Conditions: HIV-1 Infection
Keywords: HIV 3BNC117 Broadly neutralizing antibody
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 17
Healthy volunteers: no

Brief summary:
This study evaluates the effects of four infusions of 3BNC117 in preventing or delaying rebound of viral load during a brief treatment interruption of standard ART, and its safety during a brief analytical interruption of antiretroviral therapy.

Detailed description:
The proposed study is a Phase II, open label study to evaluate the safety, antiretroviral activity and pharmacokinetics of four infusions of 3BNC117 in HIV-infected individuals on combination ART and during a brief analytical treatment interruption (ATI).

Study participants will be administered four intravenous infusions of 3BNC117, administered at 30 mg/kg on day 0, week 12, week 24 and week 27. Antiretroviral therapy will be discontinued 2 days after the third 3BNC117 infusion (week 24), until week 36.

The ART regimen will be resumed at week 36 or sooner if plasma HIV-1 RNA level is ≥ 200 copies/ml, CD4+ T cell count drops \< 350 cells/microliter, and results are confirmed upon repeat measurement during the next weekly scheduled visit. If plasma HIV-1 RNA level is ≥ 1,000 copies/ml, the participant will be asked to return for a repeat measurement prior to the next scheduled visit, and ART will be resumed if results are confirmed. ART will also be resumed early if the participant becomes pregnant or if otherwise clinically indicated. If ART is resumed before week 27, the fourth 3BNC117 infusion will not be administered.

Participants will be followed weekly during the analytical treatment interruption phase for safety assessments and for monitoring plasma HIV-1 RNA levels. CD4+ T cell counts will be monitored every 2 weeks during the analytical treatment interruption phase.

Participants may remain off antiretroviral therapy after week 36, with weekly viral load monitoring, if viral rebound does not occur by week 36.

All participants will be followed for a total of 60 weeks from enrollment.

Arms:
arm 1: Four intravenous infusions of 3BNC117 (30mg/kg) at weeks 0, 12, 24 and 27, and antiretroviral treatment interruption (ART)at week 24.

Interventions: intervention 1: 3BNC117 intervention 2: Antiretroviral Treatment Interruption
Intervention descriptions: intervention 1: 3BNC117 infusions intervention 2: Antiretroviral therapy will be discontinued 2 days after the third 3BNC117 infusion, at week 24, and resumed at week 36.

Protocol document:
Prot_SAP_000.pdf: 
The Rockefeller University
IND: 118225/0014
September 27, 2017
 
PROTOCOL # MCA-0866
CONFIDENTIAL
1
An Open Label, Phase 2 Study of the Safety and Antiretroviral Activity of 3BNC117 
in HIV-Infected Individuals on Combination Antiretroviral Therapy
Clinical Trial Phase: 2
Local Protocol Number: MCA-0866
DAIDS-ES Document Number: 12054
NIAID Funding Mechanism and Principal Investigator (PI): 
National Institute of Allergy and Infectious Diseases (NIAID)
1U01AI118536-01
PI: Marina Caskey, MD
Other Collaborators: 
Bill and Melinda Gates Foundation
Pharmaceutical and other Study Product Support Provided by: 
Celldex Therapeutics, Inc.
IND Sponsor: The Rockefeller University 
IND # 118,225
Principal Investigator/Protocol Chair: Marina Caskey, MD
DAIDS Medical Officer/Medical Monitor:  Michael Thigpen, MD
Draft or Version Number: Version 2.1
Version Day Month Year: 27 September 2017
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IRB NUMBER: MCA-0866
IRB APPROVAL DATE: 10/09/2017
IRB EXPIRATION DATE: 06/30/2018


The Rockefeller University
IND: 118225/0014
September 27, 2017
 
PROTOCOL # MCA-0866
CONFIDENTIAL
2
Confidentiality Statement
This document is confidential and is to be distributed for review only to investigators, 
potential investigators, consultants, study staff, and applicable independent ethics 
committees or institutional review boards. The contents of this document shall not be 
disclosed to others without written authorization from The Rockefeller University, unless 
it is necessary to obtain informed consent from potential study participants.
Statement of Compliance
The clinical trial will be conducted in compliance with the protocol, with the 
International Conference on Harmonization Good Clinical Practice E6 (ICH-GCP), and 
with 45 CFR 46 and 21 CFR 50, 56 and 312. All protocol investigators have completed 
Protection of Human Subjects Training.
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IND: 118225/0014
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PROTOCOL # MCA-0866
CONFIDENTIAL
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Signature Page 1
The signature below constitutes the approval of this protocol and the attachments, and 
provides the necessary assurances that this trial will be conducted according to all 
stipulations of the protocol, including all statements regarding confidentiality, and 
according to local legal and regulatory requirements and applicable U.S. federal 
regulations and ICH guidelines.
The Lead Principal Investigator (Protocol Chair) should sign Signature Page 1. A copy of 
this Signature Page 1 should be filed with the holder of the Regulatory documents and a 
copy should be maintained at the site.
Principal Investigator: _______________________________________________
Print/Type
Signed: ______________________________      Date:  ____________________
Name/Title 
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The Rockefeller University
IND: 118225/0014
September 27, 2017
 
PROTOCOL # MCA-0866
CONFIDENTIAL
4
Signature Page 2
The signature below constitutes the approval of this protocol and the attachments, and 
provides the necessary assurances that this trial will be conducted according to all 
stipulations of the protocol, including all statements regarding confidentiality, and 
according to local legal and regulatory requirements and applicable U.S. federal 
regulations and ICH guidelines. 
The Investigator(s) of Record (signature(s) on 1572) from each participating clinical site 
should sign the Signature Page 2 as appropriate. This Signature Page 2 should be 
maintained at each site.
Investigator(s) of Record: _______________________________________________
Print/Type
Signed: _________________________________  Date: ______________________
Name/Title
Additional Investigators: _______________________________________________
Print/Type
Signed: ________________________________   Date: ______________________
Name/Title
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IND: 118225/0014
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PROTOCOL # MCA-0866
CONFIDENTIAL
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TABLE OF CONTENTS
1
KEY ROLES...........................................................................................................................12
1.1
Institutions.........................................................................................................................12
1.2
Individuals.........................................................................................................................13
2
LAY SUMMARY ...................................................................................................................14
3
Objectives and Rationale .......................................................................................................14
3.1
Introduction.......................................................................................................................14
3.1.1
Background................................................................................................................14
3.1.2
The Investigational Product, 3BNC117.....................................................................18
3.1.3
Preclinical Toxicity Studies with 3BNC117 ..............................................................19
3.1.4
Clinical Experience with 3BNC117...........................................................................20
3.2
Hypothesis.........................................................................................................................21
3.3
Aims..................................................................................................................................21
3.4
Primary Outcome(s)..........................................................................................................22
3.5
Secondary Outcome(s)......................................................................................................22
4
Study Design ...........................................................................................................................23
5
Study Population ....................................................................................................................24
5.1
Inclusion Criteria...............................................................................................................24
The participant must meet all of the following inclusion criteria to participate in this study:...24
5.2
Exclusion Criteria .............................................................................................................25
6
Methods and Procedures .......................................................................................................26
6.1
Screening Procedure and Study Visits..............................................................................26
6.1.1
Pre-Screening ............................................................................................................26
6.1.2
Screening Visit...........................................................................................................26
6.1.3
Pre-Infusion Visit.......................................................................................................27
6.1.4
3BNC117 Infusion Visits............................................................................................27
6.1.5
Post-3BNC117 Administration Visits ........................................................................28
6.1.6
ART interruption and re-initiation of combination ART ...........................................29
6.1.7
Final Visit/Early termination Visit ............................................................................30
6.1.8
Discontinuation of 3BNC117 infusion and/or volunteer withdrawal from study......30
6.2
Study Procedures...............................................................................................................31
6.2.1
Consent Procedure ....................................................................................................31
6.2.2
Study Assignment.......................................................................................................32
6.2.3
3BNC117  Infusions...................................................................................................32
6.2.4
Medical History and Physical Examination..............................................................33
6.2.5
Laboratory Evaluations.............................................................................................33
6.2.6
Leukapheresis ............................................................................................................35
6.2.7
Monitoring for cytokine release associated adverse events and treatment of cytokine 
release syndrome....................................................................................................................35
6.2.8
Family Planning Counseling .....................................................................................35
6.2.9
Compensation ............................................................................................................36
6.2.10
Safety Assessments...................................................................................................36
6.2.11
Viral Sensitivity, Antiretroviral and Immunogenicity Assessments.........................37
6.2.12
Pharmacokinetic evaluations...................................................................................40
7
Investigational Product..........................................................................................................40
7.1
Regimen ............................................................................................................................40
7.2
Study Product Formulation and Preparation.....................................................................40
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7.3
Dispensing and Handling of Investigational Product .......................................................40
7.4
Accountability and Disposal of Used and Unused Investigational Product .....................41
7.5
Assessment of Participant Adherence with Study Product...............................................41
7.6
Concomitant Medications and Procedures........................................................................41
7.7
Permitted Medications and Procedures.............................................................................41
7.8
Prohibited Medications and Procedures............................................................................41
7.9
Precautionary Medications and Procedures ......................................................................41
7.10
Required Medications .....................................................................................................42
7.11
Rescue Medications ........................................................................................................42
8
Data Analysis ..........................................................................................................................42
8.1
Design ...............................................................................................................................42
8.2
Analysis of Antiretroviral effects, Safety and Pharmacokinetics .....................................43
8.3
Sample Size Considerations..............................................................................................44
8.4
Enrollment/Stratification/Randomization/Blinded Procedures: .......................................45
8.5
Participant Enrollment and Follow-Up.............................................................................45
9
Data and Sample Storage.......................................................................................................46
9.1
Quality Control and Quality Assurance............................................................................46
10
Recruitment Plan..................................................................................................................46
10.1
Participant Retention.......................................................................................................47
11
Potential Benefits to Participants........................................................................................47
12
Potential Risks to Participants ............................................................................................47
13
Procedures to minimize risk................................................................................................49
14
Alternative methods or treatments .....................................................................................51
15
Data and Safety Monitoring Plan .......................................................................................51
15.1
Safety Monitoring Committee ........................................................................................51
15.2
Safety Review .................................................................................................................53
15.3
Clinical Site Monitoring..................................................................................................53
15.4
Adverse Event Classification..........................................................................................54
15.5
Reporting Adverse Events ..............................................................................................54
15.6
Reporting Unanticipated AEs .........................................................................................54
15.7
Clinical Laboratory Improvement Amendment/Clinical Laboratory Evaluation Program 
(CLIA/CLEP) .............................................................................................................................54
15.8
Toxicity Management and Stopping Rules.....................................................................54
15.9
Other Disease Events ......................................................................................................55
15.10
Critical Event Reporting ...............................................................................................55
16
Clinical Trial Registration...................................................................................................55
17
Study Discontinuation..........................................................................................................55
18
Bibliography..........................................................................................................................56
Figure 1. Study Design....................................................................................................................9
Figure 2. Study Design..................................................................................................................23
Table 1. Upper bound Confidence Interval for a sample size of n=15, calculated using 
binom.test R function, package stats...........................................................................................45
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List of Abbreviations
3BNC117
Anti-HIV-1 bNAb targeting the CD4 binding site of gp120
Ab
Antibody
AE
Adverse Event/Adverse Experience
ART
Antiretroviral Therapy
ATI
Analytic Treatment Interruption
bNAbs
Broadly Neutralizing Antibodies
CD4
T-cell Surface Glycoprotein CD4
CFR
Code of Federal Regulations
cGMP
Current Good Manufacturing Practices
CONSORT
Consolidated Standards of Reporting Trials
CRF 
Case Report Form
CRSO 
Clinical Research Support Office
CTSA 
Clinical and Translational Science Award
CCTS 
Center for Clinical and Translational Science
DC 
Dendritic Cell
DNA
Deoxyribonucleic Acid
DSMB 
Data and Safety Monitoring Board
EOS
End of Study
FDA 
Food and Drug Administration
FWA 
Federal-Wide Assurance
GCP 
Good Clinical Practice
gp120
HIV-1 Envelope Glycoprotein 120
HIPAA 
Health Insurance Portability and Accountability Act
HIV-1 
Human immunodeficiency virus
hu-mice
Humanized Mice
ICF 
Informed Consent Form
ICH 
International Conference on Harmonization
I.M. 
Intramuscularly
IND 
Investigational New Drug
IRB 
Institutional Review Board
I.V. 
Intravenously
N 
Number (typically refers to participants)
NIAID 
National Institute of Allergy and Infectious Diseases, NIH
NIH 
National Institutes of Health
OHRP 
Office for Human Research Protections
OHSR 
Office for Human Participants Research
PBMC
Peripheral Blood Mononuclear Cell
PI 
Principal Investigator
RU 
The Rockefeller University
RUH 
The Rockefeller University Hospital
QA 
Quality Assurance
QC 
Quality Control
RNA
Ribonucleic Acid
SAE 
Serious Adverse Event/Serious Adverse Experience
S.C. 
Subcutaneously
SHIV
Chimeric Simian/Human Immunodeficiency Virus
SMC
Safety Monitoring Committee
SOP 
Standard Operating Procedure
T cell
T lymphocyte
V3 loop
Third Variable Loop of the HIV-1 Virion Envelope Glycoprotein 120
WCMC
Weill Cornell Medical College
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CONFIDENTIAL
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Protocol Summary
Title
An open label, phase 2 study of the safety and antiretroviral activity of 3BNC117 in HIV-
infected individuals on combination antiretroviral therapy. 
Short Title
3BNC117 mAb in HIV-infected individuals on combination antiretroviral therapy (ART)
Protocol 
Number
MCA-0866
Phase
Phase 2
IND Sponsor
 The Rockefeller University 
Study 
Center(s)
The Rockefeller University (RUH), New York, NY
Weill Cornell Medical Center (WCMC), New York, NY
Principal 
Investigators
Marina Caskey, MD
Leah Burke, MD
Study Design
The proposed study is a Phase 2, open label study to evaluate the safety, antiretroviral 
activity and pharmacokinetics of four infusions of 3BNC117 in HIV-infected individuals 
on combination ART and during a brief analytical treatment interruption (ATI) (Figure 
1. Study Design). 
Fifteen study participants will receive four intravenous infusions of 3BNC117, 
administered at 30 mg/kg on day 0, week 12, week 24 and week 27.  Antiretroviral 
therapy will be discontinued 2 days after the third 3BNC117 infusion (week 24), until 
week 36. 
The ART regimen will be resumed at week 36 or sooner if plasma HIV-1 RNA level is ≥ 
200 copies/ml, CD4+ T cell count drops < 350 cells/l, and results are confirmed upon 
repeat measurement during the next weekly scheduled visit. If plasma HIV-1 RNA level is 
≥ 1,000 copies/ml, the participant will be asked to return for a repeat measurement prior to 
the next scheduled visit, and ART will be resumed if results are confirmed. ART will also 
be resumed early if the participant becomes pregnant or if otherwise clinically indicated. If 
ART is resumed before week 27, the fourth 3BNC117 infusion will not be administered.
Participants will be followed weekly during the analytical treatment interruption phase for 
safety assessments and for monitoring plasma HIV-1 RNA levels. Participants may return 
to clinic between scheduled visits for additional VL measurements, if they desire to do so. 
CD4+ T cell counts will be monitored every 2 weeks during the analytical treatment 
interruption phase. 
If HIV-1 RNA remains undetectable at week 36, participants will be offered to continue 
off ART with close monitoring, in conjunction with the participant’s primary medical 
provider, as long as HIV-1 viral rebound does not occur.  ART resumption will follow 
same criteria as detailed above. All participants will be followed for a total of 60 weeks 
from enrollment.
Rockefeller University Institutional Review Board
IRB NUMBER: MCA-0866
IRB APPROVAL DATE: 10/09/2017
IRB EXPIRATION DATE: 06/30/2018


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PROTOCOL # MCA-0866
CONFIDENTIAL
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Study 
Schema
Figure 1. Study Design
Schedule 
of 
Procedures/
Evaluations
See Appendix A
Study 
Duration
15 months/per participant
Total planned study duration: 30 months
Objectives
The primary objectives are:
- Evaluate the effect of four infusions of 3BNC117 at 30 mg/kg in preventing or delaying 
virologic rebound during a short analytical treatment interruption. 
- Evaluate the safety and tolerability of four intravenous infusions of 3BNC117, dosed at 
30 mg/kg, in HIV-infected individuals with suppressed viremia on ART and during 
interruption of ART.
The secondary objectives are to evaluate the pharmacokinetics of four intravenous 
infusions of 3BNC117, dosed at 30 mg/kg in HIV-infected individuals with suppressed 
viremia on ART and during interruption of ART.
Exploratory objectives include an evaluation of the effects of 3BNC117 in combination 
with standard ART on the size of the HIV-1 reservoir. In addition, a phylogenetic 
comparison of viruses grown from PBMCs collected from participants while on ART to 
rebound viruses collected after ART interruption and analysis of escape mutations that 
might arise after administration of 3BNC117 will be performed. HIV-1-specific immune 
responses and levels of chronic inflammation markers following 3BNC117 infusions will 
also be evaluated. 
Outcomes
The primary outcomes are rate of virologic rebound (plasma HIV-1 RNA ≥ 200 copies/ml 
on two separate occasions) at week 36 (12 weeks post ART interruption), time to rebound 
following ART interruption, and frequency of adverse events and laboratory 
abnormalities. 
The secondary endpoints are serum elimination half-life, and decay kinetics, as well as 
other PK/PD measurements.
Number 
of 
Participants
15
Study 
Population
Adults, male and female, ages 18-65 with well-controlled HIV-1 infection on standard 
ART.
Inclusion Criteria. 

Informed consent obtained and signed.

Male and females, age 18 to 65.

HIV-1 infection confirmed by two independent methods.

Plasma HIV-1 RNA < 50 copies/ml for at least 12 months while on combination ART 
and < 20 copies/ml at the screening visit. [Note: One or two viral blips of < 200 
copies/mL prior to enrollment are permitted if preceded and followed by test results 
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showing VL less than or equal to 50 copies/ml on the same ARV regimen.]

CD4 cell count > 500 cells/l. CD4 cell count nadir > 200 cells/l.

If sexually active male or female, and participating in sexual activity that could lead 
to pregnancy, agrees to use an effective method of contraception throughout the study 
period. Participants should also agree to use male or female condoms while off ART.

If on an NNRTI-based regimen willing to switch for 4 weeks to a dolutegravir-based 
regimen.
Exclusion Criteria

Have a history of AIDS-defining illness within 1 year prior to enrollment.

Have a history of resistance to two or more antiretroviral drug classes.

History of systemic corticosteroids, immunosuppressive anti-cancer, or other 
medications considered significant by the trial physician within the last 6 months.

Chronic hepatitis B or hepatitis C.

Participant report, or chart history, of significant coronary artery disease, myocardial 
infarction, percutaneous coronary intervention with placement of cardiac stents.

Participant report, or chart history, of diabetes type 1 or 2 and/or current use of insulin 
or oral hypoglycemic medications.

Uncontrolled hypertension, as defined by a systolic blood pressure > 180 and/or 
diastolic blood pressure > 120, in the presence or absence of anti-hypertensive 
medications.

Total cholesterol level > 240 mg/dl or LDL level > 190 mg/dl at screen.

Known family history of myocardial infarction or stroke in a first-degree relative aged 
< 60 years.

Any other clinically significant acute or chronic medical condition, such as 
autoimmune diseases, that in the opinion of the investigator would preclude 
participation.

Current cigarette use in excess of 1 pack per day.

Laboratory abnormalities in the parameters listed below: 

Absolute neutrophil count  1,000 cells/l

Hemoglobin  10 g/dL

Platelet count  125,000 cells/l

ALT  2.0 x ULN

AST  2.0 x ULN

Total bilirubin  1.5 ULN 

Creatinine  1.1 x ULN

Coagulation parameters  1.5 x ULN

Current antiretroviral regimen includes maraviroc or enfuvirtide.

Pregnancy or lactation.

Any vaccination within 14 days prior to 3BNC117 administration.

Receipt of monoclonal antibody therapy of any kind in the past. 

History of severe reaction to drug infusions or history of severe allergic reactions.

Participation in another clinical study of an investigational product currently or within 
past 12 weeks, or expected participation during this study.
Study 
Product, 
Dose, Route, 
Regimen
3BNC117 is a recombinant, fully human monoclonal antibody (mAb) of the IgG1κ 
isotype that specifically binds HIV-1 envgp120. 
 
Four intravenous infusions of 3BNC117 mAb will be administered on day 0, week 12, 
week 24 and week 27 via a peripheral vein over 60 minutes.
Dose level to be tested: 30 mg/kg.
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Statistical 
Methodology
A one-sided upper confidence interval will be constructed for the probability of rebound 
using the Clopper-Pearson method. As such, with a sample size of 15 HIV-infected 
individuals, the null hypothesis (p(rebound)=0.85) will be rejected with at least 80% 
power if at least 6 participants do not rebound (an effect size equal or higher than 0.32). 
Kaplan-Meier survival curves will be used to address the second variable, “time to 
rebound”. If 10 or more participants experience viral rebound prior to week 29 [5 weeks 
after ART interruption and 2 weeks after last 3BNC117 infusion], additional participants 
will not undergo ATI.
The number and percentage of participants experiencing one or more AEs will be 
summarized by relationship to study drug, and severity. AEs will also be summarized by 
severity grade and by relationship to study drug according to the DAIDS AE Grading 
Table v2.0. The CTCAE v4.03 grading scale will be used for reporting and grading 
adverse events related to infusion reactions (Appendix B). 
Pharmacokinetic parameters will be calculated using standard non-compartmental analysis 
methods. 
A 95% repeated measures ANOVA F-test will be used to compare the levels of latently 
infected resting CD4+ T cells in peripheral blood; levels of plasma HIV-1 RNA by single 
copy assay; and levels of cell-associated HIV-1 RNA and DNA, at baseline and at weeks 
12, 23 (or 24) and 36. For repeated measures ANOVA F-test, a sample size of 15 
participants allows the detection of an effect size of 0.44, with 80% power and 95% 
confidence. 
Genotyping of HIV-1 isolates will be performed to phylogenetically compare viruses 
grown from PBMCs collected from participants while on ART to rebound viruses 
collected after treatment interruption, and to analyze the induction of escape mutations.
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1
KEY ROLES
1.1 Institutions
Study Sites:
- The Rockefeller University Hospital, New York NY 
1230 York Ave.
New York, NY 10065
Contact Person: Marina Caskey, MD
Phone Number: (212) 327-7396
Fax Number: (212) 327-7234
E-mail: mcaskey@mail.rockefeller.edu
- Weill Cornell Medical Center Clinical Trials Unit, New York, NY
525 East 68th Street
New York, NY 10021
Contact Person: Leah Burke, MD
T (212) 746-7654
F (212) 746-8972
Email: lab9079@med.cornell.edu
Clinical Laboratories:
- Memorial Sloan Kettering Cancer Center
1275 York Avenue
NY, NY 10065
- New York Presbyterian – Weill Cornell Medical Center
525 East 68th Street
New York, NY 10021
- LabCorp
330 W 58th St
New York, NY, 10019
Funder: National Institute of Allergy and Infectious Diseases (NIAID)
Data Management: 
EMMES Corporation
401 N. Washington St. Suite 700
Rockville, MD 20850
Independent Safety Monitoring: 
International AIDS Vaccine Initiative (IAVI)
125 Broad Street, 9th Floor
New York, NY 10004 
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DAIDS Program Officer: Stephen Smiley, PhD
DAIDS Medical Officer: Michael Thigpen, MD
1.2 Individuals
Rockefeller Site
Cornell Site
Principal Investigator:
Marina Caskey, MD
Assistant Professor of Clinical 
Investigation
The Rockefeller University
1230 York Avenue, NY, NY 10065
Phone Number: (212) 327-7396
Fax Number: (212) 327-7234
E-mail: mcaskey@mail.rockefeller.edu
Principal Investigator
Leah Burke, MD
Instructor of Medicine
Weill Cornell Medical College
1300 York Avenue, Box 125, NY, 
NY 10065
Phone Number: (212) 746-7654
Fax Number: (212) 746-8972
Email: lab9079@med.cornell.edu
Co-Investigators:Yehuda Cohen, 
MDMichel Nussenzweig, MD, 
PhD
Julio Cetrulo Lorenzi, PhDChing-Lan Lu, 
MD, PhDLeah Burke, MD
Katrina Millard, ANP Arlene Hurley, ANP
Irina Shimeliovich, MD, PhD
Maggi Pack, PhD
Allison Butler, MSN, FNP-BC
Co-Investigators:
Roy Gulick, MD, MPH
Marshall Glesby, MD, PhD
Timothy Wilkin, MD, MPH
Kristen Marks, MD, MS
Kirsis Ham, NP
Valery Hughes, NP
Nicholas Pickell, BA
Luis Lopez, BA
Collaborators / Consultants:
Robert Siliciano, MD, PhD /Janet Siliciano, PhD
Mike Seaman, PhD
Frank Maldarelli, MD
Richard Koup, MD
Georgia Tomaras, PhD / David Montefiori, PhD
Daniel Kaufman, MD
Szilard Kiss, MD (Ophthalmologist)
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CONFIDENTIAL
14
2
LAY SUMMARY
Despite the major success of combination antiretroviral therapy (ART) in suppressing 
viral replication and preventing disease progression, HIV-1 infection persists. When 
combination ART is discontinued, viral load levels rebound within 2-3 weeks in most 
participants, due to persistence of HIV-1 in latent reservoirs. 3BNC117 is a highly 
neutralizing anti-HIV-1 monoclonal antibody isolated and cloned from an HIV-infected 
individual who is a viremic controller. In preclinical studies carried out in humanized 
mice and non-human primates, 3BNC117 alone or in combination with other neutralizing 
antibodies led to protection from HIV-1 or chimeric simian/human immunodeficiency 
virus (SHIV) infection, and also to sustained suppression of HIV-1 plasma viremia. 
Moreover, 3BNC117 in combination with other bNAbs and agents that reverse HIV-1 
latency prevented viral rebound in HIV-infected humanized mice. In humans, 3BNC117 
is being evaluated under protocol MCA-835 and to date has been generally safe. 
Moreover, a single infusion of 3BNC117 transiently decreases HIV-1 viral loads in HIV-
infected individuals. The primary aims of this protocol are to evaluate 3BNC117’s effects 
on preventing virologic rebound when ART is discontinued and the safety of four 
intravenous infusions of 3BNC117. In addition, the study will evaluate 3BNC117’s 
effects on established HIV-1 reservoirs in humans, when given in combination with 
standard antiretroviral therapy to HIV-infected individuals who have achieved virologic 
suppression on ART alone. 
3
Objectives and Rationale
3.1 Introduction
3.1.1
Background
Despite the major success of combination antiretroviral therapy in suppressing viral 
replication and preventing disease progression, HIV-1 infection persists in a latent state 
as integrated proviruses in resting memory CD4+ T cells (Eisele E et al. 2012). The 
burden of daily medication regimens, toxicity, development of resistance and cost 
underscore the need for a continued search for additional complementary therapeutic 
modalities. Moreover, standard antiretroviral therapies do not fully restore health or a 
normal immune status in HIV-infected individuals and co-morbidities such as 
cardiovascular disease, bone disorders and cognitive impairment may occur (Deeks S et 
al. 2013).  
The latent reservoir is established very early during infection (Chun TW et al. 1998, 
Archin NM et al. 2012) and it is the major barrier to curing HIV-1 infection.  The HIV-1 
reservoir is maintained during ART by the long half-life of infected memory T cells, the 
homeostatic proliferation of these cells, and perhaps by low levels of cell-to-cell virus 
transfer (Barouch D Deeks S 2014). Although latently infected resting CD4+ T cells are 
largely nonpermissive for viral gene expression, it is believed that even on ART, a 
fraction of infected cells can intermittently produce virus (Bailey J et al. 2006, Tobin N et 
al. 2005).
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When ART is discontinued, virological rebound occurs within 2-3 weeks in most subjects 
(Davey RT et al. 1999; Papasavvas E et al. 2004, El-Sadr WM et al. 2006, Rothenberger 
M et al. 2015). Even in the context of suppressive ART, HIV-1 infection is characterized 
by persistent immune activation, and levels of HIV-1 viremia and cell-associated HIV-1 
remain relatively stable (Palmer S et al. 2008; Deeks S et al. 2013). Studies have shown 
that intensified antiretroviral regimens do not affect low level viremia and do not result in 
lower levels of HIV-1 persistence (Markowitz M et al. 2014; Dinoso JB et al. 2009; 
McMahon D et al, 2010).
  
A fraction of HIV-infected individuals (10 – 30%) mount a serologic response that can 
neutralize a broad spectrum of HIV-1 isolates (Simek M et al. 2009). Although broadly 
neutralizing antibodies that arise during HIV infection fail to resolve established 
infection, the selection of resistant strains indicates that bNAbs exert selective pressure 
on the virus. Importantly, several different groups of investigators have shown that 
macaque chimeric simian/human immunodeficiency virus (SHIV) infection can be 
prevented by passive transfer of broadly neutralizing anti-HIV-1 monoclonal antibodies 
(Mascola J et al. 1999, Moldt B et al. 2012, Shingai M et al. 2013). Broadly neutralizing 
antibodies might also play a role in the treatment of HIV-1 infection.
Broadly neutralizing antibodies (bNAbs) differ from other therapeutic modalities for 
HIV-1 in several respects. First, they can neutralize the pathogen directly; second, they 
have the potential to clear the virus and infected cells through engagement of innate 
effector responses; and third, immune complexes produced by the passively transferred 
antibodies may enhance immunity to HIV-1. In addition a subset of bNAbs can inhibit 
cell-to-cell transmission of HIV-1 at very low concentrations (Malbec M et al. 2013). 
Experiments in humanized mice and non-human primates indicate that bNAbs can lead to 
rapid virological suppression that is sustained for as long as mAb levels are maintained 
above a certain threshold (Klein F et al. 2012, Horwitz T et al. 2013, Shingai M et al. 
2013, Barouch D et al. 2013). 
In SHIV-infected nonhuman primates 3BNC117 induces rapid viral suppression as 
monotherapy (Shingai M et al. 2013, Barouch D et al. 2013). Also, 3BNC117 
monotherapy is able to prevent infection in macaques challenged with SHIVAD8EO or 
SHIVDH12-V3AD8 more effectively than the previously described antibody VRC01 (Shingai 
et al. 2014). 
While antibody monotherapy did not control HIV-1 infection in untreated humanized 
mice (hu-mice), a single neutralizing antibody, i.e. 3BNC117, controlled infection when 
plasma HIV-1 RNA levels were initially suppressed by antiretroviral therapy. Hu-mice 
that received ART normally rebounded immediately after the drugs were terminated, 
whereas a single antibody was sufficient to maintain virologic control after ART 
interruption in 50-86% of the hu-mice, for as long as antibody concentrations remained 
therapeutic (Horwitz J et al. 2013). Mice that escaped 3BNC117 carried resistance 
mutations in the CD4bs at positions YU2(279-281) or YU2(458/459). In contrast, viruses that 
emerged after immunotherapy was terminated did not contain antibody resistance 
mutations and remained sensitive to neutralization by the antibodies. Of interest, cell-
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associated HIV-1 DNA levels declined in plasma and lymphoid tissue following therapy 
with bNAbs alone or in combination with conventional ART in non-human primates or 
hu-mice (Barouch D et al. 2013, Horwitz J et al. 2013). Therefore, antibody monotherapy 
may be sufficient as a maintenance regimen, when combinations of antiretroviral drugs 
and/or antibodies initially suppress viremia. 
In addition to suppressing plasma viremia, broadly neutralizing antibodies can also 
interfere with the establishment of the reservoir in hu-mice by Fc-FcR mediated 
mechanisms. When hu-mice where administered bNAbs carrying Fc region mutations 
that abrogate Fc-receptor binding, bNAbs initially suppressed viremia at the same rate as 
the unmutated bNAbs, but more than half of the animals showed viral rebound within 6 
weeks after last antibody infusion, which demonstrates that bNAbs in vivo activity is at 
least partially dependent on Fc-mediated effector functions, such as ADCC (Halper-
Stromberg A et al. 2014). 
Experiments in humanized mice also showed that bNAbs have effects on established 
HIV-1 viral reservoirs. HIV-1 infected hu-mice were treated with a tri-mix of bNAbs in 
combination with one or three agents that induce viral transcription from latently infected 
cells (vorinostat, I-BET151, and α-CTLA4 mAb). When 23 mice that initially suppressed 
viremia on antibody therapy were treated with the combination of three inducers and 
followed for 62-105 days after the last antibody injection, 57% of mice failed to rebound. 
Moreover, proviral DNA could not be detected at the terminal time point in the majority 
of mice that did not rebound, whereas the majority of mice that did rebound had 
detectable HIV-1 DNA at the end of follow up. These results show that combination 
therapy with antibodies and inducers of viral transcription can significantly alter the 
latent HIV-1 reservoir in hu-mice (Halper-Stromberg A et al. 2014). Even in the absence 
of latency reversing agents, bNAbs have the potential to eliminate infected cells that 
intermittently produce viruses despite ART by Fc-mediated mechanisms, such as ADCC. 
Therefore, bNAbs in combination with ART might deplete the reservoir over time. 
Eliminating the HIV-1 reservoir in chronic infection is essential to eradicating HIV-1 
infection, but direct measurement of the latent reservoir to evaluate therapeutic 
eradication strategies remains difficult (Siliciano J et al. 2014). Quantitative viral 
outgrowth assays and PCR-based assays of integrated DNA yield conflicting results 
(Eriksson G et al. 2013), in part because PCR cannot distinguish between inactive and 
permanently disabled proviruses, while outgrowth assays underestimate reservoir size 
(Ho YC et al. 2013). Time to viral rebound after ART is discontinued may prove to be a 
useful measurement to evaluate strategies that aim to decrease the size of the reservoir 
(Siliciano J et al. 2014). It is possible that data generated in this study will allow us to 
examine if 3BNC117 potential effects on the reservoir (measured by the assays above) 
correlate with delayed time to viral rebound, particularly if participants who do not 
experience viral rebound by week 12 remain off ART until 3BNC117 levels are no longer 
detected. 
The SMART randomized trial demonstrated that episodic ART, guided by drop in CD4+ 
count (ART reinitiated if CD4+ count < 250 cells/l), leads to increased risk of 
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opportunistic infections or death from any cause, as compared with continuous ART, 
during a median follow-up time of 16 months (El-Sadr W et al. 2006). While structured 
treatment interruptions (STIs) have traditionally been avoided given safety concerns, it 
should be noted that, in the first 16 weeks following randomization into the SMART 
study, there were no deaths in either treatment group (continuous ART or episodic ART).  
In addition, the difference in risk of opportunistic diseases and major cardiovascular, 
renal, and hepatic diseases between the two groups occurred predominantly after 16 
weeks and increased over time.  Recent evidence suggests that short analytical treatment 
interruption (ATI; limited to a maximum of 16 weeks), in patients with preserved CD4 
count and virologic suppression, is safe and is an accepted tool to evaluate new 
therapeutic modalities (Rothenberger M et al. 2015; Routy JP et al. 2012; Kutzler MA et 
al. 2008). Thus, brief ART interruption can be used to study the role that recently isolated 
anti-HIV-1 bNAbs might have in controlling or preventing HIV-1 replication.
Passive administration of less potent, earlier generation anti-HIV-1 bNAbs has been 
evaluated in ART-interruption settings in humans, but not in combination with ART. In 
these studies, 13-16 antibody infusions were administered intravenously at doses ranging 
from 0.5 to 2 g and were generally found to be safe and well-tolerated. One of the 
administered antibodies (2G12) seemed to delay viral rebound in some participants. This 
effect was rather limited, as 2G12 did not neutralize subject’s viral isolates with sufficient 
potency (Mehandru S et al. 2007, Trkola A et al. 2005). However both studies found 
some correlation between the baseline sensitivity of the subject’s virus to 2G12 and delay 
in viral rebound. Therefore, in this study we will test the sensitivity of the participant’s 
provirus to 3BNC117 at baseline (day 0) and will correlate the effects on viral rebound 
and on the HIV-1 reservoir with baseline 3BNC117 sensitivity. 
Since highly potent second generation bNAbs have not been evaluated before in the 
setting of ART-interruption in humans, it is not known which serum antibody levels will 
be required to prevent viral rebound. In hu-mice, levels of 3BNC117 decreased to levels 
as low as 0.5 g/ml (10 times the IC50 value for the HIV-1 strain used) before viral 
rebound occurred during ART-interruption (Horwitz et al., 2013). In the setting of 
antibody monotherapy in nonhuman primates, 3BNC117 serum levels above 1-10 g/ml 
(10-100 times the IC50 value for the respective strain) were required to prevent rebound. 
In this study, an additional infusion of 3BNC117 will be administered 3 weeks into the 
ATI period in order to maintain 3BNC117 serum levels above 50-100 g/ml, for at least 
6 weeks after ART is discontinued. This will allow us to investigate the ability of 
3BNC117 to prevent viral rebound beyond the period of 2-3 weeks, during which 
rebound usually occurs after ART is discontinued (Davey RT et al. 1999; Papasavvas E 
et al. 2004, El-Sadr WM et al. 2006, Rothenberger M et al. 2015). 
This study aims to evaluate the effects of 3BNC117, one of the most highly potent and 
broadly neutralizing anti-HIV-1 antibodies, on preventing or delaying viral rebound after 
ART is discontinued. In addition, the study will evaluate the safety of four infusions of 
3BNC117, and its effects on established HIV-1 reservoirs in humans, when given in 
combination with standard antiretroviral therapy to HIV-infected individuals who have 
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achieved viral suppression on ART alone. Lastly, pharmacokinetic evaluations will be 
performed. 
Analytical interruption of ART is included in this protocol to evaluate if 3BNC117 alone 
can maintain viral suppression and delay viral rebound. ART will be interrupted for 12 
weeks only in order to avoid negative outcomes as observed in the SMART trial 
(discussed above). However, participants who do not experience viral rebound by week 
12, will have the option to remain off ART with continued weekly follow up. Since viral 
rebound occurs between weeks 2-3 in most individuals, we expect to be able to measure 
an effect of 3BNC117 should viral rebound not occur until week 12.
3.1.2
The Investigational Product, 3BNC117
3BNC117 is a broadly neutralizing and highly potent anti-HIV-1 antibody. 3BNC117 
was initially cloned from B cells isolated from a volunteer infected with HIV-1 clade B, 
who controls his HIV-1 infection without antiretroviral therapy. The initial study was 
conducted under protocol MNU-0628. 3BNC117 targets the CD4 binding site (CD4bs) 
within HIV-1 envelope gp-120. 3BNC117 showed an average IC80 on a combined group 
of 95 tier 2 viruses of 1.4 g/ml (Scheid J et al. 2011) when evaluated by in vitro 
neutralization assays. 3BNC117 also showed in vivo activity in HIV-1 or SHIV-infected 
humanized mice and non-human primates. In chronically infected animals, passive 
administration of 3BNC117 alone or in combination with other potent neutralizing 
antibodies suppressed plasma viremia to levels below detection (Horwitz J et al. 2013; 
Shingai M et al. 2013; Barouch D et al. 2013). Moreover, the combination of 3BNC117 
with two other bNAbs and latency reversing agents prevented viral rebound in HIV-
infected humanized mice (Halper-Stromberg A et al. 2014). 
3BNC117 has been manufactured for clinical use under cGMP by Celldex Therapeutics.  
The manufacture of the recombinant human monoclonal 3BNC117 was carried out by in 
vitro serum-free CHO cell culture. 3BNC117 was manufactured as a sterile solution 
intended for parenteral use, in compliance with Good Manufacturing Practices (GMP). 
No animal-derived raw materials were used during the cell culture, purification, and 
formulation of the drug substance. Testing for adventitious agents was performed in 
accordance to FDA Points to Consider in the Manufacture and Testing of Monoclonal 
Antibody Products for Human Use (1997). An ongoing drug product stability testing 
program monitors the quality of 3BNC117 over the duration of the clinical dosing period. 
Stability is evaluated in real time at the recommended storage conditions of 5 ± 3°C as 
well as at accelerated temperature conditions of 25 ± 2°C / 60 ± 5% RH. 
Clinical Safety of Other anti-HIV Monoclonal Antibodies.
Monoclonal antibodies are a growing part of the therapeutic arsenal. While each mAb 
product has unique safety issues related to its mechanism of action, the major safety 
concern related to mAbs in general is infusion/hypersensitivity reactions, which are more 
common for mAbs that contain murine elements. 3BNC117 is a fully human recombinant 
form of a naturally existing human mAb. Passive administration of antibodies is 
successfully used to prevent or treat several viral diseases and several monoclonal 
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antibodies are being developed for use in either prevention or treatment of infectious 
diseases.
Passive administration of anti-HIV-1 antibodies has also been evaluated in humans. HIV 
Immune Globulin (HIVIG) was in clinical use in the 1990s before the advent of highly 
effective ART. HIVIG was also evaluated in HIV-infected pregnant females and their 
newborns in a phase III trial to assess whether HIVIG plus single dose nevirapine given 
to mothers and infants would provide additional benefit over single dose nevirapine alone 
for prevention of peripartum HIV-1 transmission. While there was no demonstrable 
difference in treatment efficacy, the study showed that that there were no significant 
differences in mortality or serious AEs between the two arms of the trial (Onyango-
Makumbi, C et al. 2011).
Several monoclonal antibodies that target HIV-1 gp120 have been evaluated in clinical 
studies. For example, 2F5 and 4E10 are IgG1 (kappa) monoclonal antibodies that target 
the membrane-proximal ectodomain of gp41, while 2G12 binds to a carbohydrate moiety 
on the silent face of gp120. These neutralizing antibodies were evaluated in combination 
in HIV-infected individuals (Armbruster C et al. 2002; Armbruster C et al. 2004). The 
antibodies were administered intravenously at 0.5 to 1 gm doses; 4 to 8 weekly infusions 
were given. The antibodies were safe and well tolerated and no clinical or laboratory 
abnormalities were observed throughout the studies. A low-level antibody response 
against 2G12 was found in two individuals. Another neutralizing antibody KD-247, 
which targets the V3 loop, was evaluated in viremic HIV-infected individuals. The 
antibody was administered as 3 weekly infusion administered as doses ranging from 4 to 
16 mg/kg. KD-247 was well tolerated at the doses tested and showed some virologic 
activity at the higher dose levels (Matsushita S et al. 2015). 
Two other studies included HIV-infected individuals on combination ART and plasma 
viral levels < 50 copies/ml (Trkola, A et al. 2005), n = 14;  Mehandru M et al. 2007), n 
=10). The antibodies were administered intravenously at doses ranging from 1 to 2 gm 
for each antibody; 13-16 antibody infusions were given weekly. ART was interrupted 
following 1 or 4 antibody infusions. Antibody infusions were well tolerated in most 
individuals; mild and transient side effects were reported only occasionally. No serious 
adverse events (SAEs) were recorded. In both studies, the use of mAbs was safe and 
generally delayed, but did not prevent, viral rebound. The emergence of resistance to 
2G12, however, demonstrated that the antibody exerted selective pressure on the 
circulating viral strains. It is important to note that the antibodies used in these studies 
have far lower potency and breadth than the more recently isolated neutralizing 
antibodies, such as 3BNC117. Moreover, in contrast to 3BNC117, these antibodies had 
very limited effect in the treatment of HIV-1 in humanized mice (Poignard et al., 1999).
3.1.3
Preclinical Toxicity Studies with 3BNC117 
A tissue cross-reactivity study, performed on a full panel of tissues from humans and rats, 
showed good concordance of binding between the two species. While 3BNC117 showed 
widespread cytoplasmic binding, it is generally understood that cytoplasmic binding is 
considered of little to no toxicologic significance.  Membrane binding of 3BNC117 was 
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restricted to two limited/rare cell types in conjunctival recesses and in the urinary bladder 
(neither of which correlated with findings in the repeat dose toxicology study).
The antibody 3BNC117 was evaluated for safety in a multidose study in rats. Despite 
some animals producing anti-drug antibodies, the rats appeared to have maintained 
adequate drug exposure in the study, with twice per week dosing for four weeks. Aside 
from injection site findings, there were no 3BNC117 related effects, in the Main and 
Recovery group animals, on clinical observations, body weight, food consumption, body 
temperature, clinical pathology parameters, organ weights or macroscopic and 
microscopic observations, and the NOAEL (no observable adverse effect level) was 
determined to be the high dose of 60 mg/kg twice a week for four weeks. 
3.1.4
Clinical Experience with 3BNC117
3BNC117 is currently being evaluated in a phase 1 study in both HIV-uninfected and 
HIV-infected individuals (protocol MCA-835) and in an exploratory phase 2 study in 
HIV-infected subjects (protocol MCA-867). 
In protocol MCA-835, study participants are administered one or two intravenous 
infusions of 3BNC117 at increasing dose levels (1 mg/kg, 3 mg/kg, 10 mg/kg or 30 
mg/kg), and are followed for 24 weeks after last infusion. As of 17 Aug 2015, total of 55 
individuals were enrolled in the study (22 HIV-uninfected, 19 viremic HIV-infected and 
14 HIV-infected individuals on ART). Five subjects (HIV-uninfected) have received two 
doses of 30 mg/kg, 12 weeks apart. Twenty-two subjects (3 HIV-uninfected and 19 HIV-
infected) have been administered one dose of 30 mg/kg. 
Overall, 3BNC117 has been generally safe and well-tolerated, mild transient myalgia, 
fatigue and headache have occurred. Some participants reported ophthalmic complaints, 
but a causal relationship with 3BNC117 was not established. To date, no serious adverse 
events (SAEs) were reported during study follow up and no dose-limiting toxicities 
(DLT’s) deemed possibly, probably or definitely related to 3BNC117 have occurred. 
Preliminary PK data show that 3BNC117’s half-life is approximately 17.6 days in HIV-
uninfected and 9.6 days in viremic HIV-infected individuals. PK data from ART-treated 
participants, with VLs < 20 copies/ml, who received a single 3BNC117 infusion of 10 
mg/kg show that 3BNC117’s t1/2 in this setting is similar to HIV-uninfected individuals.
In HIV-uninfected individuals, dosed at 30 mg/kg, 3BNC117 levels were maintained 
around 75 μg/ml for 3-4 weeks after infusion and around 5 g/ml for 12 weeks after a 
single 3BNC117 infusion. In addition, 3BNC117 decay rate following first and second 10 
mg/kg infusions were similar in HIV-uninfected individuals who received two 3BNC117 
infusions at 10 mg/kg, administered 12 weeks apart. 
In this study, we expect that 3BNC117 serum trough levels will be around 5 g /ml 
during the 3BNC117 dosing period, while ART is maintained. Since 3BNC117 has not 
yet been tested in the setting of ATI, the decay rate of 3BNC117 in this setting is not yet 
known and may be relatively faster than seen in HIV-uninfected or ART-treated HIV-
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infected individuals.
A transient decline in HIV-1 viremia, of approximately 0.5 log10, occurred following the 
administration of 3 mg/kg of 3BNC117 to three HIV-infected individuals with detectable 
viremia. Of the 2 individuals off ART receiving the 10 mg/kg dose of antibody, 1 
responded with a 1.36 log10 decline in viremia and the other did not respond. The 
individual that did not respond was infected with 3BNC117-resistant virus (IC50 > 
20µg/ml at baseline). All nine individuals that received the 30mg/kg dose of 3BNC117 
showed rapid decreases in their viral loads that varied between individuals from 0.8 to 2.5 
log10. The median time to reach the nadir in viremia was 7 days, and the mean drop in VL 
was 1.48 log10 at nadir. Interestingly, emergence of resistant viral strains was variable, 
with some individuals remaining sensitive to 3BNC117 for a period of 28 days after 
infusion (Caskey, Klein et al. 2015). Virologic data will continue to be analyzed under 
protocol MCA-835, as additional HIV-infected individuals are enrolled. 
In protocol MCA-867, HIV-infected individuals on suppressive cART are administered 
two 30 mg/kg intravenous infusions of 3BNC117 at week 0 and week 3. cART is 
discontinued 2 days after the first 3BNC117 infusion. Subjects are followed weekly and 
cART is resumed if viral rebound occurs or CD4+ T cell counts decline to < 350 
cells/mm3. As of 17 August 2015, 8 individuals have been enrolled. 3BNC117 infusions 
have been well tolerated. Most reported AEs were transient, of grade 1 severity, and 
include headache, fatigue and myalgia.
3.2 Hypothesis 
The administration of four infusions of 3BNC117 (30 mg/kg) will be safe, well tolerated, 
and will prevent or delay the return of HIV-1 viremia during a brief analytical treatment 
interruption. In addition, 3BNC117 infusions in combination with standard ART might 
be associated with a decrease in the size of the HIV-1 reservoir in ART-treated HIV-
infected individuals. 
3.3 Aims 
Primary Objectives:
-
Evaluate the effect of four infusions of 3BNC117 at 30 mg/kg in preventing or 
delaying virologic rebound during a short analytical treatment interruption. 
-
Evaluate the safety and tolerability of four intravenous infusions of 3BNC117, dosed 
at 30 mg/kg, in HIV-infected individuals with suppressed viremia on ART and during 
interruption of ART.
Secondary Objectives:
-
Evaluate the pharmacokinetics profile of four intravenous infusions of 3BNC117, 
dosed at 30 mg/kg, in HIV-infected individuals with suppressed viremia on ART and 
during interruption of ART.
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Exploratory Objectives:
-
Evaluate the effects of 3BNC117 in combination with standard ART on the size of 
the HIV-1 reservoir. The reservoir will be measured by: 
1) Quantitative PCR-based assays to measure cell-associated HIV-1 DNA;
Viral outgrowth assays that measure infectious units per million (IUPM) in CD4+ 
resting T cells.
-
Correlate baseline 3BNC117 sensitivity of participant’s proviruses to the observed 
effects on viral rebound and on the HIV-1 reservoir.
-
Evaluate HIV-1-specific immune responses and chronic inflammation markers 
following 3BNC117 infusions. 
-
Phylogenetically compare viruses grown from PBMCs collected from participants 
while on ART to rebound viruses collected after treatment interruption.
3.4 Primary Outcome(s)
-
Rate of viral rebound (plasma HIV-1 RNA ≥ 200 copies/ml on two separate 
occasions) post ART interruption by plasma HIV-1 RNA levels at week 36 (12 weeks 
after ART is discontinued).
-
Time to viral rebound post ART interruption by plasma HIV-1 RNA levels.
-
Safety will be evaluated by frequency of adverse events and laboratory abnormalities. 
3.5 Secondary Outcome(s)
-
PK will be evaluated by serum elimination half-life, and decay kinetics, as well as 
other PK/PD measurements.
Other evaluations:
-
Levels of latently infected CD4+ resting T cells measured by viral outgrowth assay at 
baseline and week 23. 
-
Levels of cell-associated HIV-1 DNA determined in PBMCs at baseline and at week 
24.
-
Levels of cell-associated HIV-1 RNA determined in PBMCs at baseline and at week 
24.
-
Levels of HIV-1 RNA determined by single copy assay when HIV-1 RNA is < 20 
copies/mL by standard clinical assay at baseline and at week 24.
-
Phylogenetic comparison of viruses grown from PBMCs collected from participants 
while on ART to rebound viruses collected after treatment interruption.
-
Analysis of 3BNC117-induced escape mutations.
-
Compare 3BNC117 effects on preventing or delaying viral rebound (rate and time to 
rebound) and on the HIV-1 reservoir (decrease in IUPM in CD4+ resting T cells) 
between subjects with baseline 3BNC117 IC50 against autologous viruses of < 2 
μg/ml or ≥ 2 μg/ml.
-
Evaluate the effects of 3BNC117 on serum levels of inflammation markers, such as 
C-reactive protein, D-dimers, IL-6 and soluble CD14, at baseline and week 24.
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-
Evaluate HIV-1 specific T and B cell immune responses following administration of 
3BNC117, including CD8+ T cell expression of immune activation markers, such as 
HLA-DR, CD38 and PD-1, at baseline and week 24.
4
Study Design 
The proposed study is an exploratory Phase 2, open label study to evaluate the safety and 
antiretroviral activity of four infusions of 3BNC117 in HIV-infected individuals on 
combination ART and during a brief analytical treatment interruption (Figure 2. Study 
Design). PK assessments are also included.
After meeting enrollment criteria, fifteen participants with 3BNC117-sensitive virus will 
be enrolled sequentially and will receive four intravenous infusions of 3BNC117, 
administered at 30 mg/kg on day 0, week 12, week 24 and week 27.  ART will be 
continued for 2 days after the third 3BNC117 infusion to allow for initial redistribution of 
the antibody, and will then be discontinued. Based on PK data from study MCA-835 we 
expect this dosing regimen to maintain 3BNC117 serum levels above 50-100 g/ml for at 
least 6 weeks. This exceeds the typical period of viral rebound after ATI, which ranges 
from 2-3 weeks (Davey RT et al. 1999; Papasavvas E et al. 2004, El-Sadr WM et al. 
2006, Rothenberger M et al. 2015).
Figure 2. Study Design
 
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have longer elimination half-
lives than other antiretroviral classes. In order to avoid the risk of inadvertent 
monotherapy, which can select NNRTI resistant strains, if the participant’s ART regimen 
includes an NNRTI, the NNRTI will be switched to dolutegravir (an integrase inhibitor), 
4 weeks prior to discontinuing all other antiretroviral drugs. Dolutegravir will be 
provided to the participants for that time period.
Participants will be followed weekly during the analytical treatment interruption (ATI) 
phase of the study for safety assessments and for monitoring plasma HIV-1 RNA levels. 
Participants may return to clinic between scheduled visits for additional VL 
measurements, if they desire to do so. CD4+ T cell counts will be measured every other 
week.
 
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The same ART regimen will be resumed at week 36. ART will be resumed sooner if 
plasma HIV-1 RNA level is ≥ 200 copies/ml) or CD4+ T cell count drops < 350 cells/l 
and either value is confirmed upon repeat measurement, during the next weekly 
scheduled visit. If plasma HIV-1 RNA level is ≥ 1,000 copies/ml, the participant will be 
asked to return for a repeat measurement prior to the next scheduled visit and ART will 
be resumed if results are confirmed. ART will also be resumed early if the participant 
becomes pregnant or if otherwise clinically indicated. If ART is resumed before week 27, 
the fourth 3BNC117 infusion will not be performed.
If HIV-1 RNA remains undetectable at week 36, participants will be offered to continue 
off ART through week 60 with close monitoring, in conjunction with the participant’s 
primary medical provider, as long as viral rebound does not occur. In the continued ATI 
phase of the study, participants will return for follow up every week while off ART. ART 
resumption will follow same criteria as detailed above. After ART is resumed, study 
participants will return for follow up according to the Main Schedule (i.e. wk 40, 48 and 
60) (Appendix A).
Study investigators will provide non-research laboratory results as well as other relevant 
clinical information to the participant’s primary care physician during all phases of the 
study. The participant’s primary care physician will be consulted on any changes in 
treatment.
All participants will be followed for a total of 60 weeks from enrollment.   
Safety and PK assessments will be performed at multiple time points following 3BNC117 
infusions (see Appendix A). The effects of 3BNC117 on the HIV-1 reservoir will be 
evaluated by several assays. These evaluations will occur at baseline (day -14), prior to 
second (week 12) and third (week 23 or 24) 3BNC117 infusions, and at week 36) if viral 
rebound did not occur. 
We expect that enrollment will be completed in 6 – 18 months.
5
Study Population
Adults, males and females, ages 18-65 with well-controlled HIV-1 infection on standard 
ART.
5.1 Inclusion Criteria
The participant must meet all of the following inclusion criteria to participate in this 
study: 

Informed consent obtained and signed.

Males and females, age 18 to 65.

HIV-1 infection confirmed by two independent methods.

Plasma HIV-1 RNA < 50 copies/ml for at least 12 months while on combination ART 
and < 20 copies/ml at the screening visit. [Note: One or two viral blips of < 200 
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copies/mL prior to enrollment are permitted if preceded and followed by test results 
showing VL less than or equal to 50 copies/ml on the same ARV regimen.]

CD4 cell count > 500 cells/l. CD4 cell count nadir > 200 cells/l.

If sexually active male or female, and participating in sexual activity that could lead 
to pregnancy, agrees to use an effective method of contraception throughout the study 
period. Participants should also agree to use a male or female condom while off ART.

Female study participants of reproductive potential are defined as pre-menopausal 
women who have not had a sterilization procedure (e.g. hysterectomy, bilateral 
oophorectomy, tubal ligation or salpingectomy). Women are considered 
menopausal if they have not had a menses for at least 12 months and have a FSH 
of greater than 40 IU/L or if FSH testing is not available, they have had 
amenorrhea for 24 consecutive months.

Acceptable forms of contraception must include one of the following: condoms 
(male or female) with or without a spermicidal agent, diaphragm or cervical cap 
with spermicide, IUD, or hormone-based contraceptive.

If on an NNRTI-based regimen willing to a switch for 4 weeks to a dolutegravir-
based regimen.
5.2 Exclusion Criteria
Participants meeting any exclusion criterion at baseline will be excluded from study 
participation:  

Have a history of AIDS-defining illness within 1 year prior to enrollment.

Have a history of resistance to two or more antiretroviral drug classes.

History of systemic corticosteroids, immunosuppressive anti-cancer, or other 
medications considered significant by the trial physician within the last 6 months.

Chronic hepatitis B or hepatitis C.

Participant report, or chart history, of significant coronary artery disease, myocardial 
infarction, percutaneous coronary intervention with placement of cardiac stents.

Participant report, or chart history, of diabetes type 1 or 2 and/or current use of 
insulin or oral hypoglycemic medications.

Uncontrolled hypertension, as defined by a systolic blood pressure > 180 and/or 
diastolic blood pressure > 120, in the presence or absence of anti-hypertensive 
medications.

Total cholesterol level > 240 mg/dl or LDL level > 190 mg/dl at screen.

Known family history of myocardial infarction or stroke in a first-degree relative 
aged < 60 years.

Any other clinically significant acute or chronic medical condition, such as 
autoimmune diseases, that in the opinion of the investigator would preclude 
participation.

Current cigarette use in excess of 1 pack per day;

Laboratory abnormalities in the parameters listed below: 

Absolute neutrophil count  1,000 cells/l

Hemoglobin  10 g/dL

Platelet count  125,000 cells/l

ALT  2.0 x ULN
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
AST  2.0 x ULN

Total bilirubin  1.5 ULN 

Creatinine  1.1 x ULN

Coagulation parameters  1.5 x ULN.

Current antiretroviral regimen includes maraviroc or enfuvirtide.

Pregnancy or lactation.

Any vaccination within 14 days prior to 3BNC117 administration.

Receipt of monoclonal antibody therapy of any kind in the past.

History of severe reaction to drug infusions or history of severe allergic reactions.

Participation in another clinical study of an investigational product currently or within 
past 12 weeks, or expected participation during this study.
6
Methods and Procedures
6.1 Screening Procedure and Study Visits
The Time of Events Schedule summarizes the frequency and timing of various study 
assessments. See Appendix A. Recruitment, screening and post-3BNC117 visits are 
performed either at The Rockefeller University Hospital (RUH) outpatient clinic or the 
Weill Cornell Medical Center (WCMC). 3BNC117 infusion visits will only be performed 
at RUH. 
6.1.1
Pre-Screening 
Potential participants will first undergo pre-screening by telephone to assess medical 
history, and qualification for the study. Potential volunteers will have the opportunity to 
discuss the study and ask questions of the study recruiter at this time. Those who are 
eligible and interested in participating will attend a screening visit at the RUH Outpatient 
Clinic or at the WCMC Clinical Trials Unit. 
6.1.2
Screening Visit
Screening Visit:
Study personnel will answer any questions about the study. Written informed consent 
will be obtained prior to conducting any study procedures. To ensure informed consent, 
the principal investigator or designee will discuss the following processes individually 
with each volunteer:
1. Pregnancy avoidance counseling. Sexually active males and females, participating 
in sexual activity that could lead to pregnancy, should use a reliable form of 
contraception for the duration of the trial (as described in section 5.1 Inclusion 
Criteria).
2. Risk reduction counseling. Sexually active males and females will be asked to use 
condoms during ART interruption due to the risk of intermittent viremia.
3. One must assume that no improvement in control of HIV-1 infection will occur 
given the experimental nature of this monoclonal antibody.
4. Participants agree to stopping their antiretroviral medications as planned in the 
protocol and agree to return for weekly follow up visits for monitoring of plasma 
viremia levels.
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If the volunteer consents to participate, site personnel will:

Obtain a complete medical history (including concomitant medications);

Review participant’s previous HIV-1 viral load and CD4/CD8 measurements 
(HIV-1 viral load measurements should be available for at least 1 year prior to 
screening);

Perform a general physical examination including height, weight, vital signs 
(pulse, respiratory rate, blood pressure and temperature), examination of skin, 
respiratory, cardiovascular and abdominal systems, and an assessment of cervical 
and axillary lymph nodes;

Collect blood and urine specimens for all tests as indicated in the Time of Events 
Schedule, including plasma HIV-1 RNA levels and CD4/CD8 counts.

Perform a pregnancy test for all female volunteers (excluding those who are post- 
menopausal).
If the screening visit occurs more than 49 days prior to the date of the first 3BNC117 
mAb infusion, then study procedures for the screening visit must be repeated. The most 
recent set of procedures will be used if there is a discrepancy.
6.1.3
Pre-Infusion Visit 

Participants will have an ophthalmologic assessment (including slit lamp exam), 
at no cost to the participant.
6.1.4
3BNC117 Infusion Visits
3BNC117 infusions (day 0, week 12, week 24 and week 27) and assessments 1 day post 
each 3BNC117 infusion will occur at the Rockefeller University Hospital (RUH). Other 
visits will occur at the original study site (the RUH or WCMC).
Prior to drug infusion, site personnel will:

Answer any questions about the study;

Review interim medical history (including concomitant medications);

Review safety laboratory data;

Review the informed consent form administered at screening visit with the 
volunteer;

Perform a physical examination including weight, vital signs (pulse, respiratory 
rate, blood pressure and temperature) and any further examination indicated by 
history or observation;

Collect blood and urine specimens for all tests as indicated in the Time of Events 
Schedule (Appendix A);

Perform pregnancy and safe sex counseling;

Perform a pregnancy test for all pre-menopausal female volunteers (blood will be 
sent STAT) and obtain results prior to drug infusion;

Perform baseline assessment and record any systemic symptoms;

3BNC117 will be prepared for administration according to the Rockefeller 
University Pharmacy Standard Operating Procedures;

3BNC117 mAb will be administered via a peripheral vein by slow intravenous 
infusion.
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
The infusion will take approximately 60 minutes. Participants will be closely 
observed for 4 hours after drug infusion in the inpatient unit of the RUH. Vital 
signs (pulse, respiratory rate, blood pressure and temperature) will be monitored 
at end of infusion, 30 (+/- 5 minutes), 2 (+/- 10 minutes), and 4 hours (+/- 10 
minutes) post infusion. Presence or absence of adverse events will be recorded at 
30 – 45 minutes and at 4 hours. The study staff will record solicited and 
unsolicited adverse events during clinic visits as shown in Time of Events 
Schedule (Appendix A).

If volunteers develop acute infusion reaction during 3BNC117 administration, the 
infusion will be held. Rescue medications, including acetaminophen, 
diphenhydramine and glucocorticoids will be available in the RUH inpatient unit 
for use if clinically indicated. Infusion may be reinitiated after symptoms 
improve, and the remaining dose will be administered over 3 hours. 
Specific procedures to be performed at each treatment visit are illustrated in the Time of 
Events Schedule (Appendix A).  
6.1.5
Post-3BNC117 Administration Visits
Study participants will be followed through week 60. 
During ART interruption follow up visits will be performed on a weekly basis (Appendix 
A, Time of Events Schedule). 

Review of interim medical history and use of concomitant medications;

If symptoms are present, perform a symptom-directed physical examination;

Solicited and unsolicited adverse events will be assessed;

Pregnancy counseling and pregnancy testing;

Safe sex counseling;

Vital Signs;

Collect blood and urine specimens for all tests as indicated in the Time of Events 
Schedule (Appendix A);

At post-infusion study visits, participants will be asked about symptoms of ocular 
disease (such as blurry vision, increased lacrimation, redness, dryness, pain) and 
the study investigators will perform a directed exam of the eyes. If participants 
develop symptoms or signs of ocular disease, they will be referred to an 
ophthalmologist for diagnosis and management;

Participants will have a scheduled ophthalmologic assessment at week 48.

In case of adverse event(s), the volunteer will be assessed and followed up by the 
clinical team. Supplemental visit(s) for further investigation can be planned at the 
discretion of the principal investigator or designee. Supplemental visit(s) may be 
recommended if clinically indicated or to clarify observations.
Specific procedures to be performed at each follow up visit are illustrated in the Time of 
Events Schedules (Appendix A). 
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Any abnormalities (adverse events) attributed to study drug, including laboratory 
abnormalities, should be subsequently followed until the event or its sequelae resolve or 
stabilize. 
6.1.6
ART interruption and re-initiation of combination ART 
ART regimen will be discontinued 2 days after the third 3BNC117 infusion, at week 24 
(last dose of ART will be taken on day 169). 
NNRTIs have longer elimination half-lives (> 20 hours) compared with most nucleoside 
reverse transcriptase inhibitors (NRTIs). In order to avoid a period of NNRTI 
monotherapy, which can lead to the development of resistance, if the participant’s ART 
regimen includes an NNRTI, the NNRTI will be switched to dolutegravir (an integrase 
inhibitor) at week 20, 4 weeks before all other antiretroviral drugs are discontinued. 
Dolutegravir will be provided to the participants for that time period.
The same ART regimen will be resumed at week 36. ART regimen will be resumed 
sooner if plasma HIV-1 RNA level is ≥ 200 copies/ml or CD4+ T cell count drops < 350 
cells/l, and either result is confirmed upon repeat measurement, during the next weekly 
scheduled visit. If plasma HIV-1 RNA level is ≥ 1,000 copies/ml, the participant will be 
asked to return for a repeat measurement prior to the next scheduled visit and ART will 
be resumed if results are confirmed. ART will also be resumed early if the participant 
becomes pregnant, or if otherwise clinically indicated. If ART regimen is resumed before 
week 27, the fourth 3BNC117 infusion will not be administered.
Participants will be followed weekly during the analytical treatment interruption phase of 
the study for safety assessments and for monitoring plasma HIV-1 RNA levels. 
Participants may return to clinic between scheduled visits for additional VL 
measurements, if they desire to do so. CD4+ T cell counts will be measured every other 
week.
If HIV-1 RNA remains undetectable at week 36, participants will be offered to continue 
off ART with close monitoring, as long as HIV-1 viral rebound does not occur. In the 
continued ATI phase of the study participants will return for follow up every week, while 
off ART. ART resumption will follow same criteria as detailed above. After ART is 
resumed, study participants will return for follow up according to the Extension Schedule 
– Off ART Follow up (i.e. wk 40, 48, 56 and 60) (Appendix A).
The participant’s primary care physician will be consulted on any changes in treatment. 
During the ART-interruption phase of the study participants may be at increased risk of 
transmitting HIV-1 to their partners if they become viremic, and of HIV-1 superinfection 
from an HIV-infected partner. Therefore, participants will be asked to use male or female 
condoms for the duration of ART interruption. In the event of a high-risk exposure to an 
HIV-infected partner, the participant will be advised to seek evaluation by his/her 
primary care provider to determine the need to reinitiate ART.  
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6.1.7
Final Visit/Early termination Visit
End of study (EOS) visit procedures will occur according to the Time of Events Schedule 
(Appendix A). Any participant who is withdrawn from the study should be seen for an 
EOS visit (Appendix A) as soon as possible. The study team will ensure the participant 
has appropriate follow-up with his/her primary care physician.
6.1.8
Discontinuation of 3BNC117 infusion and/or volunteer withdrawal from 
study
6.1.8.1
Discontinuation of 3BNC117 infusion
The 3BNC117 infusion will be discontinued for any of the following reasons:
1. Any immediate hypersensitivity reaction (such as urticarial rash; bronchospasm; 
laryngeal edema; anaphylaxis; syncope).
2. Life threatening medical event during 3BNC117 infusion.
6.1.8.2
Discontinuation of further 3BNC117 infusions
Volunteers will be discontinued from further 3BNC117 infusions for any of the 
following reasons:
1. If ART regimen is resumed before week 27 due to viral rebound. ART regimen is 
resumed if plasma HIV-1 RNA level is ≥ 200 copies/ml or if CD4+ count drops < 
350 cells/l and either result is confirmed upon repeat measurement, during the 
next weekly scheduled visit; or if plasma HIV-1 RNA level is ≥ 1,000 copies/ml, 
and confirmed by a repeat measurement prior to the next scheduled visit. 
2. A disease, condition or an adverse event that may develop, regardless of 
relationship to 3BNC117, if the principal investigator or designee is of the 
opinion that another 3BNC117 infusion will jeopardize the safety of the 
volunteer.
3. An abnormal laboratory event based on the following criteria:
-
For a grade 2 laboratory event, the laboratory test must be repeated and the 
event determined to be resolved or improved in the opinion of the principal 
investigator or designee prior to 3BNC117 infusion;
-
For a grade 3 or greater laboratory abnormality, even if resolved, the SMC 
must be consulted before making a decision to administer 3BNC117.
4. Any immediate hypersensitivity reaction (such as urticarial rash; bronchospasm; 
laryngeal edema; anaphylaxis; syncope).
5. Life threatening medical event following 3BNC117 unless not related to the 
investigational product.
6. Intercurrent use of immunosuppressive medication considered significant by the 
trial physician (e.g., systemic corticosteroids).
7. Pregnancy.
8. Participant’s request to discontinue further 3BNC117 infusions.
6.1.8.3
Withdrawal from the study (Early Termination)
     Volunteers may be withdrawn from the study permanently for the following reasons:
1. Volunteers may withdraw from the study at any time if they wish to do so, for any 
reason.
2. Following an adverse event at the discretion of the investigator (or designee).
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3. Request of the primary care provider if s/he thinks the study is no longer in the 
best interest of the participant.
4. Participant judged by the investigator to be at significant risk of failing to comply 
with the protocol in a manner that might lead to harm to self or seriously interfere 
with the validity of the study results.
5. At the discretion of the FDA or investigator.
6.1.8.4
Follow up after withdrawal from study (Early Termination)
Any adverse event resulting in withdrawal of a volunteer will be followed up until 
resolution or until the adverse event is judged by the principal investigator or designee to 
have stabilized where possible.
At the time of withdrawal, provided the volunteer is willing, all the requested termination 
visit procedures (EOS visit procedures) will be performed according to the Time of 
Events Schedule (Appendix A).
The date and reason for withdrawal from the study (early termination) should be 
collected and reported to the Safety Monitoring Committee (SMC), the Clinical Research 
Office and the IRB. Whenever possible, volunteers who are withdrawn from the study 
will be followed until the time of their final planned visit.
A pregnant volunteer will not receive 3BNC117 infusions. If pregnancy occurs after any 
3BNC117 infusion, the volunteer will be asked to return for follow up every 4-6 weeks 
until delivery (see section 6.2.8 Family Planning Counseling). 
6.2 Study Procedures
6.2.1
Consent Procedure
Prior to the initiation of any study related procedures, the potential participants will be 
given a copy of the most recent IRB stamped and approved informed consent to read. 
Additionally, the PI or study staff member who has been designated to consent will 
discuss the specifics of the study including but not limited to the purpose of the research, 
procedures, time commitment, required tasks, test article, alternative treatments, benefits, 
risks, confidentiality etc. in a comprehensible (non-scientific) manner, using language 
readily understandable by the participant. Participants will be told that participation is 
voluntary and that, if they do not consent, they will not be penalized. The person 
consenting will assure the voluntariness of the participant.
A private, confidential setting will be provided for the potential participant to read and 
discuss the informed consent free from coercion, undue influence or constraints of time. 
All participants will be given a chance to ask questions and express concerns. They will 
be given the option to take the consent home and discuss it with family, friends, and /or 
health care providers. After a participant and the person conducting the consenting 
process signs and dates the consent, the participant will be given a copy of the signed 
informed consent form. 
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An enrollment note will be written in the source document as to who obtained consent, 
how, when, were questions asked and answered, and that a copy of the informed consent 
was given to the participant.
 
The "Teach Back" method will be used in the clinical research setting to ask research 
participants to repeat or “teach back” the information, concepts and directions that the 
staff member has attempted to convey to the participant. This method is used to assess 
comprehension and retention of protocol requirements, adverse event information, risks 
and benefits, and the participant's rights described in the Informed Consent process.
 
Spanish-speaking volunteers may be enrolled in the study. For these potential volunteers, 
a certified Spanish translation of the IRB-approved informed consent form (ICF) will be 
used. For unexpected or isolated volunteers who are candidates for this study, who are 
native speakers of other languages, a telephonic interpreting service (such as Pacific 
Interpreters) will be used to facilitate the explanation of the study. The investigator will 
send the interpreter a copy of the study’s ICF and a Short Form in the language that needs 
to be interpreted.  The consenting process will be conducted by reading the English ICF 
while the interpreter repeats the words in the language of choice. The interpreter will also 
translate questions and answers that occur during the informed consent discussion. At the 
end of the consenting process, if the participant agrees, he/she will sign the Short Form in 
his/her native language in the presence of the investigator. The interpreter will sign both 
the IRB-approved ICF and Short Form as a witness, and will fax or email the signed 
copies to the investigator. The investigator will sign the IRB-approved ICF as the person 
conducting the consent discussion.
6.2.2
Study Assignment
This is an open-label study and participants will be enrolled sequentially as they meet 
enrollment criteria. The RUH pharmacist will dispense 3BNC117 in a piggy-back, 
diluted in sterile normal saline, ready for use. This study is open-label, both study 
investigators and volunteers will know the study allocation.
6.2.3
3BNC117  Infusions
3BNC117 will be provided in single-use vials containing 5 ml of the product at a 
concentration of 20 mg/ml. The volume of 3BNC117 to be administered will be 
calculated by the RUH research pharmacist, according to study assignment. The 
appropriate volume of 3BNC117 will be administered as a slow intravenous infusion over 
60 minutes in the inpatient unit of the RUH. The calculated dose of 3BNC117 will be 
diluted in sterile normal saline to a volume of 250 ml. 
A maximum of two participants will receive a 3BNC117 infusion per day. Infusions will 
not be given simultaneously.
3BNC117 will be administered intravenously, via a peripheral vein in one of the upper 
extremities. The administration site should be free of potentially complicating 
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dermatologic conditions. At the end of infusion, the IV line will be flushed with 20ml of 
Normal Saline to ensure all the medication has been delivered.
Volunteers will be closely observed for 4 hours after drug infusion. If volunteers develop 
acute infusion reaction during 3BNC117 administration, the infusion will be held. Rescue 
medications, including acetaminophen, diphenhydramine and glucocorticoids will be 
available in the RUH inpatient unit for use if clinically indicated. Infusion may be 
reinitiated after symptoms improve, and the remaining dose will be administered over 3 
hours.
6.2.4
Medical History and Physical Examination
At the time of screening, a past medical history will be collected that will include details 
of any previous reaction to vaccination, and contraceptive practices. Interim medical 
histories will be collected at time points according to the Time of Events Schedule 
(Appendix A). 
A general physical examination will be conducted including weight, height, vital signs, 
and examination of skin, respiratory, cardiovascular, central nervous and abdominal 
systems. At the time of 3BNC117 infusions and at selected time-points thereafter, general 
and/or directed physical examinations will be performed according to the Time of Events 
Schedule (Appendix A). A directed physical examination will include weight, vital signs, 
examination of infusion site, and any further examination indicated by history or 
observation.
6.2.5
Laboratory Evaluations
Venous blood will be collected at every study visit, usually from the antecubital fossa, 
according to the Time of Events Schedule (Appendix A). At no time will the total volume 
of blood collected exceed 550 mL over an 8-week period. Two large blood draws (250-
300 ml) will occur in the study: on weeks 12 and 36. At all other study visits, total blood 
volume collected will not exceed 100 ml. Participants will undergo a leukapheresis 
procedure on day -14 and week 23.
All specimens will be handled according to SOPs that were developed in the GLP-like-
Processing Lab within the Laboratory of Molecular Immunology.
6.2.5.1
Specimen Shipment Preparation, Handling and Storage
- Safety labs: Specimens collected for safety labs at RUH will be transported to Memorial 
Sloan Kettering Cancer Center laboratory (MSKCC) via a courier. At the Cornell site, 
safety labs will be processed at the local laboratory. Specimens for LabCorp will be 
picked up by LabCorp staff at both clinical sites.
- Research labs:
Specimens collected at the Rockefeller and Cornell Sites will be transported to the 
Sample Processing lab in the Laboratory of Molecular Immunology by laboratory staff. 
The buildings are adjacent to each other and are connected by an underground tunnel.
1. Peripheral Blood Mononucleated Cells (PBMC) (isolated from ACD tubes or from 
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leukapheresis): PBMC isolation will be performed at the Laboratory of Molecular 
Immunology. PBMCs are isolated using density gradient centrifugation with Histopaque. 
The isolated PBMC layer is washed twice with Hanks Balanced Salt Solution before a 
final wash in R10. Cells are counted with a Vi-cell XR (Beckman Coulter) before being 
frozen at a concentration of 1 x 107 cells per aliquot. PBMCs will be stored in liquid 
nitrogen freezer. 
PBMC samples will be shipped to the laboratory of Dr. Richard Koup and the laboratory 
of Dr. Daniel Kaufman, who will perform monitoring of cellular immune responses. 
Samples will also be shipped to the laboratory of Dr. Robert Siliciano for viral outgrowth 
assays. The remaining aliquots will be stored in a liquid nitrogen freezer located in the 
Lab. of Molecular Immunology.
2. Plasma: Samples will be collected from ACD tubes after an initial centrifugation step, 
prior to PBMC isolation. The collected plasma sample goes through a second 
centrifugation step and is aliquoted in 1 or 10 ml volumes and stored at -80 degrees 
Celsius. 
Plasma samples will be shipped to the Laboratory of Dr. David Montefiori for monitoring 
of humoral immune responses. The remaining aliquots will be stored in the Lab. of 
Molecular Immunology.
3. Serum: Samples will be collected in Serum Separation Tubes (SST). Following 
centrifugation, serum from multiple tubes, from the same volunteer, will be pooled, 
divided in 1ml aliquots and stored at -80 degrees Celsius. 
Serum samples will be shipped to Celldex Therapeutics in Needham, Massachusetts and 
to the laboratory of Dr. Michael Seaman in Boston. Serum samples will be used for 
measurement of 3BNC117 levels, anti-3BNC117 antibodies and for in vitro 
neutralization assays. The remaining aliquots will be stored in the Lab. of Molecular 
Immunology.
All infectious specimens will be transported using packaging mandated in the Code of 
Federal Regulations, 42 CFR Part 72.  Member carriers such as FedEx will accept or 
reject packages of dangerous goods on strict adherence to the International Air 
Transportation Association (IATA) Dangerous Goods Regulations (DGR).  Shipments 
will be compliant with IATA DGR requirements. 
6.2.5.2  Biohazard Containment 
As the transmission of HIV-1 and other blood-borne pathogens can occur through contact 
with contaminated needles, blood, and blood products, appropriate blood and secretion 
precautions will be employed by all personnel in the drawing of blood and shipping and 
handling of all specimens for this study, as currently recommended by the Centers for 
Disease Control and Prevention and the National Institutes of Health.
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6.2.6
Leukapheresis
Leukapheresis will be performed for all study participants. The procedure will occur at 
day -14 and week 23 in the RUH inpatient unit. Collected samples will be used for viral 
outgrowth assays to measure levels of latently infected resting CD4+ T cells.
Stat PT/PTT and CBC with differential will be sent prior to the procedure.
6.2.7
Monitoring for cytokine release associated adverse events and treatment of 
cytokine release syndrome
Based on previous clinical experience with similar monoclonal antibodies and with 
3BNC117 (protocol MCA-835), it is unlikely that administration of 3BNC117 will lead 
to cytokine release syndrome. However, a potential side effect of a monoclonal antibody 
can be the stimulation of a massive release of cellular cytokines, which can have 
profound effects on blood pressure, vascular integrity, and myocardial, lung, liver, and 
kidney functions. If cytokine release syndrome occurs, the volunteer may need to be 
treated with intravenous fluids, vasopressors, and high-dose corticosteroids and may 
require ventilatory support. 
Study participants will be closely monitored for 4 hours post infusion in the RUH 
inpatient unit. Access to a twenty-four hour on-call physician is available. The RUH 
outpatient and inpatient units and the WCMC Clinical Trial Unit are equipped with crash 
carts for immediate medical care. Supportive medications, including acetaminophen, 
diphenhydramine and glucocorticoids, will be available at both clinical sites for use if 
clinically indicated. In case of an emergency, after stabilization of the volunteer, he/she 
will be transferred to the neighboring tertiary care center, New York Presbyterian 
Hospital (Cornell) for specialized medical care. 
6.2.8
Family Planning Counseling
During screening and subsequent study visits, study personnel will counsel volunteers 
about the importance of prevention of pregnancies and the use of condoms, as well as 
other effective family planning methods. Condoms will be provided.
Pregnancy tests will be conducted at follow up visits as outlined in the Time of Events 
Schedule (Appendix A). 
Should pregnancy occur, a pregnant volunteer will not receive 3BNC117 infusions. If 
pregnancy occurs after any 3BNC117 infusion, a pregnant volunteer will be asked to 
return for follow up every 4-6 weeks until delivery. Should pregnancy occur, ART will 
not be discontinued or will be resumed as soon as the study investigators become aware 
of the pregnancy. Approximately 2-4 weeks after delivery, a pediatrician will examine 
the baby to assess her/his health status. The outcome of the pregnancy and the health 
status of the baby will be reported to the local IRBs, Clinical Research Office at the 
RUH, the SMC and the Antiretroviral Pregnancy Registry.
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6.2.9
Compensation
There will be no compensation for the screening visit. Each study volunteer will be 
compensated $200 for each 3BNC117 infusion visit, $ 200 for each leukapheresis and 
$50 for each ophthalmologic evaluation. They will be compensated $60 dollars for each 
post infusion follow up visit and for weekly visits during the ART interruption phase. For 
late follow up visits, they will be compensated $100. In total, participants will be 
compensated $2,660, if all study visits are completed. 
Volunteers that agree to remain off ART after week 36 will return to clinic every week 
for follow up. These volunteers will be compensated $50 for each of these additional 
visits, up to $1,200. In total, these volunteers may receive up to $3,860 if they remain off 
ART until the final study visit at week 60.  
If volunteers are asked to return for an unscheduled visit, they will be compensated $25 
each time.
Compensation is provided to help cover travel expenses, as well as child care and time 
lost from gainful employment. Volunteers will be compensated only for the visits they 
complete.
6.2.10 Safety Assessments
6.2.10.1 Solicited Adverse Events
Solicited adverse events in this study include presence of feverishness, chills, headache, 
nausea, vomiting, malaise, myalgia and arthralgia, as well as ocular complaints such as 
conjunctival erythema, excessive tearing or burning, and will be collected prospectively 
by structured interviews on 3BNC117 infusion and post-infusion follow up visits; 
recorded and graded according to pre-established criteria (see Appendix B). The DAIDS 
AE Grading Table v2.0 will be used to grade adverse events. In addition, the CTCAE 
v4.03 grading scale will be used for reporting and grading adverse events related to 
infusion reactions and cytokine release syndromes. 
Vital signs (pulse, respiratory rate, blood pressure and temperature) will be 
monitored at end of infusion, 30 (+/- 5 minutes), 2 (+/- 10 minutes), and 4 hours 
(+/- 10 minutes) post infusion. All medications required for treatment of adverse events 
will be recorded.
6.2.10.2 Other Adverse Events
Other adverse events will be recorded following an open question to volunteers, with the 
dates of commencement and resolution and any medication required. All adverse events 
will be followed to resolution. Serious Adverse Events will be recorded during the entire 
study period. They will be graded as indicated in Appendix B. 
6.2.10.3 Routine Laboratory Parameters
Laboratory parameters will routinely include CD4+ and CD8+ T cell counts and HIV-1 
viral loads (VL), hematology (WBC and differential, RBC, hemoglobin/hematocrit, 
platelets), clinical chemistry (Na, K, Cl, Ca, Creatinine, Glucose, Total and Direct 
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bilirubin, Alkaline phosphatase, AST and ALT), and urinalysis. ANA will be performed 
at screening, day 0 and at week 60, and as clinically indicated. Coagulation tests (PT and 
PTT) will be performed at screening.
At screening and prior to each 3BNC117 infusion, female volunteers (except post-
menopausal women) will have serum beta-HCG assessed and at follow up visits they will 
have urine beta-HCG checked. The laboratory samples for these tests will be collected at 
the time points indicated in the Time of Events Schedule (Appendix A). In the event of 
an abnormal laboratory value, volunteers may be asked to have an additional sample 
collected at the discretion of the principal investigator or designee. 
Volunteers will be screened for syphilis and viral hepatitis (HBsAg and HCV-RNA) at 
the Screening Visit. 
6.2.11 Viral Sensitivity, Antiretroviral and Immunogenicity Assessments
Sensitivity of the participant’s virus to 3BNC117 will be assayed by:
1. Viral outgrowth assay to evaluate the sensitivity of autologous viruses to 
3BNC117 will be performed in the Laboratory of Molecular Immunology.
Briefly, autologous viruses will be outgrown from participant’s PBMCs in co-
cultures with healthy donor PBMCs, and 3BNC117’s neutralizing activity against 
culture supernatants containing autologous viruses will be determined by TZM.bl 
assay. The presence of HIV-1 in supernatant will be determined by p24 ELISA. 
TCID50s will be determined for all HIV-1 containing supernatant and the 
3BNC117 IC50s determined in a TZM.bl neutralization assay, which will be 
performed in the laboratory of Dr. Michael Seaman of the Beth Israel Deaconess 
Hospital in Boston (a Core Laboratory sponsored by the Collaboration for AIDS 
Vaccine Discovery, CAVD) (Laird et al., 2013, Caskey, Klein et al, 2015).
Plasma HIV-1 RNA levels will be assessed by:
1. Standard HIV-1 viral load assay (CLEP-certified) will be performed at a 
contracted laboratory, LabCorp. The detection range of the assay is 20-10x106 
copies/ml. HIV-1 viral load will be determined at multiple time points before and 
after 3BNC117 administrations.
The HIV-1 reservoir will be evaluated by the following assays:
2. Single copy HIV-1 viral load assay. This is a more sensitive assay with a limit of 
detection of 1 copy of HIV-1 RNA/ml of plasma. These assays will be performed 
in the laboratory of Dr. Frank Maldarelli (NCI/NIH).
3. Viral outgrowth assay for latency. The levels of latently infected resting CD4+ T 
cells (measured as infectious units per million CD4+ resting T cells) will be 
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evaluated by a viral outgrowth assay, performed in the Laboratory of Dr. Robert 
Siliciano from Johns Hopkins University. This assay requires large number of 
PBMCs, and samples will be collected at day -14 and weeks 12, 23 and 36 (if 
virologic rebound does not occur by week 36).
4. HIV-1 cell associated DNA and RNA levels in PBMCs will be determined in the 
Laboratory of Molecular Immunology, at baseline and weeks 12, 24 and 36 (if 
virologic rebound does not occur by week 36). 
The effects of 3BNC117 on host immune responses and on infecting HIV-1 strains will 
be evaluated by the following assays:
5. TZM-bl neutralization assay will be performed in the laboratory of Dr. Michael 
Seaman of the Beth Israel Deaconess Hospital in Boston (a Core Laboratory 
sponsored by the Collaboration for AIDS Vaccine Discovery, CAVD). In vitro 
neutralization assays will be performed with serum from study participants before 
and after administration of 3BNC117 against a panel of HIV-1 env pseudoviruses 
representing multiple clades. 
6. T cell assays - HIV-1 Env and Gag specific responses will be evaluated in 
PBMC’s by multiparametric cytokine flow cytometry. Phenotypic analysis, 
specifically the expression of immune activation/exhaustion markers on CD8+ T 
cells will also be evaluated. These assays will be performed at the Laboratory of 
Molecular Immunology, the laboratory of Dr. Richard Koup at the Vaccine 
Research Center (VRC) at NIH, a core lab of the Collaboration for AIDS Vaccine 
Development (CAVD), and the laboratory of Dr. Daniel Kaufman at the 
University of Montreal. 
7. B cell assays – HIV-1 Env and Gag specific binding antibody responses will be 
evaluated in serum or plasma samples in the laboratory of Dr. Georgia Tomaras 
(Duke University, a core laboratory of the CAVD).
8. Levels of inflammation markers, such as C-reactive protein, D-dimers, IL-6, and 
soluble CD14 will be performed in plasma or serum samples, prior to and after 
3BNC117 infusions. These will be performed at the Laboratory of Molecular 
Immunology, or by clinical assays at MSKCC or LabCorp.
9. Genotyping – Viral strains will be isolated/cultured ex-vivo and sequencing of 
HIV-1 env will be performed in samples collected at baseline and after 3BNC117 
infusions, at the time of virologic rebound. Genotyping will be performed in the 
Laboratory of Molecular Immunology by reverse transcription followed by PCR 
amplification and sequencing of HIV-1 envelope genes. This will allow us to 
analyze the induction of escape mutations, if virologic rebound occurs. Results 
will be descriptive. 
Genotypic analysis of antiretroviral resistance in rebounding viral strains (samples 
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with HIV-1 RNA levels > 400 copies/ml) will be performed by a CLEP-certified 
assay at LabCorp.  
10. Resistance testing of amplified HIV-1 envelope genes will be performed as 
previously described (Klein F et al., 2012). Amplified HIV-1 envelope genes will 
be cloned and expressed as pseudoviruses followed by evaluation of resistance to 
3BNC117 in TZM-bl neutralization assays. Envelope gene amplification and 
cloning will be performed in the Laboratory of Molecular Immunology, TZM-bl 
neutralization assays in the laboratory of Dr. Michael Seaman. Results will be 
descriptive.
11. Evaluation of HIV-1 integration sites by deep sequencing will be performed in the 
Laboratory of Molecular Immunology, before and after administration of 
3BNC117.
The pharmacokinetics and immunogenicity of 3BNC117 will be evaluated by the 
following assays:
12. Measurement of 3BNC117 levels by a validated sandwich ELISA using a murine 
anti-idiotype antibody to 3BNC117. These assays will be performed by Celldex 
Therapeutics. 3BNC117 levels will be measured in serum or plasma.
13. Anti-drug (3BNC117) antibody responses in serum or plasma. Assays will be 
performed by Celldex Therapeutics.
Adherence to ART interruption will be confirmed at weeks 27 and 32, and at selected 
later study visits if participants remain off ART beyond week 36 (Appendix A) by the 
following assays: 
14. Levels of antiretroviral medications (i.e. NNRTI’s or PI’s) will be measured by 
CLEP-certified assays performed at a contract laboratory (LabCorp). 
15. TZM-bl infection with HIV-1 pseudotyped with murine leukemia virus, 
performed in the laboratory of Dr. Michael Seaman of the Beth Israel Deaconess 
Hospital in Boston (a Core Laboratory sponsored by the Collaboration for AIDS 
Vaccine Discovery, CAVD). This is not a standardized assay. However, negative 
controls and positive controls with sera from patients treated with representative 
drug classes will be used.  
All immune responses and antiretroviral activity will be evaluated for proportion of 
responders and the mean responses will be compared. Research samples collected at the 
RUH and WCMC will be processed and stored in the Laboratory of Molecular 
Immunology. Optimal sample collection, processing, cryopreservation, archiving and 
storage will be maintained. Additional studies will be performed as warranted at the 
discretion of the investigators.
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6.2.12 Pharmacokinetic evaluations
Pharmacokinetic parameters will be calculated using standard non-compartmental 
analysis methods. Descriptive results will be presented for the pharmacokinetic 
parameters. 
PK assessments will be performed on plasma or serum samples before 3BNC117 
administration, at the end of each 3BNC117 infusion, 1 day, 1 week and 4 weeks after 
each infusion, at the time of viral rebound and at later time points, as outlined in the Time 
of Events Schedule (Appendix A). Pharmacokinetic parameters to be assessed will 
include maximum concentration (Cmax) elimination half-life (t1/2), clearance (CL/F), 
volume of distribution (Vz/F), AUC and decay curve. 
3BNC117 serum or plasma levels will be measured by a sandwich ELISA using a murine 
anti-idiotype antibody to 3BNC117. The assays will be performed at Celldex 
Therapeutics.  
7
Investigational Product 
- Investigational Drug Name:
3BNC117
3BNC117 is a recombinant, fully human monoclonal antibody (mAb) of the IgG1κ 
isotype that specifically binds HIV envgp120. 
- Manufacturer of study drug:
Celldex Therapeutics, Inc.
- FDA Approved:
No
- IND Number:
118,225
- IND Sponsor:
Sarah Schlesinger, MD 
7.1 Regimen
3BNC117 will be administered intravenously at 30 mg/kg dose level, on day 0, week 12, 
week 24 and week 27. 
7.2 Study Product Formulation and Preparation
 3BNC117 will be provided by Celldex Therapeutics in single-use vials containing 5 ml 
of the product at a concentration of 20 mg/mL.
The volume of 3BNC117 to be administered will be calculated by the RUH research 
pharmacist. 3BNC117 will be diluted in sterile normal saline to a volume of 250 mL, and 
administered as a slow intravenous infusion over 60 minutes. 
7.3 Dispensing and Handling of Investigational Product
3BNC117 will be shipped from Celldex Therapeutics and will be stored in the RU 
Pharmacy at 2 - 8C. 3BNC117 will be dispensed by the RU Hospital Pharmacy. Trial 
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personnel will ensure that the study ID number on the piggy-back matches the study ID 
assigned to the volunteer prior to administration. 
The appropriate dose will be calculated by the RU pharmacist according to participant’s 
weight. 3BNC117 will be dispensed in a piggy-back, and diluted in normal saline (NaCl 
0.9%), to a volume of 250 ml. It will be dispensed ready for administration by study 
investigators.
7.4 Accountability and Disposal of Used and Unused Investigational Product
The date, allocation number and location of storage of the vials will be recorded in a log.  
During the trial, the product accountability form, and the dispensing log will be 
monitored. At the end of the trial, unused vials will be returned to Celldex Therapeutics 
or destroyed.
7.5 Assessment of Participant Adherence with Study Product
Not applicable. Participants will be administered 3BNC117 in the inpatient unit of the 
RUH.
7.6 Concomitant Medications and Procedures
Use of concomitant medications will be reviewed at each study visit.  Each participant 
will have a medication reconciliation record. It will be updated if schedule or dose level 
changes, and if new medications are initiated.   
Participants will continue their ART regimen until week 24. If ART regimen includes an 
NNRTI, the NNRTI will be switched to dolutegravir 4 weeks prior to ART interruption. 
The participant’s primary care physician will be consulted on any changes in treatment.
7.7 Permitted Medications and Procedures
We do not anticipate significant drug interactions with the study product at this time, 
therefore, if clinically necessary, volunteers can be initiated on other medications for 
intercurrent illnesses that might occur during their study participation.
7.8 Prohibited Medications and Procedures
We do not anticipate significant drug interactions with the study product at this time. 
Participants that enroll in the study agree to not participate in other studies of 
investigational drugs. In addition, they should not participate in studies that require 
frequent blood sample collection.
7.9 Precautionary Medications and Procedures
We do not anticipate significant drug interactions with the study product at this time. 
Participants that enroll in the study agree to not participate in other studies of 
investigational drugs. In addition, they should not participate in studies that require 
frequent blood sample collection.
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7.10 Required Medications
Volunteers will continue their ART regimen until week 24. Volunteers on an NNRTI-
based regimen will be switched to dolutegravir for 4 weeks prior to stopping all other 
antiretroviral medications.  Dolutegravir will be provided to participants during that time 
period.
7.11 Rescue Medications
If volunteers develop acute infusion reaction during 3BNC117 administration, the 
infusion will be held. Rescue medications, including acetaminophen, diphenhydramine 
and glucocorticoids will be available in the RUH inpatient unit for use if clinically 
indicated. Infusion may be reinitiated after symptoms improve, and the remaining dose 
will be administered over 3 hours.
8
Data Analysis
8.1 Design
The proposed study is an exploratory phase 2, open label study to evaluate the 
antiretroviral activity and safety of four 3BNC117 infusions in HIV-infected individuals 
on combination antiretroviral therapy and during a brief analytical treatment interruption. 
The study will also obtain additional data on 3BNC117’s effects on the HIV-1 reservoir. 
Study participants will be administered four intravenous infusions of 3BNC117, 
(administered at 30 mg/kg). Antiretroviral therapy will be discontinued 2 days after the 
third 3BNC117 infusion, at week 24. We project screening 50 participants in order to 
achieve 15 evaluable participants. An over-enrollment of 2 participants will be allowed if 
participants do not complete all four 3BNC117 infusions. Participants that do not receive 
the fourth infusion because viral rebound occurred prior to week 27 will not be replaced. 
Additional participants will be enrolled after study withdrawal is confirmed.
The same ART regimen will be resumed at week 36 or sooner if plasma HIV-1 RNA 
level is ≥ 200 copies/ml or CD4+ T cell count drops < 350 cells/l, during the next 
weekly scheduled visit. If plasma HIV-1 RNA level is ≥ 1,000 copies/ml, the participant 
will be asked to return for a repeat measurement prior to the next scheduled visit, and 
ART will be resumed if results are confirmed. ART will also be resumed early if the 
participant becomes pregnant or if otherwise clinically indicated. If ART regimen is 
resumed before week 27, the fourth 3BNC117 infusion will not be administered.   
Volunteers will be followed weekly during the analytical treatment interruption phase for 
safety assessments and for monitoring plasma HIV-1 RNA levels. CD4+ T cell counts 
will be monitored every 2 weeks. (Appendix A).
 Volunteers will be followed for 60 weeks from enrollment.    
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8.2 Analysis of Antiretroviral effects, Safety and Pharmacokinetics
Primary Objective:
1. 3BNC117’s effect on virologic rebound:
A one-sided upper confidence interval will be constructed for the probability of rebound 
using the Clopper-Pearson method (Clopper, C. et al., 1934). Kaplan-Meier estimator will 
be used to address the second variable, “time to rebound” (Kaplan, E. et al., 1958).
2. Analysis of safety
The number and percentage of participants experiencing one or more AEs will be 
summarized by relationship to study drug, and severity. AEs will be summarized by the 
number and percentage of participants who experienced the event, according to system 
organ class (SOC) and preferred term. AEs will also be summarized by severity grade 
and by relationship to study drug according to the DAIDS AE Grading Table v2.0 (see 
Appendix B). The CTCAE v4.03 grading scale will be used for reporting and grading 
adverse events related to infusion reactions and cytokine release syndromes. 
The changes in hematology, chemistry, and other laboratory values will be summarized 
descriptively. Changes will be calculated relative to the values collected at baseline.
Secondary and Exploratory Objectives:
1. Pharmacokinetics: 
Pharmacokinetic parameters will be calculated using standard non-compartmental 
analysis methods, using WinNolin software, version 6.3. Pharmacokinetic parameters, 
including AUC, Cmax, T½, Tmax and others will be summarized. Pharmacokinetic 
parameters will be examined to correlate exposure with safety and pharmacodynamic 
parameters, and variance based on population intrinsic factors such as weight and gender 
will be explored. 
2. 3BNC117 effects on the size of the HIV-1 reservoir:
A 95% repeated measures ANOVA F-test will be used to compare the following 
variables, before each infusion for all participants and at week 36, for participants that do 
not rebound:

levels of latently infected resting CD4+ T cells in peripheral blood;

levels of cell-associated HIV-1 RNA  and DNA in PBMCs; 

levels of plasma HIV-1 RNA by single copy assay.
3. Host immune responses:
A 95% repeated measures ANOVA F-test will be used to compare the following 
variables, at baseline, at 4 weeks after each infusion and at week 36.

serum levels of inflammation markers, such as: C-reactive protein, D-dimers, 
IL-6 and soluble CD-14. 

CD8+ T cell expression of activation markers such as: HLA-DR, CD38 and 
PD-1. 
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
HIV-1 gag and env-specific T and B cell immune responses will be evaluated 
by intracellular cytokine staining and multiplex ELISA.
4. Other measurements:
The frequency and levels of anti-3BNC117 antibodies, after each 3BNC117 infusion, will 
be calculated and displayed in tables. 
Genotyping of HIV-1 isolates will be performed in the Laboratory of Molecular 
Immunology by reverse transcription followed by PCR amplification and sequencing of 
HIV-1 envelope genes. This will allow us to phylogenetically compare viruses grown 
from PBMCs collected from participants while on ART to rebound viruses collected after 
treatment interruption, and analyze the induction of escape mutations. In addition, 
amplified HIV-1 envelope genes will be cloned and produced in pseudoviruses in order 
to test for resistance to 3BNC117 by TZM-bl neutralization assay. Results will also be 
descriptive. 
A Fisher exact test will allow us to contrast the rate of rebound between participants with 
baseline 3BNC117 IC50 against autologous viruses of < 2 μg/ml or ≥ 2 μg/ml. The 
Kruskal–Wallis one-way analysis of variance will be used to compare the mean time to 
rebound and mean reduction in infectious units per million (IUPM) in CD4+ resting T 
cells according to baseline 3BNC117 sensitivity of autologous viruses (IC50 < 2 μg/ml or 
≥ 2 μg/ml). For both tests a 95% significance level will be assumed. 
Continuous data will be summarized by descriptive statistics, including the sample size, 
mean, standard deviation, median and range. Categorical data will be summarized by the 
number and percentage of participants. If necessary Log2 of variables will be used.
8.3 Sample Size Considerations
In this pilot study we intend to enroll a convenient sample size of 15 evaluable 
participants. 
A one-sided upper confidence interval will be constructed for the probability of rebound 
using the Clopper-Pearson method. As such, a sample size of 15 HIV-infected individuals 
will allow the rejection of the null hypothesis (rate=0.85) with 80% power for an effect 
size equal or higher than 0.32, if at least 6 participants do not rebound. The one-sided 
95% Clopper-Pearson confidence intervals calculated for a varying number of observed 
rebounds are presented in Table 1.  
Number of Rebounds
UCI
0
0.1810
1
0.2794
2
0.3634
3
0.4398
4
0.5108
5
0.5774
6
0.6404
7
0.7000
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Table 1. Upper bound Confidence Interval for a 
sample size of n=15, calculated using 
binom.test R function, package stats
If 10 or more participants experience viral 
rebound prior to week 29 [5 weeks after ART 
interruption and 2 weeks after last 3BNC117 
infusion], additional participants will not undergo ATI.
The safety population will include all participants who receive a 3BNC117 infusion. A 
baseline measurement and at least one laboratory, vital sign, or other safety-related 
measurement obtained after at least one dose of study treatment may be required for 
inclusion in the analysis of a specific safety parameter. With sample size of 15, if none of 
the participants experience a grade 2 adverse event related to 3BNC117, the 95% upper 
confidence bound for the rate of adverse events in the population is 21.8%. 
This study also aims at evaluating possible effects of 3BNC117 on the HIV-1 reservoir. 
A 95% repeated measures ANOVA F-test will be used to compare levels of latently 
infected resting CD4+ T cells in peripheral blood; levels of plasma HIV-1 RNA by single 
copy assay; and levels of cell-associated HIV-1 RNA and DNA, at baseline and at weeks 
12, 23 (or 24) and 36, if viral rebound does not occur. For repeated measures ANOVA F-
test, a sample size of 15 participants allows to detect a Cohen f2 effect size (Cohen, J, 
1988) of 0.44, with 80% power and 95% confidence. The detectable effect size is 
common for all the variables since it depends on power, significance level and sample 
size. The detectable change will depend on the observed standard deviation of each 
variable. 
8.4 Enrollment/Stratification/Randomization/Blinded Procedures:
This will be an open-label, single-arm study.  Patients will be enrolled sequentially as 
they meet enrollment criteria for study participation. 
8.5 Participant Enrollment and Follow-Up
The total number of enrolled participants in the study will be 15. 
An over-enrollment of 2 participants will be allowed if participants do not complete all 
four 3BNC117 infusions. Participants that do not receive the fourth infusion because viral 
rebound occurred prior to week 27 will not be replaced. Additional participants will be 
enrolled after study withdrawal is confirmed. If a participant drops out after receiving 1 
or more infusions of the study drug, he/she will be followed for safety.  
8
0.7563
9
0.8091
10
0.8583
11
0.9033
12
0.9432
13
0.9758
14
0.9966
15
1.0000
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We expect it will take up to 18 months to recruit 15 participants and they each will be 
followed for a total of 60 weeks.
9
Data and Sample Storage
The site Principal Investigator will oversee how the data are collected, entered, and 
protected. All study data will be collected by the clinical study staff using designated 
source documents and entered onto the appropriate electronic case report forms (eCRFs). 
Data collection forms (DCFs) will be provided by EMMES for use as source documents 
as appropriate.  All study data must be verifiable to the source documentation. All source 
documents will be kept in a locked facility at the clinical site and remain separate from 
volunteer identification information (name, address, etc.) to ensure confidentiality. All 
medical records (when not being reviewed by the research team) will be kept under lock 
and key in the Medical Record Department of the hospital with access limited to the 
appropriate RUH personnel. At the Cornell site, source documents will be kept in a 
locked office in the WCMC Clinical Trials Unit. Source documentation will be available 
for review to ensure that the collected data are consistent with the eCRFs. 
All eCRFs and laboratory reports will be reviewed by the clinical team, who will ensure 
that they are accurate and complete.
All research samples will have a unique identifier.  The site PI will be responsible for 
ensuring project compliance, data analysis and entry, regulatory monitoring, and 
coordination of the activities of the entire study team.  Standard GCP practices will be 
followed to ensure accurate, reliable and consistent data collection.
Source documents include, but are not limited to:
-
Signed Informed Consent Documents
-
Dates of visits including dates of 3BNC117 infusions
-
Documentation of any existing conditions or past conditions relevant to eligibility 
-
Reported laboratory results
-
All adverse events 
-
Concomitant medications 
Study records will be kept for five years after completion of the study.
9.1 Quality Control and Quality Assurance 
Quality control checks (manually and automated) will be run on the EMMES generated 
database. Any missing data or data anomalies will be communicated to the site for 
clarification/resolution.
10 Recruitment Plan 
Both men and women ages 18 through 65 will be recruited for the study from the 
community at large and will be referred by physicians in the community.   We will make 
every effort to recruit minorities and women. We project screening 50 participants in 
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order to achieve 15 evaluable participants. An over-enrollment of 2 participants will be 
allowed if participants do not complete all four 3BNC117 infusions. 
- Advertisements – The Clinical Research Support Office at the Rockefeller University 
Hospital (CRSO) will utilize the Volunteer Repository. Advertisements will also be 
placed: online (e.g. Craigslist, Centerwatch, etc), in newspapers (Metro, AMNY) and on 
campus.
- Centralized Call Management – The CRSO will conduct telephone screenings of 
selected Volunteer Repository members, and of volunteers who call 1800-RUCARES, to 
facilitate screening efficiently. Based on IRB approved eligibility criteria, potentially 
eligible candidates pre-screened by CRSO staff will be referred to the study 
coordinator/investigator for further evaluation. 
Participants may also be referred by physicians in the community.
10.1Participant Retention 
This study requires frequent follow up visits, which can be challenging to participants. 
The study staff will review the study schedule in detail with potential participants in 
advance of enrollment and attempt to facilitate transportation to the clinical site, if 
needed. Frequent visits allow ongoing communication between study investigators and 
participants and can decreased the risk of participants being lost to follow up. Participants 
will be contacted by phone or email (whichever is preferred to the participant) prior to 
their next appointment, not more than 3-5 days in advance. Study investigators will 
consult participant’s primary care physician on any changes in treatment, which can also 
improve participant retention. 
11 Potential Benefits to Participants
It is unlikely that study participants will benefit from participating in this study.
12 Potential Risks to Participants 

This study entails moderate risk to participants since 3BNC117 is an investigational 
new drug with limited human safety data. The study also includes a period of ART 
interruption.  It has been shown that episodic ART guided by CD4+ count decline 
leads to increased risk of opportunistic infections as compared with continuous ART 
(El-Sadr W et al. 2006, SMART trial). However, different groups have now shown 
that short analytical treatment interruption is safe (Rothenberger M et al. 2015; Routy 
JP et al. 2012). ART will be resumed if plasma HIV-1 RNA levels increase to ≥ 200 
copies/ml and confirmed upon repeated measurement (performed within 1 week of 
first measurement).

If the HIV-1 viremia rebounds after ART is discontinued, absolute CD4+ counts 
might drop. However participants will be followed very closely and ART will be 
resumed if CD4+ cell count drops < 350 cells/l and confirmed upon repeat 
measurement. 
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
During ART interruption, participants might experience symptoms of acute retroviral 
syndrome, such as fever, rash, swollen glands, headache, sore throat, nausea, 
vomiting. ART will be resumed if acute retroviral syndrome is suspected by study 
investigators.

Resistant viral strains to previous ART medications might arise during the analytical 
treatment interruption. 

During the ART-interruption phase of the study participants may be at increased risk 
of transmitting HIV-1 to their partners, if they become viremic, and of HIV-1 
superinfection from an HIV-infected partner. 

3BNC117 has now been administrated to 63 volunteers and was generally safe and 
well tolerated in all doses tested. Ten HIV-uninfected individuals have received two 
3BNC117 infusions at 10 mg/kg (n=5) or 30 mg/kg dose levels (n=5), administered 
12 weeks apart. This study will for the first time evaluate the safety of four infusions 
of 3BNC117, as well as the safety of administering two infusions three weeks apart. 
The risk of repeated 3BNC117 infusions is not yet known. 

While each mAb product has unique safety issues related to its mechanism of action, 
the major safety concern related to mAbs in general is an infusion/hypersensitivity 
reaction. These types of reactions are more common for mAbs that contain murine 
elements compared to human mAbs, such as 3BNC117. Passive administration of 
anti-HIV-1 antibodies has been evaluated in humans in the past. As observed with 
other monoclonal antibodies, anti-HIV-1 antibodies were generally safe and well 
tolerated and most adverse events observed were infusion-related events. 

Immunologic symptoms such as listed below are possible with administration of a 
monoclonal antibody and will be considered adverse events of interest.  Potential 
allergic-type reactions during and immediately following the administration of 
3BNC117 will be carefully monitored.  
o
Constitutional symptoms, such as fever, rigors/chills;
o
Infusion site reaction/extravasation changes, pruritus, urticaria;
o
Serum sickness-like syndromes as evidenced by fever, rash, arthralgia, 
arthritis, 
nephritis;
o
Deposition of immune complexes in the kidneys leading to renal 
insufficiency; 
o
Adult Respiratory Distress Syndrome, bronchospasm/wheezing, anaphylaxis;
o
Cytokine release syndrome/ acute infusion reaction. 

3BNC117-resistant viral strains might arise following administration of 3BNC117. 
Development of 3BNC117 resistance might limit the future use of 3BNC117 by the 
study participant, if this monoclonal antibody is licensed for clinical use by the FDA. 

In the cross-reactivity study in human tissues, 3BNC117 was found to bind to cells in 
the conjunctival recesses. It is possible that this binding could lead to conjunctival 
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toxicity. However when rats and non-human primates were administered 3BNC117, 
conjunctival toxicity was not observed. 63 participants have received 3BNC117 to 
date, and 12 participants reported mild ophthalmic complaints (such as pruritus, 
conjunctival erythema, increased lacrimation) during study follow up. In all instances 
symptoms resolved without specific treatment and ophthalmologic evaluations 5 
months after 3BNC117 administration did not show changes from baseline. 

Blood drawing and phlebotomy can be associated with pain, bruising, anemia or 
infection at the site of venipuncture. Rarely, fainting may follow phlebotomy.

The adverse effects 3BNC117 administration would have in a fetus or unborn child 
are unknown. 

Leukapheresis is a well-tolerated procedure, which is commonly used for blood cell 
donations. The risks associated with a leukapheresis are mild pain or discomfort with 
catheter insertion (common) in both arms, temporary numbness of lips or extremities 
(occasionally), ecchymosis, nausea, chills, transient numbness and infection (rare). 
The best method to obtain the number of cells needed for this research is 
leukapheresis.
13 Procedures to minimize risk

As outlined above, this study will be an exploratory phase 2 trial of 3BNC117 in 
humans. Potential trial volunteers will be informed about the possible risks of the 
monoclonal antibody and that there may be unknown risks. 

Medical records and routine laboratory data will be handled with HIPAA compliance 
and protected by the rules and regulations of the RUH and WCMC, JCAHO-
approved institutions.

With any new medicine or monoclonal antibody, there is a possibility of totally 
unexpected side effects. Participants will be closely monitored for 4 hours post 
infusion in the RUH inpatient unit. The RUH inpatient unit is equipped for providing 
emergency medical interventions in the unlikely event of acute allergic or other 
reactions. In case of an emergency, after stabilization of the participant, he/she will be 
transferred to the neighboring tertiary care center, New York Presbyterian Hospital 
(Cornell) for specialized medical care.

Participants will be closely monitored for the development of symptoms of ocular 
disease (such as blurry vision, increased lacrimation, redness, dryness, pain) and the 
study investigators will perform a directed exam of the eyes. If participants develop 
symptoms or signs of ocular disease, they will be referred to an ophthalmologist for 
diagnosis and management. These evaluations will be performed at no cost to the 
participant.

During the treatment interruption phase of the study, plasma HIV-1 RNA levels will 
be monitored weekly and CD4+ T cell counts will be monitored every other week. 
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Participants may return to clinic between scheduled visits for additional VL 
measurements, if they desire to do so. 

ART regimen will be resumed if plasma HIV-1 RNA level is ≥ 200 copies/ml, CD4+ 
T cell count drops < 350 cells/l, and either result is confirmed upon repeat 
measurement, during the next weekly scheduled visit. If plasma HIV-1 RNA level is 
≥ 1,000 copies/ml, the participant will be asked to return for a repeat measurement 
prior to the next scheduled visit, and ART will be resumed if results are confirmed. 
ART will also be resumed early if the participant becomes pregnant copies/ml, or if 
otherwise clinically indicated. If ART regimen is resumed before week 27, the fourth 
3BNC117 infusion will not be administered (Appendix A).
 

In order to minimize the risk of resistance to the previous ART regimen, all 
antiretroviral drugs will be stopped simultaneously and ART will be resumed if 
plasma HIV-1 RNA level is ≥ 200 copies/ml and confirmed upon repeat 
measurement. Non-nucleoside reverse transcriptase inhibitors have longer elimination 
half-lives than other antiretroviral classes. Therefore, in order to avoid the risk of 
inadvertent monotherapy, which can select NNRTI resistant strains, if the 
participant’s ART regimen includes an NNRTI, the NNRTI will be switched to 
dolutegravir (an integrase inhibitor) 4 weeks prior discontinuing all other 
antiretroviral drugs. Dolutegravir will be provided to the participants for that time 
period.

 In order to minimize the risk of transmitting HIV-1 to their partners and of HIV-1 
superinfection from an HIV-infected partner, participants will be asked to use male or 
female condoms for the duration of ART interruption. In the event of a high-risk 
exposure to an HIV-infected partner, participant may re-initiate ART as clinically 
indicated by his/her primary care physician.

Since the safety profile of 3BNC117 is not fully known and since interruption of ART 
has been associated in the past with increased risk of cardiovascular complications, 
participants with certain co-morbid conditions (such as coronary artery disease, 
uncontrolled hypertension, diabetes, auto-immune diseases) will be excluded to 
ensure a healthy population of participants are selected.

To minimize risks associated with phlebotomy, blood drawing will be performed by 
experienced phlebotomists. Should discomfort occur, they will provide appropriate 
treatment.

To minimize risks associated with blood drawing, volunteers will be closely 
monitored for signs and symptoms of anemia.

Female study volunteers of reproductive potential who participate in sexual activity 
that might lead to pregnancy will be advised to use a reliable form of contraception 
for the duration of the study. In addition, a pregnancy test will be performed at 
screening, on the day of each drug infusion, and throughout the course of the study.  
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Males who are not anatomically sterile and who participate in sexual activity that 
might lead to pregnancy will be advised to use condoms from screening throughout 
the duration of the study to avoid pregnancy in a spouse or partner. Condoms will be 
provided. 

Participants will have regularly scheduled study visits and Routine safety laboratories 
[CBC, clinical chemistries, liver function tests, and urinalysis] will be checked 
according to the Time of Events Schedule (Appendix A). HIV-1 viral load and 
CD4/CD8 counts will be closely monitored according to the Time of Events Schedule 
(Appendix A). 

Adverse events will be monitored and graded using the DAIDS AE Grading Table 
v2.0. The CTCAE v4.03 grading scale will be used for reporting and grading adverse 
events related to infusion reactions and cytokine release syndromes (Appendix B).

Adverse events will be managed by the clinical trial team who will assess and treat 
the event as appropriate, including referral to an independent physician and/or 
department. 
Safety monitoring at both clinical sites will be conducted both by the International AIDS 
Vaccine Initiative (IAVI) and by an external Study Monitoring Committee (SMC). The 
RUH and WCMC IRBs will conduct the initial review of the proposed study and will 
follow progress through annual reports and by immediate notification of serious adverse 
events. 
Any serious and unanticipated adverse events will be reviewed by the study investigators 
immediately. Site investigators will notify the local IRB and the sponsor at the 
Rockefeller University within 2 working days from the investigators being made aware of 
the event. The RU sponsor will notify the FDA, per 21 CFR 312. The SMC will be 
available to the investigators for consultation and review of grade 3 or greater toxicity 
adverse events if needed. 
14 Alternative methods or treatments
This does not apply to this study.
15 Data and Safety Monitoring Plan
This is an exploratory phase 2 study which exposes the participants to “moderate risk”. A 
Study Monitoring Committee (SMC) will be established to monitor the study.
15.1 Safety Monitoring Committee
The charter of the SMC is to provide an ongoing assessment of volunteer safety during 
the conduct of the study.  The SMC consists of three independent individuals who have 
no relationship to the Principal Investigator and Co-Investigators involved in the trial. No 
member of the SMC will have any direct responsibility for the clinical care of trial 
volunteers.  No representative of Celldex Therapeutics, the Rockefeller University, or 
their designees may be a member of the SMC. However, the SMC may invite the 
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principal investigators (PI) or designee and a Celldex Therapeutics, and/or Rockefeller 
University representative to an open session of a SMC meeting to provide information on 
study conduct, present data, or to respond to the members’ questions. 
The names, university affiliation and title, area of expertise, and contact information of 
each of the SMC members are provided below:
Michael Keefer, MD
Professor of Medicine
University of Rochester Medical Center School of Medicine and Dentistry
Phone: (585) 275-5871 
Michael_Keefer@urmc.rochester.edu
Clinical expertise: infectious diseases, vaccines, HIV vaccines.
Karolina Palucka, MD
Professor of Medicine
Jackson Laboratories
Phone:(207) 288-6000
Karolina.Palucka@jax.org
Clinical expertise: immunotherapy, cancer vaccines
Eric Daar, MD
Chief, Division of HIV Medicine
Harbor-UCLA Medical Center
Professor of Medicine
David Geffen School of Medicine at UCLA
1124 W. Carson St., CDCRC 205
Torrance, CA 90502
(424) 201-3000 x7317
EDaar@LABioMed.org
Clinical expertise: clinical management of HIV infection
All available safety data will be reviewed by the SMC three weeks after the first five 
participants receive the second 3BNC117 infusion, and every 6 months thereafter. The 
study will not pause, but following the review, SMC member(s) will make a 
recommendation to the principal investigator(s) regarding the continuation of the trial.
In addition, the SMC will review all safety data in the event of two or more adverse 
events graded as grade 3 or greater toxicity, and deemed at least possibly related to 
3BNC117. Further enrollment or 3BNC117 infusions will not occur until SMC review. 
Enrollment will stop but participants will continue to be monitored by the study 
investigators. Following the review SMC member(s) will make a recommendation to the 
principal investigator(s) regarding the continuation of the trial.
SAEs and unanticipated adverse events will be reported to the SMC within 2 working 
days of the site becoming aware of the event. If there is one SAE judged as possibly, 
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probably or definitely related to the administration of 3BNC117 by the principal 
investigator or designee, no additional enrollment or 3BNC117 infusions will take place 
pending a review by at least two members of the SMC. Following this review, 
the SMC member(s) will make a recommendation to the principal investigator regarding 
the continuation of the trial.
All updated versions of the protocol, investigator’s brochure, and related documents will 
be provided to the SMC members and the DAIDS Medical Officer (MO) and DAIDS 
Program Officer (PO). The review of trial data by the SMC will take place at least every 
6 months. For these reviews, the study team will provide the SMC with updated records 
of all adverse events (AEs) of grade 2 or greater toxicity.
   
The SMC will provide a written report to the sponsor at the RU and the site PIs after each 
evaluation. The PIs in turn will distribute these reports to the study team and the local 
IRBs and the DAIDS MO and DAIDS PO.
15.2 Safety Review 
Participants will be closely monitored for 4 hours post infusion in the RUH inpatient unit. 
The RUH inpatient unit is equipped for providing emergency medical interventions in the 
unlikely event of acute allergic or other reactions. RU Hospital outpatient and inpatient 
units and the WCMC Clinical Trials Unit are equipped with crash carts for immediate 
medical care, should the need arise. In case of an emergency, after stabilization of the 
volunteer, he/she will be transferred to the neighboring tertiary care center, New York 
Presbyterian Hospital (Cornell) for specialized medical care. 
The study investigators will review and grade AE’s on an ongoing basis for the duration 
of the study. Safety monitoring will be conducted by IAVI, which will review clinical 
records and adverse events. 
15.3 Clinical Site Monitoring
Safety monitoring at both sites will be conducted by the study investigators and by IAVI. 
An external SMC will review SAEs and Unanticipated AEs and will be available to the 
study investigators for consultation. The RU and WCMC IRBs will conduct the initial 
review of the proposed study and will follow progress through annual reports and by 
immediate notification of SAEs and UAEs. 
 
Prior to initiation of clinical activities at both Rockefeller and Cornell sites, a site 
initiation visit (SIV) will take place to discuss protocol-specific procedures with study 
investigators, pharmacy, nursing and laboratory staff. IAVI monitors will be present at 
both SIVs. SIV reports will be distributed to the DAIDS MO and DAIDS PO.  
Furthermore, DAIDS may opt to conduct a site visit prior to initiation of clinical 
activities, in part to ensure deficiencies identified during the SIV have been rectified.
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IAVI Monitors will verify that the clinical trial is conducted and data are generated, 
documented, and reported in compliance with the protocol, GCP, and the applicable 
regulatory requirements.
Monitoring reports will be provided to the study investigators and IRB once every 6-10 
weeks plus or minus 2 weeks. Monitoring reports will be submitted to the DAIDS MO 
and DAIDS PO. Each clinical trial site will provide direct access to all trial related sites, 
source data/documents, and reports for the purpose of monitoring by IAVI, and 
inspection by local and regulatory authorities. IAVI is primarily responsible for site 
monitoring but DAIDS may follow-up directly with the site to ensure issues are resolved 
and/or write directly to the sites if DAIDS identifies issues that were not raised by IAVI.
15.4Adverse Event Classification
The DAIDS AE Grading Table will be used for grading of AEs, The CTCAE v4.03 
grading scale will be used for reporting and grading adverse events related to infusion 
reactions and cytokine release syndromes (Appendix B).
 
15.5 Reporting Adverse Events
All adverse events will be reported to the local IRBs at least annually.  Serious Adverse 
Events, (SAEs) will be reported to the local IRBs, the DAIDS medical officer (DAIDS 
MO) and DAIDS program officer (DAIDS PO), and to the RU sponsor according to 
policy, within two working days of identification of the SAE.  The RU sponsor will 
report SAEs to the FDA, per 21 CFR 312.
15.6 Reporting Unanticipated AEs
Unanticipated Adverse Events (UAEs) will be reported to the local IRBs.  UAEs that are 
related and greater than grade 2 severity will be reported to the local IRBs, the DAIDS 
MO and DAIDS PO, and to the RU sponsor according to policy, within two working 
days of identification of the UAE.  The RU sponsor will report UAEs to the FDA, per 21 
CRF 312. 
15.7 Clinical Laboratory Improvement Amendment/Clinical Laboratory Evaluation 
Program (CLIA/CLEP)
This study includes tests that are not CLIA/CLEP certified. The results of such tests will 
not be used in clinical decision-making or shared with participants or their health care 
providers.
15.8 Toxicity Management and Stopping Rules
A dose limiting toxicity (DLT) will be defined as any adverse event of grade 3 or greater 
toxicity, if the study investigators recognize a possible, probable or definite attribution to 
3BNC117. 
Investigators at WCMC will promptly notify the PI and Sponsor at the Rockefeller 
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University in the event of any DLT. Both clinical sites will also notify the DAIDS MO 
and DAIDS PO of the occurrence of a DTL.
In case of two or more DLTs, further enrollment or 3BNC117 infusions will not occur 
until investigators and SMC review the event and all available safety data. Enrollment 
will stop but participants will continue to be monitored by the study investigators. 
The SMC member(s) will make a recommendation to the principal investigator(s) 
regarding the continuation of the trial (see section 15.1 Safety Monitoring Committee).
Participants will be withdrawn from the study for the reasons listed in section 6.1.8.3 
Withdrawal from the study (Early Termination).
15.9 Other Disease Events 
Adverse events will be followed until resolved or considered stable during each 
scheduled study visit or during unscheduled study visits if warranted.  If adverse events 
deemed related to the study agents are not resolved at the time of final study visit, 
participants will be referred for appropriate medical care until the symptoms resolve or 
the participant’s condition becomes stable.
15.10 Critical Event Reporting
All critical events, as defined by the DAIDS Critical Events Manual, will be reported to 
DAIDS as per the Critical Events Manual.
16 Clinical Trial Registration
The proposed study involves testing of FDA regulated drugs or biologics and will be 
registered at www.ClinicalTrials.gov.
17 Study Discontinuation
The study may be discontinued at any time by the IRB, NIAID, the FDA or other 
government entities as part of their duties to ensure that research participants are 
protected.
In the event that the study is discontinued, 3BNC117 infusions will be halted and 
volunteers will be followed to ensure resolution of all adverse events. It is not applicable 
in this study to have participants continue therapy elsewhere as the investigational 
product does not provide the volunteers any direct benefit. In addition, the study does not 
have placebo recipients.
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18 Bibliography
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highly active antiretroviral therapy (HAART) in patients with a history of 
sustained viral suppression”. Proc Natl Acad Sci USA. 96(26):15109-14.
Deeks SG, R. Tracy, et al. (2013). “Systemic effects of inflammation on health during 
chronic HIV infection”. Immunity. 39(4):633-45.
Dinoso J.B., S.Y. Kim, et al. (2009). “Treatment intensification does not reduce residual 
HIV-1 viremia in patients on highly active antiretroviral therapy”.  Proc Natl 
Acad Sci USA. 106(23):9403-8.
Eisele E, Siliciano RF (2012). "Redefining the viral reservoirs that prevent HIV-1 
eradication." Immunity. 37(3):377-88. 
El-Sadr, W.M., J. Lundgren, et al. (2006). “CD4+ count-guided interruption of 
antiretroviral treatment. Strategies for Management of Antiretroviral Therapy 
(SMART)”. N Engl J Med. 355(22):2283-96.
Eriksson S, Graf EH,et al. (2013). "Comparative analysis of measures of viral reservoirs 
in HIV-1 eradication studies". PLoS Pathog. 9(2):e1003174. 
Halper-Stromberg A, Lu CL, et al. (2014) Broadly Neutralizing Antibodies and Viral 
Inducers Decrease Rebound from HIV-1 Latent Reservoirs in Humanized Mice". 
Cell. 158(5):989-99.
Ho YC, Shan L, et al. (2013). "Replication-competent noninduced proviruses in the latent 
reservoir increase barrier to HIV-1 cure". Cell. 155(3):540-51. 
Rockefeller University Institutional Review Board
IRB NUMBER: MCA-0866
IRB APPROVAL DATE: 10/09/2017
IRB EXPIRATION DATE: 06/30/2018


The Rockefeller University
IND: 118225/0014
September 27, 2017
 
PROTOCOL # MCA-0866
CONFIDENTIAL
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Horwitz, J. A., A. Halper-Stromberg, et al. (2013). "HIV-1 suppression and durable 
control by combining single broadly neutralizing antibodies and antiretroviral 
drugs in humanized mice." Proc. Natl. Acad. Sci. USA 110(41): 16538-16543.
Klein, F., A. Halper-Stromberg, et al. (2012). "HIV therapy by a combination of broadly 
neutralizing antibodies in humanized mice." Nature 492(7427): 118-122.
Kutzler M.A., J.M. Jacobson, et al. (2008). “Treatment interruption as a tool to measure 
changes in immunologic response to HIV-1”. Curr Opin HIV AIDS. 3(2):131-5.
Laird, G.M., Eisele, et al. (2013). "Rapid quantification of the latent reservoir for HIV-1 
using a viral outgrowth assay". PLoS pathogens 9, e1003398.
Malbec M, F. Porrot, et al. (2013). “Broadly neutralizing antibodies that inhibit HIV-1 
cell to cell transmission”. J Exp Med. 210(13):2813-21.
Markowitz M, T.H. Evering, et al. (2014). “A randomized open-label study of 3- versus 
5-drug combination antiretroviral therapy in newly HIV-1-infected individuals”. J 
Acquir Immune Defic Syndr.  66(2):140-7. 
Mascola, J. R., M. G. Lewis, et al. (1999). "Protection of macaques against pathogenic 
simian/human immunodeficiency virus 89.6PD by passive transfer of neutralizing 
antibodies." J. Virol. 73(5): 4009-4018.
Matsushita S, Yoshimura K, Ramirez KP, Pisupati J, Murakami T; KD-1002 Study 
Group (2015). "Passive transfer of neutralizing mAb KD-247 reduces plasma 
viral load in patients chronically infected with HIV-1”. AIDS. 29(4):453-62.
McMahon D, J. Jones, et al. (2010). “Short-course raltegravir intensification does not 
reduce persistent low-level viremia in patients withHIV-1 suppression during 
receipt of combination antiretroviral therapy”. Clin Infect Dis. 50(6):912-9
Mehandru, S., B. Vcelar, et al. (2007). "Adjunctive passive immunotherapy in human 
immunodeficiency virus type 1-infected individuals treated with antiviral therapy 
during acute and early infection." J. Virol. 81(20): 11016-11031.
Mehandru, B., E. G. Rakasz, et al. (2012). "Highly potent HIV-specific antibody 
neutralization in vitro translates into effective protection against mucosal SHIV 
challenge in vivo." Proc. Natl. Acad. Sci. USA 109(46): 18921-18925.
Moldt, B., E. G. Rakasz, et al. (2012). "Highly potent HIV-specific antibody 
neutralization in vitro translates into effective protection against mucosal 
SHIV challenge in vivo." Proc. Natl. Acad. Sci. USA 109(46): 18921-18925.
Onyango-Makumbi, C., S. B. Omer, et al. (2011). "Safety and efficacy of HIV 
hyperimmune globulin for prevention of mother-to-child HIV transmission in 
HIV-1-infected pregnant women and their infants in Kampala, Uganda 
(HIVIGLOB/NVP STUDY)." J. Acquir. Immune Defic. Syndr. 58(4): 399-407.
Palmer S, F. Maldarelli, et al. (2008). “Low-level viremia persists for at least 7 years in 
patients on suppressive antiretroviral therapy.” Proc Natl Acad Sci U S A. 
105(10):3879-84.
Papasavvas E., J.R. Kostman, et al. (2004). “Randomized, controlled trial of therapy 
interruption in chronic HIV-1 infection”. PLoS Med. 1(3):e64. 
Poignard, P., Sabbe, R., et al. (1999). "Neutralizing antibodies have limited effects on the 
control of established HIV-1 infection in vivo". Immunity 10, 431-438.
Rothenberger MK, Keele 
BF, Wietgrefe 
SW, Fletcher 
CV, Beilman 
GJ, Chipman 
JG, Khoruts A, Estes JD, Anderson J, Callisto SP, et al (2015). Large number of 
rebounding/founder HIV variants emerge from multifocal infection in lymphatic 
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IRB EXPIRATION DATE: 06/30/2018


The Rockefeller University
IND: 118225/0014
September 27, 2017
 
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tissues after treatment interruption. Proc Natl Acad Sci U S A. 2015 Feb 23. pii: 
201414926. [Epub ahead of print]
Routy J.P, M.R. Boulassel, et al. (2012). “Assessing risk of a short-term antiretroviral 
Routy therapy discontinuation as a read-out of viral control in immune-based 
therapy”. J Med Virol. 84(6):885-9.
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and potent HIV antibodies that mimic CD4 binding." Science 333(6049): 1633-
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Shingai, M., Y. Nishimura, et al. (2013). "Antibody-mediated immunotherapy of 
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Shingai, M., Donau, O.K., et al. (2014). “Passive transfer of modest titers of potent and 
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antiretroviral therapy through passive transfer of human neutralizing antibodies." 
Nat. Med. 11(6): 615-622.
Rockefeller University Institutional Review Board
IRB NUMBER: MCA-0866
IRB APPROVAL DATE: 10/09/2017
IRB EXPIRATION DATE: 06/30/2018

ICF_001.pdf: 
Clinical Investigation Consent Form 
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DAIDS Protocol Version 3.0 
 
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DAIDS Protocol Version 3.0 
 
Revised 6/16/2016 
 
Clinical Investigation Consent Form                                  IRB Rev 2013 
The Rockefeller University Hospital 
1230 York Avenue 
New York, New York 10065 
Principal Investigator: Marina Caskey, MD 
Phone:  212.327.7396 
Fax: 212.327.7234 
E-mail: mcaskey@rockefeller.edu 
 
You are being asked to join a research study, which will take place at The Rockefeller 
University Hospital.  This form tells about the research.  You should ask questions of the 
person who is explaining this form to you.  After you feel that you understand the research, 
if you want to be part of the study, you will be asked to sign the form.  You can always ask 
more questions and can later change your mind about staying in the study. 
 
If you join the research study, you will take part for a total of 62 weeks. The research study 
as a whole will last about 3 years. 
 
About 15 people will take part in the research study.  
 
Title of the research study: 
 
An open label, phase 2 study of the safety and antiretroviral activity of 3BNC117 in 
HIV-infected individuals on combination antiretroviral therapy 
 
I. 
What this research study is about, and the reasons for doing this research? 
 
The research will test a study agent called 3BNC117, which is an antibody against HIV, the 
virus that causes AIDS (acquired immune deficiency syndrome). Antibodies are naturally 
made by your body and help fight diseases. The study agent we are testing in this study is 
an antibody made in the laboratory. This study agent attaches to HIV, and can clear HIV 
from your blood. In the future, this study agent may be used to treat or prevent HIV 
infection.  
 
In this study we will test 3BNC117 in HIV-positive people who are on HIV medications, 
and have undetectable viral loads (undetectable means the amount of virus cannot be 
measured by a blood test). The study agent, 3BNC117, was discovered by scientists at 
Rockefeller University and was made at Celldex Therapeutics Inc. The United States Food 
and Drug Administration (FDA) has not approved this new agent for general use by the 
public.  
 
This study will test if the study agent can keep the viral load low when your HIV 
medications are stopped for a period of time. Another reason to do this study is to find out 


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if the study agent does not cause significant side effects. We will also measure the time it 
takes for the study agent to be cleared from your body.  
 
You are being asked to participate in this research study because you are HIV-infected and 
you are on HIV medications. 
  
The study agent will be given directly into your blood stream. This means that the medicine 
is given into a vein. How this will be done is explained in Section II, What is going to 
happen in this research study? 
 
Requirements to join this research: 
 
-  Age from 18 to 65 years old; 
-  HIV-1 infection confirmed by a blood test; 
- Undetectable HIV viral loads for at least 12 months while taking a combination of HIV 
medications; 
-  CD4 cell count more than 500 cells/µl and lowest CD4 more than 200 cell/ µl; 
- You agree to stop taking (pause) your HIV medications for 3 months after you receive the 
third dose of 3BNC117, and agree to return to the clinic every week for follow up visits; 
-  If you are a sexually active male or female, participating in sexual activity that could lead 
to pregnancy you must agree to use an effective method of birth control throughout the 
study period. You must also agree to use male or female condoms during the time of 
pausing your HIV medications. If you are female, you will have pregnancy tests at most 
study visits. 
- If your HIV medications include a type of HIV medication called a Non-Nucleoside 
Reverse Transcriptase Inhibitor (NNRTI), for example Atripla Complera, Intelence or 
Sustiva, you must be willing to switch to a different HIV medication called dolutegravir 
(Tivicay) for a period of 4 weeks.  The study team can provide Tivicay to you during this 
time. 
 
You cannot join this research if you have: 
 
- 
Had certain illnesses that are related to your HIV infection called AIDS-defining 
illnesses in the past year. The study doctor will explain to you what AIDS-defining 
illnesses are, and ask if you have had any of them in the past year;  
- 
Used systemic corticosteroids, immunosuppressive anticancer (these are types of drugs 
that can affect how well your body fights off diseases), or other medications considered 
significant by the trial physician within the last 6 months; 
- 
Any medical condition, other than HIV, that the study doctor thinks may affect your 
ability to be in the study; 
- 
Chronic (ongoing) Hepatitis B or Hepatitis C infection (these are infections of the 
liver); 
- 
History of  heart problems or diseases, like heart attacks; 
- 
History of diabetes and/or current use of insulin or other medications to treat high blood 
sugar; 


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- 
Current cigarette use of more than 1 pack per day; 
- 
Uncontrolled high blood pressure, whether or not you are on medications for high 
blood pressure; 
- 
Received a vaccine (such as the flu vaccine) within 14 days before receiving the study 
agent; 
- 
Received another monoclonal antibody therapy (of any kind) in the past; 
- 
If you are currently participating in another research study where you are getting 
another study agent; or you participated in another research study in the last 3 months 
and you received a study agent; or you plan to be in another research study that 
includes receiving another study agent while you are in this study; 
- 
If you have ever become very sick, or had a bad response (like not being able to 
breathe) after receiving a vaccine or medicine in your vein;   
- 
If you are pregnant or breastfeeding. 
 
II. 
What is going to happen in this research study? 
 
Consent Process   
 
Informed consent is a process to help you understand why we are doing this research study, 
what will happen in the study, possible risks and benefits, and your right to stop being a 
part of the study at any time. All of this information will be explained to you in detail.  You 
should ask any questions you have until you feel that you understand what is asked of you 
to participate.  You may then want to join the study, or you may decide not to join the 
study.  The decision to participate is entirely up to you.  Even after the study has started, 
you may at any time ask more questions, and decide to stop being in the study. 
 
Pre-Screening 
 
Before screening, you will have been able to review information about the study. You will 
be able to talk to the study team and ask them questions.  
 
Initial Screening Visit 
 
• Screening will determine whether or not you can participate in the study.  
• If you agree to be screened, you will sign a copy of the Informed Consent Form 
confirming that you have been told about the study and voluntarily (on your own) 
agree to take part. You will be given a signed copy of this consent form and the 
original consent form will be kept in your medical record. 
• You will be asked questions about your general health.  
• If prior results are not available, an HIV test will be done to confirm HIV-1 
infection. Before having the HIV test, you will be asked to sign a separate informed 
consent form. 
• Up to 30 ml (2 tablespoons) of blood will be drawn to test for hepatitis B, hepatitis 
C, syphilis, to evaluate liver and kidney functions, for complete blood count, to see 


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if your blood is able to clot, for a pregnancy test, and to evaluate other health 
conditions.  
• You will be asked to give a urine sample so that the study doctor can check that 
your kidneys are normal. 
All sexually active study volunteers will be asked to use a reliable form of birth 
control during the entire study, and to use female or male condoms while not taking 
the HIV medications. 
• The study team will ask questions about your medical history and will do a physical 
exam. The exam includes checking your blood pressure, heart rate, respiration, 
weight, height (at screening only) and temperature.   
• You may not be allowed to participate in this study if the tests indicate you have an 
acute or chronic infection, other than HIV, or if you are pregnant or breastfeeding. 
 
If you are a female who can have a baby, a pregnancy test will be done.  
 
Blood will also be taken to measure the amount of HIV in your blood (HIV viral load).  We 
will also measure the CD4 and CD8 cell counts. CD4 cells (also called helper T cells) work 
for the immune system by helping other cells in the body fight infections. CD4 cell counts 
drop during HIV infection. Up to 15 ml (1 tablespoon) of blood will be taken for these 
tests. 
 
The study doctor will review the results of these tests, your medical history and your 
examination. If your screening test results, medical history and examination are acceptable 
you may participate in the study. 
 
With your permission, the study doctor will also speak to your primary care doctor about 
the study before you start.  The study doctor will tell your primary care doctor what the 
study is about.   
 
Study Participation 
 
If you want to participate in the study and the study doctor agrees, you will receive a total 
of four doses of the study agent, given into a vein in your arm. You will be followed for 60 
weeks (1 year and 3 months) after the first dose of the study agent).   
 
Some parts of this study are experimental.  Here, the word “experimental” means that the 
test or the study agent given is “not part of the usual routine care of patients”.  Research 
blood tests will evaluate the amount of HIV in your body after you receive the study agent 
and the function of your blood cells that protect you from infection. These tests are 
experimental. 
 
Pre-Infusion Visit: 
Before you receive the first dose of the study agent, you will have a leukapheresis 
procedure on the pre-infusion visit (about 2 weeks before the first dose of the study agent). 


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Leukapheresis is the name of a procedure commonly done in blood banks. It requires 
insertion of a needle into both arms similar to what you might have had if you ever donated 
blood. During this procedure, the blood goes through a machine. The machine filters and 
collects the white cells (a component of your blood), and then returns the other cells and 
most of the liquid (plasma) back to you. If you experience numbness of the lips or tingling 
in your extremities, you will be given Tums to relieve those symptoms. The procedure 
normally takes 2-4 hours and is performed in a hospital or outpatient setting under close 
supervision by experienced personnel from the New York Blood Center. The advantage of 
this procedure is that it allows the researchers to obtain many more white cells than can be 
obtained by a routine blood draw.  
 
Eye exam: 
 
Before you receive the first dose of the study agent, you will also be examined by an eye 
doctor to check the health of your eyes.  
 
Study Agent Infusions 
 
During the study, you will receive four doses of the study agent (30 mg/kg). The doses will 
be given at study day 0, week 12, week 24 and week 27. The study doctor will know how 
much study agent to give you based on how much you weigh. For example, if you weigh 
70 kg (or 154 lbs), you will receive 2,100 mg of the study agent (30 mg of study agent for 
each kg of body weight). 
 
After you receive the study agent, blood will be taken to find out how much study agent is 
in your blood and the effect of the study agent on blood cells and on your HIV viral load. 
You will also be asked questions to find out if you are having any side-effects from the 
study agent. Details of the study procedures are found below. 
 
Infusion Visits:  
 
•  On the days you receive the study agent you will be monitored in the inpatient unit of 
the Rockefeller University Hospital for 4 hours after the study agent is given. 
  
During these visits, before you get the study agent, the following things will happen:  
 
o You will have a chance to talk to the study team and ask any questions; 
o A physical examination will be done, and your vital signs will be checked; 
o You will be asked questions about your health and medications;  
o Up to 10 ml (2 teaspoons) of blood will be drawn to evaluate liver and kidney 
functions, for complete blood count, to see if your blood is able to clot, and for a 
pregnancy test; 
o Additional blood samples will be collected for research purposes. At week 12 
you will have a large blood draw of about 250 ml (about 17 tablespoons or half-
pint of blood). 


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o  A urine sample will be collected; 
 
• The study agent will be given directly into your blood stream through a vein in your 
arm (an IV). This means a small, plastic tube will be placed into a vein in your arm and 
the study agent will be given through the plastic tube. It will take about 60 minutes to 
give the study agent. The IV will be removed after the study agent is given and a blood 
sample is collected. 
 
• On the day following each dose of the study agent, you will return to the study clinic. 
During these visits, your vital signs will be checked, you will be examined and the 
study team will ask you about any new complaints. 
 
ART Discontinuation (Pausing your HIV Medications) 
 
You will stop taking your HIV medications two days after the third dose of the study agent 
(week 24 of the study).  The study team will see you and check your viral load every week 
while you are off your HIV medications. You may also return to clinic between scheduled 
visits for additional viral load measurements, if you desire to do so.  
 
If your HIV medications include a type of HIV medication called a Non-Nucleoside 
Reverse Transcriptase Inhibitor (NNRTI), for example Atripla Complera, Intelence, you 
will be switched to a medication called dolutegravir (Tivicay).  This switch will happen at 
week 20 of the study, which is 4 weeks before you pause all of your HIV medications. The 
study team will call you at week 20 to remind you about the switch in medication. The 
study doctor will give you the Tivicay to take for those 4 weeks. The study doctor will also 
talk to your primary care doctor about the change in your HIV medications, so your 
primary care doctor will know.  
 
Restarting your HIV Medications 
You will start taking your HIV medications again 3 months after you stopped them (which 
will be week 36 of the study).  You may have to restart your HIV medications before week 
36 and the reasons to do that are listed below: 
 
• You become pregnant; 
• Your HIV viral load is more than or equal to 200 copies/ml, and a second test 1 
week later shows the same or higher viral load; 
• Your CD4+ count drops below 350 cells/µl, and a second test 2 weeks later shows 
the same or lower CD4 count; 
• If your HIV viral load is more than 1,000 copies/ml, you will be asked to return to 
the study clinic before the next scheduled visit for a second measurement. If the 
second test shows a viral load of 200 copies/ml or more, you will be asked to restart 
your HIV medications; 
• If you start to feel like you have a fever, rash, swollen glands, headache, sore throat, 
nausea or vomiting, you will be asked to come in to the study clinic for a visit. Your 


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HIV medications will be started again if the study team finds that you are feeling 
sick because the amount of HIV in your blood has gone up (increased viral load).  
 
If you need to restart your HIV medications within 3 weeks after you stop them, you will 
not receive the fourth dose of the study agent at week 27. 
 
If you did not need to restart your HIV medications by week 36, your study doctor will ask 
if you would like to stay off your HIV medications while in the study. If you choose to stay 
off your HIV medicationss after week 36, your HIV viral load will be checked every week. 
You may continue off HIV medications until the end of the study at week 60. However, 
you may have to restart taking your HIV medications sooner for the same reasons listed 
above.  
 
Follow-up visits:  
 
You will be asked to return to the study clinic for a total of 24 visits.  These visits will be at 
1 day, 1 and 4 weeks after each dose of the study agent, weekly while you are off your HIV 
medications from weeks 24 through 36, and at weeks 40, 48, 56 and 60.  
 
If you did not have to restart your medications by week 36 and you choose to remain off 
your HIV medications, you will return to the clinic for extra weekly visits. 
 
During these follow up visits, vital signs will be taken, you will be asked about any new 
complaints and any changes in your medications. In addition, the study doctor may 
examine you. 
 
A pregnancy test will be done at most study visits (except at 1 day after each dose of the 
study agent and at week 23). 
 
At week 48, an eye doctor will examine your eyes. The eye doctor will compare this exam 
to the first exam you received before receiving the study agent.  
 
Depending on the specific study visit, approximately 3-8 tablespoons of blood will be 
drawn to study any effect of the study agent on your blood cells.  
In addition, your blood counts, liver and kidney functions will be checked many times 
during the study: at 1 and 4 weeks after each dose of the study agent and every 4 to 8 
weeks after that, for the rest of the time you are on the study. 
 
Blood will also be taken to measure the amount of HIV in your blood (viral load) at the 
screening visit, on the visits when you receive the study agent, 1 month after each dose of 
the study agent, weekly while you remain off ART, and at weeks 36, 40, 48, 56 and 60.   
 
If your viral load increases to more than 400 copies/ml after you stop your HIV 
medications, a blood sample will also be collected to test the sensitivity of the virus to your 
HIV medications (this test is called “HIV genotype”). 


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We will also measure the CD4 and CD8 cell counts at the screening visit, on day 0, weeks 
4, 12, 16 and 24, every 2 weeks while you remain off ART, and at weeks 48 and 60. Up to 
15 ml (1 tablespoon) of blood will be taken for these tests at these visits.  
 
Blood samples will also be taken to measure the amount of study agent in your blood 
before and right after you receive each dose of the study agent, and 1 day, 1 week, and 4 
weeks after you receive each dose of the study agent. Blood samples for these 
measurements will then be taken every 4 to 8 weeks for the rest of the time you are on the 
study. 
 
At weeks 12 and 36, a large blood draw will occur (250 ml or approximately 17 
tablespoons or half-pint of blood will be collected). 
 
You will have a second leukapheresis procedure on week 23.  
 
Given the close monitoring of safety and extensive research blood draws that will be 
performed during the study, a volume of 550 ml (approximately 34 tablespoons or 1 pint of 
blood) may be drawn over periods of 8 weeks.  
 
Laboratory testing done on your blood during the research study will fall into two general 
categories, 1) New York State-approved tests, and 2) experimental tests that have not been 
certified by New York State.  
 
We will tell you or your doctor about any tests related to the research protocol that are 
performed by a New York State-approved laboratory, if the results may affect your health 
or safety. 
 
In this study, you will not receive routine care for any other medical conditions that you 
have. 
 
Your medical information and test results will be written in your Hospital chart.  The 
researchers of the study may also keep separate records with information about you and 
your study tests. 
 
Dr. Caskey and her research team will also keep separate records with information about 
you, including research results. Your name will not appear in these records. 
 
If we need to get medical information from other doctors or other health care providers 
who have seen you, we will ask you to sign a consent form to get this information. We will 
also ask you to sign a separate form if we need information from other hospitals where you 
have been treated.   
 
III. 
What are the risks of taking part in this research study? 
There may be some risks and discomforts in taking part in a research study.  We know that 


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these risks and discomforts may happen during this research study: 
 
 
Study Agent:  
 
This study agent, 3BNC117, has been tested in a small group of research participants, 
including 12 HIV-infected participants who received one dose of 3BNC117 and were on 
HIV medications. These participants tolerated the dose well. 
 
This is the first time that this study agent will be given more than two times, and the first 
time that two doses will be given three weeks apart. In addition, the study agent has not yet 
been tested during a pause of standard HIV treatment. In another study with this study 
agent, participants received only one or two doses of the study agent. When two doses were 
given, they were given 3 months apart. It is possible that side effects that we do not know 
about will occur when four doses are given. You will return to the study clinic many times 
during the study, so that you can let the study team know if you feel any discomfort and 
they can examine you. 
 
It is possible that you may feel the side effects listed below after receiving the study agent:  
 
• 
Infusion of medications like 3BNC117 may lead to pain or burning at the place 
where you have the IV (where the plastic tube enters the skin). 
 
• 
People can be allergic to many things including substances like 3BNC117. An 
allergic reaction means that the body is very sensitive to something. If you are allergic to 
any part of the study agent or to the liquid used to mix the study agent, you may develop a 
rash on your skin, fever, chills or trouble breathing. Very rarely, severe allergic reactions 
may result in a severe reaction or even death. The severe reaction is called “anaphylaxis”.  
 
• 
Medications like 3BNC117 may cause body aches, sore muscles, fever, chills, 
shakes, pain in the stomach, or pain in the back. Some participants in another study said 
they felt tired and experiences headache after receiving the study agent. 
 
• 
There is small chance that the study agent could cause a release of chemicals from 
your cells during the infusion. This could cause nausea, headache, rapid heartbeat, 
shortness of breath and rash. If severe, your blood pressure could drop affecting how 
organs like heart, lungs and liver work. It is very unlikely that this reaction will happen. 
None of the participants that have received 3BNC117 experienced this. 
 
• 
By joining with other substances in your body, medications like 3CBC117 can form 
something called immune complexes. This happens when the antibody and parts of the 
HIV or something like HIV become linked. These complexes can go through and stay in 
the kidneys. If this happens then you can get blood or protein in your urine. Sometimes this 
can also affect how well your kidneys work. 
 
• 
The study agent attaches to HIV, but when it was tested on different human tissues 


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outside the body, it was found that 3BNC117 can also attach to cells in the conjunctival 
tissue (the lining that covers the inside of the eyelids and the white part of the eyes). This 
binding can lead to inflammation of the eyes. “Inflammation” can cause your eyes to be 
red, swollen, itchy, or you could feel pain. Some participants who received the study agent 
in another study said they felt itching in the eyes, watery eyes or eye redness. These 
complaints did not last long. It is possible that you will feel some of the same discomforts 
they did after you receive the study agent. 
 
• 
To avoid these problems your study team will see you often during the study and 
talk to you about how you feel. If you your eyes start to bother you, the study doctor will 
send you to an eye doctor to have your eyes checked. You will not have to pay to see the 
eye doctor.  The study team will also examine you and take blood and urine tests. You will 
be told the results of the tests to make sure that you are not having side effects from the 
study agent. 
 
• 
 HIV strains (viruses) in your body that are “resistant” to (not blocked by) the study 
agent could become detectable in your blood after you receive the study agent. However, 
the study does not interfere with approved HIV medicines. Standard HIV medications 
should be able to control the growth of these viruses. If you get resistance to the study 
agent, this may limit your future use of it, if the FDA approves its use. 
 
• 
With any new medicine, there is a possibility of totally unexpected side effects. The 
Rockefeller University Hospital inpatient unit (where you will receive the study agent) has 
the medications needed to take care of you, if you have an allergic reaction to the study 
agent.  In case of an emergency, you will receive immediate necessary treatment at the 
Rockefeller University Hospital and then you will be sent to New York Presbyterian 
Hospital (Cornell) for specialized medical care. 
 
• 
Because we don’t know how the study agent would affect your baby or your unborn 
child, if you are a woman who can become pregnant, or are the partner of a woman who 
can become pregnant, you will need to practice an effective form of birth control before 
receiving the study agent and during the entire study.  If you think that you or your partner 
is pregnant, you should tell your study doctor or nurse at once.  
 
Effective forms of birth control for a female include:  
• 
Condoms (male or female) with or without a spermicidal agent 
• 
Intrauterine device (IUD) 
• 
Hormonal [birth control pills, injections, or implants] 
• 
Diaphragm or cervical cap with spermicide 
 
If you are a sexually active male participating in sexual activity that could lead to 
pregnancy and you have not had a vasectomy you must agree to use an effective method of 
birth control and condoms from screening until your ‘End of Study’ clinic visit. 


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For female participants: If you become pregnant you will not receive any more doses of 
the study agent.  If you become pregnant after you have already received the study agent, 
the study doctor will request that you return to the clinic every 4 to 6 weeks for follow up 
until delivery. If you become pregnant you will not stop your HIV medications, or you will 
be asked to start taking them again.  The study doctor will ask that a pediatrician examine 
your baby to check his/her health about 2-4 weeks after delivery. The health of the baby 
will be reported to the local IRBs, Clinical Research Office at the Rockefeller University 
Hospital, the Safety Monitoring Committee and the Antiretroviral Pregnancy Registry. 
 
• 
Because there may be side effects associated with the study agent that we do not yet 
know, and since pausing HIV medications was associated in the past with side-effects 
related to the heart, participants with certain medical problems such as history of heart 
attack and other heart problems, diabetes, auto-immune diseases – for example, lupus, 
rheumatoid arthritis, Crohn’s disease will not be able to participate in the study. This will 
be done to make sure a healthy population of participants is selected. 
 
Pausing HIV medications:  
 
• 
There is a chance that your HIV viral load will increase when you stop your HIV 
medications.  If this happens, your CD4 cell counts might drop. However you will be 
followed very closely and your HIV medications will be restarted if your HIV viral load 
increases to more than 200 copies/ml or if your CD4 count cell drops to less than 350 
cells/µl, two weeks in a row. If your viral load becomes detectable and your HIV meds are 
restarted within three weeks from when you stopped taking them, you will not receive the 
fourth dose of the study agent. 
 
• 
If you become pregnant while not taking your HIV medications, the study doctors 
will ask you to restart your medications immediately because there is a chance that you 
could transmit HIV to your unborn child while you are off your medications.  
 
• 
When your HIV medications are stopped, you might experience symptoms similar to 
when you first got HIV, such as fever, rash, swollen glands, headache, sore throat, nausea, 
vomiting. If you develop these symptoms, the study doctors will evaluate you and your 
HIV medications will be resumed if the symptoms are believed to be due to increased HIV 
levels. 
 
• 
 Resistance to your HIV meds might occur, since your HIV meds will be stopped for 
about 3 months. In order to decrease that risk, you will be asked to restart your HIV meds if 
your viral load increases to ≥ 200 copies/ml, two weeks in a row. 
 
•     While you are off your HIV medications, you are at increased risk of transmitting 
HIV to a sexual partner and at increased risk of HIV “superinfection” from an HIV-
infected partner. Therefore you are asked to practice safer sex and use condoms at all times 
during the study. If you feel you have been exposed to HIV while off your HIV 


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medications you may restart your medication if your primary care physician recommends 
this. 
 
Leukapheresis Procedure: Leukapheresis is a well-tolerated procedure which is commonly 
used for blood cell donations. The risks associated with a leukapheresis are mild pain or 
discomfort with catheter insertion (common) in both arms, temporary numbness of lips or 
extremities (occasionally), bleeding under the skin, nausea, chills, transient numbness and 
infection (rare). The best method to obtain the number of cells needed for this research is 
leukapheresis.  
 
Blood draw: the risks associated with a blood draw are generally minor.  They are mild 
pain at the needle site (common), local bruising at needle site (rare), infection and fainting 
(extremely rare). 
 
Privacy and Confidentiality Risks: There is the risk that there could be computer security 
breaches which could reveal your identity. There may be the risk that data about you may 
become public, and could be used by employers or law enforcement agencies. These 
privacy risks are described in greater detail below. 
 
There may be other risks and discomforts that we do not know about now, but we will tell 
you any new information discovered which might affect your decision to participate or 
remain in the study. 
 
IV. 
What are the alternatives to participating in this research study? 
 
You do not have to participate in this study. You can still receive your usual HIV treatment 
from your primary care doctor.   
 
V. 
What are the benefits of taking part in this research study? 
 
You are unlikely to have any direct benefits from participating in this study.  It is possible 
that this study agent, 3BNC117, may help future patients have better control of their 
infection and improve their treatment.  
 
VI. 
Who will be able to see the information learned about you in this research 
study? 
 
We will protect your personal information and will do our best to keep this information 
confidential.  We will listen to what you say we may do with this information, and we will 
follow the law.  For example, by New York State law hospitals must inform the New York 
State Department of Health if we find that you have a reportable communicable disease(s), 
such as sexually transmittable diseases like chlamydia, hepatitis, gonorrhea, syphilis. Also, 
the researchers must report to the authorities if they believe that child abuse or neglect has 
happened, or to prevent serious harm to you or others. 
 


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Whenever possible, data about you will be unlinked from your name and identified by a 
code.  Sponsors and members from the Safety Monitoring Committee receive your data 
linked only to a code.  However, auditors and regulators from government agencies that 
oversee research, study monitors from the International AIDS Vaccine Initiative (IAVI), 
and people at the Rockefeller University Hospital and at Rockefeller University may see 
your information in the course of their duties. 
 
We will share information about you only with the government agency that oversees this 
research, and the people at the Hospital and the Rockefeller University in connection with 
their duties.   
 
During the research study, only the researchers will know that your samples came from 
you, because your stored samples will be identified only by a special code instead of your 
name.  As a result, the others who study your samples will not know that they came from 
you and will not be able to figure out that they came from you.   
 
If the researchers publish the results of this study, they will not mention your name or other 
information that could identify you.  
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. Law. This website will not include information that can identify you. At 
most, the website will include a summary of the results. You can search this website at any 
time. 
Genetic Information Nondiscrimination Act 
A Federal law, called the Genetic Information Nondiscrimination Act (GINA), generally 
makes it illegal for health insurance companies, group health plans, and most employers to 
discriminate against you based on your genetic information. Additional information is 
available in the outpatient or inpatient information handbook. 
VII. 
What are the payment arrangements? 
 
There is no cost to you for being in this research study. 
 
Payment will be made to participants who fill out a form from The Rockefeller University 
Finance Office and are eligible for and want to receive payment. 
 
There will be no compensation for the initial screening visit.   
 
Each study volunteer will be compensated $200 for each 3BNC117 infusion visit, $ 200 for 
each leukapheresis and $50 for each eye exam. You will be compensated $60 dollars for 
each post infusion follow up visit and for weekly visits during the pause of your HIV 
medications (from weeks 25 to 36). For late follow up visits, you will be compensated 
$100. If you complete all study visits, you will be receive a total of $ 2,660.  


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If your HIV viral load remains suppressed by week 36 and you choose to remain off your 
HIV medications, you will return to the clinic every week for follow up. You will be 
compensated $50 for each of these additional visits. In total, you may receive up to $3,860 
if you remain off your HIV medications until the final study visit at week 60.  
 
If the study doctors ask that you return for an unscheduled visit, you will be compensated 
$25 each time. 
 
Compensation is provided to help cover your travel expenses, as well as child care and time 
lost from gainful employment. If you stop participating in the study before the last study 
visit, you will be paid for the portion of the study you completed.  
 
Dr. Nussenzweig and Dr. Scheid, co-investigators on this study, are inventors of the study 
agent and are named on a patent application for their invention.  Dr. Nussenzweig has 
financial interests in Celldex, the company that made the study agent. Dr. Nussenzweig, the 
Rockefeller University, and Celldex may benefit financially if the study agent is sold to a 
pharmaceutical company. 
 
If research using your samples helps develop a drug or another product that is sold to the 
public, the drug company, the University and the researcher may share in some of the 
profits.  For example, a cell line from your samples could be used to make a product for 
sale.  There are no plans to pay you any money resulting from such discoveries.  However, 
by signing this form, you do not give up any rights you may have. 
 
VIII. What happens if you don’t want to stay in this study or your participation is 
ended? 
 
You can choose if you want or do not want to be part of this study.  If you do not join, there 
is no penalty and no one will hold this against you.  If you decide to join this study, you 
may change your mind and stop taking part in this study at any time, and this will not be 
held against you.  Information about you up to that time may stay a part of the study. 
 
During this study, the researchers may learn new information that might make you change 
your mind about whether you want to stay in the study.  You will be given that information 
promptly. 
 
If you decide to join this study but later want to stop, you should let the researchers know. 
The study team would still like to follow all volunteers who received the study agent for 
safety reasons. 
 
The researchers also may stop you from taking part in this study, even if you do not choose 
to stop being in it.  You may be asked to leave the study if: 
 
• You fail to keep appointments  


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• The research study is terminated or canceled by the investigator, the FDA or the 
Rockefeller University Institutional Review Board, NIAID or other government 
entities.  
• There is a significant adverse event to you or to other participants in the study 
• If your primary care doctor requests that you no longer participate in the study 
because he/she believes it isn’t in your best interest to stay in the study. 
 
If the study doctor ends your participation in the study before the study is over, you will be 
asked to return to the study clinic for a last study visit. During this visit, the study doctor 
will re view your medical history and talk to you about any discomfort you may have, will 
examine you and will collect urine and blood samples. These samples will be used for a 
pregnancy test, measure your blood counts and liver and kidney functions, viral load, CD4 
and CD8 counts and levels of the study agent in your blood.  Additional samples will be 
collected for experimental tests to check how your body responded to the study agent. The 
study doctor will make sure you have appropriate follow up with your primary care 
physician. 
 
 
IX. 
Consent to the use, storage and sharing of your samples or data for separate 
research studies  
 
The scientific value of your samples and the information obtained from them is greatly 
increased if we can share them with other scientists at universities, pharmaceutical and 
technology companies worldwide. May we store, use and share your blood/or tissue 
samples and data with other investigators at the Rockefeller and elsewhere for separate 
studies for many years?  Your samples will either be stripped of information identifying 
them as yours or coded (we will hold the key to the code) so that they cannot be identified 
as having come from you.  Other data related to your sample, but that does not identify you 
may accompany your samples.  
 
Any time in the future, you may withdraw your consent to use any samples that have not 
already been used in research or shared.  If you withdraw your consent, the remaining 
unused samples will be destroyed, unless the samples cannot be identified as having come 
from you. 
 
Would you like us to store, use and share your blood/or tissue samples/associated data as 
described above?   
 
 
 
Yes  
 
 
 
No  
 
  
 
If you say “no” to this question, this will not affect your participation in this study. 
 
 
X. 
Who do you call if a medical problem results from this research study? 
 
If you believe that this study has led to a medical problem, you should call the researcher 


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DAIDS Protocol Version 3.0 
 
Revised 6/16/2016 
listed below right away.  The investigator will help you to get the appropriate, available 
medical care.   
Name: Marina Caskey, MD 
Phone: 212-327-7396 
Fax: 212-327-7234 
E-mail: mcaskey@rockefeller.edu 
 
The Rockefeller University does not plan to pay for medical care that you may have as a 
result of taking part in a research study at The Rockefeller University Hospital. If you are 
injured, the Rockefeller University Hospital will give you immediate necessary treatment 
for your injuries. You will not have to pay for this treatment. You will be referred and/or 
transferred to where you can receive additional treatment for your injuries. The U.S. 
National Institutes of Health (NIH) does not have a mechanism to pay money or give other 
forms of compensation for research related injuries. However, you do not give up any 
rights you may have to seek compensation by signing this form.  
 
XI. 
Who do you contact if you have questions about the research study? 
 
Please ask as many questions as you want about this research study and this consent form.  
If you agree to take part in this study and have questions later on, you may contact the 
following researcher:  
 
Name: Allison Settler, FNP 
Phone: 212-327-7394 
Fax: 212-327-7234 
E-mail: asettler@rockefeller.edu  
 
If you have any concerns about your experience while taking part in this research study, 
you may contact The Rockefeller University Institutional Review Board (IRB) Office at 
(212) 327-8410, or the Office of Clinical Research at (212) 327-8408.  
 
XII. 
May we have permission to contact you about future studies? 
 
May we contact you by phone to find out if you are interested in hearing about new 
research studies?  Contact would be made by the Rockefeller staff of the Clinical 
Research Support Office for Recruitment.  If you decide at any time that you no longer 
want to be contacted, please tell us, and we will stop calling you. 
 
Would you like us to contact you about future research studies?  
 
Yes ____________ 
 
 
No ____________ 
 
If you say “no” to this question, this will not affect your participation in this study. 
 
 


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AGREEMENT TO PARTICIPATE -- SIGNATURES REQUIRED 
 
I have read this consent form, and my questions have been answered. 
 
A copy of this consent form will be given to you.  Please keep a copy of the form as it 
contains important information that you may wish to refer to during the research study and 
thereafter. 
 
I hereby voluntarily consent to take part in this research study.  
 
 
Name of the Study Participant (Print)  
 
 
 
 
 
 
 
Signature of Study Participant 
Date (To Be Filled in by Study Participant) 
 
Signature of the Person Conducting the Informed Consent Discussion 
 
I have explained the research protocol and this consent form to the participant and have 
answered the participant’s questions about this research study and/or the consent process.  
 
 
Name of Person (Print)  
 
 
 
 
 
 
 
Signature 
of 
Person 
Discussing 
Consent 
 Date (To Be Filled in by Person Discussing   
 Consent) 
 
 
Signature of the Witness to the Informed Consent Discussion 
 
 
Name of Person (Print)  
 
 
 
 
 
 
Signature of Witness 
 Date (To Be Filled in by Witness)