Conditions: Healthy
Keywords: ALT-803 PK
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 20
Healthy volunteers: yes

Brief summary:
This is a single center, open-label, pharmacokinetic study of ALT-803 administered as a subQ injection to healthy volunteers.

Detailed description:

Arms:
arm 1: 1.0 mg/ml ALT-803 arm 2: 2.0 mg/ml ALT-803

Interventions: intervention 1: ALT-803
Intervention descriptions: intervention 1: Subjects randomized to Group A will receive ALT-803 at a concentration of 1.0 mg/mL and subjects randomized to Group B will receive ALT-803 at a concentration of 2.0 mg/mL. Subjects will receive a single 10 µg/kg subQ dose of ALT-803 on Day 1 of study period 1. After a rest period, subjects will receive a single 20 µg/kg subQ dose of ALT-803 on Day 1 of study period 2.

Protocol document:
Prot_000.pdf: 
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BIOLOGIC:              
ALT-803 
STUDY NUMBER(S): 
CA-ALT-803-03-17 
PROTOCOL(S) TITLE:
QUILT-1.004: A single center, open-label, 
pharmacokinetic study of subcutaneous ALT-803 
IND NUMBER: 
118280 
SPONSOR: 
Altor BioScience 
ORIGINAL PROTOCOL DATE: 
09 November 2017 
VERSION NUMBER: 
1.0 
VERSION DATE: 
09 November 2017 






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STUDY SYNOPSIS 
Title:  
A single center, open-label, pharmacokinetic study of subcutaneous ALT-803  
  
 
 
 
 
 
 
 
 
 
 
  
 
Study 
Population: 
 
The study population consists of healthy male and female volunteers, aged 18 
- 65 years.  
 
Number of 
Subjects: 
 
16 
 
Objectives:  
Primary: To determine the PK profile after single dose subQ injection(s) of 10 
μg/kg and 20 μg/kg ALT-803 at concentrations of 1.0 mg/mL or 2.0 mg/mL.  
 
Secondary: To assess safety after single dose subQ injection(s) of 10 μg/kg 
and 20 μg/kg ALT-803 at concentrations of 1.0 mg/mL or 2.0 mg/mL.  
 
Study Design: This is a single center, open-label, pharmacokinetic study of ALT-803 
administered as a subQ injection to healthy volunteers.  
 
Subjects meeting the entry criteria will be randomized in a 1:1 ratio (n = 8; 
Groups A and B) to one of two ALT-803 drug concentrations. Subjects 
randomized to Group A will receive 1.0 mg/mL ALT-803 and subjects in 
Group B will receive 2.0 mg/mL ALT-803. Groups A and B will receive a 
single 10 µg/kg subQ dose of ALT-803. After a Rest Period, groups A and B 
will receive a single 20 µg/kg subQ dose of ALT-803. 
  
Blood samples to determine serum levels of ALT-803 will be collected prior 
to dosing, and at 1, 4, 24, 48, 72, 96, 120, 144, 168 and 192 hours after dosing. 
Vital signs (heart rate, blood pressure, respiration, temperature) will be 
monitored.  
 


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Safety will be assessed for all subjects and will include monitoring of vital 
signs, and incidence and severity of adverse events. Blood samples will be 
collected for hematology and chemistry, immune cell levels and activity, 
immune cell phenotype subsets, cytokine levels, and immunogenicity testing, 
which include assays for anti-ALT-803 antibodies.  
 
Subjects will be followed for 6 days after study period 2, and will have an End 
of Study visit on Day 15 which will include safety labs. 
 
Primary 
Endpoint:  
Serum concentration will be used to calculate the following PK 
parameters:  
• 
half-life (t½) 
• 
apparent (extravascular) volume of distribution (Vz/F) 
• 
apparent (extravascular) clearance (CL/F) 
• 
maximum observed concentration (Cmax) 
• 
time of the observed maximum concentration (Tmax) 
• 
area under the plasma concentration curve from time 0 through the 
last measurable concentration (AUC0-t) 
• 
area under the plasma concentration curve from time 0 extrapolated 
to infinite time (AUC0-inf) 
 
 
Secondary 
Endpoint: 
 
1. Safety, as assessed by the incidence and severity of adverse events.  
 
Measures of 
Interest: 
1. Blood samples will be collected for immune cell levels and activity, 
immune 
cell 
phenotype 
subsets, 
cytokine 
levels 
and 
immunogenicity testing, which include assays for anti-ALT-803 
antibodies.  
2. General health as assessed by the RAND General Health 
Questionnaire (SF-36). 
 


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STUDY SCHEMATIC  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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TABLE OF CONTENTS 
CLINICAL PROTOCOL APPROVAL FORM .............................................................2 
SYNOPSIS ..........................................................................................................................4 
TABLE OF CONTENTS ..................................................................................................7 
LIST OF ABBREVIATIONS .........................................................................................11 
1 
INTRODUCTION AND RATIONALE .................................................................12 
1.1 
Background ..........................................................................................................12 
1.2 
Preclinical Pharmacology ....................................................................................12 
1.3 
Non-Clinical Pharmacokinetics ..........................................................................12 
1.4 
ALT-803 Human Experience ..............................................................................13 
1.4.1 
ALT-803 Clinical Adverse Event Profile .....................................................13 
1.5 
Rationale for Study ..............................................................................................13 
1.6 
Dosing Regimen ....................................................................................................13 
2 
STUDY OBJECTIVEs .............................................................................................14 
2.1 
Primary .................................................................................................................14 
2.2 
Secondary..............................................................................................................14 
3 
STUDY ENDPOINTS ..............................................................................................15 
3.1 
Primary .................................................................................................................15 
3.2 
Secondary..............................................................................................................15 
3.3 
Measures of Interest ............................................................................................15 
4 
STUDY PLAN ...........................................................................................................16 
4.1 
Study Design .........................................................................................................16 
4.1.1 
Screening and baseline (Day -14 through Time 0) ......................................16 
4.1.2 
Study Period 1 (Day 1 – Day 9) .....................................................................16 
4.1.3 
Rest Period ......................................................................................................17 
4.1.4 
Study Period 2 (Day 1 – Day 9) .....................................................................17 
4.1.5 
Follow-up Period (Day 10 – Day 15) ............................................................17 
4.2 
Study Schematic ...................................................................................................18 
4.3 
Schedule of Assessments ......................................................................................19 
5 
POPULATION ..........................................................................................................20 
5.1 
Number of Subjects..............................................................................................20 
5.2 
Inclusion Criteria .................................................................................................20 
5.3 
Exclusion Criteria ................................................................................................21 
6 
STUDY CONDUCT..................................................................................................23 
6.1 
Subject Screening and Enrollment ID ...............................................................23 
6.2 
General Instructions ............................................................................................23 
6.3 
Study Procedures by Time Point ........................................................................23 
6.3.1 
Screening and Baseline ..................................................................................23 
6.3.2 
Study Period 1 ................................................................................................24 
6.3.3 
Study Period 2 ................................................................................................25 
6.3.4 
End of Study Visit ..........................................................................................26 
6.4 
Premature Discontinuation and Subject Replacement ....................................26 


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7 
DESCRIPTION OF STUDY PROCEDURES .......................................................27 
7.1 
Clinical Assessments and Procedures ................................................................27 
7.1.1 
Medical History ..............................................................................................27 
7.1.2 
Physical Examination ....................................................................................27 
7.1.3 
Vital Signs, Body Weight & Height ..............................................................27 
7.1.4 
General Health Questionnaire ......................................................................27 
7.1.5 
Injection Site Reaction Subject Diary and Digital Photographic 
Documentation ...............................................................................................27 
7.2 
Test Collection and Processing ...........................................................................28 
7.3 
Immune Cells (PBMCs) .......................................................................................29 
7.4 
PK, Cytokines and Immunogenicity ..................................................................32 
7.4.1 
PK ....................................................................................................................32 
7.4.2 
Cytokines ........................................................................................................33 
7.4.3 
Immunogenicity..............................................................................................33 
7.5 
Specimen Preparation for Local Pick-Up ..........................................................35 
7.6 
Adverse event assessment ....................................................................................36 
7.6.1 
ALT-803 Injection Site Reaction ..................................................................36 
7.7 
Concomitant Medications ...................................................................................37 
7.8 
Protocol Deviations ..............................................................................................37 
8 
STUDY DRUG MANAGEMENT ...........................................................................38 
8.1 
ALT-803 ................................................................................................................38 
8.1.1 
Formulation ....................................................................................................38 
8.1.2 
Storage ............................................................................................................38 
8.1.3 
Packaging and Delivery .................................................................................38 
8.1.4 
Disposal/Destruction ......................................................................................38 
8.2 
Dose and Administration .....................................................................................38 
8.3 
IP Delivery, Receipt and Approval.....................................................................39 
8.3.1 
Altor Delivery Procedures .............................................................................39 
8.3.2 
Site IP Receipt Procedures ............................................................................39 
8.3.3 
Site Shipper Return Procedures ...................................................................40 
8.3.4 
Altor IP Vial Approval ..................................................................................40 
8.3.5 
IP Dispensing, Accountability and Resupply ..............................................40 
8.3.6 
IP Study Treatment Preparation ..................................................................40 
8.3.7 
Temperature Excursions ...............................................................................40 
8.4 
Prohibited Concomitant Therapy ......................................................................41 
8.5 
Compliance ...........................................................................................................41 
8.6 
Post-dose Guidelines for ALT-803; Skin Rash in Association with subQ 
ALT-803 ................................................................................................................41 
9 
ADVERSE EVENTS ................................................................................................42 
9.1 
Monitoring, Recording and Reporting of Adverse Events...............................42 
9.2 
Evaluation of Adverse Events .............................................................................43 
9.2.1 
Seriousness ......................................................................................................43 
9.2.2 
Severity/Intensity ...........................................................................................44 
9.2.3 
Relationship to the Study Drug ....................................................................44 
9.2.4 
Duration ..........................................................................................................45 
9.2.5 
Action Taken ..................................................................................................45 


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9.2.6 
Outcome ..........................................................................................................45 
9.3 
Abnormal Laboratory Values .............................................................................45 
9.4 
SAE Report Form Completion Guidelines ........................................................45 
9.5 
Pregnancy .............................................................................................................48 
9.5.1 
Females of Child-Bearing Potential .............................................................48 
9.6 
Reporting of Adverse Events ..............................................................................49 
9.7 
Expedited Reporting of Adverse Events ............................................................50 
10 STATISTICS .............................................................................................................50 
10.1 
General Procedures .............................................................................................50 
10.2 
Sample Size ...........................................................................................................50 
10.3 
Populations for Analysis ......................................................................................51 
10.4 
Statistical Methods ...............................................................................................51 
10.4.1 
Demographic and Baseline Characteristics .................................................51 
10.4.2 
Study Drug Exposure ....................................................................................51 
10.4.3 
Analysis of Safety ...........................................................................................51 
10.5 
Interim Analysis ...................................................................................................51 
11 ETHICS AND RESPONSIBILITIES .....................................................................52 
11.1 
Good Clinical Practice .........................................................................................52 
11.2 
Investigator Responsibilities ...............................................................................52 
11.3 
Subject Information and Informed Consent .....................................................52 
11.4 
Confidentiality ......................................................................................................53 
11.5 
Protocol Amendment ...........................................................................................53 
11.6 
Institutional Review Board/Independent Ethics Committee Review and 
Approval ...............................................................................................................53 
11.7 
Closure of Study ...................................................................................................54 
12 Data handlinG and record keeping .........................................................................55 
12.1 
Data/Documents ...................................................................................................55 
12.2 
Data Capture and Management .........................................................................55 
12.3 
Inspection of Records ..........................................................................................55 
12.4 
Retention of Records............................................................................................55 
13 Quality control and quality assurance ....................................................................57 
13.1 
Study Monitoring .................................................................................................57 
13.2 
Deviations..............................................................................................................57 
13.3 
Audits and Inspections ........................................................................................61 
14 STUDY REPORT AND PUBLICATIONS ............................................................62 
15 CONFIDENTIALITY ..............................................................................................63 
16 REFERENCES .........................................................................................................64 
APPENDICES ..................................................................................................................65 
16.1 
APPENDIX I – ALT-803 Injection Site Reaction Subject Diary ....................65 
16.2 
APPENDIX II – General Health Questionnaire (RAND SF 36) .....................66 
16.3 
APPENDIX III –  SAE REPORT FORM AND COVER SHEET ..................72 
16.4 
APPENDIX IV – Immune Cells Storage Log ....................................................75 
16.5 
APPENDIX V – PK, Cytokine and Immunogenicity Storage Log ..................77 
16.6 
APPENDIX VI – Pregnancy Questionnaire ......................................................79 
16.7 
APPENDIX VII – Protocol Deviation Notification ...........................................81 
16.8 
APPENDIX VIII – Screening and Enrollment Log ..........................................82 


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16.9 
APPENDIX IX – Notification of Enrollment and Dosing ................................83 
16.10 APPENDIX X – Study Medication Inventory/Tracking Form (SMIT) .........84 
16.11 APPENDIX XI – Study Medication Shipping Notice/ Receipt Form (SMSNR)85 
16.12 APPENDIX XII – Study Medication Shipping Requisition Form (SMSR) ...86 
16.13 APPENDIX XIII – Study Treatment Preparation Worksheet ........................87 
16.14 APPENDIX XIV – Temperature Excursion Form ...........................................89 
16.15 APPENDIX XV – Names of Study Personnel ...................................................90 
16.16 APPENDIX XVI – Declaration of Helsinki .......................................................91 
WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI ................91 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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LIST OF ABBREVIATIONS 
AE 
Adverse Event 
AUC0-inf 
Area under the plasma concentration curve from time 0 extrapolated to 
infinite time  
AUC0-t 
Area under the plasma concentration curve from time 0 through the last 
measurable concentration  
Cmax 
Maximum observed concentration  
CL 
Clearance 
CL/F 
Apparent (extravascular) clearance  
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GHQ 
General Health Questionnaire 
HIPAA 
Health Insurance Portability and Accountability Act 
IEC 
Independent Ethics Committee 
IL 
Interleukin 
IRB 
Institutional Review Board 
IV 
Intravenous 
MedDRA 
Medical Dictionary for Regulatory Activities 
Omics 
Genomic, Transcriptomic and Proteomic analysis 
PBMC 
Peripheral Blood Mononuclear Cell  
PK 
Pharmacokinetics 
RAND 
Research and Development 
RPMI 
Roswell Park Memorial Institute 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
subQ 
Subcutaneous 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
Tmax 
time of the observed maximum concentration  
t½ 
Half-life  
Vz/F 
Apparent (extravascular) volume of distribution  
 


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1 INTRODUCTION AND RATIONALE 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 


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1.6 
Dosing Regimen 
All 16 subjects will be randomly assigned in a 1:1 ratio (n=8), to one of two ALT-803 drug 
concentrations. Subjects randomized to Group A will receive ALT-803 at a concentration of 1.0 
mg/mL, and subjects randomized to Group B will receive ALT-803 at a concentration of 2 mg/mL.  
• On Day 1 of study period 1 (study days 1 – 9), ALT-803 will be administered as a single 
subQ dose of 10 µg/kg. A 6-day minimum rest period will follow, starting the day after the 
last PK sample collection visit for Period 1. 
• On Day 1 of study period 2 (study days 1-9), ALT-803 will be administered as a single 
subQ dose of 20 μg/kg.  


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2 STUDY OBJECTIVES 
2.1 
Primary 
 
The primary objective of this study is to determine the PK profile after single dose subQ 
injection(s) of 10 μg/kg and 20 μg/kg ALT-803 at concentrations of 1.0 mg/mL or 2.0 mg/mL.  
 
2.2 
Secondary 
The secondary objective of this study is to assess safety after single dose subQ injection(s) of 10 
μg/kg and 20 μg/kg ALT-803 at concentrations of 1.0 mg/mL or 2.0 mg/mL.  
 
 
 
 
 


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3 STUDY ENDPOINTS 
3.1 
Primary 
Serum concentration will be used to calculate the following PK parameters: 
•
half-life (t½)
•
apparent (extravascular) volume of distribution (Vz/F)
•
apparent (extravascular) clearance (CL/F)
•
maximum observed concentration (Cmax)
•
time of the observed maximum concentration (Tmax)
•
area under the plasma concentration curve from time 0 through the last measurable
concentration (AUC0-t)
•
area under the plasma concentration curve from time 0 extrapolated to infinite time
(AUC0-inf)
3.2 
Secondary 
The secondary endpoint of the study is to assess safety as measured by the incidence and 
severity of adverse events.  
3.3 
Measures of Interest 
Blood samples will be collected for immune cell levels and activity, immune cell 
phenotype subsets, cytokine levels and immunogenicity testing, which include assays for 
anti-ALT-803 antibodies. 
General health will be assessed by the RAND General Health Questionnaire (SF-36). 


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4 STUDY PLAN 
4.1 
Study Design 
This is a single center, open-label, pharmacokinetic study of ALT-803 administered as a subQ 
injection to healthy volunteers. Subjects meeting the entry criteria will be randomized in a 1:1 ratio 
(Groups A or B) to one of two ALT-803 drug concentrations. Subjects randomized to Group A 
(n=8) will receive ALT-803 at a concentration of 1.0 mg/mL and subjects randomized to Group B 
(n=8) will receive ALT-803 at a concentration of 2.0 mg/mL. Subjects will receive a single 10 
µg/kg subQ dose of ALT-803 on Day 1 of study period 1. After a rest period, subjects will receive 
a single 20 µg/kg subQ dose of ALT-803 on Day 1 of study period 2. Blood samples to determine 
serum levels of ALT-803 will be collected prior to dosing, and at 1, 4, 24, 48, 72, 96, 120, 144, 
168 and 192 hours after dosing. Vital signs (heart rate, blood pressure, respiration, temperature) 
will be monitored.  
 
Safety will be assessed for all subjects, and will include monitoring of vital signs and incidence 
and severity of adverse events.  Blood samples will be collected for hematology and chemistry, 
immune cell levels and activity, immune cell phenotype subsets, cytokine levels and 
immunogenicity testing, which include assays for anti-ALT-803 antibodies.  
 
After the completion of study period 2, subjects will be followed for an additional 6 days and will 
have an End of Study visit on Day 15 which will include safety labs, immune cells, and cytokines. 
Concomitant medications and adverse events will be collected throughout the study. 
4.1.1 
Screening and baseline (Day -14 through Time 0) 
Time 0 is defined as the start of the first study treatment administration. Baseline is defined as 
Study Day 1 prior to the first dose of study treatment (Time 0). The Screening Period is the 14-day 
period prior to Baseline.  
The Principal Investigator or designee will obtain the signed Informed Consent and HIPAA 
authorization from each subject prior to performing screening tests and procedures. All results 
obtained from the screening tests and procedures must be reviewed by a study Investigator to 
determine the subject’s eligibility to participate in the study.  
Subjects that are enrolled to the study but do not receive any study treatment will be replaced. 
4.1.2 
Study Period 1, Day 1 – Day 9 
Study period 1 is defined as the 9 days following Time 0, Day 1.  
In study period 1, subjects will be administered a single subQ injection of ALT-803. Blood 
sampling for PK, immune cells, cytokines and safety labs will commence on Day 1, and will 
continue daily throughout the nine-day study period. 
 


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4.1.3 
Rest Period (>6 days) 
No study visits will occur during the rest period (please see Section 4.3). Monitoring for adverse 
events and use of concomitant medications will continue throughout this period. 
 
4.1.4 
Study Period 2, Day 1 – Day 9 
Study period 2 is defined as the 9 days following the Rest period.  
In study period 2, subjects will be administered a single subQ injection of ALT-803. For study 
period 2, blood sampling for PK, immune cells, cytokines and safety labs will commence on Day 
1, and will continue daily throughout the nine-day study period. 
 
4.1.5 
Follow-up: Study Period 2, Day 10 – Day 15 
The follow-up period is defined as the 6-day period following the completion of study period 2.  
Monitoring for adverse events and use of concomitant medications will continue throughout this 
period. Subjects will be asked to return to the clinical research site on Day 15 for an End of Study 
visit. 
 
The study schematic is presented in Section 4.2. The schedule of assessments is presented in 
Section 4.3. 
 
 
 
 
 
 
 


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4.2 
Study Schematic 
 
 
 


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4.3 
 Schedule of Assessments 
 
Tests & Procedures
Screen1
BL2
Rest 
Period
Study Day
1
1
2
3
4
5
6
7
8
9
> 6d
1 (pre-
dose)
1
2
3
4
5
6
7
8
9
End of 
Study, D15
Medical History & Demographics
X
Complete Physical Exam 
X
Routine Physical Exam
X
X
X
HIV, Hepititis B/C
X
Serum/Urine Pregnancy Test3
X
X
X
X
Urine Drug Test4
X
X
X
Alcohol Breath Test5
X
X
X
Vital Signs, Height and Weight6,7
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CBC with differential
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Chemistry (CMP)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Sampling for Immune Cells 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Sampling Cytokines
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Sampling for Immunogenicity Testing
X
X
X
Blood Sampling for ALT-803 Pharmacokinetics8
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
General Health Questionnaire
X
X
ALT-803
X
X
Injection Site Reaction (ISR) Diary9
Digital Photography of Injection Site and ISR 10
X
X
Adverse Events Monitoring
Concomitant Meds 
5A positive read (≥ 0.010% BAC) is an exclusion criteria during screening or will result in subject not being dosed while on study. 
6Vital signs will be assessed prior to dosing with ALT-803 and 1 hour post-dose. On all other days, vital signs will be collected prior to sample collection.
7Height should only be measured at screening. Weight will be measured prior to ALT-803 dose, for study periods 1 and 2.
8Blood sampling for PK will be collected prior to ALT-803 dose, 1 and 4 hours post dose and at 24, 48, 72, 96, 120, 144, 168 a nd 192 hours after dosing for study periods 1 and 2.  
10 A digital photograph of the Injection site will be taken prior to subQ injection of ALT-803. Photograph ISR's daily in 2 views through Day 6 or resolution, whichever is longer.
9Injection site reaction diaries should be completed through Day 6 or resolution of symptoms, whichever is longer.
3For women with childbearing potential only. Screening test should be serum. Baseline test may be urine.
Safety Monitoring
1Screening evaluations performed <14 days prior to dose #1 unless otherwise specified.
2Baseline (BL) evaluations will be performed on Treatment Day 1 (pre-dose).
As applicable
Continual
Continual
As applicable
As applicable
Study Period 1
Study Period 2
Drug Administration


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5 POPULATION 
5.1 
Number of Subjects 
A total of 16 evaluable subjects will be enrolled. 
5.2 
Inclusion Criteria 
Subjects must meet ALL of the following criteria for inclusion in the study: 
1. Signed Written Informed Consent 
a. Subjects must have signed and dated an IRB/IEC approved written informed 
consent form in accordance with regulatory and institutional guidelines. This must 
be obtained before the performance of any protocol related procedures that are not 
part of subject care. 
b. Subjects must be willing and able to comply with the scheduled visits, study drug 
dosing schedule, procedures, laboratory tests, and other requirements of the study. 
2. Study Population 
a. Body mass index (BMI) must be within the range of 18 to 28 kg/m2. Subjects must 
weigh between 50 and 100 kg (inclusive). 
b. Subjects must be in good health as determined by past medical history, complete 
physical examination, vital signs and laboratory tests at screening. 
3. Age and Reproductive Status  
a. Men and women, 18 - 65 years of age. 
b. Female participants of childbearing potential must adhere to using a medically 
accepted method of birth control up to 28 days prior to screening and agree to 
continue its use during the study or be surgically sterilized (e.g., hysterectomy or 
tubal ligation) WOCBP must agree to use effective contraception during the study 
and for at least 1 month following the last dose of the study drug.  
c. WOCBP must have a negative serum pregnancy test < 14 days prior to first dose of 
the study drug. Non-childbearing is defined as greater than one year 
postmenopausal or surgically sterilized.  
d. Male subjects must be willing to use barrier contraception (i.e. condoms and 
spermicide) from the day of dosing until at least 1 month following the last dose of 
study drug. 


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5.3 
Exclusion Criteria 
Subjects with ANY of the following criteria are excluded from participation in the study: 
1. Medical History and Concurrent Diseases 
a. A past medical history of clinically significant 12 lead EKG abnormalities 
b. Subjects with a history of interstitial lung disease and/or pneumonitis.  
c. HIV-positive. 
d. Significant illness within 2 weeks prior to dosing. 
e. Positive hepatitis C serology or active hepatitis B infection.  
f. Known autoimmune disease requiring active treatment. Subjects with a condition 
requiring systemic treatment with either corticosteroids (>10 mg daily prednisone 
equivalent) or other immunosuppressive medications within 4 weeks or 5 half-lives 
of registration are excluded.  
g. Psychiatric illness/social situations that would limit compliance with study 
requirements. 
h. Previous malignancies, unless basal or squamous cell carcinoma of the skin or 
cervical carcinoma in situ with a complete remission achieved at least 5 years prior 
to study entry and no additional therapy is required or anticipated to be required 
during the study period. 
i. Loss of ≥ 475 mL blood volume or blood donation transfusion of any blood product 
within 3 months prior to screening. 
j. Other illness or laboratory abnormality that in the opinion of the Investigator should 
exclude the subject from participating in this study.  
2. Prohibited Treatments and/or Restricted Therapies 
a. Use of any prescription drugs within 4 weeks (hormonal methods of contraception 
are allowed) or less than 5 half-lives prior to dosing, or over-the-counter (OTC) 
medication (vitamins, herbal supplements, dietary supplements) within 2 weeks or 
less than 5 half-lives prior to dosing.  
b. Exposure to any investigational drug or placebo within 3 months of first dose of 
study drug. 
c. Previous treatment or clinical trial participation with monoclonal antibody therapy. 
d. History of drug or alcohol abuse within 12 months prior to dosing, or those who 
have a positive urine drug test or breath alcohol test at Screening or Baseline. 


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e. Transfusion of blood or any blood product within 3 months prior to screening. 
f. History of using nicotine-containing products or smoking more than 5 cigarettes 
weekly for at least three months prior to the study through the final evaluation. 
3. Allergies and Adverse Drug Reaction 
a. History of severe hypersensitivity reactions to other monoclonal antibodies. 
b. Known history of clinically significant drug allergy at Screening or Baseline 
4. Sex and Reproductive Status 
a. Women who are pregnant or nursing. 
 
 
 


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6 STUDY CONDUCT 
6.1 
Subject Screening and Enrollment ID 
Screening and Enrolled Subject ID’s 
Once a potential subject is confirmed to meet the inclusion criteria, assign a screening ID using 
the following format: letter ‘S’, 4-digit study ID (0317), 3-digit site ID (assigned by Altor), dash, 
and single-digit number starting from ‘1’. For example, the first subject screened by site 067 will 
be S0317067-1.  
For each enrolled patient, complete the Screening and Enrollment Log (Section 16.8) after the 
patient is screened. Send the form to Altor BioScience when requested. 
Once screening is complete and the subject is enrolled, assign the subject study ID using the 
following format: 4-digit study ID (0317), dash, 3-digit site ID (assigned by Altor), dash, and 3-
digit number starting from ‘001’. For example, the first subject enrolled by site 067 will be 0317-
067-001.  
For each enrolled patient, complete the Notification of Enrollment & Dosing Form (Section 
16.9) after the patient is enrolled and the first dose is administered. Send the form to Altor 
BioScience.  
6.2 
General Instructions 
The total duration of subject participation, from Study Day 1 until the “End of Study” visit, is 29 
days.  
6.3 
Study Procedures by Time Point 
6.3.1 
Screening and Baseline 
Time 0 is defined at the start of the first dose of ALT-803. Baseline is defined as Study Day 1 prior 
to the administration of the first dose of ALT-803 (Time 0). The Screening Period is the 14-day 
period prior to Baseline. 
6.3.1.1 
Screening: Within 14 days prior to first ALT-803 dose 
The following procedures and assessments must be performed within the 14 days prior to first dose 
of ALT-803: 
• Medical History and Demographics 
• Complete Physical Exam 
• Serum Pregnancy Test  
• Urine Drug Test  
• Alcohol Breath Test 
• HIV, Hepatitis B and C serologies  
• Vital Signs  


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• Height and Weight 
• CBC with Differential 
• Blood Chemistry (CMP) 
 
6.3.1.2 
Baseline: Study Day 1, Study Period 1 
The following procedures and assessments must be performed during the baseline period (prior to 
ALT-803 dose): 
• Routine Physical Exam  
• Urine Pregnancy Test 
• Urine Drug Test 
• Alcohol Breath Test 
• Vital Signs 
• Weight 
• CBC with Differential 
• Blood Chemistry (CMP) 
• Blood Sampling for Immune Cells 
• Blood Sampling for Cytokines 
• Blood Sampling for Immunogenicity 
• Blood Sampling for PK prior to ALT-803 dose (should be drawn immediately prior to 
ALT-803 dose) 
• General Health Questionnaire 
• Digital photography of injection site 
6.3.2 
Study Period 1 
The following procedures and assessments must be performed during study period 1: 
Study Day 1: 
• ALT-803 subQ Injection 
• Vital Signs (one-hour post ALT-803 dose) 
• Blood Sampling for PK (one hour and four hours post-dose ALT-803) 
• Injection site reaction diary  
• Digital photography of injection site (prior to discharge) 
• Adverse Event Monitoring 
• Concomitant Medications 
Study Day 2-9: 
  
• Vital Signs (prior to blood sample collection) 
• CBC with Differential 
• Blood Chemistry (CMP) 
• Blood Sampling for Immune Cells 


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• Blood Sampling for Cytokines 
• Blood Sampling for PK  
• Injection site reaction diary (Day 2-6 & as applicable post-Day 6) 
• Digital photography of ISR (Day 2-6 & as applicable post-Day 6) 
• Concomitant Medications 
• Adverse Events 
6.3.3 
Study Period 2 
The following procedures and assessments must be performed during study period 2: 
Study Day 1: 
Prior to ALT-803 dose: 
• Routing Physical Exam 
• Urine Pregnancy Test  
• Urine Drug Test  
• Alcohol Breath Test  
• Vital Signs 
• Weight 
• CBC with differential  
• Blood Chemistry (CMP)  
• Blood Sampling for Immune Cells  
• Blood Sampling for Cytokines  
• Blood Sampling for Immunogenicity   
• Blood Sampling for PK (immediately prior to ALT-803 dose)  
• Digital photography of injection site  
• Adverse Event Monitoring (rest period – Day 1, Study Period 2) 
• Concomitant Medications (rest period – Day 1, Study Period 2) 
 
• ALT-803 subQ Injection 
 
Post ALT-803 dose: 
• Vital Signs (one-hour post ALT-803 dose) 
• Blood Sampling for PK (one hour and four hours post-dose ALT-803) 
• Injection site reaction diary 
• Digital photography of injection site (prior to discharge) 
• Adverse Events Monitoring 
• Concomitant Medications 
Study Day 2-9: 
  
• Vital Signs (prior to blood sample collection) 
• CBC with Differential 
• Blood Chemistry (CMP) 


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• Blood Sampling for Immune Cells 
• Blood Sampling for Cytokines 
• Blood Sampling for PK  
• Injection site reaction diary (Day 2-6 & as applicable post-Day 6) 
• Digital photography of injection site (Day 2-6 & as applicable post-Day 6) 
• Concomitant Medications 
• Adverse Events 
6.3.4 
End of Study Visit 
The following procedures and assessments must be performed at the follow-up visit: 
Study Day 15: 
• Routine Physical Exam  
• Serum Pregnancy Test  
• Vital Signs 
• CBC with Differential 
• Blood Chemistry (CMP) 
• Blood Sampling for Immune Cells 
• Blood Sampling for Cytokines 
• Blood Sampling for Immunogenicity  
• General Health Questionnaire  
• Injection site reaction diary (as applicable post-Day 9) 
• Digital photography of ISR (as applicable post-Day 9) 
• Concomitant Medications 
• Adverse Events 
 
 
6.4 
Premature Discontinuation and Subject Replacement 
Any subject who meets the following criteria will be replaced: 
• Subjects who are enrolled but do not receive ALT-803 
• Subjects who withdraw consent 
• Subjects who have a positive alcohol or drug test after enrollment 
• Subjects who miss more than one PK collection timepoint during study period 1 or study 
period 2 will be replaced. 
Subjects who are replaced will be followed for up to 14 days, following their last dose of ALT-
803 for adverse events monitoring only. 


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7 DESCRIPTION OF STUDY PROCEDURES 
7.1 
Clinical Assessments and Procedures 
7.1.1 
Medical History 
A complete medical history (e.g. review of all body systems, summary of all illnesses, surgeries, 
allergies, drug sensitivities, menstrual history for women, and methods of contraception) will be 
performed at screening. Medical history will also include history of drug, nicotine and alcohol 
consumption. 
7.1.2 
Physical Examination 
A complete physical exam [head, eyes, ears, nose, throat, skin, heart, lungs, abdomen, extremities, 
and neurological (e.g. level of consciousness, pupils, motor and sensory responses, and reflexes)] 
will be performed at screening and a routine physical exam will be performed on all study visits 
per schedule of assessments. 
7.1.3 
Vital Signs, Body Weight & Height 
Vital signs (heart rate, blood pressure, respiratory rate, body temperature) will be collected at 
screening and at study visits per Schedule of Assessments (Section 4.3). Vital signs will be 
performed prior to, and one-hour post-ALT-803 subQ injection. On PK sample collection days, 
vital signs are to be collected prior to blood draw. Height (in cm) will be measured at screening 
and body weight (in kg) will be noted before each ALT-803 subQ injection.  
7.1.4 
General Health Questionnaire 
The General Health Questionnaire (GHQ), RAND 36-item Short Form Survey 1.0 (SF-36) will be 
completed by the subject at baseline on Day 1, study period 1, and at the Follow-up visit, please 
refer to (Section 16.2). The subject must complete the GHQ at the PK Unit (research site) during 
the scheduled visit. 
7.1.5 
Injection Site Reaction Subject Diary and Digital Photographic Documentation 
The ALT-803 Injection Site Reaction Diary (Section 16.1) will be given to subjects on the day that 
the ALT-803 subQ injection is administered (Day 1 of Study Period 1 and 2). The diary is to be 
completed by the subject daily for six days or until the resolution of symptoms, whichever is 
longer. The subject will return the completed diaries to the study coordinator.  
Since injection site reactions are an adverse event, close clinical follow up is a requirement. Prior 
to subQ injection of ALT-803, a photograph should be taken of the injection area (i.e. right 
abdomen). The PI should photograph the injection site daily for six days or until the resolution of 
symptoms, whichever is longer (Schedule of Assessments, Section 4.3), a camera with a minimum 
of 10 megapixels should be used, and 2 views of the lesion (one identifying the region of the body 
and one close-up) should be taken. An adhesive label with the study I.D., PID, patient initials, date, 
time and the corresponding number of the photo (i.e. image 1 or image 2) should be placed next 
to the injection site (on the skin) for both views (please see photographic example below).  


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                                                                               (Mocci 2013) 
7.2 
Test Collection and Processing 
The following tests will be processed/performed at the study site’s (or local) laboratory: 
• Hematology: CBC (Complete Blood Count) with Differential  
• Blood Chemistry: CMP (Complete Metabolic Panel) 
• Serum/Urine Pregnancy Test 
• Alcohol Breath Test 
• HIV Test 
• Hepatitis B Test 
• Hepatitis C Test 
Blood/Urine Sample Collection and Processing 
• 
Follow standard blood/urine collection procedures according to site guidelines.  
• 
Use the sample collection tubes/containers specified by site guidelines for the following 
routine tests: Serum and urine pregnancy (if applicable), CBC with differential, and CMP. 
• 
Follow the Sponsor guidelines for PBMC isolation for immune cells (Section 7.3) and 
serum for PK, cytokines, and immunogenicity (Section 7.4). 
• 
Collect samples at the designated time points according to the Schedule of Assessments 
(Section 4.3). Screening tests are performed <14 days prior to the start of therapy unless 
otherwise specified. 
• 
The Study Coordinator or designee will review the test results as soon as possible. 
• 
The specimens should be saved until the Study Coordinator has reviewed the test results. 


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• 
The Study Coordinator will transcribe the test results into the corresponding subject case 
report forms (CRFs) and will record Adverse Events in the Adverse Event Log CRF for 
any clinically significant laboratory abnormalities.  
7.3 
Immune Cells (PBMCs) 
These assays will be performed at Altor BioScience for the purpose of monitoring immune cell 
levels and activity, and immune cell phenotype subsets. The test/collection schedule is specified 
in the Schedule of Assessments (Section 4.3).  
If available, these samples may be retained and used for additional biomarker research studies. 
Immune Cells Collection and Processing 
Materials/equipment:  
• Histopaque-1077; Sigma-Aldrich; Cat#10771-100ML 
• HBSS (1X); Gibco; Cat#14175-095 
• 1X BD FACS Lysing Solution: 
→ 10X BD FACS Lysing Solution; BD; Cat#349202 (10mL) 
→ Purified H2O 
• Roswell Park Memorial Institute Wash Media (RPMI + 10%FBS): 
→ RPMI; Gibco; Cat#22400-089 
→ Fetal Bovine Serum (FBS); Hyclone; Cat#SH30071.03 
• RPMI Freezing Media (RPMI Wash Media + 10%DMSO): 
→ RPMI Wash Media (above) 
→ Dimethyl Sulfoxide (DMSO); Sigma; Cat#D-8418 
• 15mL Conical Tubes; Corning; Cat#430790 
• Thermo Scientific Sorvall ST-16R swinging bucket Centrifuge, refrigerated. (Or 
equivalent centrifuge) 
• 0.5 or 1.7mL Eppendorf Tubes 
• Trypan Blue; Sigma-Aldrich; Cat#T8154 
• Microscope 
• Hausser Scientific Bright-Line Counting Chamber; Fisher Scientific; Cat#02-671-51B (or 
equivalent Hemocytometer w./ 0.1mm Neubauer ruling) (ViCell may also be used if 
available) 
• 2mL sterile Cryovials w./ silicone seal; Phenix Research; Cat#C-402-4 (or equivalent 2mL 
freezer tube) 
• Pipets, various. 
 






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Counting Immune cells 
23. Prior to counting, ensure the hemocytometer* and coverslip are both clean and dry. A 70% 
reagent alcohol solution or equivalent can be used. 
   *Vi-cell may be used if available 
 
24. Pipet approx. 10-15µL of isolated immune cells diluted 1:2 in Trypan Blue into the loading 
area of the counting chamber. 
25. With the chamber underneath the objective, focus the microscope and adjust the light as 
necessary. 
26. The counting area in the Neubauer Ruling should look like this: 
 
27. Within the confines of the 16 squares circled above (corner #1), count all live immune cells. 
(Live cells will appear round and opaque and dead cells will be stained blue). 
28. Count the 4 corners of the Neubauer Ruling (64 small squares) and total the live immune 
cells. 
29. Example Calculation: 
• (200 cells/ 4 corners) x 2 (dilution) x 104 = (1.00 x 106 cells/mL)  
• (1x 106 cells/mL) x 4mL (initial volume) = 4.0 x 106 cells 
• (4.0 x 106 cells) / 2mL (final volume in freezing media) = 2.0 x 106 cells/mL 
*Repeat all steps for the second purple top tube. 
7.4 
PK, Cytokines and Immunogenicity 
7.4.1 
PK 
Altor Bioscience will use validated ELISA methods for PK analysis. These tests will be performed 
at Altor BioScience. The pharmacokinetic profile of ALT-803 will be assessed using blood 
collected at the following time points: 
 
 


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Study Periods 1 & 2: 
Day 1 
Immediate Pre-dose (time 0) 
± 5 minutes 
Day 1 
1 hour post-dose 
± 5 minutes 
Day 1 
4 hour post-dose 
± 15 minutes 
Day 2 
24-hour post-dose 
± 60 minutes 
Day 3 
48-hour post-dose 
± 60 minutes 
Day 4 
72-hour post-dose 
± 60 minutes 
Day 5 
96-hour post-dose 
± 60 minutes 
Day 6 
120-hour post-dose 
± 120 minutes 
Day 7  
144-hour post-dose 
± 120 minutes 
Day 8 
168-hour post-dose 
± 120 minutes 
Day 9 
192-hour post-dose 
± 120 minutes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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7.6 
Adverse event assessment 
Subjects who have an on-going study drug-related adverse event or serious adverse event upon 
study completion or at discontinuation of the study will be contacted by the Investigator or his/her 
designee every week until the event is resolved or determined to be irreversible. Adverse event 
information will be collected for all subjects per Section 9. 
7.6.1 
ALT-803 Injection Site Reaction 
Based on current experience, localized, transient skin rashes thought to be indicative of an immune 
response to ALT-803, are common with subQ administration. Adverse event monitoring will 
include an Injection Site Reaction Subject Diary (Section 16.1) to collect incidence and severity 
of potential injection site reactions and related symptoms. 


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7.7 
Concomitant Medications 
Concomitant medications [prescription drugs and over-the counter (OTC) medications (vitamins, 
herbal supplements, analgesics)] are not permitted while on study. At screening, use of any 
prescription drugs within 4 weeks (hormonal methods of contraception are allowed) or less than 5 
half-lives prior to dosing, or OTC medications within 2 weeks or less than 5 half-lives prior to 
dosing are not permitted (for further details, please see Section 5.3, Exclusion Criteria, Prohibited 
Treatments and/or Restricted Therapies, page 23).  
7.8 
Protocol Deviations 
In general, a protocol deviation is an inadvertent excursion to, or non-compliance with, the 
institutional review board (IRB) approved protocol. The Investigator is responsible for ensuring 
the study is conducted in accordance with the procedures described in this protocol and should not 
implement any changes to the protocol unless it is required to eliminate an immediate hazard to 
the subject. If a deviation occurs and affects the safety of a subject, Altor BioScience must be 
notified immediately. Please refer to Section 13, Quality Control and Quality Assurance, for 
detailed guidance on documentation of and severity of protocol deviations. 


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8 STUDY DRUG MANAGEMENT 
8.1 
ALT-803  
8.1.1 
Formulation  
ALT-803 is a soluble complex consisting of two protein subunits of a human IL-15 variant 
associated with high affinity to a dimeric human IL-15 alpha receptor sushi domain / human IgG1 
Fc fusion protein (Xu 2013). 
8.1.2 
Storage 
ALT-803 must be maintained at a temperature between 2°C and 8°C. 
8.1.3 
Packaging and Delivery 
ALT-803 is provided in a 2 mL vial containing 1.2 mL of ALT-803 at a concentration of 1 mg/mL 
or a 2 mL vial containing 0.6 mL of ALT-803 at a concentration of 2 mg/mL. Vials are packaged 
in cartons and are delivered to the research site.  
8.1.4 
Disposal/Destruction 
No special considerations are necessary when disposing of used vials, dispose/destroy according 
to standard site guidelines. Maintain disposal/destruction records for inspection by Altor or Altor 
representative to review at a later time.  
At the end of the study or at another pre-determined time, Altor will request the return of all 
remaining unused IP vials. At that time, Altor will provide specific packaging instructions and 
packing materials. 
To record the return of IP vials, complete the following fields on the Study Medication Inventory 
Tracking (SMIT) form (Section 16.10): Date Returned, Returned By, and Returned To (e.g. Altor).  
Be sure to use the next available row on the form.  
8.2 
Dose and Administration 
Dose calculation will be based on subject’s assigned dose level and actual body weight collected 
prior to ALT-803 dose for each study period. The calculated amount of ALT-803 will be drawn 
into a syringe for subQ injection. Stability studies have been conducted on IP diluted in 0.9% 
saline. The results of the studies show that the potency of ALT-803 is maintained within the 
specifications when diluted in 0.9% saline to a concentration of 25 µg/mL and stored in a syringe 
for ≤ 24 hour at 4°C.  
The assigned concentration for study period 1 and 2 for all subjects enrolled in Group A is 1.0 
mg/mL and 2.0 mg/mL for all subjects enrolled in Group B. Doses will be drawn directly into the 
syringe for injection. If the total subQ dose is greater than 1.5 mL, the dose will be divided into 2-
3 subQ injections as needed. Injection sites should be rotated for study period 2, per institutional 


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guidelines and each injection site (preferably the abdomen) separated by at least 1 inch. The 
description of the injection site (i.e. left abdomen, left arm, right thigh, etc.), as well as any side 
effects such as redness, swelling or itching at the injection site should be recorded for each dose, 
in the Injection Site Reaction Diary (Section 16.1). No special considerations are necessary when 
handling (other than handling with gloves) the vialed product. 
 
 
 
 
8.3.1 
Altor Delivery Procedures 
Altor will deliver the IP vials at 2-8°C in a reusable Greenbox with a TempTale® temperature 
monitor. The package will be hand delivered by an Altor Bioscience representative.  
Altor will complete and include the following with each delivery: 
a) Study Medication Inventory/Tracking (SMIT) Form. The following fields in 
the first row will be completed by Altor: The Total No. of Vials, Lot No., 
Concentration (Conc.), Date Delivered and Prepared by By.  An example of the 
blank form is included in (Section 16.12). 
b) Study Medication Shipping Notice/Receipt (SMSNR) Form. The sender section 
will be completed by Altor.  An example of the blank form is included in (Section 
16.11).  
c) Study Medication Shipping Requisition (SMSR) Form. This is a blank order 
form for IP vial re-supply. An example of the blank form is included in (Section 
16.12).  
d) The first delivery will include the Certificate of Analysis for ALT-803. 
8.3.2 
Site IP Receipt Procedures 
 
1. Immediately open the package upon arrival and turn off the TempTale® by pressing the 
Stop Button (red button) for about 3 seconds until the “Stop sign” icon appears in the 
upper right corner of the display window.  
a. Notate the date/time the TempTale® was turned off on the Recipient and Return 
Section of the SMSNR Form (Section 16.11).  
b. Note: If an alarm symbol is displayed in the display window, call Altor 
immediately (954-443-8600 ext. 838 or 879). A plan of action will be determined 
by Altor at that time. 


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2. Remove the vials from the payload box, inspect each vial as you complete the questions 
on the Recipient and Return Section of the SMSNR Form (Section 16.11) and place the 
vials in a temperature controlled/monitored refrigerator at 2-8°C.  
3. The vials must remain quarantined and cannot be used until further notice from Altor. 
Notification will occur after Altor reviews the temperature report and receives the shipper 
back from your site. 
4. Email the SMSNR Form (Section 16.13) to Altor BioScience. Keep a copy of the 
SMSNR form in the pharmacy binder.  
5. Enter the Date Received and initial the “Received By” fields in the first row on the SMIT 
Form (Section 16.12). Keep this form in the pharmacy binder for Altor or Altor 
representative to review at a later time.  
8.3.3 
Site Shipper Return Procedures 
1. Place all shipping materials including the TempTale® monitor, payload box and panels back 
into the Green Box. Close the Green Box, taping is not necessary. 
2. Seal the outermost cardboard box with tape.  
3. Schedule local pick-up with representative from Altor BioScience. 
8.3.4 
Altor IP Vial Approval 
Once the shipper is received, Altor will review the temperature report and complete the bottom 
‘for Altor Use Only’ section of the SMSNR Form (Section 16.13). The form will be emailed to 
the site. Print and keep the signed form in the pharmacy binder. 
8.3.5 
IP Dispensing, Accountability and Resupply 
1. To record IP dispensing, the SMIT form (Section 16.12) is optional provided that the site has 
an equivalent accountability log (e.g. NIH-2564) or electronic record.  
2. Using the SMIT form (Section 16.12): When dispensing a vial or vials for the preparation of 
study treatment, record the No. of Vials Used, Date Dispensed, pharmacist initials in the 
“Dispensed By” column, the Subject Study ID No. and the Dose. 
8.3.6 
IP Study Treatment Preparation 
Refer to the ALT-803 Study Treatment Preparation Worksheet (Section 16.13). 
8.3.7 
Temperature Excursions 
If storage conditions for investigational product have been compromised resulting in a temperature 
excursion (from the acceptable range), or if there is any suspicion that the investigational product 
has not been properly stored the following actions must be taken: 


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1. Notify Altor representative immediately via telephone and email
2. Complete the Temperature Excursion Report Form (Section 16.14) and return via scanned
email to Altor BioScience as soon possible, within 24 hours of the noted excursion.
3. Quarantine the investigational product under the correct storage conditions until further
notice from Altor.
4. Altor will send back the Temperature Excursion Report Form (Section 16.14) with the
Temperature Excursion Assessment section (bottom) completed confirming if the
investigational product is acceptable or not acceptable for clinical use.
5. If the investigational product is not acceptable for clinical use, Altor will provide a
replacement and will provide further instructions for the quarantined vials.
6. Keep a copy of the Temperature Excursion Report Form (Section 16.14) in the pharmacy
binder.
8.4 
Prohibited Concomitant Therapy 
No investigational, commercial or OTC medications other than ALT-803 may be administered 
during the duration of the study with the exception of those listed in (Section 8.6, Post-ALT-803 
Therapy Guidelines). 
Topical steroid cream is permitted. 
8.5 
Compliance 
The protocol, specifically the Schedule of Assessments, requires complete adherence to safeguard 
subject wellbeing and ensure data integrity. Noncompliance, may result in a deviation or subject 
replacement (please see Section 6.4, Premature Discontinuation and Subject Replacement).  


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9 ADVERSE EVENTS 
9.1 
Monitoring, Recording and Reporting of Adverse Events 
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may 
appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a 
worsening concomitant illness, an injury, or any concomitant impairment of the subject’s health, 
including laboratory test values (Section 9.3), regardless of etiology. Any worsening (i.e., any 
clinically significant adverse change in the frequency or intensity of a pre-existing condition) 
should be considered an AE. A diagnosis or syndrome should be recorded on the AE page of the 
case report form (CRF) rather than the individual signs or symptoms of the diagnosis or syndrome. 
If death occurs, this must be reported as an SAE to the Sponsor or their designated safety group 
within 24 hours of learning of this event.  
An overdose, accidental or intentional, whether or not it is associated with an AE, or abuse, 
withdrawal, sensitivity or toxicity to an investigational product should be reported as an AE. If an 
overdose is associated with an AE, the overdose and AE should be reported as separate terms. In 
the event of overdose or exaggerated response, the subject should be monitored as appropriate and 
should receive supportive measures as necessary. There are no known specific antidotes for ALT-
803 overdose. Actual treatments should depend on the severity of the clinical situation and the 
judgment and experience of the treating Investigator.  
All AEs will be documented and reported by the Investigator from the time the subject is 
administered the first dose of ALT-803 to 14 days after the last dose of study drug or until the last 
study visit, whichever is longer. AEs and SAEs will be recorded on the AE page of the CRF and 
in the subject’s source documents. When an AE/SAE occurs, the Investigator is expected to review 
all documentation (e.g., hospital progress notes, consultations, laboratory and diagnostics reports) 
related to the event. The Investigator must determine the relationship between the administration 
of the study drug and the occurrence of an AE/SAE as “not suspected” or “suspected”. The 
Investigator is responsible for informing the IRB/IEC of SAEs and providing them with all 
relevant initial and follow-up information about the event as applicable. The Investigator must 
keep copies of all SAE information on file, including correspondence with Altor BioScience or 
Nant Safety and the IRB/IEC of record. 
Please report all SAEs within 24 hours of the Investigator’s awareness of the event by email 
(SAE@altorbioscience.com), using the provided Serious Adverse Event Report Form and 
SAE Fax Cover Sheet (Section 16.3). Please attach available copies of redacted/de-identified 
relevant source documents. Upon review of the SAE Report Form, Altor BioScience or its safety 
group, Nant Safety (an identical copy of the email sent to Altor will be automatically generated 
and sent to Nant Safety), may request the site to provide additional de-identified source 
documents describing the event. 


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IT IS MANDATORY THAT THE PRINCIPAL INVESTIGATOR (PI) OR SUB-
INVESTIGATOR SIGN ALL SAE REPORTS AND ASSIGN RELATIONSHIP TO ALT-
803, AND THAT HE/SHE IS LISTED ON THE FDA 1572. 
The Investigator is responsible for informing the IRB/IEC of SAEs and providing them with all 
relevant initial and follow-up information about the event as applicable. The Investigator must 
keep copies of all SAE information on file, including correspondence with Altor BioScience or 
Nant Safety and the IRB/IEC of record. 
If there are any questions regarding SAE reporting, please send all inquiries to 
SAE@altorbioscience.com (an identical copy of email sent to Altor will be automatically 
generated and sent to Nant Safety).  
9.2 
Evaluation of Adverse Events 
Assignment of a grade of adverse events based on intensity of symptoms, degree of limitation of 
daily activities, or level of abnormality of objective clinical signs or laboratory parameters using 
Terminology Criteria for Adverse Events V4.03 (CTCAE). 
9.2.1 
Seriousness 
An SAE is any AE that fulfils one or more of the following: 
•
Results in death.
•
Is life-threatening (i.e., in the opinion of the Investigator, the subject is at immediate risk
of death from the AE as it occurred).
•
Requires in-subject hospitalization or prolongation of existing hospitalization
(hospitalization is defined as an in-subject admission, regardless of length of stay).
•
Results in persistent or significant disability or incapacity (a substantial disruption of the
subject’s ability to conduct normal life functions).
•
Results in a congenital abnormality or birth defect.
•
Is an important medical event that may jeopardize the subject or may require medical
intervention to prevent one of the outcomes listed above. Important medical events are
defined as those occurrences that may not be immediately life-threatening or result in
death, hospitalization, or disability, but may jeopardize the subject or require medical or
surgical intervention to prevent one of the other outcomes listed above. Medical and
scientific judgment should be exercised in deciding whether such an AE should be
considered serious.
If an AE is considered serious, both the AE page/screen of the CRF and the SAE Report Form 
must be completed.  
For each SAE, the Investigator will provide information on severity, start and stop dates, 
relationship to the study drug, action taken regarding the study drug, and outcome. 


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9.2.2 
Severity/Intensity 
The severity/intensity of AEs and SAEs will be graded based upon the subject’s symptoms 
according to the NCI CTCAE Version 4.03.  
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf 
AEs that are not defined in the NCI CTCAE Version 4.03 should be evaluated for severity/intensity 
according to the following scale:  
•
Grade 1 = Mild: transient or mild discomfort, no limitation in activity; no medical
intervention/therapy required.
•
Grade 2 = Moderate: mild to moderate limitation in activity, some assistance may be
needed; no or minimal medical intervention/therapy required.
•
Grade 3 = Severe: marked limitation in activity, some assistance usually required; medical
intervention/therapy required, hospitalization possible.
•
Grade 4 = Life threatening: extreme limitation in activity, significant assistance required;
significant medical intervention/therapy required, hospitalization or hospice care probable.
•
Grade 5 = Death: the event results in death.
It is important to distinguish between serious and severe AEs. Severity is a measure of intensity 
whereas seriousness is defined by the criteria under Section 9.2.1. An AE of severe intensity may 
not be considered serious. Seriousness, not severity, serves as a guide for defining regulatory 
obligations. 
9.2.3 
Relationship to the Study Drug 
The Investigator must determine the relationship between the administration of the study drug and 
the occurrence of an AE/SAE as “not suspected” or “suspected,” as defined below:  
•
Not suspected: The temporal relationship of the AE or SAE to the study drug
administration makes a causal relationship unlikely or remote, or other medications,
therapeutic interventions, or underlying conditions provide a sufficient explanation for the
observed event.
•
Suspected: The temporal relationship of the AE or SAE to the study drug administration
makes a causal relationship possible, and other medications, therapeutic interventions, or
underlying conditions do not provide a sufficient explanation for the observed event.
If an event is assessed as suspected of being related to a comparator, ancillary, or additional study 
drug that has not been manufactured or provided by Altor BioScience, please provide the name of 
the manufacturer when reporting the event. 


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9.2.4 
Duration 
For all AEs and SAEs, the Investigator will provide a record of the start and stop dates of the event. 
Please see study specific CRF data entry completion guidelines and SAE report completion 
guidelines for instructions for capturing the start and stop dates of AEs and SAEs. 
9.2.5 
Action Taken 
The Investigator will report the action taken with the study drug as a result of any AE or SAE, as 
applicable (e.g., discontinuation of the study drug) and report if concomitant and/or additional 
treatments were given for the event. 
9.2.6 
Outcome 
The Investigator will report the outcome of the event for both AEs and SAEs. Non-serious AEs 
will be followed for 14 days after the subject’s last dose of the study drug. AEs will be followed 
until resolution or stabilization. All SAEs that have not resolved upon discontinuation of the 
subject’s participation in the study must be followed until recovered, recovered with sequelae, not 
recovered (death due to other cause), death (due to the SAE), lost to follow up, or otherwise 
explained. 
9.3 
Abnormal Laboratory Values 
An abnormal laboratory value is considered to be an AE if the abnormality:  
• Results in discontinuation from the study;  
• Requires treatment, modification/interruption of the study drug dose, or any other 
therapeutic intervention; or  
• Is judged to be of significant clinical importance.  
Regardless of the severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as an SAE.  
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page/screen of the CRF. If the abnormality was not a 
part of a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE. 
9.4 
SAE Report Form Completion Guidelines 
Please do not leave report fields blank.  If the information requested is unknown, please indicate 
so by placing UNK in that field. 
1. Provide reporter’s name (person completing the form).  
2. Provide date of report using date format (DD/MMM/YYYY). 
3. Provide Investigator’s name. 
4. Provide site name. 


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5. Provide site address. 
6. Provide site country. 
7. Provide site telephone number of site staff/Investigator who can be reached to answer 
questions.  Please do not provide a general office number (receptionist). 
8. Provide site email address of site staff/Investigator who can be reached via email to answer 
questions. 
9. Indicate if this is an initial or follow up SAE report.  If follow up, indicate follow-up 
number in sequential order (example: follow-up #1, follow-up #2, etc.)  
10. Provide date the site became aware of the event using date format (DD/MMM/YYYY). 
11. Provide subject initials (N/A for EU or other territories that prohibit).  
12. Provide subject study ID (10-digit ID). 
13. Provide subject gender. 
14. Provide subject date of birth (N/A for EU or other territories that prohibit) using date format 
(DD/MMM/YYYY). 
15. Provide subject weight in kilograms. 
16. Provide subject height in centimeters. 
17. Check all applicable SAE criteria and provide additional details as indicated. 
• In case of in-subject hospitalization or prolongation of hospitalization: 
- 
Record date of admission using date format (DD/MMM/YYYY) 
- 
Record date of discharge using date format (DD/MMM/YYYY) 
• In case of death: 
- 
Record date of death using date format (DD/MMM/YYYY) 
- 
Record cause of death  
- 
Indicate if death certificate was obtained by checking the appropriate box.  
If yes, attach the redacted certificate. 
- 
Indicate if the autopsy report was obtained by checking the appropriate box.  
If yes, attach the redacted report.     


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18. Provide adverse event term (the reported term must represent the event that met SAE 
criteria; for example, fever, nausea, vomiting are symptoms of flu, and therefore, 
hospitalization due to the flu is the SAE event, reported as flu). Only one event can be 
reported per SAE form.  If additional SAEs occurred, they will need to be reported 
separately on separate SAE forms.  Death is considered an outcome and should only be 
reported as the SAE term if death is the only information available at the time of reporting.  
On follow up, the SAE term will need to be amended to the event term that resulted in 
death.  
19. Provide SAE start date using date format (DD/MMM/YYYY).  Start/onset date should be 
the date the event became serious/met SAE criteria. 
20. Provide the SAE start time using 24-hour clock (if known). 
21. Provide stop date using date format (DD/MMM/YYYY).  Stop/end date should be the date 
the event no longer met the recorded SAE criteria. 
22. Provide stop time using 24-hour clock (if known). 
23. If the SAE is not resolved at the time of the report, check if ongoing. 
24. Provide event severity grade using Terminology Criteria for Adverse Events V4.03 
(CTCAE). 
25. Provide relationship to ALT-803. Please do not leave blank; attribution can be changed on 
follow up.  If not suspected, indicate cause of the event in the SAE report narrative, if 
applicable [e.g. lack of efficacy, concurrent disorder (specify), concomitant medication 
(specify), other (specify)]. 
26. Provide event outcome. In the event of a subject’s death and the reported SAE was ongoing 
at the time of death, please mark the outcome as ‘Unresolved’ and leave the SAE stop date 
blank. Please indicate in the SAE report narrative that the reported SAE will remain as 
‘Unresolved’ due to the fact that the SAE was unresolved at the time of death (this will 
keep Altor BioScience or Nant Safety from having to query for a resolution date.) If the 
reported SAE is the cause of death, the outcome should be recorded as ‘Fatal’ and the SAE 
end date should be recorded as the date of death. 
27. Provide site ID (067). 
28. Provide subject study ID (10-digit ID) and subject initials.  
29. Provide date of first dose of ALT-803 using date format (DD/MMM/YYYY). 
30. Provide date of last dose of ALT-803 prior to onset of SAE using date format 
(DD/MMM/YYYY). 
31. Provide dose amount and unit for ALT-803. 


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32. Indicate # of doses received for ALT-803.
33. Provide lot number for ALT-803.
34. Provide action taken with each study medication for this event including
abatement/reappearance/NA.
35. In the narrative, describe event fully. Include baseline medical status including relevant
medical history, signs and symptoms, diagnosis, diagnostic test results, clinical course,
treatment (all drugs/procedures used as interventions for SAE), outcome, hospital course
for hospitalizations, etc. Provide rationale for causality assessment. Document other
potential causes of the event. If additional space is needed for narrative please include
additional page.
36. Attach relevant de-identified test results and hospital records when submitting the form. If
subject was hospitalized, submit discharge summary, if available.  If not available at time
of initial report, submit discharge summary when it is available.
37. Complete AE, Medical History, applicable Study Treatment Administration, and
Concomitant Medications eCRFs as soon as possible.  Instructions regarding recording
of AEs and SAEs in the EDC are available in the eCRF Completion Guidelines.
38. Provide Principal Investigator or Sub-Investigator’s printed name, signature and date using
date format (DD/MMM/YYYY).
No Changes are to be made on the initial SAE form (this is a legal document).  Therefore, any 
changes or additional information must be documented on a follow-up SAE form. 
9.5 
Pregnancy 
9.5.1 
Females of Child-Bearing Potential 
Pregnancies and suspected pregnancies (including a positive pregnancy test regardless of age or 
disease state) of a female subject occurring while the subject is on the study drug, or within 14 
days of the subject’s last dose of the study drug, are considered immediately reportable events.  
The study drug is to be discontinued immediately. The pregnancy, suspected pregnancy, or 
positive pregnancy test must be reported to Altor BioScience/Nant Safety (an identical copy of 
email sent to Altor will be automatically generated and sent to Nant Safety) immediately by email 
(SAE@altorbioscience.com), using the Pregnancy Questionnaire (Section 16.6). The female 
subject may be referred to an obstetrician-gynecologist (not necessarily one with reproductive 
toxicity experience) or another appropriate healthcare professional for further evaluation.  
The Investigator will follow the female subject until completion of the pregnancy and must notify 
Altor BioScience Drug Safety immediately about the outcome of the pregnancy (either normal or 
abnormal outcome) using the Follow-up Pregnancy Questionnaire (Section 16.6). 


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If the outcome of the pregnancy was abnormal (e.g., spontaneous or therapeutic abortion), the 
Investigator should report the abnormal outcome as an AE. If the abnormal outcome meets any of 
the serious criteria, it must be reported as an SAE to Altor BioScience/Nant Safety by email 
(SAE@altorbioscience.com), within 24 hours of the Investigator’s knowledge of the event using 
the SAE Report Form.  
All neonatal deaths that occur within 28 days of birth should be reported, without regard to causality, 
as SAEs. In addition, any infant death after 28 days that the Investigator suspects is related to the in 
utero exposure to the study drug should also be reported to Altor BioScience/Nant Safety 
immediately by email (SAE@altorbioscience.com), within 24 hours of the Investigator’s knowledge 
of the event using the SAE Report Form. Male Subjects 
If a female partner of a male subject taking the study drug becomes pregnant, the male subject 
should notify the Investigator as soon as possible, who will provide a copy of the Pregnant Partner 
Informed Consent Form and a copy of the pregnancy questionnaire to the male study subject to 
provide to the pregnant partner.  
If the pregnant partner consents, she will check the appropriate box on the consent form, sign the 
consent form, and complete the pregnant partner questionnaire; the male subject will also sign the 
consent form and provide the pregnant partner with the Investigator’s contact information should 
she have any questions on the consent form or questionnaire. The male subject shall return the 
signed consent form and completed questionnaire to the study coordinator or Investigator. The 
pregnant partner will be contacted for information regarding outcome of the pregnancy (e.g., live 
birth, etc.) and will be contacted up to 6 months following a live birth for information on the health 
of the child. The reporting and collection of AEs will follow the process described in Section 9.4.1. 
If the pregnant partner refuses to consent, the male subject will indicate on the consent form, and 
will sign that he presented the consent to his pregnant partner. The Investigator will record that a 
pregnancy occurred and that the pregnant partner refused consent. 
9.6 
Reporting of Adverse Events 
Any AE that meets any criterion for an SAE requires the completion of an SAE Report Form in 
addition to being recorded on the AE page/screen of the CRF. All SAEs must be reported to Altor 
BioScience Drug Safety within 24 hours of the Investigator’s knowledge of the event by facsimile, 
email using the SAE Report Form. This instruction pertains to initial SAE reports as well as any 
follow-up reports.  
SAE Reporting information:  
Email: SAE@AltorBioScience.com 
(an identical copy of email sent to Altor will be automatically generated and sent to Nant Safety) 
The Investigator is required to ensure that the data on these forms are accurate and consistent. This 
requirement applies to all SAEs (regardless of relationship to the study drug) that occur during the 
study (from the time the subject signs informed consent to 14 days after the last dose of the study 
drug), and those made known to the Investigator at any time thereafter that are suspected of being 
related to the study drug.  


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The SAE report should provide a detailed description of the SAE and include summaries of 
hospital records and other relevant documents. If a subject died and an autopsy has been 
performed, copies of the autopsy report and death certificate are to be sent to Altor BioScience 
Safety as soon as these become available. Any follow-up data will be detailed in a subsequent SAE 
Report Form and sent to Altor BioScience Drug Safety. Hospital records and other relevant 
documents must be de-identified and the study identifier must be included.  
Where required by local legislation, the Investigator is responsible for informing the IRB or 
independent ethics committee (IEC) of the SAE and providing them with all relevant initial and 
follow-up information about the event. The Investigator must keep copies of all SAE information 
on file including correspondence with Altor BioScience and the IRB/IEC. 
9.7 
 Expedited Reporting of Adverse Events 
For events considered related to the study drug by the Investigator, Altor BioScience Drug Safety 
will determine the expectedness of events suspected of being related to ALT-803 based on the 
Investigational Brochure.  
 
AEs such as disease progression, death related to disease progression (in the absence of serious 
study drug-related events), and serious events due to the relapse of the studied indication will not 
be subject to expedited reporting by the Sponsor to Regulatory Authorities.  
 
Altor BioScience or its authorized representative shall notify (no later than 15 calendar days of 
receipts per regulations) the Investigator of the following information:  
• Any AE suspected of being related to the use of the study drug in this study or in other 
studies that is both serious and unexpected (i.e., SUSAR).  
• Any finding from tests in laboratory animals that suggests a significant risk for human 
subjects, including reports of mutagenicity, teratogenicity, or carcinogenicity.  
Where required by local legislation, the Investigator shall notify his/her IRB/IEC promptly of these 
new serious and unexpected AE(s) or significant risks to subjects.  
 
10 STATISTICS 
10.1 
General Procedures 
Descriptive statistical methods will be used to summarize the data from this study.  Unless 
otherwise stated, the term descriptive statistics refers to the number of subjects, mean, median, 
standard deviation, minimum, and maximum for continuous data, and frequencies and percentages 
for categorical data.  No statistical testing will be performed.   
10.2 
Sample Size 
A total of 16 patients will be enrolled (8 patients in Group A and 8 patients in Group B)   


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10.3 
Populations for Analysis 
The safety population will include subjects who receive at least one dose of ALT-803.  
The evaluable population (for pharmacokinetics) will include all subjects who have received both 
doses of ALT-803 and have no more than one missing PK sample during each study period.    
10.4 
Statistical Methods 
10.4.1 
Demographic and Baseline Characteristics 
Demographic data and baseline characteristics including age, gender, race/ethnicity, screening 
height and weight, and limited medical history will be summarized.  
10.4.2 
Study Drug Exposure 
Exposure to ALT-803 will be summarized. 
10.4.3 
Analysis of Safety 
Safety will be evaluated by vital signs, clinical laboratory tests, the subject diary and adverse 
events. Subjects will be monitored and queried throughout the entire duration of the study for 
Adverse Events (AEs). All adverse events will be graded by using the NCI Common Terminology 
Criteria for Adverse Events version 4.0 (CTCAE v4.03) and will be coded using the Medical 
Dictionary for Regulatory Activities (MedDRA). Adverse events will be summarized by system 
organ class, preferred term, and greatest severity.  Separate summaries for adverse events related 
to study drug, serious adverse events, adverse events leading to discontinuation, and adverse events 
with an outcome of death will be produced.  Separate summaries for vital signs and clinical 
laboratory tests will also be generated.   
10.5 
Interim Analysis 
No interim analysis is currently planned for this study. 


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11 ETHICS AND RESPONSIBILITIES 
11.1 
Good Clinical Practice 
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that the Sponsor, its authorized 
representative(s), and Investigator(s) abide by Good Clinical Practice (GCP), as described in the 
International Conference on Harmonization (ICH) Guideline E6 and in accordance with the 
general ethical principles outlined in the Declaration of Helsinki. The study will receive approval 
from an IRB/IEC prior to commencement. The Investigator will conduct all aspects of this study 
in accordance with applicable national, state, and local laws of the pertinent regulatory authorities. 
11.2 
Investigator Responsibilities 
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in the 
local regulations. Sponsor staff or an authorized representative will evaluate and approve all 
Investigators who in turn will select their staff.  
The Investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, study treatments, as well as study-related duties and functions. 
The Investigator should maintain a list of Sub-Investigators and other appropriately qualified 
persons to whom he or she has delegated significant study-related duties.  
The Investigator is responsible for keeping a record of all subjects who sign an informed consent 
document and are screened for entry into the study. Subjects who fail screening must have the 
reason(s) recorded in the subject’s source documents.  
The Investigator, or a designated member of the Investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to subject records (e.g., 
medical records, office charts, hospital charts, and study-related charts) for source data 
verification. The Investigator must ensure timely and accurate completion of CRFs and queries. 
11.3 
Subject Information and Informed Consent 
The Investigator must obtain written informed consent from the subject or a legal representative 
prior to performing any study-related procedures. Each Investigator has both ethical and legal 
responsibility to ensure that the subjects being considered for inclusion in this study are provided 
a full explanation of the protocol and the roles and responsibilities of the subject for participation 
in the study.  
Documentation that written informed consent was obtained prior to the study subject’s entry into 
the study and of the informed consent process should be recorded in the study subject’s source 
documents, including the date. The original informed consent document signed and dated by the 
study subject and by the person consenting the study subject prior to the study subject’s entry into 
the study must be maintained in the Investigator’s study files and a copy given to the study subject. 
In addition, if a protocol is amended and the amendment(s) impact the content of the informed 
consent, the informed consent document must be revised. Study subjects participating in the study 
when the amended protocol is implemented must be re-consented with the revised version of the 


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informed consent document. The revised informed consent document signed and dated by the 
study subject and by the person consenting the study subject must be maintained in the 
Investigator’s study files and a copy given to the study subject. 
11.4 
Confidentiality 
The Sponsor (Altor BioScience), affirms the subject's right to protection against invasion of 
privacy and to be in compliance with ICH and other local regulations (whichever is most stringent). 
The Sponsor requires the Investigator to permit the Sponsor and/or their designated representatives 
and, when necessary, representatives from regulatory authorities, to review and/or copy any 
medical records relevant to the study in accordance with local laws.  
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed informed consent document, it is the responsibility of the Investigator to obtain 
such permission in writing from the appropriate individual.  
Subjects will be identified only by initials and unique subject numbers in CRFs. 
11.5 
Protocol Amendment 
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Altor BioScience. A protocol change intended to eliminate an apparent immediate 
hazard to subjects may be implemented immediately, provided the IRB/IEC is notified within 5 
days. 
Any permanent change to the protocol must be handled as a protocol amendment. The written 
amendment must be submitted to the IRB/IEC and the Investigator must await approval before 
implementing the changes. Altor BioScience will submit protocol amendments to the appropriate 
regulatory authorities for approval. 
If in the judgment of the IRB/IEC, the Investigator, and/or Altor BioScience, the amendment to 
the protocol substantially changes the study design and/or increases the potential risk to the subject 
and/or has an impact on the subject's involvement as a study participant, the currently approved 
written informed consent form will require similar modification. In such cases, informed consent 
will be renewed for subjects enrolled in the study before continued participation. 
11.6 
Institutional Review Board/Independent Ethics Committee Review and Approval 
The Investigator must obtain IRB/IEC approval for the investigation. Initial IRB/IEC approval, 
and all materials approved by the IRB/IEC for this study, including the subject consent form and 
recruitment materials, must be maintained by the Investigator and made available for inspection.  
The final study protocol, including the final version of the Informed Consent Form, must be 
approved or given a favorable opinion in writing by an IRB or IEC as appropriate. The Investigator 
must submit written approval to Altor BioScience before he or she can enroll any subject into the 
study.  


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The Investigator is responsible for informing the IRB or IEC of any amendment to the protocol in 
accordance with local requirements. In addition, the IRB or IEC must approve all advertising used 
to recruit subjects for the study. The protocol must be re-approved by the IRB or IEC upon receipt 
of amendments and annually, as local regulations require.  
The Investigator is also responsible for providing the IRB or IEC with reports of any reportable 
serious adverse drug reactions from any other study conducted with the investigational product. 
Altor BioScience will provide this information to the Investigator. 
Progress reports and notifications of serious adverse drug reactions will be provided to the IRB or 
IEC according to local regulations and guidelines 
11.7 
Closure of Study 
Altor BioScience reserves the right to terminate this study at any time for reasonable medical or 
administrative reasons. Any premature discontinuation will be appropriately documented 
according to local requirements (e.g., IRB/IEC, regulatory authorities).  
In addition, the Investigator or Altor BioScience has the right to discontinue a single site at any 
time during the study for medical or administrative reasons such as:  
• Unsatisfactory enrollment.  
• GCP noncompliance.  
• Inaccurate or incomplete data collection.  
• Falsification of records.  
• Failure to adhere to the study protocol.  
 


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12 DATA HANDLING AND RECORD KEEPING 
 
12.1 
Data/Documents 
The Investigator must ensure that the records and documents pertaining to the conduct of the study 
and the distribution of the investigational product are complete, accurate, filed, and retained. 
Examples of source documents include hospital records, clinic and office charts, laboratory notes, 
memoranda, subject’s diaries or evaluation checklists, dispensing records, recorded data from 
automated instruments, copies or transcriptions certified after verification as being accurate copies, 
microfiche, X-ray film and reports, and records kept at the pharmacy and the laboratories, as well 
as copies of CRFs or CD-ROM. 
12.2 
Data Capture and Management 
The data for this study is being captured in an electronic data capturing (EDC) system.  Training 
and access will be provided to the study sites prior to subject screening and enrollment. For new 
study personnel requiring access to the EDC, contact Altor BioScience. The Electronic Case 
Report Form (eCRF) Completion Guidelines are provided as a separate document. Study data will 
be collected via the EDC system and will be managed through the use of programmed electronic 
edit checks. Data discrepancies will be brought to the attention of the clinical team and research 
site personnel, if necessary. An audit trail of the resolution of data discrepancies will be maintained 
in the EDC system. 
12.3 
Inspection of Records 
Altor BioScience will be allowed to conduct site visits to the investigation facilities for the purpose 
of monitoring any aspect of the study. The Investigator agrees to allow the monitor to inspect the 
drug storage area, study drug stocks, drug accountability records, subject charts and study source 
documents, and other records relative to study conduct. 
12.4 
Retention of Records 
Essential documents must be retained by the Investigator for a minimum of 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal notification to regulatory authorities of discontinuation of clinical development of the study 
drug; and for a period of at least 3 years after the Sponsor notifies the Investigator that the final 
report has been filed with regulatory authorities. The Investigator must retain these documents for 
the time period described above or according to local laws or requirements, whichever is longer. 
Essential documents include, but are not limited to, the following:  
• Signed informed consent documents for all subjects.  
• Subject identification code list, and the screening and enrollment log (Section 16.8).  
• Record of all communications between the Investigator and the IRB/IEC.  
• Composition of the IRB/IEC.  


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• Record of all communications between the Investigator, Sponsor, and their authorized 
representative(s).  
• List of Sub-Investigators and other appropriately qualified persons to whom the 
Investigator has delegated significant study-related duties, together with their roles in the 
study, curriculum vitae, and their signatures.  
• Copies of CRFs (if paper) and of documentation of corrections for all subjects.  
• Study drug accountability records.  
If it becomes necessary for Altor BioScience or the Regulatory Authority to review any 
documentation relating to the study, the Investigator must permit access to such records.  
 


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13 QUALITY CONTROL AND QUALITY ASSURANCE 
All aspects of the study will be carefully monitored by the Sponsor or its authorized 
representative(s) for compliance with applicable government regulations with respect to current 
GCP and SOPs. 
13.1 
Study Monitoring 
Before the research site can enter a subject into the study, a representative of Altor BioScience 
will:  
• Determine the adequacy of the facilities.  
• Discuss with the Investigator(s) and other personnel their responsibilities with regard to 
protocol adherence and the responsibilities of Altor BioScience or its representatives. This 
will be documented in a Clinical Study Agreement between Altor BioScience and the 
Investigator.  
During the study, a monitor from Altor BioScience or representative will have regular contacts 
with the research site, for the following:  
• Provide information and support to the Investigator(s).  
• Confirm that facilities remain acceptable.  
• Confirm that the research team is adhering to the protocol, data are being accurately 
recorded in the case report forms, and investigational product accountability checks are 
being performed.  
• Perform source data verification. This includes a comparison of the data in the case report 
forms with the subject’s medical records at the hospital or practice and other records 
relevant to the study. This will require direct access to all original records for each subject 
(e.g., clinic charts).  
• Record and report any protocol deviations not previously sent to Altor BioScience 
• Confirm AEs and SAEs have been properly documented on CRFs and confirm any SAEs 
have been forwarded to Altor BioScience and those SAEs that met criteria for reporting 
have been forwarded to the IRB/IEC.  
The monitor will be available between visits if the Investigator(s) or other staff needs information 
or advice. 
13.2 
Deviations 
Deviations are defined as any departure from the IRB-approved protocol and significant non-
compliance with good clinical practices (GCP). Deviations may lead to increased risk to the study 
participant and may jeopardize the study data integrity. All protocol deviations discovered by the 
site must be submitted to Altor within 10 working days for review and approval. Use the Protocol 
Deviation Guidelines to determine the deviation code and classification and submit the Protocol 
Deviation Notification Form (Section 16.7) to Altor BioScience. Altor will notify the site to 
confirm that the deviation is properly coded, classified (Major or Minor) and is approved for entry 


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into the applicable CRF. If a CRA/Monitor discovers a protocol deviation, the CRA/Monitor will 
provide instructions to the site for entry into the applicable CRF.  If the Protocol Deviation is 
determined to be Major, the site should report it to their IRB of record in accordance with the 
IRB’s reporting requirements. The Principal Investigator (PI) will be responsible for the final 
determination of IRB reportability. The following are examples of major protocol deviations: 
▪ Not adhering to inclusion/exclusion criteria for subject eligibility/enrollment 
▪ Missed dose of ALT-803 administration (unless held for safety) 
▪ Failure to report serious adverse events (SAE) 
▪ Failing to obtain informed consent prior to performing any study procedures 
▪ Working under an expired professional license/certification 
▪ Failure to collect immunogenicity sample from all study participants at the site 
Minor protocol deviations should be reported as required to the site’s IRB of record (most minor 
deviations will not require IRB reporting). The following are examples of minor protocol 
deviations: 
▪ The study staff did not collect a sample for a lab test required by the protocol  
▪ Subject failure to return General Health Questionnaires  
▪ Study visit out of timeframe 
▪ Failure to collect immunogenicity sample at one study visit for a subject 
In the event that the Investigator deviates from the protocol in the interest of subject safety, the PI 
should notify the Sponsor within 24 hours of the site’s knowledge of the deviation using the 
Protocol Deviation Notification Form (Section 16.7). All other deviations should be reported to 
the Sponsor within 10 working days.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Protocol Deviation Guidelines 
DEVIATION CODE  
DEVIATION DESCRIPTION 
CLASSIFICATION 
(MAJOR/MINOR) 
IRB 
REPORTABLE 
Verify site 
staff has 
been Re-
educated/        
Re-Trained 
1-INFORMED CONSENT 
Use of an outdated / expired consent 
form (provided the updated information 
does not affect subject safety), or Delay 
in re-consenting the subject using the 
most current ICF version. 
Major 
Reportable 
Y 
Informed consent signed by someone 
other than the individuals authorized to 
signed consent, (e.g. someone other 
than an Investigator or delegated study 
personnel). 
Major 
Reportable 
Y 
Inappropriate 
documentation 
of 
informed consent, including:  
1) 
A missing subject signature 
2) 
Failure to provide a copy to 
the subject signing the form 
3) 
Missing 
date 
on 
either 
subject’s signature or person 
obtaining consent’s signature 
Major 
Reportable 
Y 
Informed consent obtained after 
initiation of any other study specific 
procedures. 
Major 
Reportable 
Y 
Signature of person conducting the 
Informed Consent is missing  
Major 
Reportable 
Y 
Inappropriate 
documentation 
of 
informed consent, including: 
1) 
Someone 
other 
than 
the 
subject dated the ICF 
2) 
Missing initials on one or 
more of the consent pages 
3) 
Mismatched signature dates 
(PI/subject) 
Minor 
Non-reportable 
Y 
2-INCLUSION 
/ 
EXCLUSION CRITERIA 
Enrollment of a subject who did not 
meet all inclusion/exclusion criteria. 
Major 
Reportable 
Y 
Enrollment of a subject who did not 
meet an inclusion/exclusion criteria but 
obtained a successful waiver from the 
Sponsor prior to entry 
Major 
Reportable 
N 
3-SUBJECT DOSING 
Failure to follow Dose Preparation / 
Administration Instructions. 
Major 
Reportable 
Y 
4-ADVERSE EVENT 
Failure to report reportable serious 
adverse event to the IRB and / or 
Sponsor. 
Major 
Reportable 
Y 
Failure of Investigator to gather adverse 
event data from subject. 
Major 
Reportable 
Y 
 
 
 


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DEVIATION CODE  
DEVIATION DESCRIPTION 
CLASSIFICATION 
(MAJOR/MINOR) 
IRB 
REPORTABLE 
Verify site 
staff has been 
Re-educated/  
Re-Trained 
5-DRUG 
ACCOUNTABILITY 
Destruction of IP on site without CRA 
verification  
Minor 
Non-reportable 
Y 
Any documented record of temperature 
of IP being outside the labeled and 
protocol defined temperature range and 
approved for use by Sponsor. 
Any documented record of temperature 
of IP being outside the labeled and 
protocol defined temperature range, not 
approved for used and administered to a 
subject. 
Major 
Reportable 
6-CONCOMITANT 
MEDICATION 
Administration of Prohibited Medication  Major 
Reportable 
Y 
7-VISIT/ ASSESSMENT 
Study assessment / lab test missing or not 
performed at the scheduled visit not 
effecting 
the 
Primary/secondary 
endpoints. 
Minor 
Non-reportable 
Y 
Study assessment / lab test performed out 
of the protocol specified timeframe. 
Minor 
Non-reportable 
Y 
Any missed visits or clinical/laboratory 
assessments as a result of being 
hospitalized or indisposed due to an 
SAE. 
N/A 
NOT A DEVIATION 
8-GCP 
NON-
COMPLIANCE 
Breaches of subject confidentiality. 
Major 
Reportable 
Y 
Site personnel conducting study specific 
procedure 
prior 
to 
having 
task 
appropriately 
delegated 
and 
documented. 
Minor 
Non-reportable 
Y 
Repeated or continued negligence in 
performance of study procedures / Lack 
of Principal Investigator Oversight. 
Major 
Reportable 
Y 
Performance of any study specific 
procedures not approved by the IRB 
Major 
Reportable 
Y 
Failure of Investigator to sign signature 
pages within reasonable timeframe 
following 
protocol/Investigator 
Brochure amendments. 
Minor 
Non-reportable 
Y 
Failure to submit continuing review 
application to the IRB before study 
expiration. 
Minor 
Non-reportable 
Y 
 
 
 
 
 
 


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13.3 
Audits and Inspections 
Authorized representatives of Altor BioScience, a regulatory authority, or an IRB/IEC may visit 
the site to perform audits or inspections, including source data verification. The purpose of an 
Altor BioScience audit or inspection is to systematically and independently examine all study-
related activities and documents to determine whether these activities were conducted, and data 
were recorded, analyzed, and accurately reported according to the protocol, GCP guidelines of the 
ICH, and any applicable regulatory requirements. The Investigator is required to permit direct 
access to the facilities where the study took place, source documents, CRFs, and applicable 
supporting records of study subject participation for audits and inspections by company authorized 
representatives, regulatory authorities, and IRB/IECs. The Investigator should make every effort 
to be available for the audits and/or inspections. The Investigator should contact Altor BioScience 
immediately if contacted by a regulatory agency about an inspection. 
 


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14 STUDY REPORT AND PUBLICATIONS 
Altor BioScience is responsible for preparing and providing the appropriate regulatory authorities 
with clinical study reports according to the applicable regulatory requirements. 
The publication policy of Altor BioScience is discussed in the Investigator's Clinical Research 
Agreement. 
 
  


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15 CONFIDENTIALITY 
All information generated in this study is considered highly confidential and must not be disclosed 
to any person or entity not directly involved with the study unless prior written consent is gained 
from Altor BioScience. However, authorized regulatory officials, IRB/IEC personnel, Altor 
BioScience and its authorized representatives are allowed full access to the records. 
Identification of subjects and CRFs shall be by initials, screening and treatment numbers only. If 
required, the subject's full name may be made known to an authorized regulatory agency or other 
authorized official. 
 


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16 REFERENCES 
 
Bessard A, Solé V, Bouchaud G, Quéméner A, Jacques Y. High antitumor activity of RLI, an 
interleukin-15 (IL-15)-IL-15 receptor alpha fusion protein, in metastatic melanoma and colorectal 
cancer. Mol Cancer Ther. 2009 Sep;8(9):2736-45. 
 
Cheever MA. Twelve immunotherapy drugs that could cure cancers. Immunol Rev. 2008 
Apr;222:357-68. 
 
Han KP, Zhu X, Liu B, Jeng E, Kong L, Yovandich JL, et al. IL-15:IL-15 receptor alpha 
superagonist complex: high-level co-expression in recombinant mammalian cells, purification and 
characterization. Cytokine 2011; 56 (3):804-810. 
 
Mocci G, Marzo M, Papa A, et al. Dermatological adverse reactions during anti-TNF treatments: 
Focus on inflammatory bowel disease. J Crohns Colitis. 2013 Nov;7(10):769-79. doi: 
10.1016/j.crohns.2013.01.009. Epub 2013 Mar 1 
 
Rhode PR, Egan JO, Xu W, Hong H, Webb GM, Chen X, et al. Comparison of the Superagonist 
Complex, ALT-803, to IL15 as Cancer Immunotherapeutics in Animal Models. Cancer Immunol 
Res 2016;4(1):49-60. 
 
Xu W, Jones M, Liu B, Zhu X, Johnson CB, Edwards AC, Kong L, Jeng EK, Han K, Marcus WD, 
Rubinstein MP, Rhode PR, Wong HC. Efficacy and mechanism-of-action of a novel superagonist 
interleukin-15: interleukin-15 receptor αSu/Fc fusion complex in syngeneic murine models of 
multiple myeloma. Cancer Res. 2013 May 15;73(10):3075-86. 
 
Ward A, Anderson M, Craggs RI, Maltby J, Grahames C, Davies RA, Finch D, Pattison D, Oakes 
H, Mallinder PR. E. coli expression and purification of human and cynomolgus IL-15. Protein 
Expr Purif. 2009 Nov;68(1):42-8. 
 
Zhu X, Marcus WD, Xu W, Lee HI, Han K, Egan JO, Yovandich JL, Rhode PR, Wong HC. Novel 
human interleukin-15 agonists. J Immunol. 2009 Sep 15;183(6):3598-607.  
 
Tan, Aaron & Goh, Debbie & Farhatnia, Yasmin & G, Natasha & Lim, Jing & Teoh, Hin & 
Rajadas, Jayakumar & Alavijeh, Mohammad & Seifalian, Alexander. An Anti-CD34 Antibody-
Functionalized Clinical-Grade POSS-PCU Nanocomposite Polymer for Cardiovascular Stent 
Coating Applications: A Preliminary Assessment of Endothelial Progenitor Cell Capture and 
Hemocompatibility. 2013 Oct. PloS one. 8. e77112. 10.1371/journal.pone.0077112. 
 
 
 


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APPENDICES 
16.1 
APPENDIX I – ALT-803 Injection Site Reaction Subject Diary 


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16.2 
APPENDIX II – General Health Questionnaire (RAND SF 36) 
 
 


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16.3 
APPENDIX III –  SAE REPORT FORM AND COVER SHEET 
ALTOR BIOSCIENCE AND NANTBIOSCIENCE, INC. 
SERIOUS ADVERSE EVENT REPORT 
Send the completed form to Email: SAE@altorbioscience.com (an identical copy of email sent to Altor will be 
automatically generated and sent to Nant Safety) 
Reporter Name: 
Report Date (DD/MMM/YYYY): 
Investigator Name: 
Site Name: 
Address: 
Country:  
Telephone: 
Email: 
 Initial Report 
 Follow-up Report #: 
Awareness Date (DD/MMM/YYYY): 
Subject Identifiers and Demographics 
Subject Initials Subject Study ID 
Gender  
 M 
 F 
DOB: 
(DD/MMM/YYYY) 
Weight (kg): 
Height (cm): 
Seriousness (Check all that apply) 
 Insubject hospitalization or prolongation of 
hospitalization 
Date of admission:  
(DD/MMM/YYYY) 
Date of discharge:  
(DD/MMM/YYYY) 
 Results in 
death 
Date of death:  
________ 
(DD/MMM/YYYY): 
Cause of death:  
________ 
Death certificate? 
 No 
 Yes (attach redacted) 
Autopsy? 
 No 
 Yes (attach redacted) 
 Life-Threatening 
 Persistent 
or 
Significant 
Disability/Incapacity 
 Congenital Anomaly/Birth Defect 
 Important Medical Event, explain: 
Event Information 
Adverse Event 
(One entry only for event term) 
SAE Start Date 
(DD/MMM/YYYY) 
SAE Stop Date 
(DD/MMM/YYYY) 
Check if 
Ongoing  
  
SAE Start Time 
(24 hour clock) 
SAE Stop Time 
(24 hour clock) 
 
Severity Grade 
(NCI CTCAE Version 4.03) 
Relationship to ALT-803 
Outcome of Event 
 
Grade 1 Mild 
 
Grade 2 Moderate 
 
Grade 3 Severe 
 
Grade 4 Life-Threatening 
 
Grade 5 Death 
 
 
 
 
Suspected 
 
Not suspected 
 
 
Not 
recovered/Not 
Resolved  
 
Recovered/Resolved 
 
Recovered/Resolved with sequelae 
 
Recovering/Resolving 
 
Fatal 
 
Unknown 


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Site ID: 067 
 
Subject Study ID & Initials:   
 
Study Medication Data 
Date of First Dose 
(DD/MMM/YYYY) 
Date of Last Dose 
prior to SAE 
(DD/MMM/YYYY) 
Dose 
Amount & 
unit 
# of Doses 
Received 
Study Medication 
Lot # 
 
 
 
 
 
ALT-803 
 
Action Taken with Study Medication 
Action taken with ALT-803 due to this 
event: 
 
Dose not changed 
 
Dose interrupted 
 
Drug withdrawn  
 
Dose reduced 
 
Not applicable 
 
Dose Increased 
 
Unknown 
If study medication was stopped or 
interrupted, did the event abate? 
 
No  
 
Yes 
 
N/A 
If study medication was stopped or 
interrupted, did the event reappear 
after reintroduction? 
 
No  
 
Yes 
 
N/A 
If study medication was stopped or 
interrupted, did the event reappear 
after reintroduction? 
 
No  
 
Yes 
 
N/A 
Describe event fully. Include baseline medical status including relevant medical history, signs and symptoms, diagnosis, diagnostic test results, 
clinical course, treatment (all drugs/procedures used as interventions for SAE), outcome, hospital course for hospitalizations, etc. Attach 
relevant de-identified test results and hospital records when submitting this form. Provide rationale for causality assessments. Document other 
potential causes of the event. Complete AE, Medical History, applicable Study Treatment Administration, and Concomitant Medications 
eCRFs as soon as possible. 
 
 
 
Relevant medical hx: 
 
 
Con meds rec’d 2 weeks prior to SAE: 
 
 
Investigator’s Name (print) 
Date 
 (DD/MMM/YYYY) 
 
Investigator’s Signature 
Date 
 (DD/MMM/YYYY) 
 
 
 
 
 


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16.4 
APPENDIX IV – Immune Cells Storage Log 
 
Immune Cells Specimen Storage Log 
(Immune Cell Assays)  
Clinical Protocol CA-ALT-803-03-17 
Subject ID No.: ___________________        Subject Initials: _________ 
# of tubes* 
 
Visit 
 
Time Point 
 
Date of collection 
(dd/mmm/yyyy) 
Time of collection 
(hh:mm;0-23:0-59) 
Processed by 
(initials) 
 
Day 1 
Pre-dose 
 
 
 
 
Day 2 
N/A 
 
 
 
 
Day 3 
N/A 
 
 
 
 
Day 4 
N/A 
 
 
 
 
Day 5 
 N/A 
 
 
 
 
Day 6 
N/A 
 
 
 
 
Day 7 
N/A 
 
 
 
 
Day 9 
N/A 
 
 
 
 
Day 15 
Pre-dose 
 
 
 
 
Day 16 
N/A 
 
 
 
 
Day 17 
N/A 
 
 
 
 
Day 18 
N/A 
 
 
 


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Day 19 
N/A 
 
 
 
 
Day 20 
N/A 
 
 
 
 
Day 21 
N/A 
 
 
 
 
Day 22 
N/A 
 
 
 
 
Day 23 
N/A 
 
 
 
 
Day 29 
N/A 
 
 
 
*Should be 2 aliquots (2 freezer tubes) per time point                     ^Collected the next day. 
Please follow proper documentation guidelines (i.e. corrections should be made by crossing out the 
error with a single line, entering the correct information above the crossed-out data and initialing and 
dating next to it. Also, blank fields should be crossed out with a single line, ‘N/A’ should be entered 
next to or above the line and initial and date next to it.) 
 
Date of Local Pick-Up (dd/mmm/yyyy): _______________ 
Package Prepared By (initials): _______________ 
 
 
 
 
 
 
 
 
 
 


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16.5 
APPENDIX V – PK, Cytokine and Immunogenicity Storage Log 
 
PK, Cytokine and Immunogenicity Specimen Storage Log 
(Samples for PK, Cytokine and Immunogenicity Assays)  
Clinical Protocol CA-ALT-803-03-17 
Subject ID No.: ___________________        Subject Initials: _________ 
# of 
tubes* 
 
Visit 
 
Time Point 
  
Date of collection 
(dd/mmm/yyyy) 
Time of collection 
(hh:mm;0-23:0-59) 
Processed by 
(initials) 
2 
Day 1, 
Baseline, 
Study Period 
1 
Pre-dose 
(+/- 5 min) 
 
 
 
1 
Day 1, Study 
Period 1 
60 min 
(+/- 5 min) 
 
 
 
1 
Day 1, Study 
Period 1 
4hr 
(+/- 15 min) 
 
 
 
2 
Day 2, Study 
Period 1 
24 hr 
(+/- 60 min) 
 
 
 
2 
Day 3, Study 
Period 1 
 48 hr 
(+/- 60 min) 
 
 
 
2 
Day 4, Study 
Period 1 
72 hr 
(+/- 60 min) 
 
 
 
2 
Day 5, Study 
Period 1 
96 hr 
(+/-60 min) 
 
 
 
2 
Day 6, Study 
Period 1 
120 hr 
(+/- 120 min) 
 
 
 
2 
Day 7, Study 
Period 1 
144 hr 
(+/-120 min) 
 
 
 
2 
Day 8, Study 
Period 1 
168 hr 
(+/-120 min) 
 
 
 
2 
Day 9, Study 
Period 1 
192 hr 
(+/-120 min) 
 
 
 


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2 
Day 1, 
Baseline, 
Study Period 
2 
Predose 
(+/- 5 min) 
 
 
 
1 
Day 1, Study 
Period 2 
60 min 
(+/- 5 min) 
 
 
 
1 
Day 1, Study 
Period 2 
4 hr 
(+/- 15 min) 
 
 
 
2 
Day 2, Study 
Period 2 
24 hr 
(+/- 60 min) 
 
 
 
2 
Day 3, Study 
Period 2 
48 hr 
(+/- 60 min) 
 
 
 
2 
Day 4, Study 
Period 2 
72 hr 
(+/- 60 min) 
 
 
 
2 
Day 5, Study 
Period 2 
96 hr 
(+/- 60 min) 
 
 
 
2 
Day 6, Study 
Period 2 
120 hr 
(+/- 120 min) 
 
 
 
2 
Day 7, Study 
Period 2 
144 hr 
(+/- 120 min) 
 
 
 
2 
Day 8, Study 
Period 2 
168 hr 
(+/- 120 min) 
 
 
 
2 
Day 9, Study 
Period 2 
192 hr 
(+/- 120 min) 
 
 
 
1 
End of Study 
Visit 
N/A 
 
 
 
*Should be 2 aliquots (2 freezer tubes) per red top tube collected per time point                      
Please follow proper documentation guidelines (i.e. corrections should be made by crossing out the 
error with a single line, entering the correct information above the crossed-out data and initialing and 
dating next to it. Also, blank fields should be crossed out with a single line, ‘N/A’ should be entered 
next to or above the line and initial and date next to it.) 
 
Date of Local Pick-Up (mm/dd/yyyy): _______________ 
Package Prepared By (initials): _______________ 
 






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16.7 
APPENDIX VII – Protocol Deviation Notification 
 
Subject Study ID 
 
Subject Initials 
 
Site No. 
0 3 1 7 - 
 
 
 
- 
 
 
 
 
 
 
 
 
 
 
PROTOCOL DEVIATION NOTIFICATION 
This notification is completed because a protocol deviation occurred and Sponsor review is 
required prior to taking any further action.  
Deviation Code (check one): 
 1-Informed Consent  
 2-Inclusion/Exclusion Criteria  
 3-Subject Dosing 
 4-Adverse Event        
 5-Drug Accountability               
 6-Concomitant Medication 
 7-Visit/Assessment   
 8-GCP Non-Compliance 
The Protocol Deviation is classified as (check one):  
                                                  
  Major 
                                                  
  Minor 
Please note that final classification is determined by Altor BioScience. 
Protocol Deviation Narrative (explain details of the protocol deviation): 
 
 
 
 
 
 
Instructions: 
Complete this form and send to: mstone@altorbioscience.com or Fax: (954) 443-8610 and wait 
for further instructions. 
 
                                     
 
 
 
 
 


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16.8 
APPENDIX VIII – Screening and Enrollment Log 
Principal Investigator Name: 
Site ID: 067 
Screening 
Enrollment 
Date 
Screened 
(dd/mmm/yyyy) Screening ID  
Current 
Status 
PT 
Initials 
Protocol 
Version ICF Version Date ICF Signed 
(dd/mmm/yyyy) 
Reason(s) for Screen Failure 
(E1 to E4) 
Subject Study ID 
Date of First Dose 
(dd/mmm/yyyy) 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Current status codes:  1-Recruit pending    2-Recruit failed    3-Screening pending    4-Screening failed    5-Enrolled 
         Instructions: Send the Screening and Enrollment Log when requested to: mstone@altorbioscience.com or Fax: (954) 443-8610 
 


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16.9 
APPENDIX IX – Notification of Enrollment and Dosing 
 
Subject Screening ID 
 
Subject Initials 
 
Site No. 
S 0 3 1 7  
 
 
- 
 
 
 
 
 
 
 
 
 
NOTIFICATION OF ENROLLMENT & DOSING 
Date of First Dose:  
Subject Study ID: 
Group (circle one):             Group A                 Group B 
The Investigator approved the subject for enrollment on __ __ / __ __ __ / __ __ __ __ 
 
                                                                       (DD / MMM / YYYY)                         
                                                                                                                                                      Date of enrollment approval 
 
 
            Instructions: 
• 
Complete this form after the subject is enrolled and the first dose is administered.  
• 
Send no later than 2 days after first dose administration to: mstone@altorbioscience.com or  
Fax: (954) 443-8610 
 
 
 
 
 
 
 
 
 
Completed by:  
 
 
 
 
Name 
Signature                  
Date 
Notification Form Version 1.0 Date 06/07/2017                   Confidential                                                                               Page 1 of 1 
 


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16.10 APPENDIX X – Study Medication Inventory/Tracking Form (SMIT) 
Study Medication Inventory/Tracking Form (SMIT) 
 
Protocol #: CA-ALT-803-03-17 
 
 
    Study Medication Name: ALT-803           
Site Name: ______________________________            Site #: ________________ 
 
Total No. 
of  
Vials @ 
No. of 
Vials 
Used $ 
Lot No. 
Conc. 
(mg/mL) 
Date * 
Pick-up 
Prepared 
by (initials) 
Date * 
Received 
Received by  
(initials) 
Date * 
Dispensed 
Dispensed by 
(initials) 
Subject 
Study ID No. 
Dose  
(ug) 
Date * 
Returned 
Returned by 
(initials) 
Returned 
To 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.11 APPENDIX XI – Study Medication Shipping Notice/ Receipt Form (SMSNR) 
ALTOR BIOSCIENCE  
Study Medication Notice/Receipt Form (SMSNR) 
Form: CA-607-F3, Page 1 of 1 
SENDER SECTION 
Protocol #: ___________________________________ Name of study medication: __________________ 
Principal Investigator: ___________________________________________ Site #: __________________ 
Type of temperature monitor:   color-indicators       TempTale S/N: _______________________ (circle one) 
Study Medication Lot Number 
Number of vials 
Delivered by: ___________________________________ (sign & print) Date delivered: _______________ 
RECIPIENT & RETURN SECTION 
Please complete & sign this section as soon as you open the contents of the package. 
TempTale: Press and hold the STOP BUTTON for 3 seconds until the “Stop sign” icon appears in the 
upper right corner of the display. Notate the time turned off and if an alarm symbol is visible below: 
Digital recorder description 
Circle alarm status 
TempTale monitor (Time TURNED OFF: ____________) Alarm symbol:    yes      no   (if yes, call Altor immediately) 
The contents agree with the information stated in the Sender Section. 
 
 Yes _____  No _____ 
All the study medication vials are intact and have no noticeable damage.  
 Yes _____  No _____ 
After observing the contents of all vials, the study medication is not frozen. 
 Yes _____  No _____ 
If the answer to any of the above questions is No, please notify Altor immediately at (954) 443-8600 
Extension ________ or ________ for further instructions.  Otherwise, sign and date below: 
Package opened and inspected by: _______________________________________________(sign & print) 
Date opened: ________________________________ Time opened: _______________ am/pm (circle one) 
Email this form immediately to MikeFenn@altorbioscience.com  and cc mstone@altorbioscience.com 
or fax to: (954) 443-8610  Attn: Mike Fenn 
Return the TempTale  to Altor designee 
DO NOT USE THE STUDY MEDICATION UNTIL RECEIVING ALTOR’S NOTIFICATION 
FOR ALTOR USE ONLY  
Was the same temperature monitor returned (i.e. TempTale)?   Yes ______  No ______ N/A ______ 
Temperature conditions met the requirements and the study medication vials are acceptable for clinical 
use. 
_________________________________________________(sign & print)  Date: ___________________ 


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16.12 APPENDIX XII – Study Medication Shipping Requisition Form (SMSR) 
Protocol #:  CA-ALT-803-03-17 
Site Name: ______________________________________ Site #: ____________ 
ALT-803 (please select one): 
2 mL vial containing 1.2 mL 
of 
ALT-803 
at 
a 
concentration of 1.0 mg/mL 
2 mL vial containing 0.6 mL 
at a concentration of 2.0 
mg/mL 
Number of 
Vials 
Reason for Request 
Requested By:  _______________________________ (sign & print)  Date: _________ 
Date Study Medication Needed By (dd/mmm/yyyy): ____________________________ 
E-mail this form to:
MikeFenn@altorbioscience.com and cc mstone@altorbioscience.com
or Fax to: (954) 443-8610 Attn: Mike Fenn


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16.13 APPENDIX XIII – Study Treatment Preparation Worksheet 
ALT-803 Study Treatment Preparation Worksheet (Page 1 of 2) 
Subject Study ID:  
Subject Initials:  
Subject Weight prior to 1st dose:               kg 
Treatment Preparation Date: 
ALT-803 Lot No.:  
ALT-803 Concentration:  
No. of ALT-803 Vials Used (for this weight): 
ALT-803 Dose Level (circle one please):  
10 µg/kg           20 µg/kg 
Documentation: 
For each subject, complete this form for the first study dose. The Study Coordinator will provide the subject 
information to complete the top of the form. ALT-803 dosing will be calculated using a weight obtained 
within 5 days prior to the first dose. The dose will be re-calculated at the beginning of each subsequent 
cycle in the event of a 10% or greater weight change, complete a new form for each instance this occurs.  
Each vial of ALT-803 will either contain 1.2 mL of study drug at 1 mg/mL (1000 µg/mL) or will contain 
0.6 mL of study drug at 2 mg/mL (2000 µg/mL). Refer to the vial label to confirm the correct lot no. and 
concentration. 
 
A. ALT-803 treatment preparation for 1 mg/mL concentration vials  
1. Use the following instructions to prepare each study medication dose using 1 mg/mL concentration 
vials (Skip to Section B if 2 mg/mL concentration vials are used): 
1. Calculate the ALT-803 dose volume (mL) as follows:  
= [20 µg/kg (ALT-803 Dose level)  X  _____________  kg]    1000 µg/mL                                                                  
                                                              Subject weight  
Note: multiple vials may need to be used for each dose.  
2. Once subject is confirmed to meet dosing eligibility, withdraw the ALT-803 dose volume 
from the study drug vial(s) directly into a syringe(s) for subcutaneous injection.  
3. Label the syringe(s) at minimum with the Subject Initials and Study ID No. (or other 
applicable subject identifying information), and Date Prepared. 
4. Distribute for subject treatment. 
5. Skip to Section C to complete this form. 
 
B. ALT-803 treatment preparation for 2 mg/mL concentration vials  
2. Use the following instructions to prepare each study medication dose using 2 mg/mL concentration 
vials. ALT-803 will be diluted (1:1 dilution) to a concentration of 1 mg/mL after confirming the volume 
needed. 
1. Calculate the ALT-803 dose volume (mL) at 1 mg/mL as follows:  
= [20 µg/kg (ALT-803 Dose level)  X  _____________  kg]    1000 µg/mL                                                                  
                                                              Subject weight  
 
 
 


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ALT-803 Study Treatment Preparation Worksheet (Page 2 of 2) 
Note: multiple vials may need to be used for each dose.  
 
2. Once subject is confirmed to meet dosing eligibility, add saline using a 1:1 dilution (0.6 mL) to the 
study drug vial or to multiple vials depending on the ALT-803 dose volume required per step 1 
above.  
3. Withdraw the ALT-803 dose volume from the study drug vial(s) after dilution directly into a 
syringe(s) for subcutaneous injection.  
4. Label the syringe(s) at minimum with the Subject Initials and Study ID No. (or other applicable 
subject identifying information), and Date Prepared. 
5. Distribute for subject treatment. 
6. Proceed to Section C to complete this form. 
  
C. Signature and record keeping 
1. Record the No. of ALT-803 Vials Used (for this particular weight) at the top of this form. 
2. Sign and date at the bottom of this page and file in the pharmacy binder along with the updated 
SMIT Form (or equivalent accountability log).  These documents will be inspected and copies will 
be reviewed during on-site monitoring visits or will be requested for off-site review via fax or 
email. 
3. Used vials can be disposed of according to standard site guidelines. Maintain disposal/destruction 
records for inspection by Altor or Altor representative to review at a later time. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
      Pharmacist (or designee) signature: ___________________________  Date: ___________ 
Please follow proper documentation guidelines (i.e. corrections should be made by crossing out the error with a single line, 
entering the correct information above the crossed-out data and initialing and dating next to it. Also, blank fields should be 
crossed out with a single line, ‘N/A’ should be entered next to or above the line and initial and date next to it.) 


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16.14 APPENDIX XIV – Temperature Excursion Form 
 
Protocol #:  CA-ALT-803-03-17                                    Date of Report:  
 
Principal Investigator: _______________________________       Site #:  
 
Investigational Product: ___________________         Lot Number(s):  
 
Was a subject dosed with the 
affected medication?  
 
 Yes      
 No 
If Yes: 
 
Subject Study ID:  
 
Subject Initials:  
 
Number of doses: 
 
Additional Information: 
 
 
 
 
 
Information on excursion (please include temperature logs with the report) 
Excursion Location (e.g. refrigerator ID): 
 
What was the known duration of the excursion: 
 
What was product’s minimum temperature: 
 
What was product’s maximum temperature: 
 
Cause of Excursion: 
 
Corrective Action Taken: 
 
 
 
Completed by:  
 
 
 
 
 
Printed Name 
Signature                  
Date 
 
 
Temperature Excursion Assessment (For Altor BioScience Use Only) 
 
 Investigational Product is acceptable for use 
 
 Investigational Product is not acceptable for use (Altor will provide a replacement and will 
provide further instructions for the quarantined vials) 
Completed by:   
 
 
 
 
(sign & print) Date:  
 
 
 
QA Reviewed/Approved:  
 
 
 
 
(sign & print) Date:  
 
 
 
Clinical Reviewed/Approved:   
 
 
 
(sign & print) Date:  
 
 
 


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16.15 APPENDIX XV – Names of Study Personnel 
 
Sponsor: 
Altor BioScience  
2810 North Commerce Parkway 
Miramar, Florida 33025 
954-443-8600 
 
Medical Monitor: 
John Wrangle, MD, MPH 
173 Ashley Ave, BSB suite 102 
Charleston, SC 29425 
Phone: 843-792-4271 
FAX: 843-792-0644 
Wrangle@musc.edu 
 
Sponsor Study 
Project Manager: 
 
 
 
 
 
Monica Stone, MD, MSc. 
Altor BioScience  
2810 North Commerce Parkway 
Miramar, Florida 33025 
954-443-8600 
mstone@altorbioscience.com 
 
Sponsor Contact 
(budgets): 
Monica Jones 
Director, Regulatory Affairs & Quality Assurance  
Altor BioScience  
2810 North Commerce Parkway 
Miramar, Florida 33025 
954-443-8600 
monicajones@altorbioscience.com 
 
Sponsor Contact 
(Supplies):                        
Mike Fenn  
Clinical Operations Specialist II 
Altor BioScience 
(954) 443-8600 ext. 838 
mikefenn@altorbioscience.com 
 
 
 
 
 


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16.16 APPENDIX XVI – Declaration of Helsinki 
WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI 
 
Ethical Principles 
for 
Medical Research Involving Human Subjects 
 
Adopted by the 18th WMA General Assembly 
Helsinki, Finland, June 1964 
and amended by the 
29th WMA General Assembly, Tokyo, Japan, October 1975 
35th WMA General Assembly, Venice, Italy, October 1983 
41st WMA General Assembly, Hong Kong, September 1989 
48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996 
and the 
52nd WMA General Assembly, Edinburgh, Scotland, October 2000 
 
A. 
INTRODUCTION 
The World Medical Association has developed the Declaration of Helsinki as a statement of ethical 
principles to provide guidance to physicians and other participants in medical research involving 
human subjects. Medical research involving human subjects includes research on identifiable 
human material or identifiable data. 
It is the duty of the physician to promote and safeguard the health of the people. The physician’s 
knowledge and conscience are dedicated to the fulfillment of this duty. 
The Declaration of Geneva of the World Medical Association binds the physician with the words, 
"The health of my subject will be my first consideration," and the International Code of Medical 
Ethics declares that, "A physician shall act only in the subject's interest when providing medical 
care which might have the effect of weakening the physical and mental condition of the subject." 


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Medical progress is based on research, which ultimately must rest in part on experimentation 
involving human subjects. 
In medical research on human subjects, considerations related to the wellbeing of the human 
subject should take precedence over the interests of science and society. 
The primary purpose of medical research involving human subjects is to improve prophylactic, 
diagnostic and therapeutic procedures and the understanding of the etiology and pathogenesis of 
disease. Even the best-proven prophylactic, diagnostic, and therapeutic methods must 
continuously be challenged through research for their effectiveness, efficiency, accessibility and 
quality. 
In current medical practice and in medical research, most prophylactic, diagnostic and therapeutic 
procedures involve risks and burdens. 
Medical research is subject to ethical standards that promote respect for all human beings and 
protect their health and rights. Some research populations are vulnerable and need special 
protection. The particular needs of the economically and medically disadvantaged must be 
recognized. Special attention is also required for those who cannot give or refuse consent for 
themselves, for those who may be subject to giving consent under duress, for those who will not 
benefit personally from the research and for those for whom the research is combined with care. 
Research Investigators should be aware of the ethical, legal and regulatory requirements for 
research on human subjects in their own countries as well as applicable international requirements. 
No national ethical, legal or regulatory requirement should be allowed to reduce or eliminate any 
of the protections for human subjects set forth in this Declaration. 
 
B. 
BASIC PRINCIPLES FOR ALL MEDICAL RESEARCH 
It is the duty of the physician in medical research to protect the life, health, privacy, and dignity of 
the human subject. 
Medical research involving human subjects must conform to generally accepted scientific 
principles, be based on a thorough knowledge of the scientific literature, other relevant sources of 
information, and on adequate laboratory and, where appropriate, animal experimentation. 
Appropriate caution must be exercised in the conduct of research, which may affect the 
environment, and the welfare of animals used for research must be respected. 
The design and performance of each experimental procedure involving human subjects should be 
clearly formulated in an experimental protocol. This protocol should be submitted for 
consideration, comment, guidance, and where appropriate, approval to a specially appointed 
ethical review committee, which must be independent of the Investigator, the Sponsor or any other 
kind of undue influence. This independent committee should be in conformity with the laws and 
regulations of the country in which the research experiment is performed. The committee has the 
right to monitor ongoing trials. The researcher has the obligation to provide monitoring 


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information to the committee, especially any SAEs. The researcher should also submit to the 
committee, for review, information regarding funding, Sponsors, institutional affiliations, other 
potential conflicts of interest and incentives for subjects. 
The research protocol should always contain a statement of the ethical considerations involved and 
should indicate that there is compliance with the principles enunciated in this Declaration.  
Medical research involving human subjects should be conducted only by scientifically qualified 
persons and under the supervision of a clinically competent medical person. The responsibility for 
the human subject must always rest with a subject of the research, even though the subject has 
given consent. 
Every medical research project involving human subjects should be preceded by careful 
assessment of predictable risks and burdens in comparison with foreseeable benefits to the subject 
or to others. This does not preclude the participation of healthy volunteers in medical research. 
The design of all studies should be publicly available. 
Physicians should abstain from engaging in research projects involving human subjects unless they 
are confident that the risks involved have been adequately assessed and can be satisfactorily 
managed. Physicians should cease any investigation if the risks are found to outweigh the potential 
benefits or if there is conclusive proof of positive and beneficial results. 
Medical research involving human subjects should only be conducted if the importance of the 
objective outweighs the inherent risks and burdens to the subject. This is especially important 
when the human subjects are healthy volunteers. 
Medical research is only justified if there is a reasonable likelihood that the populations in which 
the research is carried out stand to benefit from the results of the research. 
The subjects must be volunteers and informed participants in the research project. 
The right of research subjects to safeguard their integrity must always be respected. Every 
precaution should be taken to respect the privacy of the subject, the confidentiality of the subject’s 
information and to minimize the impact of the study on the subject's physical and mental integrity 
and on the personality of the subject. 
In any research on human beings, each potential subject must be adequately informed of the aims, 
methods, sources of funding, any possible conflicts of interest, institutional affiliations of the 
researcher, the anticipated benefits and potential risks of the study and the discomfort it may entail. 
The subject should be informed of the right to abstain from participation in the study or to withdraw 
consent to participate at any time without reprisal. After ensuring that the subject has understood 
the information, the physician should then obtain the subject's freely-given informed consent, 
preferably in writing. If the consent cannot be obtained in writing, the non-written consent must 
be formally documented and witnessed. 
When obtaining informed consent for the research project the physician should be particularly 
cautious if the subject is in a dependent relationship with the physician or may consent under 


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duress. In that case the informed consent should be obtained by a well-informed physician who is 
not engaged in the investigation and who is completely independent of this relationship. 
For a research subject who is legally incompetent, physically or mentally incapable of giving 
consent or is a legally incompetent minor, the Investigator must obtain informed consent from the 
legally authorized representative in accordance with applicable law. These groups should not be 
included in research unless the research is necessary to promote the health of the population 
represented and this research cannot instead be performed on legally competent persons. 
When a subject deemed legally incompetent, such as a minor child, is able to give assent to 
decisions about participation in research, the Investigator must obtain that assent in addition to the 
consent of the legally authorized representative. 
Research on individuals from whom it is not possible to obtain consent, including proxy or advance 
consent, should be done only if the physical/mental condition that prevents obtaining informed 
consent is a necessary characteristic of the research population. The specific reasons for involving 
research subjects with a condition that renders them unable to give informed consent should be 
stated in the experimental protocol for consideration and approval of the review committee. The 
protocol should state that consent to remain in the research should be obtained as soon as possible 
from the individual or a legally authorized surrogate. 
Both authors and publishers have ethical obligations. In publication of the results of research, the 
Investigators are obliged to preserve the accuracy of the results. Negative as well as positive results 
should be published or otherwise publicly available. Sources of funding, institutional affiliations 
and any possible conflicts of interest should be declared in the publication. Reports of 
experimentation not in accordance with the principles laid down in this Declaration should not be 
accepted for publication. 
 
C. 
ADDITIONAL PRINCIPLES FOR MEDICAL RESEARCH COMBINED WITH 
MEDICAL CARE 
The physician may combine medical research with medical care, only to the extent that the research 
is justified by its potential prophylactic, diagnostic or therapeutic value. When medical research is 
combined with medical care, additional standards apply to protect the subjects who are research 
subjects. 
The benefits, risks, burdens and effectiveness of a new method should be tested against those of 
the best current prophylactic, diagnostic, and therapeutic methods. This does not exclude the use 
of placebo, or no treatment, in studies where no proven prophylactic, diagnostic or therapeutic 
method exists. 
At the conclusion of the study, every subject entered into the study should be assured of access to 
the best-proven prophylactic, diagnostic and therapeutic methods identified by the study. 


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The physician should fully inform the subject which aspects of the care are related to the research. 
The refusal of a subject to participate in a study must never interfere with the subject-physician 
relationship. 
In the treatment of a subject, where proven prophylactic, diagnostic and therapeutic methods do 
not exist or have been ineffective, the physician, with informed consent from the subject, must be 
free to use unproven or new prophylactic, diagnostic and therapeutic measures, if in the physician’s 
judgment it offers hope of saving life, re-establishing health or alleviating suffering. Where 
possible, these measures should be made the object of research, designed to evaluate their safety 
and efficacy. In all cases, new information should be recorded and, where appropriate, published. 
The other relevant guidelines of this Declaration should be followed. 
 

SAP_001.pdf: 
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QUILT-1.004 (CA-ALT-803-03-17) Statistical Analysis Plan                                 Final - Page 1 of 19 
 
 
 
 
 
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Altor BioScience 
 
 
Protocol QUILT-1.004 (CA-ALT-803-03-17) 
 
 
A Single Center, Open-label, Pharmacokinetic Study of 
Subcutaneous ALT-803 
 
 
 
Statistical Analysis Plan 
 
 
 
Final 
 
 
 
Version 3.0 
 
 
March 12, 2019 
 
 
 
 
 
 
 
 
 
 






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TABLE OF CONTENTS 
 
1. INTRODUCTION ..................................................................................................................... 7 
2. STUDY OBJECTIVES ............................................................................................................ 7 
3. STUDY OVERVIEW ................................................................................................................ 7 
3.1 Study Design .................................................................................................................... 7 
3.2 Number of Study Sites ................................................................................................... 9 
3.3 Number of Subjects ........................................................................................................ 9 
3.4 Duration of Treatment .................................................................................................... 9 
3.5 Randomization and Blinding ........................................................................................ 9 
4. STUDY ENDPOINTS .............................................................................................................. 9 
4.1 Primary Endpoints .......................................................................................................... 9 
4.2 Secondary Endpoint ..................................................................................................... 10 
4.3 Measures of Interest ..................................................................................................... 10 
5. SAMPLE SIZE ....................................................................................................................... 10 
6. ANALYSIS POPULATIONS ................................................................................................ 10 
7. STATISTICAL METHODOLOGY ....................................................................................... 10 
7.1 Analysis Conventions .................................................................................................. 10 
7.2 Interim Analysis ............................................................................................................. 12 
7.3 Subject Disposition....................................................................................................... 12 
7.4 Demographics and Baseline Characteristics ........................................................ 12 
7.5 Medical History .............................................................................................................. 12 
7.6 Prior and Concomitant Medication ........................................................................... 12 
7.7 Safety Analyses ............................................................................................................. 12 
7.7.1 Study Drug Exposure ................................................................................................ 12 
7.7.2 Adverse Events .......................................................................................................... 13 
7.7.3 Laboratory Assessments ......................................................................................... 14 
7.7.4 Vital Signs and Physical Examinations ............................................................... 14 
7.7.5 Injection Site Reaction .............................................................................................. 14 
7.7.6 General Health Questionnaire ................................................................................ 15 
7.8 IMMUNOGENICITY (Anti-Drug Antibody) METHODOLOGY ............................... 17 


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7.9 Deviations from Statistical Analyses Planned in Protocol ................................ 17 
8. REFERENCES ....................................................................................................................... 18 
9. SCHEDULE OF ASSESSMENTS ...................................................................................... 19 


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GLOSSARY OF ABBREVIATIONS 
 
 
Abbreviation 
Definition 
AE 
Adverse Event 
ATC 
Anatomical Therapeutic Chemical 
AUC0-inf 
Area under the plasma concentration curve from time 0 
extrapolated to infinite time  
AUC0-t 
Area under the plasma concentration curve from time 0 
through the last measurable concentration  
CBC 
Complete Blood Count 
CI 
Confidence Interval 
CL/F 
Apparent (extravascular) clearance  
Cmax 
Maximum observed concentration  
CMP 
Complete Metabolic Panel 
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Event 
ECG 
Electrocardiogram 
IL 
Interleukin 
MedDRA 
Medical Dictionary for Regulatory Activities 
PK 
pharmacokinetics 
PT 
Preferred Term 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous 
SOC 
System Organ Class  
SRC 
Safety Review Committee 
subQ 
Subcutaneous 
TEAE 
Treatment-Emergent Adverse Event 
Tmax 
Time of the observed maximum concentration  
t½ 
Half-life  
Vz/F 
Apparent (extravascular) volume of distribution  




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Blood samples to determine serum levels of ALT-803 will be collected prior to dosing, 
and at 1, 4, 24, 48, 72, 96, 120, 144, 168 and 192 hours after dosing.  
Vital signs (heart rate, blood pressure, respiration, temperature) will be monitored. 
Safety will be assessed for all subjects and will include monitoring of vital signs, and 
incidence and severity of adverse events. Blood samples will be collected for 
hematology and chemistry, immune cell levels and activity, immune cell phenotype 
subsets, cytokine levels, and immunogenicity testing, which include assays for anti-
ALT-803 antibodies.  
After the completion of study period 2, subjects will be followed for additional 6 days 
and will have an End of Study visit on Day 15 which will include safety labs, immune 
cells, and cytokines. 
Concomitant medications and adverse events will be collected throughout the study. 
Figure 1: Study Schema 
 
 
 
 


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3.2 Number of Study Sites 
This study will be conducted at a single study site in US. 
3.3 Number of Subjects 
The study population consists of healthy male and female volunteers, aged 18 - 65 
years. A total of 16 evaluable subjects will be enrolled (8 in Group A and 8 in Group 
B).  
Any subject who meets the following criteria will be replaced: 
 Subjects who are enrolled but do not receive ALT-803 
 Subjects who withdraw consent 
 Subjects who have a positive alcohol or drug test after enrollment 
 Subjects who miss more than one PK collection timepoint during study period 1 
or study period 2 will be replaced. 
3.4 Duration of Treatment 
This study will consist of two study periods (9 days each) and a rest period (> 6 days). 
Subjects will receive a single 10 µg/kg subQ dose of ALT-803 on Day 1 of study 
period 1. After a rest period, subjects will receive a single 20 µg/kg subQ dose of ALT-
803 on Day 1 of study period 2. In both study periods 1 and 2, blood sampling for PK 
and safety labs will commence on Day 1 and continue daily throughout the 9-day 
study period. After the completion of study period 2, subjects will be followed for 
additional 6 days and will have an End of Study visit on Day 15. 
Subjects who are replaced will be followed for up to 14 days, following their last dose 
of ALT-803 for adverse events monitoring only. 
3.5 Randomization and Blinding  
Subjects meeting the entry criteria will be randomized in a 1:1 ratio (Groups A or B) to 
one of two ALT-803 drug concentrations.  
This is an open-label study, so blinding is not applicable.  
4. STUDY ENDPOINTS  
4.1 Primary Endpoints 
Serum concentration will be used to calculate the following PK parameters:  
 half-life (t½) 


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 apparent (extravascular) volume of distribution (Vz/F) 
 apparent (extravascular) clearance (CL/F) 
 maximum observed concentration (Cmax) 
 time of the observed maximum concentration (Tmax) 
 area under the plasma concentration curve from time 0 through the last 
measurable concentration (AUC0-t) 
 area under the plasma concentration curve from time 0 extrapolated to infinite 
time (AUC0-inf) 
4.2 Secondary Endpoint  
 Safety, as assessed by the incidence and severity of adverse events.  
4.3 Measures of Interest 
 Blood samples will be collected for immune cell levels and activity, immune cell 
phenotype subsets, cytokine levels and immunogenicity testing, which include 
assays for anti-ALT-803 antibodies.  
 General health as assessed by the RAND General Health Questionnaire (SF-
36). 
5. SAMPLE SIZE 
A total of 16 patients will be enrolled (8 patients in Group A and 8 patients in Group B). 
6. ANALYSIS POPULATIONS 
Safety population: Safety population will include all enrolled subjects who received at 
least one dose of ALT-803. 
Study results will be presented for each study group as well as all subjects combined. 
7. STATISTICAL METHODOLOGY 
7.1 Analysis Conventions 
This section details general analysis conventions to be used for the statistical 
analyses. Departures from these general conventions may be given in the specific 
detailed sections of the SAP. 


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 Statistical analyses will be descriptive in nature. Descriptive statistics will 
consist of the number and percentage of subjects in each category for discrete 
variables, and the sample size, mean, median, S.D., minimum, and maximum 
for continuous variables; 
 All mean and median values will be formatted to one more decimal place than 
the measured value. Standard deviation values will be formatted to two more 
decimal places than the measured value; 
 All percentages will be rounded to whole numbers. The number and 
percentage of responses will be presented in the form XX (XX%), where the 
percentage is in the parentheses; 
 Confidence intervals (CIs) will be presented as 2-sided 95% CIs; 
 All listings will be sorted for presentation in order of treatment cohort, study site, 
subject, and date of procedure or event; 
 All analysis and summary tables will have the analysis population sample size 
(i.e., number of subjects); 
 When necessary for analysis purposes, an adverse event or medication start or 
stop dates without a specific day of the month given (i.e., JAN1999) will be 
assigned the 15th day of the month and dates without a specific day or month 
(i.e., 1999) will be assigned the 30th day of June to complete the date. If the 
incomplete date is a start date and the above imputation inappropriately results 
in a date on or before the first dose date, then the incomplete date will be 
assigned to the day following the first dose date. If either imputation results in 
an imputed start date after the stop date, then the start date will be set to the 
day prior to the stop date; 
 The day of the first dose of any study drug will be defined as Day 1; 
 Baseline value will be defined as the last value before the first dose of any 
study drug is administered; 
 Final Evaluation will be defined as the last on-treatment value;  
 MedDRA version 19.1 will be used for adverse events coding and Health 
Organization (WHO) drug dictionary version DEC2016 for medications coding; 
and  
 SAS® Version 9.4 (or later) will be used to analyze the clinical data and 
generate summary tables, listings, and figures. 


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7.2 Interim Analysis 
No interim analysis is planned for the study.  
7.3 Subject Disposition  
Subject disposition will be summarized by the number and percentage of the subjects 
enrolled, in the Safety population, who discontinued the study prematurely, and the 
reasons for premature discontinuation. 
Subject disposition, entry criteria violations, and subjects excluded from Safety 
population will be presented in a data listing.  
7.4 Demographics and Baseline Characteristics 
Summary statistics will be calculated for age, sex, ethnicity, race, height, and baseline 
body weight. Age is defined as the time from the subject’s date of birth to date of 
informed consent in years. 
7.5 Medical History 
Medical history will be collected at screening and includes any relevant medical 
history findings which will be coded using MedDRA and classified by System Organ 
Class (SOC) and Preferred Term (PT). Coded medical history data will be 
summarized.  
7.6 Prior and Concomitant Medication 
The name, route of administration, duration of use, dose, unit, frequency, and 
indication for all prior and concomitant medications taken from screening through 
study termination will be collected. Prior and concomitant medications will be coded to 
therapeutic drug classes and generic drug names using the WHO drug dictionary. 
A prior medication will be defined as any medication taken prior to the date and time 
of the first dose of ALT-803. A concomitant medication will be defined as any 
medication started on or after the first dose of ALT-803. Concomitant medications will 
be summarized by ATC level and preferred term. All available date information will be 
used in order to determine if a medication is concomitant. In the event of completely 
missing date information, the medication will be assumed concomitant. 
7.7 Safety Analyses  
7.7.1 Study Drug Exposure 
Study drug exposure will be summarized as follows: 
 Number and percentage of subjects who received doses in both study periods 
1 and 2; 


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 Number and percentage of subjects who did not receive a dose in study period 
1 and the reason(s) for that; 
 Number and percentage of subjects who did not receive a dose in study period 
2  and the reason(s) for that;  
 Summary statistics for the dose received and percentage of protocol dose in 
each study period. Percentage of protocol dose will be calculated as the dose 
received divided by the protocol dose (i.e., prescribed dose) x 100%. 
7.7.2 Adverse Events  
Several summary tables will be presented for the incidence of treatment-emergent 
adverse events (TEAEs). TEAEs will be defined as any AE that begins or worsens in 
grade after the start of study drug until 30 days after the last dose of study drug or End 
of Study, whichever is later. 
Summary tables will be tabulated alphabetically by SOC and PT based on the 
MedDRA version 19.1 coding dictionary. If a subject experiences multiple episodes of 
the same AE, the subject only will be counted once for that particular AE.  
The following TEAE tables will be presented: 
 All TEAEs, 
 Grade 3 or higher TEAEs, 
 Treatment-related TEAEs, 
 Treatment-related grade 3 or higher TEAEs, 
 Serious AEs, 
 Treatment-related SAEs, 
 TEAEs leading to discontinuation of study drug, and 
 TEAEs leading to death. 
Any AE with a missing onset date will be considered as treatment-emergent unless 
there is a non-missing end date information (i.e., month or year) that indicates it 
resolved prior to administration of study drug. 
If a subject experiences multiple episodes of the same event, the event with the 
maximum severity or strongest relationship to study medication will be used for 
analysis.  Missing severity or relationship will be presented as “Severe” or 
“Suspected”, respectively. 
SAEs, deaths, and AEs leading to discontinuation of study drug will be presented in 
data listings. Any non-TEAEs will be presented in the data listings and indicated as 
non-TEAE. 


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7.7.3 Laboratory Assessments 
The hematology including complete blood count (CBC) with differential and blood 
chemistry (Complete Metabolic Panel [CMP]) will be evaluated at baseline and 
through 2 study periods. 
Laboratory data will be summarized at baseline and as change from baseline at each 
post-baseline visit for all laboratory tests. 
7.7.4 Vital Signs and Physical Examinations  
Vital signs (heart rate, blood pressure, respiratory rate, body temperature) will be 
collected at screening and at study visits per Schedule of Assessments as described 
in Section 4.3 of the study protocol. Vital signs will be performed prior to, and one hour 
post-ALT-803 subQ injection. On PK sample collection days, vital signs are to be 
collected prior to blood draw. Height will be measured at screening and body weight 
will be noted before each ALT-803 subQ injection.  
A complete physical exam [head, eyes, ears, nose, throat, skin, heart, lungs, 
abdomen, extremities, and neurological (e.g. level of consciousness, pupils, motor 
and sensory responses, and reflexes)] will be performed at screening and a routine 
physical exam will be performed on all study visits. 
Vital signs and body weight will be summarized at baseline and as change from 
baseline at each post-baseline evaluation time point. 
Abnormal vital signs and physical examination findings will be reported as AEs. 
7.7.5 Injection Site Reaction 
The most common adverse event attributed to ALT-803 administered subcutaneously 
is an injection site reaction. Injection site reactions are localized rashes surrounding 
the ALT-803 injection site. Injection site reactions typically occur 3 days post ALT-803 
subQ injection and resolve in less than one week. 
The ALT-803 Injection Site Reaction Diary will be given to subjects on the day that the 
ALT-803 subQ injection is administered (Day 1 of study periods 1 and 2). The diary is 
to be completed by the subject daily until the resolution of symptoms. If any symptoms 
have not resolved by the next dose of ALT-803 (Day 1 of study period 2), the subject 
will need to complete two diaries. Each diary will address the individual injection sites 
and their corresponding symptoms until resolution. The subject will return the 
completed diaries to the study coordinator. 
Any of the symptoms that represent an adverse event will be reported as an AE. 
Injection site reaction data will be summarized for each injection diary as follows: 


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 Number and percentage of subjects who experienced redness at the injection 
site  
 Number and percentage of subjects who experienced firmness or swelling at 
the injection site  
 Number and percentage of subjects who experienced any pain or itching at the 
injection site 
 Number and percentage of subjects who took or applied any medication for 
injection site pain or itching 
 Number and percentage of subjects who experienced chills 
 Number and percentage of subjects with at least one daily temperature higher 
than 101oF 
 For each occurred symptom, summary statistics will be presented for the 
symptom starting day, duration of the symptom, and the worst assessment over 
the study course if applicable. 
7.7.6 General Health Questionnaire 
The General Health Questionnaire, RAND 36-item Short Form Survey 1.0 (SF-36) will 
be completed by the subject at baseline on Day 1, study period 1, and at the Follow-
up visit. 
The RAND 36-Item Health Survey (Version 1.0) taps eight health concepts: physical 
functioning, bodily pain, role limitations due to physical health problems, role 
limitations due to personal or emotional problems, emotional well-being, social 
functioning, energy/fatigue, and general health perceptions. It also includes a single 
item that provides an indication of perceived change in health. 
Scoring the RAND 36-Item Health Survey in this study is a two-step process (Hays 
1993). First, precoded numeric values are recoded per the scoring key given in Step 
1. Note that all items are scored so that a high score defines a more favorable health 
state. In addition, each item is scored on a 0 to 100 range so that the lowest and 
highest possible scores are 0 and 100, respectively. Scores represent the percentage 
of total possible score achieved. In step 2, items in the same scale are averaged 
together to create the 8 scale scores. Step 2 lists the items averaged together to 
create each scale. Items that are left blank (missing data) are not taken into account 
when calculating the scale scores. Hence, scale scores represent the average for all 
items in the scale that the respondent answered. 
Step 1: Recoding Items 
 
Item numbers  
Change original 
response category * 
To recoded 
value of: 
1, 2, 20, 22, 34, 36 
1 → 
100  


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2 → 
75 
3 → 
50  
4 → 
25 
5 → 
0 
3, 4, 5, 6, 7, 8, 9, 10, 11, 12 1 → 
0  
2 → 
50 
3 → 
100  
13, 14, 15, 16, 17, 18, 19 
1 → 
0 
2 → 
100  
21, 23, 26, 27, 30  
1 → 
100 
2 → 
80 
3 → 
60 
4 → 
40 
5 → 
20 
6 → 
0 
24, 25, 28, 29, 31 
1 → 
0 
2 → 
20 
3 → 
40 
4 → 
60 
5 → 
80 
6 → 
100 
32, 33, 35  
1 → 
0 
2 → 
25 
3 → 
50 
4 → 
75 
5 → 
100 
 
 
Step 2: Averaging Items to Form Scales  
Scale 
Number of items After recoding per Table 1, 
average the following items 
Physical functioning  
10 
3 4 5 6 7 8 9 10 11 12 
Role limitations due to physical health  
4 
13 14 15 16 
Role limitations due to emotional problems 3 
17 18 19 
Energy/fatigue 
4 
23 27 29 31 


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Emotional well-being 
5 
24 25 26 28 30 
Social functioning 
2 
20 32 
Pain 
2 
21 22 
General health 
5 
1 33 34 35 36 
 
General Health Questionnaire data will be summarized at baseline and as change 
from baseline at the follow-up visit. Eight summary scales in Step 2 will be derived and 
used in the analyses. 
7.8 IMMUNOGENICITY (Anti-Drug Antibody) METHODOLOGY 
Immunogenicity samples will be analyzed in all subjects who have received at least 
one dose of ALT-803. Samples will be collected at baseline (prior to any drug 
administration), prior to the start of Study Period 2, and at the End of Study visit. ADA 
(anti-drug antibody(s)) positivity will be listed for each subject for the screening, 
confirmatory and/or titer assays. Incidence of ADA formation will be summarized by 
cohort. 
7.9 Deviations from Statistical Analyses Planned in Protocol 
As of this date, there have been no deviations between the protocol-defined statistical 
analyses and those presented in this statistical plan. 
 
 


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8. REFERENCES 
 
1. 
Bessard A, Solé V, Bouchaud G, Quéméner A, Jacques Y. High antitumor 
activity of RLI, an interleukin-15 (IL-15)-IL-15 receptor alpha fusion protein, 
in metastatic melanoma and colorectal cancer. Mol Cancer Ther. 2009 
Sep;8(9):2736-45. 
2. 
Xu W, Jones M, Liu B, Zhu X, Johnson CB, Edwards AC, Kong L, Jeng EK, 
Han K, Marcus WD, Rubinstein MP, Rhode PR, Wong HC. Efficacy and 
mechanism-of-action of a novel superagonist interleukin-15: interleukin-15 
receptor αSu/Fc fusion complex in syngeneic murine models of multiple 
myeloma. Cancer Res. 2013 May 15;73(10):3075-86. 
3. 
National Cancer Institute. Common Terminology Criteria for Adverse Events 
(CTCAE), Version 4.0. 2010; http://evs.nci.nih.gov/ftp1/CTCAE/About.html. 
Accessed October 23, 2013. 
4. 
Ron D. Hays, Cathy Donald Sherbourne, and Rebecca M. Mazel. The 
RAND 36-item Health Survey 1.0. Health Economics, Vol. 2:217-227, 1993. 
 
 
 


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9. SCHEDULE OF ASSESSMENTS 
 
 
 
Tests & Procedures
Screen1
BL2
Rest 
Period
Study Day
1
1
2
3
4
5
6
7
8
9
> 6d
1 (pre-
dose)
1
2
3
4
5
6
7
8
9
End of 
Study, D15
Medical History & Demographics
X
Complete Physical Exam 
X
Routine Physical Exam
X
X
X
HIV, Hepititis B/C
X
Serum/Urine Pregnancy Test3
X
X
X
X
Urine Drug Test4
X
X
X
Alcohol Breath Test5
X
X
X
Vital Signs, Height and Weight6,7
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CBC with differential
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Chemistry (CMP)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Sampling for Immune Cells 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Sampling Cytokines
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Sampling for Immunogenicity Testing
X
X
X
Blood Sampling for ALT-803 Pharmacokinetics8
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
General Health Questionnaire
X
X
ALT-803
X
X
Injection Site Reaction (ISR) Diary9
Digital Photography of Injection Site and ISR 10
X
X
Adverse Events Monitoring
Concomitant Meds 
5A positive read (≥ 0.010% BAC) is an exclusion criteria during screening or will result in subject not being dosed while on study. 
6Vital signs will be assessed prior to dosing with ALT-803 and 1 hour post-dose. On all other days, vital signs will be collected prior to sample collection.
7Height should only be measured at screening. Weight will be measured prior to ALT-803 dose, for study periods 1 and 2.
8Blood sampling for PK will be collected prior to ALT-803 dose, 1 and 4 hours post dose and at 24, 48, 72, 96, 120, 144, 168 a nd 192 hours after dosing for study periods 1 and 2.  
10 A digital photograph of the Injection site will be taken prior to subQ injection of ALT-803. Photograph ISR's daily in 2 views through Day 6 or resolution, whichever is longer.
9Injection site reaction diaries should be completed through Day 6 or resolution of symptoms, whichever is longer.
3For women with childbearing potential only. Screening test should be serum. Baseline test may be urine.
Safety Monitoring
1Screening evaluations performed <14 days prior to dose #1 unless otherwise specified.
2Baseline (BL) evaluations will be performed on Treatment Day 1 (pre-dose).
As applicable
Continual
Continual
As applicable
As applicable
Study Period 1
Study Period 2
Drug Administration