Clinical trial NCT04322149
Conditions: Amyotrophic Lateral Sclerosis
Keywords: ALS Lou Gehrig's Disease motor neuron disease motor neuron degeneration AT-1501 humanized blocking antibody to CD40LG CD40L inhibitor monoclonal antibody
Sponsor: Anelixis Therapeutics, LLC
Start date: 2020-10-16; Completion date: 2022-03-24
Enrollment: 54 participants; Allocation: NA; Intervention model: SEQUENTIAL

Brief summary:
This is a Phase 2a, multi-center, open label, multiple dose study of AT-1501, a humanized monoclonal antibody antagonist to CD40 ligand (CD40L). Approximately 54 adults with Amyotrophic Lateral Sclerosis (ALS) will be enrolled into the study in the United States and Canada at approximately 13 ALS treatment sites.

Participants will be enrolled into one of four ascending doses.

Detailed description:
This is a Phase 2a, multi-center, open label, multiple dose study of AT-1501, a humanized monoclonal antibody antagonist to CD40L. Approximately 54 adults with ALS will be enrolled into the study in the United States and Canada at approximately 13 ALS treatment sites.

Four ascending doses of AT-1501 will be administered as an IV infusion to sequentially enrolling cohorts. Each participant will receive 6 bi-weekly (every other week) infusions of AT-1501 over an 11-week period.

The study is estimated to take 19 weeks for participants.

Arms: arm 1: 4 sequential dose cohorts
Interventions: intervention 1: AT-1501
Intervention descriptions: intervention 1: AT-1501 monoclonal antibody targeting CD40L given as an IV infusion

Protocol documents:
Prot_000.pdf: 
CLINICAL TRIAL PROTOCOL
Compound:
AT-1501
Protocol No:
AT-1501-A201
Protocol Title:
A Phase 2a Open-Label, Multi-Center Study to Evaluate 
the Safety and Tolerability of Multiple Doses of AT-1501 in 
Adults with ALS
Version: 
04
Date: 
08 March 2021
CONFIDENTIALITY STATEMENT
This document is a confidential communication from Anelixis Therapeutics. Acceptance of this 
document constitutes an agreement by the recipient(s) that no published information contained 
herein will be published or disclosed without prior written approval from Anelixis Therapeutics, 
except that this document may be disclosed to appropriate Institutional Review Boards/ 
Independent Ethics Committees (IRBs/IECs) or as may be required by federal, state or local laws 
or regulations under the condition that they are also required to maintain confidentiality.




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INVESTIGATOR’S AGREEMENT 
I have received and read the Clinical Protocol for the Anelixis Therapeutics, Inc. A Phase 2a 
Open-Label, Multi-Center Study to Evaluate the Safety and Tolerability of Multiple Doses of 
AT-1501 in Adults with ALS (Protocol # AT-1501-A201 (Version 04, 08 March 2021)  
I agree to conduct the study as outlined and to maintain the confidentiality of all information 
received or developed in connection with this protocol. 
 
Printed Name of Investigator 
 
Signature of Investigator 
 
Date (DD/MMM/YYYY) 






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2 
TABLE OF CONTENTS 
1 
PROTOCOL SYNOPSIS .................................................................................................... 4 
2 
TABLE OF CONTENTS ..................................................................................................... 6 
2.1 
Abbreviations and Definition of Terms .......................................................................... 9 
3 
INTRODUCTION .............................................................................................................. 10 
3.1 
Humanized Blocking Antibody to CD40LG .................................................................. 10 
3.2 
Other Experiences with Drugs Targeting CD40LG ...................................................... 10 
3.3 
Preclinical Experience with AT-1501 ........................................................................... 11 
3.4 
Dose Selection and Rationale ..................................................................................... 12 
4 
OBJECTIVES OF THE TRIAL ......................................................................................... 14 
4.1 
Primary Objective ....................................................................................................... 14 
4.2 
Exploratory Objectives ................................................................................................ 14 
5 
INVESTIGATIONAL TRIAL DESIGN ............................................................................... 14 
5.1 
Design ........................................................................................................................ 14 
5.2 
Endpoints ................................................................................................................... 15 
5.2.1 
Primary Endpoint .................................................................................................. 15 
5.2.2 
Exploratory Endpoints ........................................................................................... 16 
5.3 
Dose Escalation .......................................................................................................... 16 
5.4 
Data Monitoring Committee ........................................................................................ 17 
5.5 
Concomitant Therapy ................................................................................................. 17 
5.6 
Excluded Medications ................................................................................................. 17 
5.6.1 
Concomitant Use of Radicava® (edaravone) and Rilutek® (riluzole) or 
Tiglutik (riluzole suspension) ................................................................................. 18 
5.7 
Study Duration ............................................................................................................ 18 
6 
STUDY POPULATION ..................................................................................................... 18 
6.1 
Number of Participants ............................................................................................... 18 
6.2 
Participant Screening .................................................................................................. 18 
6.3 
Inclusion Criteria ......................................................................................................... 19 
6.4 
Exclusion Criteria ........................................................................................................ 19 
6.5 
Handling of Withdrawals ............................................................................................. 20 
6.6 
Study Drug Discontinuation ......................................................................................... 20 
7 
STUDY PROCEDURES ................................................................................................... 21 
7.1 
Screening (Week -4 to Week -1) ................................................................................. 21 
7.2 
Dosing Day (Week 1 / Day 1) ..................................................................................... 22 
7.3 
Phone Call Checks (Weeks 2, 4, 6, 8, 10 and 12; Days 8, 22, 36, 50, 64 and 78 
+/- 2 days) .................................................................................................................. 23 
7.4 
Dosing Day (Weeks 3, 5, 7, 9 and 11; Days 15, 29, 43, 57, and 71 +/- 2 days) .......... 23 
7.5 
End of Study (Week 15 +/- 1 week) ............................................................................ 24 
8 
PROCEDURES AND EVALUATIONS ............................................................................. 24 
8.1 
Assessments of Safety ............................................................................................... 24 
8.1.1 
Medical History and Physical Examination ............................................................ 24 
8.1.2 
Electrocardiogram ................................................................................................. 25 
8.1.3 
Columbia Suicide Severity Rating Scale ............................................................... 25 


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8.1.4 
Clinical Laboratory ................................................................................................ 25 
8.2 
Other Assessments .................................................................................................... 26 
 
 
 
 
9 
DESCRIPTION OF INVESTIGATIONAL PRODUCT ....................................................... 27 
9.1 
Sample Vial Label ....................................................................................................... 27 
9.2 
Drug Ordering and Storage ......................................................................................... 28 
9.3 
Dosage and Administration ......................................................................................... 28 
9.4 
Drug Accountability ..................................................................................................... 28 
10 
ADVERSE EVENTS ......................................................................................................... 29 
10.1 
Definition of Adverse Events ....................................................................................... 29 
10.1.1 
Reporting of Adverse Events ................................................................................ 29 
10.1.2 
Assessment of Severity of Adverse Event ............................................................. 30 
10.1.3 
Onset of Adverse Events ...................................................................................... 30 
10.1.4 
Relationship of Adverse Event to Investigational Product ...................................... 30 
10.2 
Serious Adverse Events ............................................................................................. 31 
10.2.1 
Definition of a Serious Adverse Event ................................................................... 31 
10.2.2 
Reporting of Serious Adverse Events .................................................................... 31 
10.3 
Stopping Rules and Dose Limiting Toxicity (DLT) ....................................................... 33 
11 
STATISTICAL EVALUATION .......................................................................................... 34 
11.1 
Justification of Sample Size ........................................................................................ 34 
11.2 
Definition of Study Analysis Sets ................................................................................ 34 
11.2.1 
Safety Analysis Set ............................................................................................... 34 
11.2.2 
Full Analysis Set ................................................................................................... 34 
11.2.3 
Evaluable Analysis Set ......................................................................................... 34 
11.3 
Statistical Analysis ...................................................................................................... 34 
11.3.1 
Study Baseline ...................................................................................................... 34 
11.3.2 
Disposition of Participants ..................................................................................... 34 
11.3.3 
Demography and Baseline Characteristics ............................................................ 35 
11.3.4 
Safety ................................................................................................................... 35 
 
 
11.3.6 
Medical History ..................................................................................................... 35 
11.3.7 
Prior and Concomitant Medications ...................................................................... 35 
11.4 
Handling of Missing Data ............................................................................................ 36 
11.5 
Interim Analysis .......................................................................................................... 36 
 
 
12 
DATA MANAGEMENT .................................................................................................... 36 
12.1 
Participant Data Protection ......................................................................................... 36 
12.2 
Data Handling ............................................................................................................. 36 
13 
ADMINISTRATIVE PROCEDURES ................................................................................. 37 
13.1 
Study Completion or Premature Closure .................................................................... 37 
13.2 
Good Clinical Practice ................................................................................................ 38 
13.3 
Institutional Review Board .......................................................................................... 38 


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13.4 
Participant Informed Consent ..................................................................................... 38 
13.5 
Regulatory Affairs ....................................................................................................... 39 
13.6 
Trial Monitoring ........................................................................................................... 39 
13.7 
Trial Audits and Inspections ........................................................................................ 39 
13.8 
Financing .................................................................................................................... 39 
13.9 
Records Retention ...................................................................................................... 39 
14 
CONFIDENTIALITY AND COMMUNICATION OF RESULTS .......................................... 40 
14.1 
Statistical and Clinical Reports .................................................................................... 40 
14.2 
Regulatory Use of Data .............................................................................................. 40 
15 
REFERENCES ................................................................................................................. 41 
Appendix A 
Schedule of Events ....................................................................................... 44 
 


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2.1 
Abbreviations and Definition of Terms 
Abbreviation 
Definition 
AE 
Adverse Event 
ALS 
Amyotrophic Lateral Sclerosis 
ALSFRS-R 
ALS Functional Rating Scale – Revised 
ALT  
Alanine aminotransferase (alanine transaminase)  
AST 
Aspartate aminotransferase (aspartate transaminase)  
CD40LG 
CD40 Ligand 
CBC 
Complete Blood Count 
CRF 
Case Report Form 
CRO 
Contract Research Organization  
C-SSRS 
Columbia Suicide Severity Rating Scale 
CTCAE 
Common Terminology Criteria for Adverse Events v 4.03 
CV 
Curriculum Vitae 
ECG 
Electrocardiogram 
FAS 
Full Analysis Set 
GMP 
Good Manufacturing Practice 
ICH 
International Conference of Harmonization 
IRB  
Institutional Review Board  
ITT 
Intent-to-Treat 
IU 
International unit 
kg  
kilogram  
MedDRA  
Medical Dictionary for Regulatory Activities  
mL 
milliliter  
MR1 
A hamster antibody targeted against murine CD40LG. 
NHP 
Non-human primate 
PP 
Per-Protocol 
PT 
MedDRA Preferred Term 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
Sec 
Seconds 
SDV 
Source Data Verification 
SOA 
Schedule of Activities 
SOC 
MedDRA System Organ Class 
SOP 
Standard Operating Procedure 
SPC 
Summary of Product Characteristics 
SVC 
Slow Vital Capacity 
TE 
Thromboembolism 
TEAE 
Treatment-Emergent Adverse Event 
WBC 
White Blood Cell Count 
All dimensional units are in standard SI units 








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Nine participants in each of the lower dose 
cohorts (1 and 2 mg/kg) will allow for initial review of safety at multiple doses while eighteen 
participants in the higher cohorts (4 and 8 mg/kg) allows for reduced variability to assess 
safety. 
 
 
 
 








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5.4 
Data Monitoring Committee  
A DMC will be established and will be comprised of 2 physicians (with ALS experience and no 
other involvement in the trial) and a statistician.   
The committee will meet following the administration of 6 doses to a minimum of 33% of 
participants, in each cohort. The meetings for dosing cohorts 1 and 2 will be held after 3 
participants have received 6 doses, for a total of 18 doses.  The meetings for dosing cohorts 3 and 
4 will be held after 6 participants have received 6 doses, for a total of 36 doses. The review will 
include all the available safety and laboratory data, including but not limited to platelet levels 
and coagulation data. 
 data may be reviewed depending on data 
availability. The committee may recommend a revision of the dose escalation scheme based on 
review of the emerging data.  
The DMC is responsible for making a recommendation to continue enrolling at the current 
concentration, escalate to the next planned dose, recommend changes in study conduct, or stop 
further dosing in the study. Specific responsibilities of the DMC are detailed in the DMC Charter 
including meeting schedules, documentation requirements, and data review. The DMC may meet 
on an ad hoc basis should an emergent safety issue be identified (see Section 10.3). 
5.5 
Concomitant Therapy 
Generally, concomitant medications can be added, changed or discontinued as medically 
necessary. Appropriate documentation for all forms of pre-medications, supportive care, and 
concomitant medications will be captured in the source documents.  This includes any 
immunizations or vaccinations received for the duration of the study. 
5.6 
Excluded Medications 
The following medications are exclusionary:  
x Systemic administration of corticosteroids (PO/IV/IM) at a dose equivalent to 
20 mg/day of prednisone for more than 14 consecutive days within 90 days prior to 
screening, 
x Administration of anti-neoplastic and/or immunomodulating agents (e.g. tumor 
necrosis factor [TNF] Į antagonists or anti-B cell antibodies) or radiotherapy within 
1 year prior to screening, 
x Cannabinoids unless prescribed or recommended by a physician, 
x Any use of experimental therapies,  
x Menopausal hormone replacement therapies containing estrogen therapy alone or a 
combination of estrogen and progesterone agent (E+P), 
x Any prior exposure to stem cell and gene therapy (see Section 0 - Exclusion 
Criteria). 


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Concomitant medications that are approved drugs or vitamin therapies which the participant may 
be taking off label are not necessarily exclusionary, recognizing that adults with ALS often take 
supplemental agents for symptom relief.  
5.6.1 
Concomitant Use of Radicava® (edaravone) and Rilutek® (riluzole) or 
Tiglutik (riluzole suspension) 
x Edaravone and riluzole are allowed if the participant has been receiving a stable dose of 
edaravone for at least 3 months and/or riluzole for at least 1 month prior to Screening.   
x Discontinuation of edaravone or riluzole must have occurred at least 3 months for 
edaravone and 1 month for riluzole prior to Screening for study eligibility. 
x The participant and treating physician must anticipate continuing the current treatment 
regimen with edaravone or riluzole for the duration of the trial.   
5.7 
Study Duration 
Study enrollment and follow-up may take up to 18 months from first patient first visit to last 
patient last visit. Each participant will have a study duration of up to 15 weeks from first dosing 
to the end of study visit. There is a screening period of up to 4 weeks.  
6 
STUDY POPULATION 
Participants will be recruited from neurology practices and through a referral network at facilities 
treating patients with ALS.  Each participating clinical site is evaluated with respect to its ability 
to enroll the necessary study participants. Strategies for recruitment and retention are discussed 
during routine monitoring visits. Men and women meeting all the inclusion criteria and none of 
the exclusion criteria will be allowed to participate.   
6.1 
Number of Participants 
The number of participants to be enrolled into the study is approximately 54 adults with ALS.   
6.2 
Participant Screening 
The purpose of Screening Visit 1 is to thoroughly inform, both verbally and in writing, the 
potential participant about the study and allow him/her the opportunity to ask questions. The 
potential participant will then sign and date the informed consent form and screening procedures 
can be performed. Once the consent form is signed the participant is considered enrolled into the 
study and any serious adverse events that occur will be captured from the date of consent until 
the end of study participation. 


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6.3 
Inclusion Criteria 
1. Men and women 18 years or older. 
2. ALS diagnosed as possible, laboratory supported probable, probable, or definite as defined by 
revised El Escorial criteria. 
3. ALSFRS-R Aggregate score of 35 or greater, and an aggregate score of 9 or greater at 
Screening for domains 10 Dyspnea, 11 Orthopnea and 12 Respiratory Insufficiency.   
4. No more than 24 months from diagnosis. 
5. Women of childbearing potential may be enrolled if a pregnancy test is negative, and they 
agree to the use of 2 forms of contraception from screening to the end of the study.  Males 
must agree to use 2 forms of contraception from screening to the end of the study if their 
partners are of childbearing potential.  
Acceptable methods of birth control which must be used together are: 
a. Oral contraceptive and condom (combination oral contraceptives containing the 
second-generation progestin (levonorgestrel) and <30 g of estrogen should be 
utilized), 
b. IUD and condom, 
c. Diaphragm with spermicide and condom. 
d. True abstinence is also an acceptable form of birth control 
6. No active suicidal ideation with a plan, or behaviors which may be indicative of a 
participant’s intent to complete suicide as determined by the completion of the C-SSRS.  
7. Able and willing to give informed consent, follow trial procedures, and make multiple 
clinical site visits. 
6.4 
Exclusion Criteria 
1. Any other central or peripheral nervous system disease that may interfere with the evaluation 
of ALS or its progression. 
2. Presence of a tracheostomy, or use of permanent assistive ventilation (ventilatory support for 
23 hours per day or more). 
3. Previous exposure to AT-1501.  
4. History of malignancy within the previous 5 years, except for localized non-melanoma skin 
cancers. 
5. Women who are pregnant, expecting to get pregnant or who are breast feeding. 
6. Abnormal function of the immune system resulting from: 
x Clinical conditions affecting the immune system (e.g. HIV infection, 
agammaglobulinemia), 
x Systemic administration of corticosteroids (PO/IV/IM) at a dose equivalent to 
20 mg/day of prednisone for more than 14 consecutive days within 90 days prior to 
screening, 


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x Administration of anti-neoplastic and/or immunomodulating agents (e.g. TNF 
Į antagonists or anti-B cell antibodies) or radiotherapy within 1 year prior to 
screening. 
7. Recipient of Stem Cell or Gene Therapy. 
8. Serum AST or ALT value greater than 3 times the ULN. 
9. Serum creatinine value greater than 1.5 times the ULN. 
10. Positive test for Hepatitis B surface antigen, Hepatitis C antibody, or HIV. 
11. History of deep venous thrombosis or pulmonary embolism. 
12. Exposure to any other experimental or investigational agent within 30 days or 5 half-lives; 
whichever is longer.   
13. History of active substance abuse within the past 2 years; 
14. History of stroke, poorly controlled or significant cardiovascular disease, diabetes or any 
other acute or chronic medical condition that would unreasonably increase the risks of the 
study procedures, as determined from an interview with the participant and/or review of 
medical records. 
15. Any other medical condition such as COVID-19, medication, or pre-planned 
medical/surgical procedure that, in the opinion of the Investigator, would compromise the 
safety of patients or the integrity of study results. 
6.5 
Handling of Withdrawals 
Participants are free to withdraw their consent to the trial at any time without providing reason(s) 
for withdrawal and without prejudice to further treatment.  
It is important to collect safety data on any participant who withdraws consent from the study 
before their last scheduled visit (End of Study Visit – Week 15). If early withdrawal occurs the 
clinical site staff is expected to contact the participant for follow-up by both telephone and mail. 
A minimum of three attempts at contact should be documented, the last with a certified letter, if 
necessary. 
If early withdrawal of consent occurs, the participant should be asked to return for their next 
scheduled visit (e.g., next study visit or phone assessment) to complete an end-of-study 
evaluation (Section 7.5). At a minimum the participant should be questioned over the telephone 
about any changes in clinical condition since their last visit, the status of any ongoing adverse 
events. The aim is to record data in the same way as for participants who complete the trial.  
Patients who withdraw or are withdrawn prior to receiving at least 4 doses of AT-1501 will be 
replaced within the same dosing cohort that was not completed (i.e. a patient withdrawn from the 
1 mg/kg dosing cohort may be replaced with another individual who will receive 1 mg/kg).  
6.6 
Study Drug Discontinuation 
Participants may be discontinued from receiving study drug for any of the following reasons: 
x Lack of cooperation with study requirements; 


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x Intercurrent illness, that in the opinion of the Investigator, would unreasonably increase the 
risks of the study procedures, or otherwise compromise the safety of the participant or the 
integrity of study results; 
x Participant refuses further treatment with AT-1501; 
x Actions taken to control the -spread of COVID-19 (e.g. no access to study drug)  
x Active COVID-19 infection 
x Participant Withdraws consent to the trial; 
x Stopping rules are met; 
x At the direction of Anelixis; 
x At the direction of the Investigator. 
The effects of AT-1501 have not been studied in patients that have been diagnosed with COVID-
19.  It is unknown whether taking the investigational drug will increase or decrease the risk of 
getting COVID-19 or the effect it may have on the clinical course of a participant who develops 
COVID-19. Potential participants for the study will be tested for COVID-19 prior to entering the 
study. If a participant tests positive they will not be allowed to participate in the study. If a 
participant is diagnosed with COVID-19 while receiving treatment in this study, the 
administration of the investigational drug will be stopped, and appropriate medical care and 
follow-up will be done. The participant will continue to be monitored for safety.  
All participants that withdraw from treatment with AT-1501 for any reason should continue to be 
followed until the end of study.  
If at any time during the study a participant experiences an adverse event the Investigator 
believes is severe enough to preclude further AT-1501 administration or the stopping rules are 
met the participant will be discontinued from study drug treatment and will receive medical 
treatment as determined by the Investigator.  The participant will be followed until the event 
resolves or until the Investigator determines the AE has reached a stable outcome or is no longer 
clinically significant.  Regardless, each participant will be followed for safety for at least 4 
weeks from the last AT-1501 infusion.  A final visit will be completed according to the end-of-
study evaluation (Section 7.6).   
7 
STUDY PROCEDURES 
The assessments to be performed during the study are outlined below.  The first day the 
participant receives AT-1501 is considered “Day 1”.  Refer to Appendix A Time and Events 
Schedule.   
7.1 
Screening (Week -4 to Week -1) 


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The Screening Visit is performed to inform the patient about the study and check eligibility for 
participation. No treatment or study related procedures will be initiated before written informed 
consent has been obtained. Results from the screening visit and procedures conducted as part of 
routine standard of care are used to determine study eligibility.  
x Record medical history and demographics 
x Record concomitant medications 
x Complete physical exam including weight and height 
x Vital signs after 5 minutes in a supine or seated position (blood pressure, heart rate, 
temperature, respiration rate) 
x ECG 
x Blood samples for serum chemistry, CBC with differential and platelet count, 
coagulation tests, Serum pregnancy test (women of child-bearing potential), Hepatitis 
B surface antigen, Hepatitis C antibody, and HIV  
x COVID-19 testing to be done no later than 1 week prior to the first infusion. 
x Urinalysis 
 
 
x Administration of the ALSFRS-R 
x Slow Vital Capacity (SVC), if available 
x Administration of the Columbia Suicide Severity Rating Scale (C-SSRS) 
7.2 
Dosing Day (Week 1 / Day 1) 
Participants who have signed informed consent and have met all the inclusion criteria and none 
of the exclusion criteria will continue to Day 1.  
Pre-Dose 
x Review concomitant medications 
x Symptom directed physical exam including weight 
x Vital signs after 5 minutes in a supine or seated position (blood pressure, heart rate, 
temperature, respiration rate) 
x Blood and urine samples for serum chemistry, CBC with differential and platelet count, 
coagulation tests, and urinalysis 
x 
 
x Urine test for pregnancy  
x 
 
x Administration of C-SSRS 


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Dose of AT-1501  
1-hour infusion 
x Vital signs after 5 minutes in a supine or seated position taken at 15 minutes into the 
infusion (blood pressure, heart rate, temperature, respiration rate) 
x AE assessment 
Post Dose 
x Assessments performed post-infusion are timed from the end of the 1-hour infusion, not 
the IV-line flush.   
x Vital signs after 5 minutes in a supine or seated position (blood pressure, heart rate, 
temperature, respiration rate) at 1 and 2 hours post-infusion   
x ECG 2 hours post-infusion  
 
  
x AE assessments 
7.3 
Phone Call Checks (Weeks 2, 4, 6, 8, 10 and 12; Days 8, 22, 36, 50, 64 and 
78 + 2 days) 
x AE assessment 
x Record concomitant medications 
7.4 
Dosing Day (Weeks 3, 5, 7, 9 and 11; Days 15, 29, 43, 57, and 71 + 2 days) 
Pre-Dose 
x Symptom directed physical exam (including examination of the injection site and 
weight) 
x Vital signs after 5 minutes in a supine or seated position (blood pressure, heart rate, 
temperature, respiration rate) 
x Record concomitant medications 
x Blood and urine samples for serum chemistry, CBC with differential and platelet count, 
coagulation tests, and urinalysis 
 
 
 
 
 
 
x Administration of C-SSRS 
 
 
 
 
x AE assessment 


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Dose 
x 1-hour infusion 
x Vital signs after 5 minutes in a supine or seated position and then taken again at 15 minutes 
into the infusion (blood pressure, heart rate, temperature, respiration rate) 
x AE assessment 
Post-Dose 
x Assessments performed post-infusion are timed from the end of the 1-hour infusion, not 
the IV-line flush.   
x Vital signs after 5 minutes in a seated position (blood pressure, heart rate, temperature, 
respiration rate) at 1 and 2 hours post-infusion  
 
  
x ECG taken 2 hours post-infusion  
x AE Assessment 
7.5 
End of Study (Week 15 + 1 week) 
x Symptom directed physical exam (including examination of the injection site and 
weight) 
x Vital signs after 5 minutes in a supine or seated position (blood pressure, heart rate, 
temperature, respiration rate) 
x Blood and urine sample for serum chemistry, CBC with differential and platelet count, 
coagulation tests, and urinalysis 
 
 
x ECG  
 
 
x Administration of C-SSRS 
x Record concomitant medications 
x AE assessment 
8 
PROCEDURES AND EVALUATIONS 
8.1 
Assessments of Safety 
8.1.1 
Medical History and Physical Examination 
A medical history is obtained through review of the participant’s medical records and personal 
interview in order to assess eligibility.  Assessment of eligibility should include a full review of 
all concomitant medications and relevant vaccinations or immunizations.   








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AT-1501 for IV Use Only 
Anelixis Therapeutics 
Single Use Vial 
 
Prior to Reconstitution: Store at 2 to 8°C 
See Pharmacy Manual for reconstitution, use and storage instructions 
 
Caution: New Drug Limited by Federal Law to Investigational Use Only 
9.2 
Drug Ordering and Storage 
AT-1501 is manufactured 
 
. The filled glass vials will be stored for distribution at Fisher Clinical Services. 
Initial orders will be addressed to the pharmacy, where the vials for use will be stored.  
Instructions on reconstitution, use and storage conditions will be provided in the Pharmacy 
Manual. 
9.3 
Dosage and Administration 
Participants in this study will be enrolled into one of four dose groups: AT-1501 1.0 mg/kg, AT-
1501 2.0 mg/kg, AT-1501 4.0 mg/kg, or AT-1501 8.0 mg/kg.   
AT-1501 will be given as a 1-hour IV infusion.  An IV pump will be used for consistency of 
delivery. Equipment required for the administration of AT-1501will be described in the 
Pharmacy Manual and supplied by the clinical site.   
A Pharmacy Manual will be provided to the sites giving instructions on reconstitution by dose 
and by timing of reconstitution as it relates to dose time.  
9.4 
Drug Accountability 
The study medication will be kept in a secure area of the pharmacy with limited access. It will be 
supplied to participants in the trial only under the supervision of the Investigator. The 
Investigator is responsible for drug accountability and maintaining accurate records of the 
dispensing of study medication. Drug accountability will be performed by a monitor. Used vials 
will be kept by the clinical site until drug accountability has been completed by the monitor and 
returned to Fisher Clinical Services, or if authorized, disposed of at the clinical site and 
documented.   


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10 
ADVERSE EVENTS 
10.1 
Definition of Adverse Events 
An AE is any untoward medical occurrence in a patient or clinical investigation participant 
administered a pharmaceutical product (which does not necessarily have a causal relationship 
with this treatment) reported during or after having received the investigational 
product/procedure. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of an 
investigational product, whether or not related to the investigational product. 
10.1.1 
Reporting of Adverse Events 
During the study, the Investigator or clinical site personnel will be responsible for querying and 
recording adverse events and serious adverse events. Events may be spontaneously reported by 
the participant, discovered during general questioning by the Investigator, or detected through 
physical examination, laboratory test or other means. Serious adverse events will be collected 
from the time of informed consent; all adverse events will be collected from the first 
administration of investigational product until completion of the final visit and will be evaluated 
by the Investigator/designee for duration, severity, seriousness, and relationship to 
investigational product, as outlined below. In addition, the actions taken for the AE will also be 
documented on the eCRF. Full laboratory data are to be collected in this study, and toxicity 
trends will be analyzed utilizing objective toxicity criteria. 
A baseline recording of any symptoms of illness will be performed before administration of the 
investigational product. Only symptoms that increase in severity or frequency after 
investigational product administration or new symptoms of illness will be recorded as AEs. If the 
event reflects worsening symptoms, then this should be captured in the event term. Untoward 
medical events which occur after signature of the informed consent but before investigational 
product administration will be recorded as medical history. 
For AEs occurring at the site of infusion the phrase “injection-site” or similar should be included 
in the event term (e.g. treatment-site erythema). AEs will be evaluated using the Common 
Terminology Criteria for Adverse Events (CTCAE Version 4.03). All AEs will receive a 
CTCAE categorization from the Investigator. AEs will also be categorized according to 
relatedness to the investigational product (see Section 0). 
The investigators are responsible for monitoring the safety of patients who have entered this 
study and for reporting to the Sponsor if serious adverse events (SAE) occur. The Investigator is 
further responsible for appropriate medical care of patients during the study. The Investigator 
remains responsible to follow, through an appropriate health care option, AEs that are serious or 
that caused the patient to discontinue before completing the study. In case of an AE, the patient 
must be followed until the event resolves or until the Investigator determines the AE has reached 
a stable outcome or is no longer clinically significant. Frequency of follow-up is left to the 
discretion of the Investigator. Participant notes throughout the study will be maintained by the 
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10.1.2 
Assessment of Severity of Adverse Event 
All AEs will be assessed using the CTCAE scale as follows: 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental Activities of Daily Living (ADL). 
Grade 3 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
self-care ADL.  
Grade 4 
Life-threatening consequences; urgent intervention indicated 
Grade 5 
Death related to AE 
10.1.3 
Onset of Adverse Events 
The Investigator will classify the onset of each AE relative to the following stages of 
treatment: 
x During AT-1501 infusion 
x After AT-1501 infusion  
10.1.4 
Relationship of Adverse Event to Investigational Product 
The Investigator’s assessment of the relationship of the AE(s) to the investigational drug will be 
assessed as Not Related, Unlikely, Possible or Probable. For these purposes, the following 
definitions will be used: 
Not Related: 
A clinical event, including laboratory test abnormality, with a temporal 
relationship to drug administration which makes a causal relationship 
improbable, and in which other drugs, chemicals, or underlying disease provide 
plausible explanations. 
Unlikely: 
A clinical event, including laboratory test abnormality, with a temporal 
relationship to drug administration which makes a causal relationship unlikely, 
and in which other drugs, chemicals or underlying disease provide plausible 
explanations. 
Possible: 
A clinical event, including laboratory test abnormality, with a reasonable time 
sequence to administration of the drug, but which could also be explained by 
concurrent disease or other drugs or chemicals. Information on drug withdrawal 
may be lacking or unclear. 
Probable: 
A clinical event, including laboratory test abnormality, with a reasonable time 
sequence to administration of the drug, unlikely to be attributed to concurrent 
disease or other chemicals, and which follows a clinically reasonable response 
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Related: 
An AE that is almost certainly related to the use of the study drug. The AE 
cannot be reasonably explained by an alternative explanation, e.g., concomitant 
drug(s), concomitant disease(s). 
For purposes of assigning relatedness – Not Related and Unlikely will be considered NOT 
RELATED. Possible, Probable and Related will be considered RELATED. 
10.2 
Serious Adverse Events 
10.2.1 
Definition of a Serious Adverse Event 
A SAE is an adverse event occurring at any dose that results in any of the following outcomes: 
Death 
Life-threatening 
Persistent or significant disability/incapacity 
Prompts a hospital admission or prolongs hospitalization 
Congenital anomaly/birth defect 
Important medical events 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious adverse events when, based upon appropriate medical 
judgment, they may jeopardize the participant and may require medical or surgical intervention 
to prevent one of the outcomes listed above. AEs that do not result in any of these outcomes are 
considered non-serious. 
Participants should be closely followed for AEs during the study. Whether or not the adverse 
events are considered related to the investigational product, they must be reported. 
SAEs occurring more than 4 weeks after a patient’s last dose of AT-1501 will NOT be reported 
unless the Investigator feels that the event may have been caused by the investigational product 
or a protocol procedure. 
Pregnancies occurring within the 3-month period after the last treatment, and coming to the 
attention of the Investigator, should be followed to document any congenital anomalies or birth 
defects, should they occur.  For purposes of consistency, pregnancies will be recorded in the 
SAE System; however, the event will then be downgraded if the outcome does not meet the SAE 
criteria.   
10.2.2 
Reporting of Serious Adverse Events 
All SAEs, whether or not thought related to the investigational product, must be reported by the 
Investigator or designee (by telephone, fax or email) 
 within 
24 hours of the Investigator becoming aware of the event. The Investigator or responsible 
clinical site staff will complete and submit the Serious Adverse Event report form and then enter 
all adverse events into the eCRF.  




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10.3 
Stopping Rules and Dose Limiting Toxicity (DLT) 
The DLT observation period to determine the safety of a dose is defined as starting with 
administration of the first dose of AT-1501 to the first participant in a cohort through the 
administration of the second dose of AT-1501 in the 6th participant in that cohort.  This will repeat 
for each dose level.   
Any of the below outlined events occurring during the DLT observation period and considered to 
be at least possibly related to AT-1501 will qualify as a DLT. 
A DLT is further defined as: 
1. 
An event which meets the laboratory criteria for potential Drug Induced Liver 
Injury (DILI) or “Hy’s Law” defined as: 
x An elevated alanine transaminase (ALT) or aspartate transaminase (AST) lab 
value that is greater than or equal to three time (3x) the upper limit of normal 
(ULN) WITH 
x An elevated total bilirubin lab value that is greater than or equal to two times 
(2x) ULN without findings of cholestasis, AND 
x At the same time, an alkaline phosphatase (ALP) lab value that is less than 2x 
ULN 
2. 
Any study drug related Grade 3 or greater toxicity with the exception of a Grade 3 
or greater laboratory abnormality that is considered clinically insignificant and does 
not meet the criteria of an adverse event.  
3. 
Any study drug related serious adverse event, regardless of severity. 
4. 
A second occurrence of a similar Grade 2 or greater study drug related event within 
a cohort. That is, if two or more participants in a cohort experience a similar drug 
related AE greater than or equal to Grade 2 toxicity, a DLT has been met. 
If any DLT criteria are met, further enrollment will be paused and the appropriate DLT data will 
be reviewed by Anelixis to determine an immediate course of action to be taken. If there are two 
or more occurrences of a DLT, the study may be temporarily halted until a more thorough safety 
review is undertaken. 
 
 


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11 
STATISTICAL EVALUATION 
11.1 
Justification of Sample Size 
Approximately 54 adults with ALS will be enrolled into the study.  All participants will receive 
AT-1501.  The sample size for this study is not based on formal statistical computation.  The 
number of participants by dose level has been chosen in order to examine initial safety at lower 
doses and to examine 
 endpoints at higher doses with a sufficient number of 
participants. The sample size may increase in order to allow for replacement of patients who are 
withdrawn or withdraw prior to receiving at least 4 infusions of AT-1501. 
11.2 
Definition of Study Analysis Sets 
11.2.1 
Safety Analysis Set 
All enrolled participants who receive at least one dose of study medication will be included in 
the Safety Analysis Set (SAS). 
11.2.2 
Full Analysis Set 
All enrolled participants who receive at least one dose of study medication and at least one post-
baseline measurement will be included in the Full Analysis Set (FAS).  
11.2.3 
Evaluable Analysis Set 
The Evaluable Analysis Set (EAS) will include all treated participants who have no important 
protocol deviations likely to seriously affect the primary outcome of the study. 
11.3 
Statistical Analysis 
A detailed description of the planned statistical methods will be documented in a statistical 
analysis plan (SAP). All statistical analyses will be performed using SAS® software ver. 9.4 or 
higher.  
All continuous variables will be summarized by treatment and visit (as applicable) using 
descriptive statistics (number of observations [n], mean, median, standard deviation, minimum 
and maximum). All categorical variables will be summarized by treatment, visit and time point 
(as applicable) using frequency counts and percentages. 
11.3.1 
Study Baseline 
Baseline will be defined as the last available observation prior to administration of the dose. 
11.3.2 
Disposition of Participants 
Participant enrollment, inclusion into each study population, discontinuation and withdrawal 
from the study will be summarized. 






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baseline examinations required for inclusion into the trial, but who were not included in the 
study. 
In the process of ensuring data completeness and accuracy, a 100% SDV will be performed. The 
Investigator will complete and maintain source documents for each participant participating in 
the study. Source data is the first place the data is recorded, regardless of where this is. AEs and 
SAEs together with visit dates and information about the disposition for each participant should 
be recorded in the participant medical chart/notes.   
For all participants, Anelixis Therapeutics, Inc. or its designee will validate the completed 
eCRFs. The Investigator will retain a copy of the printed eCRF, or equivalent. If data 
management detects eCRFs with missing or inconsistent data, queries will be sent into the 
system for correction by the Investigator. The Investigator will also receive data queries, which 
might be generated during the computerized data validation process. 
Source data, source documents, CRFs, protocol and amendments, drug accountability forms, 
correspondence, participant identification list, informed consent forms, and other essential 
documents must be retained for at least 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 investigational product. It is the responsibility of the Sponsor to inform the 
Investigator/institution as to when these documents no longer need to be retained consistent with 
regulations under ICH GCP. 
Anelixis Therapeutics, Inc. or its designee will be responsible for data processing and data 
control. Participant data will be entered into the clinical database continuously by the clinical 
site.  All original documents and CRFs will be retained in the archives of Anelixis Therapeutics, 
Inc. as long as the product under investigation remains available for human use. 
13 
ADMINISTRATIVE PROCEDURES 
13.1 
Study Completion or Premature Closure 
The Investigator will complete the study and approve the final CRF’s in satisfactory compliance 
with the protocol within approximately 2 weeks of study completion.   
Anelixis reserves the right to close the investigational site or terminate the study at any time.  
Reasons for the closure of an investigational site or termination of a study by Anelixis may include: 
1. Determination of unexpected, significant, or unacceptable risk to patients.   
2. Failure to enter patients at an acceptable rate.   
3. Insufficient adherence to protocol requirements.   
4. Insufficiently complete and/or evaluable data.   
5. Plans to modify, suspend or discontinue the development of the study drug.   


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Should the study be closed prematurely, all study materials (completed, partially completed, and 
blank CRFs, study drug, etc.) must be returned to Anelixis. 
13.2 Good Clinical Practice 
The study will be conducted in accordance with the current Good Clinical Practice/International 
Conference on Harmonization (GCP/ICH) Guidelines and relevant regulatory requirement(s). 
Compliance with this standard provides public assurance that the rights, safety, and well-being of 
study participants are being protected consistent with the principles that have their origin in the 
Declaration of Helsinki and that the clinical study data are credible. The Investigator will be 
thoroughly familiar with the appropriate use of the investigational product as described in the 
protocol and Investigator's Brochure. Essential clinical documents will be maintained to 
demonstrate the validity of the study and the integrity of the data collected. A Trial Master File 
(TMF) will be established at the beginning of the study, maintained for the duration of the study, 
and retained according to appropriate regulations. 
13.3 
Institutional Review Board 
The trial will be conducted in accordance with the Declaration of Helsinki 1964 including the 
most recent amendment (Edinburgh, Scotland, October 2000). 
The trial protocol, including the participant information and informed consent to be used, must 
be approved by the appropriate IRB. Written approval must be obtained before enrollment of any 
participants into the trial. It is the responsibility of the Investigator to supply Sponsor with the 
Letter of Approval defining the version of each document approved. 
The principal Investigator will ensure that this study is conducted in full conformance with the 
Edinburgh, Scotland, (2000) amendment to the Declaration of Helsinki 1964, 21 CFR part 50, 
and with national laws and regulations for clinical research. 
The Investigator is responsible for informing the IRB and regulatory authorities of any serious 
adverse events and/or major amendments to the protocol. The Investigator should file all 
correspondence and a copy should be sent to PRC. 
13.4 
Participant Informed Consent 
The Investigator is responsible for giving the participant complete verbal and written information 
about the nature, purpose, possible risks and benefits of the trial. Trial participants must also be 
notified that they are free to withdraw from the trial at any time. The participants should have 
reasonable time to read and digest the information before signing. The Investigator is responsible 
for obtaining signed IRB approved informed consent from each participant before performing 
any trial related procedures.  In addition to signing the ICF, the participant or legally acceptable 
representative will be required to authorize access to the participant’s protected health 
information by signing a separate authorization meeting the requirements of the Health Insurance 
Portability and Accountability Act of 1996. 


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A copy of the signed Informed Consent Form will be given to the participant. The signed consent 
form will be kept by the Investigator in the Investigator Study File. 
13.5 
Regulatory Affairs 
This study will be filed under IND 
.  Notifications and reports will be filed according to 
ICH E6: GCP and FDA guidelines. 
13.6 
Trial Monitoring 
Prior to the start of the study, the Monitor will review the protocol, CRFs and other study 
documents and procedures with the Investigator and their staff. The Investigator will be visited 
on a regular basis by the Monitor, who will check trial procedures, including safety assessments, 
drug handling, data recording and SDV. The Monitor will be allowed to review relevant clinical 
records to confirm that required protocol procedures are being followed and check consistency 
between participant record and the CRF. Incorrect or missing entries into the CRFs will be 
addressed as data queries and must be corrected immediately. Trial monitoring will not 
jeopardize participant confidentiality. 
Upon completion of the study the Monitor will make a final assessment of the conduct of the 
study and inventory all clinical supplies to be returned to Anelixis or designee. Unused or used 
vials of investigational product will be stored until the Monitor is able to perform a physical 
inventory and reconciliation with the drug accountability records. At the completion of this 
study, all unused or used vials must be returned to Anelixis, or designee, or if authorized, 
disposed of at the study site and documented. 
Regulatory authorities, the IRB or IEC and/or Anelixis’ quality assurance group, its CRO 
designee, or business partners may request access to all source documents, CRFs, and other 
study documentation for on-site audit or inspection. Direct access to these documents must be 
guaranteed by the Investigator, who must provide support at all times for these activities. 
13.7 
Trial Audits and Inspections 
During or after the trial has been completed, Anelixis Therapeutics, Inc. representatives or their 
designee may wish to carry out an audit. Regulatory bodies may also inspect the study. These 
representatives will have the same access to trial data and participant source data as the Monitor. 
If a regulatory authority contacts the Investigator with a request for an inspection, the 
Investigator must inform the Monitor immediately. 
13.8 
Financing 
A separate financial agreement (Clinical Trial Agreement) will be signed between Anelixis 
Therapeutics, Inc. and the Investigator and/or the institution involved. 
13.9 
Records Retention 
Essential documents should be retained until at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated marketing 


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applications in an ICH region or at least 2 years have elapsed since the formal discontinuation of 
clinical development of the IP, as described in 21 CFR 312.62. 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. 
14 
CONFIDENTIALITY AND COMMUNICATION OF RESULTS 
All information concerning Anelixis Therapeutics, Inc. research and product development is 
considered confidential and will remain the sole property Anelixis Therapeutics, Inc. This includes 
patent applications, manufacturing processes not previously published and Investigator Brochures. 
14.1 
Statistical and Clinical Reports 
Participant listings, including safety data, will be prepared shortly after receiving all participant 
data. In all listings, participants will be identified by their participant number and initials. Anelixis 
Therapeutics, Inc. or its designee will also draft and finalize the Clinical Study Report (CSR). If 
the trial is terminated prematurely for any reason, an abbreviated report will be prepared. 
14.2 
Regulatory Use of Data 
By signing the protocol, the investigators agree that the results of this study may be used for 
submission to national and/or international regulatory agencies. The authorities will be notified of 
the investigator’s name, address, qualifications and extent of involvement. 


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15 
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1;159(7):3104-8. 
Durie FH, Aruffo A, Ledbetter J, et al. Antibody to the ligand of CD40, gp39, blocks the 
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Early GS, Zhao W, Burns CM. Anti-CD40 ligand antibody treatment prevents the development of 
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Gerritse K, Laman JD, Noelle RJ et al. CD40-CD40 ligand interactions in experimental allergic 
encephalomyelitis and multiple sclerosis. Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2499-
504. 
Gobburu J, Tenhoor C, Rogge M, et al. Pharmacokinetics/dynamics of 5c8, a monoclonal antibody 
to CD154 (CD40 ligand) suppression of an immune response in monkeys. J Pharmacol Exp Ther. 
1998 Aug;286(2):925-30. 
Howard LM, Miga AJ, Vanderlugt CL, et al. Mechanisms of immunotherapeutic intervention by 
anti-CD40L(CD154) antibody in an animal model of multiple sclerosis. J Clin Invest. 1999 
Jan;103(2):281-90. 
Kalled SL, Cutler AH, Datta SK, et al. Anti-CD40 ligand antibody treatment of SNF1 mice with 
established nephritis: preservation of kidney function. J Immunol. 1998 Mar 1;160(5):2158-65. 
Kalunian K, Davis J, Merrill J, et al. Treatment of systemic lupus erythematosus by inhibition of 
T cell costimulation with anti-CD154. Arthritis Rheum. 2002 Dec;46(12):3251-8. 
Kanmaz T, Fechner JJ Jr, Torrealba J, et al. Monotherapy with the novel human anti-CD154 
monoclonal antibody ABI793 in rhesus monkey renal transplantation model. Transplantation. 
2004 Mar 27;77(6):914-20. 
Kawai T, Andrews D, Colvin R, et al. Thromboembolic complications after treatment with 
monoclonal antibody against CD40 ligand. Nat Med. 2000 Feb;6(2):114. 


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Kim S, Wakwe W, Higginbotham L, et al. Fc-silent anti-CD154 domain antibody effectively 
prevents nonhuman primate renal allograft rejection. Am J Transplant. 2017 May;17(5):1182-
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Koyama I, Kawai T, Andrews D, et al. Thrombophilia associated with anti-CD154 monoclonal 
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Kuwana M, Nomura S, Fujimura K, et al. Effect of a single injection of humanized anti-CD154 
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Laman JD, 't Hart BA, Brok H, et al. Protection of marmoset monkeys against EAE by treatment 
with a murine antibody blocking CD40 (mu5D12). Eur J Immunol. 2002 Aug;32(8):2218-28. 
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treatment in the SOD1 model of amyotrophic lateral sclerosis. Nat Genet. 2010 May;42(5):392-9. 
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Parker DC, Greiner DL, Phillips NE, et al. Survival of mouse pancreatic islet allografts in 
recipients treated with allogeneic small lymphocytes and antibody to CD40 ligand. Proc Natl Acad 
Sci U S A. 1995 Oct 10;92(21):9560-4. 
Samoilova EB, Horton JL, Zhang H, et al. CD40L blockade prevents autoimmune 
encephalomyelitis and hampers TH1 but not TH2 pathway of T cell differentiation. J Mol Med 
(Berl). 1997 Aug;75(8):603-8. 
Schaub M, Issazadeh S, Stadlbauer TH, et al. Costimulatory signal blockade in murine relapsing 
experimental autoimmune encephalomyelitis. J Neuroimmunol. 1999 May 3;96(2):158-66. 
Schuler W, Bigaud M, Brinkmann V, et al. Efficacy and safety of ABI793, a novel human anti-
human CD154 monoclonal antibody, in cynomolgus monkey renal allotransplantation. 
Transplantation. 2004 Mar 15;77(5):717-26. 
Shock A, Burkly L, Wakefield I, et al. CDP7657, an anti-CD40L antibody lacking an Fc domain, 
inhibits CD40L-dependent immune responses without thrombotic complications: an in vivo study. 
Arthritis Res Ther. 2015 Sep 3;17:234. 
Tan J, Town T, Crawford F, et al. Role of CD40 ligand in amyloidosis in transgenic Alzheimer's 
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Wakefield I, Harari O, Hutto D, et al. An assessment of the thromboembolic potential of CDP7657, 
a monovalent Fab' PEG anti-CD40L antibody, in rhesus macaques. Arthritis Rheum. 2010 
Jan;62:1243. 
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anti-CD40 ligand in murine systemic lupus erythematosus. J Immunol. 2002 Feb 15;168(4):2046-
53.


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Appendix A Schedule of Events 
 
Screening 
Dosing 
Telephone Check 
Dosing 
Follow-up 
Visit 
1 
2 
3, 5, 7, 9, 11, 13 
4, 6, 8, 10, 12 
14 
Study Week 
Weeks -4 to -
1 
Week 1 
Weeks 2, 4, 6, 8, 10 
and 12 
Weeks 3, 5, 7, 9 and 
11 
Week 15 
Study Day 
Day -30 to -1 
Day 1 
Pre-dose 
Day 1 
Dose 
Day 1 
Post-
dose 
Days 8, 22, 36, 50, 
64, 78 
(+/-2 days) 
Days 15, 29, 43, 57, 71 
(+/-2 days) 
Day 101  
(+/-7days) 
 
Informed Consent 
X 
 
 
 
 
 
 
Medical History and Demographics 
X 
 
 
 
 
 
 
Record Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
Review Eligibility Criteria 
X 
X 
 
 
 
 
 
Physical Examination1 
X 
X 
 
 
 
X 
X 
Vital Signs2 
X 
X 
X 
X 
 
X 
X 
Weight3 
X 
 
 
 
 
X 
 
Height 
X 
 
 
 
 
 
 
ECG4 
X 
 
 
X4 
 
X4 
X 
COVID-19 testing14 
X 
 
 
 
 
 
 
Blood/Urine Samples for 
Eligibility/Safety Testing 5, 6, 7 
X5 
X6,7 
 
 
 
X6,7 
X6 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Colombia Suicide 
Severity Rating Scale 
X 
X 
 
 
 
X (pre-dose) 
X 
AT-1501 1-hr Infusion13 
 
 
X 
 
 
X 
 
Report Serious Adverse Events only 
X 
X 
 
 
 
 
 
Assess for All Adverse Events 
 
 
X 
X 
X 
X 
X 
 
 


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1 
Complete physical examination at Screening; symptom-directed physical examination at other times.  
2 
Vital signs (blood pressure, heart rate, temperature, respiration rate) are taken after being seated/supine for 5 minutes at Screening and then pre-dose, 15 
minutes into the infusion and 1 and 2 hours post-infusion. Assessments performed post-infusion are timed from the end of the 1-hour infusion, not the IV-
line flush. Vital signs may be collected within +5 min of the 15 minute timepoint and +15 min of the 1 and 2 hour post-infusion timepoints.  
3 
Weight for dose calculation is taken at Screening and on each dosing day pre-infusion.  A weight change of 10% or greater will warrant a recalculation of 
the AT-1501 dose.  
4 
Post-infusion ECGs should be read on the day they are taken before the participant is released.   
5 
Eligibility testing includes serum chemistry, CBC with differential and platelet count, coagulation tests, serum pregnancy, HIV, HBC, HCV and urinalysis 
6 
Safety testing includes serum chemistry, CBC with differential and platelet count, coagulation tests, urinalysis and urine pregnancy test 
7 
Blood samples for safety testing pre-dose on dosing days only.   
 
 
 
  
  
 
  
13 AT-1501 to be infused over 1 hour using an IV pump.  Assessments performed post-infusion are timed from the end of the 1-hour infusion, not the IV-line 
flush.   
14 A COVID-19 test will be conducted at screening via nasal swab no longer than 1 week prior to their infusion.  If a patient arrives at the treatment center and 
is symptomatic for COVID-19 subsequent testing may be administered to determine continued study eligibility.  
 
 
 
 
 

SAP_001.pdf: 


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A Phase 2a Open-Label, Multi-Center Study to Evaluate the Safety and 
Tolerability of Multiple Doses of AT-1501 in Adults with ALS 
 
Protocol Number: 
AT-1501-A201 
SAP Version:   
1.0 
SAP Date:   
 
30SEP2021 
 


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Table of Contents 
1. 
Introduction............................................................................................................................... 6 
2. 
Study Objectives ...................................................................................................................... 6 
2.1 Study Endpoints ....................................................................................................................... 6 
2.2 Primary Endpoint ...................................................................................................................... 6 
2.3 Exploratory Endpoints .............................................................................................................. 6 
3. 
Study Design and Procedures ................................................................................................. 7 
3.1 General Study Design .............................................................................................................. 7 
3.2 Schedule of Visits and Assessments ....................................................................................... 7 
4. 
Study Treatments ..................................................................................................................... 8 
4.1 Method of Assigning Subjects to Treatment Groups ............................................................... 8 
4.2 Blinding and Unblinding ........................................................................................................... 9 
5. 
Sample Size and Power Considerations .................................................................................. 9 
6. 
Data Preparation ...................................................................................................................... 9 
6.1 Input Data ................................................................................................................................. 9 
6.2 Output Data .............................................................................................................................. 9 
7. 
Analysis Populations .............................................................................................................. 10 
7.1 Safety Analysis Set ................................................................................................................ 10 
7.2 Full Analysis Set ..................................................................................................................... 10 
7.3 Evaluable Analysis Set ........................................................................................................... 10 
8. 
General Statistical Considerations ......................................................................................... 10 
8.1 Missing or Inconclusive Data Handling .................................................................................. 10 
8.2 Derivation of Analysis Screening Visit ................................................................................... 10 
8.3 Definition of Baseline ............................................................................................................. 10 
8.4 Data Analysis Conventions .................................................................................................... 10 
8.5 Adjustment for Multiplicity ...................................................................................................... 11 
9. 
Disposition of Subjects ........................................................................................................... 11 
10. 
Demographics and Baseline Characteristics ......................................................................... 12 
11. 
Medical History and Concomitant Medications ...................................................................... 12 
11.1 Medical History ....................................................................................................................... 12 
11.2 Prior and Concomitant Medications ....................................................................................... 12 
12. 
Treatment Exposure ............................................................................................................... 13 
13. 
Safety Analyses ..................................................................................................................... 13 
13.1 Adverse Events ...................................................................................................................... 13 
13.2 Clinical Laboratory Data ......................................................................................................... 15 
13.3 Vital Signs .............................................................................................................................. 15 
13.4 Electrocardiogram .................................................................................................................. 15 


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13.5 Columbia Suicide Severity Rating Scale ................................................................................ 16 
15. 
Interim Analyses ..................................................................................................................... 18 
16. 
Changes from Protocol-Stated Analyses ............................................................................... 19 
17. 
Revision History ..................................................................................................................... 19 
18. 
Tables ..................................................................................................................................... 19 
19. 
Listings ................................................................................................................................... 20 
20. 
Figures ................................................................................................................................... 21 
 
 
 


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List of Abbreviations 
ADA 
Anti-drug Antibody 
ADaM 
Analysis Data Model 
AE 
Adverse Event 
ALS 
Amyotrophic Lateral Sclerosis 
ALSFRS-R 
ALS Functional Rating Scale - Revised 
ATC 
Anatomical Therapeutic Chemical 
BLQ 
Below the Limit of Quantitation 
BMI 
Body Mass Index 
COVID-19 
Coronavirus Disease 2019 
C-SSRS 
Columbia Suicide Severity Rating Scale 
CV 
Coefficient of Variation 
DMC 
Data Monitoring Committee 
EAS 
Evaluable Analysis Set 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
FAS 
Full Analysis Set 
ICH 
International Conference on Harmonisation 
IL6 
Interleukin 6 
IP 
Investigational Product 
IV 
Intravenous 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCI-CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
PT 
Preferred Term 
QTcF 
QT Interval Corrected with Fridericia’s Formula 
RTF 
Rich Text Format 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SDC 
Statistics & Data Corporation 
SDTM 
Study Data Tabulation Model 
SOC 
System Organ Class 
SVC 
Slow Vital Capacity 
TEAE 
Treatment-Emergent Adverse Event 
WHODrug 
World Health Organization Drug Dictionary 
 


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1. Introduction 
The purpose of this statistical analysis plan (SAP) is to describe the planned analyses and reporting for 
protocol AT-1501-A201, Version 04 dated 08MAR2021. 
This SAP is being written with due consideration of the recommendations outlined in the most recent 
International Conference on Harmonisation (ICH) E9 Guideline entitled Guidance for Industry: Statistical 
Principles for Clinical Trials and the most recent ICH E3 Guideline entitled Guidance for Industry: Structure 
and Content of Clinical Study Reports. 
This SAP describes the data that will be analyzed and the subject characteristics, safety and tolerability, 
efficacy, biomarker, immunogenicity, and pharmacokinetic (PK) assessments that will be evaluated. This 
SAP provides details of the specific statistical methods that will be used. The statistical analysis methods 
presented in this document will supersede the statistical analysis methods described in the clinical protocol. 
If additional analyses are required to supplement the planned analyses described in this SAP, they may be 
completed and will be identified in the clinical study report. 
2. Study Objectives 
The primary objective of the study is to determine the safety and tolerability of intravenous (IV) 
administration of multiple doses of AT-1501 (planned 1.0, 2.0, 4.0, and 8.0 mg/kg). 
2.1 
Study Endpoints 
2.2 
Primary Endpoint 
• 
Safety and tolerability variables include incidence of adverse events (AEs) and changes in 
physical examination, vital signs, electrocardiograms (ECGs), laboratory parameters, and the 
Columbia Suicide Severity Rating Scale (C-SSRS). 


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3. 
Study Design and Procedures 
3.1 
General Study Design 
This is a Phase 2a, multi-center, open label, multiple dose study of AT-1501, a humanized monoclonal 
antibody antagonist to CD40LG. Approximately 54 adults with ALS will be enrolled into the study at up to 
12 ALS treatment sites in the United States and one site in Canada. 
Four ascending doses of AT-1501 (1.0 mg/kg, 2.0 mg/kg, 4.0 mg/kg, and 8.0 mg/kg) will be administered 
as a 1-hour IV infusion to sequentially enrolling cohorts. The 1.0 mg/kg and 2.0 mg/kg cohorts will consist 
of 9 participants each and the 4.0 mg/kg and 8.0 mg/kg cohorts will consist of 18 participants each. The 
participants in each cohort will receive 6 bi-weekly (every other week) infusions of AT-1501 over an 11-
week period. 
This study consists of a 4-week screening period, an 11-week dosing period in which participants are dosed 
once every other week, and a 4-week follow-up period. On Day 1, eligible participants will receive their first 
1-hour IV infusion of AT-1501 and will be observed for at least 2 hours post infusion before being released. 
They will return on Weeks 3, 5, 7, 9, and 11 for subsequent infusions and will remain at the clinical site for 
at least 2 hours for observation and assessments before being released. Participants will be called weekly 
between dosing visits (Weeks 2, 4, 6, 8, 10, and 12) by a member of the research team to record AEs and 
changes in concomitant medications. Participants will be followed for an additional 4 weeks after their last 
dose to monitor for safety, with an end of study clinic visit occurring at Week 15. 
Each participant will be monitored for safety throughout the study. Safety will be assessed by evaluation of 
AEs, changes in safety laboratory parameters, physical examination including vital signs, ECGs, and the 
C-SSRS. 
 
 
 
 
The Data Monitoring Committee (DMC) will meet following the administration of 6 doses to a minimum of 
33% of participants in each cohort to review safety data and to make dose escalation recommendations to 
Anelixis. The meetings for Dosing Cohorts 1 and 2 will be held after 3 participants have received 6 doses, 
for a total of 18 doses. The meetings for Dosing Cohorts 3 and 4 will be held after 6 participants have 
received 6 doses, for a total of 36 doses. The Schedule of Visits and Assessments is provided in the 
Appendix. Full details of each assessment and other design considerations can be found in the study 
protocol. 
3.2 
Schedule of Visits and Assessments 
The schedule of visits and assessments is provided in the Appendix. 




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once the last participant enrolled to the current cohort has received their first dose. The same process will 
be followed to move to the next dose cohort. The planned dose escalation scheme may be amended based 
on review of the emerging data. Additional cohorts may be added, and smaller cohort sizes may be 
implemented based on safety data and AT-1501 serum concentration results. 
4.2 
Blinding and Unblinding 
This study is an open label study, therefore blinding and unblinding procedures do not apply. 
5. 
Sample Size and Power Considerations 
Approximately 54 adults with ALS will be enrolled into the study. All participants will receive AT-1501. The 
sample size for this study is not based on formal statistical computation. The number of participants by 
dose group has been chosen in order to examine initial safety at lower doses 
 
The sample size may increase 
in order to allow for replacement of subjects who are withdrawn or withdraw prior to receiving at least 4 
infusions of AT-1501.  
6. 
Data Preparation 
6.1 
Input Data 
All clinical study data will be recorded on the electronic case report forms (eCRF) using electronic data 
capture (EDC) system, iMedNetTM version 1.194.1. In addition, study data which is not captured directly 
within the EDC system but is obtained from external vendors (chemistry, hematology, coagulation, 
urinalysis, serology, 
) will also be included for 
analysis. These data sources are described in detail in data transfer agreements developed between data 
management and the respective external laboratory. 
Final analysis will be carried out after the following have occurred: 
• 
Database lock has occurred, including receipt of all final versions of external vendor data, with 
written authorization provided by appropriate SDC and Sponsor personnel. Any changes to the 
database after data have been locked can only be made with the approval of the Sponsor in 
consultation with SDC 
• 
Protocol deviations have been identified and status defined (major/minor deviations). 
• 
Analysis populations have been determined. 
6.2 
Output Data 
Data from EDC and data received from external vendors will be transferred to Biostatistics and incorporated 
into standard formats following the Study Data Tabulation Model (SDTM). Data will then be mapped to 
analysis datasets using the Analysis Data Model (ADaM). Both SDTM- and ADaM-formatted data will be 
used to create the subject listings, while all tables and figures will be based on the ADaM-formatted data. 


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SDTM will follow the SDTM version 1.8 model and will be implemented using the SDTM Implementation 
Guide version 3.3 and the SDTM Controlled Terminology version 2020-11-06. ADaM data will follow the 
ADaM version 2.1 model and will be implemented using the ADaM Implementation Guide version 1.2. Both 
SDTM and ADaM will be validated using Pinnacle 21 version 3.1. Any discrepancies in the validation will 
be noted in reviewer’s guides accompanying the final data transfers. 
Define.xml will be created for SDTM and ADaM using the Define-XML version 2.1 model. 
7. 
Analysis Populations 
7.1 
Safety Analysis Set 
All enrolled participants who receive at least one dose of study medication will be included in Safety Analysis 
Set. 
7.2 
Full Analysis Set 
All enrolled participants who receive at least one dose of study medication and at least one post-baseline 
measurement will be included in Full Analysis Set (FAS).  
7.3 
Evaluable Analysis Set 
The Evaluable Analysis Set (EAS) will include all treated participants who have no important protocol 
deviations likely to seriously affect the primary outcome of the study. 
8. 
General Statistical Considerations 
8.1 
Missing or Inconclusive Data Handling 
All analyses will be based on observed data only unless otherwise specified. 
8.2 
Derivation of  Screening Visit 
Subjects may be rescreened when failing initial screening or falling out of the screening window. To 
incorporate the results from the rescreening visit, screening will be derived as the last visit before the dosing 
visit on Day 1, inclusive of unscheduled assessments. This screening result will be reported in summary 
tables, demographic, and study drug dosing listings. 
8.3 
Definition of Baseline 
Baseline will be defined as the last available observation among scheduled or unscheduled visits prior to 
administration of the first dose of study medication. 
8.4 
Data Analysis Conventions 
All data analysis described in this SAP, will be performed by SDC. Statistical programming and analyses 
will be performed using SAS® version 9.4 or higher. Output will be provided in rich text format (RTF) for 
tables and portable document format (PDF) for tables, listings, and figures using landscape orientation. 
Unless otherwise specified, all study data will be listed and sorted by dose group, subject ID, visit/time 
point, and parameter as applicable. Summary tables will be presented by dose group and visit as applicable.  


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Summaries for continuous and ordinal variables will include the number of observations (n), arithmetic 
mean, standard deviation (SD), median, minimum, and maximum. Minima and maxima will be reported with 
the same precision as the raw values; means and medians will be presented to one additional decimal 
place than reported in the raw values. Standard deviations will be presented to two additional decimal 
places than reported in the raw values. Summaries for discrete variables will include counts and 
percentages. All percentages will be rounded to one decimal place (ie, XX.X%). Change from baseline will 
be calculated as follow-up visit minus baseline.  
Any inferential statistics produced for this study will be exploratory in nature. All statistical tests will be two-
sided with a significance level of 0.05 (α = 0.05) unless otherwise specified. Confidence intervals (CI) for 
differences between treatment groups will be two-sided at 95% confidence unless otherwise specified. All 
p-values will be rounded to 4 decimal places; p-values less than 0.0001 will be presented as “<0.0001”; p-
values greater than 0.9999 will be presented as “>0.9999.”. 
8.5 
Adjustment for Multiplicity 
Adjustments for multiplicity will not be made in this early phase study. 
9. 
Disposition of Subjects 
Disposition will be presented in terms of numbers and percentage of subjects by dose group and for all 
subjects. Percentages will be calculated using treated subjects as the denominator unless otherwise 
specified.  
The number of subjects who screened, screen failed, enrolled, and treated will be presented.  
The number and percentages of subjects in each analysis set (Safety, Full, and Evaluable) will be 
presented. 
The number and percentages of subjects who completed the study or discontinued from the study will be 
presented. The reasons for study discontinuation will include AE, death, lost to follow-up, physician 
decision, protocol violation, study terminated by sponsor, withdrawal of consent, and other.  
The number and percentages of subjects with any protocol deviation, major deviation, and minor deviation 
will be presented. Major and Minor deviations will be further classified into the following sub-categories : 
informed consent, inclusion/exclusion or treatment assignment, test article/study drug infusion and 
assignment at site, improper protocol procedures at site (missed, repeated, not per protocol), site’s failure 
to report serious SAE/AE, visit out of window (missed), visit out of window (early, late), subject’s use of 
prohibited concomitant medication, subject’s failure to follow instructions, investigator documented review 
and/or signature missing, inadequate source documents, other, and COVID-19 related. The percentages 
for each sub-category of major or minor deviation category will be based on the total number of subjects 
with major or minor deviations.  


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Subject listings including subject disposition, inclusion/exclusion criteria, and protocol deviations, will be 
provided.  
10. 
Demographics and Baseline Characteristics 
The demographic variables including age, sex, ethnicity, race, and female subjects’ childbearing potential 
will be summarized using Safety Analysis Set.  
Age (years) will be summarized by dose group and for all subjects using continuous descriptive statistics. 
In addition, age will be categorized into two age groups, <65 and >=65, and summarized using counts and 
percentages.  
Sex, race, and ethnicity will be summarized by dose group and all subjects using discrete descriptive 
statistics. Subjects who record more than one race will be grouped into a single category denoted as 
Multiple. Female childbearing potential will be summarized by counts and percentages based on the 
number of females in each dose group. 
Other baseline characteristics, including weight and body mass index (BMI) at the Screening visit; ALSFRS-
R total score at the Screening Visit and at baseline; dyspnea, orthopnea, and respiratory insufficiency 
ALSFRS-R sub-scores at the Screening visit and at baseline; time since ALS symptom onset (days); and 
time since ALS diagnosis (days), will be summarized by dose group and for all subjects using continuous 
descriptive statistics.  
A subject listing for demographic variables along with weight and BMI at the Screening visit will be provided. 
Additionally, separate subject listings for ALS diagnosis at Screening and pregnancy test results for female 
subjects with childbearing potential will be provided.  
11. 
Medical History and Concomitant Medications 
11.1 Medical History  
Medical history will be coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 23.1. 
Medical history will be summarized using discrete summary statistics by dose group by system organ class 
(SOC) and preferred term (PT) using the Safety Analysis Set. Percentages will be based on the number of 
subjects in each dose group.  If a subject reports the same PT multiple times within the same SOC, that PT 
will only be reported once within that SOC. As with the PT, if a subject reports multiple conditions within the 
same SOC, that SOC will only be reported once. In the summaries, SOCs and PTs within an SOC are listed 
in alphabetical order. On study procedures or surgeries will be coded using MedDRA 23.1 and reported 
with medical history.  
A subject listing for medical history including procedure or surgeries will be provided. 
11.2 Prior and Concomitant Medications 
Prior and concomitant medications will be coded using World Health Organization Drug Dictionary 
(WHODrug) Global (B3, March 2020) and summarized to the therapeutic drug class (Anatomical 


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Therapeutic Chemical [ATC] 4 classification) and preferred name. If the ATC 4 classification is not provided, 
the next highest classification that is provided in the coding dictionary will be used. The preferred name will 
be defined as the active ingredient; if the active ingredient is not provided or includes more than two 
ingredients (e.g., multivitamins), then the drug name will be summarized as the preferred name.  
Prior medications are those medications taken before the date of the first dose of study drug. Concomitant 
medications are defined as those medications listed as having been taken (1) prior to initiation of study drug 
administration and continuing for any period of time following the first administration of study drug or (2) 
starting at any time following the first administration of study drug. For any medications with missing 
information such as unknown start and end dates and unclear status (if taken prior to the study, or if 
ongoing), the medications will be reported as concomitant medications. Concomitant medications will be 
summarized using the Safety Analysis Set. Medications will be tabulated for each dose group using discrete 
summary statistics. Subjects may have more than one medication per ATC class. At each level of subject 
summarization, a subject will be counted once if he/she reports one or more medications. Percentages will 
be based on the number of subjects in each dose group. In the summaries, ATC classes and preferred 
names within an ATC class are listed in alphabetical order. 
A subject listing of prior and concomitant medication will be provided. 
12. Treatment Exposure 
Calculated dose (mg/kg) will be derived as described below and summarized along with total dose received 
(mg) by dose group and visit using continuous descriptive statistics and Safety Analysis Set. Counts and 
percentages for the number of doses administered will be summarized by dose group.  
Calculated Dose (mg/kg) = Total Dose Received (mg) / Weight (kg),  
where weight is the weight at Screening. If there is a weight change of 10% or greater from the weight at 
Screening to a dosing visit, the weight at the dosing visit will be used. 
A subject listing of the study drug dosing will be provided along with the subject weight at each dosing visit 
and calculated dose (mg/kg). A subject listing of the phone calls made following the dosing week will be 
provided as well. 
13. 
Safety Analyses 
All safety analyses will be conducted using the Safety Analysis set. Safety will be summarized by dose 
group.  
13.1 Adverse Events 
An AE is any untoward medical occurrence in a subject or clinical investigation subject administered a 
pharmaceutical product (which does not necessarily have a causal relationship with this treatment) 
reported during or after having received the investigational drug/procedure. An AE can therefore be any 
unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease 


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temporally associated with the use of an investigational product (IP), whether or not related to the IP. 
Treatment-emergent adverse events (TEAEs) are defined as any event that occurs or worsens on or after 
the first dose of study medication. All TEAEs will be collected from the first administration of IP until 
completion of the final visit. 
A serious adverse event (SAE) is an AE that results in any of the following outcomes: death, life-
threatening, persistent, or significant disability/incapacity, prompts a hospital admission or prolongs 
hospitalization, congenital anomaly/birth defect, or other important medical events. All SAEs will be 
collected from the time of informed consent until completion of the final visit. 
All AEs will be evaluated by the Investigator/designee for duration, severity, seriousness, and relationship 
to investigational product. In addition, the actions taken for the AE will also be documented on the eCRF. 
Only symptoms that increase in severity or frequency after IP administration or new symptoms of illness 
will be recorded as AEs in the eCRF. If the event reflects worsening symptoms, then this should be 
captured in the event term. Untoward medical events which occur after signature of the informed consent 
but before IP administration will be recorded as medical history. 
Serious adverse events recorded in the eCRF which began prior to the first dose of study medication will 
not be included in the summary tables but will be included in the AE data listings. AEs will be coded using 
MedDRA Version 23.1. Severity of AEs will be assessed as Grade 1 (lowest severity) to 5 (highest 
severity) using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-
CTCAE) Version 4.03. Relationship to study drug will be categorized as Not Related, Unlikely, Possible, 
Probable, and Related. Related AEs will be classified as those categorized as Probable, Possible, 
Related; or those missing an assessment of relationship to study drug. 
An overall summary will be presented that includes the number of TEAEs and the number and percentage 
of subjects who experienced at least one TEAE by dose group and for all subjects. This summary will also 
include SAEs, drug-related TEAEs, drug-related SAEs, Grade 2 or higher TEAEs, drug-related Grade 2 or 
higher TEAEs, TEAEs by maximum CTCAE grade, TEAEs leading to study drug withdrawal, and TEAEs 
leading to death.  
Separate summaries will be provided for TEAEs using discrete summary statistics and presented by dose 
group and for all subjects by SOC and PT. If a subject reports the same PT multiple times within the same 
SOC, that PT will only be reported once within that SOC. If a subject reports multiple conditions within the 
same SOC, that SOC will only be reported once. In the summary, SOCs and PTs within each SOC will be 
listed in order of decreasing frequency for all subjects. The summaries include: 
• 
All TEAEs  
• 
Drug-related TEAEs 
• 
SAEs 


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A summary of TEAEs will be provided by dose group and for all subjects by PT only. In the summary, PTs 
will be listed in order of decreasing frequency for all subjects. In addition, summaries of TEAEs by maximum 
CTCAE grade will presented using discrete summary statistics by SOC, PT, maximum grade for each dose 
group and all subjects.AS To count the number of subjects with any TEAEs, if a subject has multiple TEAEs 
coded to the same SOC, or multiple TEAEs coded to the same PT within the same SOC, the subject will 
be counted once under the maximum grade. 
Individual subject listing will be provided for all AEs, SAEs and AEs leading to study drug withdrawal. 
13.2 Clinical Laboratory Data 
Clinical laboratory data including chemistry, hematology, coagulation, serology, and urinalysis are collected 
at Screening, pre-dose on each dosing day, and at the end of study. Continuous parameters of chemistry, 
hematology, coagulation, and urinalysis will be summarized using continuous descriptive statistics at each 
scheduled visit (including a summary of baseline values) by dose group. Change from baseline to each 
post-baseline visit will be summarized. Serology lab data will only be presented in a listing. Box plots of 
laboratory data will be presented by dose group and visit.  
Subject listings of all clinical laboratory results will be provided. In addition, separate subject listings of 
clinical laboratory abnormal results will be provided. Laboratory tests needing to be repeated for eligibility 
or safety that can not be sent to the central lab may be collected at the local laboratory and will be presented 
in a separate listing. 
13.3 Vital Signs 
Vital signs will be obtained at Screening; on the dosing day at pre-dose, 15 minutes into the infusion, and 
1- and 2- hours post-infusion; and at the end of study visit. Vital signs, including systolic blood pressure 
(mmHg), diastolic blood pressure (mmHg), heart rate (bpm), respiratory rate (breaths/min), and temperature 
(C) will be summarized with continuous descriptive statistics at each scheduled visit (including a summary 
of baseline values) and time point by dose group. Change from baseline to each post-baseline visit and 
change from pre-dose within each visit will be summarized.  
A subject listing of the vital sign results will be provided. 
13.4 Electrocardiogram  
Electrocardiograms will be obtained at Screening, post-infusion on dosing days, and at the end of study 
visit. Electrocardiogram parameters, including PR interval, QRS interval, RR interval, QT interval, and QTcF 
(QT Interval Corrected by Fridericia’s Formula), will be summarized using continuous descriptive statistics 
by dose group at each scheduled visit. Change from baseline to each post-baseline visit will also be 
summarized. 
A subject listing of the ECG results will be provided. 


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13.5 Columbia Suicide Severity Rating Scale  
The C-SSRS will be administered at Screening, pre-dose on each dosing day, and at the end of study. The 
C-SSRS includes Yes/No questions and prompts for suicidal ideation and suicidal behavior.  
A subject listing of the C-SSRS results will be provided. 


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15. 
Interim Analyses 
No interim analysis is planned for this study. 










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1 Complete physical examination at Screening; symptom-directed physical examination at other times. 
2 Vital signs (blood pressure, heart rate, temperature, respiration rate) are taken after being seated/supine for 5 minutes at Screening and then pre-dose, 15 
minutes into the infusion and 1 and 2 hours post-infusion. Assessments performed post-infusion are timed from the end of the 1-hour infusion, not the IV-line 
flush. Vital signs may be collected within +5 min of the 15-minute timepoint and +15 min of the 1- and 2-hour post-infusion timepoints. 
3 Weight for dose calculation is taken at Screening and on each dosing day pre-infusion. A weight change of 10% or greater will warrant a recalculation of the 
AT-1501 dose. 
4 Post-infusion ECGs should be read on the day they are taken before the participant is released. 
5 Eligibility testing includes serum chemistry, CBC with differential and platelet count, coagulation tests, serum pregnancy, HIV, HBC, HCV, and urinalysis 
6 Safety testing includes serum chemistry, CBC with differential and platelet count, coagulation tests, urinalysis, and urine pregnancy test 
7 Blood samples for safety testing pre-dose on dosing days only. 
13 AT-1501 to be infused over 1 hour using an IV pump. Assessments performed post-infusion are timed from the end of the 1-hour infusion, not the IV-line flush. 
14 A COVID-19 test will be conducted at Screening via nasal swab no longer than 1 week prior to their infusion. If a subject arrives at the treatment center and is 
symptomatic for COVID-19 subsequent testing may be administered to determine continued study eligibility.