A Phase 1 Study of MGD020 as a Single Agent or in Combination With MGD014 in Persons With HIV-1 on Antiretroviral Therapy
Phase: PHASE1
Conditions: Human Immunodeficiency Virus I Infection, Immunodeficiency Virus Type 1, Human, Human Immunodeficiency Virus Type 1
Sponsor: MacroGenics

MGD020, MGD014
MacroGenics, Inc.
Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
CLINICAL STUDY PROTOCOL: CP-MGD020-01
PROTOCOL AMENDMENT 1 
Study Title:
A Phase 1 Study of MGD020 as a Single Agent or in Combination 
with MGD014 in Persons with HIV-1 on Antiretroviral Therapy
Study Number:
CP-MGD020-01
Study Phase:
Phase 1
Product Number:
MGD020, MGD014
IND Number:
EudraCT Number:
Not applicable
DAIDS Document 
ID:
Indication:
Persons with human immunodeficiency virus-1 on antiretroviral 
therapy
Coordinating 
Principal 
Investigator:
Sponsor:
MacroGenics, Inc.
9704 Medical Center Drive
Rockville, MD 20850
301-251-5172
Sponsor’s Medical 
Monitor:
Refer to study contact list
Confidentiality Statement
This document is confidential. It contains proprietary information of MacroGenics, Inc. that 
can only be used for the purpose of reviewing or performing this study. Any use, viewing or 
disclosure of such information that is not authorized in writing by the sponsor is strictly 
prohibited.
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MGD020, MGD014
MacroGenics, Inc.
Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
REVISION HISTORY 
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Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
TABLE OF CONTENTS
SPONSOR SIGNATURES ........................................................................................................... 8 
 
1
SYNOPSIS ........................................................................................................................ 15 
2
BACKGROUND INFORMATION .................................................................................. 18 
2.1
Disease Background................................................................................................. 18 
2.2
Rationale for Study .................................................................................................. 18 
2.3
Background on Study Drugs .................................................................................... 19 
2.3.1
Background on MGD020 ............................................................................... 20 
2.3.1.1
MGD020 Clinical Experience .............................................................. 20 
2.3.1.2
MGD020 Non-Clinical Experience ...................................................... 20 
2.3.2
Background on MGD014 ............................................................................... 22 
2.3.2.1
MGD014 Clinical Experience .............................................................. 23 
2.3.2.2
MGD014 Non-Clinical Experience ...................................................... 24 
2.4
Dose Selection ......................................................................................................... 24 
2.4.1
MGD020 Dose Selection ............................................................................... 24 
2.4.1.1
Rationale for Every 2 Week Administration ........................................ 24 
2.4.2
MGD020 and MGD014 Combination Dose Selection .................................. 24 
2.4.3
Post-Infusion Monitoring ............................................................................... 25 
2.5
Risk Benefit Assessment .......................................................................................... 25 
2.5.1
Risk Assessment ............................................................................................. 25 
2.5.2
Benefit Assessment ........................................................................................ 25 
2.5.3
Overall Assessment ........................................................................................ 26 
3
STUDY OBJECTIVES ..................................................................................................... 27 
3.1
Primary Objective .................................................................................................... 27 
3.2
Secondary Objectives............................................................................................... 27 
3.3
Exploratory Objectives ............................................................................................ 27 
4
STUDY DESIGN .............................................................................................................. 29 
4.1
Overall Study Design ............................................................................................... 29 
4.1.1
Part 1A: Single Ascending Dose of MGD020 ............................................... 29 
4.1.2
Part 1B: Single Ascending Dose of MGD020 and Fixed-Dose of 
MGD014 ........................................................................................................ 30 
4.1.3
Part 2: Multi-Dose Expansion Cohort: Fixed-Dose of MGD020 
and Fixed-Dose of MGD014 ......................................................................... 31 
4.2
Dose Escalation Rules.............................................................................................. 32 
4.3
Dose-Limiting Toxicity ............................................................................................ 32 
4.4
Guidelines for Dose Modification ........................................................................... 33 
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Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
4.4.1
Dose Delays ................................................................................................... 33 
4.5
Study Drug Discontinuation .................................................................................... 33 
4.6
Follow-Up ................................................................................................................ 34 
4.7
Study Discontinuation .............................................................................................. 34 
4.8
Study Duration ......................................................................................................... 34 
4.9
End of Study ............................................................................................................ 35 
5
ELIGIBILITY CRITERIA ................................................................................................ 36 
5.1
Inclusion Criteria ..................................................................................................... 36 
5.2
Exclusion Criteria .................................................................................................... 37 
6
STUDY DRUG DOSING ................................................................................................. 41 
6.1
Description of Dosing Regimens ............................................................................. 41 
6.2
Method of Assigning Participants to Cohorts .......................................................... 41 
6.3
Blinding.................................................................................................................... 41 
6.4
Study Drugs and Supplies ........................................................................................ 41 
6.4.1
MGD020 ........................................................................................................ 41 
6.4.1.1
Storage and Handling of MGD020 ...................................................... 42 
6.4.2
MGD014 ........................................................................................................ 42 
6.4.2.1
Storage and Handling of MGD014 ...................................................... 43 
6.4.3
 Vehicle ........................................................................................... 43 
6.4.3.1
Storage and Handling of 
Vehicle ......................................... 44 
6.5
Study Drug Preparation and Administration ............................................................ 44 
6.5.1
Monitoring Post-administration ..................................................................... 44 
6.6
Compliance .............................................................................................................. 44 
6.7
Accountability .......................................................................................................... 45 
6.8
Disposition of Study Drug at End of Study ............................................................. 45 
7
ADVERSE EVENTS AND SUPPORTIVE CARE MEASURES ................................... 46 
7.1
Infusion Related Reactions Including Cytokine Release Syndrome ....................... 46 
7.1.1
Grading and Management of Infusion Reactions .......................................... 46 
7.1.2
Premedication ................................................................................................ 46 
7.1.3
Management of Observed Infusion Reactions ............................................... 46 
7.2
COVID-19/SARS-CoV-2 Infection or Vaccination ................................................. 48 
8
CONCOMITANT THERAPY AND RESTRICTIONS ................................................... 49 
8.1
Concomitant Therapy ............................................................................................... 49 
8.1.1
Prohibited Therapy ......................................................................................... 49 
8.1.2
Permitted Therapy .......................................................................................... 49 
8.1.3
Contraception ................................................................................................. 50 
9
STUDY PROCEDURES .................................................................................................. 51 
9.1
Study Visits .............................................................................................................. 51 
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Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
9.2
Informed Consent..................................................................................................... 51 
9.3
Screening Period ...................................................................................................... 51 
9.4
Enrollment and Registration .................................................................................... 52 
9.5
Medical History ....................................................................................................... 52 
9.6
Concomitant Medications and Procedures............................................................... 52 
9.6.1
Concomitant Medications .............................................................................. 52 
9.6.2
Concomitant Procedures ................................................................................ 52 
9.7
Antiretroviral Therapy ............................................................................................. 53 
9.8
Physical Examination............................................................................................... 53 
9.9
Vital Signs ................................................................................................................ 53 
9.10
Optional Leukapheresis ........................................................................................... 53 
9.11
Laboratory Tests ....................................................................................................... 53 
9.11.1
Clinical Laboratory Tests ............................................................................... 53 
9.11.2
Central Laboratory Tests ................................................................................ 54 
9.11.3
Sample Collection, Storage, and Shipping .................................................... 54 
9.12
Electrocardiography ................................................................................................. 54 
9.13
End of Study ............................................................................................................ 55 
10
ASSESSMENT OF PHARMACOKINETICS AND PHARMACODYNAMICS ........... 56 
10.1
Pharmacokinetic Assessments ................................................................................. 56 
10.2
Immunogenicity Assessments .................................................................................. 56 
10.3
Pharmacodynamic Assessments............................................................................... 56 
10.3.1
Serum Cytokines ............................................................................................ 56 
10.3.2
T-Cell Binding ................................................................................................ 56 
10.3.3
T-Cell Phenotype and Function ...................................................................... 56 
10.3.4
Persistent Human Immunodeficiency Virus-1 ............................................... 57 
11
ASSESSMENT OF EFFICACY ....................................................................................... 58 
12
ADVERSE EVENT REPORTING AND ASSESSMENT OF SAFETY ......................... 59 
12.1
Definitions................................................................................................................ 59 
12.1.1
Adverse Event ................................................................................................ 59 
12.1.2
Adverse Drug Reaction .................................................................................. 59 
12.1.3
Adverse Event of Special Interest .................................................................. 59 
12.1.4
Serious Adverse Event ................................................................................... 59 
12.1.5
Assessment of Causality ................................................................................ 60 
12.1.6
Severity Criteria ............................................................................................. 61 
12.2
Adverse Event Collection and Documentation ........................................................ 61 
12.2.1
Adverse Events .............................................................................................. 61 
12.2.2
Serious Adverse Events .................................................................................. 62 
12.2.3
Pregnancy ....................................................................................................... 63 
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Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
12.2.4
Other Reporting Situations ............................................................................ 64 
12.2.4.1
Adverse Events of Special Interest....................................................... 64 
12.2.4.2
Study Drug Overdose ........................................................................... 64 
12.2.4.3
Product Quality .................................................................................... 64 
12.2.4.4
Discontinuation of Study Drug Due to an Adverse Event ................... 64 
13
PRODUCT QUALITY COMPLAINT HANDLING ....................................................... 65 
14
STATISTICAL ANALYSIS .............................................................................................. 66 
14.1
Determination of Sample Size ................................................................................. 66 
14.2
Analysis Populations ................................................................................................ 66 
14.3
Demographics and Baseline Characteristics ............................................................ 66 
14.4
Study Drug Exposure and Concomitant Medications .............................................. 66 
14.5
Pharmacokinetic and Pharmacodynamic Analysis .................................................. 67 
14.5.1
Pharmacokinetic Analysis .............................................................................. 67 
14.5.2
Immunogenicity Analysis .............................................................................. 67 
14.5.3
Pharmacodynamic Analysis ........................................................................... 67 
14.5.3.1
Serum Cytokines .................................................................................. 67 
14.5.3.2
T-Cell Binding ...................................................................................... 67 
14.5.3.3
T-Cell Phenotype and Function ............................................................ 67 
14.5.3.4
Quantitative Viral Outgrowth Assay .................................................... 67 
14.5.3.5
Intact Proviral Deoxyribonucleic Acid Assay ...................................... 68 
14.5.3.6
Resting CD4+ T-Cell-Associated HIV-1 gag RNA .............................. 68 
14.5.3.7
Plasma Viremia by Single Copy Assay ................................................ 68 
14.6
Efficacy Endpoints and Analyses ............................................................................. 68 
14.7
Safety Endpoints and Analyses ................................................................................ 68 
14.7.1
Adverse Events .............................................................................................. 68 
14.7.2
Laboratory Values .......................................................................................... 69 
14.7.3
Other Safety Endpoints .................................................................................. 69 
14.8
Other Assessments or Analyses ............................................................................... 69 
14.9
Cohort Analyses and Monitoring ............................................................................. 69 
15
QUALITY CONTROL AND ASSURANCE ................................................................... 70 
15.1
Monitoring, Auditing, and Inspections .................................................................... 70 
15.2
Data Collection and Management ............................................................................ 71 
16
ADMINISTRATIVE CONSIDERATIONS...................................................................... 72 
16.1
Institutional Review Board ...................................................................................... 72 
16.2
Ethical Conduct of the Study ................................................................................... 72 
16.3
Participant Information and Consent ....................................................................... 72 
16.4
Participant Confidentiality ....................................................................................... 73 
16.5
Source Documents ................................................................................................... 73 
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Protocol Amendment 1, 12 January 2023
16.6
Retention of Data ..................................................................................................... 73 
16.7
Sample Retention and Secondary Research ............................................................. 73 
16.8
Financial Disclosure................................................................................................. 73 
16.9
Publication and Disclosure Policy ........................................................................... 74 
16.10
Discontinuation of the Study or Study Sites ............................................................ 74 
16.11
Identification of the Coordinating Principal Investigator ........................................ 74 
17
REFERENCE LIST .......................................................................................................... 75 
LIST OF TABLES 
Table 1
MGD020 Dose Escalation Scheme (Part 1A) .................................................... 30 
Table 2
MGD020 and MGD014 Combination Dose Escalation Scheme 
(Part 1B) ............................................................................................................. 31 
Table 3
MGD020 and MGD014 Combination Multi-Dose Expansion 
Cohort Scheme (Part 2) ...................................................................................... 31 
Table 4
MGD020 Drug Product Composition ................................................................ 42 
Table 5
MGD014 Drug Product Composition ................................................................ 43 
Table 6
Clinical Laboratory Tests .................................................................................... 54 
Table 7
Time and Events Schedule (Part 1A and Part 1B) .............................................. 77 
Table 8
Time and Events Schedule (Part 2) .................................................................... 80 
Table 9
Pharmacokinetic, Immunogenicity, and Pharmacodynamic 
Sampling Schedule: Part 1A ............................................................................... 83 
Table 10
Pharmacokinetic, Immunogenicity, and Pharmacodynamic 
Sampling Schedule: Part 1B ............................................................................... 84 
Table 11
Pharmacokinetic, Immunogenicity, and Pharmacodynamic 
Sampling Schedule: Part 2 .................................................................................. 85 
LIST OF FIGURES 
Figure 1
DART Molecule Structure and Mechanism for Redirected T-cell 
Cytolysis of Human Immunodeficiency Virus-1-infected Envelope-
expressing Cells .................................................................................................. 19 
LIST OF APPENDICES 
APPENDIX 1
TIME AND EVENTS SCHEDULES
APPENDIX 2
PHARMACOKINETICS, IMMUNOGENICITY, AND 
PHARMACODYNAMIC SAMPLE COLLECTION SCHEDULE
APPENDIX 3
PRINCIPAL INVESTIGATOR’S AGREEMENT
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Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
SPONSOR SIGNATURES 
Study Title:
A Phase 1 Study of MGD020 as a Single Agent or in Combination 
with MGD014 in Persons with HIV-1 on Antiretroviral Therapy
Study Number: 
CP-MGD020-01
DAIDS Document ID: 
38879
This clinical study protocol has been approved by the sponsor:
Signed: 
See Appended Electronic Signature Page
Date:
 
Vice President, Clinical Development
MacroGenics, Inc.
Signed:
See Appended Electronic Signature Page
Date:
Executive Director, Biostatistics
MacroGenics, Inc.
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Protocol Amendment 1, 12 January 2023
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Protocol Amendment 1, 12 January 2023
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Protocol Amendment 1, 12 January 2023
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Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
LIST OF ABBREVIATIONS 
The list of abbreviations of specialist terms does not include standard scientific abbreviations of 
temperature, weight, and volume.
ADA 
anti-drug antibody 
AE 
adverse event 
AESI 
adverse event of special interest 
AIDS 
acquired immunodeficiency syndrome 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ART 
antiretroviral therapy 
AST 
aspartate aminotransferase 
AUC0-inf 
area under the concentration-time curve from time zero to infinity 
AUCtau 
area under the concentration-time curve for a dosing interval 
CD 
cluster of differentiation 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CL 
clearance 
Cmax 
maximum concentration 
COVID-19 
coronavirus disease 2019 
CRS 
cytokine release syndrome 
CSR 
clinical study report 
Ctrough 
trough concentration 
DAIDS 
Division of AIDS 
DLT 
dose-limiting toxicity 
DNA 
deoxyribonucleic acid 
DP 
drug product 
EC50 
half-maximal effective concentration 
ECG 
electrocardiogram 
E/CIA 
enzyme or chemiluminescence immunoassay 
EDC 
electronic data capture 
env 
envelope; specifically, the HIV-1 env glycoprotein 
EOSV 
end of study visit 
Fc 
fragment crystallizable 
FcγR
fragment crystallizable-gamma receptor 
FDA 
Food and Drug Administration 
FSH 
follicle stimulating hormone 
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Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
GCP 
Good Clinical Practice 
gp 
glycoprotein 
HCV 
hepatitis C virus 
HIV-1 
human immunodeficiency virus-1 
HLA 
human leukocyte antigen 
IB 
investigational brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IFN-γ 
interferon gamma 
IgG 
immunoglobulin G 
IL 
interleukin 
IND 
Investigational New Drug 
INR 
international normalized ratio 
IOCBP 
individual of childbearing potential 
IPDA 
intact proviral DNA assay 
IRB 
Institutional Review Board 
IRR 
infusion related reaction 
IUPM 
infectious units per million 
IV 
intravenous(ly) 
KD 
equilibrium binding constant 
mAb 
monoclonal antibody 
MABEL 
minimum anticipated biological effect level 
MAD 
maximum administered dose 
MedDRA 
Medical Dictionary for Regulatory Activities 
MTD 
maximum tolerated dose 
NIAID 
National Institute of Allergy and Infectious Diseases 
NNRTI 
non-nucleoside reverse transcriptase inhibitors 
NOAEL 
no observed adverse effect level 
PBMC 
peripheral blood mononuclear cell 
PCR 
polymerase chain reaction 
PD 
pharmacodynamics 
Ph. Eur. 
European Pharmacopoeia 
PK 
pharmacokinetics 
PO 
oral administration 
PQC 
product quality complaint 
PRF 
participant registration form 
PWH 
persons with HIV 
Q2W 
once every 2 weeks 
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QVOA 
quantitative viral outgrowth assay 
rca-RNA 
resting CD4+ T-cell-associated HIV-1 gag RNA 
RNA 
ribonucleic acid 
RPR 
rapid plasma reagin 
SAE 
serious adverse event 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SCA 
single copy assay 
SHIV 
simian-human immunodeficiency virus 
SUSAR 
suspected unexpected serious adverse reaction 
t1/2 
terminal half-life 
t1/2,β 
beta phase half-life 
Tmax 
time to maximal concentration 
TNF-α 
tumor necrosis factor-alpha 
ULN 
upper limit of normal 
US 
United States 
USP 
United States Pharmacopeia 
Vss 
steady-state volume of distribution 
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Protocol Amendment 1, 12 January 2023
1 
SYNOPSIS 
Sponsor: MacroGenics, Inc. 
IND Number:
 
Name of Product: MGD020, MGD014 
Study Title: A Phase 1 Study of MGD020 as a Single Agent or in Combination with MGD014 in Persons with 
HIV-1 on Antiretroviral Therapy 
Study Number: CP-MGD020-01 
Study Phase: Phase 1 
Investigators/Centers: 
The study will be conducted at 3-5 institutions in the United States. 
Primary Objective: 
x
Characterize safety and tolerability of MGD020 as a single agent and in combination with MGD014
Secondary Objective(s): 
x
Assess pharmacokinetics (PK) and immunogenicity (anti-drug antibody [ADA]) of MGD020
x
Assess PK and immunogenicity (ADA) of MGD014
x
Assess serum cytokine levels
Study Drugs: 
MGD020 (HIV7B2 x CD3) and MGD014 (HIVA32 x CD3) are Fc-bearing DART molecules identical in structure 
except for the sequences of the anti-HIV-1 envelope (env) arms, which recognize different epitopes. DART 
molecules are bispecific, antibody-based molecules that can bind two distinct antigens simultaneously. MGD020 
and MGD014 are designed to target HIV-1-infected, env-expressing cells for recognition and elimination by 
CD3-expressing T lymphocytes as effector cells. 
Study Design: 
Study CP-MGD020-01 is a phase 1, open-label, dose-escalation, and multi-dose expansion study of MGD020 as 
a single agent or in combination with MGD014 in persons with HIV-1 (PWH) on antiretroviral therapy (ART). 
The study is designed to characterize the safety, tolerability, PK, immunogenicity, and pharmacodynamics (PD) 
of the study drugs. The study consists of 3 parts (Part 1A, Part 1B, and Part 2). In all parts, the participant’s
standard of care ART regimen is continued throughout the study period. 
Part 1A evaluates single ascending doses of MGD020 with a 1+3 design for cohorts 1–3, and a 3+3 design for 
cohorts 4–6. In the 6 cohorts, the MGD020 dose ranges from 1 to 300 mcg/kg. A 2-week dose-limiting toxicity 
(DLT) period is observed prior to escalation to the next cohort level. Dose escalation proceeds until either the 
maximum tolerated dose (MTD) or maximum administered dose (MAD) is determined.  
Part 1B commences only after the MTD or MAD of single-agent MGD020 has been determined in Part 1A. 
During Part 1B, participants will be enrolled and treated with a single ascending dose of MGD020 in combination 
with a fixed dose of 300 mcg/kg MGD014. Dose escalation uses a 3+3 design with up to 3 dose cohorts, 
including 1 dose de-escalation cohort. The first cohort will be treated with a single dose of MGD020, at a dose 
determined to be one dose level lower than the single-agent MTD/MAD from Part 1A (i.e., one dose level lower 
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than MTD1A/MAD1A), and a single 300 mcg/kg dose of MGD014. Dose escalation proceeds until either the MTD 
or MAD of the combination is determined. 
Part 2 commences only after an MTD or MAD of MGD020 in combination with MGD014 has been determined 
in Part 1B. Part 2 is a multi-dose expansion cohort with sequential infusions of a fixed dose of MGD020 in 
combination with a fixed dose of MGD014 administered every 2 weeks (Q2W) for 3 combination doses over 
4 weeks. MGD020 is dosed at the MTD/MAD determined in Part 1B (i.e., MTD1B/MAD1B); MGD014 is dosed at 
300 mcg/kg. Up to 6 participants may be enrolled in Part 2 using a conventional 3+3 design. 
The study consists of a screening phase of up to 8 weeks, and an approximately 6-week (Part 1A and Part 1B) or 
11-week (Part 2) study period (dosing and follow-up), which concludes with an end of study visit approximately
6 weeks (Part 1A and Part 1B) or 7 weeks (Part 2) after the last dose of study drug. Thus, the total study duration
for each participant is approximately 14 weeks (Part 1A and Part 1B) or 19 weeks (Part 2). If a participant is
unable to complete the study, but has not withdrawn consent, the end of study visit is conducted 30 days (+3 day
window) after the last dose of study drug.
An independent safety monitor will provide study oversight and evaluate cumulative safety and other clinical data 
at regular intervals. 
Dose-limiting Toxicities: 
Dose-limiting toxicity (DLT) is defined based on treatment-related adverse events (AEs) that occur during the 
DLT period following study drug administration. The DLT period is defined as the period from initial infusion of 
study drug(s) through 2 weeks following the last infusion of study drug(s). 
Severity of AEs is graded according to the National Institute of Allergy and Infectious Diseases (NIAID) 
Division of Acquired Immunodeficiency Syndrome (DAIDS) Table for Grading the Severity of Adult and 
Pediatric Adverse Events, corrected version 2.1, July 2017. 
A DLT is any ≥ Grade 2 treatment-related AE, with the following exceptions, based on the medical judgement of 
the investigator (or designee) and medical monitor: 
x
Grade 2 laboratory abnormality that lasts < 72 hours and is not otherwise associated with clinical
complications.
x
Grade 2 fatigue that lasts < 7 days.
Number of Participants Enrolled: 
The study plans to enroll up to approximately 54 participants in total, including up to 30 participants in Part 1A, 
18 participants in Part 1B, and 6 participants in Part 2. The exact number of participants cannot be determined 
precisely in advance but depends upon the occurrence of DLTs and potential need for expanded cohorts. 
Study Population/Key Entry Criteria: 
The target population consists of PWH (18 to 70 years old) on ART with plasma HIV-1 RNA < 50 copies/mL for 
24 months prior to enrollment. Participants must have adequate organ function and no serious concurrent illnesses 
that would increase the risk to the participant or confound study results. 
Duration of Treatment and Study Duration: 
For individual participants, the study duration is approximately 14 weeks in Part 1A and Part 1B or 
approximately 19 weeks in Part 2. The study duration includes screening, dosing, follow-up, and an end of study 
visit. 
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The overall study duration is approximately 24 months. This estimate of timing may vary from that observed in 
the actual conduct of the study. 
Criteria for Evaluation: 
Safety Assessments 
The safety assessment is based on evaluation of AEs occurring from the first administration of study drug(s) 
through the end of study visit or 30 days after the last dose of study drug(s), whichever is later. The assessment is 
based on signs, symptoms, physical examination findings, and laboratory test results.  
Pharmacokinetic Assessments 
Serum concentrations of study drug(s) will be assessed using quantitative validated bioanalytical methods. Single 
and multiple dose PK parameters will be derived from serum concentration versus time data. Population PK 
analyses may be conducted using data from this study alone or combined with data from other sponsor-conducted 
studies. 
Immunogenicity Assessments 
Incidence of ADA to study drug(s) will be assessed using validated bioanalytical methods. 
Pharmacodynamic Assessments 
All study parts: assessment of serum cytokines, T-cell binding, T-cell phenotype and function, and markers of 
persistent HIV-1 by intact proviral DNA assay (IPDA). 
Part 2 only: assessment of markers of persistent HIV-1 by quantitative viral outgrowth assay (QVOA), plasma 
HIV-1 RNA levels by single copy assay (SCA), and resting CD4+ T-cell-associated HIV-1 gag RNA (rca-RNA). 
Analysis Populations: 
Study analyses will be performed on the safety population, defined as all participants who received at least one 
dose of either study drug. This population will be used to summarize safety data. This population will also be 
used to summarize baseline data for PK, pharmacodynamics, and immunogenicity analyses. 
Statistical Methods: 
A statistical analysis plan and statistical programming plan will describe the statistical methods and govern the 
analysis. 
Sample Size: 
The study plans to enroll up to approximately 54 participants in total, including up to 30 in Part 1A, 18 in 
Part 1B, and 6 in Part 2. The sample size in Part 1A is based on a 1+3 design with 3 planned cohorts 
(12 participants) and 3+3 design for 3 cohorts (18 participants). The sample size in Part 1B is based on a 3+3 
design with 3 planned cohorts (18 participants). Part 2 of the study may enroll up to 6 participants based on a 3+3 
design with 1 cohort. 
Safety: 
Adverse events will be coded to the Medical Dictionary for Regulatory Activities (MedDRA) dictionary. 
Treatment-emergent AEs will be summarized in tables and listings. All AEs prior to treatment (e.g., due to study-
related procedures) will be presented in listings only. Adverse events will be summarized by system organ class, 
preferred term, relationship to study drug(s), and highest severity. Summaries of laboratory values will display 
descriptive statistics for numerically quantified labs. 
Efficacy: 
Not applicable. 
Pharmacodynamics: 
Exploratory analyses are described in the protocol body. 
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MGD020, MGD014
MacroGenics, Inc.
Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
2 
BACKGROUND INFORMATION 
2.1 
Disease Background 
An estimated 1,173,900 persons (aged ≥ 13 years) in the United States (US) at the year-end 2018 
were living with human immunodeficiency virus (HIV) infection (5). The prevalence rate was 
427 per 100,000 population. Of those with HIV in 2018, about 76% received some HIV care, 
58% were retained in care, and 65% were virally suppressed (6). 
Antiretroviral therapy (ART) for the treatment of HIV-1 infection has improved steadily since the 
advent of potent combination therapy in 1996. ART has dramatically reduced HIV-1-associated 
morbidity and mortality and has transformed HIV-1 infection into a manageable chronic 
condition, with life expectancy approaching that for people without HIV-1 (12). Life-long ART is 
required to prevent rebound of viremia and return of disease, due to the persistence of long-lived 
viral reservoirs (13).
2.2 
Rationale for Study 
Despite use of ART, HIV-1 persists in a latent, transcriptionally quiescent state. This latent HIV-1 
reservoir is the major obstacle to a cure for HIV-1 (1, 9, 10). Persons with HIV-1 (PWH) are now 
taking ART over much longer periods of time, and the resulting potential cumulative toxicity that 
can emerge is not fully understood. Not only could such long-term toxicity lead to poor health 
status and a diminished quality of life but ART-related adverse events (AEs) that ultimately result 
in increases in morbidity and mortality risk may contribute significantly to healthcare resource 
utilization and costs associated with HIV-1 treatment (8). Thus, new approaches to deplete 
persistent HIV-1 infection are needed.
In this study, MGD020 will be evaluated first as a single agent then in combination with 
MGD014. MGD020 and MGD014 are bispecific DART® molecules that bind HIV-1 envelope 
(env) glycoprotein antigen and human cluster of differentiation (CD)-3 antigen. DART molecule-
mediated co-engagement of HIV-1-infected, env-expressing cells and CD3+ T cells induces 
cytolysis of HIV-1 infected cells. The combination of MGD020 and MGD014 has the potential 
to enhance the recognition of rare actively infected cells in individuals that express env 
glycoproteins encoded by diverse and mutable HIV-1 isolates. This broadened clearance activity 
is due to the ability of each DART molecule to recognize a distinct, highly conserved epitope of 
the HIV-1 env antigen.
The combination of MGD014 and MGD020 is justified by in vitro and in vivo nonclinical data. 
In vitro binding studies demonstrate that MGD014 and MGD020 bind independently (i.e., 
without competition) to their respective HIV-1 Env epitopes, which will increase the probability 
of recognition of HIV-1 Env-expressing cells. In vitro studies on redirected CD8 T-cell killing of 
HIV-1-infected CD4 cells conducted with CD4/CD8 cells from different human donors (HIV-1-
infected or uninfected) and different HIV-1 virus isolates demonstrate that the combination of 
MGD014 + MGD020 mediates potent and high activity across all conditions more consistently 
than the individual DART molecules. In vivo studies in HIV-1-infected humanized mice on ART 
demonstrate that treatment with the combination of MGD014 + MGD020 is significantly more 
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MGD020, MGD014
MacroGenics, Inc.
Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
effective than treatment with the individual DART molecules in decreasing levels of cell-
associated viral RNA and delaying rebound viremia following ART interruption. 
2.3 
Background on Study Drugs 
The non-clinical studies of MGD020 and MGD014 are summarized in the respective investigator 
brochures (IBs). 
MGD020 (HIV7B2 x CD3) and MGD014 (HIVA32 x CD3) are fragment crystallizable (Fc)-
bearing DART molecules identical in structure except for the sequences of the anti-HIV-1 env 
arms, which recognize different epitopes of the HIV-1 env. DART molecules are bispecific, 
antibody-based molecules that can bind two distinct antigens simultaneously. MGD020 and 
MGD014 are designed to target HIV-1-infected, env-expressing cells for recognition and 
elimination by CD3-expressing T lymphocytes as effector cells. A schematic depicting the 
structure and mechanism of action of an HIV-1 x CD3 DART molecule is shown in Figure 1. 
Prior pre-clinical and clinical studies with MGD014, which is structured exactly like MGD020 
except for the identity of the MGD020 anti-HIV-1 env arm, were conducted to evaluate 
pharmacokinetics (PK) and anti-drug antibodies (ADA). MGD020 and MGD014 are structurally 
and functionally similar. Therefore, MGD020 will likely have similar PK and ADA in PWH on 
ART. The first in human dose of MGD020 is based on the minimum anticipated biological effect 
level (MABEL). 
Figure 1
DART Molecule Structure and Mechanism for Redirected T-cell 
Cytolysis of Human Immunodeficiency Virus-1-infected Envelope-
expressing Cells
The anti-CD3 arm (orange) of the HIV-1 x CD3 DART molecule binds to CD3 (brown) at the surface of CD3+ 
T cells (effector cell), and the anti-HIV-1 env arm (dark blue) of the HIV-1 x CD3 DART molecule binds to 
HIV-1 env antigen at the surface of HIV-1 infected CD4+ T cells (target cell). Cell surface HIV-1 env 
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MGD020, MGD014
MacroGenics, Inc.
Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
glycoprotein (light blue) may be in the form of functional mature trimers or nonfunctional variant forms such 
as cleaved or uncleaved gp160 monomers or gp41 stumps (17); gp160 is the full-length HIV-1 env precursor 
which is cleaved by furin to generate gp120 and gp41. HIV-1 x CD3 DART molecule-mediated co-engagement 
of target and effector cells results in activation of CD3+ T-cell cytolytic responses toward HIV-1-infected, 
env-expressing target cells. 
2.3.1 
Background on MGD020 
MGD020 (HIV-17B2 x CD3) is an HIV-1 env x CD3 DART molecule. MGD020 is designed to 
target HIV-1-infected, env-expressing cells for recognition and elimination by CD3-expressing 
T lymphocytes as effector cells. The anti-HIV-1 env arm is derived from non-neutralizing human 
monoclonal antibody (mAb) 7B2, which binds to highly conserved residues (cluster I) in the 
glycoprotein 41 (gp41) subunit of HIV-1 env and is broadly reactive with HIV-1 env from 
diverse isolates of HIV-1. The 9 HIV-1 env residues that comprise the linear epitope plus 2 
accessory (non-epitope) residues that may influence binding to the 7B2 epitope are conserved at 
an average frequency of 98.5% (range: 95.5–99.8%) across all HIV-1 subtypes (based on 
analysis of 5923 HIV-1 env sequences in the Los Alamos National Laboratory database). The 
anti-CD3 arm of MGD020 is derived from humanized mAb hXR32, which binds to human CD3 
and cross-reacts with cynomolgus or rhesus monkey CD3. MGD020 contains a human 
immunoglobulin G (IgG)-1 Fc domain that was mutated to greatly reduce or eliminate undesired 
binding to Fc-gamma receptor (FcγR) or complement, while retaining binding to neonatal Fc 
receptor (FcRn), which allows MGD020 to take advantage of the IgG salvage pathway to 
prolong the circulating half-life.
2.3.1.1 
MGD020 Clinical Experience 
No information is available about the effects of MGD020 in humans. Study CP-MGD020-01 is 
the first-in-human study. No other clinical studies have been conducted with MGD020. 
2.3.1.2 
MGD020 Non-Clinical Experience 
The non-clinical program was designed to characterize the biological activity of MGD020 to 
support development as a single agent and in combination with MGD014. A summary is 
provided in the subsections below. Please refer to the MGD020 IB for details on non-clinical 
studies with MGD020.
2.3.1.2.1 
Pharmacology 
In vitro binding studies with MGD020 demonstrated binding affinities (equilibrium binding 
constant [KD] values) of 4.1–41 nM for HIV-1 env glycoproteins and 15.7 or 16.4 nM for human 
or cynomolgus/rhesus monkey CD3ε protein, respectively. Virion capture studies demonstrated 
MGD020 binding to HIV-1 virions; this contrasts with MGD014, which binds HIV-1 virions 
inefficiently. MGD020 binds to primary CD3+ T lymphocytes (CD4+ and CD8+ subsets), HIV-1-
env-expressing human cell lines and HIV-1 infectious molecular clone (IMC)-infected human 
CD4+ cells. MGD020 and MGD014 can bind simultaneously, without competition, to their 
respective epitopes on purified HIV-1 env protein, HIV-1-env-expressing human cell lines or 
HIV-1 IMC-infected human CD4+ cells.
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MGD020, MGD014
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Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
MGD020 redirected T cells to lyse human CD4+ cells infected in vitro by IMCs derived from 
HIV-1 transmitted/founder isolates (subtype B CH040, subtype C 1086c, or subtype C DU151) 
with high potency; median half-maximal effective concentration (EC50) was 7.0 ng/mL. 
Similarly, MGD020 redirected T cells to lyse human Jurkat and HEK293 cell lines engineered to 
express HIV-1 env from different HIV-1 isolates (subtype 01_AE CM244, subtype B JRFL, 
subtype B HXBc2, or subtype C CH505); median EC50 was 7.6 or 12 ng/mL, depending on assay 
method used. T-cell activation (CD25 upregulation and tumor necrosis factor-α [TNF-α] 
production) was induced concomitantly with redirected T-cell cytolytic activity. However, with 
target cells expressing very low levels of HIV-1 env, MGD020 had minimal or no effect on T-cell 
activation yet mediated potent redirected cytolysis. These data are consistent with mechanistic 
studies demonstrating that induction of cytokines may not be required for cytotoxic T-cell 
activity mediated by CD3-bispecific antibodies (16).
A 1:1 combination of MGD020 plus MGD014 generally mediated redirected T-cell cytolytic 
activity in vitro with greater potency than MGD020 alone; median EC50 values for the 
combination ranged from 1.0 to 3.7 ng/mL. The MGD020 plus MGD014 combination 
consistently mediated cytolytic activity that was comparable to that of the more active individual 
DART molecule, which varied depending on HIV-1 isolate or T-cell donor. Thus, MGD020 and 
MGD014 effectively complemented each other to maximize redirected cytolysis regardless of 
target cell or effector cell identities.
MGD020 mediated antiviral activity in HIV-1-infected humanized mice on suppressive ART. 
Intravenous (IV) administration of MGD020 significantly reduced cell-associated viral RNA and 
delayed rebound in viremia following ART interruption. The MGD020 plus MGD014 
combination mediated a greater decline in cell-associated viral RNA and longer delay in rebound 
viremia than MGD020 or MGD014 alone, which supports use of the MGD020 plus MGD014 
combination.
2.3.1.2.2 
Pharmacokinetics and Toxicology 
MGD020 was well tolerated when administered at 1 mg/kg/dose via 30-minute IV infusion once 
weekly for 6 weeks to simian-human immunodeficiency virus (SHIV)-infected rhesus monkeys 
maintained on long-term suppressive ART. There were no MGD020-related clinical signs or 
changes in body weight, hematology parameters, levels of serum cytokines, or activation status 
of circulating T cells, despite high levels of MGD020 binding to CD4+ or CD8+ T cells at 
24 hours post-dosing. Mean MGD020 clearance (CL) was 0.47–0.63 mL/hr/kg, which is lower 
than the glomerular filtration rate, indicating that renal excretion is not a significant clearance 
pathway. Mean volume of distribution at steady state (Vss) was 66–106 mL/kg, which is greater 
than the plasma volume, but less than the extracellular volume of rhesus monkeys, which 
suggests minimal binding or partitioning into tissues. Mean maximum concentration (Cmax) was 
27.2 mcg/mL. Mean terminal half-life (t1/2) was 3.3 days and the beta phase half-life (t1/2,β) was 
7.9 days. 
MGD020 did not reduce cell-associated viral RNA or delay rebound viremia in SHIV-infected 
rhesus monkeys following ART interruption. The absence of MGD020-mediated antiviral 
activity was likely due to the rarity of target cells (SHIV-infected cells expressing env protein) in 
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MGD020, MGD014
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Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
study animals maintained on long-term ART. These results contrast with those from the HIV-1-
infected humanized mouse model which used short-term ART.
MGD020 in immobilized form, but not in soluble form, induced cytokines (especially 
interferon-γ [IFN-γ] and TNF-α) when incubated with peripheral blood mononuclear cells 
(PBMCs) from healthy or HIV-1-infected human donors. Induction of IFN-γ production was the 
most sensitive cytokine response; the mean EC50 values of 200 or 1800 ng/mL with PBMCs from 
HIV-1-infected or healthy human donors, respectively, were much higher than those for in vitro 
redirected T-cell cytolytic activity. There were no additive or synergistic elevations in cytokines 
when MGD020 and MGD014 were combined. Induction of cytokine production by PBMCs with 
MGD020 in immobilized form is expected because of formation of artificial molecular 
aggregates at high concentrations that allow the monovalent anti-CD3 arms to interact 
multivalently with CD3 receptors on T cells and induce their activation. However, cytokine 
responses measured by these supra-physiologic conditions in vitro are not predictive of systemic 
cytokine responses in vivo, as evidenced by the lack of increase in serum cytokines following 
MGD020 administration at 1 mg/kg to SHIV-infected rhesus monkeys, which resulted in a mean 
Cmax serum concentration of 27,200 ng/mL. 
In vitro binding studies demonstrated MGD020 interactions with cardiolipin-containing 
phospholiposomes. No binding was observed with MGD020 at 10 mcg/mL, but weak to 
moderate binding was observed with MGD020 at 50 or 100 mcg/mL. MGD014 exhibited a 
similar binding profile. This binding property resides within the anti-CD3 portion of the DART 
molecules. The potential for clinical adverse effects due to phospholiposome binding by 
MGD020 is minimal. The anticipated clinical maximal administered dose (MAD) for MGD020 
is 300 mcg/kg, which will yield Cmax of ~5 mcg/mL, a concentration below the threshold for 
detection for binding to cardiolipin-containing phospholiposomes.
No unexpected cross-reactivity was detected for MGD020 by a GLP tissue cross-reactivity study 
conducted on a standard panel of normal human tissues. In addition, no off-target interactions 
were identified for MGD020 or MGD014 by screening a cell-based microarray consisting of 
~5900 human plasma membrane proteins, secreted proteins tethered to the cell surface, and 
heterodimeric receptors.
In summary, administration of MGD020 via IV infusion once weekly for 6 weeks was well 
tolerated at 1 mg/kg/dose in SHIV-infected, ART-suppressed rhesus monkeys. All animals 
survived to the end of the study. There were no MGD020-related clinical signs or changes in 
body weight, hematology parameters, levels of serum cytokines, or activation status of 
circulating T cells.
2.3.2 
Background on MGD014 
MGD014 (HIVA32 x CD3) is an HIV-1 env x CD3 DART molecule. MGD014 is designed to 
target HIV-1-infected, env-expressing cells for recognition and elimination by CD3-expressing 
T lymphocytes as effector cells. The anti-HIV-1 env component of MGD014 is derived from 
A32, a non-neutralizing mAb that recognizes highly conserved regions (C1-C2) of the gp120 
subunit of HIV-1 env and is broadly reactive with env from diverse isolates of HIV-1. The 24 
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MGD020, MGD014
MacroGenics, Inc.
Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
HIV-1 env residues that comprise the conformational epitope plus 12 accessory residues that may 
influence binding to the A32 epitope are conserved at an average frequency of 99.0% (range: 
95.2-99.9%) across all HIV-1 subtypes (based on analysis of 5923 HIV-1 env sequences in the 
Los Alamos National Laboratory database). The anti-human CD3 component of MGD014 is 
derived from mAb hXR32, which is cross-reactive with similar affinity to cynomolgus or rhesus 
monkey CD3. To prolong circulating half-life, MGD014 contains a human IgG1 Fc domain that 
has been mutated to greatly reduce or eliminate effector function via binding to FcγRs and 
complement, while retaining binding to the neonatal Fc receptor to take advantage of the IgG 
salvage pathway mediated by this receptor.
A schematic depicting MGD014 DART molecule structure and mechanism of action is shown in 
Figure 1. Refer to the MGD014 IB for additional information.
2.3.2.1 
MGD014 Clinical Experience 
One clinical study of MGD014, Study CP-MGD014-01, is complete. This trial was a Phase 1, 
open-label, single-center study to evaluate the safety, immunologic, and virologic responses of 
MGD014. Refer to the MGD014 IB for additional information.
As of 26 September 2020, Study CP-MGD014-01 enrolled 21 PWH on ART and dosed with 
single-dose MGD014 as follows: 1 participant each at 0.1 and 0.3 mcg/kg; 4 participants at 
1 mcg/kg; and 3 participants each at 3, 10, 30, 100, and 300 mcg/kg MGD014.
Treatment-related AEs were reported among 4 of 21 (19.0%) participants receiving MGD014. 
These included AEs of feeling hot (n = 1 at 3.0 mcg/kg), diarrhea (n = 1 at 10 mcg/kg), flushing 
(n = 1 at 100 mcg/kg), and electrocardiogram QT prolonged and sensory disturbance (both in the 
same participant at 100 mcg/kg). All AEs were Grade 1 in severity, possibly related to MGD014, 
and occurred on the day of study drug infusion. All treatment-related AEs resolved without 
intervention. No dose-limiting toxicity (DLT), serious adverse events (SAEs), deaths, or 
treatment-related AEs leading to study drug discontinuation were reported.
Eighteen participants were evaluable for preliminary PK analysis following single administration 
of 0.1, 0.3, 1, 3, 10, 30, or 100 mcg/kg of MGD014. Dose normalized values of Cmax and area 
under the concentration-time curve from time zero to infinity (AUC0-inf) are approximately 
constant for the 3 to 100 mcg/kg doses, indicating dose proportionality in MGD014 PK for this 
dose range. Estimates for t1/2, volume of distribution in liters, and CL of MGD014 are 
10-12.5 days, 11-22 L, and 0.04 L/hr, respectively.
There were no increases in serum cytokine (IFN-γ, TNF-α, interleukin [IL]-2, IL-5, IL-6, or 
IL-10) concentrations or increases in activation markers (CD25, CD69, CD134, or CD137) on 
circulating CD4+ or CD8+ T cells following MGD014 administration. Most circulating CD4+ or 
CD8+ T cells exhibited MGD014 binding at 24 hours following MGD014 administration at 
100 or 300 mcg/kg.
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MGD020, MGD014
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Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
2.3.2.2 
MGD014 Non-Clinical Experience 
Non-clinical studies necessary to support clinical studies with MGD014 have been performed 
and are summarized in the MGD014 IB.
2.4 
Dose Selection 
2.4.1 
MGD020 Dose Selection 
A first-in-human starting dose of 1 mcg/kg MGD020 is proposed. Rationale supporting this dose 
selection is based on nonclinical data with MGD020 and nonclinical and clinical data with 
MGD014. MGD014 is a DART molecule with a structure like MGD020 but with specificity for a 
different HIV-1 env epitope. The MGD020 MABEL of 7 ng/mL corresponds to the median EC50 
for in vitro redirected T-cell cytolysis of human CD4+ cells infected by HIV-1 IMCs. An 
MGD020 starting dose of 1 mcg/kg is projected to yield a Cmax of ~24 ng/mL, which exceeds the 
MABEL by ~3-fold. The 1 mcg/kg dose is expected to be a safe starting dose for MGD020 based 
on the rarity of target cells (HIV-1-infected, env-expressing cells) in PWH on ART, and thus the 
risk of adverse effects due to cytokine release or T-cell activation resulting from MGD020-
mediated activity is minimal. The starting dose is supported by a study conducted in SHIV-
infected rhesus monkeys on ART in which MGD020 was well tolerated when administered at 
1 mg/kg weekly for 6 weeks. The 1 mg/kg dose yielded mean Cmax of 27,200 ng/mL with no 
increases in serum cytokines or activation of circulating T cells. The starting dose is also 
supported by clinical experience with MGD014. MGD014 was well tolerated in Study 
CP-MGD014-01 conducted in PWH on ART when administered at doses ranging from 0.1 to 
300 mcg/kg with mean Cmax of 23.7 ng/mL at 1 mcg/kg and 5108 ng/mL at 300 mcg/kg. No DLT 
or SAEs were observed. There were no increases in serum cytokines or activation of circulating 
T cells following MGD014 administration at all dose levels examined.
2.4.1.1 
Rationale for Every 2 Week Administration 
Part 2 uses multi-dose, sequential administration of the combination of a fixed dose of MGD020 
and a fixed dose of MGD014 on a Q2W schedule. The Q2W dosing is based on simulation of PK 
data of the MGD014 dose escalation part of Study CP-MGD014-01. Because the PK of 
MGD020 and MGD014 were comparable in a study conducted in SHIV-infected rhesus monkeys 
on ART, PK of both MGD020 and MGD014 DART molecules is expected to be comparable in 
PWH on ART.
2.4.2 
MGD020 and MGD014 Combination Dose Selection 
In Part 1B, a single ascending dose of MGD020 will be combined with a fixed dose of MGD014. 
The 300 mcg/kg dose of MGD014 was selected on the basis of non-clinical studies and available 
clinical data from Study CP-MGD014-01 (see Section 2.3.2.1). In Study CP-MGD014-01, doses 
ranging from 0.1 to 300 mcg/kg were examined in the single ascending dose part of the study. 
MGD014 was well tolerated with no observed DLTs, SAEs, or treatment-related AEs leading to 
study drug discontinuation. A dose of 300 mcg/kg was selected for evaluation in the multiple-
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MGD020, MGD014
MacroGenics, Inc.
Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
ascending dose part of Study CP-MGD014-01, where MGD014 is administered by IV infusion 
Q2W for a total of 3 infusions over 4 weeks.
In Part 1B, the starting dose of MGD020 is the dose determined to be one dose level lower than 
the MTD/MAD determined in Part 1A. A dose de-escalation design is employed. 
In Part 2, the MGD020 dose will be the MTD/MAD from Part 1B combined with 300 mcg/kg 
MGD014.
2.4.3 
Post-Infusion Monitoring 
Events of infusion related reaction (IRR) including cytokine release syndrome (CRS) typically 
occur within the first hours (up to 24 hours) after infusion of a biologic. These events generally 
appear in the dose finding phase of studies (3, 15, 18, 19). No events of IRR or CRS have been 
observed in participants dosed with MGD014 in Study CP-MGD014-01 to date. 
As a conservative measure, participants will be monitored on-site per Section 6.5.1 following 
study drug infusion(s).
2.5 
Risk Benefit Assessment 
2.5.1 
Risk Assessment 
Details for information on risks of MGD020 and MGD014 are provided in their respective IBs.
One clinical study of MGD014 is ongoing (Study CP-MGD014-01) as described in 
Section 2.3.2.1. MGD014 infusions were well tolerated with no SAEs, DLTs, or increase in 
serum cytokine levels. No clinical studies of MGD020 have been conducted. It is expected 
MGD020 will have similar risks as MGD014, because MGD020 and MGD014 are based on the 
same DART molecule structure. Refer to the respective IBs for a summary of non-clinical 
information.
The combination of MGD020 and MGD014 is expected to have risks similar to administration of 
either study drug alone.
Infusion related reaction and CRS are potential risks of DART molecules. These risks typically 
occur within the first hours after infusion of the study drug. Management of CRS and IRR is 
based on the severity of reaction, including temporarily stopping the infusion, administering 
histamine blockers, corticosteroids, and resuming the infusion of study drug at a slower rate 
(see Section 7.1) (15, 18). 
2.5.2 
Benefit Assessment 
The addition of MGD020 as a single agent or in combination with MGD014 to a participant’s 
ART regimen provides no direct benefit to participants. Participation contributes to ongoing 
HIV-1 research, potentially resulting in the development of new treatments for HIV-1 infection.
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MGD020, MGD014
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Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
2.5.3 
Overall Assessment 
The protocol incorporates risk mitigation measures including eligibility criteria, monitoring of 
participants, and discontinuation criteria. An independent safety monitor will provide study 
oversight and evaluate cumulative safety and other clinical data at regular intervals. Anticipated 
AEs are expected to be managed using standard of care. The risk-benefit profile supports 
investigation of MGD020 as a single agent or in combination with MGD014 in the study 
population. 
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MGD020, MGD014
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Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
3 
STUDY OBJECTIVES 
3.1 
Primary Objective 
Primary Objective 
Outcome or Endpoint
Characterize safety and tolerability of MGD020 as 
a single agent and in combination with MGD014
1. Incidence of treatment-emergent AEs,
SAEs, and AEs leading to
discontinuation
Abbreviations: AE: adverse event; SAE: serious adverse event.
3.2 
Secondary Objectives 
Secondary Objective 
Outcome or Endpoint
Assess PK and immunogenicity (ADA) of 
MGD020
1.Serum MGD020 concentrations
2. Summary PK parameters for MGD020
3. Incidence of ADA to MGD020
Assess PK and immunogenicity (ADA) of 
MGD014
1. Serum MGD014 concentrations
2. Summary PK parameters for MGD014
3. Incidence of ADA to MGD014
Assess serum cytokine levels
1.Serum cytokine concentrations
Abbreviations: ADA: anti-drug antibody; PK: pharmacokinetics.
3.3 
Exploratory Objectives 
Results of exploratory objectives may not be included in the clinical study report (CSR) unless 
they represent meaningful findings.
Exploratory Objective
Outcome or Endpoint
Explore T-cell binding
1.Percentages of peripheral CD4 and CD8 T cells with
study drug bound over time
Explore immunologic responses
1.Changes in markers of activation or exhaustion on
peripheral CD4 and CD8 T cells over time
Explore markers of persistent HIV-1
1.Changes in frequency of resting CD4+ T-cell
infection by QVOA and/or IPDA
2.Changes in levels of rca-RNA
3.Changes in levels of residual low-level HIV-1
viremia quantified by SCA
Explore correlations between 
virologic and immunologic markers
1.Association between changes in immunologic and
virologic markers
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MGD020, MGD014
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Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
Abbreviations: CD: cluster of differentiation; HIV-1: human immunodeficiency virus-1; IPDA: intact proviral 
DNA assay; QVOA: quantitative viral outgrowth assay; rca-RNA: resting CD4+ T-cell-associated HIV-1 gag 
RNA; RNA: ribonucleic acid; SCA: single copy assay. 
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MGD020, MGD014
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Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
4 
STUDY DESIGN 
4.1 
Overall Study Design 
Study CP-MGD020-01 is a phase 1, open-label, dose-escalation, and multi-dose expansion study 
of MGD020 as a single agent or in combination with MGD014 in PWH on ART. The study is 
designed to characterize the safety, tolerability, PK, immunogenicity, and PD of the study drugs. 
The study consists of 3 parts (Part 1A, Part 1B, and Part 2). In all parts, the participant’s standard 
of care ART regimen is continued throughout the study period.
Part 1A evaluates single ascending doses of MGD020, Part 1B evaluates single ascending doses 
of MGD020 in combination with fixed-dose MGD014, and Part 2 is a multi-dose expansion 
cohort with sequential administration of combination MGD020 and MGD014 Q2W for 
3 combination doses over 4 weeks.
The study consists of a screening phase of up to 8 weeks, and an approximately 6-week (Part 1A 
and Part 1B) or 11-week (Part 2) study period (dosing and follow-up), which concludes with an 
end of study visit (EOSV) approximately 6 weeks (Part 1A and Part 1B) or 7 weeks (Part 2) after 
the last dose of study drug. Thus, the total study duration for each participant is approximately 
14 weeks (Part 1A and Part 1B) or 19 weeks (Part 2). If a participant is unable to complete the 
study, but has not withdrawn consent, the EOSV is conducted 30 days (+3 day window) after the 
last dose of study drug.
An independent safety monitor will provide study oversight and evaluate cumulative safety and 
other clinical data at regular intervals as described in Section 14.9.
4.1.1 
Part 1A: Single Ascending Dose of MGD020 
Part 1A evaluates single ascending doses of MGD020 with a 1+3 design for cohorts 1–3 and a 
3+3 design for cohorts 4–6. A 2-week DLT period is observed prior to escalation to the next 
cohort level.
Part 1A has 6 cohorts (Table 1). For cohorts 1–3, each cohort consists of 1 participant, unless a 
DLT occurs, which prompts expansion of the cohort to add an additional 3 participants. For 
cohorts 4–6, each cohort consists of 3 participants, with at least 24 hours between dosing of each 
participant within the cohort. If a DLT is experienced in 1 of the 3 participants in the cohort, the 
cohort will be expanded to add 3 additional participants. If one or more of the additional 3 
participants treated at any given dose level also experiences a DLT, then that dose level will be 
defined as exceeding the MTD. The MTD will then be defined as the next lower dose level of 
MGD020. Escalation proceeds according to the rules described in Section 4.2 until either the 
MTD or MAD is determined.
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Table 1
MGD020 Dose Escalation Scheme (Part 1A) 
Cohort 
MGD020 Dose (mcg/kg) 
Design 
1 
1 
1+3 
2 
3 
1+3 
3 
10 
1+3 
4 
30 
3+3 
5 
100 
3+3 
6 
300 
3+3 
4.1.2 
Part 1B: Single Ascending Dose of MGD020 and Fixed-Dose of 
MGD014 
Part 1B commences only after the MTD or MAD of single-agent MGD020 has been determined 
in Part 1A. During Part 1B, participants will be enrolled and treated with a single ascending dose 
of MGD020 in combination with a fixed dose of 300 mcg/kg MGD014. 
MGD020 and MGD014 will be administered at the doses shown in Table 2 using a 3+3 design, 
beginning with Cohort 1, with at least 72 hours between dosing of each participant within a 
cohort. The first cohort will be treated with a single dose of MGD020 at a dose determined to be 
one dose level lower than the MTD/MAD from Part 1A (i.e., one dose level lower than 
MTD1A/MAD1A). MGD014 is dosed at 300 mcg/kg, as determined from Study CP-MGD014-01. 
In Part 1A, the MGD020 dose is increased in half-log increments from 1 to a maximum of 
300 mcg/kg. In Part 1B, the maximum starting dose of MGD020 for Cohort 1 of Part 1B will 
thus be 100 mcg/kg (one dose level below the Cohort 6 dose of 300 mcg/kg). In combination 
with MGD014 at 300 mcg/kg, this would yield a maximum total DART dose of 400 mcg/kg for 
Cohort 1 of Part 1B, which is less than a half-log increment over the total DART dose that would 
have been tolerated in Part 1A.
Escalation to the next cohort follows the rules described in Section 4.2.
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Table 2
MGD020 and MGD014 Combination Dose Escalation Scheme 
(Part 1B) 
Cohort 
MGD020 a (mcg/kg) 
MGD014 (mcg/kg) 
Design 
-1 b
MGD020 MTD1A/MAD1A -2
300 
3+3 
1 
MGD020 MTD1A/MAD1A -1 
300 
3+3 
2 
MGD020 MTD1A/MAD1A
300 
3+3 
a 
Dosing for Part 1B will begin with Cohort 1. The MGD020 dose in Cohort 1 will be one dose level below the 
single-agent MTD/MAD in Part 1A. For example, if the MTD/MAD in Part 1A for MGD020 is 300 mcg/kg, 
Cohort 1 of Part 1B would receive 100 mcg/kg MGD020 + 300 mcg/kg MGD014. 
b 
If the dose level in Part 1B Cohort 1 exceeds the MTD, de-escalation to Cohort -1 may be considered. For 
example, if MTD is exceeded when the Part 1B Cohort 1 dose is 100 mcg/kg MGD020 + 300 mcg/kg 
MGD014, Cohort -1 of Part 1B would receive 30 mcg/kg MGD020 (MTD1A/MAD1A -2 dose from Part 1A) + 
300 mcg/kg MGD014. 
Participants who completed Part 1A may be considered for enrollment in Part 1B, provided they 
meet all eligibility criteria, did not experience DLT in Part 1A, and do not have detectable ADA 
against MGD014 and/or MGD020 at the completion of Part 1A.
4.1.3 
Part 2: Multi-Dose Expansion Cohort: Fixed-Dose of MGD020 
and Fixed-Dose of MGD014 
Part 2 commences only after an MTD or MAD of MGD020 in combination with MGD014 has 
been determined in Part 1B. Part 2 is a multi-dose expansion cohort with sequential infusions of 
a fixed dose of MGD020 in combination with a fixed dose of MGD014 administered Q2W for 
3 combination doses over 4 weeks (Table 3). MGD020 is dosed at the MTD/MAD determined in 
Part 1B (i.e., MTD1B/MAD1B). MGD014 is dosed at 300 mcg/kg, as determined from Study 
CP-MGD014-01. 
Up to 6 participants may be enrolled in Part 2 using a conventional 3+3 design. If 2 or more 
participants in the cohort of 6 participants experience a DLT, enrollment and further dosing of 
ongoing participants will be suspended pending further assessment of safety data. 
Table 3
MGD020 and MGD014 Combination Multi-Dose Expansion 
Cohort Scheme (Part 2)     
Cohort 
MGD020 a (mcg/kg) 
MGD014 (mcg/kg) 
Design 
1 
MGD020 MTD1B/MAD1B 
300 
3+3 
a 
The MGD020 dose is determined by the combination MTD or MAD in Part 1B. 
Participants who completed Part 1 may be considered for enrollment in Part 2, provided they 
meet all eligibility criteria, did not experience DLT in Part 1, and do not have detectable ADA 
against MGD014 and/or MGD020 at the completion of Part 1.
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4.2 
Dose Escalation Rules 
Dose escalation from one dose cohort to the next higher dose cohort depends upon the clinical 
safety profile (e.g., evaluation of AEs, vital signs, ECGs, and clinical laboratory parameters) of 
the dose administered up to and including the preceding dose cohort. Dose escalation to the next 
dose level is permitted only after the participants enrolled in the current dose cohort have 
completed the DLT evaluation period and the safety data have been reviewed by the sponsor 
medical monitor and the study investigators. Evaluation of safety data from each cohort will 
include an assessment of the proportion of participants who receive planned doses, and the 
percentage of participants that require dose reductions or dose discontinuations for toxicity. 
Available data from participants both during and beyond the 2-week DLT evaluation period will 
be considered when making dose escalation decisions. 
Dose escalation continues until all cohorts are enrolled, provided the MTD is not exceeded. If 2 
or more of the participants in a dose cohort experience a DLT, the MTD will have been 
exceeded. If a DLT occurs in 1 participant in a dose cohort, the dose cohort will be expanded to 
an additional 3 participants. Prior to dosing any additional participants at the same dose, study 
drug safety and tolerability are evaluated over the entire 2-week DLT period for the first 
additional participant.
If the first additional participant does not experience a DLT during the DLT period, the 2 other 
additional participants can proceed to receive study drug at this dose with a minimum of 
24 hours between dosing of each participant. If none of the 3 additional participants experience a 
DLT during the DLT period, dose escalation to the next dose cohort may proceed.
If any of the 3 additional participants experiences a DLT during the DLT period (≥ 2 DLTs within 
the same dose cohort), no further participants will receive a dose at this dose level, as the MTD 
will have been exceeded. Part 1B then proceeds at one dose level below the single-agent 
MTD1A/MAD1A of MGD020 determined in Part 1A. If only 1 participant was enrolled at the 
prior dose level in Part 1A, an additional 3 participants will be enrolled at the prior dose for 
evaluation of the MTD/MAD.
Participants who do not complete the DLT period for reasons other than study drug-related 
toxicity may be replaced in the same dose cohort. At the discretion of the sponsor, dose 
escalation may be stopped before an MTD is reached. In this case, the MAD may be chosen 
based on an assessment of PK, pharmacodynamics (PD), and safety data. For example, dose 
escalation may be stopped if study drug binding to CD3+ T cells exceeds 95% within a dose 
cohort.
4.3 
Dose-Limiting Toxicity 
DLT is defined based on treatment-related AEs that occur during the DLT period following study 
drug administration. The DLT period is defined as the period from initial infusion of study 
drug(s) through 2 weeks following the last study drug infusion.
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Severity of AEs is graded according to the National Institute of Allergy and Infectious Diseases 
(NIAID) Division of Acquired Immunodeficiency Syndrome (DAIDS) Table for Grading the 
Severity of Adult and Pediatric Adverse Events, corrected version 2.1, July 2017 (see 
Section 12.1.6). 
A DLT is any ≥ Grade 2 treatment-related AE, with the following exceptions, based on the 
medical judgement of the investigator (or designee) and medical monitor:
x
Grade 2 laboratory abnormality that lasts < 72 hours and is not otherwise associated
with clinical complications.
x
Grade 2 fatigue that lasts < 7 days.
4.4 
Guidelines for Dose Modification 
No dose modifications are allowed. A reduction of the infusion rate is allowed during 
re-challenge for an infusion reaction (Section 7.1). 
4.4.1 
Dose Delays 
Hold study drug administration for toxicity, pending assessment, management, and resolution of 
the AE. If the AE is assessed as unrelated to study drug(s) or does not meet DLT criteria, study 
drug(s) may be restarted at the previous dose and schedule, after appropriate recovery. 
In Part 2, a dose delay of up to 7 days is allowed for drug-related or non-drug related AEs. Refer 
to Section 7.1 for specific guidance on restarting study therapy after infusion reactions. A dose 
delay > 7 days due to drug-related toxicity will prompt study drug discontinuation.
4.5 
Study Drug Discontinuation 
Administration of study drug(s) may continue as specified in the protocol until any of the 
following conditions are met:
x
Adverse event requiring study drug discontinuation (including DLT)
x
Completed dosing per protocol
x
Death
x
Lost to follow-up
x
Investigator decision
x
Pregnancy
x
Major protocol deviation requiring study drug discontinuation
x
Study terminated
x
Participant decided to discontinue study drug
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x
Participant withdrew consent from study
4.6 
Follow-Up 
In Part 1A and Part 1B, after completion of study drug dosing, participants enter the follow-up 
period, i.e., visits 2 through 7, per the schedule in Appendix 1.
In Part 2, after study drug discontinuation or completion of all 3 combination doses, participants 
enter the follow-up period, i.e., visits 7 through 9, per the schedule in Appendix 1, if feasible. 
Visit 7 should be scheduled approximately 14 days after study drug discontinuation. Additional 
and/or more frequent safety laboratory tests may be performed as clinically indicated per the 
investigator’s discretion.
In all study parts, if a participant is unable to complete the study but has not withdrawn consent, 
the EOSV (i.e., visit 8 in Part 1A and Part 1B, and visit 10 in Part 2) is conducted 30 days 
(+3 day window) after the last dose of study drug.
Participants may be classified as lost to follow-up after both of the following criteria are met: 
x
Failure of participant to respond or reply to 3 documented phone or electronic mail
contact attempts.
x
Failure of participant to respond to a certified letter.
4.7 
Study Discontinuation 
Participants who discontinue study drug(s) but are still on study in the follow-up period can be 
terminated from the study for the following reasons:
x
Completed protocol-defined follow-up period
x
Death
x
Lost to follow-up
x
Investigator decision
x
Study terminated
x
Participant withdrew consent from study
4.8 
Study Duration 
For individual participants, the study duration is approximately 14 weeks in Part 1A and Part 1B. 
The study duration is approximately 19 weeks in Part 2. The study duration includes screening, 
dosing, follow-up, and an end of study visit.
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The overall study duration is approximately 24 months. This estimate may vary from that 
observed in the actual conduct of the study.
4.9 
End of Study 
The end of study for each participant occurs when study discontinuation criteria are met per 
Section 4.7. 
The end of the overall study occurs at the time of study database lock. Database lock occurs 
when the last participant has met off-study criteria and the data collection process is complete.
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5 
ELIGIBILITY CRITERIA 
All inclusion criteria and no exclusion criteria must be met to enroll. No exceptions to these 
criteria will be granted by the sponsor.
5.1 
Inclusion Criteria 
1. Ability to provide informed consent. Participants must be willing and able to comply
with study procedures.
2. Aged ≥ 18 years and ≤ 70 years of age.
3. HIV-1 infection documented by rapid HIV test or HIV enzyme or chemiluminescence
immunoassay (E/CIA) test and confirmed by Western blot or a second antibody test
(other than the initial rapid HIV test or E/CIA), HIV-1 antigen, or plasma HIV-1 RNA
viral assay.
4. Plasma HIV-1 RNA viral load must meet the following conditions:
a.
< 50 copies/mL at 2 time points within 24 months prior to screening (1 time point
within 12 months prior to screening).
b. < 50 copies/mL at screening.
c.
Not ≥ 50 copies/mL on 2 consecutive time points within 24 months nor
> 1000 copies/mL at any time within 6 months prior to screening.
5. On continuous ART for at least 24 months prior to screening and must continue ART
throughout the study. Participant must not have missed > 9 total days or > 4
consecutive days in the 3 months prior to screening. No changes in ART medication or
modifications of ART dosing are allowed within 30 days prior to screening. Permitted
ART regimens include:
a.
At least 3 ART drugs (< 200 mg ritonavir [total daily dose] or cobicistat [any dose]
are not considered as one of the 3 ART drugs). One of the ART drugs must include
an integrase inhibitor, non-nucleoside reverse transcriptase inhibitor (NNRTI), or
boosted protease inhibitor.
or
b. At least 2 ART drugs, in which one of the drugs is either a boosted protease
inhibitor or an integrase inhibitor, that are Food and Drug Administration (FDA)
approved or are recommended by Department of Health and Human Services
Treatment Guidelines.
6. CD4 cell count > 350 cells/mm3 at screening.
7. Hepatitis C virus (HCV) antibody negative or HCV RNA negative.
8. Hepatitis B surface antigen negative.
9. Adequate vascular access.
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10. Clinical laboratory parameters obtained at screening as follows:
a.
Platelet count ≥ 125 × 103/μL.
b. Absolute neutrophil count ≥ 1.5 × 103/μL.
c.
Hemoglobin ≥ 12 g/dL (male) and ≥ 11 g/dL (females)
d. Prothrombin time or international normalized ratio (INR) ≤ 1.1 × upper limit of
normal (ULN)
e.
Serum total bilirubin < 1.5 × ULN. If total bilirubin is elevated, direct bilirubin
< 2 × ULN. If ART includes atazanavir, direct bilirubin must be ≤ 1.0 mg/dL.
f.
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 ×
ULN
g. Alkaline phosphatase (ALP) ≤ 1.5 × ULN
h. Estimated glomerular filtration rate (eGFR) > 60 mL/min as determined by the
Chronic Kidney Disease Epidemiology Collaboration equation.
i.
Negative serum pregnancy test for individuals of childbearing potential (IOCBP)
11. IOCBP, defined as assignment of female sex at birth, not surgically sterilized
(hysterectomy, bilateral salpingectomy, and bilateral oophorectomy), and between
menarche and 1-year post menopause, must have a negative serum pregnancy test
performed within 72 hours prior to initiation of study drug. IOCBP must agree to
abstain from egg donation during the course of the study.
12. IOCBP and male participants with partners of IOCBP must agree to use highly
effective methods of contraception according to Section 8.1.3 from the time of
consent through 6 months after discontinuation of study drug. Male participants must
agree to abstain from sperm donation during the course of the study.
13. IOCBP is not pregnant, expecting to become pregnant, or breastfeeding or male
participant is not expecting to father children within the projected duration of the
study, starting with screening visit through 6 months after the last dose of study drug.
5.2 
Exclusion Criteria 
1. History or other evidence of severe illness, immunodeficiency other than HIV-1, or
any other condition, such as known psychiatric or substance abuse disorder, that in the
opinion of the investigator would impair the ability to receive, tolerate, or comply with
study drug administration or study procedures.
2. History of any HIV-1 vaccine or HIV-1 immunotherapy, except MGD014 or
MGD020, within 6 months prior to screening.
3. Clinically significant cardiovascular disease within 12 months prior to screening
(unless otherwise stated) including but not limited to:
a.
Myocardial infarction or unstable angina within the past 6 months.
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b. Cardiac arrhythmias.
c.
Uncontrolled hypertension at screening: systolic blood pressure > 180 mmHg,
diastolic blood pressure >100 mmHg that is sustained on repeat measurement
(without intervention).
d. Deep vein thrombosis or pulmonary embolism within the past 6 months.
e.
Cerebrovascular accident within the past 6 months.
f.
QTc prolongation > 480 millisecond calculated from the average of 3 repeat
electrocardiograms (ECGs) obtained at screening in approximately 1-minute
intervals.
g. Congestive heart failure (New York Heart Association class III-IV).
h. Pericarditis.
i.
Pericardial effusion.
j.
Myocarditis.
4. Diabetes mellitus ≥ Grade 3 per DAIDS criteria (defined as uncontrolled despite
treatment modification or hospitalization for immediate glucose control indicated).
5. Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral
antibiotic, antiviral, or antifungal treatment within 7 days prior to the initiation of
study drug. Participants requiring any systemic antiviral, antifungal, or antibacterial
therapy for active infection must have completed treatment no less than 1 week prior
to initiation of study drug.
6. Active coronavirus disease 19 (COVID-19)/severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) infection. While SARS-CoV-2 testing is not mandatory
for study entry, testing should follow local clinical practice guidelines/standards. A
positive test result for SARS-CoV-2 infection, known asymptomatic infection, or
suspected infection is exclusionary.
7. Active, untreated syphilis (defined as rapid plasma reagin [RPR] positive at screening
without history of treatment).
8. Known allergic hypersensitivity to recombinant proteins, 
 or any
excipient contained in the study drug or vehicle formulation for MGD020 or
MGD014.
9. History of severe allergic reaction with generalized urticarial, angioedema, or
anaphylaxis.
10. History of malignancy that may require systemic anti-cancer therapy or radiation
therapy. A history of non-melanoma skin cancer with documentation of complete
resection or resolution per licensed and board-certified dermatologist is not
exclusionary.
11. History of uncontrolled seizure within the past 2 years. A seizure disorder controlled
on anti-epileptic therapy is not exclusionary.
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12. History of organ or tissue transplantation.
13. History of autoimmune disease, including type I diabetes mellitus, with the specific
exceptions of:
a.
Vitiligo.
b. Resolved childhood atopic dermatitis.
c.
Psoriasis (except psoriatic arthritis) not requiring systemic treatment (within the
past 2 years).
d. Euthyroid Graves’ disease or non-autoimmune hypothyroidism.
14. History of unstable asthma, including any of the following events within the past
12 months:
a.
> 1 exacerbation of asthma symptoms treated with oral/parenteral corticosteroids.
b. Emergency care, urgent care, hospitalization, or intubation for asthma.
15. History of coagulopathy or other bleeding disorder.
16. Participation in another investigational clinical research study within 60 days prior to
screening. The following exceptions apply:
a.
Enrollment in an ART study using FDA-approved ART.
b. Enrollment in the ACTG 5332 REPRIEVE study (NCT02344290) and using
FDA-approved pitavastatin provided the participant has been on study for
≥ 4 months.
17. Use of any of the following within 90 days prior to planned first dose of study drug:
any blood product, immune globulin, immunomodulatory therapy, cytokine therapy, or
growth stimulating factors such as systemic corticosteroids, cyclosporine,
methotrexate, azathioprine, anti-CD25 antibody, interferon, IL-2, systemic cytotoxic
chemotherapy, or investigational therapy. Intent to use immunomodulators (e.g., IL-2,
IL-12, interferons, or tumor necrosis factor [TNF] modifiers) during the study.
18. History of virologic failure on an ART regimen containing FDA-approved HIV-1 entry
inhibitors (e.g., maraviroc, enfuvirtide, fostemsavir, and/or ibalizumab). Virologic
failure is defined as a confirmed plasma HIV-1 RNA ≥ 150 copies/mL following
assessment of drug adherence, repeat HIV-1 RNA testing with continued treatment,
and/or resistance testing.
19. Current use of an FDA-approved HIV-1 entry inhibitor.
20. For participants with prior exposure to MGD020, positive ADA to MGD020.
21. For participants with prior exposure to MGD014, positive ADA to MGD014 (Part 1B
or Part 2 only).
22. Prisoners or other individuals who are involuntarily detained.
23. Employees of the sponsor unless approved by the Institutional Review Board (IRB) of
record.
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24. Any investigative site personnel directly affiliated with this study.
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6 
STUDY DRUG DOSING 
6.1 
Description of Dosing Regimens 
Study drug(s) are administered either as a single dose of MGD020 (Part 1A), a sequential 
infusion of MGD020 and MGD014 for a single combination dose (Part 1B), or sequential 
infusions of the MGD020 and MGD014 combination dosed Q2W for a total of 3 combination 
doses (Part 2).
MGD020 is infused first on days when both MGD020 and MGD014 are administered. Infusion 
of MGD014 will start at least 30 minutes after the end of MGD020 infusion. The infusions are 
not to be administered at the same time to ensure that rapid onset infusion reactions (e.g., 
anaphylaxis) can likely be attributed to a single study drug. The interval between infusions was 
selected empirically, based on the time required to set up a second infusion, the required post-
infusion observation period, and a desire to keep the day as short as possible for the participant. 
Infusions may be administered into the same arm as local reactions with DART molecule 
administration are unlikely. Infusion reactions that are delayed (i.e., occur after the completion of 
study drug infusion) will by necessity be attributed to both drugs as it will not be possible to 
determine which drug (or both) caused the event.
Refer to Sections 6.4.1, 6.4.2, and the pharmacy manual for further information on study drug 
dosing.
6.2 
Method of Assigning Participants to Cohorts 
Participants are assigned sequentially to the dose escalation and multi-dose expansion cohorts. 
Procedures for enrollment, registration, and cohort assignment are specified in Section 9.4.
6.3 
Blinding 
This is an open-label study.
6.4 
Study Drugs and Supplies 
6.4.1 
MGD020 
The concentration and function of each component in the DP are summarized in Table 4.
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MGD020 is supplied as a sterile aqueous solution packaged in a United States Pharmacopeia 
(USP) and European Pharmacopoeia (Ph. Eur.) conforming Type I borosilicate, 10 cc clear flint 
glass vial with a 20 mm West 4023/50 gray butyl rubber serum stopper with B2-40® and 
FluroTec® coating on the plug. The vial is sealed with a 20 mm TruEdge® aluminum closure with 
a plastic overseal.
MGD020 will generally be administered over 60 minutes by IV infusion after dilution in 
 Infusion may be 
slowed for IRR (see Section 7.1) but should be completed within 120 minutes. MGD020 must 
not be administered as an IV push or bolus.
6.4.1.1 
Storage and Handling of MGD020 
Vials containing MGD020 should be stored upright under refrigerated condition at 2–8°C (36–
46°F) in an appropriate, locked room accessible only to pharmacy personnel, the study 
investigator, or duly designated personnel. MGD020 vials should be protected from light during 
storage and should not be shaken or frozen during storage. Standard laboratory practices should 
be used for avoidance of contact with MGD020.
Additional details regarding MGD020 storage, handling, and accountability can be found in the 
pharmacy manual.
6.4.2 
MGD014 
 
 
 
 
 
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MGD014 is supplied as a sterile aqueous solution packaged in a USP and Ph. Eur. conforming 
Type I borosilicate, 10 cc clear flint glass vial with a 20 mm West 4023/50 gray butyl rubber 
stopper with B2-40® and FluroTec® coating on the plug. The vial is sealed with a 20 mm 
TruEdge® aluminum closure with a plastic overseal.
MGD014 will generally be administered over 60 minutes by IV infusion after dilution in 
 Infusion may be 
slowed for IRR (see Section 7.1) but should be completed within 120 minutes. MGD014 must 
not be administered as an IV push or bolus.
6.4.2.1 
Storage and Handling of MGD014 
Vials containing MGD014 should be stored upright under refrigerated condition at 2–8°C (36–
46°F) in an appropriate, locked room accessible only to pharmacy personnel, the study 
investigator, or duly designated personnel. MGD014 vials should be protected from light during 
storage and should not be shaken or frozen during storage. Standard laboratory practices should 
be used for avoidance of contact with MGD014.
Additional details regarding MGD014 storage, handling, and accountability can be found in the 
pharmacy manual.
6.4.3 
Vehicle 
MGD020 DP must be diluted in a 
 Vehicle 
 
 prior to administration. MGD014 DP must also be diluted in the 
 Vehicle prior to administration.
 Vehicle is supplied as a sterile aqueous solution packaged in a USP and Ph. Eur. 
conforming Type I borosilicate, 50 cc clear flint glass vial with a 20 mm West 4432/50 gray butyl 
rubber serum stopper with FluroTec® coating on the plug. The vial is sealed with a 20 mm 
TruEdge® aluminum closure with a plastic overseal.
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6.4.3.1 
Storage and Handling of 
 Vehicle 
Vials containing 
Vehicle should be stored upright under refrigerated condition at 
2–8°C (36–46°F) in an appropriate, locked room accessible only to pharmacy personnel, the 
study investigator, or duly designated personnel. 
 Vehicle vials should not be frozen and 
should be protected from light during storage. Standard laboratory practices should be used for 
avoidance of contact with 
Vehicle.
Additional details regarding 
Vehicle storage, handling, and accountability can be found 
in the pharmacy manual.
6.5 
Study Drug Preparation and Administration 
MGD020, MGD014, and 
Vehicle will be supplied by the sponsor.
Instructions on the preparation of the study drugs are each detailed separately in the respective 
pharmacy manuals.
6.5.1 
Monitoring Post-administration 
Infusion reactions (including CRS) may occur with administration of protein-based DART 
molecules such as MGD020 or MGD014. Precautions for anaphylaxis should be observed during 
study drug administration. Please refer to Section 7.1.3 for specific guidelines regarding the 
management of infusion reactions. Supportive measures will be provided throughout the study 
according to institutional standards.
The duration of on-site monitoring following study drug infusion will vary from 2 to 12 hours 
post-infusion depending on the protocol stage:
x
Part 1A and Part 1B: Each participant will be monitored for 12 hours post-infusion
of study drug(s).
x
Part 2: Each participant will be monitored for 6 hours following their first MGD020
and MGD014 sequential infusion. The duration of direct monitoring may be reduced
to 2 hours for subsequent sequential infusions; participants may be requested to stay
on site for an additional 2 hours to facilitate sample collection per Appendix 2.
During the monitoring period, participants are observed for clinical AEs. Vital signs, ECGs, and 
blood samples are obtained per the schedules in Appendix 1 and Appendix 2. When indicated, 
PK, ADA, and serum cytokine samples may be obtained selectively at additional time points for 
participants experiencing IRR and/or CRS (Appendix 2).
6.6 
Compliance 
Study drug will be administered by qualified healthcare professionals under the supervision of 
the investigator. Records of dose calculation, administration, and dosing regimen will be 
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maintained by study staff. The sponsor or designated monitor will review the study site 
pharmacy and participant medical records according to the clinical monitoring plan.
6.7 
Accountability 
Accounting of all study drugs must be maintained. The investigator agrees to keep an inventory 
of study drugs using the institution’s drug accountability logs or logs provided by sponsor. The 
investigator will maintain records of temperature monitoring of study drugs. Drug disposition 
records must be kept in compliance with applicable guidelines and regulations.
A pharmacy manual will be provided to the investigator or designee. When the study is 
completed, copies of all study drug accountability records must be provided to the sponsor. 
Original accountability records for study drugs must be maintained with the rest of the 
documentation for inspection by the study monitors. 
6.8 
Disposition of Study Drug at End of Study 
All unopened vials of study drug will be destroyed on site unless return to depot is authorized by 
the sponsor or its representative. Additional details regarding storage, handling, and 
accountability can be found in the pharmacy manual.
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7 
ADVERSE EVENTS AND SUPPORTIVE CARE MEASURES 
7.1 
Infusion Related Reactions Including Cytokine Release Syndrome 
Infusion reactions including CRS may occur with MGD020 and/or MGD014. These reactions 
may manifest with signs and symptoms that may include, but are not limited to fever, chills, 
headache, rash, pruritus, arthralgia, hypo- or hypertension, and/or bronchospasm. These reactions 
should be managed according to the standard practice of medicine. General guidelines for the 
management of such reactions are provided in this section. Severe reactions may require 
intensive interventions including, but not limited to, hospitalization, steroids, anti-TNF-α 
antibodies, and/or IL-6 inhibitors.
The infusion room/area must have immediate access to medications and supportive measures for 
the treatment of severe hypersensitivity reactions, inclusive of resuscitation equipment and 
necessary supplies for emergency management of an allergic/toxic reaction. 
7.1.1 
Grading and Management of Infusion Reactions 
Infusion reactions and CRS will be graded according to the criteria in the DAIDS Table for 
Grading the Severity of Adult and Pediatric Adverse Events, corrected version 2.1, July 2017.
7.1.2 
Premedication 
The following are guidelines for the investigator to be followed to mitigate potential infusion 
reactions. Equivalent medications may be substituted based on the local practice of medicine and 
availability.
Approximately 60 minutes prior to infusion of study drug, premedicate as follows:
x
Acetaminophen 650 mg oral administration (PO)
x
H1-antagonist: Diphenhydramine 50 mg PO or IV or equivalent
x
H2-antagonist: Famotidine 40 mg PO or 20 mg IV or equivalent
Hydrocortisone (50 to 100 mg IV) or dexamethasone (10 to 20 mg IV), may be added to the 
infusion prophylaxis regimen if ≥ Grade 2 IRR occurs with the first infusion. 
7.1.3 
Management of Observed Infusion Reactions 
The following are suggested guidelines regarding management of infusion reactions including 
CRS. These guidelines may be modified as needed by the investigator or designee according to 
institutional standards. Equivalent medications may be substituted based on the local practice of 
medicine and availability.
Record modifications of the infusion of study drug(s) including interruption, reduction in 
infusion rate, and duration of interruption.
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Grade 1:
x
Slow the infusion rate by 50%.
x
Monitor the participant for worsening of condition.
x
If the infusion reaction recurs and/or persists at the decreased rate of infusion, the
infusion rate may be further reduced by 50% one additional time only.
x
Continue rate at 50% reduction and increase dose rate to the original rate by doubling
the infusion rate after 30 minutes, as tolerated. If applicable, consider beginning all
subsequent infusions at 50% rate and increasing as tolerated.
x
If symptoms persist but do not worsen, completion of the infusion will be at the
discretion of the site investigator or designee, with careful monitoring.
Grade 2:
x
Stop the infusion.
x
Administer diphenhydramine hydrochloride 25–50 mg IV.
x
Acetaminophen (or equivalent) 650–1000 mg PO or ibuprofen 400 mg PO for fever.
x
Oxygen and bronchodilators as needed.
x
Resume the infusion at 50% of the prior rate once the infusion reaction has resolved or
decreased to Grade 1. The rate may then be escalated to the original rate after
30 minutes, as tolerated. If applicable, consider beginning all subsequent infusions at
50% rate and increasing as tolerated.
x
Monitor for worsening condition. If symptoms recur, discontinue the infusion; no
further study drug will be administered at that visit.
Grade 3:
x
STOP THE INFUSION AND DISCONNECT THE INFUSION TUBING FROM THE
PARTICIPANT. NO FURTHER STUDY DRUG SHOULD BE ADMINISTERED AT
THIS VISIT.
x
TO AVOID EXACERBATION OF INFUSION REACTION OR CRS: DO NOT
FLUSH THE TUBING – ASPIRATE RESIDUAL DRUG FROM THE VASCULAR
ACCESS DEVICE.
x
Administer diphenhydramine hydrochloride 25–50 mg IV, dexamethasone 10–20 mg
IV (or equivalent), and other medications/treatment as medically indicated. Higher
doses of corticosteroids (e.g., methylprednisolone 2–4 mg/kg IV or equivalent) may
also be considered for acute management.
x
Consider administering tocilizumab (an IL-6 receptor inhibitor) 4–8 mg/kg IV, in the
absence of colitis.
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x
Consider IV fluids, supplemental oxygen, and bronchodilators as appropriate.
x
The participant may restart study drug(s) at the next scheduled dose if symptoms have
completely resolved within 12 hours. A 50% infusion rate reduction is required.
Grade 4:
x
STOP THE INFUSION AND DISCONNECT THE INFUSION TUBING FROM THE
PARTICIPANT. NO FURTHER STUDY DRUG SHOULD BE ADMINISTERED.
x
TO AVOID EXACERBATION OF INFUSION REACTION OR CRS: DO NOT
FLUSH THE TUBING – ASPIRATE RESIDUAL DRUG FROM THE VASCULAR
ACCESS DEVICE.
x
Administer diphenhydramine hydrochloride 50 mg IV, dexamethasone 20 mg IV (or
higher doses of steroids, e.g., methylprednisolone 2–4 mg/kg IV or equivalent, as
appropriate) and other medications/treatment as medically indicated.
x
Consider administering tocilizumab (an IL-6 receptor inhibitor) 4–8 mg/kg IV, in the
absence of colitis.
x
Give epinephrine or bronchodilators as indicated.
x
Support ventilation and blood pressure as indicated.
x
Permanently discontinue study drug(s).
7.2 
COVID-19/SARS-CoV-2 Infection or Vaccination 
Symptoms of COVID-19 will be carefully assessed and treated based on the assessment of the 
investigator (or designee). An evaluation for infection, including COVID-19, should be 
performed.
Participants with confirmed (positive by regulatory authority approved/authorized test) or 
presumed (test pending/clinical suspicion) COVID-19/SARS-CoV-2 infection will be 
discontinued from study drug.
At the discretion of the investigator, SARS-CoV-2 vaccine may be administered per local 
practice (refer to Section 8.1.1 for further guidance on vaccination).
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8 
CONCOMITANT THERAPY AND RESTRICTIONS 
8.1 
Concomitant Therapy 
Concomitant medications administered from within 4 weeks prior to first dose of study drug, 
during the participation in the study, and until the end of study visit must be recorded in the 
source document and on the electronic case report form (eCRF). 
The ART regimen is a concomitant therapy and recorded in the source document and eCRF. 
Participants are required to continue their baseline ART throughout the study. ART will not be 
provided by the study.
8.1.1 
Prohibited Therapy 
Refer to the respective IBs for information on special warnings, precautions for use, interaction 
with other medicinal products, other forms of interaction, and undesirable effects associated with 
study drug(s).
The following rules apply during study participation:
x
Participants may not receive other investigational drugs.
x
Participants may not be switched to another ART regimen.
x
Use of other immune-suppressive agents including corticosteroids is prohibited, unless
used to treat an AE.
x
Vaccinations are prohibited within 14 days prior to first administration of study drug
through 14 days after the last dose of study drug(s).
8.1.2 
Permitted Therapy 
Participants may receive the following concurrent therapy after consultation with the sponsor:
x
Antipyretics, analgesics, antidepressants, sleep medications, megestrol acetate,
testosterone, and other medications for chronic conditions that do not interact with
ART regimen, MGD020, or MGD014.
x
Oral and topical antibiotics for bacterial infection.
x
Intermittent inhaled (e.g., for chronic pulmonary disease or asthma), otic, ophthalmic,
and topical corticosteroids (e.g., creams) to small areas of the skin (approximately
15 cm2) are permitted only if not receiving ritonavir or cobicistat as part of their
current ART regimen.
x
Non-steroidal anti-inflammatory drugs for treatment of IRR (Grade 1 and Grade 2).
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8.1.3 
Contraception 
Highly effective contraceptive measures are specified below. Male participants are required to 
use a condom regardless of their IOCBP partner’s method of contraception.
Note: If IOCBP is receiving ritonavir or cobicistat, estrogen-based contraceptives are not 
reliable, and an alternative method must be used.
x
Combined (estrogen and progestogen containing) hormonal contraception associated
with inhibition of ovulation:
o
Oral
o
Intravaginal
o
Transdermal
x
Progestogen-only hormonal contraception associated with inhibition of ovulation:
o
Oral
o
Injectable
o
Implantable
x
Intrauterine device
x
Intrauterine hormone-releasing system
x
Bilateral tubal occlusion
x
Vasectomized partner is a highly effective birth control method provided that the
vasectomized partner is the sole sexual partner of the IOCBP trial participant and that
the vasectomized partner has received medical assessment of the surgical success.
x
Sexual abstinence is considered a highly effective method only if defined as
refraining from heterosexual intercourse during the entire period of risk associated
with the study drug(s). The reliability of sexual abstinence needs to be evaluated in
relation to the duration of the clinical trial and the preferred and usual lifestyle of the
participant.
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9 
STUDY PROCEDURES 
This section provides a general description of the procedures and assessments associated with 
this study. The timing of the study procedures is presented in Appendix 1. All data will be 
recorded in source documents and entered into the eCRF. 
9.1 
Study Visits 
During the COVID-19 pandemic, alternative methods for conducting study assessments should 
be considered when compliance, feasibility, and safety can be assured. These methods may 
include:
x
Remote visits, e.g., via telephone/video (using compliant video-conference tools as
permitted by regulations, i.e., Health Insurance Portability and Accountability Act).
x
Use of primary care centers and local laboratories for blood draws and
imaging/radiographs.
If alternative methods are used, local laboratory reference ranges will be documented and 
submitted to the sponsor. If local laboratory testing is used, results and laboratory accreditation 
will be documented in study records.
9.2 
Informed Consent 
The investigator is responsible for ensuring informed consent is obtained prior to performing any 
study-related assessments, evaluations, or procedures that are not part of standard of care. 
Informed consent for this study must be provided by signing an IRB -approved informed consent 
document. A copy of the relevant signed informed consent document must be provided to the 
participant or participant’s legal representative, included in medical records, and the original 
maintained according to institutional procedures. 
9.3 
Screening Period 
The first dose of study drug(s) may be administered within 8 weeks of signing the informed 
consent. This period is defined as the screening period. Participants will enter the study upon 
signing the informed consent document. No screening activities outside of usual standard of care 
will be performed prior to obtaining informed consent.
Participants who sign the informed consent form but fail to meet the eligibility criteria are 
defined as screen failures. Demographic information, reason for screen failure, and serious 
adverse events (SAEs) related to study procedures must be recorded on the eCRF.
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9.4 
Enrollment and Registration 
The participant must be registered with the sponsor after eligibility is confirmed. The following 
information is provided during registration: 
x
Year of birth
x
Date of signed informed consent
x
Planned date of first dose of study drug
The sponsor will assign a dose cohort after informed consent is obtained and necessary baseline 
assessments are completed. The investigator or site staff will complete a participant registration 
form (PRF) and send it to the designated sponsor study team member. The sponsor will assign a 
participant identification number, which is used on all eCRF pages and other study-related 
documentation or relevant correspondence.
9.5 
Medical History 
Obtain a complete medical history. Record all concurrent medical conditions in the last 60 days 
and any significant medical conditions noted in medical records (e.g., hospitalizations, surgeries, 
prior medical history). Medical history obtained at screening includes demographic information 
(e.g., date of birth, gender, race, and ethnicity), HIV-1 testing history (CD4 and viral load), and 
HIV-1 genotypes if available. 
Any untoward event that occurs prior to the first dose of study drug(s) should be recorded as 
medical history and not as an AE (unless due to a protocol-related procedure).
9.6 
Concomitant Medications and Procedures 
9.6.1 
Concomitant Medications 
Record all prescription and non-prescription medications taken within 30 days prior to screening. 
Record all medications, HIV-1 ART regimen, and blood product transfusions from screening 
through the end of study visit.
During the study, record all modifications to the participant’s ART regimen since the last study 
visit or at the study visit including change in medication(s), interruptions, dose modifications, 
formulation modifications, and permanent discontinuations.
9.6.2 
Concomitant Procedures 
Record all non-protocol specified medical or surgical procedures from screening through the end 
of study visit.
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9.7 
Antiretroviral Therapy 
Adherence to ART is required to remain on study and is reviewed according to the schedule in 
Appendix 1. Record any missed doses while on study. Continuance on study will be contingent 
on ART adherence. 
9.8 
Physical Examination 
The complete physical examination includes skin, head, eyes, ears, nose, throat, lymph nodes, 
heart, chest, lungs, abdomen, genitourinary, musculoskeletal/extremities, and neurologic system 
according to schedule in Appendix 1. A directed physical exam will be performed at the visits 
indicated in Appendix 1 which includes vital signs. The targeted or directed physical 
examination addresses any previously identified or new event experienced since the last study 
visit or any unresolved signs or symptoms previously experienced. 
Weight is recorded per the schedule in Appendix 1. Height is required at screening only.
9.9 
Vital Signs 
Vital signs include temperature, pulse, blood pressure, and respiratory rate. It is recommended 
vital signs are obtained in a seated, semi-recumbent, or supine position after appropriate rest. 
9.10 
Optional Leukapheresis 
Leukapheresis is optional and performed in Part 2 only. The leukapheresis procedure occurs at 
baseline and at approximately 2 weeks after last dose of study drug administration (+2 week 
window) as specified in Appendix 1.
9.11 
Laboratory Tests 
9.11.1 
Clinical Laboratory Tests 
Clinical laboratory tests on blood and urine samples collected are described in Table 6. 
Hematology, chemistry, pregnancy, urinalysis, coagulation, and other specified tests are 
performed locally. Clinical laboratory tests scheduled for Day 1 of study drug infusion can be 
performed up to 7 days prior to infusion and must be reviewed before dosing.
Depending on site capability, human leukocyte antigen (HLA) typing may be performed in a 
central laboratory designated by the sponsor.
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Table 6
Clinical Laboratory Tests 
Pregnancy test:
Serum or urine human chorionic gonadotropin 
Hematology:
Hemoglobin 
Hematocrit 
Platelets 
Leukocytes 
Absolute neutrophils, lymphocytes, monocytes, 
eosinophils, and basophils 
Serum chemistry:
Albumin 
Alkaline phosphatase 
Alanine aminotransferase 
Aspartate aminotransferase 
Bicarbonate 
Bilirubin: total and direct (indirect is required if 
participant on atazanavir) 
Blood urea nitrogen 
Calcium 
Chloride 
Creatinine 
Glucose 
Magnesium 
Phosphate 
Potassium 
Sodium 
Coagulation:
Prothrombin time 
Activated partial thromboplastin time 
Prothrombin international normalized ratio 
Urinalysis:
Protein 
Occult blood 
If abnormal protein or occult blood, reflex test for 
microscopic evaluation 
Other tests: 
CD4, CD8, and CD4/CD8 
HIV-1 PCR viral load 
Human leukocyte antigen typing 
Rapid plasma reagin 
Hepatitis B virus surface antigen 
Hepatitis C virus antibody or RNA (reflex PCR viral 
load test performed only if positive to antibody) 
Follicle stimulating hormone (optional for proof of 
menopause) 
9.11.2 
Central Laboratory Tests 
Samples for PK, ADA, cytokine, and PD assays are collected per Appendix 2. These assays are 
performed in a central laboratory designated by the sponsor. 
9.11.3 
Sample Collection, Storage, and Shipping 
Details on laboratory specimen processing, storage, and shipping are provided in the laboratory 
manual.
9.12 
Electrocardiography 
Twelve-lead ECGs including QTc interval are assessed per Appendix 1. To account for intrinsic 
variability, ECGs are obtained in triplicate (3 ECGs per time point at approximately 1-minute 
intervals).
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9.13 
End of Study 
The EOSV occurs after the last dose of study drug(s) and completion of the follow-up period per 
Appendix 1. If a participant is unable to complete the study, but has not withdrawn consent, the 
EOSV is conducted 30 days (+3 day window) after the last dose of study drug.
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10 
ASSESSMENT OF PHARMACOKINETICS AND 
PHARMACODYNAMICS 
10.1 
Pharmacokinetic Assessments 
Serum concentrations of study drug(s) will be assessed using quantitative validated bioanalytical 
methods. Single-dose and multiple-dose PK parameters will be derived from serum 
concentration versus time data. These parameters may include maximum concentration (Cmax), 
time to maximal concentration (Tmax), area under the concentration-time curve for a dosing 
interval (AUCtau), trough concentration (Ctrough), clearance (CL), volume at steady state (Vss), and 
terminal half-life (t1/2). 
Analysis of PK data will be performed using industry standard software. Population PK analyses 
may be conducted using data from this study alone or combined with data from other sponsor-
conducted studies.
10.2 
Immunogenicity Assessments 
Incidence of ADA to study drug(s) will be assessed using validated bioanalytical methods.
10.3 
Pharmacodynamic Assessments 
The PD samples are prospectively collected and retrospectively analyzed.
10.3.1 
Serum Cytokines 
Serum samples will be analyzed for concentrations of serum cytokines, including but not limited 
to IFN-γ, IL-2, IL-5, IL-6, IL-10, and TNF-α.
10.3.2 
T-Cell Binding
Peripheral blood samples will be analyzed using flow cytometry to determine the percentage of 
study drug bound to CD4 and CD8 T cells.
10.3.3 
T-Cell Phenotype and Function
Peripheral blood samples will be analyzed using flow cytometry to determine the expression of 
cell surface markers of T-cell activation and exhaustion. Functional changes in circulating CD8 
T cells may also be assessed.
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10.3.4 
Persistent Human Immunodeficiency Virus-1 
Measurements of persistent HIV-1 may include the following:
x
Changes in pre- and post-dose measurements of the frequency of resting CD4+ T-cell
infection by quantitative viral outgrowth assay (QVOA) in participants who complete
the optional leukapheresis.
x
Changes in pre- and post-dose measurements of the frequency of resting CD4+ T-cell
infection by intact proviral DNA assay (IPDA).
x
Changes in pre- and post-dose measurements of the level of resting CD4+ T-cell-
associated HIV-1 gag RNA (rca-RNA).
x
Changes in pre- and post-dose measurements of levels of residual low-level HIV-1
viremia quantified by single copy assay (SCA).
Although exposure to DART molecules in this study is brief, and latency reversing agents are not 
included in the experimental intervention at this time, there is a possibility that some persistently 
infected cells may be depleted. Exploratory assays are limited by blood volumes and the 
practical considerations of apheresis, but sufficient samples will be available to assess changes in 
IPDA, rca-RNA, and SCA. When possible, QVOA will be measured. In our experience, 
performing multiple assays, when possible, is desirable, given the biological and assay variations 
of these assessments.
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11 
ASSESSMENT OF EFFICACY 
Not applicable.
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12 
ADVERSE EVENT REPORTING AND ASSESSMENT OF SAFETY 
The safety assessment is based on evaluation of AEs occurring from the first administration of 
study drug(s) through the EOSV or 30 days after the last dose of study drug(s), whichever is 
later. The safety assessment is based on signs, symptoms, physical examination findings, and 
laboratory test results.
12.1 
Definitions 
12.1.1 
Adverse Event 
An AE means any untoward medical occurrence associated with the use of a drug in humans. 
AEs may or may not be drug related. An AE is:
x
Any unfavorable and unintended sign, symptom or disease temporally associated with
the use of a medicinal product.
x
Any medical occurrence that is new or has increased in severity or frequency from the
baseline condition.
x
Any abnormal results of diagnostic procedures, including laboratory test
abnormalities.
12.1.2 
Adverse Drug Reaction 
An adverse drug reaction is a noxious and unintended response to the medicinal product related 
to any dose. The phrase “response to a medicinal product” means that a causal relationship 
between a drug and an AE is at least a reasonable possibility.
12.1.3 
Adverse Event of Special Interest 
An adverse event of special interest (AESI) is a noteworthy event that a sponsor may wish to 
monitor carefully. It could be serious or non-serious and could include events that might be 
potential precursors or prodromes for more serious medical conditions in susceptible individuals. 
Currently, there are no protocol-specified AESIs for MGD020 or MGD014 in this study.
12.1.4 
Serious Adverse Event 
An SAE is any AE that results in any of the following outcomes:
x
Death
x
Life-threatening (immediate risk of death)
x
Inpatient hospitalization for longer than 24 hours or prolongation of existing
hospitalization (even if the event is Grade 1)
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x
Persistent or significant disability or incapacity
x
Congenital anomaly/birth defect
x
Important medical events
12.1.5 
Assessment of Causality 
Assessment of causality is a determination that describes the relationship or association of the 
drug with an AE. 
This assessment of causality is made by the investigator based on 1) temporal relationship of the 
event to the administration of study drug; 2) whether an alternative etiology has been identified, 
and 3) biological plausibility. 
Causality assessments that are considered not related to study drug:
x
None: The event is related to an etiology other than the study treatment. An
alternative etiology should be documented in the participant’s medical record.
x
Unlikely: The event is unlikely to be related to the study treatment and likely to be
related to factors other than study treatment. An alternative explanation is more likely
(e.g., concomitant drugs, concomitant disease), or the relationship in time suggests
that a causal relationship is unlikely.
If an SAE causality assessment is “unlikely” or “none”, the investigator should document the 
likely causative mechanism for the event.
Causality assessments that are considered related to study drug:
x
Possible: There is a temporal association of the event with the administration of the
study drug. There is a plausible mechanism for relationship to the study drug.
However, there is an alternative explanation, such as the participant’s clinical status
or underlying disease.
x
Probable: There is a temporal association of the event with the administration of the
study drug. There is a plausible mechanism for relationship to the study drug. There is
no other reasonable explanation.
x
Definite: There is a temporal association of the event with the administration of the
study drug. There is a plausible mechanism for relationship to the study drug. Causes
other than the study drug are ruled out, or the event re-appeared on re-exposure to the
study drug.
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12.1.6 
Severity Criteria 
Severity of AEs is assigned per investigator assessment using the DAIDS grading table, 
corrected version 2.1: https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-
grading-tables
Severity Grade for Adverse Events Not Identified in the Grading Table:
The functional table below should be used to grade the severity of an AE that is not specifically 
identified in the DAIDS version 2.1 grading table.
ADVERSE 
EVENT
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY 
LIFE-
THREATENING
GRADE 5
FATAL
Clinical adverse 
event not 
identified in the 
DAIDS 
version 2.1 
grading table 
Mild symptoms 
causing no or 
minimal 
interference 
with usual 
social and 
functional 
activities with 
intervention not 
indicated  
Moderate 
symptoms 
causing greater 
than minimal 
interference 
with usual 
social and 
functional 
activities with 
intervention 
indicated  
Severe 
symptoms 
causing 
inability to 
perform usual 
social and 
functional 
activities with 
intervention or 
hospitalization 
indicated 
Potentially life-
threatening 
symptoms causing 
inability to 
perform basic 
self-care functions 
with intervention 
indicated to 
prevent 
permanent 
impairment, 
persistent 
disability, or 
death  
Death 
12.2 
Adverse Event Collection and Documentation 
12.2.1 
Adverse Events 
AEs and SAEs will be collected from the time the participant consents to study participation. 
AEs and SAEs reported between the time the participant signs the informed consent form and 
administration of the first dose of study drug will be captured as concurrent medical history 
unless the events are attributed to protocol-specified procedures. 
Events attributed to protocol-specified procedures will be collected on the AE eCRFs and SAE 
Report Form, as appropriate. 
AEs, regardless of seriousness, severity, or relationship to study drug(s), are documented in the 
source and the eCRF, including: 
x
Duration, severity, and seriousness of each AE.
x
Action taken with respect to the study drug(s).
x
Investigator’s attribution/causality assessment.
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x
Any medications used to treat the AE.
x
Outcome of the event.
A diagnosis should be recorded when signs and symptoms are due to a common etiology (e.g., 
cough, runny nose, sneezing, sore throat, and head congestion should be reported as "upper 
respiratory infection"). All treatment measures for AE management will be recorded. All 
non-serious AEs should be entered into the eCRFs within 10 days of study site awareness.
Clinical Laboratory Changes: Clinical laboratory test results are evaluated by the investigator for 
clinical significance. The investigator is responsible for reviewing the results of all laboratory 
tests in a timely manner. The investigator may repeat the laboratory test or request additional 
tests to verify the results of laboratory tests. 
Clinically significant laboratory abnormalities are reported as AEs. A laboratory abnormality is 
considered clinically significant if it is associated with study drug discontinuation, study drug 
dose reduction or delay, requires an intervention, or it is suggestive of disease or organ toxicity. 
Laboratory abnormalities associated with a diagnosed AE are not reported as separate AEs. For 
example, report renal failure or hematuria, not the laboratory abnormality (e.g., elevated 
creatinine or urine red blood cells increased).
The sponsor reports all suspected unexpected serious adverse reactions (SUSARs) to the 
regulatory authorities and the investigator. The investigator must report SUSARs to the IRB of 
record as required by the site’s institutional policy. 
If reporting to the regulatory authorities such as FDA or IRB is required, a copy of the report will 
also be sent to the NIAID Program Officer or Contracting Officer’s Representative, per the 
NIAID Clinical Terms of Award (https://www.niaid.nih.gov/grants-contracts/niaid-clinical-terms-
award). 
For this study, the participant must be provided with a “wallet (study) card” and instructed to 
carry this card with them for the duration of the study indicating at least the following: 
x
Study number
x
Statement that the participant is participating in a clinical study
x
Investigator name and 24-hour contact telephone number
x
Participant number
12.2.2 
Serious Adverse Events 
All SAEs, regardless of causality, occurring from first administration of study drug through 
30 days after the last dose of study drug must be reported to the sponsor. SAEs related to study 
drug(s) may be reported at any time. The investigator must report the SAE to the sponsor.
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x
Within 24 hours of becoming aware of an SAE, the investigator should send the
sponsor a completed SAE Report form by email, 
or
fax, 
 The SAE Report Form and Completion Guidelines, and Contact
Information for Reporting SAEs, are provided by the sponsor. Upon receipt of SAE
follow-up information, a follow-up SAE Report form should be submitted within
24 hours of becoming aware of the follow-up information. SAEs should be entered
into the eCRFs within 5 calendar days of the site’s awareness.
x
The investigator must follow all SAEs until resolution and record the date of
resolution. Resolution of an event is defined as the return to pre-treatment status or
stabilization of the condition with the expectation that it will remain chronic.
Unresolved SAEs must be followed until:
o
The event resolves.
o
The event stabilizes.
o
The event returns to baseline, if a baseline value/status is available.
o
The event can be attributed to etiology other than the study drug or to factors
unrelated to study conduct.
o
It becomes unlikely that any additional information can be obtained
(participant or health care practitioner refusal to provide additional
information, lost to follow-up after demonstration of due diligence with
follow-up efforts).
x
Any event requiring hospitalization (or prolongation of hospitalization) that occurs
during the study must be reported as a SAE, except:
o
A standard hospitalization for administration of the study drug.
o
A procedure for protocol/disease-related investigations (e.g., surgery, scans,
endoscopy, sampling for laboratory tests, bone marrow sampling,
pharmacokinetic or biomarker blood sampling).
o
Hospitalizations not intended to treat an acute illness or AE (e.g., social
reasons such as pending placement in long-term care or hospice facility).
o
Surgery or procedure planned before entry into the study (must be
documented in the eCRF).
x
Any SAE of suspected transmission of an infectious agent via a medicinal product
will be reported.
12.2.3 
Pregnancy 
All pregnancies in IOCBP participants or IOCBP partners of male participants must be reported 
to the sponsor. The pregnancy exposure form is sent to the sponsor within 24 hours of study site 
awareness. The reporting period is from consent through 24 weeks after the last dose of study 
drug. Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
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congenital anomalies, ectopic pregnancy) are considered SAEs, and reported according to the 
method in Section 12.2.2. Participants with a positive pregnancy test result at any time during 
the study must discontinue study drug(s). 
The investigator must attempt to follow the pregnancy to term or termination and report the 
outcome and health status of the mother and child. The investigator should discuss with and 
encourage the pregnant partner to allow collection of follow up information. The pregnant 
partner information release form must be signed prior to collecting follow-up information. 
Follow-up information will be collected for all live newborns at birth and 6 months after birth. 
Information will be collected to assess study drug effects on the newborn. If appropriate, 
follow-up will be extended.
12.2.4 
Other Reporting Situations 
12.2.4.1 
Adverse Events of Special Interest 
Currently, there are no protocol-specified AESIs for MGD020 or MGD014 in this study.
12.2.4.2 
Study Drug Overdose 
Overdose is administration of a dose of study drug ≥ 20% above the assigned dose. An AE 
related to study drug overdose must be reported to sponsor within 24 hours of awareness. 
12.2.4.3 
Product Quality 
Any suspected transmission of an infectious agent via a medicinal product or other product 
quality issue that results in an event of clinical consequence are AEs. The product quality issue 
must be reported within 24 hours of awareness of the event. See Section 13 for product quality 
complaint handling.
12.2.4.4 
Discontinuation of Study Drug Due to an Adverse Event 
Any AE resulting in the study drug discontinuation must be reported to the sponsor within 
24 hours. Follow up of AEs resulting in study drug discontinuation will continue until resolution 
or stabilization of the AE, unless the participant withdraws consent for further follow up, or until 
the EOSV. For SAEs, refer to Section 12.2.2 for follow-up requirements.
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13 
PRODUCT QUALITY COMPLAINT HANDLING 
A product quality complaint (PQC) is defined as any suspicion of a product defect related to 
manufacturing, labeling, or packaging, i.e., any dissatisfaction relative to the identity, quality, 
durability, or reliability of a product, including its labeling or package integrity. A PQC may have 
an impact on the safety and efficacy of the product. Timely, accurate, and complete reporting and 
analysis of PQC information from studies are crucial for the protection of participants, 
investigators, and the sponsor, and are mandated by regulatory agencies worldwide. The sponsor 
has established procedures in conformity with regulatory requirements worldwide to ensure 
appropriate reporting of PQC information; all studies conducted by the sponsor or its affiliates 
will be conducted in accordance with those procedures.
All PQCs must be reported to the sponsor within 24 hours of awareness of the event.
If the product defect results in an SAE, the study-site personnel must report the PQC to the 
sponsor according to the SAE reporting timelines (refer to Section 12.2.2, SAEs). A sample of 
the suspected product should be maintained under correct storage conditions for further 
investigation if requested by the sponsor.
The name(s) and corresponding telephone numbers of the individuals who should be contacted 
regarding PQC issues are listed on the contact information page, which is provided as a separate 
document.
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14 
STATISTICAL ANALYSIS 
This section outlines the statistical methodology and principles which will be used for data 
analysis in this study. A statistical analysis plan and statistical programming plan will describe 
the statistical methods and govern the analysis. 
14.1 
Determination of Sample Size 
The study plans to enroll up to approximately 54 participants in total, including up to 30 in 
Part 1A, 18 in Part 1B, and 6 in Part 2. The exact number of participants cannot be determined 
precisely in advance but depends upon the occurrence of DLTs and potential need for expanded 
cohorts.
The sample size in Part 1A is based on a 1+3 design with 3 planned cohorts (12 participants) and 
3+3 design for 3 cohorts (18 participants). The sample size in Part 1B is based on a 3+3 design 
with 3 planned cohorts (18 participants). Part 2 of the study may enroll up to 6 participants based 
on a 3+3 design with 1 cohort.
The number of participants is not based on statistical power calculations. No inferential statistics 
will be calculated. The sample size is considered sufficient to evaluate the primary objective of 
this study (characterize safety and tolerability of the study drugs).
14.2 
Analysis Populations 
Study analyses will be performed on the following population:
x
Safety population: All participants who received at least one dose of either study
drug. This population will be used to summarize safety data. This population will also
be used to summarize baseline data for PK, PD, and immunogenicity analyses.
14.3 
Demographics and Baseline Characteristics 
Participant disposition, demographics, baseline characteristics, disease history, and medical 
history will be summarized using descriptive statistics.
14.4 
Study Drug Exposure and Concomitant Medications 
Study drug exposure and concomitant medications will be summarized by descriptive statistics. 
The summary of study drug exposure will include descriptive statistics as well as frequency 
counts for the number of doses received, the total dose actually administered as well as the total 
dose intended, and the dose intensity which is calculated as percentage of total dose actually 
administered divided by total dose intended during whole treatment period.
Concomitant medications are coded using the World Health Organization Drug Dictionary.
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14.5 
Pharmacokinetic and Pharmacodynamic Analysis 
14.5.1 
Pharmacokinetic Analysis 
Summary statistics will be tabulated for PK parameters by dose. Geometric means and percent 
coefficients of variation may be reported for Cmax, AUCtau, and Ctrough; arithmetic means and 
standard deviations may be reported for t1/2, CL, and Vss; and medians, minimum, and maximum 
may be reported for Tmax. Population PK analyses may be conducted using data from this study 
alone or combined with data from other sponsor-conducted studies.
14.5.2 
Immunogenicity Analysis 
The proportions of participants negative for ADA at baseline with a positive ADA result on 
study, negative at baseline and remain negative, and positive ADA at baseline that increases or 
decreases in titer on study will be summarized. Samples with a positive ADA result may be 
evaluated for further immunogenicity including but not limited to neutralizing capacity. The 
incidence of neutralizing antibodies may be summarized if available.
14.5.3 
Pharmacodynamic Analysis 
Summary statistics for PD parameters listed in Section 10.3 and changes from baseline will be 
summarized. Analyses may be presented graphically with possible associations between changes 
in PD measures of interest and study drug dose and exposure.
14.5.3.1 
Serum Cytokines 
Data will be tabulated and summarized by dose and time. Plots of serum cytokine levels versus 
time may be provided. Additional analyses may be conducted to characterize the relationship 
between study drug concentrations and serum cytokines (e.g., an exposure-response analysis), if 
deemed appropriate. 
14.5.3.2 
T-Cell Binding
Percentages of CD4+ or CD8+ cells in blood with bound MGD020 (Part 1A) or bound with both 
MGD020 and MGD014 (Part 1B and Part 2) will be calculated.
14.5.3.3 
T-Cell Phenotype and Function
Percentages of CD4+ or CD8+ cells in blood with expression of markers of activation (e.g., 
CD25, CD69, CD134, CD137) or exhaustion (e.g., PD-1, LAG-3, TIM-3, TIGIT, CTLA-4) will 
be calculated.
14.5.3.4 
Quantitative Viral Outgrowth Assay 
In Part 2 only, for participants who complete the optional leukapheresis, changes in pre- and 
post-dose measurements of the frequency of resting CD4+ T-cell infection by QVOA (2) will be 
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assessed. Data will be reported as infectious units per million (IUPM) and 95% CI values will be 
determined from the maximum likelihood method. Statistical significance of changes in QVOA 
values following dosing will be evaluated by a nonparametric 2-sided exact sign test. The exact 
sign test used for this analysis makes minimal statistical assumptions and is based solely upon 
whether IUPM values decrease following dosing. As QVOA is a robust and reproducible assay, 
declines of more than 50% in QVOA values from serial measurements are infrequently seen and 
would be suggestive evidence for HIV-1 reservoir depletion (11, 14).
14.5.3.5 
Intact Proviral Deoxyribonucleic Acid Assay 
In Parts 1A, 1B and 2, pre- and post-dose measurements of the frequencies of resting CD4+ T-
cell infection by IPDA (4) will be analyzed. Data will be reported as intact HIV-1 provirus per 
million CD4+ T-cells. 95% CIs for IPDA values will be determined and the statistical 
significance of changes following dosing will be evaluated by a nonparametric 2-sided exact sign 
test. Like QVOA, declines of more than 50% in IPDA values from serial measurements would be 
suggestive evidence for HIV-1 reservoir depletion.
14.5.3.6 
Resting CD4+ T-Cell-Associated HIV-1 gag RNA 
In Part 2 only, changes in pre- and post-dose measurements of rca-RNA will be assessed. TATA 
binding protein RNA will be used as the reference to normalize HIV gene expression given its 
reported stability across treatment conditions (7). Data will be log-transformed and Wilcoxon 
Two-Sample test will be used for statistical analysis of rca-RNA of pre- and post-DART 
treatment as previously reported (13). 
14.5.3.7 
Plasma Viremia by Single Copy Assay 
In Part 2 only, changes in pre- and post-dose measurements of levels of residual low-level HIV-1 
viremia quantified by SCA will be assessed. Data will be reported as HIV-1 copies per mL 
plasma. 95% CIs for the SCA values will be determined and the statistical significance of 
changes following dosing will be evaluated by a nonparametric 2-sided exact sign test. 
14.6 
Efficacy Endpoints and Analyses 
Not applicable.
14.7 
Safety Endpoints and Analyses 
14.7.1 
Adverse Events 
Treatment-emergent AEs will be summarized in tables and listings. All AEs prior to treatment 
(e.g., due to study-related procedures) will be presented in listings only. Tables will display the 
number and percent of participants that experience the given event.
AEs will be coded to the Medical Dictionary for Regulatory Activities (MedDRA) dictionary. 
AEs will be summarized by system organ class, preferred term, relationship to study drug, and 
highest severity.
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14.7.2 
Laboratory Values 
Summaries of laboratory values will display descriptive statistics for numerically quantified 
laboratory assessments. Summaries will be grouped by laboratory panel (hematology, blood 
chemistry, and urinalysis) and will be displayed by study visit for each laboratory parameter. 
Shift tables may be produced. 
14.7.3 
Other Safety Endpoints 
ECGs will be collected and analyzed. Vital signs will be summarized with descriptive statistics at 
each study visit and time point collected. Shift tables may be produced.
14.8 
Other Assessments or Analyses 
Any additional analyses will be defined in the statistical analysis plan.
14.9 
Cohort Analyses and Monitoring 
As described in Section 4.2, the decision to escalate doses from cohort to cohort will only occur 
based on consensus supporting escalation by the investigator (or designee) and medical monitor. 
The review will include aggregate safety data through the DLT period for all dosed participants 
from the prior dose cohort.
An independent safety monitor will receive monthly study progress and safety monitoring 
reports. Study feasibility and the achievement of study milestones will be assessed in these 
reports. Additionally, accrual, baseline characteristics, conduct of the study (including premature 
study discontinuations), any interruptions of ART, virologic failures, and all reported toxicities 
and events will be monitored during the study on a monthly basis. Safety data will be reviewed 
to assess the relationship of reported toxicities and AEs to study drug(s).
If at any time during the study, 2 or more participants (in any part of the study) experience a 
toxicity that is Grade 3 or higher and considered related to study drug (per investigator 
assessment) or 2 or more participants experience the same toxicity that is Grade 2 or higher and 
considered related to study drug (per investigator) then enrollment and further dosing of ongoing 
participants will be suspended and the independent safety monitor will be asked to review all 
safety data, review study drug attribution to the event(s), and recommend how the study should 
proceed with respect to resuming enrollment and continuing study drug.
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15 
QUALITY CONTROL AND ASSURANCE 
Quality review activities will be undertaken to ensure accurate, complete, and reliable data. The 
sponsor and/or its representatives will do the following:
x
Provide instructional material to the study sites, as appropriate.
x
Conduct a start-up training session (investigator meeting or study initiation visit) to
instruct the investigators and study coordinators. This session will give instruction on
the protocol, the completion of the eCRFs, and study procedures.
x
Make periodic visits to the study site to monitor protocol compliance and general
GCP compliance.
x
Be available for consultation and stay in contact with the study site personnel by mail,
e-mail, telephone, and/or fax.
x
Review and evaluate eCRF data and use standard computer checks to detect and
query errors in data collection.
x
Conduct a quality review of the database.
15.1 
Monitoring, Auditing, and Inspections 
To ensure participant safety in the study, compliance with applicable regulations, and ensure 
accurate, complete, and reliable data, the investigator will keep records of laboratory tests, 
clinical notes, and medical records in participant files as source documents for the study.
The sponsor or its designee will monitor the study on a regular basis throughout the study period. 
The investigator will allocate adequate time for such monitoring activities. The study monitor 
periodically will conduct a cross-check of participant data recorded on eCRFs against source 
documents at the study site. The sponsor or designated monitor will review study pharmacy and 
medical records according to the clinical monitoring plan. The investigator will also ensure that 
the designated study monitor is given access to all the above noted study-related documents, 
source documents (regardless of media) and study-related facilities (e.g., investigational 
pharmacy, etc.), and has adequate space to conduct the monitoring visit. Queries may be raised if 
any data are unclear or contradictory. The investigator and study site personnel must address all 
queries.
Participation as an investigator in this study implies acceptance of the potential for inspection by 
the study sponsor or representatives, US or non-US government regulatory authorities, IRB of 
record, and applicable compliance and quality assurance offices. The investigator will permit 
study-related audits and inspections and will provide access to all study-related documents (e.g., 
source documents, regulatory documents, data collection instruments, study data, etc.). The 
investigator will ensure the capability for inspections of applicable study-related facilities (e.g., 
pharmacy, diagnostic laboratory, etc.).
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15.2 
Data Collection and Management 
Site personnel will record all data through eCRFs using an electronic data capture (EDC) system 
provided and approved by the sponsor. Additional information, if any, regarding eCRFs used as 
source documentation will be provided by the sponsor. Study sites must complete eCRFs after 
each participant visit per the eCRF completion guidelines. The investigator must sign the 
investigator statement in each eCRF.
The EDC system automatically generates queries resulting from the computer edit checks 
embedded into the system to ensure data accuracy, quality, consistency, and completeness. 
Manual queries resulting from review by study and medical monitors, medical coders, and data 
management staff are also generated from within the EDC system. Study sites are expected to 
resolve the queries and correct the entered data accordingly. Every change to data is captured in 
the EDC system audit trail. Upon completion of the study, or after reaching a pre-specified point 
in the study, data management will lock the database and generate the SAS datasets necessary for 
analysis and reporting. Each study site will receive the eCRFs for each of their participants. 
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16 
ADMINISTRATIVE CONSIDERATIONS 
16.1 
Institutional Review Board 
The study protocol, any related documents, and participant-facing materials will be submitted to 
the IRB of record for review and approval. Written approval of the study protocol and the 
informed consent forms (ICFs) will be in the possession of the investigator and the sponsor 
before the study drug is shipped to the investigator’s site. This approval must include the date of 
review, the protocol title and/or study number and version number, and ICF version number or 
date. A stamped version of the IRB of record-approved consent is acceptable. If the IRB of 
record or institution uses its own unique number for the protocol instead of the sponsor’s 
number, that unique number should be noted on the approval statement. The investigator should 
provide the sponsor with a statement of compliance from the IRB of record indicating 
compliance with the applicable regulations in the region and ICH.
Protocol modifications or changes may not be initiated without approval from the sponsor and 
prior written IRB of record approval (when required), except when necessary to eliminate 
immediate hazards to participants. Such modifications will be submitted to the IRB of record; 
and written verification that the modification was submitted should be obtained. The investigator 
must submit all changes and updates to required documents to the IRB of record.
16.2 
Ethical Conduct of the Study 
The investigational study will be conducted according to the Protection of Human Subjects 
(21 CFR [Code of Federal Regulations] 50), Institutional Review Boards (21 CFR 56), 
Obligations of Clinical Investigators (21 CFR 312.60  312.69), the current ICH Guideline for 
Good Clinical Practice (ICH E6), Office for Human Research Protections (45 CFR 46), and all 
other applicable regulations.
16.3 
Participant Information and Consent 
The investigator will obtain, document, and retain IRB or record-approved written informed 
consent from the participant, as specified in Section 9.2. Where required, the investigator will 
use an appropriately translated and IRB of record-approved version. The sponsor reserves the 
right to delay initiation of the study at a site where ICFs do not meet the standards of applicable 
local regulations or ICH E6.
Information should be given to the participant in both oral and written form, and participants 
must be given ample opportunity to inquire about details of the study. The ICF must be signed 
and dated by the participant, and by the person who conducted the discussion of the informed 
consent. 
All versions of each participant’s signed ICF must be kept on file by the investigator for possible 
inspection by regulatory authorities and/or authorized sponsor personnel. 
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16.4 
Participant Confidentiality 
To maintain participant confidentiality, all laboratory specimens, evaluation forms, reports, and 
other records will be identified by a coded number. Clinical information will not be released 
without written permission of the participant, or the participant’s legally authorized 
representation, except as necessary for monitoring by the relevant regulatory authorities, the 
sponsor, or the sponsor’s representative. The investigator must comply with all local applicable 
privacy regulations regarding the protection of participant data. 
16.5 
Source Documents 
Source data in a clinical study are the original records or certified copies where clinical 
observations are first recorded, which may include, but are not limited to, the participant’s 
medical file, original laboratory reports, histology, and pathology reports (as applicable). The 
investigator is responsible for maintaining adequate and accurate medical records from which 
accurate information will be entered into the eCRFs.
16.6 
Retention of Data 
All essential documents, including eCRFs, source documents (regardless of media), and signed 
ICFs, should be retained by the investigator, per the guidance in ICH E6 or other regulatory 
retention requirements. There may be other circumstances for which the sponsor is required to 
maintain study records for longer periods; therefore, the sponsor should be contacted before 
study records are removed from the control of the study site for any reason. The investigator 
must obtain written permission from the sponsor prior to destruction of study documents.
16.7 
Sample Retention and Secondary Research 
Samples acquired for protocol-specified assays are retained according to local and regional 
regulatory requirements. If the participant consents, or the participant’s legal representative 
consents, to the use of their study samples for secondary research purposes, samples may be used 
for exploratory testing and retained up to 15 years from the end of study.
16.8 
Financial Disclosure 
The investigator and sub-investigators are required to disclose in writing any applicable financial 
arrangement as defined in US regulation. The investigator’s disclosure will be signed and dated 
prior to participating in the study.
The information, as defined in 21 CFR 54, will be collected about the investigators, their spouses 
and each dependent child. Investigators must update the sponsor with any changes in reported 
information up to 1 year following the end of the study.
In accordance with US Securities and Exchange Commission regulation (17 CFR 229.404), 
investigators and sub-investigators must disclose if they are employees of the sponsor, or if an 
immediate family member of a sponsor employee, officer, or board director.
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16.9 
Publication and Disclosure Policy 
Data collected in this clinical study belong to the study sponsor. The publication terms regarding 
use of study data are noted in the clinical trial agreement. This includes authorship; scheduling 
and prioritizing analyses for reports, publications, and presentations; and developing a review 
and approval process.
16.10 
Discontinuation of the Study or Study Sites 
Site participation may be discontinued by the sponsor, the investigator, a regulatory authority, or 
the IRB of record. The study may be discontinued by a regulatory authority or at the discretion of 
the sponsor.
16.11 
Identification of the Coordinating Principal Investigator 
is the coordinating principal investigator for 
this study.
The coordinating investigator’s responsibilities include review of the final CSR. Agreement with 
the final CSR is documented by the dated signature of the coordinating principal investigator.
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17 
REFERENCE LIST 
Note: Newly added literature references are in colored text. Previously cited submitted literature 
references are in black text.
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2.
Archin NM, Liberty AL, Kashuba AD, Choudhary SK, Kuruc JD, Crooks AM, et
al., Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral
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Baldo BA, Adverse events to monoclonal antibodies used for cancer therapy: Focus on
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Bruner KM, Wang Z, Simonetti FR, Bender AM, Kwon KJ, Sengupta S, et al., A
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CDC. Estimated HIV incidence and prevalence in the United States, 2014–2018. 2020;
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CDC. Monitoring Selected National HIV Prevention and Care Objectives by Using HIV
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Ceriani C, Streeter GS, Lemu KJ, James KS, Ghofrani S, Allard B, et al., Defining
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Chawla A, Wang C, Patton C, Murray M, Punekar Y, de Ruiter A, et al., A Review
of Long-Term Toxicity of Antiretroviral Treatment Regimens and Implications for an
Aging Population. Infect Dis Ther, 2018. 7(2): p. 183-195.
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Chun TW, Davey RT, Jr., Engel D, Lane HC, and Fauci AS, Re-emergence of HIV
after stopping therapy. Nature, 1999. 401(6756): p. 874-5.
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Chun TW, Carruth L, Finzi D, Shen X, DiGiuseppe JA, Taylor H, et al.,
Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection.
Nature, 1997. 387(6629): p. 183-8.
11.
Crooks AM, Bateson R, Cope AB, Dahl NP, Griggs MK, Kuruc JD, et al., Precise
Quantitation of the Latent HIV-1 Reservoir: Implications for Eradication Strategies. J
Infect Dis, 2015. 212(9): p. 1361-5.
12.
DHHS. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the
Use of Antiretroviral Agents in Adults and Adolescents with HIV. Department of Health
and Human Services. 2019; Available from:
https://clinicalinfo.hiv.gov/sites/default/files/inline-files/AdultandAdolescentGL.pdf.
13.
Gay CL, Kuruc JD, Falcinelli SD, Warren JA, Reifeis SA, Kirchherr JL, et al.,
Assessing the impact of AGS-004, a dendritic cell-based immunotherapy, and vorinostat
on persistent HIV-1 Infection. Sci Rep, 2020. 10(1): p. 5134.
14.
Gay CL, James KS, Tuyishime M, Falcinelli SD, Joseph SB, Moeser MJ, et al.,
Stable Latent HIV Infection and Low-level Viremia Despite Treatment With the Broadly
Neutralizing Antibody VRC07-523LS and the Latency Reversal Agent Vorinostat. J
Infect Dis, 2022. 225(5): p. 856-861.
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Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
15.
Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, et al., Current
concepts in the diagnosis and management of cytokine release syndrome. Blood, 2014.
124(2): p. 188-195.
16.
Li J, Piskol R, Ybarra R, Chen YJ, Li J, Slaga D, et al., CD3 bispecific antibody-
induced cytokine release is dispensable for cytotoxic T cell activity. Sci Transl Med,
2019. 11(508).
17.
Moore PL, Crooks ET, Porter L, Zhu P, Cayanan CS, Grise H, et al., Nature of
nonfunctional envelope proteins on the surface of human immunodeficiency virus type 1.
J. Virol, 2006. 80(5): p. 2515-2528.
18.
Vogel WH, Infusion reactions: diagnosis, assessment, and management. Clin J Oncol
Nurs, 2010. 14(2): p. E10-21.
19.
Winkler U, Jensen M, Manzke O, Schulz H, Diehl V, and Engert A, Cytokine-release
syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte
counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8).
Blood, 1999. 94(7): p. 2217-24.
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MacroGenics, Inc.
Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
Appendix 1 
Time and Events Schedules 
Table 7
Time and Events Schedule (Part 1A and Part 1B) 
Procedure 
Screening a
Dosing
Follow-up Period
End of 
Study b
Visit 
Screen
1
2
3
4
5
6
7
8
Study Day 
Day -56 
to -1
Day 1
Day 2
Day 3
Day 8
(± 2 days)
Day 15
(± 2 days)
Day 22
(± 2 days)
Day 29
(± 2 days)
Day 43
(± 3 days)
Study Drug Administration
MGD020 infusion (Part 1A and Part 1B) c 
X 
MGD014 infusion (Part 1B only) 
X 
Clinical Procedures
Informed consent 
X 
Inclusion/exclusion criteria 
X 
Enrollment 
X 
Medical history 
X 
Demographics 
X 
Physical examination d 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs e 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weight 
X 
X 
Height 
X 
ART adherence 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECG f 
X 
X 
X 
Adverse events g 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Laboratory Collection h 
Hematology 
X 
X i 
X 
X 
X 
X 
Chemistry 
X 
X i 
X 
X 
X 
X 
Coagulation 
X 
X 
Urinalysis 
X 
X 
Pregnancy test j 
X 
X j 
X 
X 
Optional FSH 
X 
CD4/CD8 
X 
X 
HIV-1 PCR viral load 
X 
X 
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MacroGenics, Inc.
Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
Table 7
Time and Events Schedule (Part 1A and Part 1B) 
Procedure 
Screening a
Dosing
Follow-up Period
End of 
Study b
Visit 
Screen
1
2
3
4
5
6
7
8
Study Day 
Day -56 
to -1
Day 1
Day 2
Day 3
Day 8
(± 2 days)
Day 15
(± 2 days)
Day 22
(± 2 days)
Day 29
(± 2 days)
Day 43
(± 3 days)
Rapid plasma reagin 
X 
Hepatitis B surface antigen 
X 
HCV antibody or RNA k 
X 
Research Laboratory Sample Collection
PK/ADA/PD/cytokines/HLA 
See Table 9 (Part 1A) or Table 10 (Part 1B) in Appendix 2 
a 
Results of standard-of-care tests or examinations performed prior to obtaining informed consent and within the 56 day window may be used for screening. 
b 
If a participant is unable to complete the study, but has not withdrawn consent, the end of study visit (EOSV) is conducted 30 days (+3 day window) after the 
last dose of study drug(s). 
c 
MGD020 is infused first on days when both MGD020 and MGD014 are administered (Part 1B only). 
d 
Full physical exams are performed at screening and EOSV. All other physical exams are directed physical exams based on signs and symptoms, and as 
clinically indicated. 
e 
At the dosing visit, vital signs are measured pre-infusion; at 15 and 30 min after start of infusion (± 5 min); at end of infusion (EOI) of all study drug(s) 
(± 5 min); at 15, 30, 45, and 60 min post-infusion of last study drug (± 5 min); then every 60 min (± 10 min) until 6 hours after EOI or until the end of the 
monitoring period (see Section 6.5.1), whichever comes first. For participants on Parts 1A and 1B, vital signs are also measured at 10 hours (± 10 min) after 
the EOI. At non-dosing in-person visits, vital signs are assessed once. 
f 
ECGs are performed in triplicate (approximately 1 min apart). At screening and EOSV, ECGs will be taken at one time point. At the dosing visit (Day 1), 
ECG is recorded pre-infusion, at EOI of all study drug(s), at 30 and 60 min after EOI of last study drug, and as clinically indicated. ECGs after EOI have a 
± 10 min window. 
g 
Assess participants for adverse events. Participants are also instructed to contact the study coordinator or investigator if any signs or symptoms of an AE 
occur at any time during the study. 
h 
Additional and/or more frequent safety laboratory tests may be performed as clinically indicated per the investigator’s discretion. 
i 
Clinical laboratory assessments scheduled for Day 1 can be obtained within 7 days prior to infusion. See Section 9.11 for detailed list of assessments. 
Indirect bilirubin is required if participant on atazanavir. 
j 
Participants of childbearing potential only. Serum pregnancy test is required at screening. Subsequent pregnancy tests may use serum or urine. Results must 
be reviewed before study drug infusion. If screening test is performed within 72 hours of study drug infusion, repeat testing on Day 1 may be deferred. 
k 
Reflex HCV PCR viral load test is performed only if positive for HCV antibody. 
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Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
Abbreviations: ADA: anti-drug antibody; ART: antiretroviral therapy; CD: cluster of differentiation; ECG: electrocardiogram; EOI: end of infusion; EOSV: end 
of study visit; FSH: follicle stimulating hormone; HCV: hepatitis C virus; HIV-1: human immunodeficiency virus-1; HLA: human leukocyte antigen; PCR: 
polymerase chain reaction; PD: pharmacodynamics; PK: pharmacokinetics.
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Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
Table 8
Time and Events Schedule (Part 2) 
Procedure 
Screening
a
Dosing Period 
Follow-up Period 
End of 
Study b 
Visit 
Screen 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Study Day 
Day -56 
to -1 
Day 1 
Day 2 
Day 4 
Day 8 
(± 1 day) 
Day 15 
(± 1 day) 
Day 29 
(± 1 day) 
Day 43 
(± 2 days) 
Day 50 
(± 2 days) 
Day 64 
(± 3 days) 
Day 78 
(± 3 days) 
Study Drug Administration
MGD020 infusion c 
X 
X 
X 
MGD014 infusion 
X 
X 
X 
Clinical Procedures
Informed consent 
X 
Inclusion/exclusion criteria 
X 
Enrollment 
X 
Medical history 
X 
Demographics 
X 
Physical exam d 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
X 
Vital signs e 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weight 
X 
X 
X 
X 
Height 
X 
ART adherence 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECG f 
X 
X 
X 
X 
X 
Adverse events g 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Optional leukapheresis h 
X h 
X h 
Clinical Laboratory Collection i 
Hematology 
X 
X j 
X 
X 
X k 
X 
Chemistry 
X 
X j 
X 
X 
X 
Coagulation 
X 
X 
Urinalysis 
X 
X 
Pregnancy test l 
X 
X l 
X 
X 
X 
X 
Optional FSH 
X 
CD4/CD8 
X 
X 
HIV-1 PCR viral load 
X 
X 
Rapid plasma reagin 
X 
Hepatitis B surface antigen 
X 
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Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
Table 8
Time and Events Schedule (Part 2) 
Procedure 
Screening
a
Dosing Period 
Follow-up Period 
End of 
Study b 
Visit 
Screen 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Study Day 
Day -56 
to -1 
Day 1 
Day 2 
Day 4 
Day 8 
(± 1 day) 
Day 15 
(± 1 day) 
Day 29 
(± 1 day) 
Day 43 
(± 2 days) 
Day 50 
(± 2 days) 
Day 64 
(± 3 days) 
Day 78 
(± 3 days) 
HCV antibody or RNA m 
X 
Research Laboratory Sample Collection
PK/ADA/PD/cytokines/HLA 
See Table 11 in Appendix 2 
a 
Results of standard-of-care tests or examinations performed prior to obtaining informed consent and within the 56 day window may be used for screening. 
b 
If a participant is unable to complete the study, but has not withdrawn consent, the end of study visit (EOSV) is conducted 30 days (+3 day window) after the 
last dose of study drug(s). 
c 
MGD020 is infused first on days when both MGD020 and MGD014 are administered. 
d 
Full physical exams are performed at screening and EOSV. All other physical exams are directed physical exams based on signs and symptoms, and as 
clinically indicated. 
e 
On dosing visits (Day 1, 15, and 29), vital signs are measured pre-infusion; at 15 and 30 min after start of infusion (± 5 min); at end of infusion (EOI) of all 
study drug(s) (± 5 min); at 15, 30, 45, and 60 min post-infusion of last study drug (± 5 min); then every 60 min (± 10 min) until 6 hours after EOI or until the 
end of the monitoring period (see Section 6.5.1), whichever comes first (until 2 hours after EOI on Day 15 and 29). During non-dosing in-person visits, vital 
signs are assessed once. 
f 
ECGs are performed in triplicate (approximately 1 min apart). At screening and EOSV, ECGs will be taken at one time point. On dosing visits (Day 1, 15, 
and 29), ECG is recorded pre-infusion, at EOI of all study drug(s), at 30 and 60 min after EOI of last study drug, and as clinically indicated. ECGs after EOI 
have ± 10 min window. 
g 
Assess participants for adverse events. Participants are also instructed to contact the study coordinator or investigator if any signs or symptoms of an AE 
occur at any time during the study. 
h 
Optional leukapheresis is performed only after the participant is enrolled in the study. If the participant consents to this optional procedure, a baseline 
leukapheresis is completed. If a baseline leukapheresis was performed, a second leukapheresis procedure is completed 2 weeks (+2 week window) following 
the final study drug infusion. 
i 
Additional and/or more frequent safety laboratory tests may be performed as clinically indicated per the investigator’s discretion. 
j 
Clinical laboratory assessments scheduled for Day 1 can be obtained within 7 days prior to infusion. See Section 9.11 for detailed list of assessments. 
Indirect bilirubin is required if participant on atazanavir. 
k 
Day 43 hematology is assessed only for participants undergoing leukapheresis. This hematology assessment is performed within the window for the 
scheduled leukapheresis. 
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Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
l
Participants of childbearing potential only. Serum pregnancy test is required at screening. Subsequent pregnancy tests may use serum or urine. Results must
be reviewed before study drug infusion on Day 1, Day 15, and Day 29. If screening test is performed within 72 hours of first infusion, repeat testing on
Day 1 may be deferred.
m Reflex HCV PCR viral load test is performed only if positive for HCV antibody. 
Abbreviations: ADA: anti-drug antibody; ART: antiretroviral therapy; CD: cluster of differentiation; ECG: electrocardiogram; EOI: end of infusion; EOSV: end 
of study visit; FSH: follicle stimulating hormone; HCV: hepatitis C virus; HIV-1: human immunodeficiency virus-1; HLA: human leukocyte antigen; PCR: 
polymerase chain reaction; PD: pharmacodynamics; PK: pharmacokinetics. 
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Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
Appendix 2 
Pharmacokinetics, Immunogenicity, and Pharmacodynamic Sample Collection Schedule 
Table 9
Pharmacokinetic, Immunogenicity, and Pharmacodynamic Sampling Schedule: Part 1A 
Study Day 
Time Point 
Window 
PK
(Serum) a
ADA to MGD020 
(Serum) 
Cytokines 
(Serum) 
PD: T-cell Binding 
& Phenotype 
(Whole Blood) 
PD: IPDA
(PBMCs)
HLA Typing 
(Whole Blood) 
-56 to -1
Screening 
N/A 
X 
1 
Pre-MGD020 infusion 
N/A 
X 
X 
X 
X 
X 
1 
EOI MGD020 
+ 10 min
X 
1 
1 h after EOI MGD020 
± 5 min 
X 
X 
X 
1 
4 h after EOI MGD020 
± 5 min 
X 
X 
X 
2 
No specific time 
N/A 
X 
X 
X 
3 
No specific time 
N/A 
X 
8 
No specific time 
± 2 days 
X 
X 
X 
15 
No specific time 
± 2 days 
X 
X 
22 
No specific time 
± 2 days 
X 
29 
No specific time 
± 2 days 
X 
X 
IRR-CRS b 
No specific time b 
N/A 
X 
X 
X 
43/EOS 
EOS 
± 3 days 
X 
X 
X 
a 
Obtain pre-infusion PK samples before start of infusion on visit day (dosing day) or day before. When collecting multiple samples, collect PK sample first. 
b 
PK, ADA, and cytokine samples may be obtained selectively at additional time points in participants who experience signs and symptoms of IRR or CRS. 
Abbreviations: ADA: anti-drug antibody; CRS: cytokine release syndrome; EOI: end of infusion; EOS: end of study; HLA: human leukocyte antigen; IPDA: 
intact proviral DNA assay; IRR: infusion related reaction; N/A: not applicable; PBMC: peripheral blood mononuclear cell; PD: pharmacodynamic; 
PK: pharmacokinetic.
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MacroGenics, Inc.
Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
Table 10
Pharmacokinetic, Immunogenicity, and Pharmacodynamic Sampling Schedule: Part 1B 
Study Day 
Time Point 
Window 
PK a 
(Serum)
ADA 
(Serum)
Cytokines 
(Serum) 
PD: T-cell Binding 
& Phenotype 
(Whole Blood) 
PD: IPDA
(PBMCs)
HLA Typing
(Whole Blood)
MGD020 
MGD014 
MGD020 
MGD014 
-56 to -1
Screening 
N/A 
X b 
X b 
1 
Pre-MGD020 
infusion 
N/A 
X 
X 
X 
X 
X 
X 
1 
EOI MGD020 
+ 10 min
X 
1 
EOI MGD014 
+ 10 min
X 
1 
1 h after EOI 
MGD014 
± 5 min 
X 
X 
X 
X 
1 
4 h after EOI 
MGD014 
± 5 min 
X 
X 
X 
X 
2 
No specific time 
N/A 
X 
X 
X 
X 
3 
No specific time 
N/A 
X 
X 
8 
No specific time 
± 2 days 
X 
X 
X 
X 
15 
No specific time 
± 2 days 
X 
X 
X 
X 
22 
No specific time 
± 2 days 
X 
X 
29 
No specific time 
± 2 days 
X 
X 
X 
X 
IRR-CRS c 
No specific time c 
N/A 
X 
X 
X 
X 
X 
43/EOS 
End of study 
± 3 days 
X 
X 
X 
X 
X 
a 
Obtain pre-infusion PK samples before start of infusion on visit day (dosing day) or day before. When collecting multiple samples, collect PK sample first.  
b 
For participants who have been previously exposed to MGD014 or MGD020, obtain screening samples for ADA (MGD014 and MGD020) at least 21 days 
prior to enrollment to allow for results to be reported before enrollment.  
c 
PK, ADA and cytokine samples may be obtained selectively at additional time points in participants who experience signs and symptoms of IRR or CRS. 
Abbreviations: ADA: anti-drug antibody; CRS: CRS: cytokine release syndrome; EOI: end of infusion; EOS: end of study; HLA: human leukocyte antigen; 
IPDA: intact proviral DNA assay; IRR: infusion related reaction; N/A: not applicable; PBMC: peripheral blood mononuclear cell; PD: pharmacodynamic; PK: 
pharmacokinetic.
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MacroGenics, Inc.
Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
Table 11
Pharmacokinetic, Immunogenicity, and Pharmacodynamic Sampling Schedule: Part 2 
Study Day 
Time Point 
Window 
PK a 
(Serum) 
ADA 
(Serum) 
Cytokines 
(Serum) 
PD: T-cell Binding 
& Phenotype 
(Whole Blood) 
PD: IPDA 
& rca-
RNA 
(PBMCs) 
HLA Typing 
(Whole 
Blood) 
PD:
QVOA 
(Leuka-
pheresis) 
PD: SCA 
(Plasma) 
MGD020 MGD014 MGD020 MGD014 
-56 to -1
Screening 
N/A 
X b 
X b 
X c 
1 
Pre-MGD020 
infusion 
N/A 
X 
X 
X 
X 
X 
X 
X 
1 
EOI MGD020 
+ 10 min
X 
1 
EOI MGD014 
+ 10 min
X 
1 
1 h after EOI 
MGD014 
± 5 min 
X 
X 
X 
X 
1 
4 h after EOI 
MGD014 
± 5 min 
X 
X 
X 
X 
2 
No specific time 
N/A 
X 
X 
X 
X 
4 
No specific time 
N/A 
X 
X 
8 
No specific time 
± 1 day 
X 
X 
X 
X 
15 
Pre-MGD020 
infusion 
N/A 
X 
X 
X 
X 
X 
X 
15 
EOI MGD020 
+ 10 min
X 
15 
EOI MGD014 
+ 10 min
X 
15 
4 h after EOI 
MGD014 
± 5 min 
X 
X 
X 
X 
29 
Pre-MGD020 
infusion 
N/A 
X 
X 
X 
X 
X 
X 
29 
EOI MGD020 
+ 10 min
X 
29 
EOI MGD014 
+ 10 min
X 
29 
4 h after EOI 
MGD014 
± 5 min 
X 
X 
X 
X 
43 
No specific time 
± 2 days 
X 
X 
X 
X c 
X 
50 
No specific time 
± 2 days 
X 
X 
64 
No specific time 
± 3 days 
X 
X 
IRR-CRS d 
No specific time d 
N/A 
X 
X 
X 
X 
X 
78/EOS 
EOS 
± 3 days 
X 
X 
X 
X 
X 
a 
Obtain pre-infusion PK samples before start of infusion on visit day (dosing day) or day before. When collecting multiple samples, collect PK sample first. 
b 
For participants who have been previously exposed to MGD014 or MGD020, obtain screening samples for ADA (MGD014 and MGD020) at least 21 days prior to enrollment 
to allow for results to be reported before enrollment. 
c 
Optional leukapheresis is performed only after the participant is enrolled in the study. If the participant consents to this optional procedure, a baseline leukapheresis is 
completed. If a baseline leukapheresis was performed, a second leukapheresis procedure is completed 2 weeks (+2 week window) following the final study drug infusion. 
d 
PK, ADA, and cytokine samples may be obtained selectively at additional time points in participants who experience signs and symptoms of IRR or CRS. 
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MGD020, MGD014
MacroGenics, Inc.
Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
Abbreviations: ADA: anti-drug antibody; CRS: cytokine release syndrome; EOI: end of infusion; EOS: end of study; HLA: human leukocyte antigen; IPDA: intact proviral DNA 
assay; IRR: infusion related reaction; N/A: not applicable; PBMC: peripheral blood mononuclear cell; PD: pharmacodynamic; PK: pharmacokinetic; QVOA: quantitative viral 
outgrowth assay; rca-RNA: resting CD4+ T-cell-associated HIV-1 gag RNA; SCA: single copy assay.  
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MGD020, MGD014
MacroGenics, Inc.
Clinical Study Protocol: CP-MGD020-01
Protocol Amendment 1, 12 January 2023
Appendix 3 
Principal Investigator’s Agreement 
Study Title:
A Phase 1 Study of MGD020 as a Single Agent or in Combination 
with MGD014 in Persons with HIV-1 on Antiretroviral Therapy
Study Number:
CP-MGD020-01
DAIDS Document ID: 
38879
I have read the protocol described above.
I have fully discussed the objectives of this study and the contents of this protocol with the 
sponsor’s representative.
I understand that the information in this protocol is confidential and should not be disclosed, 
other than to those directly involved in the execution of the ethical review of the study, without 
written authorization from the sponsor. It is, however, permissible to provide information to a 
participant in order to obtain consent.
I understand that the sponsor may decide to suspend or prematurely terminate the study at any 
time for whatever reason; such a decision will be communicated to me in writing. Conversely, 
should I decide to withdraw from execution of the study, I will communicate my intention 
immediately in writing to the sponsor.
I agree to conduct this trial according to this protocol and to comply with its requirements, 
subject to ethical and safety considerations and guidelines, and to conduct the study in 
accordance with ICH guidelines on GCP and with the applicable regulatory requirements.
Signed:
Date:
Printed name:
Title:
Affiliation:
Address:
Phone number:
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