Conditions: Alzheimer Disease
Keywords: Alzheimer's Dementia ATH-1017 Open Label
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 423
Healthy volunteers: no

Brief summary:
The objective of this study is to determine the safety and tolerability of fosgonimeton (ATH-1017) in subjects with mild to moderate Alzheimer's disease who completed the 26-week randomized treatment in Study ATH-1017-AD-0201 or Study ATH-1017-AD-0202.

Detailed description:
This is a multicenter, seamless, open-label extension (OLEX) study of ATH-1017 treatment in subjects with a clinical diagnosis of mild to moderate Alzheimer's disease who completed 26 weeks treatment in the randomized, placebo-controlled, double-blind studies, ATH-1017-AD-0201 and ATH-1017-AD-0202. This OLEX study will provide additional, longer-term safety and tolerability information on ATH-1017 administration up to 48 months in subjects with mild to moderate Alzheimer's disease.

Arms:
arm 1: Daily subcutaneous (SC) injection of ATH-1017 - 40mg Dosage

Interventions: intervention 1: ATH-1017
Intervention descriptions: intervention 1: Daily subcutaneous (SC) injection of ATH-1017 in a pre-filled syringe

Protocol document:
Prot_000.pdf: 
Athira Pharma, Inc.  
Protocol ATH-1017-AD-0203  
Clinical Study Protocol 
CONFIDENTIAL 
 
Version 4 
 Page 1 of 66 
12-APR-2024 
 
Clinical Study Protocol 
Open-Label Extension of Studies ATH-1017-AD-0201 and  
ATH-1017-AD-0202 in Subjects with Mild to Moderate Alzheimer’s Disease 
 
Sponsor: 
Athira Pharma, Inc. 
18706 North Creek Parkway 
Suite 104 
Bothell, WA 98011 
USA 
Protocol No.: 
ATH-1017-AD-0203 
IND No.: 
135103 
Investigational Medicinal Product (IMP) 
Name: 
Fosgonimeton (ATH-1017) 
Development Phase: 
Phase 3 
Emergency Telephone Number: 
(Refer to the study contacts page) 
SAE Reporting FAX Number/Email: 
 
  
Date of Final Protocol: 
12 APR 2024 
Version: 
4 
 
 
This clinical study will be conducted in accordance with the International Council for 
Harmonisation Tripartite Guideline for Good Clinical Practice (GCP) (E6), the protocol and with 
other applicable regulatory requirements. 
 
Confidentiality Statement 
This document contains confidential information of Athira Pharma, Inc. 
Do not copy or distribute without written permission from the Sponsor. 
 
 




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SIGNATURE PAGE 
Declaration of the Principal Investigator 
Protocol Title: Open-Label Extension of Studies ATH-1017-AD-0201 and ATH-1017-AD-0202 
in Subjects with Mild to Moderate Alzheimer’s Disease 
This clinical study protocol was subjected to critical review. The information it contains is 
consistent with current knowledge of the risks and benefits of the investigational medicinal 
product (IMP), as well as with the moral, ethical, and scientific principles governing clinical 
research in accordance with the International Council for Harmonisation Tripartite Guideline for 
Good Clinical Practice (GCP) (E6 R2), the ethical principles outlined in the Declaration of 
Helsinki, the protocol and with other applicable regulatory requirements applicable to this 
clinical study. 
 
Principal Investigator 
I have read this protocol and agree to conduct this study in accordance with all stipulations of the 
protocol and in accordance with International Council for Harmonisation Tripartite Guideline for 
Good Clinical Practice (GCP) (E6 R2), the ethical principles outlined in the Declaration of 
Helsinki and with other regulatory requirements applicable to this clinical study. 
I agree that the Sponsor or its representatives shall have access to any source documents from 
which case report form information may have been generated. 
I further agree not to originate or use the name Athira Pharma Inc. and/or ATH-1017 in any 
publicity, news release, or other public announcement, written or oral, whether to the public, 
press, or otherwise, relating to this protocol, to any amendment hereto, or to the performance 
hereunder, without prior written consent of Athira Pharma Inc. 
 
 
Signature of Site Principal Investigator 
 
 
Date (dd mmm yyyy) 
Printed Name of Site Principal Investigator 
 
Institution 
Name:__________________________ 
 
 
 
 




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label active treatment with ATH-1017 at a dose of 40 mg/day, unless the safety results 
obtained at Visit 7 of the parent studies or new baseline safety labs suggest otherwise, 
in which case they will not be eligible for this OLEX study.. Subjects who do not 
tolerate ATH-1017 40 mg/day, and/or who meet the stopping criteria, will be 
withdrawn from the study. As of v3 of this protocol (01 JUN 23), the dose of 
70 mg/day ATH1017 was discontinued- and subjects who were previously assigned to 
this dose were reassigned to the dose of 40 mg/day ATH-1017. 
Study drug will be administered by subcutaneous (SC) injection once daily (OD), 
preferably during the daytime. Subjects will take their last dose of blinded IMP 
(assigned to them in Study ATH-1017-AD-0201 or Study ATH-1017-AD-0202) on site 
under supervision of site staff at Visit 8/Day 182 of the parent studies (i.e., Visit 1/ 
Day 0 of this OLEX study). The first dose of open-label IMP from this study will be 
administered by subject or caregiver at the clinic the next day (Visit 2/Day 1), followed 
by a safety observation window of 1 hour (± 15 minutes) post-dose. Subjects must not 
take more than one dose within 8 hours of the previous dose. The subject should 
withhold study drug administration on the day of clinic visits; study drug 
administration will be done on site under supervision of site staff at these visits. Each 
subject is required to have a primary caregiver willing to accept responsibility for 
supervising or, if required, administering study drug, in accordance with all protocol 
requirements. During the open-label treatment period, clinic visits will take place on 
Day 0 and thereafter at Day 1, Weeks 2, 6, 12, 18, 22, 26, 32, 38, 44, 50, 56, 62, 68, 74, 
80, 86, 92, 98, 104, 110, 116, 122, 128, 134, 140, 146, 152, 158, 164, 170, 176, 182, 
188, 194, 200, and 206. Telephone call visits are scheduled for Week 1 (Day 7), and 
Week 4 (Day 28). A safety follow-up visit is scheduled 4 weeks after completion of the 
open-label period at Week 210 (see Table 1 for Schedule of Assessments). Subjects 
may live at home, in a senior residential setting, or an institutional setting without the 
need for continuous nursing care. The end of the study is defined as the date of the 
safety follow-up visit, Visit 41/Week 210. Subjects who terminate prior to Visit 40 are 
to complete same assessments as Visit 40/early termination (ET) within 2 weeks of the 
date of ET.  
An independent Data Safety Monitoring Board will conduct periodic review and 
assessments of safety data (AEs, labs, ECG, etc.) throughout the study to ensure the 
safety of study subjects. 


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Treatments 
Administered:  
Subjects will not be randomized to treatment in this OLEX study. All subjects who 
complete the Week 26 visit of either of the two parent studies, and meet the 
inclusion/exclusion criteria of Study ATH-1017-AD-0203, with no safety concerns 
from results obtained at Visit 7 of either of the two parent studies, will be assigned to 
open-label active treatment with ATH-1017 at a dose of 40 mg/day. -  
Investigational 
Medicinal Products: 
Open-label Treatment: ATH-1017 will be presented in prefilled 1 mL syringes of 
40 mg/mL. 
Prior to v3 of this protocol (01 JUN 2023), the 70 mg/mL dose was also presented in 
prefilled 1 mL syringes. 
Number of Subjects: 
It is estimated that up to approximately 450 subjects will enter this OLEX study; 
subjects will roll over from Studies ATH-1017-AD-0201 and ATH-1017-AD-0202 
(the parent studies). 
Duration of 
Treatment: 
The study will consist of 206 weeks open-label treatment and a 4-week safety 
follow-up. 
Study Population: 
Inclusion 
1. 
Subject has completed the Week 26 visit of either of the two parent studies.  
2. 
Male subjects and their partners must agree to continue to use a double-barrier 
method of contraception during the study, including the follow-up period, unless 
the partner is not of childbearing potential. Only female subjects of non-
childbearing potential (i.e., permanently sterilized, postmenopausal) are eligible 
for participation. 
3. 
Reliable and capable support person/caregiver, who is willing to accept 
responsibility for supervising the treatment or, if required, administering study 
drug in accordance with all protocol requirements. The support person/caregiver 
must see the subject at least once daily for administering or supervising dose 
administration. 
4. 
Subject capable of giving signed informed consent, which includes compliance 
with the requirements and restrictions listed in the Informed Consent Form and in 
this protocol. If the subject is incapable of giving informed consent in the 
judgment of the investigator, then consent may be provided by a legally 
acceptable representative. 
5. 
Written informed consent from a) the subject or legally acceptable representative 
and b) caregiver/support person has been obtained prior to any study-related 
procedures, including prior to initiating procedures to evaluate eligibility for the 
study. 
6. 
Written documentation has been obtained in accordance with the relevant country 
and local privacy requirements, where applicable (e.g., Written Authorization for 
Use and Release of Health and Research Study Information). 
7. 
Subjects and caregivers/support persons are able, as assessed by the investigator, 
and willing to follow study instructions and likely to complete all required study 
visits. 


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8. 
Subjects must be in generally good health as assessed by the investigator from 
medical history and physical/neurological examination, vital signs, ECG, and 
standard laboratory tests. 
Exclusion 
9. 
Subject has experienced a serious treatment-related AE during either of the two 
parent studies, which in the opinion of the investigator could present an increased 
safety risk to the subject during the OLEX study, in discussion with the Medical 
Monitor. 
10. New diagnosis of severe major depressive disorder even without psychotic 
features. Any subject with formalized delusions or hallucinations are excluded. 
11. Significant suicide risk as defined by suicidal ideation based on the C-SSRS at 
Visit 1 (i.e., a ‘yes’ response to Question 4 or 5, or any specific behaviours). 
12. Newly diagnosed malignant tumor, except for the following conditions that are 
stable in the judgement of the investigator: 
a) Adequately treated squamous and basal cell carcinoma, or squamous and 
basal cell carcinoma in situ; 
b) Prostate carcinoma in situ; 
c) Fully-excised (biopsy-proven) melanoma in situ; prior Medical Monitor 
approval is required. 
13. The subject has a condition or is in a situation which, in the investigator’s 
opinion, may put the subject at significant risk, may confound the study results, or 
may interfere significantly with the subject’s compliance or participation in the 
study. 
Statistical Methods: 
General Statistical Methods and Types of Analysis:  
Safety analyses will be based on the Safety Population consisting of all subjects who 
received at least one dose of the study medication. All safety parameters will be 
summarized descriptively. 
 
Sample Size Considerations: 
For this OLEX study, no formal sample size calculation was used.  




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Open-label Treatment Period (206-week) (continued) 
Assessment 
Visit: 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
27 
Week: 
32 
38 
44 
50 
56 
62 
68 
74 
80 
86 
92 
98 
104 
110 
116 
122 
128 
Day: 
224 
(±7) 
266 
(±7) 
308 
(±7) 
350 
(±7) 
392 
(±7) 
434 
(±7)  
476 
(±7) 
518 
(±7) 
560 
(±7) 
602 
(±7) 
644 
(±7) 
686 
(±7) 
728 
(±7) 
770 
(±7) 
812 
(±7) 
854 
(±7) 
896 
(±7) 
Weight 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
C-SSRSb 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Drug 
Dispensinge 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
OL Dose of 
IMP in clinicg 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Drug 
Accountability 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical and  
Neurological 
Exam 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECGi 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signsj 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Safety Labsk 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AEl 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Conmedsm 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 




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e Dispensing of kits containing study drug will occur during clinic visits at the study site or as needed by direct-to-subject shipment; larger provision of study drug is permitted 
to accommodate personal need, e.g., vacation; drug returns will be recorded and compliance calculated. IMP administration by the subject or caregiver will be assessed at all 
clinic visits. 
f Subjects should withhold last dose of DB IMP (from Study ATH-1017-AD-0201 or Study ATH-1017-AD-0202) on Day 0 (Visit 1) (Visit 8 of the parent studies); IMP 
administration will be done on site under supervision of site staff at this visit; investigator discharge from the clinic will be required. 
g Subjects should withhold OL IMP dose on the day of clinic visits, whereupon IMP administration will be done on site under supervision of site staff. There is no specified 
in-clinic observation period for clinic visits (except for Visit 1/Day 0), but investigator discharge from the clinic will be required. 
h Subjects will administer first dose of OL IMP (from this study, ATH-1017-AD-0203) at the clinic, followed by a safety observation window of 1 hour (± 15 minutes) 
post-dose.  
i 12-lead ECGs will be performed 30 (± 15) minutes post-dose in triplicate, sequentially. 
j Vital signs will be performed pre-dose at all visits. Supine BP and HR recordings will be made after the subject has been supine for at least 5 minutes. Orthostatic BP will be 
recorded as follows: the first blood pressure will be the average of 3 measurements recorded after the subject is supine for 5 minutes; the second blood pressure will be 
recorded after the subject stood for up to 3 minutes. 
k Safety labs include chemistry, hematology, and urinalysis (see footnote ‘a’ also, regarding lab values at Visit 1 being confirmatory). 
l AEs will be reported by the subject (or, when appropriate, by a caregiver, support person, or the subject’s legally authorized representative). AE reporting will begin after the 
first dose of open-label IMP at Visit 2 (Day 1) and will continue until the end of the study (Visit 41 – Safety Follow-up). 
m Prior or concurrent medications. 
 
o Subjects who terminate prior to Visit 40 are to complete same assessments as Visit 40/ET (early termination) unless they completed the assessment within 4 weeks of the ET 
visit. 
 
 
  
* Visit 3 (Day 7/Week 1) and Visit 5 (Day 28/Week 4) are phone call visits. 
‡ Visit 9 (Week 22) is a dispensing visit; caregivers will also provide information on drug accountability, AEs, and concomitant medication at this visit. 
† Procedures performed at Visit 8 (Week 26) of Study ATH-1017-AD-0201 or Study ATH-1017-AD-0202 do not need to be repeated at Visit 1/Day 0 in the open-label study. 
# For subjects who completed the Visit 9 (Week 30-safety follow-up) of the parent studies before entering this open-label study, Visit 1 (Day 0) is not applicable. Procedures 
performed at Visit 8 (Week 26) of Study ATH-1017-AD-0201 and Study ATH-1017-AD-0202 will be repeated in Visit 2 (Day 1) during the first visit of the open-label 
study; inclusion/exclusion, informed consent, and drug dispensing for the open-label study will be performed at Visit 2 (Day 1) in such cases. If Visit 2 of this open-label 
study is ≤ 2 weeks from completion of Visit 9 of one of the parent studies, the visit will follow the schedule of assessments as outlined in the table above. If Visit 2 of this 
open-label study is > 2 weeks from completion of Visit 9 of one of the parent studies, then the inclusion/exclusion criteria, informed consent, 
 and safety-related 


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assessments (C-SSRS, vital signs, safety labs, 12-Lead ECG, physical exam/neurological exam, AEs, and concomitant medications) will be performed at Visit 2 (Day 1) 
prior to administration of the first dose of open-label study treatment. 
 


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TABLE OF CONTENTS 
SIGNATURE PAGE .................................................................................................................2 
SIGNATURE PAGE .................................................................................................................3 
PROTOCOL SYNOPSIS ..........................................................................................................4 
TABLE OF CONTENTS ........................................................................................................ 13 
LIST OF TABLES .................................................................................................................. 15 
LIST OF FIGURES ................................................................................................................ 16 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS......................................... 17 
1 
INTRODUCTION .............................................................................................. 19 
1.1 
Background ..................................................................................................... 19 
1.2 
Rationale for the Clinical Study ....................................................................... 21 
1.3 
Risk-Benefit Assessment ................................................................................. 22 
2 
STUDY OBJECTIVES AND ENDPOINTS ...................................................... 24 
3 
OVERALL DESIGN AND PLAN OF THE STUDY ........................................ 25 
3.1 
Justification for Study Design .......................................................................... 26 
3.2 
Justification for Dose ....................................................................................... 26 
4 
STUDY POPULATION ..................................................................................... 27 
4.1 
Number of Subjects ......................................................................................... 27 
4.2 
Inclusion Criteria ............................................................................................. 27 
4.3 
Exclusion Criteria ............................................................................................ 28 
4.4 
Caregiver / Support Person Eligibility and Responsibility ................................ 28 
5 
INVESTIGATIONAL MEDICINAL PRODUCT ............................................ 30 
5.1 
Identity of the Investigational Medicinal Products............................................ 30 
5.2 
Supply, Packaging, Labeling, and Storage ....................................................... 30 
5.3 
Drug Accountability, Dispensing, and Destruction ........................................... 30 
5.4 
Subject Identification ....................................................................................... 31 
5.5 
Administration of Investigational Medicinal Products ...................................... 31 
5.6 
Compliance with Investigational Medicinal Products ....................................... 31 
5.7 
Blinding and Breaking the Blind ...................................................................... 32 
5.8 
Stopping Criteria ............................................................................................. 32 
5.9 
Treatment of Overdose .................................................................................... 33 
5.10 
Treatment after the End of the Study ................................................................ 33 


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6 
VARIABLES AND METHODS OF ASSESSMENT ........................................ 34 
6.1 
Safety Variables............................................................................................... 34 
6.1.1 
Adverse Events.......................................................................................... 34 
6.1.2 
Pregnancy ................................................................................................ 41 
6.1.3 
Clinical Laboratory Assessments .............................................................. 41 
6.1.4 
Vital Signs ................................................................................................ 42 
6.1.5 
12-Lead Electrocardiogram ...................................................................... 43 
6.1.6 
Physical and Neurological Examination ................................................... 43 
6.1.7 
Columbia-Suicide Severity Rating Scale (C-SSRS) .................................... 44 
6.2 
 
 
 
 
 
 
 
 
 
 
 
7 
STUDY CONDUCT ........................................................................................... 47 
7.1 
Schedule and Order of Assessments ................................................................. 47 
7.1.1 
Unscheduled Visit(s) ................................................................................. 47 
7.2 
Pandemic Response ......................................................................................... 47 
7.3 
Data Safety Monitoring Board ......................................................................... 48 
7.4 
Supportive Care Measures for Potential Adverse Events .................................. 48 
7.5 
Concomitant Medications and Treatments ....................................................... 49 
7.5.1 
Prohibited Treatments During the Study ................................................... 49 
7.5.2 
Permitted Treatments ................................................................................ 50 
7.5.3 
Other Restrictions ..................................................................................... 51 
7.6 
Subject Withdrawal ......................................................................................... 51 
7.6.1 
Discontinuation of Study Treatment .......................................................... 51 
7.6.2 
Withdrawal from the Study ........................................................................ 51 
7.7 
Lost to Follow-up ............................................................................................ 53 
7.8 
Termination of the Clinical Study .................................................................... 53 
8 
STATISTICAL METHODS .............................................................................. 54 
8.1 
Populations for Analysis .................................................................................. 54 


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8.1.1 
Safety population ...................................................................................... 54 
8.2 
General Considerations .................................................................................... 54 
8.3 
Safety Summaries ............................................................................................ 54 
8.3.1 
Adverse Events.......................................................................................... 54 
8.3.2 
Laboratory parameters ............................................................................. 55 
8.3.3 
12-Lead Electrocardiogram ...................................................................... 55 
8.3.4 
Columbia-Suicide Severity Rating Scale.................................................... 55 
8.4 
Determination of Sample Size .......................................................................... 55 
 
 
 
 
 
 
 
 
8.9 
Interim Analysis .............................................................................................. 56 
9 
ETHICAL, LEGAL, AND ADMINISTRATIVE ASPECTS ........................... 57 
9.1 
Data Quality Assurance ................................................................................... 57 
9.2 
Access to Source Data/Documents ................................................................... 58 
9.3 
Archiving Study Documents ............................................................................ 58 
9.4 
Good Clinical Practice ..................................................................................... 58 
9.5 
Informed Consent ............................................................................................ 59 
9.6 
Protocol Approval and Amendment(s) ............................................................. 60 
9.7 
Confidentiality Data Protection ........................................................................ 60 
9.8 
Publication Policy ............................................................................................ 60 
10 
REFERENCE LIST ........................................................................................... 62 
11 
APPENDICES .................................................................................................... 64 
11.1 
Appendix 1: List of Prohibited Medications ..................................................... 64 
 
LIST OF TABLES 
Table 1 
Schedule of Assessments (Subjects Rolling Over Directly) ........................................8 
Table 2 
Identity of Investigational Medicinal Products ......................................................... 30 
Table 3 
Assessment of Relationship of Adverse Events to IMP/Study Procedure .................. 37 
Table 4 
Clinical Laboratory Assessments ............................................................................. 41 
Table 5 
Supportive Care Measures and Follow-up of Potential Adverse Events .................... 48 
 


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LIST OF FIGURES 
Figure 1 
Mechanism of ATH-1017 ........................................................................................ 20 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
 
 
AD 
Alzheimer’s disease 
AE 
Adverse event 
AKT 
Protein kinase B 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
ApoE 
Apolipoprotein E 
aPTT 
Activated partial thromboplastin time 
AST 
Aspartate aminotransferase 
CBC 
Complete blood count 
CPK 
Creatine phosphokinase 
CNS 
Central nervous system 
CRO 
Contract Research Organization 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
CYP3A4 
Cytochrome P450 3A4 
DSMB 
Data Safety Monitoring Board 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EEG 
Electroencephalogram 
ERP 
Event-related potential(s) 
ET 
Early termination 
GCP 
Good Clinical Practice 
 
 
GGT 
Gamma-glutamyl transferase 
HGF 
Hepatocyte growth factor 
HR 
Heart rate 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent ethics committee 
IMP 
Investigational medicinal product 
INR 
International normalized ratio 
IRB 
Institutional review board 
IRT 
Interactive response technology 
LAR 
Legally authorized representative 
LTP 
Long-term potentiation 
MAPK 
Mitogen-activated protein kinase 


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MET 
MET receptor tyrosine kinase 
MMSE 
Mini-Mental State Examination 
NfL 
Neurofilament light chain 
NMDA 
N-methyl-D-aspartate 
OD 
Once daily 
OLEX 
Open-label extension 
P 
Phosphorylated 
PD 
Pharmacodynamic(s) 
PI3K 
Phosphoinositide 3-kinase 
PK 
Pharmacokinetic(s) 
PKC 
Protein kinase C 
PLCγ 
Phospholipase C-gamma 
PM 
Plasma membrane 
PSP 
Post-synaptic potential 
 
 
PT 
Prothrombin time 
qEEG 
Quantitative electroencephalogram 
QTcF 
Corrected QT interval using Fridericia’s formula 
RAC1 
Ras-related C3 botulinum toxin substrate 1 
RAF 
Rapidly accelerated fibrosarcoma (protein) 
RAS 
Rat sarcoma (protein) 
RBC 
Red blood cells 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SBP 
Systolic blood pressure 
SC 
Subcutaneous 
SOP 
Standard operating procedure 
STAT3 
Signal transducer and activator of transcription 3 
ULN 
Upper limit of normal 
US(A) 
United States (of America) 
WBC 
White blood cells 
 
 


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1 
INTRODUCTION 
Fosgonimeton (ATH-1017) is an experimental Alzheimer’s disease (AD) treatment, formulated 
as a sterile solution for subcutaneous (SC) injection. ATH-1017 is a prodrug, which is rapidly 
converted to the active drug ATH-1001 in the plasma after SC injection. ATH-1017 was 
developed as a water-soluble prodrug of ATH-1001 to allow SC dosing in aqueous vehicles. The 
active drug ATH-1001 acts as a positive modulator at the hepatocyte growth factor (HGF) and its 
tyrosine kinase, MET, receptor system. Central nervous system (CNS) MET expression is crucial 
in maintaining the healthy adult brain (Hawrylycz, 2015), and is reduced in AD, particularly in 
the hippocampus and frontal cortex (Hamasaki, 2014). The HGF/MET system presents a new 
therapeutic target to treat neurodegeneration and restore cognitive function in AD and other 
neurodegenerative disorders. 
1.1 
Background 
Dementia of the Alzheimer’s type (hereafter referred to as AD) is the most common form of 
dementia and the largest unmet medical need in neurology (Citron, 2010). AD can be further 
classified based on age of onset and genetic risks. Individuals under age 65 have early-onset AD, 
and many of whom have a dominant genetic mutation (i.e., familial AD with known mutations in 
the following genes: amyloid precursor protein, presenilin-1, and presenilin-2). Late-onset AD 
patients have an age of onset at 65 years and older, who typically have no dominant genetic risks 
(i.e., sporadic AD), with disease onset involving a complex interplay of aging, Apolipoprotein E 
(ApoE)-ε4 genotype, environmental, and lifestyle risk factors. The late-onset sporadic cases 
account for about 95% of the total AD population. Although age is the biggest risk factor, AD is 
not a part of normal aging. 
Growing evidence suggests that complex CNS disorders, like AD, are unlikely to be caused by a 
single route of pathology; they are likely the result of a multifactorial interplay related to 
genetics, age, and environment. Pharmacological stimulation of a critical neurotrophic factor 
system (HGF/MET) may stop neurodegeneration and promote neuro-regeneration. Neurotrophic 
factors represent a promising therapeutic target for the treatment of AD and other dementias, and 
drugs that stimulate neurotrophic systems have the potential to address neurodegeneration and 
improve cognition by protecting existing neurons, promoting connectivity, inducing 
neuro-regenerative mechanisms, as well as addressing multiple aspects of the AD pathology, by 
decreasing inflammation and improving cerebral blood flow (Funakoshi, 2011). The therapeutic 
promise of neurotrophic factors in neurodegenerative disorders is hampered by the lack of 
efficient and non-invasive delivery to the brain. Gene therapy strategies, primarily using 
adeno-associated viral vectors, have been developed and clinically evaluated for therapeutic 
potential in AD and Parkinson’s disease patients. These strategies are largely hindered by 
challenges related to gene delivery and transduction with limited brain exposure, uncontrollable 
dose over long-term treatment, and potential immune complications (Piguet, 2017). Therefore, a 


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small molecule approach capable of passing the blood brain barrier and entering all regions of 
the brain, presents a superior therapeutic strategy for targeting neurotrophic factors to treat 
neurodegenerative disorders.  
ATH-1017 represents a new approach to treat AD in a systemic approach. The mechanism of 
action of ATH-1017 via its active metabolite is augmentation of HGF function and facilitation of 
signal transduction through MET phosphorylation (Figure 1).  
Figure 1 
Mechanism of ATH-1017 
 
AKT = protein kinase B; EEG = electroencephalogram; HGF = hepatic growth factor; LTP = long-term potentiation; 
MAPK = mitogen-activated protein kinase; MET = MET receptor tyrosine kinase; NMDA = N-methyl-D-aspartate; 
P = phosphorylated; PI3K = phosphoinositide 3-kinase; PKC = protein kinase C; PLCγ = phospholipase C-gamma; 
PM = plasma membrane; PSP = post-synaptic potential; RAC1 = Ras-related C3 botulinum toxin substrate 1; 
RAF = rapidly accelerated fibrosarcoma (RAF) kinase; STAT3 = signal transducer and activator of transcription 3. 
 


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After SC injection, the prodrug ATH-1017 is rapidly converted in plasma to the active 
metabolite ATH-1001, which binds to HGF and enhances MET activation. Interaction of the 
ligand HGF with its receptor MET induces MET phosphorylation (activation) and recruitment of 
effector proteins that potentiate downstream signaling through the PI3K/AKT and 
RAS/RAF/MAPK pathways, among others (Organ, 2011). In the CNS, HGF/MET activity has 
neuroprotective and neurotrophic effects and modulates neurogenesis and neuronal maturation 
(Ebens, 1996; Maina, 1999; Shang, 2011). As a critical regulator of inflammation, HGF/MET 
activity reduces the expression of the pro-inflammatory cytokine interleukin-6 and promotes 
expression of the anti-inflammatory interleukin-10 (Molnarfi, 2015). HGF/MET activity also 
leads to protein kinase C (PKC)-mediated potentiation of N-methyl-D-aspartate (NMDA) 
receptor current, synaptic localization of NMDA receptors, and long-term potentiation (Tyndall, 
2007), processes important for memory formation. 
1.2 
Rationale for the Clinical Study 
The Sponsor has completed a Phase 1a/b study of ATH-1017 in which preliminary safety and 
tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) based on 
electroencephalogram (EEG), including quantitative electroencephalogram (qEEG) and 
event -related potentials (ERP), was established. Quantitative EEG was employed in both 
preclinical and clinical studies providing a translatable biomarker of neuronal network activity, 
as a function of pharmacological intervention. The qEEG analysis, combined with PK-PD 
modeling, and preclinical behavioral study results, have supported the identification of an active 
clinical dose range in humans (see Section 3.2). Additionally, in an ERP auditory oddball 
paradigm, ATH-1017 treatment in 11 AD subjects with 40 mg/day SC once daily (OD) 
significantly reduced P300 latency (p=0.027) after 8 days of treatment when compared to 
placebo (Hua, 2022). This finding suggests ATH-1017 treatment has potentially beneficial 
effects on cognitive processing and working memory access in AD. 
The sponsor has completed a Phase 2 study (ATH-1017-AD-0202 [ACT-AD]) of ATH-1017 in 
77 mild to moderate Alzheimer’s subjects over 6 months of treatment. The results of the study 
suggested ATH-1017 had positive effects on measures of cognition and neurodegeneration in 
subjects taking ATH-1017 without background acetylcholinesterase inhibitor, compared to 
placebo at 26 weeks (data on file). Subjects who completed the Week 26 visit of study 
ATH-1017-AD-0202 will be eligible to enroll in this open-label extension (OLEX) study, 
ATH-1017-AD-0203. 
The Phase 3 study, ATH-1017-AD-0201, was subsequently initiated as a double-blind, 
randomized, placebo-controlled, 26-week, multi-center trial, designed to demonstrate efficacy in 
mild to moderate AD subjects and establish long-term safety information. Eligible participants, 
prior to version 7 of ATH-1017-AD-0201 protocol, will receive OD SC injections of ATH-1017 
(40 mg or 70 mg) or placebo, over a 26-week double-blind, randomized period, followed by a 
4-week safety follow-up. Based on the results of the ATH-1017-AD-0202 ACT-AD study, no 


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additional subjects on acetylcholinesterase inhibitor therapy will be enrolled and, as of v7 of 
ATH-1017-AD-0201 protocol, subjects will no longer be randomized to receive 70 mg of 
ATH-1017, since 40 mg is the dose intended for further development. The 70 mg OD dose was 
tested in the ATH-1017-AD-0202 study; clinical and biomarker endpoints did not consistently 
favor 70 mg OD when compared to 40 mg OD. While ATH-1017 has demonstrated a favorable 
safety profile in all completed and ongoing studies to date, there appears to be better tolerability 
in the 40 mg cohort when compared to 70 mg. By discontinuing the 70 mg cohort, with no 
further plans to develop the 70 mg formulation, it will also decrease the burden on clinical trial 
healthcare resources (e.g., clinical site utilization, availability of eligible subjects, caregiver 
commitments), and subjects will be randomized to ATH-1017 40 mg, OD or placebo, in a 
1:1 ratio. Subjects already randomized to receive the 70 mg dose will complete the study as 
planned. Subjects who complete the double-blind study will have the option to roll over into a 
long-term (206-week) OLEX study. 
This OLEX study is designed to collect longer term clinical and biomarker measurements on 
ATH-1017 administration in subjects with mild to moderate AD over an additional 206-week 
period. All eligible subjects will receive OD SC injections of ATH-1017 (40 mg) over a 
206-week period, followed by a 4-week safety follow-up. As of v3 of this protocol 
(01 JUN 2023), the dose of 70 mg/day ATH-1017 was discontinued and subjects who were 
previously assigned to this dose were reassigned to the dose of 40 mg/day ATH-1017.  
1.3 
Risk-Benefit Assessment 
While qEEG and ERP results in humans are indicative of CNS penetration and target 
engagement, ATH-1017 efficacy in subjects with AD (in terms of cognitive, functional, or 
behavioral improvement) and long-term safety has not been established. Therefore, the benefit to 
study subjects of participating in this OLEX study is not yet known. 
In clinical studies of ATH-1017, single SC administration of 2, 6, 20, 40, 60, and 90 mg in 
healthy young subjects, and multiple administration of 20, 40, 60, and 80 mg (SC, OD, over 
9 consecutive days) in healthy elderly subjects, and 40 mg (SC, OD, over 9 consecutive days) in 
AD subjects were safe and well tolerated.  
Injection site reaction, eosinophilia, and transaminase elevations are considered as nonserious 
adverse drug reactions to ATH-1017. 
Injection site reactions have been observed commonly in clinical trials and are characterized by 
localized symptoms including swelling, erythema, pruritus, pain, and/or irritation around the 
injection site. They have usually been mild, appear during the first weeks of injections, though in 
some cases ISRs may appear later. Most ISRs were mild and recovered shortly without 
treatment, while some were more persistent. 


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Transient absolute eosinophil count (AEC) elevations without signs of clonality and without 
associated clinical symptoms have been observed in subjects. The majority of these elevations 
stayed below 3 × 103/μL and resolved without intervention during continued IMP administration. 
Very few subjects experienced elevations above 5 × 103/μL. No AEs potentially associated with 
eosinophilia were reported. None of the subjects fulfilled the criteria for a hyper-eosinophilic 
syndrome. All AEC elevations have resolved without sequela, and the vast majority of subjects 
continued in the trials. 
Non-clinical data identified a potential risk for hepatotoxicity and will be closely monitored in 
this study. The sponsor reviewed clinical data from the Phase 1 trial ATH-1017-0103, and 
6 healthy subjects in the 140 mg cohort had elevated transaminases. Repeat testing showed 
resolution towards normal in all subjects, with no reports of associated complications. No serious 
events of transaminase elevations have been reported and there have been no cases meeting Hy’s 
Law criteria. 


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2 
STUDY OBJECTIVES AND ENDPOINTS 
The primary objective of this study is the extended determination of the safety and tolerability of 
ATH-1017 over an additional 206-week period in subjects with mild to moderate AD who 
completed the 26-week randomized treatment in Study ATH-1017-AD-0201 or Study 
ATH-1017-AD-0202. 
Safety and tolerability will be assessed by analysis of adverse events (AEs), including injection 
site AEs; changes from baseline for the following variables: vital signs, 12-lead 
electrocardiogram (ECG), laboratory tests (chemistry, hematology, urinalysis), concomitant 
medication assessments, physical and neurological exams, and Columbia-Suicide Severity 
Rating Scale (C-SSRS). 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


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3 
OVERALL DESIGN AND PLAN OF THE STUDY 
This is a multicenter, OLEX study of ATH-1017 treatment in subjects with a clinical diagnosis 
of mild to moderate Alzheimer’s disease (AD) who completed 26 weeks of treatment in the 
randomized, placebo-controlled, double-blind studies, ATH-1017-AD-0201 and 
ATH-1017-AD-0202; hereafter referred to as the ‘parent studies’. The study will be conducted at 
approximately 65 centers across the United States (US) for a total of 206 weeks’ (47.5 months) 
open-label treatment. Eligible subjects will roll over directly from the parent studies, such that 
Visit 1 (Day 0) of this study is the Week 26 visit from either of the two parent studies. All 
subjects who complete the Week 26 visit of either of the two parent studies and meet the 
inclusion/exclusion criteria of Study ATH-1017-AD-0203 will be assigned to open-label active 
treatment with ATH-1017 at a dose of 40 mg/day, unless the safety results obtained at Visit 7 of 
the parent studies or new baseline safety labs suggest otherwise, in which case they will not be 
eligible for this OLEX study. Subjects who do not tolerate ATH-1017 40 mg/day, and/or who 
meet the stopping criteria, will be withdrawn from the study. 
Study drugs will be administered by SC injection OD, preferably during the daytime. Subjects 
will take their last dose of blinded IMP (assigned to them in Study ATH-1017-AD-0201 or Study 
ATH-1017-AD-0202) on site under supervision of site staff at Visit 8/Day 182 of the parent 
studies (i.e., Visit 1/Day 0 of this OLEX study). The first dose of open-label IMP from this study 
will be administered by subject or caregiver at the clinic the next day (Visit 2/Day 1), followed 
by a safety observation window of 1 hour (±15 minutes) post-dose. Subjects must not take more 
than one dose within 8 hours of the previous dose. The subject should withhold study drug 
administration on the day of clinic visits; study drug administration will be done on site under 
supervision of site staff at these visits. Each subject is required to have a primary caregiver 
willing to accept responsibility for supervising or, if required, administering study drug, in 
accordance with all protocol requirements. 
During the open-label treatment period, clinic visits will take place on Day 0 and thereafter at 
Day 1, Weeks 2, 6, 12, 18, 22, 26, 32, 38, 44, 50, 56, 62, 68, 74, 80, 86, 92, 98, 104, 110, 116, 
122, 128, 134, 140, 146, 152, 158, 164, 170, 176, 182, 188, 194, 200, and 206. Telephone call 
visits are scheduled for Week 1 (Day 7) and Week 4 (Day 28). A safety follow-up visit is 
scheduled 4 weeks after completion of the open-label period at Week 210 (see Table 1 for 
Schedule of Assessments). Subjects may live at home, in a senior residential setting, or an 
institutional setting without the need for continuous nursing care. The end of the study is defined 
as the date of the safety follow-up visit, Visit 41/Week 210. Subjects who terminate prior to 
Visit 40 are to complete same assessments as Visit 40/early termination (ET) within 2 weeks of 
the date of ET. 
 
 


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An independent Data Safety Monitoring Board will conduct periodic review and assessments of 
safety data (AEs, labs, ECG, etc) throughout the study to ensure the safety of study subjects 
(see Section 7.3). 
3.1 
Justification for Study Design 
This OLEX study provides an opportunity for all subjects who consented to participate in 
placebo-controlled studies ATH-1017-AD-0201 and ATH-1017-AD-0202 to receive active 
treatment over an additional 206-week period. The study will provide extended exposure 
information on ATH-1017 administration, primarily at a dose of 40 mg/day, in subjects with 
mild to moderate AD (based on the National Institute on Aging-Alzheimer’s Association 
diagnostic criteria [McKhann, 2011]) and the inclusion/exclusion criteria of the parent studies, 
ATH-1017-AD-0201 and ATH-1017-AD-0202). This allows for continued safety data collection 
at the 40 mg/day dose level. Subjects who do not tolerate ATH-1017 40 mg/day, and/or who 
meet the stopping criteria, will be withdrawn from the study. As of v3 of this protocol 
(01 JUN 2023), the dose of 70 mg/day ATH-1017 was discontinued and subjects who were 
previously assigned to this dose were reassigned to the dose of 40 mg/day ATH-1017.  
The safety assessments for the study are generally accepted measures for ensuring safety of 
subjects during a clinical trial. In addition, subject safety will be closely monitored; stopping 
criteria will be implemented (see Section 5.8. As for the parent studies, this study will also 
employ an independent Data Safety Monitoring Board (DSMB) which will conduct periodic 
review and assessments of safety data (AEs, labs, ECG, etc.) throughout the study. 
3.2 
Justification for Dose 
The dose selection for this clinical study is based on the targeted dose in the ongoing pivotal 
ATH-1017-AD-0201 study, which is supported by nonclinical and clinical data. 
The doses of ATH-1017 selected for the initial studies, ATH-1017-AD-0201 and 
ATH-1017-AD-0202 (40 mg/day and 70 mg/day), cover the nonclinical effects and the clinical 
PD range, were well-tolerated in humans based on safety data from the Phase 1a/b study, and are 
covered by the 6- and 9-month- Good Laboratory Practice nonclinical toxicology studies in 
animals at equivalent doses. 
For further details on justification of dose, please refer to Section 3.2 of the ATH-1017-AD-0201 
and ATH-1017-AD-0202 Clinical Study Protocols. 


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4 
STUDY POPULATION 
All subjects must meet all the inclusion criteria and none of the exclusion criteria.  
Protocol exemptions related to enrollment criteria are only allowed with prior Investigator and 
Sponsor approval, supported by documented agreement from the IRB/IEC. 
Evaluation of safety lab data from Visit 7 of either of the two parent studies is allowed for 
assessment of subject eligibility. Subjects who are considered by the investigator to have safety 
or tolerability issues at Visit 7 of either of the two parent studies should be carefully 
re-considered for transition into this OLEX study at the final study visit of Study 
ATH-1017-AD-0201 or Study ATH-1017-AD-0202 (i.e., Visit 1 of this study, 
ATH-1017-AD-0203). Safety lab data from Visit 7 of the parent studies is to be confirmed with 
safety lab data from Visit 1 of this study. Subjects who are subsequently found to be not eligible 
based on safety lab data from Visit 1 will be discontinued. 
4.1 
Number of Subjects 
It is estimated that up to approximately 450 subjects from Studies ATH-1017-AD-0201 and 
ATH-1017-AD-0202 will enter this OLEX study. 
4.2 
Inclusion Criteria 
1. Subject has completed the Week 26 visit of either of the two parent studies.  
2. Male subjects and their partners must agree to continue to use a double-barrier method of 
contraception during the study, including the follow-up period, unless the partner is not of 
childbearing potential. Only female subjects of non-childbearing potential (i.e., permanently 
sterilized, postmenopausal) are eligible for participation. 
3. Reliable and capable support person/caregiver, who is willing to accept responsibility for 
supervising the treatment or, if required, administering study drug in accordance with all 
protocol requirements. The support person/caregiver must see the subject at least once daily 
for administering or supervising dose administration. 
4. Subject capable of giving signed informed consent, which includes compliance with the 
requirements and restrictions listed in the Informed Consent Form (ICF) and in this protocol. 
If the subject is incapable of giving informed consent in the judgment of the investigator, 
then consent may be provided by a legally acceptable representative. 
5. Written informed consent from a) the subject or legally acceptable representative and b) 
caregiver/support person has been obtained prior to any study-related procedures, including 
prior to initiating procedures to evaluate eligibility for the study. 


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6. Written documentation has been obtained in accordance with the relevant country and local 
privacy requirements, where applicable (e.g., Written Authorization for Use and Release of 
Health and Research Study Information). 
7. Subjects and caregivers/support persons are able, as assessed by the investigator, and willing 
to follow study instructions and likely to complete all required study visits. 
8. Subjects must be in generally good health as assessed by the investigator from medical 
history and physical/neurological examination, vital signs, ECG, and standard laboratory 
tests. 
4.3 
Exclusion Criteria 
9. Subject has experienced a serious treatment-related AE during either of the two parent 
studies, which in the opinion of the investigator could present an increased safety risk to the 
subject during the OLEX study, in discussion with the Medical Monitor. 
10. New diagnosis of severe major depressive disorder even without psychotic features. Any 
subject with formalized delusions or hallucinations are excluded. 
11. Significant suicide risk as defined by suicidal ideation based on the C-SSRS at Visit 1 (i.e., a 
‘yes’ response to Question 4 or 5, or any specific behaviours). 
12. Newly diagnosed malignant tumor except for the following conditions that are stable in the 
judgement of the investigator: 
a) Adequately treated squamous and basal cell carcinoma, or squamous and basal cell 
carcinoma in situ; 
b) Prostate carcinoma in situ; 
c) Fully-excised (biopsy-proven) melanoma in situ; prior Medical Monitor approval is 
required. 
13. The subject has a condition or is in a situation which, in the investigator’s opinion, may put 
the subject at significant risk, may confound the study results, or may interfere significantly 
with the subject’s compliance or participation in the study. 
4.4 
Caregiver / Support Person Eligibility and Responsibility 
For the purpose of this study, all subjects must have a suitable designated caregiver/support 
person who must meet the following eligibility criteria: 
1. Understand and agree with the potential risks and benefits to subjects as well as the nature of 
all procedures and restrictions associated with this study 
2. Understand, agree to, and sign a separate caregiver/support person’s ICF 


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3. Willing to receive caregiver training related to the conduct of this study 
4. Willing and able to administer and/or supervise the administration of all study drugs 
5. Willing and able to evaluate the subject’s tolerability to study drugs and any associated AEs 
6. Able to communicate by phone/email/text message or in person between clinic visits 
7. Able to accompany the subject to all clinic visits 
Site personnel will instruct the caregiver / support person about: 
• Study drug administration and disposal of empty syringes 
• Study drug storage requirements 
• The nature of expected AEs 
• How to report AEs 
A consistent caregiver/support person is necessary for the conduct of the study. If an unforeseen 
change in caregiver/support person occurs during the course of study, please inform your 
assigned Study Monitor immediately. The replacement caregiver/support person must meet all 
requirements as outlined in the protocol and discussed with the Contract Research Organization 
(CRO) and/or Sponsor. 


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5 
INVESTIGATIONAL MEDICINAL PRODUCT 
5.1 
Identity of the Investigational Medicinal Products 
The products that will be used in this study are outlined in Table 2. 
Table 2 
Identity of Investigational Medicinal Products 
Study Drug Name 
Formulation 
Strength 
Route 
Manufacturer 
In Use 
 
 
 
 
ATH-1017 40 mg 
Injection 
40 mg/mL 
SC 
Patheon 
Discontinueda 
 
 
 
 
ATH-1017 70 mg 
Injection 
70 mg/mL 
SC 
Patheon 
SC = subcutaneous 
a 
The 70 mg/day ATH-1017 dose was discontinued as of v3 of this protocol (01 JUN 2023). 
Pre-filled syringes of active IMP at 40 mg will contain 1.0 mL of 40 mg/mL ATH-1017 in a 
solution of 10 mM sodium phosphate and 0.5% NaCl, adjusted to pH of approximately 7.6. 
Prior to discontinuation of the 70 mg/mL dose, pre-filled syringes of active IMP at 70 mg 
contained 1.0 mL of 70 mg/mL ATH-1017 in a solution of 10 mM sodium phosphate, adjusted to 
pH of approximately 7.6. 
5.2 
Supply, Packaging, Labeling, and Storage 
IMP (ATH-1017) will be provided as unblinded subject kits and will be labeled according to 
applicable local and regulatory requirements. 
IMP will be stored under refrigerated conditions (between 2°C and 8°C) during storage at study 
sites in a securely locked area, accessible to authorized persons only. Once dispensed, study 
subjects may store the product under ambient conditions up to 4 weeks (between 15°C and 25°C) 
or refrigerated conditions (between 2°C and 8°C). 
5.3 
Drug Accountability, Dispensing, and Destruction 
Dispensation will be controlled by an interactive response technology (IRT) system and will 
occur at clinic visits through Week 18 (Day 1, and Weeks 2, 6, 12, and 18), the Week 22 
dispensing visit, and every clinic visit starting from Week 26 through Week 200, or as needed by 
direct-to-subject shipment. Larger provision of study drug will be permitted to accommodate 
personal need, e.g., vacation. Study subjects will be provided with sharps containers for proper 
disposal of used IMP.  
The caregiver/support person will supervise and record daily administration of IMP. Each site 
will ship any product materials (kits and sharps containers) to a central location for destruction or 
will destruct on-site. Reconciliation of IMP will be managed at each study site. 


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5.4 
Subject Identification 
In this OLEX study, subjects will retain the subject identification number originally assigned to 
them on entry to the preceding (parent) studies, ATH-1017-AD-0201 and ATH-1017-AD-0202. 
5.5 
Administration of Investigational Medicinal Products 
Capable subjects will be allowed to self-administer upon judgement of site staff; those not 
capable will require caregiver-assisted administration after deemed capable by site staff. If stored 
at refrigerated conditions, pre-filled syringes should be kept at room temperature for at least 
30 minutes after taking out of the refrigerator before administering the injection. 
Subjects will take their last dose of blinded IMP on site under supervision of site staff at 
Visit 8/Week 26 of Study ATH-1017-AD-0201 or ATH-1017-AD-0202 (corresponding to 
Visit 1/Day 0 of this study, ATH-1017-AD-0203). The first dose of open-label IMP will be 
administered by subject or caregiver at the clinic the next day (Visit 2/Day 1), followed by a 
safety observation window of 1 hour (±15 minutes) post-dose. 
Site staff will be expected to observe dose administration on study visit days to ensure safe and 
effective use. During study visits, there is no specified in-clinic observation period post-IMP 
administration (except for Visit 2/Day 1 when a safety observation window of 1 hour 
± 15 minutes post-dose is specified); however, the subject is required to be discharged from the 
study site by the investigator. 
Should self-administration or caregiver-assisted administration not be judged adequate, a suitable 
caregiver must be identified, otherwise subject discontinuation will be required. 
5.6 
Compliance with Investigational Medicinal Products 
IMP compliance will be determined from daily records of IMP administration recorded by the 
caregiver/support person. Drug accountability information is collected at clinic visits (Day 1, 
Weeks 2, 6, 12, 18, 22, 26, 32, 38, 44, 50, 56, 62, 68, 74, 80, 86, 92, 98, 104, 110, 116, 122, 128, 
134, 140, 146, 152, 158, 164, 170, 176, 182, 188, 194, 200, and 206 as applicable), and 
additionally at telephone call visits (Weeks 1 and 4). 
If a subject demonstrates consistent poor compliance during the study (< 80%), the investigator 
should evaluate whether the subject should be discontinued from the study, in discussion with 
the Sponsor. However, subjects who are off drug for ≥ 14 consecutive days may be prematurely 
discontinued from the study, in discussion with the Sponsor.  
The study centers will keep an accurate drug disposition record that specifies the subject kit ID 
number, number of kits dispensed to each subject, and the date of dispensation. 


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5.7 
Blinding and Breaking the Blind 
In this OLEX study, treatment allocation will not be blinded; all subjects will receive open-label 
ATH-1017 at a dose of 40 mg/day. 
5.8 
Stopping Criteria 
For all subjects, at any time during the study, study treatment should be discontinued and the 
subject will be withdrawn if any of the following criteria/AEs do not resolve in a satisfactory 
timeframe per investigator judgment: 
• 
ALT or AST > 8 × upper limit of normal (ULN) 
• 
ALT or AST > 5 × ULN for more than 2 weeks 
• 
ALT or AST > 3 × ULN and (total bilirubin > 2 × ULN, or international normalized ratio 
[INR] > 1.5) 
• 
ALT or AST > 3 × ULN with symptoms (the appearance of fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness, fever, rash, and/or eosinophilia > 5%) 
• 
AEs: 
− Any AE of severe intensity and related causality  
− Any serious adverse event (SAE) of related causality 
(Note: causality as determined by the Sponsor) 
• 
Other clinical laboratory criteria (confirmed on repeat): 
− Creatine phosphokinase (CPK) ≥ 3 × ULN (that cannot be attributed to causes other than 
the study treatment; i.e., vigorous exercise) 
− Serum creatinine > 1.5 × ULN 
− A decrease from Baseline in hemoglobin concentration > 2 g/dL 
− Absolute neutrophil count < 1,000/μL 
− Platelets < 50,000/μL 
• Vital sign criteria: 
− Hypotension (systolic blood pressure [SBP] < 90 mmHg and symptomatic). If 
hypotension is observed during the study and the subject is symptomatic, then a 
minimum of 2 repeat blood pressure measurements should be obtained approximately 
5 minutes apart. The mean of the 3 SBP measurements will be used to determine stopping 
criteria. 
− Tachycardia defined as heart rate (HR) > 120 beats per minute (bpm) lasting longer than 
30 minutes or with impaired consciousness 
• ECG criterion: 


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− QTcF > 500 msec (if prolonged QTcF interval is observed during the study, then a 
minimum of 2 sets of repeat ECGs in triplicate should be obtained over a brief period. 
The mean of the 3 sets of ECGs will be used to determine stopping criterion). For QTcF 
readings that are borderline, or difficult to interpret due to e.g., presence of a Branch 
Bundle Block, or in those where the T and U waves are superimposed or connected, a 
manual, local reading using the same ECG device should be considered to determine 
applicability of this ECG stopping criterion, in discussion with the Medical Monitor. The 
conditions of parent study eligibility and OLEX study Baseline should be taken into 
account when considering the ECG stopping criterion. 
In addition, if any of the above criteria are met, the event must be reported and discussed with 
the Medical Monitor. 
The responsibilities of the independent DSMB are defined in a DSMB Charter and shall include 
making recommendations regarding subject continuation (as described in Section 7.3, and of the 
study itself. 
5.9 
Treatment of Overdose 
Overdose: Unintentional administration of a quantity of the study treatment given per 
administration or per day that is above the maximum recommended dose (i.e., 40 mg/day) 
according to the protocol for the study treatment. 
There is no prior knowledge of clinical symptoms occurring with ATH-1017 overdose. In case of 
suspected or reported overdose, treatment of any clinical signs will be symptomatic. 
5.10 
Treatment after the End of the Study 
Access to study treatment will be limited to the period of study participation. 
Upon discontinuation of study treatment, subjects may continue with their original treatment 
following consultation with their primary care physician; tapering off study medication is not 
required.  
The investigator will determine whether additional care is needed after the subject completes or 
discontinues from the study. 


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6 
VARIABLES AND METHODS OF ASSESSMENT 
6.1 
Safety Variables 
6.1.1 
Adverse Events 
AE reporting will begin after the first dose of open-label IMP at Visit 2 (Day 1) and will 
continue until the end of the study (28 days from last dose of IMP, Visit 41 – Safety Follow-up). 
AEs will be reported by the subject (or, when appropriate, by a caregiver, support person, or the 
subject’s legally authorized representative). 
The investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE or SAE and remain responsible for following up AE 
(see Section 6.1.1.5). 
6.1.1.1 
Definitions 
An AE is any untoward medical occurrence in a study subject which does not necessarily have a 
causal relationship with this treatment. An AE can therefore be any unfavorable and unintended 
sign (including a clinically significant abnormal laboratory finding), symptom, or disease (new 
or exacerbated), whether or not considered related to the IMP. 
Events meeting the definition of AE include: 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECGs, vital signs measurements), including those that 
worsen from Baseline, considered clinically significant in the medical and scientific 
judgment of the investigator (i.e., not related to progression of underlying disease) 
• Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition 
• New condition detected or diagnosed after Day 1 even though it may have been present 
in the medical history before the start of the study 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdoses should be reported regardless of sequelae. 


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Events not meeting the definition of AE include: 
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the subject’s condition 
• The disease/disorder being studied or expected progression, signs, or symptoms (clearly 
defined) of the disease/disorder being studied, unless more severe than expected for the 
subject’s condition 
• Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that leads 
to the procedure is the AE 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital) 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen (note: pre-existing conditions will be 
recorded as part of the subject’s medical history) 
6.1.1.2 
Recording of Adverse Events 
AEs should be collected and recorded for each subject from after the first dose of open-label IMP 
at Visit 2 (Day 1) until the end of their participation in the study, i.e., from Visit 2 until the 
subject has discontinued or completed the study, including the post-treatment Safety Follow-up 
period (at the end of the 206-week open-label period) at the timepoints specified in the Schedule 
of Assessments (Table 1). If AEs occur, the first concern will be the safety of the study subjects. 
AEs may be volunteered spontaneously by the study subject, or discovered by the study staff 
during physical examinations or by asking an open, non-leading question such as ‘How have you 
been feeling since you were last asked?’ All AEs and any required remedial action will be 
recorded. The nature of AE, date (and time, if known) of AE onset, date (and time, if known) of 
AE outcome to date, severity, and action taken of the AE will be recorded together with the 
investigator’s assessment of the seriousness of the AE and causal relationship to IMP and/or 
study procedure on an AE electronic case report form (eCRF).  
When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation 
(e.g., hospital progress notes, laboratory reports, and diagnostics reports) related to the event. It 
is not acceptable for the investigator to send photocopies of the subject’s medical records to the 
sponsor in lieu of completion of the AE/SAE eCRF page. 
There may be instances when copies of medical records for certain cases are requested by the 
Sponsor and/or CRO. In this case, all subject identifiers, with the exception of the subject 
number, will be redacted on the copies of the medical records before submission. 


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All AEs should be recorded individually in the study subject’s own words (verbatim) unless, in 
the opinion of the investigator, the AEs constitute components of a recognized condition, disease 
or syndrome. In the latter case, the condition, disease or syndrome should be named rather than 
each individual symptom. 
6.1.1.3 
Assessment of Adverse Events 
Each AE will be assessed by the investigator with regard to the categories discussed in the 
sections below. 
Intensity 
The investigator will assess all AEs for severity in accordance with the following standard 
ratings: 
• Mild: Ordinarily transient symptoms, does not influence performance of subject’s daily 
activities. Treatment is not ordinarily indicated or may be minimal. 
• Moderate: Marked symptoms, sufficient to make the subject uncomfortable. Moderate 
influence on performance of subject’s daily activities. Treatment may be necessary to 
alleviate symptoms. 
• Severe: Symptoms cause considerable discomfort. Substantial influence on subject’s 
daily activities, or significantly affects clinical status. May be unable to continue in the 
study and intensive treatment may be necessary. 
When changes in the intensity of an AE occur more frequently than once a day, the maximum 
intensity recorded for the event should be noted. 
Note: an event is defined as serious when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE (see later), NOT when it is rated as severe. 
Causality 
The investigator will assess the causality/relationship between the AE and IMP/study procedure. 
One of the categories described in Table 3 should be selected based on medical judgment, 
considering the definitions below and all contributing factors. In this study AEs will be 
considered related to IMP/study procedure if causality is ascribed as either related, probably 
related, or possibly related. 
For each AE/SAE, the investigator must document in the medical notes that he/she has reviewed 
the AE/SAE and has provided an assessment of causality. 
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to the Sponsor. However, it is very important that 


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the investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to the Sponsor. 
The investigator may change his/her opinion of causality in light of follow-up information and 
send an SAE follow-up report with the updated causality assessment. 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
Table 3 
Assessment of Relationship of Adverse Events to IMP/Study Procedure 
Related 
 
A clinical event, including laboratory test abnormality, which occurs in a 
plausible time relationship to treatment administration, and which concurrent 
disease or other drugs or chemicals cannot explain. The response to withdrawal 
of the treatment (dechallenge*) should be clinically plausible. The event must be 
definitive pharmacologically or phenomenologically, using a satisfactory 
rechallenge† procedure if necessary. 
Probably related 
 
A clinical event, including laboratory test abnormality, with a reasonable time 
sequence to administration of the treatment, unlikely to be attributed to 
concurrent disease or other drugs or chemicals, and which follows a clinically 
reasonable response on withdrawal (dechallenge). Rechallenge information is 
not required to fulfill this definition. 
Possibly related 
 
A clinical event, including laboratory test abnormality, with a reasonable time 
sequence to administration of the treatment, but which could also be explained 
by concurrent disease or other drugs or chemicals. Information on treatment 
withdrawal may be lacking or unclear. 
Unlikely to be 
related 
 
A clinical event, including laboratory test abnormality, with a temporal 
relationship to treatment administration which makes a causal relationship 
improbable, and in which other drugs, chemicals or underlying disease provide 
plausible explanations. 
Unrelated 
 
A clinical event, including laboratory test abnormality, with little or no temporal 
relationship with treatment administration. May have negative dechallenge and 
rechallenge information. Typically explained by extraneous factors (e.g., 
concomitant disease, environmental factors or other drugs or chemicals). 
*Dechallenge is when a drug suspected of causing an AE is discontinued. If the symptoms of the AE disappear partially 
or completely, within a reasonable time from drug discontinuation, this is termed a positive dechallenge. If the 
symptoms continue despite withdrawal of the drug, this is termed a negative dechallenge. Note that there are 
exceptions when an AE does not disappear upon discontinuation of the drug, yet drug-relatedness clearly exists (for 
example, as in bone marrow suppression, fixed drug eruptions, or tardive dyskinesia). 
†Rechallenge is when a drug suspected of causing an AE in a specific subject in the past is readministered to that 
subject. If the AE recurs upon exposure, this is termed a positive rechallenge. If the AE does not recur, this is termed 
a negative rechallenge. 
 


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Seriousness 
An SAE is defined as any untoward medical occurrence that at any dose: 
• Results in death. 
• Is life-threatening; this means that the subject was at risk of death at the time of the event; 
it does not mean that the event hypothetically might have caused death if it were more 
severe. 
• Requires hospitalization or prolongation in existing hospitalization; in general, 
hospitalization signifies that the subject has been detained (usually involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that 
would not have been appropriate in the physician’s office or outpatient setting.  
Complications that occur during hospitalization are AEs. If a complication prolongs 
hospitalization or fulfills any other serious criteria, the event is serious. When in doubt as to 
whether hospitalization occurred or was necessary, the AE should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
Baseline is not considered an AE. 
• Results in persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions. 
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (e.g., sprained ankle) which may interfere with or prevent everyday life 
functions but do not constitute a substantial disruption. 
• Is a congenital anomaly or birth defect, or 
• Is another important medical event (see below) 
Important medical events that do not result in death, are not life-threatening or do not require 
hospitalization may be considered SAEs when, based on appropriate medical judgment, they 
may jeopardize the subject and may require medical or surgical intervention to prevent one 
of the outcomes listed above. Examples of such medical events include invasive or malignant 
cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, 
blood dyscrasias or convulsions that do not result in hospitalization, or development of drug 
dependency or drug abuse. 
A distinction should be drawn between serious and severe AEs. Severity is a measure of intensity 
whereas seriousness is defined by the criteria above. For example, a mild degree of 


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gastrointestinal bleeding requiring an overnight hospitalization for monitoring purposes would be 
considered an SAE, but is not necessarily severe. Similarly, an AE that is severe in intensity is 
not necessarily an SAE. For example, headache may be assessed as severe in intensity but would 
not be considered an SAE. 
Medical and scientific judgment should be exercised in deciding if an AE is serious and if 
expedited reporting is appropriate. 
6.1.1.4 
Reporting of Serious Adverse Events 
Prompt (within 24 hours) notification by the investigator to the Sponsor’s designated Drug 
Safety and Pharmacovigilance vendor, i.e., MMS, of an SAE is essential so that legal obligations 
and ethical responsibilities towards the safety of subjects and the safety of a study treatment 
under clinical investigation are met. 
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study treatment under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, institutional review boards (IRBs)/independent ethics committees 
(IECs), and investigators. 
The investigator will review each SAE and evaluate the intensity and the causal relationship of 
the event to IMP/study procedure. All SAEs will be recorded from after the first dose of open-
label IMP at Visit 2 (Day 1) until completion of the Safety Follow-up. SAEs occurring after the 
Safety Follow-up Visit and coming to the attention of the investigator must be reported only if 
there is (in the opinion of the investigator) reasonable causal relationship with the IMP. 
The investigator is responsible for updating the Electronic Data Capture system and providing 
notification to the MMS Drug Safety and Pharmacovigilance of any SAE, whether deemed IMP-
related or not, that a subject experience during their participation in study within 24 hours of 
becoming aware of the event to: 
Email : 
  
Fax : 
 
The MMS Drug Safety and Pharmacovigilance is responsible for providing notification to the 
Sponsor of any SAE as soon as they become aware of the event. 
As a minimum requirement, the initial notification should provide the following information: 
• Identifiable subject 
• Identifiable event (including causality assessment) 
• Identifiable IMP 


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• Identifiable reporter 
The MMS Drug Safety and Pharmacovigilance will request clarification of omitted or discrepant 
information from the initial notification. The Principal Investigator or an authorized designee is 
responsible for faxing or emailing the requested information to the MMS Drug Safety and 
Pharmacovigilance within 24 hours of the request. 
It is not acceptable for the investigator to send photocopies of the subject’s medical records to 
the sponsor in lieu of appropriate completion of SAE Report Form. Additional information (copy 
of lab reports, consultant reports, copy of discharge summaries, etc.) should be provided on 
request of study Medical Monitor of MMS Drug Safety and Pharmacovigilance.  
If a new SAE Report Form is faxed or emailed, then the Principal Investigator must sign and date 
the form. In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE Report Form, sent by email 
 or Fax 
 Initial notification via telephone does not 
replace the need for the investigator to complete and sign the SAE Report Form within the 
designated reporting time frames. Contacts for SAE reporting can be found on the protocol title 
page. 
All SAE reports submitted by the Investigator will be reviewed by the study Sponsor and 
assessed for meeting criteria of Suspected Unexpected Serious Adverse Reactions (SUSARs). 
All SUSARs will be reported by the Sponsor to Competent National Authorities and 
investigators according to local regulatory requirements and Sponsor policy. 
An investigator who receives an Individual Case Safety Report (ICSR) describing a SUSAR or 
other specific safety information (e.g., summary or listing of SAEs) from the Sponsor will 
review and then file it along with the Investigator’s Brochure and will notify the IRB/IEC, if 
appropriate according to local requirements. 
6.1.1.5 
Follow-up of Adverse Events 
All AEs experienced by a subject, irrespective of the suspected causality or seriousness, will be 
monitored until the event has resolved, until any abnormal laboratory values have returned to 
Baseline or stabilized at a level acceptable to the investigator and Medical Monitor, until there is 
a satisfactory explanation for the changes observed or until the subject is lost to follow-up. If a 
subject is lost to follow-up and has not answered any phone calls from the site (at least 3 calls), a 
final proof of contact via certified letter is required (see Section 7.7). 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the Sponsor and/or 
CRO to elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals. 


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6.1.2 
Pregnancy 
The investigator will attempt to collect pregnancy information on any male subject’s female 
partner who becomes pregnant while the male subject is in this study. Only female subjects of 
non-childbearing potential (i.e., permanently sterilized, postmenopausal) are eligible for 
participation.  
After obtaining the necessary signed informed consent from the pregnant female partner directly, 
the investigator will record pregnancy information on the appropriate form and submit it to the 
MMS Drug Safety and Pharmacovigilance within 24 hours of learning of the partner’s 
pregnancy. The female partner will also be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and child will be forwarded to the Sponsor. Generally, 
the follow-up will be no longer than 6 to 8 weeks following the estimated delivery date. Any 
termination of the pregnancy will be reported regardless of fetal status (presence or absence of 
anomalies) or indication for the procedure. 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs. 
6.1.3 
Clinical Laboratory Assessments 
The following laboratory variables will be determined as outlined in Table 4 below: 
Table 4 
Clinical Laboratory Assessments 
Test 
Parameters 
Hematology 
CBC 
HbA1c 
Hemoglobin 
Hematocrit 
Erythrocytes (RBC) 
Leukocytes (WBC)  
Differential WBC 
Platelets 
Biochemistry 
Sodium 
Potassium 
Calcium 
Chloride 
Glucose 
Creatinine 
ALP 
AST 
ALT 
GGT 
CPK 
Total bilirubin 
Total protein 
Albumin 
Total Cholesterol 
Low-density lipoprotein  
High-density lipoprotein 
Triglycerides 
 
Coagulation 
INR 
PT 
aPTT 
Urinalysis  
pH 
glucose 
ketones 
specific gravity 
nitrite 
protein 
bilirubin 
blood 
CBC = complete blood count; CPK = creatine phosphokinase; RBC = red blood cells; WBC = white blood cells; 
AST = aminotransferase; ALT = alanine transaminase; ALP = alkaline phosphatase; GGT = gamma-glutamyl transferase; 
INR = international normalized ratio; PT = prothrombin time; aPTT = activated partial thromboplastin time. 
 


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Safety laboratory assessments will be performed at the timepoints detailed in the Schedule of 
Assessments (Table 1). Any value outside the normal range will be flagged for clinical 
interpretation by the investigator or designee at the site. In this study, ALT or AST > 2 times the 
upper limit of normal, or Child-Pugh class B and C (i.e., including total bilirubin, albumin, and 
INR values), will be exclusionary. For transaminase liver enzymes, a repeat laboratory 
assessment may be performed if outside of the normal range. If the transaminases remain 
elevated the investigator should consider stopping study medication and withdrawing the subject 
as described in Section 5.8. 
A medical alert for potential Hy’s law cases (possible drug-induced liver injury) will be issued 
based on lab values and supported by Medical Monitor interpretation. Investigators, the Sponsor, 
Medical Monitor (203AD_MM@athira.com), and MMS – Sponsor’s designated CRO for Drug 
Safety and Pharmacovigilance (drugsafety@athira.com) will immediately be notified when the 
above criteria have been met through a central laboratory alert. The AE eCRF should be 
completed within 3 business days. Every effort to determine the cause of the liver enzyme 
abnormalities must be made, and close monitoring should be initiated in conjunction with the 
Medical Monitor and in accordance with the FDA Guidance for Industry, Drug-Induced Liver 
Injury: Premarketing Clinical Evaluation, July 2009. 
Criteria for potential Hy’s law cases are as follows:  
• 
ALT or AST ≥ 3 × ULN AND  
• 
Total bilirubin ≥ 2 × ULN AND  
• 
Alkaline phosphatase < 2 × ULN 
Typically, all 3 analytes will be obtained from the same sample, but they may come from 
multiple samples taken within a 24-hour period. This requirement applies from the time the 
subject signs the ICF for the study until resolution. Any clinically significant abnormalities from 
Visit 1 (Day 0) labs must be discussed with the Medical Monitor to confirm eligibility of the 
subject. Additional testing during the study may be done if medically indicated. If a clinically 
significant abnormality is found in the samples taken after dosing, during the study, and/or at the 
safety follow-up visit, it should be recorded as an AE and the subject will be followed until the 
test(s) has (have) normalized or stabilized. 
Note: clinical laboratory test results, ECGs, and vital signs evaluated at Visit 1 may be repeated 
if outside the normal range and not considered clinically significant, as per Section 7.1.1 
(Unscheduled Visits). 
6.1.4 
Vital Signs 
Vital signs will be assessed pre-dose at the timepoints detailed in the Schedule of Assessments 
(Table 1). The following vital signs will be measured:  
• Blood pressure (supine) (systolic and diastolic [mmHg]) 


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• Orthostatic blood pressure (systolic and diastolic [mmHg])) 
• Heart rate (bpm) 
• Body temperature (°C) (oral or tympanic) 
• Respiratory rate (breaths per minute) 
Orthostatic blood pressure will be recorded as specified in Table 1. The first blood pressure will 
be the average of 3 measurements recorded after the subject is supine for 5 minutes; the second 
blood pressure will be recorded after the subject stood for up to 3 minutes. A drop in blood 
pressure of ≥ 20 mmHg, or in diastolic blood pressure of ≥ 10 mmHg will be considered 
abnormal. 
6.1.5 
12-Lead Electrocardiogram 
Standard safety 12-lead ECGs will be performed 30 (± 15) minutes post-dose- at all study visits 
in triplicate sequentially, as detailed in the Schedule of Assessments (Table 1). 
The 12-lead ECGs will be performed after the subject has been resting supine for ≥ 5 minutes. 
The ECG will include all 12 standard leads and a Lead II rhythm strip on the bottom of the 
tracing. The following ECG parameters will be collected: PR interval, QRS interval, RR interval, 
QT interval, and QTcF. 
All ECGs must be evaluated by the investigator or qualified designee for the presence of 
abnormalities. Collection and analysis of ECG data will be performed by a central ECG vendor. 
For QTcF readings that are borderline, or difficult to interpret due to e.g., presence of a Branch 
Bundle Block, or in those where the T and U waves are superimposed or connected, a manual, 
local reading using the same ECG device should be considered, in discussion with the Medical 
Monitor. 
6.1.6 
Physical and Neurological Examination 
Physical and neurological examination will be performed by the investigator or designee at the 
timepoints detailed in the Schedule of Assessments (Table 1). 
The physical examination includes an assessment of general appearance and a review of systems 
— skin, head, eyes, ears, nose, mouth/throat/neck, thyroid, lymph nodes, respiratory, 
cardiovascular, gastrointestinal, extremities, musculoskeletal, neurological, and mental status 
examination. 
Body weight will be assessed at Visit 1 (Day 0), Visit 10 (Week 26), Visit 14 (Week 50), 
Visit 19 (Week 80), Visit 23 (Week 104), Visit 28 (Week 134), Visit 32 (Week 158), Visit 37 
(Week 188), Visit 40/ET (Week 206), and at Visit 41 (Safety follow-up; Week 210). 


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Neurological components include, but are not limited to, the following assessments: mental 
status, cranial nerves, muscle strength, tone, and bulk, reflexes, coordination, sensory function, 
and gait. 
6.1.7 
Columbia-Suicide Severity Rating Scale (C-SSRS) 
The C-SSRS will be performed at Visit 1 (Day 0), Visit 4 (Week 2), Visit 6 (Week 6), Visit 7 
(Week 12), Visit 8 (Week 18), Visit 10 (Week 26), and all subsequent visits through Visit 41 
(Safety follow-up) (Week 210) (Table 1). 
The C-SSRS supports suicide risk assessment through a series of simple, plain-language 
questions. The responses assist in identifying whether a subject is at risk for suicide, assesses the 
severity and immediacy of that risk, and gauge the level of support that the subject may require. 
If items 1 to 5 of the C-SSRS have a positive response and are of clinical concern, as judged by 
the investigator during the study, the Medical Monitor must be contacted. 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 




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7 
STUDY CONDUCT 
• Study procedures and their timing are summarized in the Schedule of Assessments 
(Table 1). 
• Protocol exemptions related to enrollment criteria are only allowed with prior 
Investigator and Sponsor approval, supported by documented agreement from the 
IRB/IEC. 
• Immediate safety concerns should be discussed with the Medical Monitor immediately 
upon occurrence or awareness to determine if the subject should continue or discontinue 
study treatment. 
• Adherence to the study design requirements, including those specified in the Schedule of 
Assessments, is essential and required for study conduct. 
• All Visit 1 evaluations for study eligibility (excluding safety lab data) must be completed 
and reviewed to confirm that potential subjects meet all eligibility criteria; evaluation of 
safety lab data from Visit 7 of either of the two parent studies is allowed for assessment 
of subject eligibility (to be confirmed with safety lab data from Visit 1 of this study). 
7.1 
Schedule and Order of Assessments 
Following informed consent and confirmation of eligibility at Visit 1, the study will consist of 
206 weeks of open-label treatment and a 4-week safety follow-up.  
All assessments to be performed during the study are detailed by visit/timepoint in Table 1.  
7.1.1 
Unscheduled Visit(s) 
An unscheduled visit may be performed at any time during the study as deemed necessary by the 
investigator. The date and reason for the unscheduled visit will be recorded. AE monitoring and 
concomitant medication recording should be performed by the investigator. Other procedures 
and evaluations will be completed as deemed necessary by the investigator and may include (but 
not limited to) laboratory tests, ECG, vital signs, and physical examination. Please ensure to 
discuss with the Medical Monitor prior to conducting any unscheduled visit. 
7.2 
Pandemic Response 
In the event of a pandemic that impacts study conduct, the following protocol changes will be 
implemented should the situation arise (implementation should be discussed on a case-by-case 
basis, with sponsor approval): 


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• Study visits should be conducted on-site if conditions permit, but flexibility will be 
allowed upon agreement between sites, CRO, and sponsor. Study visits are to be 
completed according to one of the following options: 
a. On-site visit with proper safety arrangements 
b. Site staff visit to the subject at home 
c. Travel nurse visits the subject at home 
d. Tele-health using phone, video call, or others 
e. Subject goes to local laboratory for biological samples to be taken 
7.3 
Data Safety Monitoring Board 
In continuation from the two parent studies, ATH-1017-AD-0201 and ATH-1017-AD-0202, an 
independent DSMB will conduct periodic review and assessments of safety data (AEs, labs, 
ECG, etc.) throughout the OLEX study (ATH-1017-AD-0203) to ensure the safety of study 
subjects. Based on safety data review, the DSMB may recommend terminating the study. 
The DSMB is composed of at least a study-independent non-Sponsor physician and a 
study-independent statistician. Additional members have been included and ad hoc members 
may also be invited depending on the safety findings and required scope of expertise. 
Details regarding the DSMB are included in the DSMB charter, including committee 
membership, data review procedures, frequency of review, and communication between the 
DSMB and others. 
7.4 
Supportive Care Measures for Potential Adverse Events 
If a subject experiences an AE relating to eosinophilia or an ISR, the investigator will take the 
appropriate follow-up action to manage clinical symptoms and monitor subject safety (Table 5). 
Table 5 
Supportive Care Measures and Follow-up of Potential Adverse Events 
Adverse Event 
Action Required 
Eosinophilia 
AEC < 3000/µL 
Continue IP as per protocol. 
AEC > 3000/µL 
Arrange repeat measurement within 2 weeks and continue IP. 
• 
If further increase of AEC on 2 repeat tests, consult with 
Medical Monitor and Sponsor. 
o 
Consider hold of IP for 2 weeks. 
• 
If trend is stable or downward on 2 repeat tests, continue IP and 
standard testing schedule as per protocol. 
AEC increase associated with other 
hematologic signs or symptoms 
Consult with Medical Monitor and Sponsor promptly and follow local 
SOP for SAE/Emergency as appropriate. 


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• 
Consider hold of IP for 2 weeks. 
Injection Site Reaction 
Mild ISR 
Consider treatment with topical hydrocortisone 1% and/or non-sedating 
antihistamines up to twice daily, as needed. 
Moderate ISR 
Immediately apply prescription strength ointment/cream (PRN up to two 
times a day) (e.g., Triamcinolone, 0.1% Betamethasone, 0.05% 
Clobetasol, and/or non-sedating antihistamines) up to twice daily, as 
needed. 
AEC = absolute eosinophil count; IP = investigational product; ISR = injection site reaction; SAE = serious adverse event; 
SOP = standard operating procedure. 
7.5 
Concomitant Medications and Treatments 
7.5.1 
Prohibited Treatments During the Study 
Concomitant use of the following drugs is excluded during the study:  
• Memantine in any form, combination, or dosage 
• Addition of acetylcholinesterase inhibitors during the study (subjects on stable doses on 
entry may remain on them) 
All allowed medications should remain stable throughout the study; for medications affecting 
cognition, the doses should be stable throughout the study, unless otherwise noted. 
The following drugs are prohibited during the study: 
• Psychoactive medications (including antipsychotics, tricyclic antidepressants, anxiolytics, 
or sedative hypnotics, including barbiturates) having significant anticholinergic effects 
and/or believed to affect cognitive function (for exceptions see Section 7.5.2). 
• Nicotine therapy (including patches), varenicline (Chantix), or similar therapeutic agent 
• Peripherally acting drugs with effects on cholinergic neurotransmission. Solifenacin is 
allowed if the subject has received a stable dose for at least 3 months before enrollment 
into the study 
• Systemic immunosuppressants, including systemic corticosteroids, if taken in clinically 
immunosuppressive doses in the judgment of the investigator (for exceptions see 
Section 7.5.2) 
• Anti-epileptic medication if taken for control of seizures. Other uses e.g., neuropathy and 
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• Chronic intake of opioid containing analgesics; PRN use is allowed (but not within 
72 hours before study visits) 
• Sedating H1 antihistamines; non-sedating H1 antihistamines are allowed 
• Systemic moderate to strong Cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., 
ketoconazole, itraconazole, fluconazole, cimetidine, clarithromycin, erythromycin, 
troleandomycin); topical applications are allowed (see Appendix 1: List of Prohibited 
Medications for non-exhaustive list) 
• Systemic moderate to strong CYP3A4 inducers (e.g., carbamazepine, rifabutin, ritonavir, 
and St. John’s wort); topical applications are allowed (see Appendix 1: List of Prohibited 
Medications for non-exhaustive list) 
Subjects that use prohibited medications listed above during the study may be discontinued from 
study drug. 
Note: The discontinuation of a subject due to use of a prohibited medication shall be discussed 
between the investigator, Medical Monitor, and Sponsor. The investigator should contact the 
Medical Monitor prior to discontinuing a subject for disallowed medications. 
See Appendix 1: List of Prohibited Medications for a non-exhaustive list of prohibited 
medications. 
7.5.2 
Permitted Treatments 
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, 
and/or herbal supplements) that the subject is receiving at the time of enrollment or receives 
during the study must be recorded along with: 
• Indication 
• Dates of administration including start and end dates 
• Dosage information including dose and frequency 
Subjects who roll over into this OLEX study from either Study ATH-1017-AD-0201 or 
ATH-1017-AD-0202 should continue to take any ongoing medications. The dosage(s) of 
concomitant medications should remain constant during the course of this study. Dose 
adjustment or termination of any ongoing medications, including for example donepezil, should 
first be discussed between the investigator and the Medical Monitor. 
Immunosuppressant use for allergy or other inflammation, e.g., asthma, topical otics, 
opthalmologics, skin creams, and intra-articular injections is allowed. 


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If the permissibility of a specific medication/treatment is in question, please contact the Medical 
Monitor. 
The Sponsor or CRO should be contacted if there are any questions regarding concomitant or 
prior therapy. 
7.5.3 
Other Restrictions 
7.5.3.1 
Food and Food Supplements 
The consumption of grapefruit or grapefruit-containing products is prohibited during the study. 
Food supplements and nutraceuticals that were being taken during a subject’s participation in 
either of the two parent studies are allowed, and may be continued during this study as long as 
they remain stable. 
7.5.3.2 
Contraceptives 
Sexually active males with female partners must ensure that a double barrier method of 
contraception is used (i.e., condom plus diaphragm, condom or diaphragm plus spermicide gel or 
foam) for the duration of the study, including the 4-week safety follow-up period. 
7.6 
Subject Withdrawal 
A subject’s participation in the study may be discontinued at any time at the discretion of the 
investigator and/or Sponsor, in accordance with his/her best professional judgment. However, it 
is encouraged that the investigator contact the Sponsor, when possible, to discuss possible 
reasons for discontinuation prior to withdrawing a subject from the study. Notification of early 
subject discontinuation from the study and the reason for discontinuation will be made to the 
Sponsor and will be clearly documented on the appropriate eCRF. 
7.6.1 
Discontinuation of Study Treatment 
All subjects who permanently discontinue study treatment, for whatever reason, will be 
withdrawn from the study. Upon discontinuation of study drug, subjects may continue with their 
original treatment following consultation with their primary care physician; tapering off study 
medication is not required. 
See the schedule of activities for data to be collected at the time of treatment discontinuation and 
follow-up and for any further evaluations that need to be completed (Table 1). 
7.6.2 
Withdrawal from the Study 
• A subject may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, 
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• Subjects must be discontinued from the study and/or receive no further study treatment, if 
any of the following criteria are met: 
o 
Any of the stopping criteria described in Section 5.8 
o 
Any AE or safety finding that may jeopardize the subject’s health in the 
investigator’s judgment, and which is considered to be at least possibly related to the 
study drug. 
o 
Withdrawal of informed consent by subject/legally authorized representative, if not 
prompted by an AE or lack of efficacy. If the latter, then that should be recorded as 
the reason for ET. 
o 
Physician decision 
o 
Non-compliance with study drug (see Section 5.6) 
o 
Site terminated by sponsor 
o 
Repeat incapacity of subject and/or caregiver (in the judgment of the investigator) to 
properly administer study drug despite training and testing 
o 
Prolonged or definitive loss of caregiver without adequate replacement 
o 
Nursing home placement 
• If the subject withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
• If a subject withdraws from the study, he/she may request destruction of any samples 
taken and not tested, and the investigator must document this in the site study records. 
• All subjects who prematurely discontinue from the study, i.e., prior to Visit 40 
(Week 206), unless the cause is screen failure, should return for an early termination visit 
and complete all the assessments scheduled for the Week 206 visit (Visit 40); see the 
schedule of activities (Table 1) for data to be collected. 
• Unless the reasons of premature discontinuation prevent further meaningful testing, 
investigators should make every effort to motivate subjects who discontinue early (and 
caregiver) to return for a Visit 40 (Week 206) for final assessments within 2 weeks of ET. 


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Upon discontinuation of study drug, subjects may continue with their original treatment 
following consultation with their primary care physician; tapering off study medication is not 
required. 
7.7 
Lost to Follow-up 
A subject will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site. 
The following actions must be taken if a subject fails to return to the clinic for a required study 
visit: 
• The site must attempt to contact the subject and reschedule the missed visit as soon as 
possible and counsel the subject on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the subject wishes to and/or should continue in the 
study. 
• Before a subject is deemed lost to follow up, the investigator or designee must make 
every effort to regain contact with the subject (where possible, 3 telephone calls/emails, 
and if necessary, a certified letter to the subject’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the subject’s study 
records. 
• Should the subject continue to be unreachable, he/she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
7.8 
Termination of the Clinical Study 
The Sponsor designee reserves the right to close the study site(s) or terminate the study at any 
time for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
• Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the Sponsor’s procedures, or Good Clinical Practice (GCP) 
guidelines 
• Discontinuation of further study treatment development 


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8 
STATISTICAL METHODS 
Before database lock, a statistical analysis plan (SAP) will be issued as a separate document, 
providing detailed methods for the analyses outlined below. Any deviations from the planned 
analyses will be described and justified in the clinical study report. 
8.1 
Populations for Analysis 
8.1.1 
Safety population 
The Safety population will include all subjects who received at least one dose of the study 
medication. Subjects will be analyzed based on actual treatment received. 
8.2 
General Considerations 
Descriptive statistics for continuous variables will include number of subjects (n), arithmetic 
mean, standard deviation, median, minimum, maximum and first and third quartile limits unless 
otherwise noted. Frequency and percentage will be calculated for categorical variables. 
Percentages are based on the number of subjects in the given population for AE summary tables, 
and additionally overall for medical history, prior and concomitant medications. For all other 
tables, percentages are based on the number of subjects with non—missing data and overall for 
the given population. 
8.3 
Safety Summaries 
The Safety population will be used for analyses of each of the safety endpoints. All concomitant 
medications will be tabulated according to drug class and preferred term using the World Health 
Organization Drug dictionary. Clinical laboratory tests, vital signs, physical and neurological 
examinations, and ECG results will be summarized by number of subjects, and frequency rates. 
The timepoint of each event will also be summarized. 
8.3.1 
Adverse Events 
AEs occurring after the start of study drug dosing at on Day 1 will be summarized descriptively 
for the Safety population. All AEs will be coded according to system organ class and preferred 
term using a Medical Dictionary for Regulatory Activities dictionary. Summary tables showing 
the number of subjects and percent within each category will be generated for each of the 
following types of AEs:  
• 
All events 
• 
Serious events 
• 
Deaths 


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• 
Events leading to study discontinuation 
• 
Events related to study treatment (study drug and injection procedure separately) 
• 
Severe events 
8.3.2 
Laboratory parameters 
Laboratory parameters and vital signs will be summarized by scheduled and unscheduled visit. 
Frequencies of high and low values with respect to the normal range will be displayed, as will 
shift tables comparing results at each treatment visit. 
8.3.3 
12-Lead Electrocardiogram 
12-lead ECG data (observed and change from Baseline) will be listed for each subject by visit. 
Observed values and change from Baseline will be summarized descriptively.  
8.3.4 
Columbia-Suicide Severity Rating Scale 
Results from the C-SSRS questionnaire will be listed and summarized using descriptive statistics 
by visit. 
8.4 
Determination of Sample Size 
For this OLEX study, no formal sample size calculation was used. It is estimated that up to 
approximately 450 subjects will enter this OLEX study from Studies ATH-1017-AD-0201 and 
ATH-1017-AD-0202. 
 
 
 
 
 
 
 
 
 
 
 


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8.9 
Interim Analysis 
Given the open label nature of this study, data may be evaluated from time to time to assess 
ongoing disease activity and safety. 


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9 
ETHICAL, LEGAL, AND ADMINISTRATIVE ASPECTS 
9.1 
Data Quality Assurance 
The CRO/Sponsor will conduct a study initiation visit to verify the qualifications of the 
investigator, inspect the facilities, and inform the investigator of responsibilities and procedures 
for ensuring adequate and correct documentation. 
The investigator must prepare and maintain adequate and accurate records of all observations 
and other data pertinent to the clinical study for each study subject. 
The investigator is responsible for ensuring that data are properly recorded on each subject’s 
eCRF and related documents in a timely manner. An investigator who has signed the protocol 
signature page should electronically sign for the eCRFs (as indicated in the eCRFs) to ensure that 
the observations and findings are recorded on the eCRFs correctly and completely. The eCRFs 
are to be submitted in a timely manner, or as otherwise specified by the Sponsor, and will be 
maintained in a central data repository. 
Frequent communication between the study site and the CRO/Sponsor is essential to ensure that 
the safety of the study is monitored adequately. The investigator will make all appropriate safety 
assessments on an ongoing basis. The Medical Monitor may review safety information as it 
becomes available throughout the study. 
All aspects of the study will be carefully monitored with respect to GCP and standard operating 
procedures (SOPs) for compliance with applicable government regulations. The Study Monitor 
will be an authorized individual designated by the Sponsor. The Study Monitor will have access 
to all records necessary to ensure integrity of the data and will periodically review the progress 
of the study with the Principal Investigator. 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator at least 2 years after the last approval of a marketing application in 
an International Council for Harmonisation (ICH) region and until there are no pending or 
contemplated marketing applications in an ICH region or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IMP. These documents should be retained 
for a longer period, however, if required by the applicable regulatory requirements or by an 
agreement with the Sponsor. It is the responsibility of the Sponsor to inform the 
investigator/institution as to when these documents no longer need to be retained. No records 
may be destroyed during the retention period without the written approval of the Sponsor. No 
records may be transferred to another location or party without written notification to the 
Sponsor. 


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9.2 
Access to Source Data/Documents 
Source documents provide evidence for the existence of the subject and substantiate the integrity 
of the data collected. Source documents are filed at the investigator’s site. 
The investigator will ensure the accuracy, completeness and timeliness of the data reported to the 
Sponsor. Data reported or entered in the eCRF that are transcribed from source documents must 
be consistent with the source documents or the discrepancies must be explained. The investigator 
may need to request previous medical records or transfer records. Also, current medical records 
must be available.  
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. The investigator or designee will cooperate with the Sponsor’s representative(s) for the 
periodic review of study documents to ensure the accuracy and completeness of the data capture 
system at each scheduled monitoring visit. 
Electronic consistency checks and manual review will be used to identify any errors or 
inconsistencies in the data. This information will be provided to the respective study sites by 
means of electronic or manual queries. 
The investigator or designee will prepare and maintain adequate and accurate study documents 
(medical records, ECGs, AE, and concomitant medication reporting, raw data collection forms, 
as well as the results of diagnostic tests such as x-rays and laboratory tests) designed to record all 
observations and other pertinent data for each subject receiving IMP. 
The investigator will allow Sponsor representatives, contract designees, authorized regulatory 
authority inspectors and the IRB/IEC to have direct access to all documents pertaining to the 
study. 
9.3 
Archiving Study Documents 
According to ICH guidelines, essential documents should be retained for a minimum of 2 years 
after the last approval of a marketing application in an ICH region and until there are no pending 
or contemplated marketing applications in an ICH region or at least 2 years have elapsed since 
the formal discontinuation of clinical development of the IMP. However, these documents 
should be retained for a longer period if required by the applicable legal requirements. 
9.4 
Good Clinical Practice 
The procedures set out in this clinical study protocol are designed to ensure that the Sponsor and 
the investigator abide by the ICH Tripartite Guideline for GCP (E6) and with other applicable 
regulatory requirements. The clinical study also will be carried out in keeping with national and 


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local legal requirements (in accordance with United States Investigational New Drug 
Regulations [21 CFR 56]). 
9.5 
Informed Consent 
Before each subject is enrolled in this OLEX clinical study, written informed consent will be 
obtained from the subject or his/her legally authorized representative (LAR) according to the 
applicable regulatory and legal requirements. As part of this procedure, the investigator or 
appropriately qualified designee must explain orally and in writing (when possible) the nature, 
duration, and purpose of the study and the action of the IMP in such a manner that the study 
subject is aware of the potential risks, inconveniences, or AEs that may occur, and answer all 
questions regarding the study. The study subject should be informed that their participation Is 
voluntary and that he/she is free to withdraw from the study at any time. If a subject, LAR, and 
caregiver/support person is not able to review consent in person at the clinic due to travel 
restrictions, documented oral review by the investigator or appropriately qualified designee with 
the subject, LAR, and caregiver/support person must occur and be documented in the subject’s 
study records. 
Subjects or their LAR will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability and 
Accountability Act requirements, where applicable, and the IRB/IEC or study center. The 
investigator or designee will provide the CRO with a copy of the IRB/IEC-approved ICF prior to 
the start of the study. 
The informed consent document must be signed and dated; the authorized person obtaining the 
informed consent must also sign the ICF. One copy will be provided to the subject/LAR and to 
the caregiver/support person, and the investigator will retain a copy as part of the clinical study 
records.  
If the caregiver/support person is different from the LAR, a specific ICF must be explained and 
this person be consented to the tasks and duties during the study; since many assessments rely 
only on the input from the caregiver/support person, it is important they understand fully their 
role in the trial. The investigator will not undertake any investigation specifically required for the 
clinical study until written consent has been obtained. The terms of the consent and when it was 
obtained must also be documented.  
If a protocol amendment is required, then the informed consent document(s) may need to be 
revised to reflect the changes to the protocol. If the informed consent document(s) are revised, 
they must be reviewed and approved by the responsible IRB/IEC, and signed by all subjects/ 
LARs/caregiver/support persons subsequently enrolled in the clinical study as well as those 
currently enrolled in the clinical study. 


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9.6 
Protocol Approval and Amendment(s) 
Before the start of the clinical study, the clinical study protocol and other relevant documents 
will be approved by the IRB/IEC, in accordance with local legal requirements. The Sponsor must 
ensure that all ethical and legal requirements have been met before the first subject is enrolled in 
the clinical study. 
This protocol is to be followed exactly. To alter the protocol, amendments must be written, 
which must be released by the Sponsor and receive IRB/IEC approval prior to implementation 
(as appropriate). 
Administrative changes may be made without the need for a formal amendment, but will also be 
mentioned in the integrated clinical study report. All amendments will be distributed to all study 
protocol recipients, with appropriate instructions. 
9.7 
Confidentiality Data Protection 
All clinical study findings and documents will be regarded as confidential. Study documents 
(protocols, Investigator Brochures, and other material) will be stored appropriately to ensure 
their confidentiality. The investigator and members of his/her research team (including the 
IRB/IEC) must not disclose such information without prior written approval from the Sponsor, 
except to the extent necessary to obtain informed consent from subjects who wish to participate 
in the trial or to comply with regulatory requirements. 
The anonymity of participating subjects must be maintained. Subjects will be specified on study 
documents by their subject number, initial or birth date, not by name. Documents that identify 
the subject (e.g., the signed informed consent document) must be maintained in confidence by 
the investigator. The subject must be informed that his/her personal study-related data will be 
used by the Sponsor in accordance with local data protection law. The level of disclosure must 
also be explained to the subject/LAR. 
9.8 
Publication Policy 
By signing the clinical study protocol, the investigator agrees with the use of results of the 
clinical study for the purposes of national and international registration, publication, and 
information for medical and pharmaceutical professionals. If necessary, the competent 
authorities will be notified of the investigator’s name, address, qualifications, and extent of 
involvement. 
The sponsor has proprietary interest in this study. Authorship and manuscript composition will 
reflect joint cooperation between multiple investigators and sites and Sponsor personnel. 
Authorship will be established prior to the writing of the manuscript. As this study involves 
multiple centers, no individual publications will be allowed prior to completion of the final 
report of the multicenter study except as agreed with the Sponsor. 


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The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 


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10 
REFERENCE LIST 
Citron, M. (2010). Alzheimer’s disease: strategies for disease modification. Nature Reviews 
Drug Discovery 9, 387-398. 
Ebens, A., et al. (1996). Hepatocyte growth factor/scatter factor is an axonal chemoattractant and 
a neurotrophic factor for spinal motor neurons. Neuron 17:1157-1172. 
FDA Guidance for Industry, Drug-Induced Liver Injury: Premarketing Clinical Evaluation, July 
2009. 
 
 
Funakoshi, H., and Nakamura, T. (2011). Hepatocyte Growth Factor (HGF): Neurotrophic 
functions and therapeutic implications for neuronal injury/diseases. Current Signal Transduction 
Therapy 6:156–167. 
 
 
Hamasaki, H., et al. (2014). Down‐regulation of MET in hippocampal neurons of Alzheimer’s 
disease brains. Neuropathology 34, 284–290. PMID 24444253. 
Hawrylycz, M., et al. (2015). Canonical genetic signatures of the adult human brain. Nature 
Neuroscience 18, 1832–1844. PMID 26571460.Hyman, B.T., et al. (2012). National Institute on 
Aging – Alzheimer’s Association guidelines on neuropathologic assessment of Alzheimer’s 
disease. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association 8, 1–13. 
 
 
Hua, X., et al. (2022). Safety, tolerability, pharmacokinetics, and pharmacodynamics of the 
positive modulator of HGF/Met, Fosgonimeton, in healthy volunteers and subjects with 
Alzheimer’s disease: randomized, placebo-controlled, double-blind, Phase 1 clinical trial. 
Journal of Alzheimer’s Disease 86, 1399-1413. 
Maina, F., and Klein, R. (1999). Hepatocyte growth factor, a versatile signal for developing 
neurons. Nature Neuroscience 2(3):213-217. 
McKhann, G.M., et al. (2011). The diagnosis of dementia due to Alzheimer’s disease: 
Recommendations from the National Institute on Aging – Alzheimer’s Association workgroups 
on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia: The Journal of the 
Alzheimer’s Association 7, 263 – 269. 


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Molnarfi, N., Benkhoucha, M., Funakoshi, H., Nakamura, T., and Lalive, P.H. (2015). 
Hepatocyte growth factor: A regulator of inflammation and autoimmunity. Autoimmun Rev 14, 
293–303. 
Organ, S.L, Tsao, M-S. (2011). An overview of the c-MET signaling pathway. Ther Adv Med 
Oncol 3(1):S7-S19. 
Piguet et al. (2017) Clinical Gene Therapy for Neurodegenerative Diseases: Past, Present, and 
Future. Human Gene Therapy 28(11):988-1003. 
 
 
Shang, J., et al. (2011). Strong neurogenesis, angiogenesis, synaptogenesis, and antifibrosis of 
hepatocyte growth factor in rats brain after transient middle cerebral artery occlusion. J. 
Neurosci. Res. 89, 86–95. 
Tyndall, S.J et al. (2007). Hepatocyte growth factor-induced enhancement of dendritic branching 
is blocked by inhibitors of N-methyl-D-aspartate receptors and calcium/calmodulin-dependent 
kinases. J. Neurosci. Res. 85, 2343–2351. 
 


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11 
APPENDICES 
11.1 
Appendix 1: List of Prohibited Medications 
This is not an exhaustive list; if the permissibility of a specific medication is in question, please 
contact the Medical Monitor. 
Category of Prohibited Medications 
Examples: General Name (Trade Name) 
NMDA Receptor Antagonists 
• Memantine (Namenda) in any form, combination 
or dosage 
Peripherally acting anticholinergics 
• Fesoterodine (Taviaz) 
• Oxybutynin (Ditropan, Ditropan XL, Gelnique, 
Oxytrol) 
• Tolterodine (Detrol, Detrol LA) 
• Trospium (Sanctura, Sanctura XR) 
Nicotine therapy  
• Nicotine patches, gum, sprays, inhalers, 
lozenges, etc. 
• Varenicline (Chantix) or similar therapeutic 
agent 
Psychoactive medications having 
significant anticholinergic effects 
and/or believed to affect cognitive 
function including antipsychotics, 
anti-depressants (tricyclic), anxiolytics 
or sedative hypnotics. 
  
Antipsychotics (Please refer to Exclusion 23c for 
conditions under which antipsychotics may be 
allowable) 
• Haloperidol (Haldol, Serenace) 
• Pimozide (Orap) 
• Perazine (Peragal, Perazin, Pernazinum, Taxilan) 
• 
Perphenazine (Trilafon) 
• 
Prochlorperazine (Compazine) 
• 
Promethazine (Avomine, Phenergan) 
• 
Trifluoperazine (Stelazine) 
• 
Clopenthixol (Sordinol) 
• 
Tiotixene (Navane, Thixit) 
• 
Loxapine (Adasuve, Loxitane) 
• 
Amoxapine (Asendin) 
• 
Aripiprazole (Abilify)  
• 
Asenapine (Saphris, Sycrest)  
• 
Clozapine (Clozaril)  
• 
Iloperidone (Fanapt, Fanapta) 
• 
Lurasidone (Latuda) 
• 
Olanzapine (Zyprexa)  
• 
Paliperidone (Invega) 
• 
Quetiapine (Seroquel)  
• 
Risperidone (Risperdal)  
• 
Trimipramine (Surmontil) 
• 
Ziprasidone (Geodon, Zeldox)  


Athira Pharma, Inc.  
Protocol ATH-1017-AD-0203  
Clinical Study Protocol 
CONFIDENTIAL 
 
Version 4 
 Page 65 of 66 
12-APR-2024 
 
Category of Prohibited Medications 
Examples: General Name (Trade Name) 
Tricyclic antidepressants 
• Clomipramine (anafranil) 
• Imipramine (tofranil, Janimine, Praminil) 
• Desipramine (Norpramin, Pertofrane) 
• Nortriptiline (Pamelor, Aventyl, Norpress) 
• Protriptyline (Vivactil) 
• Amitriptyline (Tryptomer, Elavil, Endep) 
• Amitripyilinoxide (Amioxid, Ambivalon, 
Equilibrin) 
• Amoxapin (Asendin) 
• Trimipramine (Surmontil) 
• Doxepin (Adapin, Sinequan) 
Other 
• Sedating H1 antihistamines 
• Chronic opioids 
• S-ketamine 
• Anti-epileptics 
Systemic moderate or strong CYP3A4 
inhibitors 
• Boceprevir (Victrelis) 
• Cannabidiol  
• Cimetidine 
• Clarithromycin (Biaxin, Prevpac) 
• Conivaptan (Vaprisol) 
• Diltiazem 
• Erythromycin 
• Fluconazole 
• Indinavir (Crixivan) 
• Itraconazole (Onmel, Sporanox) 
• Ketoconazole (Exina, Ketozole, Nizoral) 
• Lopinavir/ritonavir (Kaletra) 
• Mibefradil 
• Nefazodone (Serzone) 
• Nelfinavir (Viracept) 
• Posaconazole (Noxafil) 
• Ritonavir (Norvir) 
• Saquinavir (Fortovase, Invirase) 
• Telaprevir (Incivek) 
• Telithromycin (Ketek) 
• Troleandomycin 
• Verapamil 
• Voriconazole (Vfend) 


Athira Pharma, Inc.  
Protocol ATH-1017-AD-0203  
Clinical Study Protocol 
CONFIDENTIAL 
 
Version 4 
 Page 66 of 66 
12-APR-2024 
 
Category of Prohibited Medications 
Examples: General Name (Trade Name) 
Systemic moderate or strong CYP3A4 
inducers 
• 
Avasimibe 
• 
Carbamazepine (Tegretol, Tegretol XR, 
Carbatrol, Epitol, Equetro, Teril) 
• 
Mitotane (Lysodren) 
• 
Modafinil (at doses 400 mg qd and above) 
• 
Nafcillin (Unipen, Nallpen) 
• 
Phenobarbital (Solfoton, Luminal) 
• 
Phenytoin (Dilantin, Cerebyx, Phenytek, 
Phenytex) 
• 
Primidone (Mysoline) 
• 
Rifampin (Rifater, Rimactane, Rifamate, 
Rifadin) 
• 
St. John’s wort 
• 
Rifabutin (Mycobutin) 
• 
Ritonavir (Norvir) 
Systemic immunosuppressants 
 
• Tacrolimus 
• Sirolimus 
• Cyclophosphamide 
• Methotrexate 
• Azathioprine 
• Prednisone 
• Prednisolone 
• Methylprednisolone 
 



SAP_001.pdf: 




ATH-1017-AD-0203 OLEX Analysis Summary 
Athira Pharma, Inc. 
ATH-1017 Program 
Version 1.1  
 
3 of 63 
 
Document History - Changes Compared to Previous Version 
Version 
Date 
Changes 
1.0 
02Oct2024 
Initial Version 
1.1 
05Dec2024 
Added 4 Listings, 1 Figure and updated footnotes for some 
outputs to note participants might be counted for both dose 
groups. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


ATH-1017-AD-0203 OLEX Analysis Summary 
Athira Pharma, Inc. 
ATH-1017 Program 
Version 1.1  
 
4 of 63 
 
TABLE OF CONTENTS 
TABLE OF CONTENTS 
4 
ABBREVIATIONS 
5 
1 
INTRODUCTION AND SCOPE 
6 
2 
TLF TABLE OF CONTENTS 
6 
3 
TLF DRY RUN APPROACH 
7 
ATTACHMENT A – TLF SPECIFICATIONS 
8 
 


ATH-1017-AD-0203 OLEX Analysis Summary 
Athira Pharma, Inc. 
ATH-1017 Program 
Version 1.1  
 
5 of 63 
 
ABBREVIATIONS 
AE 
Adverse Event 
AD 
Alzheimer’s Disease 
ApoE 
Apolipoprotein E 
ERP 
Event related potential 
FDA 
Food and Drug Administration 
FPI 
First Patient In 
FTP 
File Transfer Protocol 
GCP 
Good Clinical Practice 
MMSE 
Mini-Mental State Examination 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SPO 
Share Point Online 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TMF 
Trial Master File 
TLFs 
Tables, Listings, and Figures 






ATH-1017-AD-0203 OLEX Analysis Summary 
Athira Pharma, Inc. 
ATH-1017 Program 
Version 1.1  
 
8 of 63 
 
 
ATTACHMENT A – TLF SPECIFICATIONS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
9 of 63 
 
ICH E3 TLG NUMBERING GUIDELINE 
 
• Guideline for Industry: Structure and Content of Clinical Study Reports  
This is a summary of the guideline as it applies to numbering tables, listings and graphs for programmers and 
statisticians.  To ensure most current guideline is being followed, reference the link on fda.gov.  
https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm073113.pdf  
 
• Section 14.x TABLES, FIGURES, AND GRAPHS REFERRED TO BUT NOT INCLUDED IN THE TEXT 
o 14.1 Demographic Data Summary figures and tables 
o 14.2 Efficacy Data Summary figures and tables 
o 14.3 Safety Data Summary figures and tables 
o 14.3.1 Displays of Adverse Events 
o 14.3.2 Listings of Deaths, Other Serious and Significant Adverse Events 
o 14.3.3 Narratives of Deaths, Other Serious and Certain Other Significant Adverse Events  
o 14.3.4 Abnormal Laboratory Value Listing (each patient)  
 
• Section 16.x APPENDICES  
o 16.1 Study Information  
o 16.2 Patient Data Listings 
▪ 16.2.1 Discontinued participants 
▪ 16.2.2 Protocol deviations 
▪ 16.2.3 Participants excluded from the efficacy analysis 
▪ 16.2.4 Demographic data 
▪ 16.2.5 Compliance and/or drug concentration data (if available) 
▪ 16.2.6 Individual efficacy response data 
▪ 16.2.7 Adverse event listings (each patient) 
▪ 16.2.8 Listing of individual laboratory measurements by patient, when required by regulatory authorities 
o 16.3. Case Report Forms (CRF's)  
▪ 16.3.1 CRF's for deaths, other serious adverse events, and withdrawals for adverse events 
▪ 16.3.2 Other CRF's submitted 
o 16.4 Individual Patient Data Listings 
 
• If there are multiple listings that belong in one of the ICH appendix sections, the number format should be 16.2.X.Y. 
(X=ICH number listed above, Y = sequential number). Example, if there are 5 AE listings then they would be number 16.2.7.1 
to 16.2.7.5. If there is only one, then use 16.2.7. 
 
 


 
 
10 of 63 
 
DISPOSITION, DEMOGRAPHICS, AND BASELINE CHARACTERISTICS 
 
 
 


 
 
11 of 63 
 
Athira Pharma, Inc. 
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ATH-1017-AD-0203 
Confidential 
Table 14.1.1.4 
Participant Disposition, Early Withdrawal from the Study 
Safety Population 
  
 
Disposition/ 
  Reason 
40 mg ATH-1017 
n (%) 
70 mg ATH-1017 
n (%) 
Overall 
n (%) 
 
 
 
 
Safety population 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Ongoing Study 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Completed Study 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Discontinued Study 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Primary reason for discontinuation of the study – n (%) 
 
 
 
  Any Adverse Event 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Lack of Efficacy 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Withdrawal by Subject or Legally Authorized Representative (LAR) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Physician Decision 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Non-Compliance with Study Drug 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Site Terminated by Sponsor 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Repeat incapacity of subject and/or caregiver (in the judgement of 
the investigator to properly administer drug) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Prolonged or definitive loss of caregiver without adequate 
replacement 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Nursing home replacement 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Lost to Follow-up 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Other 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Week of Early Withdrawal 
 
 
 
  0-2 Weeks 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  2-4 Weeks 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  … 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  32-34 Weeks 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  MISSING END OF STUDY DATE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   
 
 
 


 
 
12 of 63 
 
 
 
- Percentages are calculated using the number of participants in each treatment group as the denominator. 
- Participants receiving both 40 mg and 70 mg are counted in both dose groups; Overall is not a summation of the dose groups. 
 
 
Generated from program.sas on DDMMMYYYY HH:MM:SS. Source dataset(s): ADxx. Date of data extraction: DDMMMYYYY.  
Page X of Y 
 
NOTE: Ensure that the primary reason for discontinuation of study listed in the shell matches the options in the CRF. 
 
Programming Notes: 
• 
Week of Early Withdrawal displayed in the interval of 2 weeks till last available week data. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
13 of 63 
 
Athira Pharma, Inc. 
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ATH-1017-AD-0203 
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Table 14.1.1.5 
Major Protocol Deviations 
Safety Population 
  
 
Major Protocol Deviation/ 
 Reasons 
40 mg ATH-1017 
(N=xxx) 
n(%) 
70 mg ATH-1017 
(N=xxx) 
n(%) 
Overall 
(N=xxx) 
n(%) 
Number of participants with at least 1 major protocol 
deviation 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Inclusion/Exclusion Criteria 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Informed Consent Procedures 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Other 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Study Procedures 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Visit Schedule/Interval 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
- A participant with multiple protocol deviations within a deviation category or deviation term is counted only once. 
- Participants may have multiple protocol deviations. 
- Participants with a reported major protocol deviation in 70mg will be counted in the 70mg column. If that same participant switched to 40mg and 
reported a major protocol deviation during the 40mg timeframe, that new major protocol deviation is reported in the 40mg column. If the same major 
protocol deviation reported while taking 40mg and 70mg then it is counted in both 40mg and 70mg groups; Overall is not a summation of the dose 
groups.  
- If deviation start date is missing, the deviation is counted in each dose groups.  
 
 
 
Generated from program.sas on DDMMMYYYY HH:MM:SS. Source dataset(s): ADxx. Date of data extraction: DDMMMYYYY.  
Page X of Y 
 
 
Programming Notes: 
• 
Please add all the possible major protocol reasons as per the data collected. 
 
 


 
 
14 of 63 
 
Athira Pharma, Inc. 
Version: DRAFT 
ATH-1017-AD-0203 
Confidential 
 
Table 14.1.2.1 
Demographics and Baseline Characteristics 
Safety Population 
  
 
Parameter  
 Statistic 
 
40 mg ATH-1017 
(N=xxx) 
70 mg ATH-1017 
(N=xxx) 
Overall 
(N=xxx) 
Age at Informed Consent (years) 
n 
 
xxx 
xxx 
xxx 
Mean (SD) 
 
xx.x (x.xx) 
xx.x (x.xx) 
xx.x (x.xx) 
Median 
 
xx.x 
xx.x 
xx.x 
(Q1, Q3) 
 
(xx.x, xx.x) 
(xx.x, xx.x) 
(xx.x, xx.x) 
Min, Max 
 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
P-value  
 
                        x.xxxx 
 
 
 
Age Group - n(%) 
<65 years 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
>= 65 years 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Not Available 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
P-value  
 
                        x.xxxx 
 
 
 
Ethnicity - n(%) 
Hispanic Or Latino 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Not Hispanic Or Latino 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Not Specified 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Unknown 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Not Available 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
P-value  
 
                        x.xxxx 
 
 
 
Race - n(%) 
American or Alaskan Native 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Asian 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Black 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Hawaiian or Pacific Islander 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
White 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Other 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Not Available 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
American or Alaskan Native 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
P-value  
 
                        x.xxxx 
 
 
 
Sex - n(%) 
Male 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Female 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Not Available 
 
 
 
 
P-value  
 
                        x.xxxx 
 
 
 


 
 
15 of 63 
 
Parameter  
 Statistic 
 
40 mg ATH-1017 
(N=xxx) 
70 mg ATH-1017 
(N=xxx) 
Overall 
(N=xxx) 
Years of Education 
n 
 
xxx 
xxx 
xxx 
Mean (SD) 
 
xx.x (x.xx) 
xx.x (x.xx) 
xx.x (x.xx) 
Median 
 
xx.x 
xx.x 
xx.x 
(Q1, Q3) 
 
(xx.x, xx.x) 
(xx.x, xx.x) 
(xx.x, xx.x) 
Min, Max 
 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
P-value  
 
                        x.xxxx 
 
 
 
Height (cm) 
n 
 
xxx 
xxx 
xxx 
Mean (SD) 
 
xx.x (x.xx) 
xx.x (x.xx) 
xx.x (x.xx) 
Median 
 
xx.x 
xx.x 
xx.x 
(Q1, Q3) 
 
(xx.x, xx.x) 
(xx.x, xx.x) 
(xx.x, xx.x) 
Min, Max 
 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
P-value  
 
                        x.xxxx 
 
 
 
Weight (kg) 
n 
 
xxx 
xxx 
xxx 
Mean (SD) 
 
xx.x (x.xx) 
xx.x (x.xx) 
xx.x (x.xx) 
Median 
 
xx.x 
xx.x 
xx.x 
(Q1, Q3) 
 
(xx.x, xx.x) 
(xx.x, xx.x) 
(xx.x, xx.x) 
Min, Max 
 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
P-value  
 
                        x.xxxx 
 
 
 
Body Mass Index (kg/m2) 
n 
 
xxx 
xxx 
xxx 
Mean (SD) 
 
xx.x (x.xx) 
xx.x (x.xx) 
xx.x (x.xx) 
Median 
 
xx.x 
xx.x 
xx.x 
(Q1, Q3) 
 
(xx.x, xx.x) 
(xx.x, xx.x) 
(xx.x, xx.x) 
Min, Max 
 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
P-value  
 
                        x.xxxx 
 
 
 
- SD: Standard Deviation, Q1: 1st Quartile, Q3: 3rd Quartile; n: number of participants with values for given treatment group. 
- Percentages are calculated using the number of participants in each treatment group as the denominator. 
- MMSE Severity = Mild if MMSE total Score is between 20-24. MMSE Severity = Moderate if MMSE total Score is between 14-19. 
- p-values presented test for a difference between participants who received 40mg ATH-1017 and participants who received 40mg ATH-1017. A 2 sample 
t-test is used to test the difference for continuous variables and a chi-squared test of independence is used to test the difference for 
categorical variables. N: number of Participants in the specified population without Acetylcholinesterase Inhibitors for given treatment group. 
Safety population includes all participants who received at least one dose of study medication, classified by actual treatment received.  
 
 
 
Generated from program.sas on DDMMMYYYY HH:MM:SS. Source dataset(s): ADxx. Date of data extraction: DDMMMYYYY.  
Page X of Y 
 
 
 


 
 
16 of 63 
 
Exposure 
 
 


 
 
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Table 14.1.4.1 
Duration of Exposure to Study Treatment 
Safety Population 
 
 
Category 
 
 
 
40 mg ATH-1017 
(N=xxx) 
 
 
 
 
70 mg ATH-1017 
(N=xxx) 
 
 
 
Overall 
(N=xxx) 
 
 
Duration of study treatment (days) 
  n 
  Mean 
  SD 
  Min 
  Median 
  Q1,Q3 
  Max 
 
 
Duration of exposure, n(%) 
  At least 1 dose 
 
 
 
 
 
xx 
xx.x 
xx.xx 
xx 
xx.x 
xx,xx 
xx 
 
 
xx (xx.x) 
 
 
 
 
 
 
xx 
xx.x 
xx.xx 
xx 
xx.x 
xx,xx 
xx 
 
 
xx (xx.x) 
 
 
 
 
 
xx 
xx.x 
xx.xx 
xx 
xx.x 
xx,xx 
xx 
 
 
xx (xx.x) 
 
 
 
  2 days to <4 weeks 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
 
  4 weeks to <8 weeks  
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
 
  8 weeks to <12 weeks 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
 
  12 weeks to <16 weeks  
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
 
  16 weeks to <20 weeks  
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
 
  20 weeks to <24 weeks 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
 
  24 weeks to <48 weeks 
  48 weeks to <72 weeks 
  72 weeks to <96 weeks 
  96 weeks or more 
xx (xx.x) 
xx (xx.x)    
xx (xx.x) 
xx (xx.x) 
 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 


 
 
18 of 63 
 
- SD: Standard Deviation, Q1: 1st Quartile, Q3: 3rd Quartile 
- Day is relative to first dose date. 
- Duration of Exposure (Days) defined as date of last dose - date of first dose +1 
- Participants receiving both 40 mg and 70 mg are counted in both dose groups for their respective time in each dose group; Overall is not a 
summation of the dose groups. 
 
Generated from program.sas on DDMMMYYYY HH:MM:SS. Source dataset(s): ADxx. Date of data extraction: DDMMMYYYY.  
Page X of Y 
 
 
 
Programming Notes: 
• 
Duration of Exposure (Days) defined as date of last dose - date of first dose +1. For participants ongoing at time of the data cut, 
the date of cut-off was used as the date of last dose. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
19 of 63 
 
 
SAFETY DATA 
Displays of Adverse Events 
 
 
 
 


 
 
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Table 14.3.1.1 
Overall Summary of Adverse Events 
Safety Population 
  
 
40 mg ATH-1017 
(N=xxx) 
n(%) 
70 mg ATH-1017 
(N=xxx) 
n(%) 
Overall 
(N=xxx) 
n(%) 
 
 
 
 
Number of participants with at least 1 AE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Number of participants with at least 1 TEAE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Number of participants with at least 1 Treatment-Related TEAE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Participants with serious or other significant TEAEs 
 
 
 
  Death 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  SAE(s) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Treatment-Related Serious TEAE(s) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  TEAEs Leading to Study Drug Withdrawal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  TEAEs Leading to Study Drug Interruption 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  TEAEs Leading to Study Withdrawal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
- AE: Adverse Event; TEAE: Treatment Emergent Adverse Event; SAE: Serious Adverse Event. N: number of Participants in the specified population for 
given treatment group. Related includes related, probably related, and possibly related events. 
- Percentages are based on the Safety Population; Deaths are AEs with reported outcome of Fatal. 
- All AE terms were coded to Medical Dictionary for Regulatory Activities Terminology (MedDRA®) version 24.0. 
- Safety population includes all participants who received at least one dose of study medication, classified by actual treatment received. 
- Participants with a reported AE in 70mg will be counted in the 70mg column. If that same participant switched to 40mg and reported an AE during 
the 40mg timeframe, that new AE is reported in the 40mg column. If the same event reported while taking 40mg and 70mg then it is counted in both 
40mg and 70mg groups; Overall is not a summation of the dose groups. 
 
 
Generated from program.sas on DDMMMYYYY HH:MM:SS. Source dataset(s): ADxx. Date of data extraction: DDMMMYYYY.  
Page X of Y 
 
 
 
Programming Notes: 
• 
 
 
 


 
 
21 of 63 
 
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Table 14.3.1.2  
Treatment Emergent Adverse Events by Primary System Organ Class and Preferred Term 
Safety Population 
  
 
System Organ Class (SOC) 
   Preferred Term (PT) 
40 mg ATH-1017 
(N=xxx) 
         n (%)  
70 mg ATH-1017 
(N=xxx) 
n (%)   
Overall 
(N=xxx) 
n (%)    
 
 
 
 
Number of participants with at least 1 TEAE 
xx (xx.x)  
xx (xx.x)  
xx (xx.x)  
 
 
 
 
System Organ Class 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Preferred term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Preferred term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
System Organ Class 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Preferred term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Preferred term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
  
- TEAE: Treatment Emergent Adverse Event; n = number of participants with at least one TEAE occurring; % = (n/N) *100; N: number of 
participants in the specified population for given treatment group. Percentages based on Safety Population. SOCs are presented 
alphabetically; PTs are sorted by decreasing frequency in the Overall column. A participant with multiple adverse events within a 
primary SOC and PT is counted only once for raw incidence rates. All AE terms were coded to Medical Dictionary for Regulatory 
Activities Terminology (MedDRA®) version 24.0. Safety population includes all participants who received at least one dose of study 
medication, classified by actual treatment received. Participants with a reported AE in 70mg will be counted in the 70mg column. If 
that same participant switched to 40mg and reported an AE during the 40mg timeframe, that new AE is reported in the 40mg column. If 
the same event reported while taking 40mg and 70mg then it is counted in both 40mg and 70mg groups; Overall is not a summation of the 
dose groups. 
 
 
 
 
 
Generated from program.sas on DDMMMYYYY HH:MM  Data as of: DDMMYYYY 
Page X of Y 
 
 
• 
 
 
 


 
 
22 of 63 
 
 
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Table 14.3.1.3 
Treatment-Related TEAEs by Primary System Organ Class and Preferred Term 
Safety Population 
  
 
 
Repeat Table 14.3.1.2 for Treatment-Related TEAEs. 
Replace first row with “Number of participants with at least 1 Treatment-Related TEAE” 
 
 
Programming Notes: Add below footnote additionally  
- Related includes related, probably related, and possibly related events. 
 
 
 


 
 
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Table 14.3.1.4 
Serious TEAEs by Primary System Organ Class and Preferred Term 
Safety Population 
  
 
Use the Table 14.3.1.2 shell. 
Replace first row with “Number of participants with at least 1 Serious TEAE” 
NOTE: subset this table to show Serious TEAEs. 
 
Programming Notes: 
Table 14.3.1.5 
Treatment-Related Serious TEAEs by Primary System Organ Class and Preferred Term 
Safety Population 
  
 
Use the Table 14.3.1.2 shell. 
Replace first row with “Number of participants with at least 1 Treatment-Related Serious TEAE” 
NOTE: subset this table to show Treatment-Related Serious TEAEs. 
 
Programming Notes: Add below footnote additionally  
- Related includes related, probably related, and possibly related events. 
 
 
Table 14.3.1.6 
Adverse Events Leading to Study Drug Withdrawal by Primary System Organ Class and Preferred Term 
Safety Population 
  
 
Use the Table 14.3.1.2 shell. 
Replace first row with “Number of participants with at least 1 AE leading to study drug withdrawal” 
NOTE: subset this table to show AEs leading to study drug discontinuation only. 
 
Programming Notes: 
 
• 
 


 
 
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Table 14.3.1.7 
Adverse Events Leading to Study Drug Interruption by Primary System Organ Class and Preferred Term 
Safety Population 
  
 
Use the Table 14.3.1.2 shell. 
Replace first row with “Number of participants with at least 1 AE leading to study drug interruption” 
 
NOTE: subset this table to show AEs leading to study drug interruption only. 
 
Programming Notes: 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
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Table 14.3.1.8 
Treatment Emergent Adverse Events by Primary System Organ Class, Preferred Term, and Maximum Severity  
Safety Population 
  
 
Primary System Organ Class (SOC)/ 
 Preferred Term (PT) 
    
Severity 
40 mg ATH-1017 
(N=xxx) 
n(%) 
70 mg ATH-1017 
(N=xxx) 
n(%) 
Overall 
(N=xxx) 
n(%) 
Number of participants with at least 1 TEAE 
Overall 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Mild 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Moderate 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Severe 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
System organ class 1 
Overall 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Mild 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Moderate 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Severe 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 Preferred Term 1 
Overall 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Mild 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Moderate 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Severe 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 Preferred Term 2 
Overall 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Mild 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Moderate 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Severe 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
- TEAE: Treatment Emergent Adverse Event. A participant with multiple adverse events within a SOC or PT and a given severity is counted only once 
n = number of participants with at least one TEAE occurring; % = (n/N) *100. N: number of participants in the specified population for given 
treatment group. Percentages are based on the Safety Population. SOCs are presented alphabetically; PTs are sorted within SOC in descending 
frequency in the 40mg ATH-1017 column. All AE terms were coded to Medical Dictionary for Regulatory Activities Terminology (MedDRA®) version 
24.0. Safety population includes all participants who received at least one dose of study medication, classified by actual treatment received. 
Participants with a reported AE in 70mg will be counted in the 70mg column. If that same participant switched to 40mg and reported an AE during 
the 40mg timeframe, that new AE is reported in the 40mg column. If the same event reported while taking 40mg and 70mg then it is counted in both 
40mg and 70mg groups; Overall is not a summation of the dose groups. 
 
 
Generated from program.sas on DDMMMYYYY HH:MM:SS. Source dataset(s): ADxx. Date of data extraction: DDMMMYYYY.  
Page X of Y 
 


 
 
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Table 14.3.1.9  
Injection Site Reactions by Preferred Term 
Safety Population 
  
 
Preferred Term (PT) 
40 mg ATH-1017 
(N=xxx) 
     n (%)  
70 mg ATH-1017 
(N=xxx) 
n (%)   
Overall 
(N=xxx) 
n (%)  
 
 
 
 
Number of participants with at least 1 ISR TEAE 
xx (xx.x)  
xx (xx.x)  
xx (xx.x)  
 
 
 
 
Preferred term 1 
xx (xx.x)  
xx (xx.x)  
xx (xx.x)  
Preferred term 2 
xx (xx.x)  
xx (xx.x)  
xx (xx.x)  
Preferred term 3 
xx (xx.x)  
xx (xx.x) 
xx (xx.x)  
Preferred term 4 
xx (xx.x)  
xx (xx.x) 
xx (xx.x)  
 
 
 
 
 
 
  
- ISR = Injection site reaction; TEAE = treatment-emergent adverse event;  
- n = number of participants with at least one TEAE occurring; % = (n/N) *100;  
- N: number of participants in the specified population for given treatment group.  
- All AE terms were coded to Medical Dictionary for Regulatory Activities Terminology (MedDRA®) version 24.0. 
  - Participants with a reported ISR in 70mg will be counted in the 70mg column. If that same participant switched to 40mg and reported 
an ISR during the 40mg timeframe, that new ISR is reported in the 40mg column. If the same ISR reported while taking 40mg and 70mg then 
it is counted in both 40mg and 70mg groups; Overall is not a summation of the dose groups. 
 
 
Generated from program.sas on DDMMMYYYY HH:MM  Data as of: DDMMYYYY 
Page X of Y 
 
 
Programming Notes: 
• 
Table should be sorted by the descending frequency of the ISR PT in the Overall column. 
 
 
 
 
 
 
 
 
 
 


 
 
27 of 63 
 
Listings of Deaths, Other Serious and Significant Adverse Events 
 
 
 
 
 
 


 
 
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Listing 14.3.2.1  
Deaths Reported  
Safety Population 
  
 
Treatment 
Participant 
ID 
 
 
 
 
TEAE 
 
 
 
Relationship 
to IMP 
AChEI 
Usage/Age/Sex/ 
Race 
Start 
Date/Time of 
Study 
Treatment 
(Day) 
Last Date/Time 
of Study 
Treatment (Day) 
Death 
Date/Time 
(Day) 
Reason for Death/ 
Preferred Term 
 
 
 
 
 
 
 
 
 
XXXXXXXXX xxxxxxxx 
Y 
xxxxxx 
Y/xx/M/ 
xx 
YYYY-MM-DD 
HH:MM (xx) 
YYYY-MM-DD 
HH:MM (xx) 
YYYY-MM-DDT 
HH:MM (xx) 
xxxxxxxxx/ 
xxxxxxxx 
 
 
 
 
 
 
 
 
 
XXXXXXXXX xxxxxxxx 
N 
xxxxxx 
N/xx/F/ 
xx 
YYYY-MM-DD 
HH:MM (xx) 
YYYY-MM-DD 
HH:MM (xx) 
YYYY-MM-DDT 
HH:MM (xx) 
xxxxxxxxx/ 
xxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
- AChEI: Acetylcholinesterase inhibitor; M: Male; F: Female; IMP: Investigational Medicinal Product; 
- Day is relative to the date of first drug administration.  
- Missing dates are based on imputed dates (see SAP Appendix 4 for details). 
- Race Codes: 1: American Indian or Alaska Native; 2: Asian; 3: Black or African American; 4: Native Hawaiian or Other Pacific Islander; 5: 
White; 6: Other. 
- All AE terms were coded to Medical Dictionary for Regulatory Activities Terminology (MedDRA®) version 24.0. 
- Safety population includes all participants who received at least one dose of study medication, classified by actual treatment received. 
 
 
Generated from program.sas on DDMMMYYYY HH:MM:SS. Source dataset(s): ADxx. Date of data extraction: DDMMMYYYY.  
Page X of Y 
 
 
Programming Notes: 
• 
 
 
 
 


 
 
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Listing 14.3.2.2 
Serious Adverse Events 
Safety Population 
  
 
Treatment 
Participant 
ID  
AChEI 
Usage/Age/ 
Sex/ 
Race 
System Organ 
Class (SOC)/ 
Preferred Term 
(PT)/ 
Reported Term 
Start Date (Day)/ 
End Date (Day) or 
Ongoing 
 
 
 
 
TEAE Severity 
Treatment Given for AE/  
Relationship to IMP/ 
Relationship to Study Procedure/ 
Action Taken/ 
Outcome 
 
 
 
 
 
 
 
 
XXXXXXXX 
xxxxxxxx 
Y/xx/ 
M/ 
xx 
xxxx/ 
xxxx/ 
xxxx 
YYYY-MM-DD HH:MM (xx)/  
YYYY-MM-DD HH:MM(xx) 
Y 
MILD 
Y/ 
Related/ 
Related/ 
Dose not changed/ 
Recovered/resolved 
 
 
 
 
 
 
 
N/ 
Unrelated/ 
Related/ 
Dose not changed/ 
Recovered/resolved 
XXXXXXXX 
xxxxxxxx 
N/xx/ 
F/ 
xx 
xxxx/ 
xxxx/ 
xxxx 
YYYY-MM-DD HH:MM (xx)/  
YYYY-MM-DD HH:MM (xx) 
N 
MOD 
Treatment Given for AE/  
Relationship to IMP/ 
Relationship to Study Procedure/ 
Action Taken/ 
Outcome 
 
 
 
 
 
 
 
 
 
- TEAE: Treatment Emergent Adverse Event; IMP: Investigational Medicinal Product; AChEI: Acetylcholinesterase inhibitor; M: Male; F: Female. 
- Race Codes: 1: American Indian or Alaska Native; 2: Asian; 3: Black or African American; 4: Native Hawaiian or Other Pacific Islander; 5: White; 
6: Other. 
- Day is relative to the date of first drug administration.  
- All AE terms were coded to Medical Dictionary for Regulatory Activities Terminology (MedDRA®) version 24.0. 
- Safety population includes all participants who received at least one dose of study medication, classified by actual treatment received. 
 
Generated from program.sas on DDMMMYYYY HH:MM:SS. Source dataset(s): ADxx. Date of data extraction: DDMMMYYYY.  
Page X of Y 
 
Programming Notes: 
• 
 
 
 


 
 
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Listing 14.3.2.3 
Adverse Events  
Safety Population 
  
 
Use the Listing 14.3.2.2 shell  
 
Programming Notes: Repeat for AEs 
• 
 
 
 
 
 


 
 
31 of 63 
 
Laboratory Results 
 
Consider the following decimal precision as a guide for the mean for each parameter, if reported in SI units. 
 
Parameter 
Decimal Precision 
for Mean 
Hematology: Hemoglobin, platelets 
Chemistry: sodium, chloride, bicarbonate, creatinine, protein, albumin, ALT, AST, GGT, ALP, CK, LDH 
1 
Hematology: erythrocytes, leukocytes, lymphocytes, neutrophils, basophils/leukocytes, 
eosinophils/leukocytes, lymphocytes/leukocytes, monocytes/leukocytes, neutrophils/leukocytes 
Chemistry: potassium, glucose (fasting and non-fasting), urea nitrogen, total bilirubin (total, direct, 
indirect), triglycerides, cholesterol (total, LDL, HDL) 
Coagulation: prothrombin time, INR, APTT 
2 
Hematology: Hematocrit, basophils, eosinophils, monocytes 
Chemistry: calcium, phosphate 
3 
 
Note: 
• 
SD = mean + 1, 
• 
Median = mean 
• 
Min/Max = mean – 1 
 
Chemistry results are usually displayed in alphabetical order. For hematology results, the following order is suggested: 
• 
HGB, HCT, WBC, BASO, EOS, LYM, MONO, NEUT, BASOLE, EOSLE, LYMLE, MONOLE, NEUTLE, RBC, PLAT. 
 
 


 
 
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Table 14.3.4.3 
Shift from Baseline to Post-Baseline Visits and Worst Post-Baseline Visit in Hematology Values 
Safety Population 
 
Parameter: xxxx (units) (Low:<xxx/High:>xxx), (Low:<xxx/High:>xxx), (Low:<xxx/High:>xxx), (Low:<xxx/High:>xxx) 
 
Treatment 
Baseline 
Grade 
Worst Value During Study 
Low 
Normal 
High 
Overall 
 
n 
(%) 
n 
(%) 
n 
(%) 
n 
(%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Overall (N=xxx) 
Low 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
 
Normal 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
 
High 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
 
Total 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
- n: the number of participants who have values at both baseline (normal and abnormal) and post-baseline (abnormal). 
- Baseline is defined as the last measurement prior to first dose. 
- Overall column is the number of unique participants that have non-missing baseline values.  
- Percentage for each grade is calculated using the number of participants in the Overall column.  
- If a participant had a post-baseline value equal to LOW and another equal to HIGH, the participant is counted in each respective column. 
- Low / Normal / High thresholds are based on the lower and upper limits of normal. 
- Safety population includes all participants who received at least one dose of study medication, classified by actual treatment received. 
 
Generated from program.sas on DDMMMYYYY HH:MM:SS. Source dataset(s): ADxx. Date of data extraction: DDMMMYYYY.  
Page X of Y 
 
Programming Notes: 
• 
Replace highlighted Low/High with given low/high for parameter. 
• 
For the subtitle of Parameter and the low/high values, if there are multiple reference ranges for a specific parameter, please display 
all range pairs. 
 
 
 
NOTE:  
• 
Worst value should be defined in the Protocol as low, high, or both or sponsor can confirm. 
• 
If the missing category is not needed, then it can be omitted if a footnote is added specifying that only the participants with non-
missing baseline and at least 1 non-missing post-baseline are included. This table can be repeated for specific time points instead 
of “worst value during study”. 
 
Programming Notes: 


 
 
33 of 63 
 
• 
Please add missing rows or columns as per data requirements for completeness. 
• 
The Visits will be displayed and also Worst Post-Baseline Visit - <High/Low> assessment also displayed here. 
• 
Please sort in this order: HGB, HCT, WBC, BASO, EOS, LYM, MONO, BASOLE, EOSLE, LYMLE, MONOLE, NEUTLE, RBC, PLAT. 
 
 


 
 
34 of 63 
 
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Table 14.3.4.6 
Shift from Baseline to Post-Baseline Visits and Worst Post-Baseline Visit in Chemistry Values 
Safety Population 
  
 
 
Use the Table 14.3.4.3 shell. 
NOTE: subset this table to show Chemistry lab parameters. 
 
 
Programming Notes:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
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Table 14.3.4.9A 
Shift from Baseline to Post-Baseline Visits in Urinalysis Values (Normal/Abnormal) 
Safety Population 
  
 
Use the Table 14.3.4.3 shell. 
NOTE: subset this table to show Urinalysis lab parameters. 
 
Table 14.3.4.9B 
Shift from Baseline to Post-Baseline Visits and Worst Post-Baseline Visit in Urinalysis Values (Low/Normal/High) 
Safety Population 
  
 
 
Use the Table 14.3.4.3 shell. 
NOTE: subset this table to show Urinalysis lab parameters. 
 
 
Programming Notes:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
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Table 14.3.7.9 
Summary of Liver Related Laboratory Abnormalities 
Safety Population 
Parameter/Potentially 
Clinically   
Significant Criterion 
 
 
40 mg ATH-1017 
(N=xxx) 
 
 
70 mg ATH-1017 
(N=xxx)  
 
 
Overall 
(N=xxx)  
N1 
n (%)  
N1 
n (%)  
N1 
n (%)   
 
 
 
 
 
 
 
Alanine Aminotransferase 
xx 
 
xx 
 
xx 
 
  <LLN 
 
xx (xx.x)  
 
xx (xx.x) 
 
xx (xx.x) 
  Normal (>=LLN - <=ULN) 
 
xx (xx.x)  
 
xx (xx.x) 
 
xx (xx.x) 
  >1 - 3 x ULN 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
  >3 - 5 x ULN 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
  >5 - 10 x ULN 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
  >10 - 20 x ULN 
 
xx (xx.x)  
 
xx (xx.x) 
 
xx (xx.x) 
  >20 x ULN 
 
xx (xx.x)  
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
Aspartate Aminotransferase 
xx  
 
xx  
 
xx  
 
  <LLN 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
  Normal (>=LLN - <=ULN) 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
  >1 - 3 x ULN 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
  >3 - 5 x ULN 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
  >5 - 10 x ULN 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
  >10 - 20 x ULN 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
  >20 x ULN 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
Alkaline Phosphatase 
xx  
 
xx  
 
xx  
 
  <LLN 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
  Normal (>=LLN - <=ULN) 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
  >1 - 2 x ULN 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
  >2 x ULN 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
Bilirubin 
xx 
 
xx 
 
xx 
 
  <LLN 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
  Normal (>=LLN - <=2 x ULN) 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
  >2 x ULN 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
Hy's Law: ALT/AST>=3 x ULN and 
BILI>=2xULN 
xx 
 
xx 
 
xx 
 
  Criteria Not Met 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
  With ALP <2 x ULN 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
  With ALP >=2 x ULN 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
ALP >=2 x ULN 
xx 
 
xx 
 
xx 
 
  Criteria Not Met 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
  With ALT/AST <2 x ULN 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 


 
 
37 of 63 
 
  With ALT/AST >=2 x ULN 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
- ULN: Upper Limit of Normal; LLN: Lower Limit of Normal. n = the number of participants with at least once post-baseline for the 
corresponding parameter. N1 = the number of participants who had at least 1 post-baseline assessment for the corresponding parameter; 
Percentages are based on N1. N: number of participants in the specified population for given treatment group. 
- Safety population includes all participants who received at least one dose of study medication, classified by actual treatment 
received. Participants with an abnormality in 70mg will be counted in the 70mg column. If that same participant switched to 40mg and 
reported an abnormality during the 40mg timeframe, that new abnormality is reported in the 40mg column. If the same abnormality 
reported while taking 40mg and 70mg then it is counted in both 40mg and 70mg groups; Overall is not a summation of the dose groups. 
- Lab ranges between 201 and 203 differ due to differing lab vendors used.  
 
 
 
Programming notes: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 


 
 
38 of 63 
 
 
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Table 14.3.7.11 
Summary of Eosinophil Lab Abnormalities 
Safety Population 
 
Parameter 
  PCS Criterion 
40mg ATH-1017 
(N=xxx) 
70mg ATH-1017 
(N=xxx) 
Overall 
(N=xxx) 
 
N1 
n (%) 
 
N1 
n (%) 
 
N1 
 
n (%) 
 
 
 
 
 
 
 
 
 
 
 
Eosinophilia 
 
xx 
 
 
xx 
 
 
xx 
 
 
 
  Eosinophils >= 1500/uL  
 
xx (xx.x) 
 
 
xx (xx.x) 
 
 
 
xx (xx.x) 
 
  Eosinophils >= 3000/uL 
 
 
xx (xx.x) 
 
 
xx (xx.x) 
 
 
 
xx (xx.x) 
 
  Eosinophils >= 5000/uL 
 
 
xx (xx.x) 
 
 
xx (xx.x) 
 
 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
- PCS: potentially clinically significant. 
- n = the number of participants that met PCS criteria at least once post-baseline for the corresponding parameter.  
- N1 = the number of participants who had at least 1 post-baseline assessment for the corresponding parameter; Percentages are based on N1.  
- N: number of participants in the specified population for given treatment group. 
- Safety population includes all participants who received at least one dose of study medication, classified by actual treatment received. 
- Participants with an abnormality in 70mg will be counted in the 70mg column. If that same participant switched to 40mg and reported an 
abnormality during the 40mg timeframe, that new abnormality is reported in the 40mg column. If the same abnormality reported while taking 40mg and 
70mg then it is counted in both 40mg and 70mg groups; Overall is not a summation of the dose groups. 
 
Generated from program.sas on DDMMMYYYY HH:MM:SS. Source dataset(s): ADxx. Date of data extraction: DDMMMYYYY.  
Page X of Y 
 
 
Programming Notes: 
• 
Split pages after 70mg group if doesn’t fit 
 
 
 
 
 
 


 
 
39 of 63 
 
 
 
Vital Signs 
 
 


 
 
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Table 14.3.6.2 
Potential Vital Signs Values of Concern at Any Time Post-Baseline  
Safety Population 
  
 
Vital Sign 
 Abnormal Category 
40 mg ATH-1017 
(N=xxx) 
70 mg ATH-1017 
(N=xxx) 
Overall 
(N=xxx) 
N1 
n(%) 
N1 
n(%) 
N1 
n(%) 
 
 
 
 
 
 
Orthostatic Diastolic BP (mmHg) 
xx 
 
xx 
 
xx 
     
 Standing Diastolic BP Decrease >=10mmHg 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 Standing Diastolic BP Increase >=20mmHg 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 Standing Diastolic BP >100mmHg 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 Standing Diastolic BP >100 and Increase >=20mmHg 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 Standing Diastolic BP <50 and Decrease >=10mmHg 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 Standing Diastolic BP <50mmHg 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
Orthostatic Systolic BP (mmHg) 
xx 
 
xx 
 
xx 
     
 Standing Systolic BP Decrease >=20mmHg 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 Standing Systolic BP Increase >=20mmHg 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 Standing Systolic BP >160mmHg 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 Standing Systolic BP >160 and Increase >=20mmHg 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
Systolic Blood Pressure (mmHg) 
 
 
 
 
 
     
 Systolic BP Decrease >=20mmHg 
xx 
xx (xx.x) 
xx 
xx (xx.x) 
xx 
xx (xx.x) 
 Systolic BP Increase >=20mmHg 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 Systolic BP >160mmHg 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 Systolic BP >160 and Increase >=20mmHg 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
Diastolic Blood Pressure (mmHg) 
 
 
 
 
 
     
 Diastolic BP Decrease >=10mmHg 
xx 
xx (xx.x) 
xx 
xx (xx.x) 
xx 
xx (xx.x) 
 Diastolic BP Increase >=20mmHg 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 Diastolic BP >100 and Increase >=20mmHg 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 Diastolic BP <50 and Decrease >=10mmHg 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 Diastolic BP >100mmHg 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
Pulse Rate (beats/min) 
xx 
 
xx 
 
xx 
     
 Abnormal Heart Rate (<50 or >100 BPM) 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 Heart Rate Change >= 30 BPM 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 


 
 
41 of 63 
 
- N1: the number of participants who have values at both baseline and post-baseline. 
- Percentages are based on the Safety population. Participants may fall into more than one category. 
- Participants with a potential value of concern in 70mg will be counted in the 70mg column. If that same participant switched to 40mg and 
reported a potential value of concern during the 40mg timeframe, that new potential value of concern is reported in the 40mg column. If the same 
potential value of concern reported while taking 40mg and 70mg then it is counted in both 40mg and 70mg groups; Overall is not a summation of the 
dose groups. 
 
Generated from program.sas on DDMMMYYYY HH:MM:SS. Source dataset(s): ADxx. Date of data extraction: DDMMMYYYY.  
Page X of Y 
 
Programming Notes: 
• 
Visit can be added as a column to the left, if requested 
 
 


 
 
42 of 63 
 
ECG Tables 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
43 of 63 
 
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Table 14.3.7.4 
ECG Interpretation at Any Time Post-Baseline 
Safety Population 
  
 
Parameter 
 Finding 
40 mg ATH-1017 
(N=xxx) 
n(%) 
70 mg ATH-1017 
(N=xxx) 
n(%) 
Overall 
(N=xxx) 
n(%) 
 
 
 
Interpretation – N1 
xxx 
xxx 
xxx 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Abnormal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
- N1: the number of participants who have values at both baseline and post-baseline. 
- N: number of participants in the specified population for given treatment group. 
- Percentages are based on N1.  
- A participant is counted only once for each finding category they fall into; if a participant has at least 1 abnormal record it is counted in 
the abnormal category. 
- Safety population includes all participants who received at least one dose of study medication, classified by actual treatment received. 
- Participants with an interpretation in 70mg will be counted in the 70mg column. If that same participant switched to 40mg and reported a 
interpretation during the 40mg timeframe, that new interpretation is reported in the 40mg column. If the same interpretation reported while 
taking 40mg and 70mg then it is counted in both 40mg and 70mg groups; Overall is not a summation of the dose groups. 
 
Generated from program.sas on DDMMMYYYY HH:MM:SS. Source dataset(s): ADxx. Date of data extraction: DDMMMYYYY.  
Page X of Y 
 
Programming Notes: 
• 
Any abnormal finding for any post baseline visit will be counted as Abnormal. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
44 of 63 
 
 
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Table 14.3.7.5 
Shift from Baseline to Post-Baseline Visits in ECG Values 
Safety Population 
  
 
Use the Table 14.3.4.3 shell. 
NOTE: This table to show ECG parameters. 
 
 
Programming Notes: 
• 
Please add missing rows as per data requirements for completeness. 
• 
Use “Visit (Timepoint)” concatenated in place of ‘Visit” used in the Table 14.3.4.9A. The Visits will be displayed and also Worst 
Post-Baseline (Abnormal any time Post-Baseline) visit assessment also displayed here. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
45 of 63 
 
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Table 14.3.7.6 
Potential ECG Values of Concern at Any Time Post-Baseline  
Safety Population 
  
 
ECG Parameter 
 Abnormal Category 
40 mg ATH-1017 
(N=xxx) 
70 mg ATH-1017 
(N=xxx) 
Overall 
(N=xxx) 
N1 
n(%) 
N1 
n(%) 
N1 
n(%) 
 
 
 
 
 
 
ECG Mean Heart Rate 
xx 
 
xx 
 
xx 
 
 Heart Rate < 50 bpm 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
QRS Duration, Aggregate 
xx 
 
xx 
 
xx 
 
 QRS Duration > 120 msec 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 QRSAG Change > 25 msec 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
PR Interval, Aggregate 
xx 
 
xx 
 
xx 
 
 PR Interval > 250 msec 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 PRAG Change > 50 msec 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
QTcB Interval, Aggregate 
xx 
 
xx 
 
xx 
 
 QTcB Value >= 500 msec 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 QTcB Change >= 60 msec 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 QTcB Value >= 500 and Change >= 60 msec 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
QTcF Interval, Aggregate 
xx 
 
xx 
 
xx 
 
 QTcF Value >= 500 msec 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 QTcF Change >= 60 msec 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 QTcF Value >= 500 and Change >= 60 msec 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
- ECG: Electrocardiogram; QRS: Quantronic Resonance System: PR: P-wave to QRS complex; QTcB: Heart rate-corrected QT Interval; QTcF: QT Interval 
Corrected using Fridericia’s Formula; QRSAG: QRS Aggregate; N1: the number of participants who have values at both baseline and post-baseline. 
- N: number of participants in the specified population for given treatment group. Percentages are based on N1. Participants may fall into more 
than one category. Safety population includes all participants who received at least one dose of study medication, classified by actual treatment 
received. Participants with a potential value of concern in 70mg will be counted in the 70mg column. If that same participant switched to 40mg 
and reported a potential value of concern during the 40mg timeframe, that new potential value of concern is reported in the 40mg column. If the 
same potential value of concern reported while taking 40mg and 70mg then it is counted in both 40mg and 70mg groups; Overall is not a summation 
of the dose groups. 
 
 
Generated from program.sas on DDMMMYYYY HH:MM:SS. Source dataset(s): ADxx. Date of data extraction: DDMMMYYYY.  
Page X of Y 
 
Programming Notes: 
 
 


 
 
46 of 63 
 
Concomitant Medications 
 
 


 
 
47 of 63 
 
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Table 14.3.8.2 
Concomitant Medications by ATC Class and Preferred Name 
Safety Population 
 
Anatomical Therapeutic Chemical Class (ATC) 
  Preferred Name 
40 mg ATH-1017 
(N=xxx) 
n(%) 
70 mg ATH-1017 
(N=xxx) 
n(%) 
Overall 
(N=xxx) 
n(%) 
 
 
 
 
Participants with at least 1 ATC class concomitant medication 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
ATC Class 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred name 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred name 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Etc. 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
ATC Class 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred name 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred name 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Etc. 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
- ATC: Anatomical Therapeutic Chemical Class; WHO: World Health Organization. N: number of participants in the specified population for given 
treatment group. Percentages are based on N. A participant with multiple occurrences within an ATC class is counted only once. Concomitant 
medications (C) are defined as those medications used following the first administration of study drug. Medications started prior to the 
administration of study drug and continuing into the treatment period are considered as both prior and concomitant medications. WHO Drug 
Dictionary Version xx used for reporting of medications. Safety population includes all participants who received at least one dose of study 
medication, classified by actual treatment received. Participants with a C in 70mg will be counted in the 70mg column. If that same participant 
switched to 40mg and reported a C during the 40mg timeframe, that new C is reported in the 40mg column. If the same C is reported while taking 
40mg and 70mg then it is counted in both 40mg and 70mg groups; Overall is not a summation of the dose groups. 
 
Generated from program.sas on DDMMMYYYY HH:MM:SS. Source dataset(s): ADxx. Date of data extraction: DDMMMYYYY.  
Page X of Y 
 
NOTE:  
• 
Suggested sorting: ATC classes are presented alphabetically; PNs are sorted within ATC class in descending frequency in the Overall 
column. 
 
Programming Notes: 
• 
ATC2 and Preferred Term will be used for display. 
 
 


 
 
48 of 63 
 
 
SECTION 16.X – PARTICIPANT DATA LISTINGS 
 
 
 
 
 
 


 
 
49 of 63 
 
Discontinued participants 
 
 


 
 
50 of 63 
 
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Listing 16.2.1 
Participant Disposition 
Safety Population 
  
 
Treatment 
Participant 
ID  
AChEI 
Usage/Age/ 
Sex/ 
Race 
 
 
 
Site 
First Dose Date 
Last Dose Date (Day) 
Date (Day) of 
Completion or 
Discontinuation 
Completed or Primary Reason 
Discontinued (Verbatim) 
 
 
 
 
 
 
 
 
xxxxxxxx 
xxxxxxxx 
Y/xx/M/xx 
xx 
YYYY-MM-DD 
YYYY-MM-DD (XX) 
YYYY-MM-DD (XX) 
Completed 
 
 
 
 
 
 
 
 
xxxxxxxx 
xxxxxxxx 
N/xx/F/xx 
xx 
YYYY-MM-DD 
YYYY-MM-DD (XX) 
YYYY-MM-DD (XX) 
Adverse event (Nausea) 
 
 
 
 
 
 
 
 
xxxxxxxx 
xxxxxxxx 
N/xx/F/xx 
xx 
YYYY-MM-DD 
YYYY-MM-DD (XX) 
YYYY-MM-DD (XX) 
Death 
 
 
 
 
 
 
 
 
xxxxxxxx 
xxxxxxxx 
N/xx/F/xx 
xx 
YYYY-MM-DD 
YYYY-MM-DD (XX) 
YYYY-MM-DD (XX) 
Other (xxxxxxxxxxxxxxxxxxxx) 
 
 
 
 
 
 
 
 
 
 
- AChEI: Acetylcholinesterase inhibitor; M: Male; F: Female; Y: Yes; N: No;  
- Race Codes: 1: American Indian or Alaska Native; 2: Asian; 3: Black or African American; 4: Native Hawaiian or Other Pacific Islander; 5: White; 
6: Other. 
- Day is relative to the first dose date 
- Safety population includes all participants who received at least one dose of study medication, classified by actual treatment received. 
 
Generated from program.sas on DDMMMYYYY HH:MM:SS. Source dataset(s): ADxx. Date of data extraction: DDMMMYYYY.  
Page X of Y 
 
 
Programming Notes: 
• 
Please add time also if available. 
• 
Treatment sorting order 40 mg ATH-1017, 70 mg ATH-1017 
 
 
 
 
 


 
 
51 of 63 
 
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Listing 16.2.1.1 
Participants Reduced to 40mg Dose 
Safety Population 
  
 
 
 
 
 
 
Participant ID 
AChEI 
Usage/Age/ 
Sex/ 
Race 
Parent Study 
Treatment 
Date of First 
Dose  
 
 
Date of Dose  
Reduction (Day)  Reason for Dose 
                 Reduction 
 
 
 
 
 
 
 
XXXXXXX 
Y/xx/M/xx 
ATH1017 xx 
mg/Placebo 
YYYY-MM-DD  
YYYY-MM-DD (XX)   xxxxxxxxxx 
 
 
 
 
 
 
 
XXXXXXX 
N/xx/F/xx 
ATH1017 xx 
mg/Placebo 
YYYY-MM-DD  
YYYY-MM-DD (XX)   xxxxxxxxxx 
 
 
 
 
 
 
 
XXXXXXX 
N/xx/F/xx 
ATH1017 xx 
mg/Placebo 
YYYY-MM-DD  
YYYY-MM-DD (XX)   xxxxxxxxxx 
 
 
 
 
 
 
 
XXXXXXX 
N/xx/F/xx 
ATH1017 xx 
mg/Placebo 
YYYY-MM-DD  
YYYY-MM-DD (XX)   xxxxxxxxxx 
 
 
 
 
 
 
 
 
- Day is relative to first dose date. 
- M: Male; F: Female; Y: Yes; N: No; AChEI: Acetylcholinesterase inhibitor 
- Source of dose reduction data to be added as footnote 
- Safety population includes all participants who received at least one dose of study medication, classified by actual treatment received. 
 
 
Generated from program.sas on DDMMMYYYY HH:MM:SS. Source dataset(s): ADxx. Date of data extraction: DDMMMYYYY.  
Page X of Y 
 
 
Programming Notes: 
• 
Only include participants with ADSL.DOSE40MG=’Y’ 
• 
Please add time also if available. 
 
 


 
 
52 of 63 
 
Protocol deviations 
 
 


 
 
53 of 63 
 
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Listing 16.2.2 
Major Protocol Deviations 
Safety Population 
  
 
Treatment 
Participant 
ID  
AChEI 
Usage/Age/ 
Sex/ 
Race 
Date of Deviation 
(Day) 
 
 
Deviation 
Category 
Descriptions 
 
 
 
 
 
 
xxxxxxxx 
xxxxxxxx 
Y/45/M/xxxx 
YYYY-MM-DD (XX) 
xxxxxxxxxxx 
XXXXXXXXXXXXXXXXXXXXXXXX 
 
 
 
YYYY-MM-DD (XX) 
xxxxxxxxxxx 
XXXXXXXXXXXXXXXXXXXXXXXX 
 
 
 
YYYY-MM-DD (XX) 
xxxxxxxxxxx 
XXXXXXXXXXXXXXXXXXXXXXXX 
 
 
 
 
 
 
xxxxxxxx 
xxxxxxxx 
N/49/F/xxxx 
YYYY-MM-DD (XX) 
xxxxxxxxxxx 
XXXXXXXXXXXXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
- AChEI: Acetylcholinesterase inhibitor; M: Male; F: Female; Y: Yes; N: No;  
- Race Codes: 1: American Indian or Alaska Native; 2: Asian; 3: Black or African American; 4: Native Hawaiian or Other Pacific Islander; 5: White; 
6: Other. 
- Day is relative to the first dose date. 
- Safety population includes all participants who received at least one dose of study medication, classified by actual treatment received. 
 
Generated from program.sas on DDMMMYYYY HH:MM:SS. Source dataset(s): ADxx. Date of data extraction: DDMMMYYYY.  
Page X of Y 
 
 
Programming Notes: 
• 
Please add time also if available. 
• 
Only Major deviations will be displayed. 
• 
Treatment sorting order 40 mg ATH-1017, 70 mg ATH-1017 
 
 
 


 
 
54 of 63 
 
 
Demographics and Baseline Characteristics 
 
 


 
 
55 of 63 
 
Athira Pharma, Inc. 
Version: DRAFT 
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Confidential 
 
Listing 16.2.4.1 
Participant Demographics and Baseline Characteristics 
Safety Population 
  
 
Treatment 
Participant 
ID 
AChEI 
Usage/Age/ 
Sex/Race 
Ethnicity 
Weight 
(kg) 
Height 
(cm) 
BMI 
(kg/m2) 
Years of 
Education 
 
 
 
 
 
 
 
 
xxxxxxxx xxxxxxxx 
Y/xx/M/xx 
Not Hispanic 
or Latino 
xx 
xx 
xx 
xx 
xxxxxxxx xxxxxxxx 
N/xx/F/xx 
Not Hispanic 
or Latino 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
- BMI: Body Mass Index; AChEI: Acetylcholinesterase inhibitor; M: Male; F: Female; Y: Yes; N: No;  
- Race Codes: 1: American Indian or Alaska Native; 2: Asian; 3: Black or African American; 4: Native Hawaiian or Other Pacific Islander; 5: White; 
6: Other. 
- Baseline is defined as the last measurement prior to first dose for safety endpoints, and either the measurement on Day 1, or else the last  
measurement before Day 1 if there is no Day 1 measurement for efficacy endpoints. 
- Safety population includes all participants who received at least one dose of study medication, classified by actual treatment received. 
 
Generated from program.sas on DDMMMYYYY HH:MM:SS. Source dataset(s): ADxx. Date of data extraction: DDMMMYYYY.  
Page X of Y 
 
 
Programming Notes: 
• 
 
 
 


 
 
56 of 63 
 
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Listing 16.2.6  
Prior and Concomitant Medications 
Safety Population 
  
 
Treatment 
 
Participant 
ID 
P/C 
ATC Level 3/ 
Preferred name/ 
Reported name 
Start Date/Time 
(Day)/ 
End Date/Time (Day) / 
Ongoing 
Indication 
Dose and units 
Frequency 
Route 
 
 
 
 
 
 
 
 
 
xxxxxxxx 
xxxxxxxx 
X 
xxxxxx/ 
xxxxxxxxxxx/ 
xxxxxxxxxxxxxx 
YYYY-MM-DD HH:MM 
(XX)/ 
YYYY-MM-DD HH:MM (XX) 
HYPERTENSION 
xxx mg 
QD 
ORAL 
xxxxxxxx 
xxxxxxxx 
X 
xxxxxx/ 
xxxxxxxxxxx/ 
xxxxxxxxxxxxxx 
YYYY-MM-DD HH:MM 
(XX)/ 
YYYY-MM-DD HH:MM (XX) 
DIABETES 
xxx mg 
QD 
ORAL 
 
 
 
 
 
 
 
 
 
 
 
- P: Prior Medication; C: Concomitant Medication; ATC: Anatomical Therapeutic Chemical. 
- Day is relative to the first dose date. 
- Prior medications (P) are defined as those medications used prior to the administration of study drug.  
- Concomitant medications (C) are defined as those medications used following the first administration of study drug. Medications started prior to 
the administration of study drug and continuing into the treatment period are considered as both prior and concomitant medications. 
- WHO Drug Version xx.x was used for reporting of prior and concomitant medications.  
- Safety population includes all participants who received at least one dose of study medication, classified by actual treatment received. 
- '/' for End Date (Day) means no date was provided. 
 
Generated from program.sas on DDMMMYYYY HH:MM:SS. Source dataset(s): ADxx. Date of data extraction: DDMMMYYYY.  
Page X of Y 
 
Programming Notes: 
• 
 
 
 
 
 
 
 


 
 
57 of 63 
 
LAB/ECG/VS LISTINGS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
58 of 63 
 
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Listing 16.2.8.1 
Chemistry Laboratory Values Where at Least One Value is a Potential Value of Concern 
Safety Population 
 
 
 
 
 
 
Alkaline 
Phosphatase  
(U/L) 
Alanine 
Aminotransferase 
(U/L) 
Aspartate 
Aminotransferase 
(U/L) 
Bilirubin  
(umol/L) 
Treatment 
Participant 
ID 
AChEI 
Usage/ 
Age/Sex/ 
Race 
Study 
Visit 
Collection 
Date/Time (Day) 
Observed 
Value 
Change 
from 
Baseline 
Observed 
Value 
Change 
from 
Baseline 
Observed 
Value 
Change 
from 
Baseline 
Observed 
Value 
Change 
from 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXX 
xxxxxxx 
Y/xx/M/xx 
xxxx 
YYYY-MM-
DDTHH:MM (XX) 
xx.xx* 
xx.xx 
xx.x* 
xx.x 
xx.xxx* 
xx.xxx 
xx.xxx* 
xx.xxx 
 
 
 
xxxx 
YYYY-MM-
DDTHH:MM (XX) 
xx.xx 
xx.xx 
xx.x 
xx.x 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
 
 
N/xx/F/xx 
xxxx 
YYYY-MM-
DDTHH:MM (XX) 
xx.xx 
xx.xx 
xx.x 
xx.x 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
- AChEI: Acetylcholinesterase inhibitor; Y: Yes; N: No; M: Male; F: Female;  
- Race Codes: 1: American Indian or Alaska Native; 2: Asian; 3: Black or African American; 4: Native Hawaiian or Other Pacific Islander; 5: White; 
6: Other. 
- *Indicates Baseline.  
- Baseline is defined as the last measurement prior to first dose. 
- Safety population includes all participants who received at least one dose of study medication, classified by actual treatment received. 
 
Generated from program.sas on DDMMMYYYY HH:MM:SS. Source dataset(s): ADxx. Date of data extraction: DDMMMYYYY.  
Page X of Y 
 
Programming Notes: 
• 
Use code for race. 
• 
Where at least one value for that patient is marked as high or low. Display baseline only if there are High or Low values. 
• 
Run for all Chemistry variables (Albumin (g/L), Alkaline Phosphatase (U/L), Aspartate Aminotransferase (U/L), Bilirubin (umol/L), 
Calcium (mmol/L), Chloride (mmol/L), Cholesterol (mmol/L), Creatine Kinase (U/L), Creatinine (umol/L), Gamma Glutamyl Transferase 
(U/L), Glucose (mmol/L), HDL Cholesterol (mmol/L), Hemoglobin A1C (%), LDL Cholesterol (mmol/L), Potassium (mmol/L), Protein (g/L), 
Protein (g/L), Sodium (mmol/L), Triglycerides (mmol/L).  
 
 
 
 


 
 
59 of 63 
 
 
Listing 16.2.8.2 
Hematology Laboratory Values Where at Least One Value is a Potential Value of Concern 
Safety Population 
 
• 
Repeat Listing 16.2.8.1 where at least one value for that patient is marked as high or low.  
• 
Run for all Hematology variables (Basophils (10^9/L), Basophils/Leukocytes (fraction of 1), Eosinophils (10^9/L), 
Eosinophils/Leukocytes (fraction of 1), Erythrocytes (10^12/L), Hematocrit (fraction of 1), Hemoglobin (g/L), Leukocytes (10^9/L), 
Lymphocytes (10^9/L), Lymphocytes/Leukocytes (fraction of 1), Monocytes (10^9/L), Monocytes/Leukocytes (fraction of 1), Neutrophils 
(10^9/L), Neutrophils/Leukocytes (fraction of 1), Platelets (10^9/L)). 
 
Listing 16.2.8.3 
Vital Signs Values Where at Least One Value is a Potential Value of Concern 
Safety Population 
 
• 
Repeat Listing 16.2.8.1 where at least one value for that patient is marked as high or low. To identify potential value of concerns, 
please use the criteria shown below:  
 
Orthostatic Diastolic BP (mmHg) 
 Standing Diastolic BP Decrease >=10mmHg 
 Standing Diastolic BP Increase >=20mmHg 
 Standing Diastolic BP >100mmHg 
 Standing Diastolic BP >100 and Increase >=20mmHg 
 Standing Diastolic BP <50 and Decrease >=10mmHg 
 Standing Diastolic BP <50mmHg 
Orthostatic Systolic BP (mmHg) 
 Standing Systolic BP Decrease >=20mmHg 
 Standing Systolic BP Increase >=20mmHg 
 Standing Systolic BP >160mmHg 
 Standing Systolic BP >160 and Increase >=20mmHg 
Systolic Blood Pressure (mmHg) 
 Systolic BP Decrease >=20mmHg 
 Systolic BP Increase >=20mmHg 
 Systolic BP >160mmHg 
 Systolic BP >160 and Increase >=20mmHg 
Diastolic Blood Pressure (mmHg) 
 Diastolic BP Decrease >=10mmHg 
 Diastolic BP Increase >=20mmHg 
 Diastolic BP >100 and Increase >=20mmHg 
 Diastolic BP <50 and Decrease >=10mmHg 


 
 
60 of 63 
 
 Diastolic BP >100mmHg 
 Diastolic BP <50mmHg 
Pulse Rate (beats/min) 
 Abnormal Heart Rate (<50 or >100 BPM) 
 Heart Rate Change >= 30 BPM 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
61 of 63 
 
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Listing 16.2.9 
ECG Parameters Where at Least One Value is a Potential Value of Concern 
Safety Population 
 
Treatment 
Participant 
ID 
AChEI Usage/ 
Age/Sex/ 
Race 
Study Visit 
Collection Date/Time (Day) Parameter (unit) 
Abnormality 
 
 
 
 
 
 
 
XXX 
xxxxxxx 
Y/xx/M/xx 
xxxx 
YYYY-MM-DDTHH:MM (XX)* 
xx (xx) 
xxxxxxxxx 
 
 
 
 
 
xx (xx) 
xxxxxxxxx 
 
 
 
 
 
xx (xx) 
 
 
 
 
 
 
xx (xx) 
 
 
 
 
 
 
xx (xx) 
 
 
 
 
 
 
xx (xx) 
 
 
 
 
 
 
xx (xx) 
xxxxxxxxx 
 
 
 
 
 
xx (xx) 
xxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
xxxx 
YYYY-MM-DDTHH:MM (XX) 
xx (xx) 
xxxxxxxxx 
 
 
 
 
 
xx (xx) 
xxxxxxxxx 
 
 
 
 
 
xx (xx) 
xxxxxxxxx 
 
 
 
 
 
xx (xx) 
 
 
 
 
 
 
xx (xx) 
 
 
 
 
 
 
xx (xx) 
xxxxxxxxx 
 
 
 
 
 
xx (xx) 
xxxxxxxxx 
 
 
 
 
 
xx (xx) 
 
 
 
 
 
 
xx (xx) 
xxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
- ECG: Electrocardiogram. 
- *Indicates Baseline.  
- Baseline is defined as the last measurement prior to first dose. 
 
 
Generated from program.sas on DDMMMYYYY HH:MM:SS. Source dataset(s): ADxx. Date of data extraction: DDMMMYYYY.  
Page X of Y 
 
Programming Notes: 
• 
If at least one parameter has an abnormality for that visit, print all non-missing parameters for that visit, filling in the 
abnormality column when applicable. Display baseline only if there are abnormal findings. 
 
 


 
 
62 of 63 
 
STANDARD FIGURE SHELLS