24 hours of knowledge of the event. 
If the Investigator becomes aware of a pregnancy occurring in the female partner of a male 
subject participating in the study, the pregnancy should be reported to the Sponsor (or designee) 
within 24 hours of knowledge of the event. Information regarding the pregnancy must only be 
submitted after obtaining written consent from the pregnant partner. The Investigator will 
arrange counseling for the pregnant partner by a specialist to discuss the risks of continuing with 
the pregnancy and the possible effects on the fetus. 
Upon discontinuation from the study, only those procedures that would not expose the subject to 
undue risk will be performed. The Investigator should also be notified of pregnancy occurring 
during the study but confirmed after completion of the study. In the event that a subject is 
subsequently found to be pregnant after inclusion in the study, any pregnancy will be followed to 
term, and the status of mother and child will be reported to the Sponsor after delivery. 
 
Overdose 
12.7.6
The dose level of LT3001 drug product will be calculated by the Investigator or a qualified 
designee 
. Since drug accumulation is not anticipated 
due to the short half-life of LT3001 and subjects will only receive LT3001 drug product 
administered by an Investigator or a qualified designee and under close monitoring, it is 
anticipated that the risk of overdose or medication error will be low. 
Any overdose or medication errors, with or without associated AEs, should be promptly reported 
by the Investigators or designee to 
 Safety and Pharmacovigilance (see contact 
details in Section 12.7.3). Overdoses and medication errors will be documented as protocol 
deviations and communicated to the Study Monitor. 
No specific therapy for overdose of LT3001 drug product exists. In the event of overdose or 
medication error, appropriate standard of care therapy for the subject’s symptoms and clinical 
status will be provided. 
 

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14 STATISTICAL ANALYSIS 
A statistical analysis plan (SAP) will be prepared after the protocol is approved. This document 
will provide further details regarding the definition of analysis variables and analysis 
methodology to address all study objectives. The SAP will serve as a compliment to the protocol 
and supersedes it in case of differences. 
The statistical evaluation will be performed using SAS® software version 9.4 or higher 
(SAS Institute, Cary, NC). All data will be listed, and summary tables will be provided. 
Summary statistics will be presented by treatment group and overall. For continuous variables, 
data will be summarized with the number of subjects (N), mean, standard deviation, median, 
minimum, and maximum by treatment group. For categorical variables, data will be tabulated 
with the number and proportion of subjects for each category by treatment group. 
14.1 Determination of Sample Size 
Approximately 24 eligible subjects will be randomized 2:1 to LT3001 drug product or placebo. It 
is planned to have 24 subjects in the Evaluable Population, after which enrollment will stop. 
14.2 Analysis Populations 
Enrolled Population 
The enrolled population will include all individuals who sign the ICF. 
Intent-to-Treat (ITT) Population  
The ITT population will include all subjects who are randomized, irrespective of any deviation 
from the protocol or premature discontinuation. The treatment group assignment will be 
designated according to initial randomization. The ITT population will serve as the primary basis 
for the analysis of efficacy. 
  
 
 
Per-Protocol (PP) Population 
The PP population will comprise all ITT subjects who complete study procedures through 
Day 90 without a major protocol deviation. The PP population will also be used for the analysis 
of efficacy. 
 
 
 

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Safety Population 
The safety population will include all randomized subjects who receive at least 1 dose of 
investigational product. The treatment group assignment in this population will be defined by the 
treatment actually received. This population will be used for the analysis of safety. 
14.3 Safety Analysis 
 
Analysis of Primary Safety Endpoint 
14.3.1
The frequency and proportion of symptomatic intracranial hemorrhage (sICH) within 36 hours of 
dosing will be reported by treatment group and overall. Comparisons by treatment group will be 
made
 
 
Analysis of Secondary Safety Endpoints 
14.3.2
14.3.2.1 
Occurrence of sICH 
 
The frequency and proportion of sICH
 will be reported by treatment 
group and overall. Symptomatic ICH will not be imputed for subjects missing either NIHSS 
score or CT/MRI examination so the denominator will be the number of subjects in whom sICH 
could be assessed. Comparisons of treatment group will be made
 
no formal adjustment for multiple comparisons will be made. 
14.3.2.2 
Occurrence of Asymptomatic ICH
 
The frequency and proportion of asymptomatic ICH at each time point will be reported by 
treatment group and overall. Intracranial hemorrhage will not be imputed for subjects missing 
either NIHSS score or CT/MRI examination at each visit so the denominator will be the number 
of subjects in whom ICH could be assessed. Comparisons of treatment group will be made
 
 no formal adjustment for multiple comparisons will be made. 
14.3.2.3 
Occurrence of Mortality Due to Intracerebral or Other Major Bleeding 
Complications 
 
The frequency and proportion of subjects who have died due to intracerebral or other major 
bleeding complications at each time point will be reported by treatment group and overall. 
 
14.3.2.4 
Occurrence of Mortality Due to Any Reason 
 
 
The frequency and proportion of subjects who have died due to any reason will be reported at 
each time point by treatment group and overall. Comparisons of treatment group will be made 
 no formal adjustment for multiple comparisons will be made. 

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The NIHSS is a brief and reliable stroke deficit assessment scale composed of 11 components 
and the numbers of grades for each component vary; however, for each component, a score of 0 
is defined as normal while higher scores indicate increasing severity of impairment.  
 
 Data missing on 
the visit level will not be imputed, and no statistical inferences will be performed.  
The proportion of subjects with NIHSS of 0-2 points will be presented by treatment group  
 
 
Modified Rankin Scale 
14.4.4
The mRS is a global disability scale that measures the overall independence of stroke patients. 
The level of disability following a stroke is assessed via a 7-point scale (0-6), where 0 is no 
limitation or symptom and 6 is death. It is expected that all subjects will have a baseline of 1 (no 
significant disabilities despite symptoms) up to 5 (severe disability, bedridden, incontinent, and 
requiring constant nursing care and attention). 
For each shift table, missing values will not be included, so the denominator for percentages will 
be the number of subjects with a mRS score at both Baseline and the visit. No missing values 
will be imputed and no statistical inference will be performed on the shift tables. 
The frequency and percentage of subjects with each grade on the mRS 
 
will be presented by treatment group. 
The frequency and percentage of subjects who achieve a score of 0 to 2 
 
 will be presented by treatment group. 
Comparisons by treatment group will be made 
 
. No formal adjustment for multiple comparisons will 
be made. 
 
 
 
14.6 Interim Analysis  
No interim analyses are planned. 
 
 
 
 
 

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15 STUDY MANAGEMENT 
15.1 Approval and Consent 
 
Regulatory Guidelines 
15.1.1
This study will be conducted in accordance with the accepted version of the Declaration of 
Helsinki and/or all relevant regulations, as set forth in Parts 50, 56, 312, Subpart D, of Title 21 of 
the United States Code of Federal Regulations (CFR), in compliance with International Council 
for Harmonisation (ICH) and GCP guidelines, and according to the appropriate regulatory 
requirements in the countries where the study is conducted. 
 
Institutional Review Board/Independent Ethics Committee 
15.1.2
Conduct of the study must be approved by an appropriately constituted IEC/IRB. Approval is 
required for the study protocol, protocol amendments (if applicable), IB, ICFs, recruitment 
material, and subject information sheets and other subject-facing material. 
 
Informed Consent 
15.1.3
For each study subject, written informed consent will be obtained before any protocol-related 
activities. As part of this procedure, the Investigator or designee must explain orally and in 
writing the nature of the study, its purpose, procedures, expected duration, alternative therapy 
available, and the benefits and risks involved in study participation. The subject should be 
informed that he/she may withdraw from the study at any time, and the subject will receive all 
information that is required by local regulations and guidelines for ICH. The Investigator will 
provide the Sponsor or its representative with a copy of the IEC-/IRB-approved ICF(s) before the 
start of the study. 
15.2 Data Handling 
Any data to be recorded directly on the eCRFs (to be considered as source data) will be 
identified at the start of the study. Data reported on the eCRF that are derived from source 
documents should be consistent with the source documents, or the discrepancies must be 
explained. See also Section 15.3.  

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Clinical data will be entered by site personnel on eCRFs for transmission to the Sponsor. Data on 
eCRFs transmitted via the web-based data system must correspond to and be supported by source 
documentation maintained at the study site, unless the study site makes direct data entry to the 
databases for which no other original or source documentation is maintained. In such cases, the 
study site should document which eCRFs are subject to direct data entry and should have in 
place procedures to obtain and retain copies of the information submitted by direct data entry. 
All study forms and records transmitted to the Sponsor must only include coded identifiers such 
that directly identifying personal information is not transmitted. The primary method of data 
transmittal is via the secure, internet-based EDC system 
. Access to 
the EDC system is available to only authorized users via the study’s internet web site, where a 
user unique assigned username and password are required for access. 
Any changes made to data after collection will be made through the use of the EDC system. 
Electronic CRFs will be considered complete when all missing and/or incorrect data have been 
resolved. 
15.3 Source Documents 
Source documents are considered to be all information in original records and certified copies of 
original records of clinical findings, observations, data, or other activities in a clinical study 
necessary for the reconstruction and evaluation of the study. The Investigator will provide direct 
access to source documents and/or source data in the facilitation of trial-related monitoring, 
audits, review by IECs/IRBs, and regulatory inspections. 
The Investigator/institution should maintain adequate and accurate source documents and trial 
records that include all pertinent observations on each of the site’s trial subjects. Source data 
should be attributable, legible, contemporaneous, original, accurate, and complete. Changes to 
source data should be traceable, not obscure the original entry, and be explained if necessary. 
15.4 Record Retention 
Study records and source documents must be preserved for at least 15 years after the completion 
or discontinuation of/withdrawal from the study, at least 2 years after the drug being studied has 
received its last approval for sale, or at least 2 years after the drug development has stopped, and 
in accordance with the applicable local privacy laws, whichever is the longer time period. 
The Investigator agrees to comply with all applicable federal, state, and local laws and 
regulations relating to the privacy of subject health information, including, but not limited to, the 
Standards for Individually Identifiable Health Information, 45 CFR, Parts 160 and 164 (the 
Health Insurance Portability Accountability Act of 1996 [HIPAA] Privacy Regulation). The 
Investigator shall ensure that study subjects authorize the use and disclosure of protected health 
information in accordance with HIPAA Privacy Regulation and in a form satisfactory to the 
Sponsor. 

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15.5 Monitoring 
The study will be monitored according to the study’s monitoring plan to ensure that it is 
conducted and documented properly according to the protocol, GCP, and all applicable 
regulatory requirements. 
Monitoring visits (on-site and remote [telephone] or a combination of both) and contacts will be 
made at appropriate times during the study. The Principal Investigator will assure he/she and 
adequate site personnel are available throughout the study to collaborate with clinical monitors. 
Clinical monitors must have direct access to source documentation in order to check the 
completeness, clarity, and consistency of the data recorded in the eCRFs for each subject. 
The Investigator will make available to the clinical monitor all source documents and medical 
records necessary to review protocol adherence and eCRFs. In addition, the Investigator will 
work closely with the clinical monitor and, as needed, provide them appropriate evidence that the 
study is being conducted in accordance with the protocol, applicable regulations, and GCP 
guidelines. 
15.6 Quality Control and Quality Assurance 
The Sponsor or its designee will perform the quality assurance and quality control activities of 
this study; however, responsibility for the accuracy, completeness, security, and reliability of the 
study data presented to the Sponsor lies with the Investigator generating the data. 
The Sponsor will arrange audits as part of the implementation of quality assurance to ensure that 
the study is being conducted in compliance with the protocol, standard operating procedures, 
GCP, and all applicable regulatory requirements. Audits will be independent of and separate 
from the routine monitoring and quality control functions. Quality assurance procedures will be 
performed at study sites and during data management to assure that safety and efficacy data are 
adequate and well documented. 
15.7 Protocol Amendment and Protocol Deviation 
 
Protocol Amendment 
15.7.1
Amendments to the protocol that entail corrections of typographical errors, clarifications of 
confusing wording, changes in study personnel, and minor modifications that have no effect on 
the safety of subjects or the conduct of the study will be classed as administrative amendments 
and will be submitted to the IECs/IRBs for information only. The Sponsor will ensure that 
acknowledgement is received and filed. Amendments that are classed as substantial amendments 
must be submitted to the appropriate regulatory authorities and the IECs/IRBs for approval and 
will not be implemented at sites until such approvals are received other than in the case of an 
urgent safety measure. 

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Protocol Deviations 
15.7.2
Should a protocol deviation occur, the Sponsor must be informed as soon as possible. Protocol 
deviations and/or violations and the reasons they occurred will be included in the clinical study 
report. The Sponsor, or its authorized designee, will report protocol deviations to the IRB/IEC 
and in accordance with applicable regulatory authority. 
15.8 Ethical Considerations 
This study will be conducted in accordance with this protocol, the accepted version of the 
Declaration of Helsinki and/or all relevant federal regulations, as set forth in Parts 50, 56, 312, 
Subpart D, of Title 21 of the CFR; EU 536/2014, Annex 1, D, 17 (a); and in compliance with 
GCP guidelines. 
Independent ethics committees/IRBs will review and approve this protocol and the ICF. All 
subjects are required to give written informed consent before participation in the study. 
15.9 Financing and Insurance 
Before the study commences, the Sponsor (or its designee) and the Investigator (or the 
institution, as applicable) will agree on costs necessary to perform the study. This agreement will 
be documented in a financial agreement that will be signed by the Investigator (or the institution 
signatory) and the Sponsor (or its designee). 
The Investigator is required to have adequate current insurance to cover claims for negligence 
and/or malpractice. The Sponsor will provide no-exclusion insurance coverage for the clinical 
study as required by national regulations. 
15.10 Publication Policy/Disclosure of Data 
Both the use of data and the publication policy are detailed within the clinical study agreement. 
Intellectual property rights (and related matters) generated by the Investigator and others 
performing the clinical study will be subject to the terms of a clinical study agreement that will 
be agreed between the institution and the Sponsor or their designee. With respect to such rights, 
the Sponsor or its designee will solely own all rights and interests in any materials, data, and 
intellectual property rights developed by Investigators and others performing the clinical study 
described in this protocol, subject to the terms of any such agreement. In order to facilitate such 
ownership, Investigators will be required to assign all such inventions either to their institution or 
directly to the Sponsor or its designee, as will be set forth in the clinical study agreement. 

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16 REFERENCES 
1. Sacco RL, Kasner SE, Broderick JP, Caplan LR, Connors JJ, Culebras A, et al; on behalf of 
the American Heart Association Stroke Council, Council on Cardiovascular Surgery and 
Anesthesia, Council on Cardiovascular Radiology and Intervention, Council on 
Cardiovascular and Stroke Nursing, Council on Epidemiology and Prevention, Council on 
Peripheral Vascular Disease, and Council on Nutrition, Physical Activity and Metabolism. 
An updated definition of stroke for the 21st century: a statement for healthcare professionals 
from the American Heart Association/American Stroke Association. Stroke. 
2013;44(7):2064-89.. 
2. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al; on behalf of 
the American Heart Association  
3. Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke 
statistics—2016 update: a report from the American Heart Association. Circulation. 
2016;133(4):e38-e360. Available from http://circ.ahajournals.org/content/133/4/e38.long. 
4. World Heart Federation (WHF). Stroke. 2016. Available from http://www.world-heart-
federation.org/cardiovascular-health/stroke/. 
5. Deb P, Sharma S, Hassan KM. Pathophysiologic mechanisms of acute ischemic stroke: An 
overview with emphasis on therapeutic significance beyond thrombolysis. Pathophysiology. 
2010;17(3):197-218. Available from http://www.pathophysiologyjournal.com/article/S0928- 
4680(09)00136-9/pdf. 
6. Aldeen A, Pirotte M, Solomon RC. Focus on: Acute ischemic stroke. American College of 
Emergency 
Physicians News. 2009. Available from https://www.acepnow.com/article/focus-acute-
ischemic-stroke/. 
7. Wadiwala MF, Sonawalla A, Kamal AK. What is the role of free radical scavengers in acute 
stroke? J Pak Med Assoc. 2012;62(5):512-3. Available from 
http://www.jpma.org.pk/full_article_text.php?article_id=3413. 
8. Demaerschalk BM, Kleindorfer DO, Adeoye OM, Demchuk AM, Fugate JE, Grotta JC, et al; 
on behalf of the American Heart 
Association Stroke Council and Council on Epidemiology and Prevention. Scientific 
rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic 
stroke: a statement for healthcare professionals from the American Heart 
Association/American Stroke Association. Stroke. 2016;47(2):581–641. Available from 
http://stroke.ahajournals.org/content/47/2/581. 
9. Scottish Intercollegiate Guidelines Network (SIGN). Management of patient with stroke or 
TIA: assessment, investigation, immediate management and secondary prevention. A 
national clinical guideline. December 2008 [cited 2017 Mar 20] [78 screens]. Available from: 
http://www.sign.ac.uk/assets/sign108_costing_report.pdf. 
10. Nour M, Scalzo F, Liebeskind DS. Ischemia-reperfusion injury in stroke. Intervent Neurol. 

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2012;1:185-99. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4031777/. 
11. Kaur J, Zhao Z, Klein GM, et al. The neurotoxicity of tissue plasminogen activator? J Cereb 
Blood Flow Metab. 2004;24(9):945-63. Available from 
http://jcb.sagepub.com/content/24/9/945.full.pdf+html. 
12. Roth JM. Recombinant tissue plasminogen activator for the treatment of acute ischemic 
stroke. Proc (Bayl Univ Med Cent). 2011;24(3):257–9. 
13. [HMA] Heads of Medicines Agencies. Clinical Trial Facilitation Group page. 
Recommendations related to contraception and pregnancy testing in clinical trials. 
http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-
About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf. 
September 15, 2014. Accessed 12 Mar 2019. 

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17 APPENDICES 
APPENDIX 1 Contraception Guidelines  
APPENDIX 2 National Institute of Health Stroke Scale (Sample) 
APPENDIX 3 modified Rankin Scale (Sample) 
 

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APPENDIX 1. 
Contraception Guidelines 
Women of childbearing potential (WOCBP) and men whose sexual partners are WOCBP must 
use at least 1 highly effective method of contraception during the study and for 3 months after 
dosing of study treatment.  
A woman is considered to be a WOCBP (fertile) following menarche and until becoming 
postmenopausal, unless she is permanently sterile. Permanent sterilization methods include 
hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is 
defined as no menses for 12 months without an alternative medical cause. A high 
follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a 
postmenopausal state in women not using hormonal contraception or hormonal replacement 
therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is 
insufficient.  
A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. 
Highly effective methods of contraception are those which have a failure rate of <1%
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All subjects will be strongly advised that they (or the female partners of male subjects) should 
not become pregnant while on study treatment or for 3 months after dosing of investigational 
product. A female subject will be advised that she must report immediately to the study site for 
pregnancy testing and appropriate management in the event that she may be pregnant. 

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Reference 
1. [HMA] Heads of Medicines Agencies. Clinical Trial Facilitation Group page. 
Recommendations related to contraception and pregnancy testing in clinical trials. 
http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-
About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf. 
September 15, 2014. Accessed 12 Mar 2019.

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APPENDIX 2. 
Institute of Health Stroke Scale (Sample) 
 
 
 

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APPENDIX 3. 
Modified Rankin Scale (Sample) 
Score 
Description 
0 
No symptoms at all 
1 
No significant disability despite symptoms; able to carry out all usual duties and activities 
2 
Slight disability; unable to carry out all previous activities, but able to look after own 
affairs without assistance 
3 
Moderate disability; requiring some help, but able to walk without assistance  
4 
Moderately severe disability; unable to walk without assistance and unable to attend to 
own bodily needs without assistance  
5 
Severe disability; bedridden, incontinent and requiring constant nursing care and attention 
6 
Dead