Conditions: Drug Toxicity
Keywords: cognitive disorder pharmacokinetics MW151 MW01-2-151SRM PK dose escalation
Allocation: RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 40
Healthy volunteers: yes

Brief summary:
MW01-2-151SRM (=MW151), a small molecule, is being developed for the treatment of cognitive disorders. The development program is based on nonclinical evidence that MW151 improves neurocognitive outcomes in animal models of radiation-induced cognitive impairment, Alzheimer's disease, and other central nervous system (CNS) disorders.

The present study will provide safety and pharmacokinetic (PK) information on single ascending doses to support decisions for continued clinical development.

Detailed description:
The primary objective of this trial is to assess the safety and tolerability of single ascending doses of MW151 when administered orally to healthy adults.

Subjects will be screened prior to inpatient admission. Subjects will be admitted to the inpatient clinic on the day prior to dosing (Day -1) and will remain in the unit until discharge on Day 3. A follow-up visit will be done on Day 7. A single dose of study drug or placebo will be administered on Day 1. Healthy adult female subjects will be randomly assigned to one of 5 dose cohorts (8 subjects each). Each subject will receive a single dose of MW151 (10-160mg) or placebo under fasted conditions.

Following a review of safety and tolerability data for the first 24 hours of dosing in each cohort (including reported adverse events (AEs), physical examination findings, clinical laboratory results, vital signs, and electrocardiograms (ECGs), the remaining 6 subjects will be randomized in a 5:1 ratio. Dosing of the remaining subjects in a cohort may proceed after review of sentinel subject safety data collected during the first 24 hours of dosing and determination that no stopping rules are met. The remaining subjects in each cohort will be dosed sequentially, not simultaneously.

Arms:
arm 1: Participants will receive placebo. arm 2: Participants will receive 10 mg of MW151. arm 3: Participants will receive 20mg of MW151. arm 4: Participants will receive 40mg of MW151. arm 5: Participants will receive 80mg of MW151. arm 6: Participants will receive 160mg of MW151.

Interventions: intervention 1: Placebo intervention 2: MW151, 10mg intervention 3: MW151, 20mg intervention 4: MW151, 40mg intervention 5: MW151, 80mg intervention 6: MW151, 160mg
Intervention descriptions: intervention 1: Matched placebo administered orally intervention 2: 10 mg MW151, 1 x 10mg capsule administered orally intervention 3: 20 mg MW151, 1 x 20mg capsule administered orally intervention 4: 40 mg MW151, 2 x 20mg capsule administered orally intervention 5: 80 mg MW151, 1 x 80mg capsule administered orally intervention 6: 160 mg MW151, 2 x 80mg capsule administered orally

Protocol document:
Prot_SAP_ICF_000.pdf: 
Document Coversheet 
 
Study Title: A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single Ascending Dose Study 
to Evaluate the Safety, Tolerability and Pharmacokinetic Profile of MW151 Administered Orally to Healthy 
Volunteers   
Institution/Site:  
University of Kentucky 
Document (Approval/Update) Date: 
IRB 8/13/21; Protocol 10/14/20 
NCT Number: 
NCT04120233 
IRB Number 
Pro00103072 
Coversheet created: 
11/01/22 
 
 


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CLINICAL STUDY PROTOCOL NO. MW151-101 AMENDMENT 3 
Sponsor of IND: ImmunoChem Therapeutics, LLC 
IND #: 143222 
Full Protocol Title 
A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single Ascending Dose Study to Evaluate 
the Safety, Tolerability and Pharmacokinetic Profile of MW151 Administered Orally to Healthy Volunteers 
Protocol Date: 14 October  2020 (Amendment 3) (V4) 
SHORT PROTOCOL TITLE 
A Phase 1a SAD Study of MW151 
CONTACTS 
Emergency Contacts 
Medical Monitor 
Daniel T. Laskowitz, MD 
Professor and Vice Chair of Neurology 
Professor of Anesthesiology & Neurobiology 
Box 2900 Duke University Medical Center 
Durham, NC 27710 
Telephone: 1- (919) 684-0056 
E-mail: danl@neuro.duke.edu 
Safety Monitor 
Lumy Sawaki, MD, PhD 
University of Kentucky 
2050 Versailles Rd. 
Lexington KY 40504 
Cell: +1 (215) 205 2948 
Telephone: 1- (859) 323-6889 
E-mail: lumy.sawaki@uky.edu 
Other Contacts 
Principal Investigator (PI) 
Linda J. Van Eldik, PhD 
University of Kentucky 
101 Sanders-Brown Bldg. 
800 S. Limestone Street 
Lexington, KY 40536 
Telephone: 1- (859) 257-5566 
E-mail: linda.vaneldik@gmail.com 
Study Monitor 
Bluegrass Research Consultants, Inc. 
Karen Bowen, RN 
8020 Sea Hero Run 
Versailles, KY 40383 
Office: 1- (859) 396-4655 
Fax: 1- (859) 873-9963 
E-mail: bowen73@windstream.net 
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Duke Site PI 
Study Intervention Provided by: 
Jeffrey T. Guptill MD, MA, MHS 
Covance Clinical Research Unit Inc 
Associate Professor, Neurology 
3402 Kinsman Blvd 
Duke Clinical Research Institute 
Madison, WI 53704 
Durham NC 27705 
Phone: 919-668-8445 
E-mail: Jeffrey.guptill@duke.edu 
 
 
Version History 
 
Version 
Effective Date 
Reason for Amendment 
Original Protocol (V1) 
16 March 2019 
N/A 
Amendment 1 (V2) 
28 August 2019 
Inclusion of FDA comments 
Amendment 2 (V3) 
13 January 2020 
Limit enrollment to females only in 
Cohorts 2-5 
Amendment 3 (V4) 
14 October 2020 
 
Inclusion of DSMB 
recommendations 
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INVESTIGATOR SIGNATURE 
I, the undersigned Investigator, have read the following protocol and agree to conduct the study in 
compliance with the protocol, International Conference on Harmonization (ICH) Good Clinical 
Practice (GCP), Good Laboratory Practice (GLP) and all applicable regulatory requirements. 
 
I, the undersigned Investigator, agree: 
• 
To assume responsibility for the proper conduct of the study and not to deviate from the 
procedures described in the protocol. 
• 
I am thoroughly familiar with the investigational product(s) as described in the protocol, 
Investigator’s Brochure and any other relevant information sources provided to me. 
• 
I am aware of and will conduct the study in compliance with the protocol, ICH GCP 
guidelines and all applicable regulatory requirements. 
• 
I agree to permit monitoring and auditing of the study by the Sponsor and its designates, 
and inspection by appropriate regulatory authority (ies). 
• 
I agree to ensure that all persons assisting with the conduct of the study are properly 
qualified for their function. 
 
Investigator Name & Signature: 
 
 
 
 
 
Investigator Signature 
Linda J. Van Eldik, PhD 
Date 
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TABLE OF CONTENTS 
CLINICAL STUDY PROTOCOL NO. MW151-101 AMENDMENT 3 .................................................... 2 
INVESTIGATOR SIGNATURE ............................................................................................................ 4 
TABLE OF CONTENTS ...................................................................................................................... 5 
LIST OF ACRONYMS, ABBREVIATIONS, AND DEFINITIONS OF TERMS ....................................... 8 
SYNOPSIS ........................................................................................................................................ 11 
1 
STUDY OBJECTIVES ............................................................................................................... 15 
1.1 
Primary Objectives ........................................................................................................... 15 
1.2 
Secondary Objectives ...................................................................................................... 15 
2 
BACKGROUND ......................................................................................................................... 16 
2.1 
Rationale ......................................................................................................................... 16 
2.2 
Rationale for Dose Selection ............................................................................................ 17 
2.3 
Supporting Data ............................................................................................................... 17 
 
Nonclinical Studies Pharmacology: ........................................................................... 18 
3 
STUDY DESIGN ........................................................................................................................ 22 
4 
SELECTION AND ENROLLMENT OF SUBJECTS ................................................................... 23 
4.1 
Inclusion Criteria .............................................................................................................. 23 
4.2 
Exclusion Criteria ............................................................................................................. 23 
4.3 
Subject Withdrawal Criteria .............................................................................................. 24 
4.4 
Study Enrollment Procedures........................................................................................... 25 
 
Subject Recruitment and Retention ........................................................................... 25 
 
Screening Logs ......................................................................................................... 26 
 
Informed Consent ..................................................................................................... 26 
 
Assent....................................................................................................................... 26 
 
Randomization/Treatment Assignment ..................................................................... 26 
5 
STUDY INTERVENTIONS/STUDY MEDICATION/STUDY DRUG ............................................ 28 
5.1 
Study Medications/Interventions, Administration, and Duration ........................................ 28 
5.2 
Handling of Study Medications/Interventions .................................................................... 28 
5.3 
Concomitant Interventions ............................................................................................... 29 
 
Required Concomitant Medications/Interventions ..................................................... 29 
 
Prohibited Medications/Interventions ......................................................................... 29 
 
Precautionary Medications/Interventions ................................................................... 30 
5.4 
Subject compliance .......................................................................................................... 30 
6 
CLINICAL AND LABORATORY EVALUATIONS/STUDY PROCEDURES ................................ 31 
6.1 
Schedule of Activities ....................................................................................................... 31 
6.2 
Timing of Study Activities ................................................................................................. 33 
 
Screening/Pre-Randomization Evaluations/procedures ............................................ 33 
 
On-Study/On-Interventions Evaluations/procedures ................................................. 35 
 
Study Medication/Intervention Discontinuation Evaluations/Procedures.................... 38 
 
Pregnancy ................................................................................................................ 38 
6.3 
SPECIAL INSTRUCTIONS AND DEFINITIONS OF EVALUATIONS ............................... 39 
 
Informed Consent ..................................................................................................... 39 
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Protocol Amendments and Study Termination .......................................................... 39 
 
Pharmacokinetic Studies .......................................................................................... 39 
 
Laboratory Studies .................................................................................................... 40 
7 
MANAGEMENT OF ADVERSE EXPERIENCES ....................................................................... 42 
7.1 
Intensity (Severity) ........................................................................................................... 43 
7.2 
Relationship. Unrelated = None, Remote ......................................................................... 44 
7.3 
Related = Possible, Probable ........................................................................................... 44 
8 
CRITERIA FOR INTERVENTION DISCONTINUATION ............................................................ 45 
8.1 
Intolerable Dose ............................................................................................................... 45 
9 
STATISTICAL CONSIDERATIONS ........................................................................................... 46 
9.1 
General Design Issues ..................................................................................................... 46 
9.2 
Administrative and Regulatory Considerations ................................................................. 48 
 
Good Clinical Practice ............................................................................................... 48 
 
Informed Consent ..................................................................................................... 48 
 
Ethical Review .......................................................................................................... 48 
 
Protocol Compliance ................................................................................................. 49 
10 
DATA COLLECTION, SITE MONITORING, AND ADVERSE EXPERIENCE REPORTING ....... 49 
10.1 Data Management ........................................................................................................... 49 
 
Registration .............................................................................................................. 49 
 
Documentation of Data ............................................................................................. 49 
 
Source Document Verification ................................................................................... 50 
10.2 Data Management ........................................................................................................... 50 
 
Monitoring the Study Data ......................................................................................... 50 
10.3 Inspection of Records ...................................................................................................... 51 
 
Records Retention .................................................................................................... 51 
 
Quality Assurance ..................................................................................................... 51 
11 
HUMAN SUBJECTS .................................................................................................................. 52 
11.1 Institutional Review Board (IRB) Review and Informed Consent ...................................... 52 
11.2 Subject Confidentiality ..................................................................................................... 52 
11.3 Study Modification/Discontinuation .................................................................................. 52 
12 
REFERENCES .......................................................................................................................... 53 
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LIST OF TABLES 
 
Table 1: 
Summary of NOAELs from the MW151 toxicology program ............................................. 17 
Table 2: 
Summary of MW151 Efficacy and Pharmacodynamics (PD) in Preclinical Animal 
Models ............................................................................................................................. 19 
Table 3: 
Randomization Scheme ................................................................................................... 26 
Table 4: 
Laboratory Tests .............................................................................................................. 40 
Table 5: 
Criteria for Clinically Notable Vital Sign Abnormalities ...................................................... 47 
Table 6: 
Criteria for Clinically Notable ECG Abnormalities ............................................................. 47 
 
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LIST OF ACRONYMS, ABBREVIATIONS, AND DEFINITIONS OF TERMS 
Aβ 
Amyloid beta 
AD 
Alzheimer’s disease 
AE 
Adverse Event 
ApoE Apolipoprotein E 
AUC 
Area under the curve 
BP 
Blood pressure 
bpm 
Beats per minute 
CCC 
Clinical Coordination Center 
CDE 
Common Data Elements 
CFR 
Code of Federal Regulations 
CIRB Central Institutional Review Board 
Cmax 
Maximum drug concentration 
CNS 
Central Nervous System 
CRF 
Case report form 
CS 
Clinically Significant 
CSF 
Cerebrospinal fluid 
CSS PI 
Clinical Study Site PI 
C-SSRS 
Columbia Suicide Severity Rating Scale 
DCC 
Data Coordination Center 
DM 
Data Management 
DSMB Data Safety Monitoring Board 
ECG 
Electrocardiogram 
eCRF Electronic Case Report Form 
EDC 
Electronic data capture 
ET 
Early termination 
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FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
HIPAA Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IND 
Investigational New Drug 
IRB/IEC 
Institutional review board/Independent ethics committee iv Intravenous 
Kel 
Elimination rate constant 
MAD Multiple ascending dose 
MedDRA 
Medical Dictionary for Regulatory Activities 
MFD 
Maximum feasible dose 
MW151 
The investigational product 
NIA 
National Institute on Aging 
NOAEL 
No adverse events level 
PIC 
Proinflammatory cytokine 
PK 
Pharmacokinetic 
PPI 
Protocol Principal Investigator 
PSC 
Protocol Steering Committee 
RBC 
Red blood cell 
SAD 
Single ascending dose 
SAE 
Serious adverse event 
SOA 
Schedule of Activities 
TEAE Treatment emergent adverse event 
Tmax 
Time at maximum drug concentration 
T1/2 
Half-life 
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WBC White blood cell 
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SYNOPSIS 
 
Title 
A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single 
Ascending Dose Study to Evaluate the Safety, Tolerability and 
Pharmacokinetic Profile of MW151 Administered Orally to Healthy 
Volunteers 
Short Title 
Phase 1a SAD Study of MW151 
Indication 
Radiation-induced cognitive impairment 
Rationale 
MW151, a small molecule, is being developed for the treatment of 
cognitive disorders. The development program is based on 
nonclinical evidence that MW151 improves neurocognitive 
outcomes in animal models of radiation-induced cognitive 
impairment, Alzheimer’s disease, and other CNS disorders. 
The present study will provide safety and PK information on single 
ascending doses to support decisions for continued clinical 
development. 
Objectives 
Primary Objective: To assess the safety and tolerability of single 
ascending doses of MW151 when administered orally to healthy 
adults 
Secondary Objective: To assess the PK profile of single 
ascending doses of MW151 when administered orally to healthy 
adults 
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Interventions and 
Duration 
Subjects will be screened in the 28 days prior to inpatient admission. 
Subjects will be admitted to the inpatient clinic on the day prior to 
dosing (Day -1) and will remain in the unit until discharge on Day 3. A 
follow-up visit will be done on Day 7. A single dose of study drug or 
placebo will be administered on Day 1. 
40 healthy adult subjects will be assigned to one of 5 dose cohorts (8 
subjects each). The starting dose (10 mg) cohort 1 will include male 
and female subjects; cohorts 2 – 5 will include only female subjects. 
Within each cohort, 8 subjects will be randomized to receive MW151 
or placebo in the ratio 6:2. According to the dosing scheme each 
subject will receive a single dose of MW151 or placebo under fasted 
conditions. 
1. Starting dose: Dose1 (10 mg) 
2. Dose2 (20 mg) 
3. Dose3 (40 mg) 
4. Dose4 (80 mg) 
5. Dose5 (160 mg) 
As a safety consideration two sentinel subjects in each cohort will be 
administered MW151 or placebo in a 1:1 ratio. 
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Following review of sentinel safety and tolerability data for the first 24 
hours of dosing in each cohort (including reported adverse events 
[AEs], physical examination findings, clinical laboratory results, vital 
signs, and electrocardiograms [ECGs]), the remaining 6 subjects will 
be randomized in a 5:1 ratio. Dosing of the remaining subjects in a 
cohort may proceed after review of sentinel subject safety data 
collected during the first 24 hours of dosing and determination that 
no stopping rules are met. The remaining subjects in each cohort will 
be dosed sequentially, not simultaneously. 
After the completion of each cohort (Cohorts 1-5), the DSMB will 
review all available safety data before the dosing of the sentinel 
subjects of the next cohort. 
Patients will receive standardized meals during the Inpatient Phase. 
Data from Cohorts 1-5 will be reviewed in a blinded manner, unless 
the findings suggest the triggering of a stopping rule, in which case 
the data for the subjects in question may be unblinded (e.g, if a drug 
related serious AE [SAE] occurs, identifying whether the subject 
received MW151 or placebo to determine whether the stopping rule 
should be triggered). 
If the data raises questions about safety, the subsequent dose for 
cohorts may be modified by one of the following: 
1) repeating the previous dose, 
2) administering an intermediate dose, or 
3) terminating dose escalation. 
Study Location 
1 site located in the United States (US) 
Sample Size and 
Population 
40 healthy volunteers who are between the ages of 18-50 years 
inclusive and weight >50kg, with BMI <34 kg/m2 inclusive will be 
enrolled into this study. A complete list of all inclusion/exclusion 
criteria can be found in section 4 of this protocol. 
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All subjects who receive any study treatment will be included in the 
safety analysis grouped by treatment received. Statistical analysis of 
safety data will be descriptive. PK analysis will include, but not be 
limited to Cmax, Tmax, AUC, T½ and Kel 
Six actively treated subjects per cohort of 8 (n = 6 MW151, n = 2 
placebo) are considered sufficient to provide information on the PK 
profile and an estimation of safety and tolerability of MW151. 
Although the sample size is not based on a statistical power 
calculation, with 30 actively treated subjects the probability of 
observing at least 1 AE with true frequencies of 0.1%, 1%, 5% and 
10% is as follows: 
Statistical 
Considerations 
 
 
 
 
 
 
 
 
AE Frequency 
N=30 
0.1% 
0.030 
1% 
0.260 
5% 
0.785 
10% 
0.958 
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1 STUDY OBJECTIVES 
1.1 
Primary Objectives 
To assess the safety and tolerability of single ascending doses of MW151 when administered orally 
to healthy adult volunteers. 
1.2 
Secondary Objectives 
To assess the PK profile of single ascending doses of MW151 when administered orally to healthy 
adult volunteers. 
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2 BACKGROUND 
2.1 
Rationale 
Rationale for Study and Disease Indication: Cognitive decline and deterioration of long-term 
cognitive performance are major side effects of CNS cancer treatment. Brain metastases are the 
most common CNS malignancies and a common cause of morbidity and mortality in up to 40% of all 
cancer patients with systemic disease, affecting over 170,000 patients in the US annually (Khuntia et 
al., 2006; Langer & Mehta, 2005). The main treatment modalities for brain metastases include 
surgery, whole brain radiation therapy (WBRT) and/or stereotactic radiosurgery. Despite the 
advantages of WBRT for disease control, cognitive impairment can be seen as early as 3 to 6 months 
after WBRT, and affects approximately 80-90% of patients, with memory and executive function 
being the major cognitive domains affected (Greene-Schloesser & Robbins, 2012; Khuntia et al., 
2006; Langer & Mehta, 2005). Although the mechanisms underlying the treatment-induced cognitive 
decline are not completely understood, proinflammatory cytokine overproduction by activated glia 
after radiation therapy has been consistently implicated in the pathogenesis of WBRT-induced 
cognitive impairment (Greene- Schloesser & Robbins, 2012; Lumniczky et al., 2017; Warrington et 
al., 2013). Therefore, therapies that reduce the radiation-induced inflammatory response and 
subsequent neuronal damage should be explored as a potential adjunctive strategy for reducing 
WBRT-induced cognitive decline in patients with brain metastases. 
More broadly, neuroinflammation, or dysregulated inflammation in the brain, is generally accepted as 
a contributor to disease susceptibility and pathophysiology progression in a wide range of 
neurodegenerative disorders associated with cognitive impairment such as Alzheimer’s disease (AD) 
and related dementias, traumatic brain injury (TBI), and seizure disorders (Andreasson et al., 2016; 
Heneka et al., 2015; Heppner et al., 2015; Van Eldik et al., 2007; Van Eldik et al., 2016). A specific 
aspect of neuroinflammation, proinflammatory cytokine overproduction from abnormally activated 
glia, is associated with disease progression and is a druggable process for potential disease 
modification. However, drugs that target this pathological mechanism are severely underrepresented 
in the portfolio of candidates being advanced for CNS disorders (Cummings et al., 2018; Fillit et al., 
2017). 
Our clinical candidate MW01-2-151SRM (=MW151), was developed as part of ongoing attempts to fill 
this clinical void. MW151 is a novel, CNS-penetrant, orally bioavailable, small molecule drug 
candidate that selectively suppresses stressor-induced proinflammatory cytokine overproduction with 
resultant amelioration of synaptic damage and cognitive impairment (Hu et al., 2007). The efficacy 
and pharmacodynamics (PD) of MW151 are evident across a dozen diverse animal studies where 
cytokine overproduction is a contributor to pathophysiology progression. MW151 exhibits efficacy, at 
low doses. It does not bring about immunosuppression or a non-selective anti-inflammatory action. 
There is no evidence of suppression of basal cytokine levels characteristic of homeostasis. Function 
at efficacy doses involves restoration to homeostasis after disease or injury induced increases. 
Overall, nonclinical efficacy findings and safety profile from nonclinical safety studies suggest that 
MW151 holds the potential to be useful clinically in treating multiple CNS disorders with cognitive 
impairment complications. In addition, based on its mechanism of action, MW151 could have 
disease-modifying effects not only in dementias, but also in a number of acute CNS injuries where 
proinflammatory cytokine dysregulation is part of the pathophysiology progression mechanism. 
Finally, MW151 is attractive for development as a stand-alone disease-modifying therapeutic or as 
part of an armamentarium of therapeutic approaches to alter disease progression in cognitive 
disorders. 
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2.2 
Rationale for Dose Selection 
To calculate the doses of MW151 to use in this FIH trial, we followed the FDA Guidance for 
“Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy 
Volunteers.” We based our dose calculations on NOAEL dose levels from two rat 28- day toxicology 
studies, as well as the dose with minimal changes in ECG measurement from the dog cardiovascular 
safety pharmacology study. In one of the rat tox studies the NOAEL was 10 mg/kg in male rats and 
30 mg/kg in female rats. In the other rat toxicology study, the NOAEL was 30 mg/kg in both male and 
female rats. The dog cardiovascular safety pharmacology study revealed only minimal ECG changes 
at 10 mg/kg. Table 1 summarizes NOAELs and exposures from the MW151 non-clinical safety 
program. Based on the human equivalent dose (HED) and AUC, we based our calculations on the 
most conservative value of 10 mg/kg in male rats. For a 60 kg human subject, this corresponds to a 
HED of 96 mg. With a 10-fold safety margin, the planned starting dose for FIH clinical studies of 
MW151 is 10 mg. Therefore, cohort 1 will receive 10 mg, and we plan to double the dose in each 
subsequent cohort (cohort 2: 20 mg, cohort 3: 40 mg, cohort 4: 80 mg, cohort 5: 160 mg). Cohorts 2 
– 5 will consist of female subjects only. These doses may be varied based on the safety review. 
Efficacious doses of MW151 in mouse models range from 0.5 to 5 mg/kg, which would represent 
HED ranging from 0.04 to 0.4 mg/kg (=2.4 – 24 mg in a 60 kg human). Thus, the proposed doses in 
the phase 1a are predicted to be well within the range to provide efficacy in future phase 2 studies. 
Table 1: 
Summary of NOAELs from the MW151 toxicology program 
Study Type 
Study No. 
Strain/Species 
NOAEL 
(mg/kg) 
Cmax 
(ng/mL) 
AUClast 
(ng x 
h/mL) 
HED 
(mg/kg) 
HED 
(mg) 
28-day 
465975 
Wistar rat 
10 (M) 
473 
1,480# 
1.6 
96 
30 (F) 
937 
3,850# 
4.8 
290 
28-day 
16/301-100P 
Sprague- 
Dawley rat 
30 
2,790 
14,200 
4.8 
290 
28-day 
465997 
Beagle dog 
15 
2,220 
3,550 
8.3 
500 
28-day 
16/301-100K 
Beagle dog 
25 
1,920 
12,000 
14 
840 
CV safety 
pharmacology 
1016-2142 
Beagle dog 
10& 
n/a 
n/a 
5.6 
340 
PK parameters are provided for Day 28 or Week 4. HED conversion factors used were 6.2 and 1.8 for rat and dog, 
respectively. 
For studies with a single NOAEL for both genders, PK parameters are provided as the mean of male and females. 
# Week 4 AUC values were significantly lower than on Day 1 in this study. Day 1 AUC values in Study 465975 are 
comparable to Week 4 AUC values in Study 16/301-100P. 
& A NOAEL was not formally determined in this study. The listed dose level revealed only minimal ECG changes. 
CV: cardiovascular 
2.3 
Supporting Data 
Name and Description of Investigational Product: MW01-2-151SRM is the archival ID of the title 
compound, which is the free base (also referred to by its shortened nickname, MW151), with a 
molecular weight of 332.40. The MW151 clinical API drug substance (MW151 HCl) is known 
chemically as 2-(4-(4-methyl-6-phenylpyridazin-3-yl)piperazin-1-yl) pyrimidine dihydrochloride 
hydrate. It has a molecular formula of C19H20N6 • 2HCl • H2O and formula weight of 423.34. MW151 
HCl is a white to beige to light yellow powder that is slightly hygroscopic and soluble in water. The 
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product is available as a capsule filled with the appropriate amount of test substance. In the studies 
described here, MW151 will refer to the MW151 HCl drug substance unless explicitly stated 
otherwise. 
 Nonclinical Studies Pharmacology: 
The pharmacological mechanism of action of MW151 is to selectively suppress stressor- induced 
proinflammatory cytokine overproduction, with resultant amelioration of synaptic damage and 
cognitive impairment. In in vitro based glial activation assays, treatment with MW151 exhibited 
concentration-dependent suppression of several proinflammatory cytokines typically upregulated by 
microglia in neurodegenerative disorder, such as IL-1β and TNFα. In addition, in multiple animal 
models of CNS diseases, MW151 treatment produced histological and biochemical findings 
consistent with the ability to significantly attenuate glial activation and proinflammatory cytokine 
overproduction. The inhibition of glial proinflammatory response correlated well with attenuation of 
synaptic and behavioral deficits. Importantly, this efficacy is achieved in the absence of any signs of 
general immunosuppression or non-selective anti- inflammatory action, and no suppression of basal 
cytokine levels in normal animals. 
Preclinical Models of Radiation-Induced Impairment: The therapeutic potential of MW151 for 
radiation induced cognitive impairment was studied in adult, male Fisher 344 rats subjected to whole-
brain irradiation (WBI, 10Gy). Twenty-four hours post-WBI, treatment with once daily 5 mg/kg MW151 
i.p. or vehicle control was initiated and continued for 28 days. Proinflammatory activated microglia in 
the dentate gyrus were assayed at 2 and 9 months post-WBI. Cell proliferation and neurogenesis in 
the dentate gyrus were assayed at 2 months post-WBI. Novel object recognition and long-term 
potentiation were assayed at 6 and 9 months post-WBI, respectively. MW151 mitigated radiation-
induced neuroinflammation at both early and late time points post-WBI, selectively mitigated the 
deleterious effects of irradiation on hippocampal neurogenesis, and potently mitigated radiation-
induced deficits of novel object recognition consolidation ↓ restoring performance to sham-control 
levels ↓ and of long-term potentiation induction and maintenance (Jenrow et al., 2013). 
MW151 was also studied in a model of radiation-induced skin injury in C57BL/6 mice, which received 
focal irradiation (30Gy) on the right hind leg, followed by 5 mg/kg i.p. administration of MW151 three 
times per week for 21 days, beginning 3, 7, or 14 days post-irradiation. Infiltrating macrophages were 
persistently increased in irradiated skin and were reduced by MW151 treatment. Irradiated skin also 
exhibited persistent increases in cells expressing inflammatory cytokines, TGF-β, TNF-β and MMP9. 
Relative to radiation alone, MW151 administration initiated on days 7 and 14 dramatically reduced 
expression of these markers in skin from mice that responded to MW151 therapy when assayed at 
60–70 days post-irradiation, with skin injury scores showing improvement starting at Day 28 post-
irradiation (Jenrow et al., 2014). 
Preclinical Models of Other CNS Disorders/Injury: Complementary pharmacological findings in a 
variety of nonclinical models of CNS disease and injury indicate that MW151 can effectively limit 
upregulated glial inflammatory responses and provide neurologic and functional improvements. Table 
2 shows a summary of MW151 efficacy and PD in a variety of preclinical animal models. 
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Table 2: 
Summary of MW151 Efficacy and Pharmacodynamics (PD) in Preclinical Animal 
Models 
Experimental System 
Efficacy and PD Endpoints 
Therapeutic radiation (TR)-
induced brain injury model 
(Jenrow et al., 2013; 
PMCID:PMC3673739) 
Improved novel object recognition performance; Reduced 
microglial activation; reduced impairments in 
neurogenesis. 
TR-induced skin injury 
model 
(Jenrow et al., 2014; 
PMID:25098729) 
Attenuated skin injury; 
Reduced infiltrating macrophages and proinflammatory cytokine 
(PIC) up-regulation. 
Aβ Infusion model (Hu 
et al., 2007; 
PMCID:PMC1868432) 
Attenuated cognitive deficits; 
Suppressed PIC up-regulation; decreased astrocyte and 
microglial activation; prevented loss of synaptic proteins. 
APP/PS1 knock-in model 
(Bachstetter et al., 2012; 
PMCID:PMC4396836) 
Attenuated LTP deficits in hippocampal slices; 
Repeat long term daily administration attenuated astrocyte and 
microglial activation; prevented synaptic protein loss; selectively 
suppressed PIC up-regulation; no effect on Aβ levels or amyloid 
plaque burden. Short term daily administration prevented synaptic 
protein loss; selectively suppressed PIC up-regulation; 
no effect on Aβ levels or amyloid plaque burden. 
TBI mild diffuse CHI 
model 
(Bachstetter et al., 2015; 
PMCID:PMC4396836) 
Attenuated cognitive impairments; 
Suppressed PIC up-regulation dose-dependently; decreased 
microglia and astrocyte activation. 
TBI moderate diffuse CHI 
model 
(Lloyd et al., 2008; 
PMCID:PMC2483713) 
Attenuated cognitive impairments; 
Suppressed PIC up-regulation in hippocampus and cortex; 
attenuated astrocyte activation; reduced neuronal injury. 
TBI midline fluid 
percussion injury model 
(Bachstetter et al., 2016; 
PMCID:PMC4752278) 
Dose-dependent suppression of PIC up-regulation; no effect on 
microglia cell morphology, proliferation, migration, or 
phagocytosis. 
EAE model of multiple 
sclerosis 
Reduced incidence/severity of clinical disease; 
Reduced spinal cord TNFα levels at peak and CCL2 levels at 
(Karpus et al., 2008; 
onset and peak of clinical disease; reduced infiltration of 
PMCID:PMC2614915) 
macrophages into the spinal cord at peak clinical disease. 
Kainic acid (KA)-induced 
seizure model 
(Somera-Molina et al., 2007; 
PMID:17521344) 
Protection after early-life seizures; 
Attenuated PIC up-regulation in hippocampus; reduced astrocyte 
activation. 
KA KA Two-hit model 
(Somera-Molina et al., 2009; 
PMCID:PMC2739829) 
Treatment following early-life KA insult reduced seizure 
susceptibility and cognitive impairment after a 2nd KA insult in 
adults; 
Reduced proinflammatory cytokine upregulation, microglial & 
astrocyte activation, and neuronal injury. 
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Experimental System 
Efficacy and PD Endpoints 
INCL disease model 
(Macauley et al., 2014; 
PMCID:PMC4172802) 
In combination with AAV gene therapy, MW151 improved longevity, 
motor performance in rotorod, and eradicated seizures (chronic 
admin, 2.5 mg/kg); MW151 alone decreased seizure frequency; 
In combination with AAV gene therapy, decreased brain atrophy; 
reduced astrocyte and microglial activation; small effect on 
proinflammatory cytokine upregulation. 
TBI AD Two-hit model 
(Webster et al., 2015; 
PMCID:PMC4405562) 
Reduced cognitive impairment when administered after diffuse 
TBI in AD mice; 
Reduced PIC up-regulation and astrocyte activation. 
TBI ECS Two-Hit Model 
(Chrzaszcz et al., 2010; 
PMCID:PMC2942875) 
Treatment following TBI (1st insult) reduced seizure severity and 
cognitive impairment after electroconvulsive shock (2nd insult); 
Reduced astrocyte and microglial activation, PIC up-regulation and 
neuronal injury seen after ECS to levels achieved in animals 
given only TBI insult. 
Overall, the nonclinical pharmacology data suggest that MW151 can exert a positive influence on 
post-injury neurologic outcomes by blunting the brain's intrinsic inflammatory response to CNS insults 
or disease over a dose range of 0.5 – 10 mg/kg when administered intraperitoneally (i.p.) and 2.5 – 
15 mg/kg when administered orally (p.o.). MW151 can suppress the excessive activation of microglia, 
and their proinflammatory effector responses. The drug is effective at limiting pathophysiological 
sequelae and secondary neuronal injury in CNS-inflammatory disease relevant animal models, 
including rodent models of radiation-induced cognitive impairment. 
MW151 is moderately well, orally absorbed in rat and dog (F%=23-47%) and distributes into the CNS 
with brain-plasma ratios > 1. Plasma protein binding of MW151 is high in rat, dog and human with 
97.2, 93.9 and 97.1%, respectively. 
MW151 appears to be preferentially metabolized by CYP1A2. MW151 has the potential to inhibit 
CYP2C8 (IC50 = 1.6-12 µM) and to induce CYP3A4 at concentrations ≥ 0.4 µM. 
ECG measurements in Beagle dogs revealed increases in QTc prolongation at MW151 doses ≥ 30 
mg/kg. These findings appear to be associated with total peak plasma concentrations that are higher 
than the hERG IC50 value for MW151 (9.21 µM) or > 2,400 ng/mL. At the highest proposed clinical 
dose for the SAD Ph1 Study (160 mg), the corresponding preclinical dose in dog based on BSA 
conversion (4.8 mg/kg) would be associated with plasma Cmax values below 2,400 ng/mL. 
In 28-day repeat dose toxicity studies in rat and dog, the testes and epididymis were identified as the 
principal target organs of toxicity of MW151. Macroscopic, organ weight and microscopic findings in 
testes have been observed in Wistar rats and Beagle dogs. Sprague-Dawley rats did not show the 
same testicular toxicity effects of MW151 as Wistar rats, and instead showed only slight reduction in 
the weight of seminal vesicles at comparable dose levels. Increases in liver function enzymes and 
bilirubin were observed in some studies at the upper part of the evaluated dose spectrum. These 
findings typically were mild in nature or reversible and had no histopathological correlates in any of 
the studies performed. 
MW151 was found to be non-mutagenic in two GLP Ames assays and negative in in vivo 
micronucleus studies in mouse and rat. Two out of the three in vitro mammalian cell assays 
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suggested a genotoxic potential of MW151. MW151 showed mutagenic or weak clastogenic potential 
in the mouse lymphoma and human lymphocyte mammalian cell genotoxicity assays, respectively, 
but was negative for clastogenicity in a chromosome aberration assay in V79 Chinese hamster cells. 
Given the lack of consistent reproducibility of the genotoxic findings, the presence of two negative in 
vivo micronucleus assays and two negative bacterial reverse mutation assays, and the fact that 
potential genotoxic findings were only observed with non- GMP batches of MW151, the sponsor 
concludes that the potential for genotoxity is low and acceptable in the context of a First-in-Human 
single ascending dose study (Jacobson-Kram & Jacobs, 2005), and that the risk/benefit profile with 
respect to genotoxicity is acceptable for repeat-dosing in the intended patient population undergoing 
treatment for brain tumors. 
Based on the totality of the data, the Wistar rat was considered the most sensitive species/strain in 
the context of the MW151 toxicology program. Therefore, the NOAEL for Wistar male rats (10 
mg/kg/day) in Study No. 465975 following 28-day dosing with MW151 has been selected for the 
estimation of the safe starting dose for FIH clinical studies in healthy volunteers. Based on human 
equivalent dose (HED) conversion and a 10-fold safety factor, a FIH starting dose of 10 mg MW151 
(free base equivalent) is being proposed. 
Previous Human Experience: None. The phase 1a SAD trial will be a first-in-human study of 
MW151. 
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3 STUDY DESIGN 
Approximately 40 healthy adult subjects, ages 18-50 years, will be dosed in 1 of 5 dosing cohorts of 8 
subjects each (6 MW151, 2 matched placebo). Cohort 1 will consist of males and females; cohorts 2 
– 5 will consist of females only. Each subject will receive 1 oral dose level of MW151. Five different 
doses of MW151 will be evaluated in 5 sequential cohorts. Dosing will start at the lowest dose, then 
escalate in the 2nd cohort, then escalate sequentially in the 3rd, 4th, and 5th cohorts. Plasma samples 
drawn at sequential time points for PK analysis; safety parameters monitored. Subjects will be 
followed in a dedicated inpatient unit at the clinical site, and will receive standardized meals during 
the Inpatient Phase. 
As a safety consideration two sentinel subjects in each cohort will be administered MW151 or 
placebo in a 1:1 ratio. 
Following review of sentinel safety and tolerability data for the first 24 hours of dosing in each cohort 
(including reported adverse events [AEs], physical examination findings, clinical laboratory results, 
vital signs, and electrocardiograms [ECGs]), the remaining 6 subjects will be randomized in a 5:1 
ratio. Dosing of the remaining subjects in a cohort may proceed after review of sentinel subject safety 
data collected during the first 24 hours of dosing and determination that no stopping rules are met. 
The remaining subjects in each cohort will be dosed sequentially, not simultaneously. 
After the completion of each cohort (Cohorts 1-5), the DSMB will review all available safety data 
before the dosing of the sentinel subjects of the next cohort. There will also be an interim PK analysis 
after the completion of Cohort 2. 
Data from Cohorts 1-5 will be reviewed in a blinded manner, unless the findings suggest the 
triggering of a stopping rule, in which case the data for the subjects in question may be unblinded 
(e.g, if a drug related serious AE [SAE] occurs, identifying whether the subject received MW151 or 
placebo to determine whether the stopping rule should be triggered). 
Dosing will start in cohort 1 at 10 mg of MW151, then escalate to a planned dose doubling in each 
subsequent cohort (cohort 2: 20 mg, cohort 3: 40 mg, cohort 4: 80 mg, cohort 5: 160 mg). These 
doses may be varied based on the safety review, but the maximum dose will not exceed 160mg 
without amending the protocol. Should the safety data warrant, dose levels may be reduced or 
additional cohorts added in order to generate a comprehensive understanding of the clinical dose 
range. Should additional cohorts be required above the planned 5 cohorts or doses within the 
planned cohorts changed, a protocol amendment will be submitted to the FDA and the Independent 
Ethics Committee for approval before implementation. 
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4 SELECTION AND ENROLLMENT OF SUBJECTS 
4.1 
Inclusion Criteria 
A subject will be eligible for inclusion in the study only if all of the following criteria are met: 
1. Willing and able to provide written informed consent prior to initiation of any study- 
related procedures. 
2. For Cohort 1: Men and women aged 18 to 50 years, inclusive; For Cohorts 2-5: Women 
aged 18 to 50 years, inclusive. 
3. In good health as determined by medical history, physical exam, laboratory 
examinations, ECG, and vital signs. 
4. Weight >50kg 
5. BMI <34 kg/m2. 
6. ECG without clinically significant pathologic abnormalities and with QTcF <450 ms at 
Screening. 
7. Systolic BP ≤ 150 mmHg and diastolic BP ≤ 90 mmHg at Screening, measured after 10 
to 15 minutes of rest. 
8. No suicidal ideation, as demonstrated by a score of “0” on the Columbia Suicide Severity 
Rating Scale (C-SSRS). 
9. Women who are neither pregnant (negative pregnancy test) nor nursing, and are either: 
a) 
Surgically sterile (bilateral tubal ligation, hysterectomy), or 
b) 
Postmenopausal with last natural menses greater than 24 months, or 
c) 
Premenopausal and agrees to use an acceptable form of birth control during the 
study and for 1 month after dosing. Acceptable forms of birth control include: approved 
hormonal contraceptives (such as birth control pills, patches, implants, or injections), 
intrauterine device (IUD), or barrier methods (such as condom or diaphragm) used with 
a spermicide. All female subjects must have a negative serum pregnancy test at 
screening and negative urine pregnancy test upon admission to the unit prior to dosing. 
10. Men who are surgically sterile or who agree to use a condom with spermicide if sexually 
active during the study and for 1 month after dosing. 
11. Adequate venous access for blood draws. 
4.2 
Exclusion Criteria 
A subject will not be eligible for inclusion in the study if any of the following criteria are met: 
1. Any unstable chronic medical condition (i.e. hypertension, diabetes mellitus type 2) 
requiring interventional treatment that might increase the risk to the subject or confound 
interpretation of safety observations. Subjects who are considered stable and who have 
been receiving stable treatment for medical condition for > 3 months may be considered 
with approval of medical monitor. 
2. Evidence of active infection requiring antibiotic therapy within 14 days prior to dosing. 
3. Medical history of vasculitis or any autoimmune disease excluding seasonal allergic 
rhinitis and childhood history of atopic dermatitis. 
4. History of any treatment for cancer within the past 2 years, other than basal cell or 
squamous cell carcinoma of the skin. 
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5. Seropositive for human immunodeficiency virus (HIV). 
6. History of acute/chronic hepatitis B or C and/or carriers of hepatitis B (seropositive for 
Hepatitis B surface antigen [HbsAg] or anti-Hepatitis C [HCV] antibody). 
7. Clinically significant abnormalities in screening laboratory tests, including: 
a. Absolute neutrophil count < 1.4 x109 
b. Alanine transaminase (ALT) or aspartate transaminase (AST) > 1.5 x upper limit 
of normal (ULN) 
c. Absolute lymphocyte count < 0.6 x 109 
d. Total bilirubin level > 1.6 mg/dL 
e. eGFR < 60 mL/min 
f. 
Any lab abnormalities deemed clinically significant. 
8. Over-the-counter and herbal medications are prohibited within 10 days prior to study 
dosing (with exception of calcium/vitamin D supplements and ocular medications at the 
discretion of the Investigator). Stable doses (> to 3 months of stable dose) of prescription 
medications are allowed with the approval of the medical monitor (birth control 
medications are allowed without medical monitor approval). Subjects should not be on 
non-steroidal anti-inflammatory drugs or immunosuppressive drugs within 10 days prior 
to dosing. 
9. Use of known CYP450 CYP1A2, CYP2D6 or CYP3A4 inhibitors or inducers within 14 
days of dosing or planned use during the study. 
10. Use of an investigational drug, vaccine, device, or blood product within 3 months prior to 
dosing in this study. 
11. Any disorder that could interfere with the absorption, distribution, metabolism or 
excretion of drugs (e.g. small bowel disease, Crohn’s disease, celiac disease, or liver 
disease.) 
12.  Psychiatric history of current or past psychosis, bi-polar disorder, clinical depression, or 
anxiety disorder requiring chronic medication within the past 2* years.  
13. *Short-term (<90 days) use of antidepressants and/or anxiolytics will be assessed by 
investigator and approved by medical monitor prior to determining eligibility.History of 
substance abuse including alcohol within the past 5 years. 
14. Use of any nicotine containing products within 30 days of screening visit or Day -1 
admission. 
15. Current substance or drug dependence confirmed by positive urine drug screen at 
screening visit or Day -1 admission. 
16. Current alcohol abuse confirmed by positive breathalyzer at screening visit or Day -1 
admission. 
17. History of serious head injury as determined by the site investigator or designee. 
18. Chronic kidney disease (defined as the presence of any degree of proteinuria on urine 
analysis and/or an eGFR of <60 ml/min using the MDRD formula). 
19. Any reason or opinion of the investigator that would prevent the subject from 
participation in the study. 
20. Inability to follow the instructions or an unwillingness to cooperate with study procedures. 
21. Has donated more than 500 mL of blood within the last month prior to dosing. 
4.3 
Subject Withdrawal Criteria 
Subjects may withdraw from the study for any reason at any time. The Investigator may discontinue 
subjects from the study in order to protect subject safety and/or if the subject is unwilling or unable to 
comply with required study procedures. Subjects may also be withdrawn from the study if the 
Sponsor or Regulatory Authorities terminate the study prior to its planned end date. 
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Should a dosed subject terminate prematurely from the residential phase of the study, the 
Investigator will make every effort to complete the Early Termination evaluations as scheduled for 
Day 3 before the subject is discharged. 
Subjects discontinuing after randomization but before dosing may be replaced. Subjects 
discontinuing after dosing may be replaced. If a dosed subject is withdrawn or withdraws due to 
safety reasons, they will not be replaced. Decisions to replace dosed subjects for other reasons will 
be made on a case-by-case basis depending on the timing of the discontinuation. 
4.4 
Study Enrollment Procedures 
Subjects will be identified by a unique ID number and initials throughout their participation in the trial. 
Once randomized, each subject will also have a unique randomization number. Subjects will only be 
identified numerically in final data tables and listings; no initials will be presented. 
Sufficient numbers of subjects will be enrolled into the Screening Phase to ensure at least 8 eligible 
subjects are available for dosing in each dosing group. 
A subject who screen fails at any point pre-dose (Screening through Day 1 pre-dose, inclusive) due 
to exclusionary findings may not be rescreened for the study. 
A subject who has been screened but not randomized for non-exclusionary reasons may still qualify 
for entry into the study as follows: 
A subject admitted to the clinical research unit based on acceptable Day -1 findings but who is not 
randomized on Day 1 (i.e., alternate or logistical/administrative reason) is permitted to remain in the 
clinical research unit for up to an additional 2 overnight stays to be re-evaluated for dosing. Dosing 
must occur within 28 days of Screening. Subjects must remain ‘residential’ during this time and must 
follow all other restrictions as previously outlined. Day -1 tests need not be repeated, however, any 
new medical history must be recorded and all Day 1 pre-dose tests must be performed on the ‘new’ 
Day 1. 
A subject admitted to the clinical research unit based on acceptable Day -1 findings but who is not 
randomized on Day 1 (i.e. alternate or logistical/administrative reason) and is discharged from the 
clinic may return once to repeat Day -1 tests and be re-evaluated for dosing. Dosing must occur 
within 28 days of Screening and all Day -1 procedures must be repeated. 
A subject who has been screened but not randomized due to non-exclusionary reasons and is 
outside the 28 day Screening window may be rescreened once. The subject must repeat the entire 
Screening visit. 
 Subject Recruitment and Retention 
Participants may be recruited from clinics or existing recruitment registries at the participating site. 
Postings may be placed on the participating site website. Flyers about the study may be sent to 
community neurologists. Webinars will be conducted for participant recruitment as needed. Interested 
participants will be contacted by the investigators or their staff and invited to participate. These 
recruitment strategies will include a mechanism by which the patients can provide their contact 
information. 
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 Screening Logs 
Screening logs to document reasons for ineligibility and reasons for nonparticipation of eligible 
subjects will be stored centrally. 
 Informed Consent 
Written informed consent will be obtained from each study participant before any study-specific 
procedures or assessments are done and after the aims, methods, anticipated benefits, and potential 
hazards are explained. The participant’s willingness to participate in the study will be documented in 
writing in a consent form approved by the Institutional Review Board (IRB), which will be signed by 
the participant with the date of that signature indicated. The investigator will keep the original consent 
forms and a copy will be given to the participant. It will also be explained to the participant that they 
are free to refuse entry into the study and free to withdraw from the study at any time without 
prejudice to future treatment. 
Written and/or oral information about the study in a language understandable by the participant will 
be given to all participants. 
 Assent 
Not Applicable 
 Randomization/Treatment Assignment 
An independent statistician will be responsible for generating the randomization scheme. 
The randomization scheme for this study will assign subjects to treatment or placebo in sentinel 
groups of 2 subjects with a 1:1 ratio (1 drug: 1 placebo), followed by groups of 6 individuals with a 5:1 
ratio (5 drug: 1 placebo), so that in each dosing cohort 6 subjects will receive MW151 and 2 subjects 
will receive placebo (see Table 3). Randomization numbers will start at 001. 
Table 3: 
Randomization Scheme 
Groups 
Subjects per Group 
(MW151: Placebo) 
Dose Level 
Subjects per Dose Level 
(MW151: Placebo) 
1 
2 
2 (1:1) 
6 (5:1) 
10 mg MW151 or placebo 
8 (6:2) 
3 
4 
2 (1:1) 
6 (5:1) 
20 mg MW151 or placebo 
8 (6:2) 
5 
6 
2 (1:1) 
6 (5:1) 
40 mg MW151 or placebo 
8 (6:2) 
7 
8 
2 (1:1) 
6 (5:1) 
80 mg MW151 or placebo 
8 (6:2) 
9 
10 
2 (1:1) 
6 (5:1) 
160 mg MW151 or placebo 
8 (6:2) 
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After a subject is confirmed eligible for dosing on the afternoon/evening of Day -1 or morning of Day 
1, the study staff will allocate the next available randomization number to the subject, starting at the 
lowest number and continuing in a consecutive manner. 
 
Once a randomization number has been assigned, it cannot be re-assigned to any other subject. To 
respect treatment allocation and the overall study design, replacement subjects will receive the same 
treatment assignment as the original subject who is being replaced and their randomization number 
will be the initial randomization number plus 100 (i.e. a subject replacing ‘009’ will have the number 
‘109’). 
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5 STUDY INTERVENTIONS/STUDY MEDICATION/STUDY DRUG 
5.1 
Study Medications/Interventions, Administration, and Duration 
Drug or placebo will be administered orally in a filled capsule. Subjects will receive a single dose on 
day 1. Subjects will be dosed in an inpatient facility at the study site. 
At the proposed single clinical doses, adverse events related to target organ toxicities observed in 
non-clinical studies (testicular toxicity, QT interval prolongation) are unlikely to occur, but the 
investigator should be aware of these findings. There may be other risks, discomforts, or side effects 
that are currently unknown. These may include rashes, GI upset, or allergic reactions. 
After dosing, the Medical Monitor may prescribe any concomitant therapy deemed necessary to 
provide adequate supportive medical care. More details are given below. 
5.2 
Handling of Study Medications/Interventions 
Drug appearance, packaging and storage: The preparation of the study drug (filling of MW151 
drug substance into capsules without any excipients just before use) will be done by a qualified 
compounding pharmacy, and supplied to the site pharmacy. The study medication will be prepared 
for the required dose of each cohort. 
Study drug must always be stored in a secure location with access limited to designated study staff 
members. Study drug must be stored in a refrigerator at 2-8oC. Temperature logs will be maintained 
to verify correct storage conditions throughout the trial. 
Blinding and Emergency Code Envelopes: During this study, subjects and all study staff will be 
blinded to treatment allocation, except as noted below. Sponsor staff will be blinded to treatment 
allocation. However, Sponsor staff member(s) will be designated as unblinded to enable handling and 
review of PK data and drug accountability prior to database lock. Safety reviews between dosing 
cohorts will be performed in a blinded manner unless the data warrants unblinding due to safety 
concerns. 
The site pharmacy staff will be unblinded so that the appropriate test article (MW151 or placebo) can 
be dispensed appropriately as per the randomization schedule. The unblinded staff will not participate 
in any other study evaluations. 
In an emergency, the blind may be broken and unblinded safety data provided to the Medical Monitor 
if requested. Should unblinding of the Medical Monitor occur, this must be recorded in the source 
documents and the study PI should be notified as soon as possible. Breaking of the blind for non-
safety reasons will be considered a protocol violation. 
Product Preparation: Drug and matched placebo will be provided as an oral capsule(s) containing 
the appropriate amount of drug required for each cohort. All doses will be administered to the 
subjects by appropriately qualified personnel. 
Product Accountability: The site will use Sponsor-approved product accountability records. The 
completeness and accuracy of all accountability records will be monitored throughout the course of 
the study, including study drug receipt, preparation and use, destruction and return. 
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Upon receipt of a shipment of MW151, site staff will check the condition of the shipping containers 
and perform a reconciliation of study drug with the shipment logs, notifying the monitor immediately of 
any problems. In situations where study drug (MW151 or placebo) is dispensed but not used, the 
dispensed medication should be returned to the pharmacy and segregated until review by the 
unblinded monitor. After accountability is complete, unused study drug can be discarded according to 
the study site’s normal procedures. All study drug (used/unused) remaining at the completion of the 
study will either be returned to the pharmacy or will be destroyed at the study site. In case of the 
latter, the study site will supply destruction records to the investigator. 
In accordance with local regulatory requirements, the investigator, designated site staff, or head of 
the medical institution (where applicable) must document the amount of investigational product 
dispensed and/or administered to study subjects, the amount received from the central pharmacy, 
and the amount destroyed upon completion of the study. An investigator is responsible for ensuring 
product accountability records are maintained throughout the course of the study. The inventory will 
include details of MW151 received and dispensed to subjects, batch, and ID numbers. All unused 
capsules must be kept until reconciliation of delivery records with accountability logs by the monitor. 
After the monitor has performed accountability, the site will be instructed to either destroy the 
remaining study medication or return it to the Central Pharmacy or manufacturer. An accounting must 
be made of any drug deliberately or accidentally destroyed. Discrepancies between the amount of 
MW151 received and dispensed drug must be reconciled. 
5.3 
Concomitant Interventions 
After dosing, the site PI or qualified designee may prescribe any concomitant therapy deemed 
necessary to provide adequate supportive medical care. After discharge the subject should refrain 
from any medication other than that required for supportive medical care. All medications will be 
recorded in subject charts. 
 Required Concomitant Medications/Interventions 
Subjects are required to fast for at least 10 hours before all safety laboratory samples. Subjects are 
allowed water ad libitum. Breakfast may be given on Day 1 before dosing; other meals and snacks 
may be served at the study site’s standard times. The study site will provide subjects with standard 
meals and snacks while in the Phase 1 unit. The daily menu information will be included in the final 
clinical report as an appendix. 
 Prohibited Medications/Interventions 
Describe procedure for handling situation(s) when subject uses prohibited intervention during study 
participation. This may also be detailed in section 8: Criteria for Intervention Discontinuation. 
Any antibiotic use within 14 days of Day 1 is prohibited. Subjects are not permitted any prescribed 
medication (other than birth control or other stable medications previously approved by the medical 
monitor) or any over-the-counter medication, health/herbal supplement or vitamin by any route of 
administration within 10 days of Day 1 inclusive other than to manage an adverse event. 
Subjects are required to refrain from smoking, using nicotine-based products, alcohol and food or 
drinks containing caffeine throughout the residential phase. Subjects should refrain from strenuous 
physical exercise for 48h prior to entry into the Phase 1 unit until the Follow-up visit. Subject should 
refrain from alcohol consumption after discharge until the Follow-up visit is complete. 
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Subjects may not donate blood during the study. 
 Precautionary Medications/Interventions 
None anticipated 
5.4 
Subject compliance 
The phase 1a SAD study will be done in an inpatient facility, and therefore compliance of subjects 
with the study invention will be directly monitored by study personnel. 
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6 CLINICAL AND LABORATORY EVALUATIONS/STUDY 
PROCEDURES 
6.1 
Schedule of Activities 
Day/Procedures 
Screening 
(1) 
-1 
Admission 
1 
2 
3 
Discharge (2) 
7 
FU visit 
Informed consent 
X 
Inclusion/Exclusion Review 
X 
X 
Demographics 
X 
Medical History 
X 
X 
X 
Columbia Suicide Severity Rating Scale 
X 
Physical Examination (3) 
X 
X 
X 
X 
Infection Screen (4) 
X 
Body Temperature (5) 
X 
X 
X 
X 
X 
X 
Neurological Examination (6) 
X 
X 
Safety Laboratory Tests (7) 
X 
X 
X 
X 
Drug Screen (urine) 
X 
X 
Alcohol Screen (breathalyzer) 
X 
X 
Hepatitis B & C/ HIV Screen 
X 
TB test (blood test) 
X 
Pregnancy Test (serum at 
Screening/urine on D-1) 
X 
X 
12-lead ECG (8) 
X 
X 
X 
X 
X 
X 
Vital signs (BP/HR) (9) 
X 
X 
X 
X 
X 
X 
PK blood sampling (10) 
X 
X 
Admit to Unit/Randomization (11) 
X 
Dosing (12) 
X 
Apolipoprotein E (blood test) (13) 
X 
Adverse Event Assessment 
X 
X 
X 
X 
Concomitant Medication Review 
X 
X 
X 
X 
X 
X 
Discharge from Unit 
X 
Footnotes to Schedule of Activities 
(1) Screening will occur within 28 days of dosing. 
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(2) Subjects who discontinue from the study should undergo all Early Termination assessments as per 
the Day 3 visit. 
(3) Weight will be measured during all physical examinations and height will be measured at 
Screening only. Physical examination will include general appearance; head, eyes, ears, nose, throat 
(HEENT); cardiovascular; lung; abdominal; musculoskeletal; and skin. 
(4) On Day -1, subjects will be screened for the presence of infection as part of physical examination, 
body temperature, recent/current antibiotic use, recent surgery, evidence of dental abscess, unhealed 
skin lesions etc. On Day 1 before dosing, subjects will be screened for emergence of acute illness. 
(5) Body temperature will be measured at the following time-points: 
• 
Screening 
• 
Day -1 
• 
Day 1 before dosing and again at 12h post-dose 
• 
Day 2 – Day 3 approximately 24h and 48h, respectively, after dosing 
• 
Day 7 
(6) Neurological examination will include mental status evaluation, cranial nerves 2-12 testing, motor 
system and coordination testing, reflex evaluation and sensory system evaluation. The neurological 
examination should be conducted at the same time as the physical examination when both are scheduled 
on the same study day. 
(7) Safety laboratory samples (Hematology/Coagulation/Biochemistry/Urinalysis) will be taken after the 
subject has fasted for a minimum of 10 hours as follows: 
• 
Screening (all except creatine kinase, amylase, lipase) 
• 
Day -1 
• 
Day 2 
• 
Day 7 
(8) A 12-lead ECG will be performed (after lying quietly for 5 minutes). Triplicate tracings (3x) will be 
taken at Day -1 only and will serve as the Baseline (pre-dose measurement). ECGs will be performed at 
the following time points. 
• 
Screening 
• 
Day -1 
• 
Day 1: approximately 1h, 2h, 4h, and 12h post-dose 
• 
Day 2: approximately 24h post-dose 
• 
Day 3 
• 
Day 7 
Subjects will be monitored on telemetry from approximately 30 min prior to dosing through the 
4 hour post-dose ECG. 
 
(9) Vital signs will include BP and HR. At each time point where vital signs are measured, heart rate and 
blood pressure will first be checked in the supine position and then in the standing position with at least 2 
minutes between the supine and standing measurements. Vitals will be performed at the following time- 
points: 
• 
Screening 
• 
Day -1 
• 
Day 1: Pre-dose and at 1h, 2h, 4h, and 12h post-dose 
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• 
Day 2: approximately 24h and 36h post-dose 
• 
Day 3 
• 
Day 7 
(10) PK samples will be taken at the following time-points, anchored to the start of dosing. 
• 
Day 1: Pre-dose, and 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h post-dose 
• 
Day 2: 24h and 36h post-dose 
(11) Randomization is expected to occur on D-1, but if there are delays in receiving prequalification safety 
labs randomization may occur on D1 prior to dosing. 
(12) Dosing will be by oral capsule administration, on day 1. 
(13) ApoE will be collected pre-dose on Day 1 
6.2 
Timing of Study Activities 
Order of Tests: When several assessments are required at the same time point, evaluations should 
be completed in the following order, with PK sample collection at the required time. As such, it is 
understood that ECGs and vital sign measurements may be performed before the actual time point to 
allow for rest times and procedures: 
• 
Fasting safety laboratory sample 
• 
ECG (supine) 
• 
Vital signs 
• 
PK sample 
o Allowable Windows: 
 
PK window for 15min, 30min and 1h post-dose samples: ± 5 minutes 
 
PK window for ≥ 2h post-dose samples: ± 10 minutes 
• 
Day 7 Follow-up visit: ± 1 day 
 Screening/Pre-Randomization Evaluations/procedures 
Screening: Having given written informed consent, each subject will be required to undergo a 
medical screen within 28 days of Day 1. The subject will undergo the following procedures: 
• 
Demographics 
• 
Medical history 
• 
Concomitant medication review 
• 
Columbia Suicide Severity Rating Scale (C-SSRS) 
• 
Body temperature 
• 
12-lead ECG 
• 
Vital signs (BP, HR) 
• 
Physical examination (must be performed by an Investigator), weight and height 
• 
Safety laboratory tests (fasting, minimum 10 hours). Note: During the phone screen, the 
subject will be asked to fast prior to her screening visit.  After the subject consents at the 
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screening visit, they will be asked about their fasting status. If the subject states that 
they have not been fasting for the required time, laboratory samples will still be obtained 
and the laboratory requisition will be marked accordingly. The investigator will assess 
the results and if the glucose is within laboratory defined references or deemed not 
clinically significant by the PI or designee, then the laboratory test does not need to be 
repeated. In the event that the glucose is abnormal and potentially clinically significant, 
then the subject may be scheduled to come for an unscheduled visit to have a fasting 
laboratory glucose drawn. 
• 
Serum pregnancy test (females only) 
• 
Follicle Stimulating Hormone (suspected postmenopausal females only) 
• 
Alcohol screen (breathalyzer) 
• 
Hepatitis B, Hepatitis C, HIV screen 
• 
Urine drug screen 
• 
Quantiferon TB Gold PLUS test 
Once complete, the screening evaluations should be reviewed against inclusion/ exclusion criteria to 
determine the subject’s eligibility for continuation. The Sponsor may be involved in the eligibility 
review and the Medical Monitor may request subject exclusion for safety reasons. 
• 
For those subjects who fail study screening the reason for screen failure will be recorded in 
the Screening Log. Data for screen failures will not be entered into database for this study. 
Infection Screen: On Day -1, subjects will be screened for the presence of infection. This will be 
evaluated using physical examination findings, body temperature, evaluation of recent/current 
antibiotic use, any recent surgery, any evidence of dental abscess, unhealed skin lesions etc. 
Presence of, or the suggestion of infection are exclusionary. 
Neurological Examination: The neurological examination will include: 
Mental Status: Test for orientation to time, place and person: asking date, current location and what 
is his/her name. The subject should be able to follow at least one complicated command such as “lift 
your right shoulder”. 
Cranial Nerves 2-12: Test visual fields, visual acuity, pupillary reflexes, eye movements, fundoscopy, 
facial strength (including facial expression and mastication), hearing to finger rub, tongue, palate and 
head rotation movements, check for dysarthria and shoulder elevation. 
Motor System and Coordination: Test strength in upper and lower limbs bilaterally, pronator drift, 
finger tapping, rapid pronation and supination movements, finger-nose, heel shin, tandem gait, 
walking on heels. 
Reflexes: Test biceps, triceps, knee, ankle and plantar responses (Babinski’s reflex). 
Sensory System: Test light touch, vibration, Romberg test. 
Safety Exclusions: Safety laboratory tests performed as part of Screening and Day -1 assessments 
may not be repeated if any quantitative exclusion criteria are met. 
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Pre-dose vital signs (Screening, Day -1, Day 1 pre-dose) may be repeated once at each visit to 
confirm exclusionary findings. In cases where the initial assessment is exclusionary and the repeat 
assessment is not, the Investigator must evaluate both sets of data and determine whether or not the 
subject may continue. 
Pre-dose ECGs (Screening, Day -1 pre-dose) may not be repeated if any quantitative exclusion 
criteria (QTcF) are met. Other abnormal ECGs may be repeated once at each visit to confirm non-
quantitative exclusionary findings. In cases where the initial assessment is exclusionary and the 
repeat assessment is not, the Investigator must evaluate both sets of data and determine whether or 
not the subject may continue. 
Subjects must not be randomized if there are any clinically significant pre-dose findings on vital signs, 
ECGs, safety laboratory tests, physical examinations and/or neurological examinations. 
Electrocardiogram: A standard 12-lead ECG will be collected at required time points (after lying 
quietly for 5 minutes). ECG parameters including HR, PR, QT, QTcB, QTcF, QRS, and RR intervals 
will be collected. 
At Day -1, pre-dose triplicate ECG tracings will be obtained and will serve as the Baseline. At all other 
time points, a single ECG tracing will be obtained. 
The tracings may be reviewed and reported both locally by the site PI or qualified designee and by a 
blinded Medical Monitor. The Day -1 pre-dose ECGs will be evaluated for Inclusion/ Exclusion by the 
Investigator and the Investigator’s evaluation will prevail for any immediate subject safety 
management purposes. All clinically significant (CS) values should be reported as AEs and recorded 
into the AE source document/eCRF. All ECG tracings and central reader reports will be filed with 
each subject’s chart. 
Vital Signs: Vital signs will include BP and HR. 
At each time point where vital signs are measured, heart rate and blood pressure will first be checked 
in the supine position and then in the standing position with at least 2 minutes between the supine 
and standing measurements. An appropriately sized cuff (cuff bladder encircling at least 80% of the 
arm) should be used to ensure accuracy of measurements. The arm used for measurements should 
be consistent throughout the study. 
 On-Study/On-Interventions Evaluations/procedures 
During the time the subject is in the Phase 1 unit, subjects’ observations about the tolerability of the 
capsule administration will be recorded. 
Admission Procedures (Day -1): Subjects will arrive at the Phase 1 unit on Day -1 and will undergo 
procedures: 
• 
Medical history (to determine any changes since Screening) 
• 
Concomitant medication review 
• 
Infection screen 
• 
Body temperature 
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• 
Vital signs (BP, HR) 
• 
ECG (triplicate) 
• 
Physical examination (must be performed by an Investigator), weight 
• 
Neurological exam (must be performed by an Investigator) 
• 
Safety laboratory tests (fasting, minimum 10 hours) 
• 
Urine pregnancy test (females only) 
• 
Breathalyzer 
• 
Urine drug screen 
• 
Randomize the subject. Only subjects whose admission procedures, including safety 
labs performed on Day -1, meet eligibility criteria will be randomized. Randomization 
may occur on morning of Day 1 if necessary (e.g., delay in safety laboratory test 
reporting). 
Day 1 – Dosing: A light breakfast will be given prior to dosing. 
• 
Pre-dose vital signs 
• 
Pre-dose body temperature 
• 
Final eligibility review. Only subjects who are confirmed ‘eligible’ by the Investigator will 
continue for dosing. 
• 
Start telemetry monitoring approximately 30 min prior to dosing 
• 
Pre-dose PK and ApoE blood sample 
• 
Administer study drug to subject (Time 0) 
• 
0.25h PK sample 
• 
0.5h PK sample 
• 
1h ECG 
• 
1h vitals 
• 
1hr PK sample 
• 
2h ECG 
• 
2h vitals 
• 
2h PK sample 
• 
4h ECG 
• 
4h vitals 
• 
4h PK sample 
• 
8h PK sample 
• 
12h ECG 
• 
12h vitals 
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• 
12h body temperature 
• 
12h PK sample 
• 
Adverse event (AE) assessment (continual throughout Day 1) 
• 
Concomitant medication review (continual throughout Day 1) 
PK samples will be taken at the actual required time and the other evaluations should be scheduled 
around the PK sample. 
Day 2: Day 2 times are anchored to the Day 1 dosing time (Time 0). Subjects will fast for a minimum 
of 10 hours. Water is allowed. 
• 
Fasting safety laboratory tests (blood and urine) 
• 
Light breakfast (subject may decline) 
• 
ECG approximately 24h post-dose 
• 
24h PK sample 
• 
24h vital signs 
• 
Physical exam (must be performed by an Investigator), weight 
• 
Neurological exam (must be performed by an Investigator) 
• 
24h body temperature 
• 
36h PK sample 
• 
36h vital signs 
• 
AE assessment (continual throughout Day 2) 
• 
Concomitant medication review (continual throughout Day 2) 
PK sample will be taken at the required time and the other evaluations should be scheduled around 
the PK sample. 
Day 3: Discharge. Assessments and Procedures on Day 3 are anchored to the dosing time on Day 1 
(Time 0). 
• 
Vital signs 
• 
Body temperature 
• 
ECG 
• 
Light breakfast (subject may decline) 
• 
AE assessment 
• 
Concomitant medication review 
Day 7 Follow-up Visit: May be scheduled on Day 6, 7, or 8. 
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Subjects will fast for a minimum of 10 hours. Water is allowed. Subjects will undergo the following 
procedures: 
• 
Fasting safety laboratory tests (blood and urine) 
• 
ECG 
• 
Vital signs 
• 
Body temperature 
• 
Physical examination (must be performed by an Investigator), weight 
• 
AE assessment 
• 
Concomitant medication review 
Treatment-related AEs ongoing at the Follow-up assessment will be followed until resolution or 
deemed stable, where feasible. Any Follow-up safety laboratory tests that are deemed clinically 
significant by the Investigator will be repeated and followed until stabilization at the discretion of the 
Investigator/Sponsor. 
 Study Medication/Intervention Discontinuation Evaluations/Procedures 
Sufficient numbers of subjects will be enrolled into the Screening Phase to ensure 8 eligible subjects 
are available for dosing in each dosing group. 
Subjects may withdraw from the study for any reason at any time. The Investigator may discontinue 
subjects from the study in order to protect subject safety and/or if the subject is unwilling or unable to 
comply with required study procedures. Subjects may also be withdrawn from the study if the 
Sponsor or Regulatory Authorities terminate the study prior to its planned end date. 
Should a dosed subject terminate prematurely from the residential phase of the study, the 
Investigator will make every effort to complete the Early Termination evaluations, which consist of the 
procedures scheduled for Day 3 before a subject is discharged and a physical examination. A PK 
sample may be drawn at the discretion of the Investigator. 
Subjects discontinuing after randomization but before dosing may be replaced. Subjects 
discontinuing after dosing may be replaced. If a dosed subject is withdrawn or withdraws due to 
safety reasons, they will not be replaced. Decisions to replace dosed subjects will be made on a 
case-by-case basis depending on the timing of the discontinuation. 
 Pregnancy 
Women who are pregnant at screening or on Day -1 testing will not be allowed to enter into the study. 
The likelihood of a female subject becoming pregnant while receiving MW151 is highly unlikely 
because of the requirement for a negative pregnancy test on Day -1 and the requirement that an 
acceptable barrier form of birth control be used during the study. Therefore, a pregnancy consent 
form will not be needed and no additional evaluations will take place. 
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6.3 
SPECIAL INSTRUCTIONS AND DEFINITIONS OF EVALUATIONS 
 Informed Consent 
Written informed consent will be obtained from each participant by a study team member authorized 
to obtained consent. Informed consent will be obtained before any study-specific procedures or 
assessments are performed and after the aims, methods, anticipated benefits, and potential hazards 
are explained. The participant’s willingness to participate in the study will be documented in writing in 
a consent form, approved by the IRB, which will be signed by the participant with the date of that 
signature indicated. The investigator will keep the original consent forms and copies will be given to 
the participants. It will also be explained to the participants that they are free to refuse entry into the 
study and free to withdraw from the study at any time without prejudice to future treatment. Written 
and/or oral information about the study in a language understandable by the participant will be given 
to all participants. HIPAA guidelines for confidentiality and the principles of medical ethics will be 
adhered to during the study. 
 Protocol Amendments and Study Termination 
All revisions and/or amendments to this protocol must be approved in writing by the Sponsor and the 
IRB. The Investigator will not make any changes to the conduct of the study or the protocol without 
first obtaining written approval from the Sponsor and the IRB, except where necessary to eliminate 
an apparent immediate hazard to a study subject. 
The Sponsor reserves the right to discontinue the study at a clinical study site(s) for safety or 
administrative reasons at any time. Should the study be terminated and/or the clinical study site 
closed for any reason, all documentation and study medication pertaining to the study must be 
returned to the Sponsor or its representative. 
 Pharmacokinetic Studies 
Samples will be taken as described in Sections 6.1 and 6.2. Blood samples can be drawn via direct 
venipuncture or an indwelling catheter may be used. Catheters will be flushed with saline before and 
after sampling. Heparin flushing is not permitted. 
If using a catheter, after the saline flush, withdraw and discard approximately 1.5 mL of blood before 
obtaining the sample to avoid sample dilution. Next, take 5 mL of blood into a pre-labeled plasma 
collection tube. Refer to the Laboratory Manual for the specific type of plasma collection tube to be 
used and for detailed sample processing instructions. 
To avoid cross contamination of MW151 and placebo samples, separation of plasma aliquots should 
be done for one subject at a time, changing gloves between subject samples. 
Following processing, plasma will be split into two aliquots. The 1st tube will be sent for PK analysis, 
and the 2nd tube will be a PK retention sample. Until samples are shipped to the analytical facility they 
will be frozen at -70°C (+ 10°C). Samples will be sent frozen on sufficient dry ice to maintain frozen 
conditions for at least 72 hours. The Sponsor will provide direction regarding the timing of sample 
shipment and sample destruction as applicable. 
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 Laboratory Studies 
Laboratory samples will be taken at the time points described in Section 6.1 and Section 6.2.2. 
Samples will be labelled per laboratory specifications. The parameters listed in Table 4 will be 
evaluated: 
Table 4: 
Laboratory Tests 
Hematology & Coagulation 
Biochemistry 
Urinalysis 
• 
Hemoglobin (Hb) 
• 
Hematocrit 
• 
Red blood cell 
count (RBC) 
• 
White blood cell 
count (WBC) 
• 
Mean cell Hb 
• 
Mean cell 
Hb 
concentratio
n 
• 
Mean cell volume 
• 
Platelet count 
• 
Red Cell Distribution 
Width 
• 
% Basophils 
• 
% Eosinophils 
• 
% Lymphocytes 
• 
% Monocytes 
• 
% Neutrophils 
• 
Basophil count 
• 
Eosinophil count 
• 
Lymphocyte count 
• 
Monocyte count 
• 
Neutrophil count 
• 
Reticulocyte count 
• 
Activated partial 
thromboplastin time 
• 
Pregnancy Test (serum) 
• 
Follicle Stimulating 
Hormone 
• 
Sodium 
• 
Potassium 
• 
Calcium 
• 
Chloride 
• 
Phosphorus 
• 
Glucose 
• 
Total protein 
• 
Albumin 
• 
Creatinine 
• 
Amylase 
• 
Lipase 
• 
BUN 
• 
Bilirubin 
• 
ALP 
• 
AST 
• 
ALT 
• 
GGT 
• 
Creatine kinase 
• 
Total cholesterol 
• 
High density lipoprotein 
• 
Low density lipoprotein 
• 
Triglycerides 
• 
pH 
• 
Protein 
• 
Blood 
• 
Ketones 
• 
Glucose 
• 
Bilirubin 
• 
Nitrite 
• 
Specific gravity 
• 
Leucocytes   
 
If any abnormal value 
is observed on the urine 
dipstick test the sample 
should be further 
analyzed with urine 
microscopy: 
 
• 
WBC 
• 
 RBC 
• 
 Cellular casts 
• 
 Granular casts 
• 
 Hyaline casts 
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Genetic Testing 
Drugs of Abuse (Urine) & 
Alcohol Testing 
Serology Screen & 
TB Test 
Apolipoprotein E 
Cannabinoids 
Amphetamines 
Barbiturates 
Cocaine 
Opiates Benzodiazepines 
Phencyclidine 
Methadone 
Alcohol (ethanol) 
Hepatitis B surface antigen 
Hepatitis C antibody 
HIV 1 & 2 antibodies 
Quantiferon TB Gold PLUS 
test 
All values falling outside the laboratory normal range must be assessed for clinical significance. 
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7 MANAGEMENT OF ADVERSE EXPERIENCES 
Adverse Event: An adverse event is any untoward medical occurrence associated with the use of a 
drug in humans, whether or not considered drug related. An adverse event (also referred to as an 
adverse experience) can be any unfavorable and unintended sign (e.g., an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a drug, without any judgment 
about causality. An adverse event can arise from any use of the drug (e.g., off- label use, use in 
combination with another drug) and from any route of administration, formulation or dose, including 
an overdose. 
Adverse Reaction: An adverse reaction means any adverse event caused by a drug. Adverse 
reactions are a subset of all suspected adverse reactions for which there is reason to conclude that 
the drug caused the event. 
Suspected Adverse Reaction: Suspected adverse reaction means any adverse event for which 
there is a ‘reasonable possibility’ that the drug caused the adverse event. For the purposes of IND 
safety reporting, ‘reasonable possibility’ means there is evidence to suggest a causal relationship 
between the drug and the adverse event. A suspected adverse reaction implies a lesser degree of 
certainty about causality than adverse reaction, which means any adverse event caused by the drug. 
The types of evidence that would suggest a casual relationship between the drug and the adverse 
event include, but are not limited to: 
A single occurrence of an event that is uncommon and known to be strongly associated with drug 
exposure (e.g., angioedema, hepatic injury, Stevens-Johnson Syndrome) 
One or more occurrences of an event that is not commonly associated with drug exposure, but is 
otherwise uncommon in the population exposed to the drug. 
An aggregate analysis of specific events observed in a clinical trial (such as known consequences of 
the underlying disease or condition under investigation or other events that commonly occur in the 
study population independent of drug therapy) that indicates those events occur more frequently in 
the drug treatment group than in a concurrent or historical control group. 
Unexpected Adverse Event: An adverse event or suspected adverse reaction is considered 
‘unexpected’ if it is not listed in the Investigator Brochure or is not listed at the specificity or severity 
that has been observed. 
Serious Adverse Event: An adverse event or suspected adverse reaction is considered ‘serious’ if, 
in the view of either the Medical or Safety Monitor, it results in any of the following outcomes: 
• 
Death 
• 
A life-threatening adverse event 
• 
In-patient hospitalization or prolongation of existing hospitalization 
• 
Persistent or significant incapacity or substantial disruption of the ability to conduct normal 
life functions 
• 
Congenital anomaly/birth defect 
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Important medical events that may not result in death, be life-threatening, or require hospitalization 
may be considered serious 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 allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in 
subject hospitalization, or the development of drug dependency or drug abuse. 
Life Threatening Adverse Event: An adverse event or suspected adverse reaction is considered 
‘life-threatening’ if, in the view of either the Investigator or Sponsor, its occurrence places the subject 
at immediate risk of death. It does not include an adverse event or suspected adverse reaction that, 
had it occurred in a more severe form, might have caused death. 
Reporting a Serious Adverse Event to the Sponsor: The Investigator is required to inform the 
Medical Monitor by e-mail/telephone/fax within 24h of his/her becoming aware of any serious adverse 
event. The notification should be followed by a written report within 1 working day of such an event. 
The follow up observation period for the subject(s) affected will be jointly decided upon by the 
Investigator and the Medical Monitor. The Investigator is responsible for notification of serious 
adverse events to the applicable Institutional Review Board/Independent Ethics Committee 
(IRB/IEC). The Sponsor is responsible for all IND Safety Reporting to the US Food and Drug 
Administration (FDA). 
Collection of Safety Information: Adverse events (AEs) and serious adverse events (SAEs) will be 
monitored and reported throughout the study from the time of dosing to the end of study. Each 
subject will be monitored for AEs throughout the study. Subjects will be asked “how are you feeling?” 
during each study visit and throughout the day during the residential phase of the study. AEs will be 
followed to resolution/stabilization, where feasible/possible, regardless of whether the subject is still 
participating in the study. Follow-up on AEs may include subject referrals to specialists and/or other 
health care providers. When applicable, the Investigator will obtain reports and/or medical records 
from non-study providers regarding the AE. In cases of AEs such as rashes, photographs may be 
taken for the purpose of documentation. Due regard for subject confidentiality will be employed. 
The Investigator is not obliged to follow-up with subjects for AEs or SAEs that begin after study 
completion, however if an SAE is reported to the Investigator after a subject has completed the study, 
and it is possibly related to the study drug, then the Investigator will report it to the Sponsor. 
All abnormal laboratory analytes, ECG results, vital signs and examination findings will be reviewed 
by the Investigator for clinical significance. If the Investigator deems a post-dose finding to be 
clinically significant, it will be documented as an AE. Pre-dose clinically significant findings are 
exclusionary. Pre-dose events will be analyzed separately from treatment emergent AEs in the final 
analysis. 
Assessment of Adverse Events: Investigators will assess each AE based on the following 
definitions. 
7.1 
Intensity (Severity) 
Mild: The AE is generally transient, does not interfere with usual activities, and is easily tolerated by 
the subject. 
Moderate: The AE causes sufficient discomfort and interferes with usual activities. 
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Severe: The AE causes considerable interference with usual activities and may be incapacitating. 
7.2 
Relationship. Unrelated = None, Remote 
None (unrelated, not related, no relation): 
An unreasonable temporal relationship between administration of the study drug and the onset of the 
AE (e.g. the event occurred either before, or too long after administration of the study drug for it to be 
considered drug-related); 
A causal relationship between the study drug and the AE is biologically implausible (e.g. death as a 
passenger in an automobile accident); 
A clearly more likely alternative explanation for the AE is present (e.g. typical adverse reaction to a 
concomitant drug and/or typical disease-related event). 
Remote (unlikely, doubtful, improbable): 
There is little evidence to suggest there is a causal relationship and there is another reasonable 
explanation for the event. 
7.3 
Related = Possible, Probable 
• 
Possible: There is some evidence to suggest a causal relationship (e.g. the event 
occurred within a reasonable time frame after administration of the study drug); however, 
the influence of other factors may have contributed to the event (e.g. the subject’s 
clinical condition, other concomitant medications, or concurrent illness). 
• 
Probable: There is evidence to suggest a causal relationship and the influence of other 
factors is unlikely. 
Consider the following when assessing causality: 
• 
Temporal associations between the study drug and the event 
• 
Pre-existing risk factors or concurrent illness 
• 
A plausible mechanism 
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8 CRITERIA FOR INTERVENTION DISCONTINUATION 
8.1 
Intolerable Dose 
After the safety review, if the Medical Monitor, based on good clinical judgement, considers a dose 
level to be intolerable, then dose escalation to the next level will not proceed. Depending on the 
duration and potential seriousness of safety findings, the Sponsor and Investigator will determine 
whether the current dose level may be repeated, or if a lower dose level may be tested. 
If any of the following sentinel halting criteria are met the rest of the cohort will not be dosed until 
review by the Medical and Safety Monitors, Sponsor and Investigator: 
• 
Any subject develops a Grade 3 (severe) AE that is related to the study drug within 24 
hours of dosing. 
• 
Any subject develops an SAE related to the study drug. 
The following criteria constitute specific study halting criteria: 
• 
Two or more subjects experience AEs of severe intensity in the same organ class 
(Grade 3 according to the “Toxicity Grading Scale for Healthy Adult and Adolescent 
Volunteers Enrolled in Preventive Vaccine Clinical Trials,” Version September 
2007) regardless of relatedness to study drug. 
• 
One subject with a reported SAE, unless that SAE is determined to be clearly unrelated 
to the investigational drug product. 
• 
Occurrence of a life-threatening allergic/hypersensitivity reaction (anaphylaxis) in any 
subject, manifested by bronchospasm with or without urticaria or angioedema requiring 
hemodynamic support with pressor medications or mechanical ventilation. 
• 
Death of a dosed subject following dosing and prior to the subject’s last visit that was not 
the result of trauma or accident, regardless of relatedness to study product. 
• 
Any other event(s) in the good clinical judgment of the responsible physician that is 
thought to be related to investigational product and comprises a serious risk to subject 
safety. 
If any of the following dose escalation halting criteria are met escalation to the next planned dose 
cohort will not proceed until all available study data have been reviewed by the DSMB: 
• 
Any subject develops an SAE related to the study drug 
• 
Any subject experiences a Grade 3 (severe) AE related to the study drug 
• 
2 or more subjects in a cohort experience a Grade 2 (moderate) or greater AE that is 
related to the study drug and is of the same type (preferred term) and occurring in the 
same SOC. 
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9 STATISTICAL CONSIDERATIONS 
9.1 
General Design Issues 
Detailed statistical analysis plans will be created for the study and signed off in advance of database 
lock. One plan will be created for the analysis of PK data and a separate plan will be created for the 
analysis and presentation of all other study data. General statistical approaches are presented below. 
Baseline is defined as the last evaluation before dosing. 
Safety Analysis: All subjects who receive any study treatment will be included in the safety analysis 
grouped by treatment received. Statistical analysis of safety data will be descriptive. 
For continuous variables, summaries will include sample size, mean, standard deviation, minimum, 
and maximum. For categorical variables, the summaries will include frequencies and corresponding 
percentages. No inferential hypothesis testing will be performed on the safety variables. Repeat or 
unscheduled results will not be included in the summaries, but will be listed. Data from placebo 
subjects will be pooled for final presentations. Confidence intervals (90%, 95%) may be used in 
safety summaries. 
Adverse Events: AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). 
AEs will be listed and summarized by treatment group and dose level. Where applicable, AEs may 
also be summarized by severity, seriousness, relationship to study treatment and by system organ 
class and preferred term. The number and percentage of subjects who experience events will be 
shown in the summaries. Listings for all AEs will be presented. 
A treatment-emergent AE is an AE, regardless of relationship to study drug that occurs during or after 
the first dose of study treatment. 
Laboratory Assessments: Summary statistics of observed and change from baseline data will be 
presented for each treatment group and dose level where applicable. Summary statistics will include 
number of subjects, mean, standard deviation, minimum, and maximum. Shift tables summarizing the 
numbers of subjects shifting from normal pre-dose values to abnormal post- dose values will also be 
presented where applicable. Listings for all laboratory assessments will be presented. 
Vital Signs (BP, HR, Body Temperature): Summary statistics for BP and HR and change from 
baseline (predose) summaries will be presented for each treatment group and dose level where 
applicable. Summary statistics will include number of subjects, mean, standard deviation, minimum, 
and maximum. Listings for all vital signs will be presented. 
Post-dose clinically notable vital signs will be listed and summarized by treatment and dose. Notable 
abnormalities are indicated in Table 5 below: 
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Table 5: 
Criteria for Clinically Notable Vital Sign Abnormalities 
Parameter 
High Threshold 
Low Threshold 
Systolic BP (supine) 
> 30 mmHg increase from 
baseline 
> 30 mmHg decrease from 
baseline 
Diastolic BP (supine) 
> 20 mmHg increase from 
baseline 
> 30 mmHg decrease from 
baseline 
Heart Rate 
> 120 bpm and an increase in 
HR of ≥ 15 bpm from baseline 
< 40 bpm and a decrease in 
HR of ≥ 15 bpm from baseline 
Body Temperature 
> 39.0oC (> 102.2oF) 
< 35.0oC (< 95.0oF) 
12-Lead ECG: ECG results from the central reader will be used in the analysis. Shift tables 
summarizing the numbers of subjects shifting from normal pre-dose values to abnormal post- dose 
values will also be presented. Numeric ECG data will be summarized by treatment group and dose 
level and mean summary tables, including change from baseline will be presented. 
The ECG results will be listed by treatment group and dose level. 
Post-dose clinically notable ECGs will be listed and summarized by treatment and dose. Notable 
abnormalities are indicated in Table 6 below: 
Table 6: 
Criteria for Clinically Notable ECG Abnormalities 
Parameter 
High Threshold 
Low Threshold 
PR interval 
PR ≥ 220 ms 
PR ≤ 120 ms 
QRS duration 
QRS duration ≥ 120 ms and an 
increase of ≥ 20 ms from 
baseline 
- 
QT interval 
QT interval > 500 ms 
- 
QTcF interval 
Men: QTcF interval 
≥ 450 ms and an increase of 
≥ 60 ms from baseline 
OR 
QTcF interval > 500 ms 
Women: QTcF interval 
≥ 470 ms and an increase of 
≥ 60 ms from baseline 
OR 
QTcF interval > 500 ms 
- 
 
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Pharmacokinetic Analysis: The plasma concentrations of MW151 will be determined, and used to 
estimate appropriate PK parameters including Cmax, Tmax, AUC, T½ and Kel by non- compartmental 
analysis. The PK analysis population will include all subjects who received the active study drug and 
who have sufficient MW151 plasma concentrations to calculate at least 1 PK parameter. 
PK parameters will be listed for each individual subject and summarized for each dose level; the 
summary will consist of number of subjects, arithmetic mean, standard deviation, and geometric 
mean, coefficient of variation, minimum, median, and maximum. Profiles for each subject will be 
presented graphically. Additionally, a mean profile will be presented by treatment group and dose 
level. 
The PK analysis will be conducted at a facility selected by the Sponsor. PK data will be provided to 
the Sponsor for inclusion into the final clinical study report. 
9.2 
Administrative and Regulatory Considerations 
 Good Clinical Practice 
The study will be conducted in accordance with good clinical practice (ICH GCP) and all applicable 
regulations including the ethical principles of the Declaration of Helsinki (Edinburgh 2000, with Note 
of Clarification, Tokyo 2004). 
 Informed Consent 
The Sponsor or designee will provide the Investigator with a template ICF for the study, which may 
be modified for local use. A study team member authorized to obtain consent will obtain a written ICF 
from each study subject prior to the performance of any study-related procedures. 
Consent will be obtained only after full disclosure of the nature of the study, its risks and benefits, in 
accordance with local and federal regulations and guidelines. The fact that informed consent was 
obtained, and the date upon which it was obtained, will be documented in each subject’s study 
records. 
If the ICF is amended at any time during the study, the Investigator must follow all applicable 
regulatory requirements to ensure review and approval of the amended consent form by the IRB/IEC. 
Subjects must sign the most current IRB/IEC-approved version of the ICF at the time of their 
participation in the study. 
 Ethical Review 
The Investigator or designee will prepare and submit all required documentation and obtain local 
IRB/IEC approval to implement the study prior to the conduct of any study procedures. At a minimum, 
the study protocol, ICF, Investigator’s Brochure, and study-related advertisements and promotional 
materials will be submitted. 
If it is necessary to amend the protocol and/or ICF during the course of the study, the Investigator 
must ensure that the IRB/IEC reviews and approves these amended documents. No amendments to 
the study protocol should be made without the agreement of the Investigator and Sponsor as well as 
the IRB/IEC, where applicable. 
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The Investigator will maintain documentation of the composition of the IRB/IEC as well as all 
correspondence with the IRB/IEC. The Investigator will comply with local requirements for routine 
reporting to the IRB/IEC, as well as local and government requirements for notifying the IRB/IEC of 
SAEs. The Investigator will prepare a final study report and submit it to the IRB/IEC within 3 months 
of study completion. The Investigator or designee will provide Sponsor or designee with copies of 
IRB/IEC approval notices, correspondence, annual reports, and final study reports. 
 Protocol Compliance 
The study will be conducted in compliance with the protocol. The Investigator is responsible for 
ensuring compliance by all study staff members. Deviations from protocol-specified procedures will 
be documented in subjects’ study records. 
10 DATA COLLECTION, SITE MONITORING, AND ADVERSE 
EXPERIENCE REPORTING 
10.1 Data Management 
Site personnel will collect, transcribe, correct, and transmit the data onto source documents, CRFs, 
and other forms used to report, track and record clinical research data. The clinical site will be 
monitored to ensure compliance with data management requirements and Good Clinical Practices. 
All study data will be collected via systems that comply with all applicable guidelines regarding patient 
confidentiality and data integrity. 
 Registration 
Registration of participants on this protocol will employ an interactive data system in which the clinical 
study site will attest to the participant’s eligibility as per protocol criteria and obtain appropriate 
informed consent. IRB approval for the protocol must be on file at the institution before accrual can 
occur from the clinical study site. 
A system of coded identifiers will be used to protect participant confidentiality. When the participant is 
registered to participate in the study, the system will assign a participant ID number. To confirm the 
correct participant ID, the data entry system will require a second entry of the unique participant ID 
and compare for consistency. In this fashion, no personal identifiers would be accessible and the 
data will be collected on the correctly identified subject. 
 Documentation of Data 
As part of the responsibilities assumed by participating in the study, the Investigator agrees to 
maintain timely case histories for the subjects treated as part of the research under this protocol, 
including accurate source documentation. A CFR21, part 11 compliant electronic data capture 
system for source data will be developed and provided for use in the clinical study. The majority of 
source data will be recorded directly into data capture system; however some source data, including, 
but not limited to, AEs, concomitant medications and protocol deviations will be recorded on paper-
based source documents. Paper-based data will be entered into a separate clinical database, and will 
be merged with the electronic data capture system during processing and analysis. ECG readings 
are printed with a machine interpretation on the ECG. This is then reviewed by the study investigator. 
If there is a question with the interpretation, the investigator can ask a cardiologist for another read. 
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ECG data will be forwarded electronically for inclusion in data reporting and analyses. The 
Investigator will be responsible for ensuring that adequate checks are carried out on all study data. 
At the completion of the study, the Sponsor will receive a complete set of data for all subjects. 
 Source Document Verification 
All (100%) subject data (electronic and paper-based source) will be reviewed by the monitors for 
accuracy and consistency. This will be conducted with due regard to subject confidentiality. 
10.2 Data Management 
Data collection processes and procedures will be reviewed and validated to ensure completeness, 
accuracy, reliability, and consistency. A complete audit trail will be maintained of all data changes. 
Electronic consistency checks and manual review will be used to identify errors or inconsistencies. 
This information will be provided to the study site by means of electronic or manual queries. 
 Monitoring the Study Data 
The conduct of the study will be monitored by the Sponsor, or designee, to ensure compliance with 
applicable regulatory requirements and GCP. The study monitor will maintain necessary telephone 
and letter contact with the Investigative site. The study monitor will verify that the study is conducted 
in accordance with the currently approved protocol and any amendments and will monitor subject 
enrolment, completeness and accuracy of subject data and reporting and recording of AEs. 
The monitor will maintain current knowledge of the study through observation, review of study 
records and discussion of the conduct of the study with the Investigator and staff.  Monitoring will be 
conducted according to Good Clinical Practice and applicable government regulations. The 
investigator agrees to allow monitors access to the clinical supplies, dispensing and storage areas, 
and to the clinical files of the study subjects, and, if requested, agrees to assist the monitors. 
Safety monitoring will include careful assessment and appropriate reporting of adverse events. 
Medical monitoring will include contemporaneous assessment of serious adverse events. 
The DSMB will meet after each cohort is completed or as needed, and will review subject recruitment, 
AE’s, side effects, withdrawals, protocol violations, and inclusion/exclusion criteria. More frequent 
meetings will take place if necessary. Roles and responsibilities for the DSMB will be outlined in a 
separate DSMB charter document. 
The Safety Monitor will review all adverse events, in a blinded fashion, on a periodic basis. In 
addition, the monitor will review all events that meet the regulatory definition of a Serious Adverse 
Event, upon receipt of notification via the Electronic Data Capture (EDC) system. 
An adverse event (AE) is any unfavorable and unintended sign (including a clinically significant 
abnormal laboratory finding, for example), symptom, or disease temporally associated with a study, 
use of a drug product or device whether or not considered related to the drug product or device. FDA, 
Office of Human Research Protection (OHRP), and IRB requirements for reporting AEs will be 
followed. Subjects will be monitored for AEs from the time they sign consent until 30 days following 
permanent discontinuation of study drug. At that point, all ongoing AEs will be followed to resolution, 
but no new AEs will be recorded. The monitor/DSMB will review cumulative AEs; the frequency of this 
review will be determined by the monitor/DSMB in conjunction with the Protocol PI. 
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The Clinical Site Medical Monitor and research team (co-Investigators, research nurse, clinical trial 
coordinator) are responsible for identifying and reporting AEs and determining the relationship of the 
event to the study drug/study procedures. Aggregate reports blinded by treatment group, detailed by 
severity, attribution (expected or unexpected), and relationship to the study drug/study procedures, 
will be available for review by the monitor. A separate report detailing protocol compliance will also be 
available monthly for review by the Protocol PI and Safety Monitor, who will provide feedback to the 
site as needed. The Safety Monitor will advise the Protocol PI as to whether the protocol or informed 
consent document requires revision based on these reports. 
10.3 Inspection of Records 
The Investigator and institution involved in the study will permit trial-related monitoring, audits, 
IRB/IEC review, and regulatory inspection(s) by providing direct access to all study records, medical 
files, and source data to enable verification of the trial data. In the event of an audit, the Investigator 
agrees to allow the Sponsor, the FDA, or other Regulatory Agency access to all study records. 
The Investigator should promptly notify the Sponsor of any audits scheduled by any Regulatory 
Authority and promptly forward copies of any audit reports received to the Sponsor. 
 Records Retention 
In accordance with all applicable regulatory requirements, the Investigator will maintain a copy of all 
site records in a safe and secure location on completion of the study. The location of the Investigator 
file archive will be made known to the Sponsor at study conclusion and if the archive location 
changes, the Investigator will notify the Sponsor. Sponsor will archive study data according to their 
normal practice. 
 Quality Assurance 
The Investigator site, facilities and all data and documentation may be audited by an independent 
auditor. The Investigator must allow the auditor access to all relevant documents and be available to 
discuss any findings/issues. 
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11 HUMAN SUBJECTS 
Documented approval from the IRB will be obtained prior to clinical trial start, according to ICH GCP, 
local laws, regulations and organization. When necessary, an extension, amendment or renewal of 
the IRB approval must be obtained. 
Evidence of training in responsible conduct of research shall be on file for each site PI and co- 
investigators. 
11.1 Institutional Review Board (IRB) Review and Informed Consent 
This protocol and the informed consent document and any subsequent modifications will be reviewed 
and approved by the IRB responsible for oversight of the study. A signed consent form, approved by 
the IRB, will be obtained from the subject. The consent form will describe the purpose of the study, 
the procedures to be followed, and the risks and benefits of participation. A copy of the consent form 
will be given to the subject, parent, or legal guardian, and this fact will be documented in the subject’s 
record. 
11.2 Subject Confidentiality 
All laboratory specimens, evaluation forms, reports, video recordings, and other records that leave 
the clinical study site will be identified only by the study specific Subject Identification Number (SID) 
to maintain subject confidentiality. All records will be kept in a locked file cabinet. All computer entry 
and networking programs will be done using study specific SIDs only. 
Clinical information will not be released without written permission of the subject, except as 
necessary for monitoring by IRB, the FDA, the OHRP, the sponsor, or the sponsor’s designee. 
11.3 Study Modification/Discontinuation 
The study may be modified or discontinued at any time by the IRB, the sponsor, the OHRP, the FDA, 
or other government agencies as part of their duties to ensure that research subjects are protected. 
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12 REFERENCES 
Andreasson KI, Bachstetter AD, Colonna M, Ginhoux F, Holmes C, Lamb B, Landreth G, Lee DC, 
Low D, Lynch MA, Monsonego A, O’Banion MK, Pekny M, Puschmann T, Russek-Blum N, Sandusky 
LA, Selenica MB, Takata K, Teeling J, Town T, Van Eldik LJ (2016) Targeting innate immunity for 
neurodegenerative disorders of the central nervous system. J Neurochem 138: 653-693. 
Bachstetter AD, Norris CM, Sompol P, Wilcock DM, Goulding D, Neltner JH, St. Clair D, Watterson 
DM, Van Eldik LJ (2012) Early stage drug treatment that normalizes proinflammatory cytokine 
production attenuates synaptic dysfunction in a mouse model that exhibits age- dependent 
progression of Alzheimer’s disease-related pathology. J Neurosci 32: 10201-10210. 
Bachstetter AD, Webster SJ, Goulding DS, Morton JE, Watterson DM, Van Eldik LJ (2015) 
Attenuation of traumatic brain injury-induced cognitive impairment in mice by targeting increased 
cytokine levels with a small molecule experimental therapeutic. J Neuroinfl 12:69. 
Bachstetter AD, Zhou Z, Rowe RK, Xing B, Goulding DS, Conley AN, Sompol P, Meier S, Abisambra 
JF, Lifshitz J, Watterson DM, Van Eldik LJ (2016) MW151 inhibited IL-1β levels after traumatic brain 
injury with no effect on microglia physiological responses. PLoS One 11:e0149451. 
Chrzaszcz MA, Venkatesan C, Dragisic T, Watterson DM, Wainwright MS (2010) Minozac treatment 
prevents increased seizure susceptibility in a mouse “two-hit” model of closed skull traumatic brain 
injury and electroconvulsive shock-induced seizures. J Neurotrauma 27: 1283- 1295. 
Cummings J, Lee G, Ritter A, Zhong K (2018) Alzheimer’s disease drug development pipeline: 2018. 
Alz & Dementia: Transl Res Clin Interven 4: 195-214. 
Fillit H, Friedman L, Hara Y, Koemeter-Cox A, McKeehan N (2017) Closing in on a cure. Alzheimer’s 
Drug Discovery Foundation 2017 Alzheimer’s Clinical Trials Report. 
Greene-Schloesser D and Robbins ME (2012) Radiation-induced cognitive impairment-from bench to 
bedside. Neuro-Oncology 14: 37-44. 
Heneka M, Golenbock D, Latz E (2015) Innate immunity in Alzheimer’s disease. Nature Immunol 16, 
229–236. 
Heppner FL, Ransohoff RM, Becher B (2015) Immune attack: the role of inflammation in Alzheimer 
disease. Nature Rev Neurosci 16: 358-372. 
Hu W, Ralay Ranaivo HR, Roy SM, Behanna HA, Wing LK, Munoz L, Guo L, Van Eldik LJ, Watterson 
DM. (2007) Development of a novel therapeutic suppressor of brain proinflammatory cytokine up-
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17:414-418. 
Jacobson-Kram D, Jacobs A. (2005) Use of Genotoxicity Data to Support Clinical Trials or Positive 
Genetox Findings on a Candidate Pharmaceutical or Impurity Now What? Int. J. Toxicol. 24: 129–134. 
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Jenrow KA, Brown SL, Lapanowski K, Naei H, Kolozsvary A. Kim JH (2013) Selective inhibition of 
microglia-mediated neuroinflammation mitigates radiation-induced cognitive impairment. Radiation 
Research 179: 549-556. 
Jenrow KA, Brown SL, Kolozsvary AJJ, Lapanowski K, Kim JH (2014) Time-dependent inhibition of 
pan-inflammatory cytokines mitigates radiation-induced skin injury in mice. Radiation Res 182: 316-
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Karpus WJ, Reynolds N, Behanna HA, Van Eldik LJ. Watterson DM (2008) Inhibition of experimental 
autoimmune encephalomyelitis by a novel small molecular weight pro- inflammatory cytokine 
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metastasis. J Clin Oncol 24: 1295-1304. 
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options. J Clin Oncol 23: 6207-6219. 
Lloyd E, Somera-Molina K, Van Eldik LJ, Watterson DM, Wainwright MS (2008) Suppression of acute 
proinflammatory cytokine and chemokine upregulation by post-injury administration of a novel small 
molecule improves long-term neurologic outcome in a mouse model of traumatic brain injury. J 
Neuroinflammation 5:28. 
Lumniczky K, Szatmari T and Safrany G (2017) Ionizing radiation-induced immune and inflammatory 
reactions in the brain. Front Immunol 8: 517. 
Macauley SL, Wong AMS, Shyng C, Augner DP, Dearborn JT, Pearse Y, Roberts MS, Fowler SC, 
Cooper JD, Watterson DM, Sands MS (2014) An anti-neuroinflammatory that targets dysregulated 
glia enhances the efficacy of CNS-directed gene therapy in murine infantile neuronal ceroid 
lipofuscinosis. J Neurosci 34: 13077-13082. 
Somera-Molena KC, Robin B, Somera CA, Anderson C, Koh S, Behanna HA, Van Eldik LJ, 
Watterson DM, Wainwright MS (2007) Glial activation links early-life seizures and long-term 
neurologic dysfunction: evidence using a small molecule inhibitor of pro-inflammatory cytokine 
upregulation. Epilepsia 48: 1785-1800. 
Somera-Molina KC, Nair S, Van Eldik LJ, Watterson DM, Wainwright MS (2009) Enhanced microglial 
activation and proinflammatory cytokine upregulation are linked to increased susceptibility to seizures 
and neurologic injury in a ‘two-hit’ seizure model. Brain Research 1282: 162-172. 
Van Eldik LJ, Thompson WL, Ralay Ranaivo H, Behanna HA, Watterson DM (2007) Glia 
proinflammatory cytokine upregulation as a therapeutic target for neurodegenerative diseases: 
function-based and target-based discovery approaches. Intl Rev Neurobiol 82:277-296. 
Van Eldik LJ, Carrillo M, Cole PE, Feuerbach D, Greenberg BD, Hendrix J, Kennedy M, Kozauer N, 
Margolin RA, Molinuevo JL, Mueller R, Ransohoff RM, Wilcock DM, Bain L, Bales K (2016) The roles 
of inflammation and immune mechanisms in Alzheimer’s disease. Alzheimer’s & Dementia: 
Translational Research & Clinical Interventions 2: 99-109. 
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Warrington JP, Ashpole N, Csiszar A, Lee YW, Ungvari Z and Sonntag WE (2013) Whole brain 
radiation-induced vascular cognitive impairment: mechanisms and implications. J Vasc Res 50(6): 
445-457. 
Webster SJ, Van Eldik LJ, Watterson DM, Bachstetter AD (2015) Closed head injury in an age- 
related Alzheimer mouse model leads to an altered neuroinflammatory response and persistent 
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Page 1 of 19 
MW151-101 SAP Version 1.0 
 
23October2019 
 
Statistical Analysis Plan 
 
MW151-101, 28 Aug 2019 V2 
IND #143222 
DEPRU #: NN09 
Clinical Trials.gov #NCT04120233 
 
 
A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single Ascending Dose 
Study to Evaluate the Safety, Tolerability and Pharmacokinetic Profile of MW151 
Administered Orally to Healthy Volunteers 
 
 
Version 1.0 
23 October 2019 
 
Sponsor of IND:  ImmunoChem Therapeutics, LLC 
Sponsor of Clinical Study: University of Kentucky 
 
 
 
 
 
 
 


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MW151-101 SAP Version 1.0 
 
23October2019 
 
 
SIGNATURE PAGE AND APPROVALS 
 
Linda J. Van Eldik, PhD 
Principal Investigator 
Director, Sanders-Brown Center on Aging 
University of Kentucky 
Date 
Jeffrey Guptill, MD 
Duke Site Principal Investigator 
Duke Early Phase Research Unit 
Date 
Christoph Hornik, MD 
Associate Director 
Pharmacometrics 
Duke Clinical Research Institute 
 
Date 
Aruna Rikhi, MPH 
Biostatistician II 
Pediatrics 
Duke University Medical Center 
Date 
 
 
 
 
 
 
 
 
 
 


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MW151-101 SAP Version 1.0 
 
23October2019 
TABLE OF CONTENTS 
1.0 
LIST OF ABBREVIATIONS .........................................................................................................4 
2.0 
INTRODUCTION ............................................................................................................................5 
3.0 
OBJECTIVES..................................................................................................................................7 
Primary Objective ...........................................................................................................................7 
Secondary Objective ......................................................................................................................7 
4.0 
SUBJECT POPULATIONS ..........................................................................................................8 
4.1 
RANDOMIZED POPULATION ......................................................................................8 
4.2 
SAFETY POPULATION ..................................................................................................8 
4.3 
PK POPULATION ............................................................................................................8 
5.0 
STUDY DISPOSITION...................................................................................................................9 
6.0 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ................................... 10 
7.0 
STATISTICAL ISSUES ............................................................................................................... 11 
 
7.1 GENERAL ANALYSIS CONVENTIONS ........................................................................... 11 
8.0 
EXTENT OF EXPOSURE ........................................................................................................... 12 
8.1 
STUDY MEDICATION ................................................................................................... 12 
9.0 
PHARMACOKINETIC ANALYSIS ............................................................................................ 13 
10.0 
SAFETY ANALYSES .................................................................................................................. 14 
10.1 
ADVERSE EVENT ASSESSMENTS .......................................................................... 14 
10.2 
CLINICAL LABORATORY TESTING ........................................................................ 14 
10.3 
VITAL SIGNS ................................................................................................................. 14 
10.4 
ELECTROCARDIOGRAM MONITORING ................................................................. 15 
10.5 
PHYSICAL EXAMINATIONS ....................................................................................... 15 
10.6 
NEUROLOGICAL EXAMINATIONS ........................................................................... 15 
11.0 
DETERMINATION OF SAMPLE SIZE ..................................................................................... 16 
 
 
 


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1.0 
LIST OF ABBREVIATIONS 
 
ABBREVIATION 
DEFINITION 
AE 
Adverse Event 
DEPRU 
Duke Early Phase Research Unit 
DSMB 
Data Safety Monitoring Board 
ECG 
Electrocardiogram 
PK 
Pharmacokinetic 
SAD 
SAE 
Single Ascending Dose 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
TEAE 
Treatment Emergent Adverse Event 
 
 
 


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2.0 
INTRODUCTION 
 
MW01-2-151SRM (hereafter called MW151) is a CNS-penetrant, orally bioavailable, small 
molecule drug candidate that selectively suppresses stressor-induced proinflammatory 
cytokine overproduction with resultant amelioration of synaptic damage and cognitive 
impairment. The efficacy and pharmacodynamics of MW151 are evident across a dozen 
diverse animal studies where cytokine overproduction is a contributor to pathophysiology 
progression. MW151 exhibits efficacy, at low doses. It does not bring about 
immunosuppression or a non-selective anti-inflammatory action. There is no evidence of 
suppression of basal cytokine levels characteristic of homeostasis. Function at efficacy doses 
involves restoration to homeostasis after disease or injury induced increases.    
 
MW151 is being developed for the treatment of cognitive disorders. The development program 
is based on nonclinical evidence that MW151 improves neurocognitive outcomes in animal 
models of radiation therapy-induced cognitive impairment, Alzheimer’s disease and related 
dementias, and other cognitive disorders. 
The present first-in-human study will provide safety and pharmacokinetic (PK) information on 
single ascending doses (SAD) of MW151 to support decisions for continued clinical 
development. This study will assess the safety, tolerability, and PK profile of escalating single 
doses of MW151 in healthy adult participants. The trial design will be a double-blind, placebo-
controlled, SAD study of MW151 in healthy volunteers. Five dosing cohorts are initially planned. 
All subjects and the study personnel responsible for assessing adverse events (AEs) will be 
blinded. This statistical analysis plan (SAP) provides a more technical and detailed elaboration 
of the statistical analyses of safety and tolerability data as outlined in the protocol.  
 
In the study design, 40 healthy male and female volunteers, ages 18-50 years, will be dosed in 
1 of 5 dosing cohorts of 8 subjects each. Subjects will be admitted to the inpatient clinic on the 
day prior to dosing (Day -1) and will remain in the unit until discharge on Day 3.  A follow-up visit 
will be done on Day 7.  
 
A single dose of study drug or placebo will be administered as an oral capsule(s) on Day 1. Five 
different doses of MW151 will be evaluated in 5 sequential cohorts.  Dosing will start at the 
lowest dose, then escalate in the 2nd cohort, then escalate sequentially in the 3rd, 4th, and 5th 
cohorts. 
 
Cohort 1: Dose1: MW151/101 10 mg (or matched placebo), 1 x 10 mg capsule administered 
orally. 
Cohort 2: Dose2: MW151/101 20 mg (or matched placebo), 1 x 20 mg capsule administered 
orally. 
Cohort 3: Dose3: MW151/101 40 mg (or matched placebo), 2 x 20 mg capsule administered 
orally. 
Cohort 4: Dose4: MW151/101 80 mg (or matched placebo), 1 x 80 mg capsule administered 
orally. 
Cohort 5: Dose5: MW151/101 160 mg (or matched placebo), 2 x 80 mg capsule administered 
orally. 
As a safety consideration, two sentinel subjects in each cohort will be administered MW151 or 
placebo in a 1:1 ratio.  Dosing of the remaining subjects in a cohort may proceed after review of 
sentinel subject safety and tolerability data collected during the first 24 hours of dosing and 


University of Kentucky 
 
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MW151-101 SAP Version 1.0 
 
23October2019 
determination that no stopping rules are met.  The remaining 6 subjects will be randomized in a 
5:1 ratio. The remaining subjects in each cohort will be dosed sequentially, not simultaneously. 
After the completion of each cohort (Cohorts 1-5), the Data Safety Monitoring Board (DSMB) will 
review all available safety data before the dosing of the sentinel subjects of the next cohort. 
Data from Cohorts 1-5 will be reviewed in a blinded manner, unless the findings suggest the 
triggering of a stopping rule, in which case the data for the subjects in question may be 
unblinded (e.g., if a drug related serious AE [SAE] occurs, identifying whether the subject 
received MW151 or placebo to determine whether the stopping rule should be triggered). Doses 
may be varied based on the safety review, but the maximum dose will not exceed 160mg. 
Should the safety data warrant, dose levels may be reduced or additional cohorts added in 
order to generate a comprehensive understanding of the clinical dose range. Should additional 
cohorts be required above the planned 5 cohorts or doses within the planned cohorts changed, 
a protocol amendment will be submitted to the FDA and the Independent Ethics Committee for 
approval before implementation. 
Screening will be conducted in the 28 days prior to inpatient admission. After giving written 
informed consent, each subject will undergo a medical screen consisting of the following 
procedures: demographics; medical history; concomitant medication review; body temperature; 
12-lead ECG; vital signs (BP, HR); physical exam; alcohol and drug screen; Hepatitis B, 
Hepatitis C, HIV, Columbia Suicide Severity Rating Scale and TB screens; and safety laboratory 
work and pregnancy testing.  
 
One day prior to dosing (Day -1), subjects will be admitted to the Duke Early Phase Research 
Unit (DEPRU) Phase 1 unit for final qualification assessments. These assessments will include 
inclusion/exclusion review, medical history, physical exam, infection screen, body temperature, 
alcohol and drug screen, vital signs, pregnancy test, neurological exam, and safety laboratory 
tests.  
 
A single dose of study drug or placebo will be administered as an oral capsule(s) on Day 1. 
During dosing, subjects will be continuously monitored with 12-lead ECG, blood pressure, and 
heart rate.  Plasma samples will be drawn at sequential time points for PK analysis. 
 
Subjects will remain in the clinical research unit until discharge on Day 3. Follow-up will be done 
through a clinic visit on Day 7. The follow-up visit will consist of safety lab work, body temperature, 
ECG, vital signs, concomitant medication review, and assessment of adverse events (AEs).  
 
 
 


University of Kentucky 
 
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MW151-101 SAP Version 1.0 
 
23October2019 
 
3.0 
OBJECTIVES 
 
Primary Objective 
To assess the safety and tolerability of single ascending doses of MW151 when administered 
orally to healthy adult volunteers. 
The hypothesis is that MW151 will be safe in humans when administered in a SAD paradigm, 
with no severe or serious adverse events. 
Secondary Objective 
To assess the PK profile of single ascending doses of MW151 when administered orally to 
healthy adult volunteers. 
 
 


University of Kentucky 
 
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MW151-101 SAP Version 1.0 
 
23October2019 
4.0 
SUBJECT POPULATIONS 
 
Any subject who discontinues the study prior to dose administration for reasons other than AEs 
may be replaced by a different subject. The replacement subject will receive the same treatment 
as the original subject. 
 
 
4.1 
RANDOMIZED POPULATION 
 
The Randomized Population will consist of all subjects who sign informed consent and who are 
randomized to a treatment group in the study. 
 
 
4.2 
SAFETY POPULATION 
 
The Safety Population will consist of all subjects in the Randomized Population who receive any 
double-blind study medication (MW151 or placebo). 
 
 
4.3 
PK POPULATION 
 
The PK Population and analyses will be defined in the PK Analysis Plan. 
 
 


University of Kentucky 
 
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23October2019 
5.0 
STUDY DISPOSITION 
 
The number of subjects included in each study population (i.e., Randomized, Safety) will be 
summarized by cohort and active drug vs. placebo.  
The number and percentage of subjects who completed and prematurely discontinued the study 
will be presented by study drug and overall vs placebo for the Randomized Population. Reasons 
for premature discontinuation as recorded on the completion page of the CRF will be 
summarized, as applicable. 
 
 
 
 
 


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6.0 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS 
 
Demographic parameters (e.g. age, race, sex, weight, height, BMI) and other baseline 
characteristics, such as medical history, will be summarized by treatment group for the Safety 
Population. In addition, data listings will be generated. 
 
 
 
 


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7.0 
STATISTICAL ISSUES 
 
7.1 
GENERAL ANALYSIS CONVENTIONS 
 
General statistical approaches are presented below.   
All subjects in the Safety Population will be included in the safety analysis grouped by cohort 
and treatment group. Statistical analysis of safety data will be descriptive.  
Baseline is defined as the last assessment prior to dosing of study medication.   
For continuous variables, summaries will include sample size, mean, median, standard 
deviation, minimum, and maximum.  For categorical variables, the summaries will include 
frequencies and corresponding percentages. No inferential hypothesis testing will be performed. 
Repeat or unscheduled results will not be included in the summaries, but will be listed. Data 
from placebo subjects will be pooled for final presentations.   
 
Missing data results will not be imputed. Data summaries and analyses (e.g. means) will be 
calculated using all available data.  If the start day for an AE is missing, day of study drug 
administration will be used and AE will be considered treatment emergent.  Neither month nor 
year will be imputed for AE. 
Statistical analyses will be performed in SAS, Version 9.4 or newer. 
 
 
 


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23October2019 
8.0 
EXTENT OF EXPOSURE 
 
8.1 
STUDY MEDICATION 
 
Exposure to study medication for the Safety Population will be summarized in terms of the 
amount of dose administered (in mg) for each dose cohort and treatment group. Concomitant 
medications will be listed. Any instance of a subject receiving a dose other than the assigned 
dose will be listed. Descriptive statistics will be presented by treatment group.  
 
 
 
 


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23October2019 
9.0 
PHARMACOKINETIC ANALYSIS 
 
The PK analysis is outside the scope of this SAP and is described in a separate PK statistical 
analysis plan.  
 
 


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23October2019 
10.0 
SAFETY ANALYSES 
 
The safety analysis will be performed using the Safety Population. Safety and tolerability will be 
assessed on the basis of physical examination, neurological examination, vital signs, clinical 
laboratory values, ECG readings, and adverse event (AE) reports. 
Statistical analysis of safety data will be descriptive.   
 
10.1 
ADVERSE EVENT ASSESSMENTS 
 
Adverse events (AEs) will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) v21.0 – 5 Level or newer. AEs will be listed and summarized by treatment group and 
dose level. Where applicable, AEs may also be listed by severity, seriousness, relationship to 
study treatment and by system organ class and preferred term.  
A treatment-emergent AE (TEAE) is an AE, regardless of relationship to study drug, which 
occurs during or after the first dose of study treatment. TEAE will be summarized by MedDRA 
System Organ Class and Preferred Term. 
 
10.2 
CLINICAL LABORATORY TESTING 
 
Summary statistics of observed and change from baseline data will be presented for each 
treatment group and dose where applicable. Shift tables summarizing the numbers of subjects 
shifting from normal pre-dose values to abnormal post-dose values will also be presented where 
applicable. Listings for all safety laboratory assessments will be presented.   
Lab tests included will be all in the hematology and coagulation panel, biochemistry panel, and 
urinalysis panel (as needed lab tests: RBC, WBC, hyaline casts, cellular casts, and granular 
casts will only be presented as listings). 
 
10.3 
VITAL SIGNS 
 
Vital signs (supine systolic and diastolic blood pressure, orthostatic change in systolic and 
diastolic blood pressure, supine heart rate/pulse, body temperature) and changes from baseline 
at each time point will be presented by cohort and treatment group.  Listings for all vital signs 
and orthostatic change will be presented. 
 
Clinically notable vital signs will be listed and summarized by treatment group and dose. Criteria 
for Clinically Notable vital sign abnormalities are indicated in Table 2 below. 
 
 


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MW151-101 SAP Version 1.0 
 
23October2019 
Table 2: Criteria for Clinically Notable Vital Sign Abnormalities 
Parameter 
High Threshold 
Low Threshold 
Systolic BP (supine) 
> 30 mmHg increase from baseline 
> 30 mmHg decrease from baseline 
Diastolic BP (supine) 
> 20 mmHg increase from baseline 
> 30 mmHg decrease from baseline 
Heart Rate (supine) 
> 120 bpm and an increase in HR of 
 15 bpm from baseline 
< 40 bpm and a decrease in HR of  15 
bpm from baseline 
Body Temperature 
> 39.0oC (> 102.2oF) 
< 35.0oC (< 95.0oF) 
 
10.4 
ELECTROCARDIOGRAM MONITORING 
 
ECG parameters (e.g. Ventricular Heart Rate, PR interval, QRS interval, QTc interval, QTcB, 
QTcF interval, and RR interval) and changes from baseline at each assessment time point will 
be presented by cohort and treatment group.  Listings for ECG parameters will also be 
presented. 
 
Clinically notable ECGs will be listed and summarized by treatment group and dose. Criteria for 
Clinically notable ECG abnormalities are indicated in Table 3 below: 
 
Table 3: Criteria for Clinically Notable ECG Abnormalities 
Parameter 
High Threshold 
Low Threshold 
PR interval 
PR  220 ms 
PR ≤ 120 ms 
QRS duration 
QRS duration  120 ms and an increase of  20 ms 
from baseline 
- 
QT interval 
QT interval > 500 ms 
- 
QTcF interval 
Men: QTcF interval  450 ms and an increase of 60 
ms from baseline OR QTcF interval >500 ms 
Women: QTcF interval  470 ms and an increase of 
60 ms from baseline OR QTcF interval >500 ms 
- 
 
10.5 
PHYSICAL EXAMINATIONS 
 
Descriptive statistics for weight at baseline and changes from baseline at each assessment time 
point will be presented by cohort and treatment group. A listing of physical examination data for 
all subjects will be provided. 
 
 
10.6 
NEUROLOGICAL EXAMINATIONS 
 
Neurological examinations include mental status, cranial nerves 2-12, motor system and 
coordination, reflexes, and sensory system. Shift tables summarizing the numbers of subjects 
shifting from normal pre-dose values to abnormal post-dose values will be created. A listing of 
abnormal neurological examination data for all subjects will be provided.  
 


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23October2019 
11.0 
DETERMINATION OF SAMPLE SIZE 
 
This trial is designed to investigate the safety, tolerability, and PK properties of the drug MW151 
in a dose escalation Phase Ia study. The number of subjects is based upon the need to gain 
this knowledge in healthy individuals using as few subjects as possible. Since this is the first 
study of MW151 in humans, there is no prior experience upon which to base estimates of 
variability for the PK responses to SAD treatment with MW151. No power analysis is conducted 
but the cohort size is based on accepted standards in similar Phase I studies: 8 subjects per 
dose with 6 randomly assigned to active drug while the remaining 2 subjects receive placebo. 
Eight subjects per cohort was deemed sufficient for obtaining an adequate preliminary 
description of the responses of interest. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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23October2019 
Appendix A 
Table 1. Schedule of Activities 
 
Day/Procedures 
Screening 
(1) 
-1 
Admission 
1 
2 
3 
Discharge (2) 
7 
FU visit 
Informed consent 
X 
 
 
 
 
 
Inclusion/Exclusion Review 
X 
X 
 
 
 
 
Demographics  
X 
 
 
 
 
 
Medical History 
X 
X 
 
 
 
X 
Columbia Suicide Severity Rating 
Scale 
X 
 
 
 
 
 
Physical Examination (3) 
X 
X 
 
X 
 
X 
Infection Screen (4) 
 
X 
 
 
 
 
Body Temperature (5) 
X 
X 
X 
X 
X 
X 
Neurological Examination (6) 
 
X 
 
X 
 
 
  Safety Laboratory Tests (7) 
X 
X 
 
X 
 
X 
  Drug Screen (urine)  
X 
X 
 
 
 
 
Alcohol Screen (breathalyzer) 
X 
X 
 
 
 
 
  Hepatitis B & C/ HIV Screen 
X 
 
 
 
 
 
  TB test (blood test) 
X 
 
 
 
 
 
Pregnancy Test (serum at 
Screening/urine on D-1) 
X 
X 
 
 
 
 
12-lead ECG (8) 
X 
X 
X 
X 
X 
X 
Vital signs (BP/HR) (9) 
X 
X 
X 
X 
X 
X 
  PK blood sampling (10) 
 
 
X 
X 
 
 
Admit to Unit/Randomization (11) 
 
X 
 
 
 
 
Dosing (12) 
 
 
X 
 
 
 
Adverse Event Assessment 
 
 
X 
X 
X 
X 
Concomitant Medication Review 
X 
X 
X 
X 
X 
X 
Discharge from Unit 
 
 
 
 
X 
 
 
Footnotes to Schedule of Activities 
(1) Screening will occur within 28 days of dosing. 
(2) Subjects who discontinue from the study should undergo all Early Termination assessments as per 
the Day 3 visit. 


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23October2019 
(3) Weight will be measured during all physical examinations and height will be measured at Screening 
only. Physical examination will include general appearance; head, eyes, ears, nose, throat (HEENT); 
cardiovascular; lung; abdominal; musculoskeletal; and skin. 
(4) On Day -1, subjects will be screened for the presence of infection as part of physical examination, 
body temperature, recent/current antibiotic use, recent surgery, evidence of dental abscess, unhealed 
skin lesions etc. On Day 1 before dosing, subjects will be screened for emergence of acute illness. 
(5)  Body temperature will be measured at the following time-points: 
 
Screening 
 
Day -1 
 
Day 1 before dosing and again at 12h post-dose   
 
Day 2 – Day 3 approximately 24h and 48h, respectively, after dosing 
 
Day 7 
(6) Neurological examination will include mental status evaluation, cranial nerves 2-12 testing, motor 
system and coordination testing, reflex evaluation and sensory system evaluation. The neurological 
examination should be conducted at the same time as the physical examination when both are scheduled 
on the same study day. 
 
Day -1 
 
Day 2 
(7) Safety laboratory samples (Hematology/Coagulation/Biochemistry/Urinalysis) will be taken after the 
subject has fasted for a minimum of 10 hours as follows: 
 
Screening (all except creatine kinase, amylase, lipase, cholesterol, HDL/LDL/triglycerides) 
 
Day -1 
 
Day 2 
 
Day 7 
(8)  A 12-lead ECG will be performed (after lying quietly for 5 minutes). Triplicate tracings (3x) will be 
taken at Day -1 only and will serve as the Baseline (pre-dose measurement). ECGs will be performed at 
the following time points. 
 
Screening 
 
Day -1 
 
Day 1: approximately 1h, 2h, 4h, and 12h post-dose  
 
Day 2: approximately 24h post-dose   
 
Day 3 
 
Day 7  
Subjects will be monitored on telemetry from approximately 30 min prior to dosing through the 
4 hour post-dose ECG. 
(9)  Vital signs will include BP and HR.  At each time point where vital signs are measured, heart rate and 
blood pressure will first be checked in the supine position and then in the standing position with at least 2 
minutes between the supine and standing measurements. Vitals will be performed at the following time-
points: 
 
Screening 
 
Day -1 
 
Day 1: Pre-dose and at 1h, 2h, 4h, and 12h post-dose  
 
Day 2: approximately 24h and 36h post-dose   
 
Day 3  


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23October2019 
 
Day 7  
(10) PK samples will be taken at the following time-points, anchored to the start of dosing. 
 
Day 1: Pre-dose, and 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h post-dose 
 
Day 2: 24h and 36h post-dose 
(11) Randomization is expected to occur on D-1, but if there are delays in receiving prequalification safety 
labs randomization may occur on D1 prior to dosing. 
(12) Dosing will be by oral capsule administration, on day 1. 
 


Consent to Participate in a Research Study
ADULT
A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single Ascending Dose Study to 
Evaluate the Safety, Tolerability and Pharmacokinetic Profile of MW151 Administered Orally to 
Healthy Volunteers
DEPRU #: NN09
Page 1 of 17
Subject*Initials_________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
You are being asked to take part in this research study because you are a healthy female individual who 
does not have known health conditions.  Research studies are voluntary and include only people who 
choose to take part.  Please read this consent form carefully and take your time making your decision. 
As your study doctor or study staff discusses this consent form with you, please ask him/her to explain 
any words or information that you do not clearly understand.  We encourage you to talk with your 
family and friends before you decide to take part in this research study.  The nature of the study, risks, 
inconveniences, discomforts, and other important information about the study are listed below.
Please tell the study doctor or study staff if you are taking part in another research study.
This study is funded by a grant from the National Institute on Aging, awarded to University of 
Kentucky. Through this grant, University of Kentucky will pay Duke University Health System (DUHS) 
and Dr. Jeffrey Guptill to perform this research
WHO WILL BE MY DOCTOR ON THIS STUDY?
If you decide to participate, Dr. Jeffrey Guptill will be your doctor for the study and will be in contact 
with your regular health care provider throughout the time that you are in the study and afterwards, if 
needed. 
CONCISE SUMMARY
The purpose of this study is to find out whether an investigational drug, MW151, is safe and well 
tolerated. 
If enrolled, you will undergo screening procedures to see if you qualify. If you qualify and wish to 
continue, you will be asked to return to the Duke Early Phase Clinical Research Unit (DEPRU) for a 
3-night overnight stay. There is also one follow-up visit which will occur about 3-5 days after 
discharge. Your participation in the study will last up to 5 weeks. You will have the following 
procedures performed at various times throughout the study: vital signs, ECGs, blood collection, 
urine collection, physical exam, and neurological exam. You will receive a single dose of MW151, 
either 20, 40, 80, or 160 mg.  MW151 will be administered as a capsule (orally). 
There are risks to this study drug that are described in this document. Common risks include nausea 
and headache. There could also be additional risks which could be serious that have not yet been 
identified.
If you are interested in learning more about this study, please continue reading below.
DUHS IRB
IRB NUMBER: Pro00103072
IRB REFERENCE DATE: 08/13/2021
IRB EXPIRATION DATE: 08/22/2022


Consent to Participate in a Research Study
ADULT
A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single Ascending Dose Study to 
Evaluate the Safety, Tolerability and Pharmacokinetic Profile of MW151 Administered Orally to 
Healthy Volunteers
DEPRU #: NN09
Page 2 of 17
Subject*Initials_________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
WHY IS THIS STUDY BEING DONE?
The purpose of this study is to find out whether an investigational drug is safe and well tolerated. 
“Investigational” in the context of a clinical study means the drug is being tested for safety and 
effectiveness and has not been approved by the FDA for use in the United States. In this informed 
consent form, the investigational drug will be referred to as MW151 HCl. The study will also measure 
how the drug is moved to the bloodstream after administration, and how long it takes for the body to 
remove the drug from the bloodstream. 
MW151 HCl is being studied as a possible treatment for people with brain tumors who suffer from 
memory loss as a consequence of radiation therapy. Research studies conducted in animals and in test 
tubes have shown that MW151 HCl can reduce the amount of brain inflammation that occurs in the first 
few hours to days after the radiation dose. In these research studies, animals that received MW151 HCl 
were shown to recover better and faster.  
MW151 HCl has been given to humans at a single dose of 10 mg.  This study will look at the safety and 
tolerability of MW151 HCl at higher doses (20, 40, 80, 160 mg) and will look at how the amount of 
drug in the blood changes over time.   
HOW MANY PEOPLE WILL TAKE PART IN THIS STUDY?
Approximately 32 female volunteers (subjects) will take part in this study at Duke (8 subjects at each 
dose level). It may be necessary to screen as many as 80 subjects to ensure 32 people are able to 
complete the study. Duke is the only site for this study.
WHAT IS INVOLVED IN THE STUDY?
You will be randomly assigned (like the flip of a coin) to receive either MW151 HCl or placebo.  A 
placebo is an inactive substance given in the same form as the study drug. The first two volunteers dosed 
will have a 1 in 2 (50%) chance of receiving MW151 HCl or a placebo. Of remaining six subjects you 
have a 5 in 6 (83%) chance of receiving MW151 HCl and a 1 in 6 (17%) chance of receiving a placebo. 
Neither you nor the study doctor will know if you are getting MW151 HCl or placebo. However, in an 
emergency, the study doctor can find out.  
You will get one dose of study drug on Day 1. You will receive study drug by mouth in the form of a 
capsule. 
The planned dosing in the study is: 
Group 1 (8 volunteers): 10 mg of MW151 HCl or placebo
Group 2 (8 volunteers): 20 mg of MW151 HCl or placebo
DUHS IRB
IRB NUMBER: Pro00103072
IRB REFERENCE DATE: 08/13/2021
IRB EXPIRATION DATE: 08/22/2022


Consent to Participate in a Research Study
ADULT
A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single Ascending Dose Study to 
Evaluate the Safety, Tolerability and Pharmacokinetic Profile of MW151 Administered Orally to 
Healthy Volunteers
DEPRU #: NN09
Page 3 of 17
Subject*Initials_________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
Group 3 (8 volunteers): 40 mg of MW151 HCl or placebo
Group 4 (8 volunteers): 80 mg of MW151 HCl or placebo
Group 5 (8 volunteers): 160 mg of MW151 HCl or placebo
  
For safety reasons, the first 24 hours of safety data from the first 2 volunteers in each group will be 
reviewed before the rest of the volunteers may receive study drug. After all 8 volunteers in Group 2 are 
finished, safety information from Group 2 will be reviewed by the study doctor and the medical and 
safety monitors before proceeding to the next group. Similar procedures will be followed for the 
remaining groups.
The study doctor will talk to you about the things you must do or not do to participate. Please tell your 
regular health care providers and any emergency care providers that you are in this research study.
If you agree to be in this study, you will be asked to sign and date this consent form.  You will have the 
following tests and procedures performed at the Screening Visit to make sure that you are eligible. The 
Screening Visit will take about 2-3 hours to complete. 
 
Screening Visit 
The following will be done during the Screening Visit:

Before any study procedures are done, you will provide your informed consent.

You will be asked about your background and medical history. The study staff will also ask you 
questions about your age and race. 

You will be asked about your history of suicidal ideation and behavior.

You will be asked about all medicines that you take (including non-prescription medicines, 
vitamins, herbs and supplements).

You will be asked about your recent nicotine usage. 

You will have a physical exam, including measuring your height and weight.

Your vital signs will be measured, including blood pressure, heart rate, and body temperature.

Blood samples will be collected to check for tuberculosis, hepatitis B, hepatitis C and human 
immunodeficiency virus (HIV). If you have positive test results for HIV or hepatitis B or C, we 
will notify you. We are required to notify state health authorities of positive results. If these tests 
are positive you cannot take part in this research study. If you do not want to be tested, you 
should not take part in this research study. 

Female subjects will have a pregnancy test. 
DUHS IRB
IRB NUMBER: Pro00103072
IRB REFERENCE DATE: 08/13/2021
IRB EXPIRATION DATE: 08/22/2022


Consent to Participate in a Research Study
ADULT
A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single Ascending Dose Study to 
Evaluate the Safety, Tolerability and Pharmacokinetic Profile of MW151 Administered Orally to 
Healthy Volunteers
DEPRU #: NN09
Page 4 of 17
Subject*Initials_________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345

Post-menopausal women who have not had a regular period for at least 12 months in a row may 
need to have a blood sample taken to test for the amount of follicle stimulating hormone (FSH). 
This test is done to make sure that you can no longer become pregnant. 

Blood samples will be taken in order to check blood cell counts, blood chemistry, and how well 
your blood clots (these tests are called hematology, serum chemistry, and coagulation panel). 

A urine sample will be taken for testing to check for signs of infection, blood, and protein in the 
urine. 

A urine sample will be taken to test for any drugs of abuse (illegal or prescription).

An alcohol breathalyzer will be performed.

An ECG will be performed. An “ECG” or “electrocardiogram” is a test that measures the 
electrical activity of the heart. A technician will place patches connected by wires to a machine 
on your chest. The machine records the electrical activity of your heart. 

The study doctor will determine if you are eligible to continue into the study. If you will not be 
able to continue in the study, the study doctor will discuss with you.
Study Day -1 (Admission to the Study Clinic)
You will be admitted to the Duke clinic one day before you receive study drug. You will be asked to fast 
(no food or drink except water) for 10 hours before arriving at the clinic. You will stay at the clinic for 3 
nights and 4 days. On Day -1, you will repeat all of the tests and procedures described above for 
screening to make sure you continue to be eligible. The following procedures will be done on this study 
day:

You will be asked about any changes to your health since the screening visit

You will be asked about any medicines you are taking or have taken since the screening visit

Your vital signs (blood pressure and pulse) will be measured

Your temperature will be taken

Your weight will be measured

An ECG will be performed

You will have a physical exam, including an evaluation of any infection you may have (this 
includes questions about your health, medications, recent surgeries, and examining any skin 
lesions and inside your mouth for dental infections)

You will have a neurological exam (to evaluate your nervous system)

An alcohol breathalyzer will be performed.

You will give blood and urine for routine lab tests
o
Some of your urine will be tested for drugs of abuse
o
Some of your urine will be tested to check for signs of infection, blood, and protein
o
Women will have a urine pregnancy test
DUHS IRB
IRB NUMBER: Pro00103072
IRB REFERENCE DATE: 08/13/2021
IRB EXPIRATION DATE: 08/22/2022


Consent to Participate in a Research Study
ADULT
A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single Ascending Dose Study to 
Evaluate the Safety, Tolerability and Pharmacokinetic Profile of MW151 Administered Orally to 
Healthy Volunteers
DEPRU #: NN09
Page 5 of 17
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o
Your blood will be tested to check your general health, including blood cell counts, blood 
sugar, and liver function tests 
Alternate Subjects
If you are accepted into the study, you may be asked to be an alternate subject (a backup subject). If you 
are chosen as an alternate, you will be admitted to the Duke clinic on the day before the dosing starts. 
You will spend one night at the Duke clinic (the night prior to dosing). You will complete all of the 
planned study activities prior to the dosing. If another subject withdraws from the study prior to dosing, 
you may take the subject’s place and complete the study.
Study Day 1
On the morning of study Day 1, before getting the study drug, the following procedures will be done:

You will be asked how you are feeling

Your temperature will be taken

Your vital signs (blood pressure and pulse) will be measured

You will be connected to ECG telemetry

You may have an IV catheter inserted into one arm for blood draws

You will give a blood sample to measure the level of study drug in your blood

You will give a blood sample for genetic testing (see details below)

You will be given a light breakfast prior to dosing

If you remain eligible and you choose to continue, you will be given a single dose of the study 
drug (either MW151 HCl or placebo)
After getting the study drug the following procedures will be done:

You will be asked how you are feeling throughout the day

You will be asked about any medicine(s) you are taking throughout the day

You will give blood samples 7 more times throughout the day to measure the level of study drug 
in your blood

Your vital signs (blood pressure and pulse) and temperature will be measured throughout the 
day. You will have ECGs throughout the day
Study Day 2
You will be asked to fast for at least 10 hours before the Day 2 fasting blood samples are taken. The 
following procedures will be done on this study day:
DUHS IRB
IRB NUMBER: Pro00103072
IRB REFERENCE DATE: 08/13/2021
IRB EXPIRATION DATE: 08/22/2022


Consent to Participate in a Research Study
ADULT
A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single Ascending Dose Study to 
Evaluate the Safety, Tolerability and Pharmacokinetic Profile of MW151 Administered Orally to 
Healthy Volunteers
DEPRU #: NN09
Page 6 of 17
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
You will be asked how you are feeling throughout the day

You will be asked about any medicine(s) you are taking throughout the day

You will provide fasting blood samples for routine lab tests 

You will be given a light breakfast

You will have a physical exam

You will have a neurological exam

You will give two blood samples to measure the level of study drug in your blood

Your vital signs (blood pressure and pulse) will be measured throughout the day

Your temperature will be taken

An ECG will be performed 
Study Day 3 
The following procedures will be done on this study day:
 

You will be given a light breakfast 

You will have an ECG

Your vital signs (blood pressure and pulse) will be measured

Your temperature will be taken 

You will be asked how you are feeling

You will be asked about any medicine(s) you are taking
Before you leave the study clinic, the study doctor will confirm that it is safe for you to leave. 
Additional procedures may be ordered by the study doctor during the study if necessary to check your 
safety.   If it is not safe for you to leave the study doctor may ask for you to remain at the study clinic 
until it is safe for you to leave.
Study Follow-up Visit: Day 7  
You will be asked to fast for at least 10 hours before the Follow-up visit fasting blood samples are taken. 
The following procedures will be done on this study day:
 

You will provide a fasting blood sample for routine lab tests 

Your temperature will be taken 

You will have an ECG 

Your vital signs (blood pressure and pulse) will be measured

You will have a physical exam
DUHS IRB
IRB NUMBER: Pro00103072
IRB REFERENCE DATE: 08/13/2021
IRB EXPIRATION DATE: 08/22/2022


Consent to Participate in a Research Study
ADULT
A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single Ascending Dose Study to 
Evaluate the Safety, Tolerability and Pharmacokinetic Profile of MW151 Administered Orally to 
Healthy Volunteers
DEPRU #: NN09
Page 7 of 17
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
You will be asked how you are feeling 

You will be asked about any medicine(s) you are taking 
Additional procedures may be ordered by the study doctor during the study if necessary to check your 
safety. In the event of an adverse reaction, such as a rash, photographs of the affected area may be taken 
for the purpose of documentation.
Early Withdrawal from the Study 
You may be withdrawn from the study before completion, even if you want to continue. If you are 
withdrawn from the study due to safety reasons, you will be discharged from the unit only when the 
study doctor feels that it is safe to do so. If you stop the study early for any reason, the study doctor will 
ask you to perform the evaluations that are typically performed on Day 7. 
Your participation in the study may be stopped for any of the following reasons: 

Failure to follow the study requirements 

The study doctor decides it is in the best interest of your health and welfare to discontinue 

The sponsor stops development of MW151 HCl 

The FDA stops the study 
You may also decide to stop your participation in the study at any time and this will not affect your 
relationship with Duke or the sponsor.
Genetic Testing
The purpose of the genetic testing described above is to examine your genes (DNA) related to 
Apolipoprotein E (APOE), which is a protein involved in the metabolism of fats in the body. This 
testing is for research purposes only. Therefore, you will not receive results from this testing (except in 
your medical record, as described below).  It is not the purpose of this study to look for or provide you 
with any medical information or diagnoses relating to your present condition or any other disease or 
illness.  The research tests are not being used as diagnostic tests for any disease or illness. Your 
participation in this study is not a substitute for your regular medical care or check-ups.
HOW LONG WILL I BE IN THIS STUDY?
If you choose to participate in this study, your participation is expected to last up to 5 weeks, including 
up to 4 weeks for screening and 1 week for dosing and follow-up. 
DUHS IRB
IRB NUMBER: Pro00103072
IRB REFERENCE DATE: 08/13/2021
IRB EXPIRATION DATE: 08/22/2022


Consent to Participate in a Research Study
ADULT
A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single Ascending Dose Study to 
Evaluate the Safety, Tolerability and Pharmacokinetic Profile of MW151 Administered Orally to 
Healthy Volunteers
DEPRU #: NN09
Page 8 of 17
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You can stop participating at any time without penalty or loss of any benefits to which you are entitled. 
However, if you decide to stop participating in the study, we encourage you to talk to the study doctor 
first. 
WHAT ARE THE RISKS OF THE STUDY?
As a result of your participation in this study, you are at risk for the following side effects. You should 
discuss these with the study doctor and your regular health care provider if you choose.
Study Drug Risks 
Because MW151 HCl is considered “investigational,” complete information about the safety of MW151 
HCl is not yet available. At this stage of development, there is no evidence that the drug is unsafe or has 
specific risks when given to people; however, there could be risks, including death, that are as yet 
unidentified. MW151 HCl is made by chemical synthesis and many precautions have been taken in the 
making of the MW151 HCl to be used in the study. Group 1 received MW151 HCl at a 10 mg dose 
level, and there were no problems at that dose level. However, higher doses have not been tested yet. 
MW151 HCl may cause some, all or none of the following side-effects including nausea and headache 
and there could be risks, including death, that are as yet unidentified. You should discuss these with the 
study doctor and your regular health care provider if you choose.
Animals were given oral doses of MW151 HCl for up to 28 days, at multiple levels higher than those 
being studied in this clinical study. In rats, at certain doses tested, some changes were seen under the 
microscope in their testicles and sperm. Some of these changes got worse and did not resolve once the 
drug was stopped. The doses given to these rats were at least 2 times greater than the comparable dose of 
drug you could receive. Additionally, you will only be receiving a single dose. However, for maximum 
safety, Groups 2 – 5 will consist of female subjects only.
In dogs, at doses that are at least 10-times higher than the highest comparable dose you could receive, 
changes in the electrical signals in the heart (electrocardiogram, ECG) were seen. These electrical 
changes can potentially cause changes in the heart rhythm and in some severe cases could prevent your 
heart from pumping sufficient blood and you may be at risk of death. Your heart beat, blood pressure, 
heart rhythm and ECG will be closely monitored during this study, including continuously for the first 4 
hours after you receive the study drug.
In some, but not all studies in petri dishes that tested whether the study drug can damage the 
chromosomes that carry your genetic material (genes), MW151 HCl appeared to cause some damage to 
chromosomes. When a similar test was done in rats and in mice, at doses much higher than comparable 
dose you would be expected to receive, there was no damage to chromosomes seen. Since you receive 
DUHS IRB
IRB NUMBER: Pro00103072
IRB REFERENCE DATE: 08/13/2021
IRB EXPIRATION DATE: 08/22/2022


Consent to Participate in a Research Study
ADULT
A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single Ascending Dose Study to 
Evaluate the Safety, Tolerability and Pharmacokinetic Profile of MW151 Administered Orally to 
Healthy Volunteers
DEPRU #: NN09
Page 9 of 17
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only a single dose of MW151 HCl, the risk that your chromosomes become damaged by the study drug, 
is extremely low. Therefore, we believe the risk that the study drug could cause cancer is also extremely 
low. 
Because of the way the drug is thought to work, there could be a potential for MW151 HCl to affect 
your immune response (the way your body fights off infection). None of the animals tested so far has 
shown any bad change in their immune function. Subjects with any present or recent evidence of 
infection or at risk for infection are not eligible for the study. 
If you do not understand what some of these side effects or risks mean, ask the study doctor or the study 
staff to explain them to you. You will be carefully monitored throughout the study by the study doctor 
and study staff. Please report any side effects that you may notice.
Co-Occupancy During Confinement
There is an increased risk of COVID-19 with co-occupancy. For this reason, there will also be a need for 
required additional testing that is explained below.
1. Pre- admission:
a.
Participants are instructed to pay close attention to all COVID precautions, including 
masking, limiting contact with others, limiting travel, and maintaining social distancing.
b. Participants will have a COVID test within 72 hours prior to confinement and repeated 
the day of admission for the confinement period.
c.
Participants will be provided clear instructions regarding confinement expectations.
2. During confinement participants will:
a.
Immediately isolate and report development of new symptoms concerning for COVID 
b. Have a COVID test every 3 days.
c.
Eat and drink only in their assigned rooms.
d. Wear Duke provided mask unless eating, drinking, or sleeping.
e.
Remain at least 6 feet apart when not wearing a mask.
f.
Remain in their room unless scheduled time in the lounge area and only go there with 
their roommate.  Lounge time will be allocated so that participants remain with the same 
group during the confinement period in order to minimize exposure to others.
g. Perform hand hygiene with soap and water or approved hand sanitizer frequently.
h. Wipe down shared high touch surface areas after use – such as the washing machine, 
lounge table, remote control, sink handles, etc. 
DUHS IRB
IRB NUMBER: Pro00103072
IRB REFERENCE DATE: 08/13/2021
IRB EXPIRATION DATE: 08/22/2022


Consent to Participate in a Research Study
ADULT
A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single Ascending Dose Study to 
Evaluate the Safety, Tolerability and Pharmacokinetic Profile of MW151 Administered Orally to 
Healthy Volunteers
DEPRU #: NN09
Page 10 of 17
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i.
Be discharged to home for isolation and close observation should their COVID test 
become positive. 
3. Post-confinement:
a.
Participants will require quarantine and COVID testing day 5-7 post-exposure if they are 
exposed late during their confinement period.
 
Allergic Reaction Risks 
There is a risk of allergic reaction. If you have a very serious reaction to MW151 HCl or to the placebo 
you may be at risk of death. Some symptoms of allergic reactions are: rash, difficulty breathing, 
wheezing, sudden drop in blood pressure, swelling around the mouth, throat or eyes, a fast pulse, and 
sweating. Please alert the study doctor and study staff immediately if you have any of these symptoms, 
or any other side effects, during the study. 
Injection Risks/Catheter Insertion Risks/Blood Samples 
Risks associated with drawing blood from your arm include momentary discomfort and/or bruising.  
Infection, excess bleeding, clotting, or fainting are also possible, although unlikely.
A temporary needle (catheter) may be placed into your vein during the study to collect blood. This 
decreases the amount of needle sticks you would receive during these days. The study staff will keep the 
blood draw area clear and clean. Subjects may feel pain or experience bruising at the site where the 
blood is drawn or the catheter is inserted. There is a risk of subjects feeling dizzy or may faint. Infection 
at the site of the blood draw or catheter insertion is possible. Some minor discomfort may be felt when 
blood is drawn from the veins (or the catheter inserted) in your arm. 
You will be required to provide blood samples during the study. Throughout the study up to about 313 
mL (about 10.6 oz) of blood will be taken for scheduled tests. This is less than you would give during a 
regular donation to a blood service agency such as the Red Cross where a typical donation is one pint 
(about 16 oz or 475 mL). Extra blood samples may be taken, if needed, to check on your safety. 
ECGs and Blood Pressure Risks 
Electrocardiograms (ECGs) (electrical tracings of the heartbeat or heart rhythm) will be done during this 
study in which you will have pads placed on different parts of your body. There is no pain or discomfort 
during an ECG; however, removing the pads may cause some irritation to your skin. You may 
experience bruising from the blood pressure cuff.
DUHS IRB
IRB NUMBER: Pro00103072
IRB REFERENCE DATE: 08/13/2021
IRB EXPIRATION DATE: 08/22/2022


Consent to Participate in a Research Study
ADULT
A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single Ascending Dose Study to 
Evaluate the Safety, Tolerability and Pharmacokinetic Profile of MW151 Administered Orally to 
Healthy Volunteers
DEPRU #: NN09
Page 11 of 17
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Reproductive Risks
The effects of the study drug on a developing pregnancy or breastfeeding infant are not known.  Women 
who are pregnant, planning a pregnancy, or breastfeeding are not allowed to participate in studies of the 
drug. 
If you are a woman who could possibly become pregnant (you have not completed menopause, or you 
have not had a hysterectomy and/or both tubes and/or both ovaries removed) and you have a partner 
who is able to father children, a blood pregnancy test will be performed at screening, and it must be 
negative in order to continue.  In women 40 years old and older, blood pregnancy tests sometimes give a 
false positive or indeterminate result and additional testing may be needed.   A urine pregnancy test will 
be performed when you come in for your Study Day 1 visit.  
You and your partner must agree to either abstain completely from vaginal intercourse from the time of 
the screening visit until 1 month after you receive the study drug, or use an effective method of 
contraception for the same length of time.  Effective methods include (a) partner vasectomy, (b) bilateral 
tubal ligation, (c) intrauterine devices (IUDs), (d) hormonal methods (birth control pills, implants, 
injections, patches, vaginal rings, or (e) barrier methods (condoms, diaphragm, cervical cap) with a 
spermicide.   If you are not currently using one of these methods and would still like to participate in the 
study, the study doctor will discuss options with you.   
Because no birth control method is 100% effective, you should notify the study doctor immediately if 
you think there is any chance you are pregnant within 30 days after receiving the study drug.  
General Discomfort Risks 
You will be asked to fast during parts of this study. This may cause you some discomfort. In addition, 
study requirements such as overnight stays at the clinic, dietary restrictions and limitations on caffeine, 
alcohol, and smoking may also cause you some discomfort. You may experience bruising from the 
blood pressure cuff and/or irritation at the site of the patches applied to the skin for the ECG recordings. 
Serious adverse reactions and hospitalization 
Although all possible precautions are taken to prevent serious adverse reactions (side effects), if such an 
event occurs, it may be in your best interest to be admitted to hospital. Depending on the type of 
reaction, we may contact a medical specialist to be primarily responsible for your treatment. We will 
provide assistance to the hospital and doctors looking after you, but all hospital records are confidential 
and for this reason we are asking you to give us, and any emergency medical specialists we contact, 
consent to visit you and have access to your medical records.
DUHS IRB
IRB NUMBER: Pro00103072
IRB REFERENCE DATE: 08/13/2021
IRB EXPIRATION DATE: 08/22/2022


Consent to Participate in a Research Study
ADULT
A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single Ascending Dose Study to 
Evaluate the Safety, Tolerability and Pharmacokinetic Profile of MW151 Administered Orally to 
Healthy Volunteers
DEPRU #: NN09
Page 12 of 17
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Drug Interactions 
For your safety, you must tell the study doctor or nurse about all the prescribed medical foods and drugs, 
herbal products, over-the-counter (OTC) drugs, vitamins, natural remedies, and alcohol that you are 
taking before you start the study and before starting to take any of these products while you are on the 
study. 
There may be risks, discomforts, drug interactions or side effects that are not yet known.
ARE THERE BENEFITS TO TAKING PART IN THE STUDY?
If you agree to take part in this study, there will be no direct medical benefit to you. We hope the 
information learned from this study will benefit others in the future. 
WILL MY INFORMATION BE KEPT CONFIDENTIAL?
Participation in research involves some loss of privacy. We will do our best to make sure that 
information about you is kept confidential, but we cannot guarantee total confidentiality. Your personal 
information may be viewed by individuals involved in this research and may be seen by people 
including those collaborating, funding, and regulating the study. We will share only the minimum 
necessary information in order to conduct the research. Your personal information may also be given out 
if required by law. 
As part of the study, results of your study-related laboratory tests, x-rays, and procedures may be 
reported to University of Kentucky and its affiliates. In addition, your records may be reviewed in order 
to meet federal or state regulations. Reviewers may include representatives from the Food and Drug 
Administration, representatives and affiliates of University of Kentucky, the Duke University Health 
System Institutional Review Board, and others as appropriate. If any of these groups review your 
research record, they may also need to review your entire medical record.
As part of this study, you will be asked to have certain laboratory tests and/or other procedures 
performed. These test results will be recorded in your medical record and will be reported to the 
representatives and affiliates of University of Kentucky. 
The Department of Health and Human Services (HHS) has issued a Certificate of Confidentiality to 
further protect your privacy.  With this Certificate, the investigators may not disclose research 
information that may identify you in any Federal, State, or local civil, criminal, administrative, 
legislative, or other proceedings, unless you have consented for this use. Research information protected 
by this Certificate cannot be disclosed to anyone else who is not connected with the research unless:  
DUHS IRB
IRB NUMBER: Pro00103072
IRB REFERENCE DATE: 08/13/2021
IRB EXPIRATION DATE: 08/22/2022


Consent to Participate in a Research Study
ADULT
A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single Ascending Dose Study to 
Evaluate the Safety, Tolerability and Pharmacokinetic Profile of MW151 Administered Orally to 
Healthy Volunteers
DEPRU #: NN09
Page 13 of 17
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1) there is a law that requires disclosure (such as to report child abuse or communicable 
diseases but not for legal proceedings); 
2) you have consented to the disclosure, including for your medical treatment; or 
3) the research information is used for other scientific research, as allowed by federal 
regulations protecting research subjects. 
Disclosure is required, however, for audit or program evaluation requested by the agency that is funding 
this project or for information that is required by the Food and Drug Administration (FDA).
 
You should understand that a Confidentiality Certificate does not prevent you or a member of your 
family from voluntarily releasing information about yourself or your involvement in this research. If you 
want your research information released to an insurer, medical care provider, or any other person not 
connected with the research, you must provide consent to allow the researchers to release it. This means 
that you and your family must also actively protect your own privacy.
Finally, you should understand that the investigator is not prevented from taking steps, including 
reporting to authorities, to prevent serious harm to yourself or others.
The study results will be retained in your research record for at least six years after the study is 
completed. At that time either the research information not already in your medical record may be 
destroyed or information identifying you will be removed from such study results at DUHS.  Any 
research information in your medical record will be kept indefinitely.
Some information collected in research studies is maintained in your medical record. However, for this 
study that information will be inaccessible until the end of the study, unless your physician(s) decide 
that it is necessary for your care. 
This information may be further disclosed by the sponsor of this study.  If disclosed by the sponsor, the 
information is no longer covered by federal privacy regulations.
If this information is disclosed to outside reviewers for audit purposes, it may be further disclosed by 
them and may not be covered by federal privacy regulations.
While the information and data resulting from this study may be presented at scientific meetings or 
published in a scientific journal, your name or other personal information will not be revealed.
Some people or groups who receive your health information might not have to follow the same privacy 
rules. Once your information is shared outside of DUHS, we cannot guarantee that it will remain private. 
DUHS IRB
IRB NUMBER: Pro00103072
IRB REFERENCE DATE: 08/13/2021
IRB EXPIRATION DATE: 08/22/2022


Consent to Participate in a Research Study
ADULT
A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single Ascending Dose Study to 
Evaluate the Safety, Tolerability and Pharmacokinetic Profile of MW151 Administered Orally to 
Healthy Volunteers
DEPRU #: NN09
Page 14 of 17
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If you decide to share private information with anyone not involved in the study, the federal law 
designed to protect your health information privacy may no longer apply to the information you have 
shared.  Other laws may or may not protect sharing of private health information.
WHAT ARE THE COSTS TO YOU?
While you are in the study, you may still need to get regular medical care. You (and/or your health care 
payer) will still have to pay for the costs of your regular medical care that are not part of this study. 
There will be no costs to you for being in this study. You will not have to pay to receive the study drug. 
There are also no costs for the tests or procedures performed as part of the study.  
We will monitor your DUHS patient care charges to make sure that costs are directed appropriately.  If 
you have any questions or concerns about appropriate billing, contact your study team coordinator so 
that he/she can help find a resolution.
WHAT ABOUT COMPENSATION?
You will be reimbursed up to $1050 for your expenses related to your participation (parking, gas, and 
time). If you withdraw from the study, you will still receive compensation for the parts of the study you 
completed. If you are an alternate subject, you will be compensated $350.
Visit
Stipend
Screening
$100
Day -1 (Admission)
$250
Day 1
$250
Day 2
$250
Day 3 (Discharge)
$100
Day 7
$100
Total
$1050
WHAT ABOUT RESEARCH RELATED INJURIES?
Immediate necessary medical care is available at Duke University Medical Center in the event that you 
are injured as a result of your participation in this research study. However, there is no commitment by 
Duke University, Duke University Health System, Inc., or your Duke physicians to provide monetary 
compensation or free medical care to you in the event of a study-related injury.
For questions about the study or research-related injury, contact Dr. Jeffrey Guptill at (919) 684-1672 
during regular business hours and at (919) 684-8111 after hours and on weekends and holidays.
DUHS IRB
IRB NUMBER: Pro00103072
IRB REFERENCE DATE: 08/13/2021
IRB EXPIRATION DATE: 08/22/2022


Consent to Participate in a Research Study
ADULT
A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single Ascending Dose Study to 
Evaluate the Safety, Tolerability and Pharmacokinetic Profile of MW151 Administered Orally to 
Healthy Volunteers
DEPRU #: NN09
Page 15 of 17
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WHAT ABOUT MY RIGHTS TO DECLINE PARTICIPATION OR WITHDRAW FROM THE 
STUDY?
You may choose not to be in the study, or, if you agree to be in the study, you may withdraw from the 
study at any time. If you withdraw from the study, no new data about you will be collected for study 
purposes unless the data concern an adverse event (a bad effect) related to the study.  If such an adverse 
event occurs, we may need to review your entire medical record.  All data that have already been 
collected for study purposes, and any new information about an adverse event related to the study, will 
be sent to the study sponsor.
Your decision not to participate or to withdraw from the study will not involve any penalty or loss of 
benefits to which you are entitled, and will not affect your access to health care at Duke. If you do 
decide to withdraw, we ask that you contact Dr. Guptill in writing and let him know that you are 
withdrawing from the study.  His mailing address is Box 3854, DUMC, Durham, NC 27710.  
Dr. Guptill may ask you to complete the tests that would ordinarily occur when a person completes the 
study.
We will tell you about new information that may affect your health, welfare, or willingness to stay in 
this study.
Your doctor may decide to take you off this study if you have serious side effects, or if your study 
doctor determines that it is no longer in your best interest to continue.  The sponsor or regulatory 
agencies may stop this study at any time without your consent. If this occurs, you will be notified and 
your study doctor will discuss other options with you.
Your samples and/or data may be stored and shared for future research without additional consent if the 
information that identifies you are removed. If your identifying information is removed from your 
samples or data, we will no longer be able to identify and destroy them.
The use of your data and samples may result in commercial profit. You will not be compensated for the 
use of your data and samples other than what is described in this consent form.
A description of this clinical trial will be available on https://clinicaltrials.gov/  as required by U.S. Law.  
This Web site will not include information that can identify you.  At most, the Web site will include a 
summary of the results.  You can search this Web site at any time.
DUHS IRB
IRB NUMBER: Pro00103072
IRB REFERENCE DATE: 08/13/2021
IRB EXPIRATION DATE: 08/22/2022


Consent to Participate in a Research Study
ADULT
A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single Ascending Dose Study to 
Evaluate the Safety, Tolerability and Pharmacokinetic Profile of MW151 Administered Orally to 
Healthy Volunteers
DEPRU #: NN09
Page 16 of 17
Subject*Initials_________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS?
For questions about the study or a research-related injury, or if you have problems, concerns, questions 
or suggestions about the research, contact Dr. Jeffrey Guptill at (919) 684-1672 during regular business 
hours and at (919) 684-8111 after hours and on weekends and holidays.
For questions about your rights as a research participant, or to discuss problems, concerns or suggestions 
related to the research, or to obtain information or offer input about the research, contact the Duke 
University Health System Institutional Review Board (IRB) Office at (919) 668-5111.
DUHS IRB
IRB NUMBER: Pro00103072
IRB REFERENCE DATE: 08/13/2021
IRB EXPIRATION DATE: 08/22/2022


Consent to Participate in a Research Study
ADULT
A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single Ascending Dose Study to 
Evaluate the Safety, Tolerability and Pharmacokinetic Profile of MW151 Administered Orally to 
Healthy Volunteers
DEPRU #: NN09
Page 17 of 17
*
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
STATEMENT OF CONSENT
"The purpose of this study, procedures to be followed, risks and benefits have been explained to me. I 
have been allowed to ask questions, and my questions have been answered to my satisfaction. I have 
been told whom to contact if I have questions, to discuss problems, concerns, or suggestions related to 
the research, or to obtain information or offer input about the research. I have read this consent form and 
agree to be in this study, with the understanding that I may withdraw at any time.  I have been told that I 
will be given a signed and dated copy of this consent form."
__________________________________________
___________     ____________
Signature of Subject
Date
   Time
__________________________________________
___________     ____________
Signature of Person Obtaining Consent
Date
   Time
DUHS IRB
IRB NUMBER: Pro00103072
IRB REFERENCE DATE: 08/13/2021
IRB EXPIRATION DATE: 08/22/2022