An Exploratory, Open-Label Study of VRC-HIVMAB060-00-AB (VRC01) in Subjects With Chronic HIV Infection Undergoing Analytical Treatment Interruption
Phase: PHASE1
Conditions: HIV
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Protocol Version 4.0 
3-Feb-2017 
 
 
 
1 
 
 
 
An Exploratory, Open-Label Study of VRC-HIVMAB060-00-AB (VRC01) in Subjects with 
Chronic HIV Infection Undergoing Analytical Treatment Interruption 
 
 
NIAID Protocol Number: 15-I-0140 
 
Sponsored by:  
National Institute of Allergy and Infectious Diseases (NIAID) 
 
IND Sponsor: OCRPRO/DCR/NIAID/NIH 
 
IND #: 126664 
 
VRC01 Provided by: NIAID/VRC 
 
Sponsor Medical Monitor:  Marc J. Teitelbaum, MD, MS 
Clinical Monitoring Research Program 
Frederick National Laboratory for Cancer Research  
Leidos Biomedical Research, Inc.  
Support to: Regulatory Compliance & Human Subjects Protection 
Program / NIAID / NIH 
Phone (301) 228-4707 
Fax (301) 846-6224 
Marc.Teitelbaum@fnlcr.nih.gov 
 
 
Principal Investigator: Michael C. Sneller, M.D. 
 
Draft or Version Number: 4.0           February 3, 2017 
 
Principal Investigator: 
 
Michael C. Sneller, MD 
 
 
 
 
 
Laboratory of Immunoregulation (LIR)/NIAID 
 
 
 
 
 
10 Center Drive 
 
 
 
 
 
Building 10; Room 9N208 
 
 
 
 
 
Phone: 301-496-0491 
 
 
 
 
 
Email: msneller@niaid.nih.gov 
 
Associate Investigators: 
 
Tae-Wook Chun, PhD 
 
 
 
 
 
LIR/NIAID 
 
 
 
 
 
Phone: 301-496-0890 
 
 
 
 
 
Email: twchun@niaid.nih.gov 
 
 
 
 
 
 
 

Protocol Version 4.0 
3-Feb-2017 
 
 
 
2 
 
Susan Moir, PhD 
LIR/NIAID 
Phone: 301-402-4559 
Email: SMoir@niaid.nih.gov 
 
Frank Maldarelli MD, PhD 
NCI 
Phone: (301) 435-8019 
Email: fmalli@mail.nih.gov 
 
Julie Ledgerwood, DO 
VRC/NIAID 
Phone: (301) 594-8502 
Email: ledgerwood@mail.nih.gov 
 
Collaborator:  
 
 
Mathias Lichterfeld, M.D., Ph.D. 
Infectious Disease Division 
Brigham and Women’s Hospital 
Massachusetts General Hospital 
65 Landsdowne Street 
Cambridge, MA 02129 
Phone: 617-768-8399 
 
Research Contact/Study  
Coordinator(s): 
 
 
Catherine Seamon, RN CCRP 
 
 
 
 
 
Clinical Center/Critical Care Medicine Department 
 
 
 
 
 
Phone: 301-402-3481 
 
 
 
 
 
Email: cseamon@cc.nih.gov 
 
Statistician:  
Michael Proschan, PhD 
Biostatistics Research Branch/DCR 
Phone: 301-451-5129 
Email: proscham@niaid.nih.gov 
 
 

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Protocol Version 4.0 
3-Feb-2017 
 
 
 
6 
LIST OF ABBREVIATIONS 
 
 
AE 
Adverse Event/Adverse Experience 
ALP 
Alkaline Phosphatase 
AR 
Adverse Reaction 
AST 
Aspartate Aminotransferase 
ATI 
Analytical Treatment Interruption 
cART 
Combination Antiretroviral Therapy 
CFR 
Code of Federal Regulations 
CGMP 
Current Good Manufacturing Practice 
CHO 
Chinese Hamster Ovary 
CIB 
Clinical Investigator’s Brochure 
CIOMS 
Council for International Organizations of Medical Sciences 
CLIA 
Clinical Laboratory Improvement Amendment of 1988 
COI 
Conflict of Interest 
CRADA 
Cooperative Research and Development Agreement 
CRF 
Case Report Form 
CRIMSON 
Clinical Research Information Management System of the NIAID 
CSO  
Clinical Safety Office 
DCR 
Division of Clinical Research 
DHHS 
Department of Health and Human Services 
DSMB 
Data and Safety Monitoring Board 
DSMC 
Data and Safety Monitoring Committee 
ELISA 
Enzyme-Linked Immunosorbent Assay 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HCV 
Hepatitis C Virus 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IDE 
Investigational Device Exemption 
IEC 
Independent or Institutional Ethics Committee 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
IV 
Intravenous 
LIR 
Laboratory of Immunoregulation 
MAb 
Monoclonal Antibody 
N 
Number (typically refers to number of subjects/sample size) 
NCI 
National Cancer Institute, NIH 
NDA 
New Drug Application 
NHP 
Nonhuman Primate 
NIAID 
National Institute of Allergy and Infectious Diseases  
NIH 
National Institutes of Health 
NNRTI 
Non-Nucleoside Reverse Transcriptase Inhibitors 
OCRPRO 
Office of Clinical Research Policy and Regulatory Operations 
OHRP 
Office for Human Research Protections 
OHSRP 
Office of Human Subjects Research Protections 

Protocol Version 4.0 
3-Feb-2017 
 
 
 
7 
PHI 
Protected Health Information 
PI 
Principal Investigator 
PK 
Pharmacokinetics 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SAR 
Suspected Adverse Reaction 
SC 
Subcutaneous 
SMC 
Safety Monitoring Committee 
ULN 
Upper Limit of Normal 
UP 
Unanticipated Problem 
UPnonAE 
Unanticipated Problem that is not an Adverse Event 
VRC 
Vaccine Research Center/NIAID 
 
 

Protocol Version 4.0 
3-Feb-2017 
 
 
 
8 
 
PROTOCOL SUMMARY 
 
Full Title: 
An Exploratory, Open-Label Study of VRC-HIVMAB060-00-AB 
(VRC01) in Subjects with Chronic HIV Infection Undergoing 
Analytical Treatment Interruption  
Short Title: 
Therapeutic VRC01 
Clinical Phase: 
1 
IND Sponsor:  
 
OCRPRO 
Conducted by: 
 
NIAID/LIR 
Principal Investigator: 
Michael C. Sneller, MD 
Sample Size: 
N= 30  
Accrual Ceiling: 
45 
Study Population: 
 
HIV-infected adults 18-65 years of age on combination 
antiretroviral therapy (cART) with suppressed viremia 
Accrual Period: 
 
18 months 
Study Design: 
 
An exploratory, open-label, single-arm study of VRC-HIVMAB060-
00-AB (VRC01) in subjects with chronic HIV infection undergoing 
analytical treatment interruption  
Study Duration: 
 
2 years (June 2015 to June 2017) 
Study Agent/  
 
 
Intervention Description: 
HIVMAB060-00-AB (VRC01), 40 mg/kg 
 
Primary Objective:  
To evaluate safety and tolerability of multiple doses of VRC01 in 
study subjects following discontinuation of cART 
 
Secondary Objective: 
To evaluate the efficacy of VRC01 as determined by its effect on 
plasma viral rebound following discontinuation of cART 
 
Exploratory Objectives: 
• 
To examine the capacity of other antibodies (i.e., 3BNC117) 
that bind to CD4 binding site on gp120 to neutralize VRC01-
escape mutants ex vivo; 
• 
To investigate whether VRC01-mediated suppression of HIV 
replication in the absence of cART allows the development of 
anti-HIV immunity (i.e., cytotoxic T lymphocyte response) in 
infected individuals who began therapy during the chronic 
phase of infection; 
• 
To evaluate B cell responses to rebounding HIV upon 
discontinuation of cART; 
• 
To examine the relationship between the size of persistent HIV 

Protocol Version 4.0 
3-Feb-2017 
 
 
 
9 
reservoir and kinetics and timing of plasma viral rebound 
following analytical treatment interruption (ATI). 
 
Endpoints: 
• 
The rate of occurrence of grade 3 or higher adverse events 
(AEs), including serious adverse events (SAEs), that, per 
standard criteria (see safety section), are possibly related to 
VRC01. 
• 
Number of subjects who experience rebound of plasma viremia 
and meet criteria to restart cART. 
 

Protocol Version 4.0 
3-Feb-2017 
 
 
 
10 
PRÉCIS 
Recent advances in antibody cloning technologies have led to the discovery of a number of 
highly potent, HIV-specific, broadly neutralizing monoclonal antibodies from B cells of HIV-
infected individuals. It has been shown that certain broadly neutralizing HIV-specific antibodies 
can prevent acquisition of the virus, suppress viral replication, delay and/or prevent plasma viral 
rebound following treatment interruption in Simian Immunodeficiency virus (SIV)-infected 
animals and block cell-to-cell transmission of laboratory-adapted HIV in vitro. However, it is 
unclear what in vivo effects these antibodies might have on plasma viral rebound in HIV-infected 
individuals following discontinuation of combination antiretroviral therapy (cART).  
 
In this regard, it has been shown that virtually all infected individuals who initiated cART during 
the chronic phase of infection experience plasma viral rebound upon cessation of therapy. 
Current research on the treatment of HIV-infected individuals has been heavily focused on 
developing strategies aimed at achieving sustained virologic remission in the absence of cART. 
Thus, it is of great interest to investigate whether a potent HIV-specific monoclonal antibody, 
such as VRC01, can prevent plasma viral rebound in infected individuals upon discontinuation 
of cART. We propose to examine the effect of VRC01 on plasma viral rebound in HIV-infected 
individuals following analytical treatment interruption (ATI).  

Protocol Version 4.0 
3-Feb-2017 
 
 
 
11 
1 
 BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE 
 
1.1 
Background Information 
Prolonged suppression of plasma viremia is now achievable in the majority of HIV-infected 
individuals receiving combination antiretroviral therapy (cART). Consequently, cART has 
dramatically improved the clinical outcome of infected individuals. However, complete 
eradication of HIV has not been possible using cART alone and plasma viremia rapidly 
rebounds in virtually all chronically HIV-infected individuals upon cessation of therapy(1). 
Multiple studies have demonstrated that HIV persists in latently infected, resting CD4+ T cells of 
virtually all infected individuals receiving clinically effective doses of cART(2-4). The inability of 
cART to eradicate HIV is likely due to the persistence of infectious virus in CD4+ T cells and 
possibly, other cell types(1). 
 
Despite the success of cART in suppressing HIV replication and plasma viremia, the burden of 
taking daily medication for life, long-term toxicity of cART regimens, and resistance to 
antiretroviral drugs, necessitates a continued search for effective alternatives for the control of 
HIV infection. Consequently, a major thrust of HIV research over the past several years has 
been to develop therapeutic strategies that can control HIV replication in the absence of cART. 
One such strategy is passive immunization with neutralizing monoclonal antibodies (mAbs) 
against HIV. 
 
Research directed at potential pathways towards the development of an effective HIV vaccine 
has provided insights into the nature of the immune response to HIV infection(5, 6). Recent 
advances in antibody cloning technologies and B cell biology have led to the discovery of 
several highly potent and broadly neutralizing mAbs against HIV produced by B cells of some 
HIV-infected individuals(7-9). Several studies have demonstrated that certain broadly 
neutralizing HIV-specific mAbs can prevent acquisition of the virus, suppress viral replication, 
prevent plasma viral rebound following treatment interruption in infected animals(10-12), and 
block cell-to-cell transmission of laboratory-adapted HIV in vitro(13). However, it is unclear what 
in vivo effects these antibodies might have on HIV-infected humans.  
 
The rebound of HIV plasma viremia observed in infected individuals following withdrawal of 
suppressive cART occurs as a result of at least two phenomenon: the emergence of virus from 
the persistent viral reservoir and the spread of virus to neighboring bystander CD4+ T cells. 
Broadly neutralizing mAbs such as VRC01 can potentially inhibit these events by several 
mechanisms including: directly binding and neutralizing infectivity of emerging HIV; blocking 
cell-to-cell spread of HIV; facilitating the clearance of plasma virus via formation of immune 
complexes; and clearance of HIV-infected cells through initiation of cellular effector responses. 
Of note, a recent study has demonstrated that several HIV-specific mAbs (including VRC01) 
inhibited entry into CD4+ T cells of HIV isolated from the latent viral reservoir of infected 
individuals whose plasma viremia was well controlled by cART(14). Based on these 
observations, and considering the possibility of biochemical modification to extend serum half-
lives of HIV-specific antibodies, it is conceivable that infrequent administration of one or more of 
such mAbs could result in the maintenance of suppressed plasma viremia in the absence of 
cART. Thus, it is of interest to investigate whether a potent HIV-specific mAb, such as VRC01, 
can prevent plasma viral rebound in infected individuals upon discontinuation of cART.  
 

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Protocol Version 4.0 
3-Feb-2017 
 
 
 
13 
aspartate aminotransferase (AST) and alkaline phosphatase (ALP) on Day 9. By Day 30, AST 
values had returned to normal, and ALP values were returning to normal.     
 
Other than red discoloration of the administration site in one male in the SC group on Day 9, 
there were no other gross necropsy observations attributable to VRC01 administration. There 
were no histopathology findings that were considered related to IV administration of VRC01. 
However, histopathology evaluation revealed subacute inflammation at the SC injection site on 
Day 9, one day after injection, in all 10 SC administered rats; dermal inflammation was usually 
minimal or mild while SC inflammation was usually mild, moderate, or marked. By Day 30, this 
inflammation had completely resolved, and the SC dose site was normal in all rats.   
 
A “no observed effect level” (NOEL) was not determined in this study because transient 
elevations of AST and ALP were observed on Day 9 after IV administration and transient 
inflammation at the dose site was observed on Day 9 after SC administration. Because the 
elevated AST and ALP levels were transient and minor and did not correlate with histopathology 
findings, the “no observed adverse effect level” (NOAEL) for VRC01 by the IV route of 
administration in rats was 400 mg/kg, the highest dose used in this study. The systemic NOAEL 
for the SC route of administration of VRC01 in rats was 40 mg/kg, the only SC dose level 
examined in this study. 
 
For the PK analysis, a separate cohort of rats received VRC01 on Day 1 at 4 mg/kg and 40 
mg/kg by the IV route of administration and at 40 mg/kg by the SC route of administration.  
VRC01 levels in serum were determined using an enzyme-linked immunosorbent assay 
(ELISA). VRC01 administration by the IV route resulted in dose-proportional exposure.  The 
terminal elimination phase half-life (t1/2) was about 10 days, with clearance of approximately 
20 ml/day/kg and volume of distribution that was about 0.28 l/kg.  
 
Nonhuman Primate Studies of VRC01 
Several non-GLP studies of VRC01 have been completed in nonhuman primates (NHP) as pre-
clinical proof-of-concept studies for prevention or treatment of HIV infection. Table 1 is a brief 
summary of the studies performed and supports the plan to evaluate up to 40 mg/kg dose 
administered IV as a dose range of potential interest.  Refer to the IB for additional information 
about these studies. 
 
 

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Protocol Version 4.0 
3-Feb-2017 
 
 
 
15 
All three studies followed their respective dose escalation plans and reached the 40 mg/kg IV 
administration dose level without the occurrence of any safety pauses or SAEs. 
 
As of January 9, 2015, 87 subjects received one or more study product administrations, 
including 21 in VRC 601; 28 in VRC 602; and, 38 in HVTN 104. Of the 87 subjects who began 
study product administration, the schedule completion status is as follows: 
 
• 
9 subjects, on a one dose schedule, completed one dose; 
• 
40 subjects, on a two dose schedule: 37 received two doses, 3 discontinued after one 
dose; and, 
• 
38 subjects in HVTN 104, on multi-dose schedules: 36 continuing, 2 discontinued after 
two doses. 
 
• 
Of the 5 subjects discontinued from study product administration, reasons were as 
follows: 
o 1 lost to follow-up; 
o 1 unable to comply with the study schedule; 
o 1 unrelated adverse event (Streptococcal pharyngitis) that precluded timely 
administration; and, 
o Related adverse events (mild generalized rash; mild chest discomfort). 
 
Cumulatively, across VRC 601 and VRC 602 studies, there were 86 product administrations as 
follows: 
• 
6 administrations at 1 mg/kg IV; 
• 
16 administrations at 5 mg/kg IV; 
• 
19 administrations at 20 mg/kg IV; 
• 
21 administrations at 40 mg/kg IV; 
• 
15 administrations at 5 mg/kg SC; and 
• 
9 administrations of placebo SC. 
 
Cumulatively, in the HVTN 104 study, there were 138 product administrations as follows: 
• 
17 administrations at 20 mg/kg IV (Group 1: 10 as 2nd dose; 5 as 3rd dose; 2 as 4th 
dose); 
• 
29 administrations at 40 mg/kg IV (Group 1: 12 as 1st dose; Group 2: 11 as 1st dose 
and 6 as 2nd dose); 
• 
15 administrations of either VRC01 at 40 mg/kg IV or placebo IV (Group 3 1st dose); 
and, 
• 
77 administrations of either VRC01 at 5 mg/kg SC or placebo SC (Group 3: 15 as 2nd 
dose; 13 as 3rd dose; 13 as 4th dose; 13 as 5th dose; 12 as 6th dose; 7 as 7th dose; 4 
as 8th dose). 
 
The PK parameters of passively administered VRC01 to date have been evaluated in a limited 
number of healthy adults and in HIV-infected adults. The PK results as of May 2014 with these 
two populations of adults are provided in the IB and are preliminary. The results indicate that PK 
parameters are comparable in these two adult populations. When administered IV at 20 mg/kg 
(n=5) or 40 mg/kg (n=4), the mean (+ SD) maximum serum concentration were 870 + 197 and 
1611 + 258 mg/L following the first dose, respectively. The elimination half-life was similar in 
healthy and HIV-infected adults with an overall mean value of 14.6 + 4.8 days following 20 
mg/kg or 40 mg/kg doses. In healthy adults at 20 mg/kg IV (n=3) and 40 mg/kg IV (n=4), mean 

Protocol Version 4.0 
3-Feb-2017 
 
 
 
16 
28 day trough serum concentrations were approximately 32.7 + 9.1 and 60.6 + 20.1 mg/L, 
respectively, after the first administration.  At 28 days after the second IV administration, the 
mean VRC01 serum levels were 40.6 + 10.7 and 102.6 + 48.8 mg/L. The clearance of VRC01 in 
healthy adults is estimated to be 466 + 118 mL per day following IV administration of 5-40 
mg/kg (n=11) on the basis of these interim data. 
 
An interim analysis of the VRC 601 viral load data obtained from 7 viremic adults through March 
18, 2015 shows that VRC01 has a statistically significant in vivo virological effect on HIV viral 
load when administered as a single 40 mg/kg IV dose.  None of these adults were taking cART 
when enrolled into the study and had not started cART through the time periods used in this 
viral load analysis.  Five of the seven adult subjects had ≥1 log10 copies/mL decrease in viral 
load, while two subjects had viral load decreases of 0.26 and 0.18 log10 copies/mL, respectively. 
These interim data indicate the following for a single dose of VRC01 at 40 mg/kg IV: 
• 
A statistically significant change from baseline viral load post-infusion days 5 through 
9 and on day 14;  
• 
The median time to reach ≥0.5 log10 decrease in viral load is 5 days; and, 
• 
The median time to greatest decrease in viral load is 7 days. 
A 0.5 log10 copies/mL or greater decrease in viral load is considered to be a positive response to 
ART.  To have clinical benefit, such a change would need to be sustained.  In VRC 601, 
subjects were administered only one dose of VRC01 at 40 mg/kg and, thus, a sustained effect 
on viral load was not expected.  However, the interim data indicate that the established 
benchmarks can be obtained and support the hypothesis that a schedule with repetitive dosing 
may have a beneficial clinical effect.   
1.2 
Rationale 
The objectives of this study are to evaluate the safety and tolerability of multiple doses of 
VRC01 in study subjects following discontinuation of cART, and to evaluate the efficacy of 
VRC01 as determined by its effect on plasma viral rebound following discontinuation of cART. 
Up to 30 participants will be enrolled in this open-label, single-arm study. Only study participants 
on cART with documented suppression of viremia for ≥ 3 years are eligible to participate.  
 
The rationale for using the proposed dose of VRC01 is based on the safety and 
pharmacokinetic data generated from VRC 601 and 602 as well as pre-clinical NHP studies 
(Table 1).  
  
Analytical Treatment Interruption (ATI) 
Various assays measuring HIV-specific immune responses and the frequency of CD4 cells 
carrying infectious HIV have been used to assess efficacy of immune-based therapies. To date, 
none of the assays are clinically validated to predict actual antiviral efficacy. Thus, ATI has been 
used to evaluate the antiviral efficacy of immune-based therapies by testing the ability of these 
interventions to blunt or prevent the viral rebound that occurs following interruption of cART. The 
use of ATI in the design of this study is the only way to determine if administration of VRC01 
results in clinically significant antiviral activity, as evidenced by a blunted or absent plasma viral 
rebound following ATI. We feel that a 24-week ATI, with frequent clinical and laboratory 
monitoring along with strict criteria for re-initiation of cART, is a safe and acceptable strategy to 
evaluate the efficacy of VRC01 in this population of HIV-infected adults. This is supported by the 
results from current and prior therapeutic vaccine studies using ATI (15-18), as well as a recent 
subgroup analysis of the SMART study (19).  Given that essentially all HIV-infected individuals 

Protocol Version 4.0 
3-Feb-2017 
 
 
 
17 
treated during the chronic phase of HIV infection will experience rebound in plasma viremia 
following cessation of cART (20, 21), a placebo control group is not necessary to evaluate the 
potential antiviral efficacy of VRC01 in this early phase study. 
 
 
2 
STUDY OBJECTIVES 
 
2.1 
Primary Objective 
To evaluate safety and tolerability of multiple doses of VRC01 in study subjects following 
discontinuation of cART. 
 
2.2 
Secondary Objective  
To evaluate the efficacy of VRC01 as determined by its effect on plasma viral rebound following 
discontinuation of cART. 
2.3 
Exploratory Objectives 
• 
To investigate whether plasma viral rebound can be prevented or delayed by VRC01 in 
infected individuals carrying HIV/viral reservoir that does not react to VRC01. 
• 
To examine the capacity of other antibodies (i.e., 3BNC117) that bind to CD4 binding 
site on gp120 to neutralize VRC01-escape mutants ex vivo. 
• 
To investigate whether VRC01-mediated suppression of HIV replication in the absence 
of cART allows the development of anti-HIV immunity (i.e., CTL response) in infected 
individuals who began therapy during the chronic phase of infection. 
• 
To evaluate B cell responses to rebounding HIV upon discontinuation of cART. 
• 
To examine the relationship between the size of persistent HIV reservoir and kinetics 
and timing of plasma viral rebound following ATI. 
 
3 
STUDY DESIGN 
 
3.1 
Description of the Study Design 
The proposed trial will be a single-arm, open-label study to examine the effect of VRC01 on 
plasma viral rebound in HIV-infected individuals following an analytical treatment interruption 
(ATI). Thirty HIV-infected individuals who initiated cART during the chronic phase of infection 
will be studied. All study participants will receive infusions of VRC01 (40mg/kg) at study days 0, 
Week 2, Week 4, and every four weeks thereafter for up to 24 weeks (Figure 1).  
 
Analytical treatment interruption 
After study day 3, all subjects will undergo an ATI to determine if treatment with VRC01 can 
prevent rebound of plasma viremia. Individuals taking non-nucleoside reverse transcriptase 
inhibitors (NNRTIs) will switch to a protease inhibitor or an integrase inhibitor-based regimen 2 
weeks prior to enrollment to ensure that the washout period of antiretroviral agents is roughly 
equal.    
 
All subjects with detectable viremia at Week 28 will be instructed to restart cART. Subjects will 
also be instructed to restart cART if they meet any of the following criteria during the ATI:  
• 
A confirmed >30% decline in baseline CD4 cell count or an absolute CD4 cell count 
<350 cells/mm3 that is associated with a HIV RNA level >40 copies/ml. 

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Protocol Version 4.0 
3-Feb-2017 
 
 
 
19 
1. Age 18-65 years old. 
2. HIV-1 infection and clinically stable. 
3. In general good health and with an identified primary health care provider for medical 
management of HIV infection and willing to maintain a relationship with a primary health 
care provider for medical management of HIV infection while participating in the study. 
4. CD4+ cell count >450 cells/mm3 at screening. 
5. Documentation of continuous cART treatment with suppression of plasma viral level 
below the limit of detection for ≥3 years. Subjects with “blips” (i.e., detectable viral levels 
on cART) prior to screening may be included provided they satisfy the following criteria:  
a. The blips are <400 copies/mL, and  
b. Succeeding viral levels return to levels below the limit of detection on subsequent 
testing. 
6. Willingness to undergo ATI. 
7. Laboratory values within pre-defined limits at screening:  
a. Absolute neutrophil count >1,000/mm3. 
b. Hemoglobin levels >10.0 g/dL for men and >9.0 g/dL for women. 
c. Platelet count >100,000/mm3.  
d. Prothrombin time (PT) and partial thromboplastin time (PTT) <1.5 upper limit of 
normal (ULN). 
e. Estimated or a measured creatinine clearance rate of ≥50 mL/min as determined 
by the NIH Clinical Center laboratory.  
f. 
AST and ALT levels of <2.5 x ULN. 
8. Willingness to have samples stored for future research.  
 
Reproductive Risks  
 
Contraception: The effects of VRC01 on the developing human fetus are unknown.  For this 
reason, men and women of childbearing potential must agree to use adequate pregnancy 
prevention per the investigator.  This includes highly reliable established lifestyle of complete 
abstinence of potentially reproductive sexual activity, or use of BOTH a long term hormonal or 
barrier (e.g. implant, depot injection, IUD in female participant or female partner of participant) 
method of contraception that is fully effective prior to dosing, COMBINED WITH a barrier 
method (male or female condom) for all potentially reproductive sexual activity.  Pregnancy 
prevention must be maintained as effective and practiced continuously for the duration of study 
participation.  Females of childbearing-age must have a negative pregnancy test result prior to 
receiving VRC01.  During the course of the study, if a female participant, or the partner of a 
male participant suspects or in fact becomes pregnant, the effected participant should inform 
the study staff immediately, as well as the woman’s primary care physician. 
 
Subjects must use safe sex practices during the trial, and particularly during the ATI phase, 
when risk of transmission of HIV may be increased. 
4.3 
Subject Exclusion Criteria 
 

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Protocol Version 4.0 
3-Feb-2017 
 
 
 
21 
VRC01 vials are filled at 2.25± 0.1 mL/vial in 3 mL glass vials at a concentration of 100 (±10) 
mg/mL. Vials contain a clear, colorless to yellow liquid with no visible particles, which is an 
isotonic, sterile solution.  The formulation buffer is composed of 25 mM sodium citrate, 50 mM 
sodium chloride, and 150 mM L-arginine hydrochloride at pH 5.8.  Vials are intended for single 
use only and thus do not contain a preservative. 
  
In calculating the dose to administer and number of vials to thaw, it should be assumed that the 
concentration is 100 mg/mL and that a volume of about 2 mL can be withdrawn from a vial.  
Preparation of VRC01 for IV administration will require a 100 mL bag of 0.9% sodium chloride 
for injection, USP (normal saline).  Note that the normal saline bags referred to as “100 mL 
bags” in the IV administration instructions will typically have 103 mL volume before any VRC01 
is added and this is acceptable in the context of the instructions below.  
 
Study agent vials will be individually labeled with the name of the material, volume, lot number, 
concentration, storage instructions, Investigational Use Statement (“Limited by Federal Law to 
Investigational Use”), and manufacturer information. 
 
5.2 
Study Agent Storage and Stability  
The product label designates the long-term storage temperature as -35°C to -15°C. Clinical site 
storage in a qualified, continuously monitored, temperature-controlled freezer at -45°C to -10°C 
is acceptable.   
 
The site pharmacist must promptly report any storage temperature deviations outside of the 
normal allowance for the storage device to the PI and the IND Sponsor. The product must be 
quarantined in a separate area.  The IND Sponsor’s authorized representative will notify the site 
pharmacist if continued clinical use of the product is acceptable. 
 
5.3 
Preparation, Administration, and Dosage of Study Agent 
Results from a stability study conducted with VRC01 show that the product is stable in the vial 
for 8 hours at refrigerated and room temperature.  The following instructions apply to preparing 
the product for infusion: 
• 
Thaw the vial(s) containing VRC01 at ambient temperature (15°C to 25°C). 
• 
Keep the material at refrigerated or room temperature during the entire preparation 
period until use. 
 
Preparation is to be done in a clean preparation unit with limited access.  Assure that only the 
required vials are present in the preparation unit during dilution, and medication labels are 
strictly segregated to avoid mix-ups. 
 
It is expected that each vial will be used for about 2 mL withdrawal volume (200 mg VRC01); 
however, more may be withdrawn if it is possible to do so.  For each IV infusion order, the 
subject’s weight and dose level will be included in the pharmacy order.  The IV bag prepared by 
the pharmacy will include information regarding the total amount (mg) of VRC01 added to the 
103 mL normal saline bag and the final volume of the bag.  The nurse responsible for 
administration and another clinician will each check the bag label and confirm that the identifier 
is correct and that the correct total milligrams to be administered is shown based on subject 
weight and dosage level before beginning the IV administration. 
 

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Protocol Version 4.0 
3-Feb-2017 
 
 
 
23 
5.5 
Prohibited Medications and Procedures  
Treatment with immunosuppressive medications during the study is prohibited. Prohibited 
immunosuppressive medications do not include [1] corticosteroid nasal spray or inhaler; [2] 
topical corticosteroids for mild, uncomplicated dermatitis; or [3] oral/parenteral corticosteroids 
given for non-chronic conditions not expected to recur ̵length of therapy ≤10 days. 
 
6 
STUDY SCHEDULE 
For all the study visits, unless otherwise specified, subjects will come to the NIH Clinical Center 
to undergo the procedures. Unless otherwise specified, the visit window for the post-entry study 
visits is ± 5 days. 
 
6.1 
Screening  
Screening may occur over the course of several contacts/visits. All inclusion and exclusion 
criteria must be assessed within 8 weeks before enrollment, unless otherwise specified in the 
eligibility criteria.  
 
After signing informed consent, subjects will undergo the following procedures: 
• 
Medical history and a targeted physical examination, including weight, vital signs, and a 
symptom-directed evaluation based on symptoms or complaints reported by each 
participant 
• 
Assessment of concomitant medications  
• 
Blood collection for:  
o HBsAg and Hepatitis C antibody serology 
o Anti-HIV antibody test. Subjects with previous confirmed Anti-HIV serology from 
the NIH will not have this repeated. 
o Complete blood count (CBC) with differential, PT, activated PTT 
o Chemistry panel to include: ALT, AST, alkaline phosphatase, creatinine, total and 
direct bilirubin, and serum albumin levels 
o Flow cytometry panel (includes CD4+ cell count) 
o Plasma HIV and HCV viral RNA levels 
• 
Storage of serum and plasma (if needed for repeat HIV antibody testing or viral RNA 
levels) 
• 
Urinalysis 
• 
Serum or urine pregnancy test for women of child-bearing potential   
• 
Electrocardiogram (ECG) 
 
 
6.2 
Enrollment/Baseline 
The enrollment visit may take place over 2 visits to accommodate the baseline pre-treatment 
apheresis procedure. The first dose of VRC01 will be administered at this visit, and enrollment is 
defined as the day of receipt of the first dose of VRC01.  
 
Subjects will undergo the following procedures (prior to the first dose of study drug): 
• 
Medical history and a targeted physical examination, including weight, vital signs, and a 
symptom-directed evaluation based on symptoms or complaints reported by each 
participant 
• 
Assessment of concomitant medications  
• 
HIV transmission risk behavior assessment and counseling 

Protocol Version 4.0 
3-Feb-2017 
 
 
 
24 
• 
Leukapheresis for research studies  
• 
Blood collection for: 
o Flow cytometry panel (includes CD4+ cell count) 
o Plasma HIV viral RNA levels 
o HLA typing (if not already on file)  
o Storage of plasma, serum and PBMCs 
o CBC with differential 
o Chemistry panels, to include: ALT, AST, alkaline phosphatase, creatinine, total 
and direct bilirubin, and serum albumin levels 
• 
Serum or urine pregnancy test (for women of child-bearing potential-obtained within 24 
hours prior to infusion) 
 
6.3 
Study Phase 
Treatment Phase 
Subjects will be administered VRC01 on study day 0. All subjects will discontinue their cART 
regimen after study day 3. Subsequent infusions of VRC01 will occur at study Week 2, 4, and 
every four weeks thereafter until study Week 24 for a total of 8 doses (see Figure 1).   
 
Storage of plasma, cells, and plasma HIV viremia will be done at study day 3, Week 1, 2, 3, and 
4 and every 2 weeks thereafter for the duration of the ATI. Flow cytometry with CD4 count will 
be done every 2 weeks for the duration of the ATI. 
 
At infusion visits (study Week 2, 4, 8, 12, 16, 20 and 24), the following will be done in addition to 
the plasma HIV viral load: 
• 
Medical history and a targeted physical examination, including weight, vital signs, and 
a symptom-directed evaluation based on symptoms or complaints reported by each 
participant 
• 
Assessment of concomitant medications  
• 
Assessment of any new or unresolved AEs/intercurrent illnesses 
• 
Blood collection (Week 4, 8, 12, 16, 20, and 24): 
o CBC with differential 
o Chemistry panels, to include: ALT, AST, alkaline phosphatase, creatinine, 
CPK, total and direct bilirubin, and serum albumin levels 
• 
Serum or urine pregnancy test for women of child-bearing potential (results must be 
reviewed prior to infusion)   
• 
Serum for storage (except for Week 2) 
• 
Optional leukapheresis for research studies will be done within 14 days after the week 
24 infusion  
• 
HIV transmission risk behavior assessment and counseling 
 
If a subject develops one or more criteria for ending ATI prior to Week 24, he/she will be asked 
to return for assessment and confirmation of the laboratory/clinical abnormality. If the criteria 
for ending ATI are met, no further VRC01 infusions will be given; the subject will be instructed 
to restart cART and continue to be followed for 24 weeks after the last VRC01 infusion. He/she 
will undergo the schedule of procedures described in Section 6.4. 
 
 
 

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Protocol Version 4.0 
3-Feb-2017 
 
 
 
26 
Other research evaluations measuring the effect of VRC01 on the HIV pathogenesis may 
include: 
• 
Frequency of CD4+ T cells carrying HIV proviral DNA and cell-associated HIV RNA 
• 
 Frequency of HIV-specific CD4+ and CD8+ T cells 
• 
T-cell activation and soluble markers of inflammation 
• 
Residual (1-40 copies/mL) plasma viremia 
 
 
8 
POTENTIAL RISKS AND BENEFITS 
8.1 
Potential Risks 
General Risks of MAb Treatment 
 
Administration of mAb may have a risk of immune reactions such as acute anaphylaxis, serum 
sickness and the generation of antibodies; however, these reactions are rare and more often 
associated with mAb targeted to human proteins or with the use of chimeric murine monoclonal 
antibodies, which would have a risk of human anti-mouse antibodies.  In this regard, as VRC01 
is targeted to a viral antigen and is a human monoclonal antibody, it is expected to have a low 
risk of such side effects.  
 
Typically, the side effects of mAbs are mild but may include fever, chills, rigors, nausea, 
vomiting, pain, headache, dizziness, shortness of breath, bronchospasm, hypotension, 
hypertension, pruritus, rash, urticaria, angioedema, diarrhea, tachycardia or chest pain. Most 
infusion-related events occur within the first 24 hours after beginning administration.  Severe 
reactions, such as anaphylaxis, angioedema, bronchospasm, hypotension and hypoxia, are 
infrequent and more often associated with mAbs targeted to human proteins or when a 
nonhuman mAb, such as a chimeric murine mAb, is used.  
 
Delayed allergic reactions to a mAb may include a serum sickness type of reaction, which is 
characterized by urticaria, fever, lymph node enlargement, and joint pains. These symptoms 
may not appear until several days after the exposure to the mAb and is noted to be more 
common with chimeric types of mAbs. 
 
As indicated in Section 1.1.3, no signficant (>Grade 1) adverse events related to VRCO1 have 
been seen to date in the two ongoing human trials. 
 
Analytical treatment interruption  
The risks from a 24-week ATI performed under close virologic and immunological monitoring 
are minimal in this subject population. There is a theoretical risk that ATI could lead to the 
development of HIV drug resistance. This may be a particular concern for individuals taking 
NNRTIs. However, this potential risk with NNRTIs is essentially eliminated by undertaking the 
procedures described in Section 3.1(22).  Given the study population, the short duration of the 
ATI, the frequency of immunological and virologic monitoring, and strict criteria for restarting 
cART, it is extremely unlikely that the ATI will lead to the development of any opportunistic 
infections or AIDS-defining conditions. 
 
During the ATI phase, subjects may transmit HIV infection if they do not adhere to safe sex 
practices. 

Protocol Version 4.0 
3-Feb-2017 
 
 
 
27 
 
Phlebotomy/Insertion of IV Catheter  
This may be associated with discomfort, bruising, local hematoma formation and, on rare 
occasions, infections, lightheadedness, and fainting.  
 
The amount of blood drawn for research purposes will be within the limits allowed for adult 
subjects by the NIH Clinical Center (Medical Administrative Policy 95-9: Guidelines for Limits of 
Blood Drawn for Research Purposes in the Clinical Center: http://cc-
internal.cc.nih.gov/policies/PDF/M95-9.pdf). 
 
HLA typing 
Some HLA types have been associated with an increased risk of certain diseases like arthritis 
and other rheumatologic disorders, or a faster progression to AIDS. HLA typing will be 
performed on samples collected from all the enrolled subjects. Results from the HLA typing will 
become part of each subject’s medical record at NIH. Medical records containing this 
information are maintained in a secure place.  
8.2 
Potential Benefits 
Study subjects will not receive direct health benefit from study participation or study infusions. 
Others may benefit from knowledge gained in this study that may aid in the development better 
HIV treatments. 
 
9 
RESEARCH USE OF STORED HUMAN SAMPLES, SPECIMENS OR DATA 
• 
Intended Use: Stored blood samples and data collected under this protocol may be used 
to study the effect of VRC01 on the virologic and immunologic parameters listed in 
Section 7.2.1.  Samples may also be used to study other aspects of the 
immunopathogenesis of HIV infection or measure serum levels of antiretroviral agents 
during ATI.  
• 
Storage:  Access to stored samples will be limited using a locked room or a locked 
freezer. Samples and data will be stored using codes assigned by the investigators. Data 
will be kept in password-protected computers. Only investigators will have access to the 
samples and data. 
• 
Tracking: Samples will be tracked utilizing the repository operated by Leidos Biomedical, 
Inc. Data will be stored and maintained in the NIAID CRIMSON database. 
• 
Disposition at the Completion of the Protocol: At the completion of the protocol 
(termination), samples and data will either be destroyed, or after Institutional Review 
Board (IRB) approval, transferred to another existing protocol.  
• 
Reporting the Loss or Destruction of Samples/Specimens/Data to the IRB: 
o Any loss or unanticipated destruction of samples or data (for example, due to 
freezer malfunction) that meets the definition of Protocol Deviation and/or 
compromises the scientific integrity of the data collected for the study, will be 
reported to the NIAID IRB.  
o Additionally, subjects may decide at any point not to have their samples stored.  
In this case, the principal investigator will destroy all known remaining samples 
and report what was done to both the subject and to the IRB.  This decision will 
not affect the subject’s participation in this protocol or any other protocols at 
NIH. 

Protocol Version 4.0 
3-Feb-2017 
 
 
 
28 
10 REMUNERATION PLAN FOR SUBJECTS  
Eligible subjects will be compensated for travel according to the NIAID/NIH travel policy. 
Subjects will receive financial compensation for time and inconvenience according to the NIH 
Clinical Center volunteer guidelines: screening ($50), leukapheresis ($200 for a 2-pass 
leukapheresis procedure), research blood draw ($40), clinic visits ($30), VRC01 infusion 
($80).  If subject does not qualify or declines leukapheresis, an additional 80 mL research blood 
will be drawn and subject may be compensated an additional $25 for inconvenience. 
 
11 ASSESSMENT OF SAFETY 
11.1 
Definitions  
Adverse event (AE)  
An adverse event is any untoward or unfavorable medical occurrence in a human subject, 
including any abnormal sign (e.g., abnormal physical exam or laboratory finding), symptom, or 
disease temporally associated with the subject’s participation in the research, whether or not 
considered related to the research. 
 
Adverse reaction (AR)   
An adverse reaction is an AE that is caused by an investigational agent (drug or biologic). 
 
Suspected adverse reaction (SAR) 
An adverse event for which there is a reasonable possibility that the investigational agent 
caused the adverse event. ‘Reasonable possibility’ means that there is evidence to suggest a 
causal relationship between the drug and the adverse event. A suspected adverse reaction 
implies a lesser degree of certainty about causality than adverse reaction which implies a high 
degree of certainty 
 
Serious adverse event (SAE) 
A Serious Adverse Event is an AE that results in one or more of the following outcomes: 
• 
death 
• 
a life-threatening (i.e., an immediate threat to life) event 
• 
an inpatient hospitalization or prolongation of an existing hospitalization 
• 
a persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• 
a congenital anomaly/birth defect 
• 
a medically important event* 
*Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
appropriate in other situations, such as important medical events that may not be immediately life 
threatening or result in death or hospitalization, but they may jeopardize the subject or may 
require intervention to prevent one of the other outcomes listed above.  
 
Unexpected adverse event 
An AE is unexpected if it is not listed in the Investigator’s Brochure or Package  
Insert (for marketed products), or it is not listed at the specificity or severity that has been 
observed. It is the responsibility of the IND sponsor to make this determination. 
 
Serious and unexpected suspected adverse reaction (SUSAR)  
A SUSAR is a Suspected Adverse Reaction that is both Serious and Unexpected.   

Protocol Version 4.0 
3-Feb-2017 
 
 
 
29 
 
Unanticipated problem (UP)  
An unanticipated problem is an event, incident, experience, or outcome that is 
  
1. unexpected in terms of nature, severity, or frequency in relation to 
a. the research risks that are described in the IRB-approved research protocol and 
informed consent document; Investigator’s Brochure, or other study documents; and 
b. the characteristics of the subject population being studied; and 
2. possibly, probably, or definitely related to participation in the research; and 
3. places subjects or others at a greater risk of harm (including physical, psychological, 
economic, or social harm) than was previously known or recognized (per the IND 
sponsor, an AE with a serious outcome will be considered increased risk). 
 
Unanticipated problem that is not an adverse event (UPnonAE)  
An unanticipated problem that does not fit the definition of an adverse event, but which may, in 
the opinion of the investigator, involve risk to the subject, affect others in the research study, or 
significantly impact the integrity of research data. Such events would be considered a non-
serious UP. For example, we will report occurrences of breaches of confidentiality, accidental 
destruction of study records, or unaccounted-for study drug. 
11.2 
Documenting, Recording, and Reporting Adverse Events 
All AEs occurring from the time of first dose of VRC01 through the specified study follow-up 
period (24 weeks after final VRC01 dose) will be documented, recorded, and reported. 
 
At each contact with the subject, information regarding AEs will be elicited by appropriate 
questioning and examinations and will be: 
• 
immediately documented in the subject’s medical record/source document, 
• 
recorded in Crimson, and 
• 
reported as outlined below (e.g., IND Sponsor, Institutional Review Board [IRB], and 
Food and Drug Administration [FDA]). 
 
If a diagnosis is clinically evident (or subsequently determined), the diagnosis rather than the 
individual signs and symptoms or lab abnormalities will be recorded as the AE.  
 
All abnormal laboratory findings will be reviewed on a routine bases by the PI to identify 
potential safety signals. An abnormal lab not included on the toxicity table should be assessed 
in a similar fashion to the criteria above. 
11.3 
Investigator Assessment of Adverse Events 
The Investigator will assess all AEs with respect to Seriousness (criteria listed above), 
Severity (intensity or grade), and Causality (relationship to study agent and relationship to 
research) according to the following guidelines. 
 
 
 
 
 

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Protocol Version 4.0 
3-Feb-2017 
 
 
 
37 
 
Table 3: Chance of AE of Given Probability 
0.025 
0.050 
0.075 
0.100 
0.125 
0.150 
0.532 
0.785 
0.904 
0.958 
0.982 
0.992 
 
The second row is the probability of observing at least one adverse event of probability given in 
the first row. 
 
With 30 patients, the approximate width of a 95% confidence interval for the probability of 
rebound is ±0.18.  For example, if half of the 30 patients rebound, the approximate confidence 
interval will be 0.50±0.18=(0.32,0.68). Exact 95% confidence intervals for different observed 
numbers of rebounders among 30 patients are shown in Table 4.  For example, if 10 out of 30 
patients rebound, the exact 95% confidence interval for the rebound probability will be 
(0.173,0.528).  
  
Table 4: Confidence Intervals For Rebound Probability 
0 
5 
10 
15 
20 
0-0.116 
0.056-0.347 
0.173-0.528 
0.313-0.687 
0.472-0.827 
 
The second row gives exact 95% confidence intervals for rebound probability given the 
observed number of rebounders in row 1 among the 30 patients. 
 
Futility guidelines (Table 5) are based on the numbers of patients meeting virologic criteria to 
restart cART within the first 12 weeks of the study. We use Bayesian methodology whereby we 
quantify our prior opinion about the 42 day probability with monoclonal antibodies as roughly 
equivalent to having observed 4 people, 2 of whom meet virologic criteria to restart cART by 12 
weeks . This translates to a beta (2,2) prior distribution for p, the probability of meeting virologic 
critera of failure by 12 weeks. Futility is declared if the posterior probability that p exceeds 0.70, 
given the observed results, is 90% or greater.  
  
     
Table 5: Futility Guidelines 
10 
12 
16 
19 
22 
10 
13 
18 
22 
26 
 
Row 2 shows the number of patients evaluated; futility is declared if the number meeting 
virologic criteria to restart by 12 weeks is at least as large as the number shown in row 1. That 
is, the futility boundary is crossed if the first 10 patients rebound by 12 weeks, or at least 12 of 
the first 13 meet virologic criteria by 12 weeks or at least 16 of the first 18 rebound by 12 weeks 
, etc. 
   
The probabilities of crossing this futility boundary are shown in Table 6 for different true 12 week 
probabilities. 
 
 

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Protocol Version 4.0 
3-Feb-2017 
 
 
 
39 
The investigator obtaining consent will document the consent process in the participant’s 
medical record (CRIMSON), including the name of the interpreter. Further, all instances of use 
of the CC Short Written Consent Form will be reported to the IRB at the time of annual review. If 
the CC Short Written Consent Form is used three times or more for the same language, this will 
be reported to the IRB immediately. 
 
Illiterate English Speaking Participants 
As the majority of the patient populations from which the study participants are drawn are 
literate, written consent will typically be provided.  However, this population does have a small 
rate of illiteracy, and oral consent will be obtained for illiterate participants as consistent with 
NIH MAS Policy M77-2 without separate IRB approval for each specific use. At Continuing 
Reviews, the NIAID IRB will be informed of the number of illiterate participants who provided 
consent verbally. 
14.2 
Subject Confidentiality 
All records will be kept confidential to the extent provided by federal, state and local law. The 
study monitors and other authorized representatives of the Sponsor may inspect all documents 
and records required to be maintained by the Investigator, including but not limited to, medical 
records.  Records will be kept locked and all computer entry and networking programs will be 
done with coded numbers only.  Clinical information will not be released without written 
permission of the subject, except as necessary for monitoring by IRB, NIAID, OHRP, or the 
sponsor’s designee. 
 
15 DATA HANDLING AND RECORD KEEPING 
15.1 
Data Capture and Management  
Study data will be maintained in CRIMSON and collected directly from subjects during study 
visits and telephone calls, or will be abstracted from subjects’ medical records. Source 
documents include all recordings of observations or notations of clinical activities and all reports 
and records necessary to confirm the data abstracted for this study. Data entry into CRIMSON 
will be performed by authorized individuals.  Corrections to CRIMSON shall be tracked 
electronically with time, date, individual making the correction, and what was changed. 
 
The investigator is responsible for assuring that the data collected are complete, accurate, and 
recorded in a timely manner. 
15.2 
Record Retention 
The investigator is responsible for retaining all essential documents listed in the International 
Conference for Harmonization Good Clinical Practice Guidelines.  Study records will be 
maintained by the PI for a minimum of 3 years and in compliance with institutional, IRB, state, 
and federal medical records retention requirements, whichever is longest.  All stored records will 
be kept confidential to the extent required by federal, state, and local law. The FDA requires 
study records to be retained for up to two years after marketing approval or disapproval (21 
CFR 312.62), or until at least 2 years have elapsed since the formal discontinuation of clinical 
development of the investigational agent for a specific indication. 
 
Should the investigator wish to assign the study records to another party and/or move them to 
another location, the investigator will provide written notification of such intent to 

Protocol Version 4.0 
3-Feb-2017 
 
 
 
40 
OCRPRO/NIAID with the name of the person who will accept responsibility for the transferred 
records and/or their new location. Destruction or relocation of research records will not proceed 
without written permission from NIAID/OCRPRO. 
 

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Protocol Version 4.0 
7-Oct-2015 
 
 
42 
17. 
Rosenberg ES, Graham BS, Chan ES, Bosch RJ, Stocker V, Maenza J, et al. 
Safety and immunogenicity of therapeutic DNA vaccination in individuals treated 
with antiretroviral therapy during acute/early HIV-1 infection. PloS One. 
2010;5(5):e10555. 
18. 
Schooley RT, Spritzler J, Wang H, Lederman MM, Havlir D, Kuritzkes DR, et al. 
AIDS clinical trials group 5197: a placebo-controlled trial of immunization of HIV-
1-infected persons with a replication-deficient adenovirus type 5 vaccine 
expressing the HIV-1 core protein. J Infect Dis. 2010;202(5):705-16. 
19. 
Routy JP, Boulassel MR, Nicolette CA, Jacobson JM. Assessing risk of a short-
term antiretroviral therapy discontinuation as a read-out of viral control in 
immune-based therapy. J Med Virol. 2012;84(6):885-9. 
20. 
Davey RT, Jr., Bhat N, Yoder C, Chun TW, Metcalf JA, Dewar R, et al. HIV-1 and 
T cell dynamics after interruption of highly active antiretroviral therapy (HAART) 
in patients with a history of sustained viral suppression. Proc Natl Acad Sci U S 
A. 1999;96(26):15109-14. 
21. 
Strategies for Management of Antiretroviral Therapy Study G, El-Sadr WM, 
Lundgren J, Neaton JD, Gordin F, Abrams D, et al. CD4+ count-guided 
interruption of antiretroviral treatment. N Engl J Med. 2006;355(22):2283-96. 
22. 
Investigators ST, Fidler S, Porter K, Ewings F, Frater J, Ramjee G, et al. Short-
course antiretroviral therapy in primary HIV infection. N Engl J Med. 
2013;368(3):207-17. 

Protocol Version 4.0 
3-Feb-2017 
 
APPENDIX B: SCHEDULE OF PROCEDURES/EVALUATIONS 
  
Screening 
and Baseline  
Treatment Phase 
Study 
time point 
Scre
en  
Enroll
ment/ 
Baseli
ne 
Day 
3  
Wk 
1 
Wk 
2 
Wk 
3 
Wk 
4 
Wk 
6 
Wk 
8 
Wk 
10 
Wk 
12 
Wk 
14 
Wk 
16 
Wk 
18 
Wk 
20 
Wk 
22 
Wk 
24 
Repeat 
Visit for 
End ATI 
Criteria 
ASSESSMENTS 
H & P 
X 
X 
  
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
X-PRN 
HIV 
Counselin
g 
  
X 
  
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
Vital 
Signs  
X  
X 
  
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
MEDICATIONS 
Last Dose 
of cART 
  
  
STO
P 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Re-Start 
cART** 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
START-
PRN 
Infusion  
  
X 
  
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
PROCEDURES 
EKG 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Leukaphe
resis 
  
X-
OPT 
  
  
  
  
  
  
  
  
  
  
  
  
  
X-
OP
T 
  
CLINICAL LABS 
CBC/Diff 
X 
X 
  
  
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  

Protocol Version 4.0 
3-Feb-2017 
 
 
44 
aPTT/PT 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Chemistri
es 
X 
X 
  
  
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
Urinalysis  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Pregnanc
y Test*** 
X 
X 
  
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
HBsAg, 
Anti-HCV, 
HCV RNA 
Quant 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
HLA 
Typing* 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
RESEARCH LABS 
ELISA/W
B* 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
HIV-1-
RNA  
X 
X 
X 
X 
X 
X  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X-PRN 
Flow 
cytometry  
X 
X 
  
  
X 
  
X 
 X  
X 
 X  
X 
 X  
X 
 X  
X 
 X  
X 
X-PRN 
Plasma 
Storage 
X-
PRN 
 X 
 X 
 X 
X  
X  
X  
 X 
 X 
 X 
X  
 X 
 X 
 X 
 X 
X  
X  
  
Serum 
Storage 
X-
PRN 
X 
  
  
  
  
X  
  
 X 
  
X 
  
 X 
  
 X 
  
 X 
  
PBMC 
X 
 X 
 X 
X  
X  
 X 
 X 
 X 
X  
 X 
 X 
 X 
 X 
X  
 X 
 X 
  
PBL 
Storage $ 
  
 X 
  
  
  
  
  
  
  
  
  
  
  
  
  
X  
  
* Do not repeat if previously on file 
** If meets criteria for ending ATI (Section 6.3) 
*** For females of childbearing potential 
$ If not able to complete apheresis