Clinical trial NCT05019729
Conditions: Malaria
Keywords: Malaria Parasitemia Malaria Challenge First in Human Mosquito Prevention
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2021-09-13; Completion date: 2022-09-19
Enrollment: 32 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
Background:

Malaria is a parasitic disease carried by mosquitoes in tropical areas. There is no vaccine to prevent malaria infection. If not treated right away, it can become serious or deadly. Researchers want to test a drug to prevent malaria.

Objective:

To test if the drug L9LS is safe and if it prevents malaria infection in people.

Eligibility:

Healthy adults ages 18-50 who have never had malaria.

Design:

Participants were screened with a medical history, physical exam, and blood tests.

Participants were divided into 6 groups:

* Three groups received L9LS by infusion into a vein, and gave blood samples before and after infusion.
* One group received L9LS injected into the fat under the skin.
* One group did not get L9LS.
* One group received L9LS injected into the muscle.

All participants who received L9LS were monitored for side effects. They had 2-3 follow-up visits during the week after the drug was given, and gave blood samples. They received a thermometer to check their temperature daily for 7 days. They received a tool to measure any redness, swelling, or bruising at the injection site.

Most participants took part in the controlled human malaria infection (CHMI) or malaria challenge to find out if L9LS prevents malaria after being bitten by infected mosquitos. Participants in the group who received L9LS injected in the muscle were enrolled after CHMI and did not take part in the CHMI. Participants who received CHMI were bitten by mosquitoes carrying the malaria parasites. A cup containing mosquitoes was placed on their arm for 5 minutes. On days 7-17 after exposure, they received daily study visits to give blood samples. Those who got malaria were treated immediately. On day 21, all CHMI participants received treatment for malaria.

Participation lasted 2-6 months, depending on study group.

Detailed description:
This was a Phase 1, open-label, dose escalation study to evaluate the safety, tolerability, pharmacokinetics and protective efficacy of an anti-malaria human monoclonal antibody, VRC-MALMAB0114-00-AB (L9LS). The primary hypothesis was that L9LS will be safe and well tolerated when administered by either intravenous (IV),subcutaneous (SC) or intramuscular (IM) routes. The secondary objectives were that L9LS will be detectable in human sera with a definable half-life and confer protection following a controlled human malaria infection (CHMI).

The study started with enrollment into Group 1. Interim safety evaluations occurred and supported continued evaluation of L9LS prior to enrolling participants into additional dose groups. All L9LS recipients in Groups 1-4 were invited to participate in the CHMI. Group 5 participants did not receive L9LS, in order to serve as the control group for the CHMI. After CHMI, all CHMI participants were evaluated for malaria parasitemia. Participants who developed blood stage infection were treated as soon as identified per protocol criteria. Participants in Group 6 received L9LS but did not take part in the CHMI.

Study follow-up continued through 24 weeks post product administration or 8 weeks post- CHMI, whichever was the most stringent.

Study Groups:

Group 1: 5 participants - 1mg/kg IV + CHMI

Group 2: 4 participants - 5 mg/kg IV + CHMI (1 participant declined to participate in the CHMI)

Group 3: 5 participants - 5 mg/ kg SC + CHMI

Group 4: 4 participants - 20 mg/kg IV + CHMI

Group 5: 9 participants - CHMI Controls (No L9LS given; 3 back up participants were not needed so were terminated early and did not participate in the CHMI)

Group 6: 5 participants - 5 mg/kg IM

Arms: arm 1: L9LS (1 mg/kg) administered by intravenous (IV) infusion (Day 0) arm 2: L9LS (5 mg/kg) administered by IV infusion (Day 0) arm 3: L9LS (5 mg/kg) administered by subcutaneous (SC) injection (Day 0) arm 4: L9LS (20 mg/kg) administered by IV infusion (Day 0) arm 5: Control participants who did not receive L9LS and were enrolled to complete the controlled human malaria infection (CHMI) arm 6: L9LS (5 mg/kg) administered by intramuscular (IM) injection (Day 0)
Interventions: intervention 1: VRC-MALMAB0114-00-AB intervention 2: Plasmodium falciparum (P. falciparum) sporozoite challenge
Intervention descriptions: intervention 1: VRC-MALMAB0114-00-AB (L9LS) is a monoclonal antibody that binds an epitope of the Plasmodium falciparum circumsporozoite protein. intervention 2: Participants were exposed to bites on the forearm from mosquitoes infected with Plasmodium falciparum

Protocol documents:
Prot_SAP_ICF_001.pdf: 
Protocol Title: VRC 614 (000536): A Phase 1, Dose Escalation, Open-Label Clinical Trial with 
Experimental Controlled Human Malaria Infections (CHMI) to Evaluate Safety and Protective 
Efficacy of an Anti-Malaria Human Monoclonal Antibody, VRC-MALMAB0114- 00-AB 
(L9LS), in Healthy, Malaria-Naive Adults 
 
NCT: 05019729 
 
Documents: 
· IRB-approved Protocol (v2.0 03NOV2021) - Statistical Analysis Considerations located 
in Section 6 of the Protocol  
· IRB approved ICF (v2.0 03NOV2021) - IRB Approval/Document Date: 01DEC2021 


 
 
 
 
 
Version 2.0 
November 3, 2021 
 
VACCINE RESEARCH CENTER 
 
Protocol VRC 614 
NIH 000536  
 
 
 
Title: A Phase 1, Dose Escalation, Open-Label Clinical Trial with Experimental Controlled 
Human Malaria Infections (CHMI) to Evaluate Safety and Protective Efficacy of an Anti-
Malaria Human Monoclonal Antibody, VRC-MALMAB0114-00-AB (L9LS), in Healthy, 
Malaria-Naive Adults 
 
Abbreviated Title: L9LS in Healthy Adults 
  
 
IND Sponsor 
Vaccine Research Center (VRC) 
National Institute of Allergy and Infectious Diseases (NIAID) 
Bethesda, Maryland, US 
 
IND 155252 
 
 
Investigational Product L9LS Manufacturer: 
Vaccine Clinical Materials Program (VCMP) operated under contract  
by Leidos Biomedical Research, Inc.,  
Frederick, Maryland, US 
 
 
 
 
NIH Principal Investigator: Richard Wu, M.D. 
VRC/NIAID 
Email: richard.wu2@nih.gov 
 
 
 


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TABLE OF CONTENTS
 
 
TABLE OF CONTENTS .................................................................................................................2 
LIST OF TABLES ...........................................................................................................................5 
ABBREVIATIONS .........................................................................................................................6 
PRINCIPAL INVESTIGATOR PROTOCOL SIGNATURE PAGE .............................................8 
PRÈCIS 
9 
STATEMENT OF COMPLIANCE ...............................................................................................10 
1. 
INTRODUCTION ......................................................................................................11 
1.1. 
Study Rationale ...........................................................................................................11 
1.1.1. 
L9LS Development .....................................................................................................11 
1.1.2. 
Rationale for Study Design .........................................................................................12 
1.1.3. 
Addition of Intramuscular Injection Cohort in v.2.0 ..................................................12 
1.2. 
Background .................................................................................................................12 
1.2.1. 
Previous Human Experience .......................................................................................12 
1.2.2. 
Controlled Human Infections (CHI) ...........................................................................13 
1.3. 
Laboratory Assessments of L9LS ...............................................................................14 
1.3.1. 
Pharmacokinetic (PK) Analysis ..................................................................................14 
1.3.2. 
Detection of Anti-Drug Antibody ...............................................................................14 
1.4. 
Measures of mAb-Mediated Protection and Parasitemia ...........................................14 
2. 
STUDY PRODUCT AND CHMI ..............................................................................15 
2.1. 
Study Product: L9LS ..................................................................................................15 
2.2. 
Preclinical Experience ................................................................................................15 
2.2.1 
Tissue Cross-Reactivity (TCR) Study ........................................................................15 
2.2.2 
Rat Toxicity Study ......................................................................................................15 
2.3. 
Clinical Experience .....................................................................................................16 
2.4. 
Controlled Human Malaria Infection (CHMI) ...........................................................16 
3. 
STUDY OBJECTIVES ..............................................................................................17 
3.1. 
Primary Objectives .....................................................................................................17 
3.2. 
Secondary Objectives .................................................................................................17 
3.3. 
Exploratory Objectives ...............................................................................................17 
4. 
STUDY DESIGN AND CLINICAL PROCEDURES ...............................................18 
4.1. 
Study Population .........................................................................................................18 


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4.1.1. 
Inclusion Criteria ........................................................................................................18 
4.1.2. 
Exclusion Criteria .......................................................................................................20 
4.2. 
Inclusion of Vulnerable Subjects ................................................................................21 
4.2.1. 
Children ......................................................................................................................21 
4.2.2. 
Adult Subjects who Lack Capacity to Consent to Research Participation .................21 
4.2.3. 
NIH Employees ..........................................................................................................21 
4.3. 
Clinical Procedures and Evaluations ..........................................................................21 
4.3.1. 
Recruitment and Retention .........................................................................................22 
4.3.2. 
Screening ....................................................................................................................22 
4.3.3. 
Enrollment and Study Day 0 .......................................................................................23 
4.3.4. 
Product Administration ...............................................................................................23 
4.3.5. 
Post-Product Administration Follow-up .....................................................................24 
4.3.6. 
Solicited Adverse Events (Reactogenicity) ................................................................24 
4.3.7. 
CHMI Procedures .......................................................................................................25 
4.3.8. 
Post-CHMI Follow-Up ...............................................................................................26 
4.3.9. 
Parasitemia Management ............................................................................................26 
4.3.10. 
Follow-Up through End of Study ...............................................................................27 
4.4. 
Concomitant Medications ...........................................................................................27 
4.5. 
Dose Escalation Plan ..................................................................................................28 
4.6. 
Criteria for Discontinuation of Protocol Participation ................................................28 
4.6.1. 
Discontinuation from Protocol Participation ..............................................................28 
4.7. 
Criteria for Pausing and Resuming the Study .............................................................29 
4.7.1. 
Plan for Review of Pauses and Resuming Rules ........................................................29 
5. 
SAFETY AND ADVERSE EVENTS ........................................................................30 
5.1. 
Adverse Events ...........................................................................................................30 
5.2. 
Serious Adverse Events ..............................................................................................30 
5.3. 
Adverse Event Reporting to the IND Sponsor ...........................................................31 
5.4. 
IND Sponsor Reporting to the FDA ...........................................................................31 
5.5. 
Reporting to the Institutional Review Board ..............................................................32 
5.5.1. 
Unanticipated Problem ...............................................................................................32 
5.5.2. 
Non-Compliance .........................................................................................................32 
5.5.3. 
Protocol Deviation ......................................................................................................33 
5.5.4. 
Death ...........................................................................................................................34 


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5.5.5. 
New Information .........................................................................................................34 
5.5.6. 
Suspension or Termination of Research Activities ....................................................34 
5.5.7. 
Expedited Reporting to the IRB .................................................................................34 
5.5.8. 
Annual Reporting to the IRB ......................................................................................34 
6. 
STATISTICAL CONSIDERATIONS .......................................................................35 
6.1. 
Overview .....................................................................................................................35 
6.2. 
Sample Size and Accrual ............................................................................................35 
6.3. 
Statistical Analysis ......................................................................................................36 
6.3.1. 
Analysis Variables ......................................................................................................36 
6.3.2. 
Safety Analysis ...........................................................................................................37 
6.3.3. 
Pharmacokinetics Analysis .........................................................................................37 
6.3.4. 
Efficacy Analysis ........................................................................................................38 
6.3.5. 
Interim analyses ..........................................................................................................39 
7. 
PHARMACY PROCEDURES ...................................................................................40 
7.1. 
Study Product..............................................................................................................40 
7.2. 
Storage and Temperature Excursions .........................................................................40 
7.3. 
Labeling of Study Product Vial ..................................................................................40 
7.4. 
Preparation of Study Product for Administration .......................................................40 
7.4.1. 
Preparation for IV Administration ..............................................................................40 
7.4.2. 
Preparation for SC or IM Administration  ..................................................................41 
7.4.3. 
Handling of Prepared Product for IV, SC, or IM Administration ..............................41 
7.5. 
Study Product Accountability .....................................................................................42 
7.6. 
Study Product Disposition ..........................................................................................42 
8. 
HUMAN SUBJECT PROTECTIONS AND ETHICAL OBLIGATIONS................43 
8.1. 
Institutional Review Board .........................................................................................43 
8.2. 
Informed Consent .......................................................................................................43 
8.3. 
Study Discontinuation and Closure ............................................................................43 
8.4. 
Confidentiality and Privacy ........................................................................................44 
8.5. 
Risk/Benefit Assessment ............................................................................................45 
8.5.1. 
Potential Risks ............................................................................................................45 
8.5.2. 
Potential Benefits ........................................................................................................47 
8.5.3. 
Assessment of Potential Risks and Benefits ...............................................................47 
8.6. 
Plan for Use and Storage of Biological Samples ........................................................47 


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8.6.1. 
Use of Samples, Specimens and Data .........................................................................47 
8.6.2. 
Storage and Tracking of Blood Samples and Other Specimens .................................47 
8.6.3. 
Disposition of Samples, Specimens and Data at Completion of the Protocol ............48 
8.6.4. 
Loss or Destruction of Samples, Specimens or Data ..................................................48 
8.7. 
Safety Oversight .........................................................................................................48 
9. 
ADMINISTRATIVE AND OPERATIONAL OBLIGATIONS................................50 
9.1. 
Protocol Amendments and Study Termination...........................................................50 
9.2. 
Study Documentation and Storage .............................................................................50 
9.3. 
Clinical Monitoring ....................................................................................................50 
9.4. 
Data Collection and Sharing .......................................................................................51 
9.4.1. 
Data Collection ...........................................................................................................51 
9.4.2. 
Source Documents ......................................................................................................51 
9.4.3. 
Data Sharing ...............................................................................................................51 
9.5. 
Quality Assurance and Quality Control ......................................................................51 
9.6. 
Language .....................................................................................................................52 
9.7. 
Research-Related Injuries ...........................................................................................52 
9.7.1. 
NIH .............................................................................................................................52 
9.7.2. 
WRAIR .......................................................................................................................52 
9.8. 
WRAIR Facility and CHMI Management ..................................................................52 
9.8.1. 
Roles and Responsibilities for the CHMI ...................................................................53 
9.8.2. 
WRAIR Protocol Review and Reporting Requirements ............................................53 
10. 
REFERENCES ...........................................................................................................55 
APPENDIX I: SCHEDULE OF EVALUATIONS .......................................................................57 
APPENDIX II: ASSESSMENT OF AE RELATIONSHIP AND SEVERITY GRADING .........69 
APPENDIX III: STUDY PRODUCT PREPARATION ...............................................................71 
 
LIST OF TABLES 
Table 1: 
Study Schema .............................................................................................................18 
Table 2: 
Probability of Events for Different Safety Scenarios (n=5 or 23) ..............................35 
Table 3: 
95% Confidence Intervals for the True Rate at Possible Observed Number of 
Events (n=5 or n=23) ..................................................................................................36 


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ABBREVIATIONS 
 
Abbreviation
Definition
ADA 
Anti-Drug Antibody
AE 
Adverse event 
ALT
Alanine aminotransferase
ANA 
Anti-nuclear antibody 
AST 
Aspartate aminotransferase 
CBC
Complete blood count
cGLP 
Current Good Laboratory Practices 
cGMP 
Current Good Manufacturing Practices
CHI 
Controlled human infection 
CHMI 
Controlled human malaria infection
CMP
Comprehensive Metabolic Panel 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CSP 
Circumsporozoite protein
CTP
Clinical Trials Program
DoD
Department of Defense
DoDI 
Department of Defense Instruction
DNA 
Deoxyribonucleic Acid 
DOT 
Directly observed therapy
EKG 
Electrocardiogram 
ELISA 
Enzyme-linked immunosorbent assay 
FDA
Food and Drug Administration
GCP
Good Clinical Practice 
HBsAg 
Hepatitis B surface antigen
HCV
Hepatitis C virus 
HIV 
Human Immunodeficiency Virus
HRPP
Human Research Protections Program
HSBP
Human Subjects Protection Branch 
ICH 
International Conference on Harmonization
IM 
Intramuscular
IND 
Investigational New Drug Application 
IV 
Intravenous  
LIMS
Laboratory Management Information System 
mAb
Monoclonal Antibody
MedDRA 
Medical dictionary for regulatory activities
MO 
Medical Officer
NAT 
Nucleic acid test 
NHP
Non-Human Primate
NIAID 
National Institute of Allergy and Infectious Diseases  
NIH 
National Institutes of Health
NIH CC
NIH Clinical Center


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Abbreviation
Definition
PBMC
Peripheral blood mononuclear cell
PCR 
Polymerase Chain Reaction
Pf 
Plasmodium falciparum 
PfCSP
Plasmodium falciparum circumsporozoite protein 
PfSPZ 
Plasmodium falciparum whole-sporozoite
PI 
Principal Investigator
PK
Pharmacokinetics
PSRT
Protocol Safety Review Team 
QA
Quality Assurance 
RBC
Red blood cells  
rPfCSP 
Recombinant Plasmodium falciparum circumsporozoite protein 
SAE 
Serious adverse event
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
SC 
Subcutaneous
SPZ 
Sporozoite
SUSAR
Serious and unexpected suspected adverse reaction
TCR
Tissue Cross Reactivity 
U.S. 
United States 
ULN 
Upper limit of normal 
UPnonAE 
Unexpected Problem that is not an Adverse Event
VCMP 
Vaccine Clinical Materials Program
VEC
Vaccine Evaluation Clinic 
VIS 
Volunteer Infection Studies  
VIP 
Vaccine Immunology Program
VRC 
Vaccine Research Center 
WBC 
White blood cells  
WHO
World Health Organization
WRAIR
Walter Reed Army Institute of Research


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PRINCIPAL INVESTIGATOR PROTOCOL SIGNATURE PAGE 
 
VRC 614: A Phase 1, Dose Escalation, Open-Label Clinical Trial with Experimental 
Controlled Human Malaria Infections (CHMI) to Evaluate Safety and Protective  
Efficacy of an Anti-Malaria Human Monoclonal Antibody, VRC-MALMAB0114-00-AB 
(L9LS), in Healthy, Malaria-Naive Adults 
 
I, the Principal Investigator for the study site indicated below, agree to conduct the study in full 
accordance with the provisions of this protocol and all applicable protocol-related documents.  I 
agree to conduct the study in compliance with United States (US) Health and Human Services 
(HHS) regulations (45CFR 46); applicable US Food and Drug Administration (FDA) regulations; 
standards of the International Conference on Harmonization Guidelines for Good Clinical Practice 
(E6); Institutional Review Board/Ethics Committee (IRB/EC) determinations; all applicable in-
country, state, and local laws and regulations; and other applicable requirements (e.g., US National 
Institutes of Health) and institutional policies.  I will comply with all requirements regarding the 
obligations of investigators as outlined in the Statement of Investigator (Form FDA 1572), which I 
have also signed.  The protocol signature page will be signed for subsequent protocol approvals.   
I agree to maintain all study documentation pertaining to the conduct of this study, including but 
not limited to, case report forms, source documents, laboratory test results, and medication 
inventory records, per FDA regulation (21 CFR 312.62) and all applicable requirements.  No study 
records will be destroyed without prior authorization from VRC/NIAID.   
Publication of the results of this study will be governed by the VRC/NIAID policies.  Any 
presentation, abstract, or manuscript will be made available by the investigators to VRC 
Leadership for review prior to submission. 
I have read and understand the information in this protocol and will ensure that all associates, 
colleagues, and employees assisting in the conduct of the study are informed about the obligations 
incurred by their contribution to the study. 
 
Richard Wu/Clinical Fellow  
 
NIH - Vaccine Evaluation Clinic 
_______________________________    __________________________________ 
Name/Title of Principal Investigator   
  Study Site Name 
 
 
___________________________________   __________________________________ 
Signature of Principal Investigator                  Date 
 
 
 


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PRÈCIS 
Title: 
VRC 614: A Phase 1, Dose Escalation, Open-Label Clinical Trial with Experimental 
Controlled Human Malaria Infections (CHMI) to Evaluate the Safety and Protective 
Efficacy of an Anti-Malaria Human Monoclonal Antibody, VRC-MALMAB0114-00-AB 
(L9LS), in Healthy, Malaria-Naïve Adults. 
Design: 
This is the first in human study of the VRC-MALMAB0114-00-AB (L9LS) monoclonal 
antibody (mAb) targeting the Plasmodium falciparum (Pf) circumsporozoite protein 
(PfCSP) in healthy adults.  This dose-escalation study will evaluate the safety, 
tolerability, pharmacokinetics (PK), and protective efficacy of L9LS.  The primary 
hypothesis is that L9LS will be safe and well tolerated when administered by intravenous 
(IV), subcutaneous (SC) or intramuscular (IM) routes.  The secondary hypotheses are that 
L9LS will be detectable in human sera with a definable half-life and confer protection 
following a controlled human malaria infection (CHMI). 
Study Product: VRC-MALMAB0114-00-AB was isolated and developed by the Vaccine Research 
Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), National 
Institutes of Health (NIH) and binds an epitope of the PfCSP. 
Subjects: 
Healthy adults, 18-50 years of age, who are malaria-naive.  
Study Plan: 
This study will evaluate the L9LS doses and routes of administration as shown below in 
the Study Schema table. The study will start with enrollment into Group 1. Assessment of 
safety will include solicited reactogenicity, clinical observation and monitoring of 
hematological and chemical parameters at clinical visits throughout the study. Interim 
safety evaluations will occur and must support continued evaluation of L9LS prior to 
enrolling subjects into additional dose groups. L9LS recipients in Groups 1-4 will 
participate in the CHMI.  Group 5 will not receive investigational product in order to 
serve as the control group for the CHMI.  After CHMI, all participants will be evaluated 
for malaria parasitemia.  Subjects who develop blood stage infection will be treated as 
soon as identified per protocol criteria. Subjects in Group 6 will receive investigational 
product but will not take part in the CHMI. Blood sampling for PK analysis will occur 
throughout the study, including pre- and post-CHMI. 
VRC 614 Study Schema
Group 
Subjects 
L9LS Administration
CHMI 
Dose (mg/kg) 
Route
1
5
1
IV
X
2
4
5
IV
X
3
5
5
SC
X
4
4
20
IV
X
5
6
Control1
X
6 
5 
5
IM
N/A 
Total 
292 
1Two (2) additional control subjects will be enrolled as CHMI back-ups 
2Up to 40 subjects may enroll if needed for additional safety or efficacy evaluations. 
 
Duration: 
Study follow-up will continue through 24 weeks post product administration or 8 weeks 
post CHMI, whichever is most stringent.  


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STATEMENT OF COMPLIANCE 
 
The trial will be carried out in accordance with International Conference on Harmonisation Good 
Clinical Practice (ICH GCP) and the following:  
• United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 
CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812)  
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training. 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the Institutional Review Board (IRB) for review and approval.  Approval of both 
the protocol and the consent form must be obtained before any participant is enrolled.  Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study.  In addition, all changes to the consent form will be IRB-approved; a 
determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form. 


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1. 
INTRODUCTION  
Malaria is a mosquito-borne protozoan disease belonging to the genus Plasmodium that affects 
250-500 million people, and kills approximately 500,000 individuals annually, with an enormous 
economic impact in the developing world, especially sub-Saharan Africa [1-3].  The five 
recognized species of Plasmodium that cause human malaria infection are Plasmodium 
falciparum (Pf), P. vivax, P. ovale, P. malariae, and P. knowlesi.  Among these, Pf causes more 
deaths in children worldwide than any other single infectious agent.  An estimated 30,000 
travelers from North America, Europe, and Japan contract malaria per year.  Although malaria is 
preventable with chemoprophylaxis and completely curable with early intervention, drug 
treatment is not readily accessible in many parts of the world.  Additionally, the use of 
antimalarial drugs over time has been associated with the emergence of drug-resistant strains.  
Lack of compliance with preventive drug treatment by individuals travelling to endemic areas 
may also result in fatal malaria infection.  The world’s first malaria vaccine, RTS,S/AS01 
(Mosquirix™), a recombinant protein-based vaccine targeting Pf, was approved for use by 
European regulatory authorities in 2015.  It is currently being evaluated in immunization 
programs in sub-Saharan Africa despite having been found to provide only partial protection (of 
about 30-50%) against clinical malaria to children and infants [4, 5].  Therefore, the development 
of a safe and more effective malaria vaccine is an urgent priority and may take many additional 
years.  Alternatively, the use of antibodies for passive prevention of malaria provides a new and 
more immediate approach for malaria prevention that, if successful, would have a major impact 
on improving public health worldwide.  Recent development of highly potent human monoclonal 
antibodies that have changes made to improve their duration in vivo and protect in different pre-
clinical models will provide the first assessment of this approach. 
1.1. 
Study Rationale  
1.1.1. 
L9LS Development 
The Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases 
(NIAID), National Institutes of Health (NIH) has been investigating broadly-neutralizing human 
monoclonal antibodies (bNAbs) targeted at a variety of pathogens that may be utilized in clinical 
applications including preventive and therapeutic measures.  In the case of malaria, prevention 
by passive immunization has potential applications for use in travelers, military personnel, 
season control and elimination campaigns in endemic areas. 
L9LS (VRC-MALMAB0114-00-AB) is the second PfCSP-specific mAb the VRC plans to 
pursue in clinical development. L9, the wild-type parent of L9LS, was isolated by sorting the 
PfCSP-reactive memory B cells obtained from a subject immunized with a radiation-attenuated 
PfSPZ malaria vaccine in the VRC 314 clinical trial (NCT02015091) using a junctional epitope 
mimic probe designed to select for “CIS43-like” mAbs. Epitope mapping showed L9 bound to 
NPNV motifs associated with NVDP  minor repeats of PfCSP. When compared to a published 
panel of protective human PfCSP mAbs, L9 protected mice against intravenous and mosquito 
bite SPZ challenge, and demonstrated the lowest effective dose (ED)80 and effective 
concentration (EC)80 values (325.7 µg and 145.1 µg/mL, respectively) of any mAb evaluated, 
including CIS43LS (685.92 µg and 363.93 µg/mL, respectively) [6]. The unique preference of 
L9 for NPNV motifs was further underscored by the fact that all four NVDP tetrapeptide motifs 
had to be mutated to NANP to disrupt the recognition of L9 for the NPNV motifs found in 


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rPfCSP. As 100% of known Pf field isolates have one or more NVDP motifs, these data suggest 
that L9 should bind all circulating strains of malaria[6]. 
L9 was modified with the previously-described Fc-region LS mutation (L9LS) to increase 
neonatal Fc receptor (FcRn) binding and consequent antibody half-life [2-5]. Immune protection 
and half-life data acquired with L9 and L9LS identify L9LS as a promising clinical candidate for 
passive malaria prophylaxis. 
1.1.2. 
Rationale for Study Design 
This phase I trial will evaluate L9LS safety and PK at doses 1, 5 and 20 mg/kg IV,  5 mg/kg SC, 
and 5 mg/kg IM. The study will allow for the achievement of a range of antibody concentrations 
in vivo for determining a protective L9LS titer in CHMI. Because the safety and potential 
therapeutic range of this mAb is unknown, dose selection was informed by non- clinical PK data 
in non-human primates (NHP) comparing L9 and L9LS, historical dose ranges evaluated in 
clinical trials of other mAbs developed by the VRC (e.g., VRC07-523LS [IND133027] and 
N6LS [IND 134081]), and prior clinical experience in healthy adults with anti-malaria mAb 
CIS43LS (VRC 612 [NCT04206332] conducted under IND 142632 [7]) where recipients were 
protected against malaria infection when challenged in CHMI at about 4 weeks to 36 weeks post-
product administration. The lack of malaria infection in participants who received a 20 or 40 
mg/kg IV dose of CIS43LS prevented the planned regression analysis to identify a threshold 
level of protection. The higher participant numbers in the 1 mg/kg IV and 5 mg/kg SC groups 
allow for more data at the lowest dose group to try to identify a protective antibody titer 
threshold and to support future trials assessing the SC route in malarial-endemic regions, 
respectively.    
1.1.3. 
Addition of Intramuscular Injection Cohort in v.2.0 
With the version 2.0 amendment, a cohort is being added to receive a 5 mg/kg dose of L9LS by 
IM injection. The purpose of this amendment is to evaluate the safety, tolerability and PK of 
L9LS by the IM route.  Data on this route may support development of phase 2 trials in Africa as 
the IM route may allow individuals, such as children, who may not have sufficient subcutaneous 
tissue or not have intravenous access, to be able to receive L9LS. Since this arm is being added 
after the CHMI has occurred, this group will not participate in the CHMI.   
1.2. 
Background 
1.2.1. 
Previous Human Experience  
There is no human experience with L9LS prior to this trial. Prior clinical experience in 
completed and ongoing Phase 1 and 2 trials of healthy adults with human mAbs manufactured 
and formulated by the VRC that recognize pathogen-specific epitopes (i.e., VRC01, VRC01LS, 
VRC07-523LS, and mAb114) [8-11] are used to summarize the general safety risk associated 
with mAbs.   
Treatments with these mAbs have been generally well tolerated, with no reported deaths or 
serious adverse events (SAEs) assessed as related to the study products.  Typical for mAbs, the 
predominant local reactogenicity complaint has been mild pain/tenderness, although reports of 
mild injection site pruritus, redness and swelling have occurred at modestly higher frequencies 


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with SC administration.  Malaise, muscle pain, and headache have been the most frequently 
reported solicited complaints noted in the 3 days post product administration and these have also 
been mostly transient and mild in severity. Increased frequencies of fever, redness, swelling and 
pain at the injection site have been reported after IM administration. Urticaria and infusion 
reactions comprised of chills, rigors, myalgia, headache, and/or fever have been reported after IV 
infusions at product doses of 10 to 40 mg/kg; these reactions have been transient, resolved 
without sequelae within 24 hours of onset, and treated with over-the-counter analgesics and 
antipyretics. 
1.2.2. 
Controlled Human Infections (CHI)  
Controlled human infection (CHI) trials (also referred to as Volunteer Infection Studies (VIS)) 
result in the experimental infection of healthy subjects with the infectious agent of choice and are 
an unparalleled tool in infectious disease research.  CHI trials allow for the accelerated 
evaluation of novel drugs and vaccines for potential efficacy, while also providing the 
opportunity to prospectively study clinical disease progression.  The first controlled human 
malaria infection (CHMI) was performed in the mid-1980s [12].  This process involves the 
deliberate infection with malaria parasites either by mosquito bite or direct injection.  VRC has 
successfully conducted three Phase 1 CHMI studies: VRC 312 [13], VRC 314 [14], and VRC 
612 [7].   
According to a comprehensive review of CHI trials using a variety of pathogens, an estimated 
6000 subjects have received CHI [15].  Only four possibly-related SAEs have been reported, of 
which two were observed following malaria vaccination and CHMI [15].  The first cardiac event 
of possible myocarditis, reported in 2008 [16], prompted recommendation by a panel of experts 
that consideration of cardiac risk be required for clinical challenge trials and that individuals 
identified as at increased cardiovascular risk be excluded from malaria clinical challenge trials 
[17].  A second cardiac event was observed in 2013 following malaria vaccination and CHMI 
[18].  VRC was also informed of a possible 3rd, unpublished, myocarditis event in 2014.  As a 
result of these events and the recommendations, evidence of increased cardiovascular disease 
risk or an electrocardiogram (ECG) with clinically significant abnormalities will preclude trial 
enrollment as described in Section 4.1.2.  
The challenge phase in this study will be performed with Pf strain 3D7 [sensitive to Chloroquine 
and Malarone (atovaquone and proguanil)] via mosquito bite, which is the natural route of 
exposure and transmission in the field.  While subjects will be monitored closely throughout 
study duration, monitoring intensity will increase following exposure to Pf-infected mosquitoes 
to ensure rapid diagnosis and treatment.  Appropriate drug therapy will be used to treat and cure 
any subject with a confirmed Pf infection after diagnosis by PCR, the most sensitive assessment 
for detecting early malaria infection, in order to minimize the risk of developing a serious 
complication.  The Pf strain to be used for CHMI in this study can be effectively treated with and 
cured by the antimalarial medications to be used in this trial [19, 20].   
There is negligible risk of transmitting malaria to a person in the community since subjects are 
exposed to malaria-infected mosquitos only during the CHMI at a contained facility. 


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1.3. 
Laboratory Assessments of L9LS  
Some laboratory assessments in this study are also designed to characterize the investigational 
product.  This includes PK analysis and evaluation for anti-drug antibody (ADA) development 
after product exposure.  These are further described in the subsequent sections.  Other assays 
may also be performed using stored samples at a later date if additional assessments are needed.  
The VRC’s Vaccine Immunology Program (VIP), Gaithersburg, MD, will process blood and 
store coded samples, and will either perform sample testing or ship coded samples to designated 
research laboratories at the VRC or other approved collaborators.  See APPENDIX I for 
schedules, blood volumes and tube types to be used for research sample collection.  Research 
assays will be performed on samples from both study product recipients and CHMI-controls at 
baseline and throughout the study.  
Tube types for clinical labs are according to institutional requirements and are shown in the 
Schedule of Evaluations to estimate blood volumes.  Different tubes for clinical evaluations may 
be used to meet site requirements.  Research sample tube types and blood volumes must be used 
as shown or as otherwise instructed by the IND Sponsor.  In some instances, coded samples may 
be transported directly by study staff to the laboratory of an approved collaborator. 
1.3.1. 
Pharmacokinetic (PK) Analysis 
Concentrations of L9LS will be measured by Meso Scale Discovery (MSD) platform and similar 
methodology as previously described for other VRC mAb products [9].   
1.3.2. 
Detection of Anti-Drug Antibody  
Assays for detection of ADA will be performed at specified timepoints following product 
administration and CHMI compared to baseline status using a similar methodology as previously 
described for other VRC mAb products [9].  We will employ a sequential approach to screen, 
confirm, and characterize ADA in the clinical serum samples according to the Food and Drug 
Administration (FDA) guidance.  Screening and confirmation will involve an MSD 
electrochemiluminescence (ECL) bridging assay.   
1.4. 
Measures of mAb-Mediated Protection and Parasitemia 
L9LS-mediated protection will be assessed after CHMI outcomes are obtained and compared to 
control subjects’ CHMI outcomes.  The endpoint defining mAb-mediated protection for the 
CHMI is the absence of Pf parasites in blood samples obtained from L9LS-recipients collected 
daily from Day 7 through Day 17 and then on Day 21 post-CHMI.  The criteria for a case of 
malaria is confirmation of parasitemia either by the Malaria real-time PCR assay or by blood 
smear.  The Malaria real-time PCR assay targets the 18S rRNA (ribosomal RNA) gene, which is 
a DNA target.  It is the default means of monitoring for parasitemia in this protocol; a single 
positive PCR result will confirm infection [13, 21, 22]. 
A blood smear will be performed by the NIH Clinical Center Microbiology Service per their 
departmental SOPs for any subject who develops symptoms likely due to malaria despite having 
a negative PCR result.  Laboratory personnel performing PCR and blood smear testing will be 
blinded to subject group and treatment received or lack thereof, in the case of controls.  Research 
blood samples may also be used for parasite genome analysis.   


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2. 
STUDY PRODUCT AND CHMI  
2.1. 
Study Product: L9LS 
The L9LS (VRC-MALMAB0114-00-AB) mAb was discovered and developed by the VRC, 
NIAID, NIH.  The study product was manufactured under current Good Manufacturing Practice 
(cGMP) by the Vaccine Clinical Materials Program (VCMP) operated under contract by Leidos 
Biomedical Research, Inc., Frederick, MD.  
2.2. 
Preclinical Experience 
To assess L9LS as a candidate for clinical trials, research grade mAb was assessed for in vitro 
functional activity including binding properties and auto-reactivity, in vivo protection following 
challenge using a mouse infection model, and in vivo PK using an NHP model.  In mice, L9 was 
more potent than CIS43, and both L9LS and L9 mediated the same potency following challenge.  
In NHP PK studies, L9LS exhibited substantially longer half-life in blood as compared to the 
parental L9 mAb without the LS mutation. 
Two preclinical toxicology studies were conducted with a process-representative developmental 
batch of L9LS.  An in vitro tissue cross-reactivity (TCR) assay to screen for potential cross-
reactivity and an in vivo rat toxicity study to demonstrate safety were both conducted in 
compliance with Title 21 of the Code of Federal Regulations Part 58 (21 CFR 58) Good 
Laboratory Practice (GLP) for Nonclinical Laboratory Studies. 
2.2.1 
Tissue Cross-Reactivity (TCR) Study 
The TCR assay screened a standard panel of normal human tissues (three donors per tissue) and 
Sprague Dawley rat tissues (two rats per tissue).  Mammalian cells transfected to express CSP 
were used as a tissue positive control.  Two concentrations of L9LS were tested: 1.15 µg/ml 
(selected as the concentration which saturated the positive control tissue), and 11.5 µg/ml (10-
fold excess).  A negative control IgG1κ antibody (GR338422-1, no mammalian target antigen) 
was tested at the same two concentrations.  L9LS exhibited scattered specific membrane binding 
in 3/3 human salivary gland tissue samples, which localized to the epithelial cells lining the ducts 
and acini.  Binding was rare (1-5% of these epithelial cells) at 1.15 µg/ml, and rare to occasional 
(5-25% of these epithelial cells) at 11.5 µg/ml.  The cause of the salivary epithelial cell 
membrane binding has not been identified.  Specific membrane binding to salivary gland tissue 
was not observed for the negative control antibody.  L9LS did not bind to rat salivary epithelium.  
No specific membrane-binding to other human tissues was observed. 
2.2.2 
Rat Toxicity Study 
Sprague Dawley rats were dosed with L9LS to evaluate toxicity and toxicokinetics.  Rats 
received 0, 40, or 400 mg/kg by intravenous (IV) bolus injection twice (Day 1 and Day 11).  
Female rats were dosed with 10 mg/kg by subcutaneous (SC) injection once (D1); male rats were 
dosed with 10 mg/kg SC twice (D1 and D11); both male and female rats were dosed with 100 
mg/kg SC twice (Day 1 and Day 11).  For all dose-levels, the main-group was necropsied at Day 
12 to evaluate potential immediate effects, and recovery animals were necropsied at Day 46 to 
evaluate the potential for delayed effects and recovery.  Treated rats exhibited a transient 
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Serum clinical chemistry tests detected slightly-increased globulin, consistent with the 
administration of L9LS, an IgG mAb.  For IV dosing, the no observed adverse effect level 
(NOAEL) was the high dose, 400 mg/kg IV x2. For SC dosing, the NOAEL was the high-dose, 
100 mg/kg SC x2.  SC injection of L9LS did not cause reactogenicity (edema, erythema, eschar) 
in any rat.  Histopathology evaluation of the SC injection site skin reported minimal to moderate 
subcutaneous mixed cell infiltration, considered treatment-related and predictive for human 
volunteers.  One treated rat (in the 100 mg/kg SC group) was found dead; this event was 
attributed to a procedural error the previous day and is not considered treatment-related.  One 
treated female (in the 100 mg/kg SC recovery group) had grossly-visible heart enlargement 
(2-fold increase in both heart weight and heart:body weight compared to the control means), with 
normal heart histology.  Spontaneous cardiomyopathies are occasionally observed for the 
Sprague Dawley strain of rat.  Based on the singular incidence, this observation is not considered 
treatment-related. 
With reference to the CDER 2005 Guidance for Industry Estimating the Maximum Safe Starting 
Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers1, scaling based on 
body weight is appropriate for a mAb expected to distribute mainly in the vascular space.  The 
rat IV NOAEL of 400 mg/kg x2 supports the IV clinical high-dose with a 20-fold dose margin.  
The rat SC NOAEL of 100 mg/kg x2 supports the SC clinical dose with a 20-fold dose margin. 
The FDA provides guidance on “the nonclinical safety studies recommended to support human 
clinical trials” in the Guidances for Industry ICH M3(R2) Nonclinical Safety Studies for the 
Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals2 and ICH 
S6 Addendum to Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals3.  
Taken together, the L9LS TCR and rat toxicity study results meet the safety standard set in these 
guidances and support proceeding with the proposed L9LS clinical trial. 
2.3. 
Clinical Experience  
This study constitutes the first in human trial with L9LS, therefore, there is no previous 
experience in humans.  See Section 1.2.1 for more information about similar VRC mAb 
products.  As additional data about the effect of L9LS in humans is accumulated from the 
cohorts of this first-in-human Phase 1 trial, this section will be updated. 
2.4. 
Controlled Human Malaria Infection (CHMI)  
Preparation of infected mosquitoes for CHMI will be performed according to a Type II Master 
File 033797, Malaria Challenge Model, Standard Operating Procedures for the Pf model used.  
To prepare infected mosquitoes, Pf asexual and sexual erythrocytic stage parasites will be grown 
in normal human erythrocytes using standard culture medium containing 10% normal human 
serum.  The blood and serum for culture are purchased from a Food and Drug Administration 
(FDA)-accredited blood bank.  Each shipment carries a certificate of analysis certifying that the 
blood products are negative or non-reactive for immunologic evaluation and infectious disease 
testing.  
 
1 https://www.fda.gov/media/72309/download  
2 https://www.fda.gov/media/71542/download  
3 https://www.fda.gov/media/78034/download  


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3. 
STUDY OBJECTIVES 
3.1. 
Primary Objectives 
• To evaluate the safety and tolerability of L9LS administered IV at 1, 5, and 20 mg/kg in 
healthy, malaria-naive adults 
• To evaluate the safety and tolerability of L9LS administered SC at 5 mg/kg in healthy, 
malaria-naive adults 
• To evaluate the safety and tolerability of L9LS administered IM at 5 mg/kg in healthy, 
malaria-naive adults 
3.2. 
Secondary Objectives 
• To evaluate the pharmacokinetics of L9LS at each dose level throughout the study  
• To determine if IV or SC administration of L9LS mediates protection against infectious P. 
falciparum following CHMI  
3.3. 
Exploratory Objectives 
• To determine whether anti-drug antibody (ADA) to L9LS can be detected in sera of 
recipients at specific time points throughout the study 
• To assess for IgG1 allotypes and allotype-specific effects on L9LS pharmacokinetics  


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4. 
STUDY DESIGN AND CLINICAL PROCEDURES 
This open-label, dose escalation study will be conducted at the VRC Vaccine Evaluation Clinic 
(VEC) in the NIH Clinical Center (NIH CC) and the CHMI will be conducted at the Walter Reed 
Army Institute of Research (WRAIR) insectary with the oversight of NIH staff.  The primary 
hypothesis is that L9LS will be safe and tolerable when administered by either IV, SC, or IM 
routes.  The secondary hypotheses are that L9LS will be detectable in human sera with a 
definable half-life and will confer protection following a CHMI.   
This study will evaluate L9LS at the doses and routes as shown below in the Study Schema table. 
The study will start with enrollment into Group 1.  Assessment of safety will include solicited 
reactogenicity, clinical observation and monitoring of hematological and chemical parameters at 
clinical visits throughout the study.  Interim safety evaluations will occur and must support 
continued evaluation of L9LS prior to enrolling subjects into additional dose groups.  L9LS 
recipients in Groups 1-4 will participate in the CHMI.  Group 5 will not receive investigational 
product in order to serve as the control group for the CHMI.  After CHMI,  participants in 
Groups 1-5 will be evaluated for malaria parasitemia.  Subjects who develop blood stage 
infection will be treated as soon as identified per protocol criteria. Subjects in Group 6 will 
receive investigational product but will not take part in the CHMI.  Blood sampling for PK 
analysis will occur throughout the study, including pre- and post-CHMI. 
Table 1: 
Study Schema  
VRC 614 Study Schema
Group 
Subjects 
L9LS Administration
CHMI 
Dose (mg/kg) 
Route
1
5
1
IV
X
2
4
5
IV
X
3
5
5
SC
X
4
4
20
IV
X
5
6
Control1
X
6 
5 
5 
IM 
N/A 
Total 
292 
1Two (2) additional control subjects will be enrolled as CHMI back-ups. 
2Up to 40 subjects may enroll if needed for additional safety or efficacy evaluations. 
4.1. 
Study Population 
Subjects will be screened to confirm eligibility requirements for participation using the VRC 500 
screening protocol.  The screening and education process required prior to enrollment is designed 
to ensure that subjects comprehend the purpose, details and risks/benefits of the study.   
4.1.1. 
Inclusion Criteria 
A subject must meet all of the following criteria to be included: 
1. Able and willing to complete the informed consent process  
2. Able to provide proof of identity to the satisfaction of the study clinician completing the 
enrollment process 
3. Available for clinical follow-up through the last study visit 


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4. 18 to 50 years of age 
5. In good general health without clinically significant medical history 
6. Physical examination without clinically significant findings within the 56 days prior to 
enrollment 
7. Weight ≤115 kg (except Group 5) 
8. Adequate venous access if assigned to an IV group or adequate subcutaneous tissue if 
assigned to an SC group 
9. Willing to have blood samples collected, stored indefinitely, and used for research 
purposes 
10. Agrees to participate in a controlled human malaria infection (CHMI) and to comply with 
post-CHMI follow-up requirements (except Group 6) 
11. Agrees to refrain from blood donation to blood banks for 3 years following participation 
in CHMI (except Group 6) 
12. Agrees not to travel to a malaria endemic region during the entire course of study 
participation (except Group 6) 
Laboratory Criteria within 56 days prior to enrollment: 
13. WBC 2,500-12,000/mm3 
14. WBC differential either within institutional normal range or accompanied by the 
Principal Investigator (PI) or designee approval  
15. Platelets = 125,000 – 500,000/mm3  
16. Hemoglobin within institutional normal range or accompanied by the PI or designee 
approval  
17. Creatinine≤1.1xupperlimitofnormal(ULN) 
18. Alanine aminotransferase (ALT) ≤1.25xULN 
19. Negative for HIV infection by an FDA approved method of detection 
Laboratory Criteria documented any time during screening, prior to enrollment: 
20. Negative PCR for malaria (except Group 6) 
21. Negative sickle cell screening test (except Group 6) 
22. Electrocardiogram (ECG) without clinically significant abnormalities (examples may 
include: pathologic Q waves, significant ST-T wave changes, left ventricular 
hypertrophy, any non-sinus rhythm excluding isolated premature atrial contractions, right 
or left bundle branch block, advanced A-V heart block). ECG abnormalities determined 
by a cardiologist to be clinically insignificant as related to study participation do not 
preclude study enrollment (except Group 6) 
23. No evidence of increased cardiovascular disease risk; defined as >10% five-year risk by 
the non-laboratory method [23] (except Group 6) 


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Criteria Specific to Women: 
24. Postmenopausal for at least 1 year, post-hysterectomy or bilateral oophorectomy, or if of 
childbearing potential: 
a. Negative beta-humanchorionicgonadotropin(β-HCG) pregnancy test (urine or 
serum) on day of enrollment, and prior to product administration and CHMI, and 
b. Agrees to use an effective means of birth control through the duration of study 
participation 
4.1.2. 
Exclusion Criteria 
A subject will be excluded if one or more of the following conditions apply: 
25. Woman who is breast-feeding or planning to become pregnant during study participation 
26. Previous receipt of a malaria vaccine or anti-malaria monoclonal antibody 
27. History of malaria infection  
28. Any history of a severe allergic reaction with generalized urticaria, angioedema or 
anaphylaxis prior to enrollment that has a reasonable risk of recurrence during the study 
29. Hypertension that is not well controlled 
30. Receipt of any investigational study product within 28 days prior to enrollment/product 
administration (Note: SARS-CoV-2 vaccines approved by emergency use authorization 
are not exclusionary) 
31. Receipt of any live attenuated vaccines within 28 days prior to enrollment/product 
administration 
32. Receipt of any vaccine within 2 weeks prior to enrollment/product administration 
33. Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet 
disorder requiring special precautions) or significant bruising or bleeding difficulties with 
intramuscular injections or blood draws 
34. History of a splenectomy, sickle cell disease or sickle cell trait 
35. History of skeeter syndrome or anaphylactic response to mosquito-bites (except Group 6) 
36. Known intolerance to chloroquine phosphate, atovaquone or proguanil (except Group 6)  
37. Use or planned use of any drug, including antibiotics, with antimalarial activity 4 weeks 
prior to CHMI (except Group 6) 
38. History of psoriasis or porphyria, which may be exacerbated after treatment with 
chloroquine (except Group 6) 
39. Anticipated use of medications known to cause drug reactions with chloroquine or 
atovaquone-proguanil (Malarone) such as cimetidine, metoclopramide, antacids, and 
kaolin (except Group 6) 
40. History of Sjogren’s syndrome 


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41. History of chronic or recurrent salivary gland disorder diagnosed by a clinician (note: an 
isolated occurrence of parotitis, sialadenitis, sialolithiasis, or of a salivary gland tumor is 
not exclusionary) 
42. History of therapeutic head or neck radiation 
43. Any other chronic or clinically significant medical condition that in the opinion of the 
investigator would jeopardize the safety or rights of the volunteer, including but not 
limited to: diabetes mellitus type I, chronic hepatitis; OR clinically significant forms of: 
drug or alcohol abuse, asthma, autoimmune disease, infectious diseases, psychiatric 
disorders, heart disease, or cancer 
4.2. 
Inclusion of Vulnerable Subjects  
4.2.1. 
Children 
Children are not eligible to participate in this clinical trial because the study product has not been 
previously evaluated in adults.  If the product is assessed as safe for further study, other protocols 
specifically designed for children may be conducted. 
4.2.2. 
Adult Subjects who Lack Capacity to Consent to Research Participation 
Adults who are unable to provide initial informed consent are excluded to enroll. Also, adults 
who permanently lose the capacity to provide on-going consent after initial consent and during 
the study will be discontinued from protocol participation as it is described in Section 4.6.  
4.2.3. 
NIH Employees  
NIH employees and members of their immediate families may participate in this protocol.  We 
will follow the Guidelines for the Inclusion of Employees in NIH Research Studies and will give 
each employee a copy of the “NIH FAQs for NIH Staff Who are Considering Participation in 
NIH Research” published by Office of Human Research Subjects Protections on Research 
Involving NIH Staff as Subjects, Policy 404.  For NIH employee subjects, consent will be 
obtained by an individual who is independent of the employee’s team.  If the individual 
obtaining consent is a co-worker to the subject, independent monitoring of the consent process 
will be included through the Bioethics Consultation Service.  Protocol study staff will be trained 
on obtaining potentially sensitive and private information from co-workers or subordinates. 
4.3. 
Clinical Procedures and Evaluations 
Evaluation of study product safety will include laboratory studies, medical history, physical 
assessment by clinicians, and subject self-assessment.  The study schedule is presented in the 
Schedule of Evaluations, APPENDIX I.  Total blood volume drawn from each subject will not 
exceed the NIH Clinical Center Guidelines. In response to the coronavirus disease 2019 
(COVID-19) pandemic and changing information related to testing, all NIH CC epidemiologic 
and testing guidelines will be followed during study conduct. 


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4.3.1. 
Recruitment and Retention 
Study enrollments will be conducted at the NIH Clinical Center.  Study subjects will be recruited 
through on-site and off-site IRB-approved advertising done through the VRC’s screening 
protocol, VRC 500 (NCT 01375530).  Effort will be made to include women and minorities in 
proportions similar to that of the community from which they are recruited. All volunteer facing 
materials used for recruitment and other purposes will be submitted to the IRB and approved 
before use.   
a. Costs 
There are no costs to subjects for their participation in this trial.  
 
b. Compensation 
Subjects will be compensated for time and inconvenience in accordance with the standards for 
compensation of the Clinical Research Volunteer Program.  Compensation for study visit that 
includes IV product administration is $430; study visit that includes SC or IM product 
administration is $375.  If enrollment occurs on a different day than study product 
administration, then visit compensation will be $85.  Compensation will be $200 for scheduled 
follow-up visits that include venipuncture, $85 for clinic visits that do not include venipuncture, 
and $25 for timely completion of the electronic diary card.  Compensation for a CHMI visit 
including the pre-CHMI clinic visit and activities is $455.  
The total amount of compensation varies depending upon group and the visits completed.  
Compensation may also vary depending upon the number of days required for the daily 
evaluations in the period after a CHMI as those who become parasitemic early will require fewer 
days of in-clinic evaluation visits than those who have delayed or no parasitemia.  CHMI control 
subjects will be compensated similarly for comparable visit types. 
4.3.2. 
Screening 
All screening procedures for this study will be completed through the VRC’s screening protocol, 
VRC 500 (NIH 11-I-0164). The Recruitment Plan per NIH Policy 302 can be found in the NIH 
IRB approved VRC 500 protocol.  Subjects will be recruited through Institutional Review Board 
(IRB)-approved advertising.  Screening evaluations are performed to confirm eligibility and will 
include medical history review, physical exam, and the clinical laboratory tests detailed in 
APPENDIX I.  Women presumed to be of reproductive potential will be given a pregnancy test.  
A baseline electrocardiogram (EKG) will be performed.  Information related to recurrent or 
persistent dry mouth or swelling of salivary glands will be reviewed during screening per 
exclusion criteria.  Additional assessments of health may be conducted at screening under 
protocol VRC 500 based on clinical judgment; no screening procedures will be done under 
protocol VRC 614.  Pre-exposure research blood samples may be collected anytime during 
screening through enrollment and will not be subject to the “56-day prior to enrollment” 
restriction.  
Informed consent documents will be reviewed during screening.  Counseling related to potential 
risks of the study product, pregnancy prevention, and avoiding exposure to malaria will be 
performed.  An Assessment of Understanding (AoU) will be completed in association with 


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enrollment into VRC 614.  Records will be kept documenting the reason that screened subjects 
do not enroll. 
Subjects who are not up to date on standard vaccinations may receive these, if available, during 
their participation in the screening protocol or at a later date during study participation. 
4.3.3. 
Enrollment and Study Day 0 
In this study, enrollment is defined as the assignment of a study identification number and a 
study group in the clinical database.  A clinician will discuss the target dates and timing of the 
study product administration, CHMI, and sample collections before completing an enrollment to 
help ensure that the subject can comply with the projected schedule.  Informed consent must be 
obtained prior to enrollment.  For L9LS recipients, enrollment will occur at Visit 01R (Day -28 
to Day 0) and may occur on the same day as product administration at Visit 02 (Day 0) in 
advance of product administration.  For CHMI control subjects, Visit 01R (Day -56 to Day -1) is 
the enrollment day, which will be within 56 days prior to the CHMI.   
For L9LS recipients, Day 0 is defined as the day of product administration.  If Day 0 does not 
coincide with enrollment, then the enrollment day may be referred to by a negative number of 
days (i.e., Day -1).  For calculating elapsed days following Day 0, each subsequent calendar date 
is labeled by the next sequential “Study Day” as shown in APPENDIX I.  Since there may be 
more than one research sampling timepoint of interest per study day, each sample collection 
timepoint has its own “Visit Number.”  For this reason, there may be more than one visit number 
recorded on the same calendar date.  
The study will start with subject enrollment directly into Group 1.  Additional dose groups 
(Groups 2, 3, 4) will open per the dose escalation rules as outlined in Section 4.5, and subjects 
will be directly enrolled into the subsequent open groups.  Subjects in Group 5 will be able to 
choose to participate in the control group and undergo CHMI without receiving product 
administration.  In case of Group 5 dropouts prior to CHMI, replacement of control subjects and 
enrollment of a sufficient number of backup subjects is allowable to ensure a total of 6 subjects 
can serve as controls on the day of CHMI.  Subjects in Group 6 will be enrolled after  enrollment 
in all other groups is complete. Because this is an open-label design, subjects will know what 
group they are in on the day of enrollment.   
Medical history and Day 0 evaluations (prior to product administration, as applicable per study 
group) are the baseline for subsequent safety assessments except that the screening evaluations 
will be the baseline for those only done at screening.  
4.3.4. 
Product Administration  
All product administrations will be completed according to the assigned group. 
On the day of, and prior to product administration, vital signs (temperature, blood pressure, heart 
rate and respiratory rate) will be recorded, a targeted physical examination (based on signs, 
reported symptoms or interim medical history) may be conducted as needed, and women of 
childbearing potential must have a negative pregnancy test.   
If a subject is assigned to an IV administration group, the IV access will be placed in an arm vein 
in an aseptic manner.  A different site may be used for collection of PK blood samples; however, 
the same site may be used after flushing the line if another site is not available.  L9LS will be 


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administered with approximately 50-120 mL of normal saline IV over about 15-30 minutes, with 
a target of 30 minutes.  Infusions lasting longer than 30 minutes are allowed.  If the subject 
experiences side effects during the infusion, the rate of infusion may be slowed or stopped to 
alleviate the symptoms.  
If a subject is assigned to a SC administration group, the SC administration site(s) to be used 
must be assessed as acceptable by the clinician and the subject.  The preferred SC administration 
site is the abdomen, but the upper arm or thigh may be used.  Given the weight criterion in this 
study, the maximum volume needed to administer a 5 mg/kg SC dose is not expected to exceed 
3.83 mL.  The SC dose will be administered by standard needle in a maximum volume of about 
2.5 mL per injection site.  Up to two (2) SC injection sites may be used if deemed necessary by 
the clinician.  SC administration sites should be at least 2 inches apart.  
If a subject is assigned to a IM administration group, the IM administration site(s) to be used 
must be assessed as acceptable by the clinician and the subject. Injections will be administered 
into the deltoid muscle or quadriceps muscle. Given the weight criterion in this study, the 
maximum volume needed to administer a 5 mg/kg IM dose is not expected to exceed 3.83 mL. 
The IM dose will be administered by standard needle in a maximum of 1.0 mL per injection site. 
Up to four (4) IM injection sites may be used if deemed necessary by the clinician. IM 
administration sites should be at least 2 inches apart 
4.3.5. 
Post-Product Administration Follow-up  
In all study groups, the first subject in each dose group to receive a unique dose level (1, 5, or 20 
mg/kg) will be observed for at least 2 hours following completion of product administration. All 
other subjects will be observed for at least 1 hour following completion of product 
administration.  Collection of PK samples will be conducted according to the Schedule of 
Evaluations for the subject’s study group. 
Prior to discharge from the clinic, subjects will be assessed for local and systemic reactogenicity 
and vital signs will be recorded.  Any subject who is assessed as being unwell or has ongoing 
reactogenicity symptoms will be asked to remain in the clinic until evaluation and discharge by a 
study clinician.  This includes the possibility of an overnight inpatient stay to evaluate for safety.   
4.3.6. 
Solicited Adverse Events (Reactogenicity) 
Each subject will be given a 7-day diary (paper and electronic-based available), a thermometer, 
and a measuring device.  Subjects will use the diary to record their highest temperature, local and 
systemic symptoms, and concomitant medications daily for 7 days after each product 
administration.  Subjects will be provided training on diary completion and proper usage of the 
thermometer to measure temperature and the measuring device to measure injection site 
symptoms.  Completion of diary training will be noted in the source documents.  While the 
electronic diary is preferred, subjects will have the option to use a paper diary.  The paper diary, 
if used, will be transcribed into the study database and stored in the subject file for monitoring 
purposes.  When neither paper nor electronic diary is available from the subject, the study 
clinician will document the source of reactogenicity information recorded in the study database. 
The signs and symptoms solicited by the diary will include systemic events of temperature, 
feeling unusually tired or unwell, muscles aches, headache, chills, nausea, and joint pain, and 
local events at the product administration site of pain/tenderness, swelling, redness, bruising, and 


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pruritus.  Subject diaries will be reviewed by a clinician for accuracy and completeness at 
follow-up visits.  Clinicians will follow any solicited symptoms that are ongoing after 7 days 
until they have resolved. 
Diary data will be available in real-time to clinicians for subjects who use the electronic diary.  
Subjects using a paper diary will be encouraged to contact the clinic as soon as possible for any 
moderate or severe side effects that they experience in the 7 days post product administration.  A 
study clinician may contact the subject by phone if any moderate or severe side effect is 
reported.  Eventsthatmayrequireaclinicvisitincluderash,urticaria,feverof38.6˚C(Grade2)
or higher lasting greater than 24 hours or significant impairment in the activities of daily living 
(such as those consistent with Grade 2 or higher impairment).  Additionally, other clinical 
concerns may prompt a study visit based on the judgment of a study clinician. 
4.3.7. 
CHMI Procedures  
The interval between administration of study product and CHMI will vary depending on when a 
subject is enrolled.  The CHMI will only occur following an evaluation of Day 7 safety data post 
product administration and may be administered at any time ≥8 days through 12 weeks post 
product administration.  Some flexibility around the interval between the time of L9LS 
administration and CHMI is permitted given the need to work with each subject’s personal 
schedule, availability of the CHMI facility and post-CHMI follow-up.   
Prior to scheduling the CHMI, at least two emergency contact numbers will be confirmed and 
verified as authentic for each subject who will participate in the challenge.  The clinical study 
team will review each subject’s adherence to the schedule and safety follow-up to date.  This 
review will attempt to identify any likelihood of unreliability on the part of the subject during the 
CHMI phase of the study.  Any subject expressing inability to comply with study requirements 
may be deemed unsuitable for CHMI and will be excluded from the CHMI phase of the study.  
Any subject who receives study product, however, will be encouraged to remain in the study for 
safety follow-up visits.   
Women of childbearing potential must have a negative pregnancy test within 2 days prior to 
CHMI.  Use of antibiotics by CHMI participants should be avoided at least 4 weeks prior to and 
during the CHMI unless medically warranted. 
Prior to CHMI procedure on the day of CHMI, vital signs will be recorded for subjects 
participating in the CHMI. An abbreviated physical examination will be performed by an 
Advanced Practitioner to confirm the subject’s ability to participate in the CHMI procedure. 
CHMI will be conducted by experienced insectary and clinical staff.  Mosquitoes infected via 
membrane feeds in preparation for the CHMI contain sporozoites in their salivary glands and up 
to 5 at a time will be allowed to feed on each subject under controlled conditions.  Following 
exposure, the mosquitoes will be immediately dissected to confirm the presence of a blood meal 
and to determine the infectivity rate and the salivary gland score.  Additional mosquitoes will be 
allowed to feed until 5 bites showing presence of a blood meal and a minimum 2+ salivary gland 
score has been achieved for each subject. 
Prior to discharge from CHMI, subjects will be observed for a minimum of 30 minutes.  Vital 
signs will be taken and the mosquito bite site will be assessed.  Subjects will be given an 
Emergency Notification card and will also be supplied with Hydrocortisone cream.  They will 


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also be provided with counseling and written recommendations to reduce risk of natural 
mosquito exposure beginning 5 days after CHMI and continuing until completion of treatment. 
4.3.8. 
Post-CHMI Follow-Up 
The study team will be in contact with subjects at least 2 times in the first 7 days after the CHMI 
to provide close monitoring of clinical status.  Blood samples to evaluate for malaria parasitemia 
will be collected daily and run on PCR from days 7 through 17 with a final PCR performed at 
day 21 post-CHMI.  Malaria PCR testing is processed in the morning and results are available 
the same day.  If the result is positive for malaria, the subject will be contacted by phone 
immediately.  Subject will be asked to return to the clinic within two hours of notification to 
initiate malaria treatment.  Prior to Day 21, regular parasitemia evaluations will stop after 
treatment is initiated for positive cases of parasitemia.  In the absence of malaria infection, all 
subjects who have not already started treatment will be provided with directly observed 
definitive antimalarial treatment at Day 21. 
During the post-CHMI follow-up period, subjects may participate in their normal daily activities.  
A study clinician will be available 24 hours a day by telephone or in person to the site staff in 
case consultation about subject’s signs and symptoms is needed.  Any subject who is assessed as 
being unwell during the post-CHMI follow-up will be asked to remain in the clinic until 
evaluation and discharge by a study clinician.  This includes the possibility of an overnight 
inpatient stay for evaluation.   
4.3.9. 
Parasitemia Management 
Following CHMI, a case of malaria parasitemia will be defined as either a single positive PCR 
result or a thick blood smear that meets the criteria for positivity.  PCR allows for cases of 
malaria to be identified before gametocytes can develop and thus before detection of 
gametocytes by blood smear are detectable.  Malaria infection will be treated when the criterion 
for a case is met.   
Regardless of PCR or blood smear results, all CHMI participants will receive directly observed 
antimalarial treatment at Day 21 post CHMI, if they have not already been treated for 
parasitemia by this timepoint.  Subjects may also be provided with treatments like antiemetics 
and ibuprofen as needed for management of symptoms.  
Refer to the Schedule of Evaluations, APPENDIX I, for the safety laboratory evaluations that are 
required to be performed at the onset of treatment and about 2 days later. 
Malaria infections in all subjects will be treated promptly and administered as directly observed 
therapy (DOT) by a clinician until the specified course of treatment.  Treatment regimens 
subsequently described are known to be effective against the Pf strain being used in the CHMI.  
• First line of treatment: a standard atovaquone/proguanil (Malarone®) regimen: 
Four Malarone Tablets (adult strength tablet = 250 mg atovaquone/100 mg proguanil; 
total daily dose 1 g atovaquone/400 mg proguanil hydrochloride) taken as a single 
dose daily for 3 consecutive days with food or a milky drink. 


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• Alternative treatment: a standard chloroquine regimen:  
Total of 1500 mg chloroquine base (2500 mg salt) given orally in divided doses: 600 
mg base (1000 mg salt) initially, followed by 300 mg base (500 mg salt) given 6, 24, 
and 48 hours later] 
Alternative medications and regimens known to be effective in curing the Pf strain administered 
for the CHMI may be used in the event of allergies, intolerances or lack of availability of 
treatments listed above.  
Following treatment for a positive case of malaria, cure will be documented by a PCR negative 
result at 26 days (± 5 days) after the completion of treatment.  Subjects who remain PCR 
negative will be contacted by phone at 26 (days ±5 days) after last negative PCR. 
4.3.10. 
Follow-Up through End of Study 
Study follow-up will continue via clinical visits through 24 weeks after the product 
administration or 8 weeks post final CHMI, whichever is most stringent.  The visit schedule is 
based on intervals of time after product administration or CHMI.  The schedule of visits, 
allowable windows for completing the visits, and evaluations performed at each visit are shown 
in the Schedule of Evaluations, APPENDIX I.  Out of window study visits will be discouraged 
and recorded as protocol deviations but may be permitted at the discretion of the PI in the 
interest of obtaining safety and PK evaluations following exposure to the investigational study 
product or conduct of a CHMI.   
Any subject who receives investigational product will be required to follow the product 
administration schedule for a complete safety and research evaluation through study duration.  
Subjects who undergo CHMI will be required to follow the CHMI Schedule of Evaluations to 
completion.  When visits from both schedules occur on the same day, all required components of 
the required visits for each schedule must be completed. 
Subjects who receive study product but do not receive CHMI as scheduled are expected to 
continue follow-up according to the schedule for IV, SC, or IM group through 24 weeks, except 
that research sample collections may be discontinued for pregnant women or others in which it is 
contraindicated.  
Refer to Section 4.6 for criteria for discontinuing product administration and/or study 
participation. 
4.4. 
Concomitant Medications 
Only routine prescription medications will be entered in the database at the time of enrollment.  
Subsequently, concomitant medications are only updated or recorded in the study database if 
there is an occurrence of an adverse event (AE) that requires expedited reporting, a change to 
pre-existing condition treatment, or the development of a new chronic condition that requires 
ongoing medical management.  Treatment with antimalarial drugs will be recorded on a Malaria 
Endpoint Case Report Form (CRF).  Otherwise, the concomitant medication changes throughout 
the study will be recorded in the subject’s chart as needed for general medical records but will 
not be recorded in the study database.   


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4.5. 
Dose Escalation Plan 
This study will include a series of interim safety reviews to assess product safety in a stepwise 
manner. The activation of additional dose groups will proceed in a staged manner that is 
governed by the outcome of the planned interim PSRT data reviews. The PSRT must assess the 
data as showing no significant safety concerns before proceeding with group activation. If there 
are discontinuations from the study before there are sufficient data to conduct the dose escalation 
review for a specific group, then additional subjects may be enrolled to complete the dose 
evaluation.  
The study will begin with direct enrollment of subjects into Group 1, with one subject enrolled 
per day for the first 3 subjects.  The first dose escalation review (from 1 mg/kg IV to 5 mg/kg 
IV) will occur when 3 subjects who received the 1 mg/kg dose by IV have completed the Day 7 
safety follow-up visit.  The PSRT review will determine whether enrollment into Group 2 may 
begin.  
The second dose escalation review (from 5 mg/kg IV to 20 mg/kg IV) will occur when 3 subjects 
who received the 5 mg/kg dose by IV have completed the Day 7 safety follow-up visit.  The 
PSRT review will determine whether enrollment into Group 4 may begin. 
Group 3 (5 mg/kg SC) can enroll at any time and is not contingent upon the dose escalation 
reviews for the IV doses.   
If there are discontinuations from the study before there are sufficient data to conduct the dose 
escalation review for a specific group, then additional subjects may be enrolled to complete the 
dose evaluation.  Additionally, AEs assessed as related to study product at the time of a dose 
escalation review may warrant enrollment of additional subjects into a dose group to reassess 
safety before proceeding to a higher dose.  Consultation with the IRB or FDA as per study pause 
criteria may occur if indicated.   
Group 6 (5 mg/kg IM) was added after completion of the dose escalation process and can enroll 
at any time. 
4.6. 
Criteria for Discontinuation of Protocol Participation 
All participants who received the study product will remain on study and continue safety follow-
up to Visit 14 (i.e., week 24). Participants who have completed the CHMI, but did not receive 
study product, will remain on study and continue safety follow-up to Visit C18. Decisions by the 
PI or designee to discontinue a subject from protocol participation will be made with the 
following criteria. 
4.6.1. 
Discontinuation from Protocol Participation 
A subject will be discontinued from protocol participation for the following reasons: 
1. Subject voluntarily withdraws; 
2. Subject is lost to follow-up 


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4.7. 
Criteria for Pausing and Resuming the Study  
The study team will closely monitor and review study data as they become available to make 
determinations regarding the presence, severity and attribution of AEs.  Study product 
administrations and new enrollments will be paused if any of the following criteria are met:  
• One (or more) subject experiences a SAE that is assessed as related (possibly, probably or 
definitely) to the study product, or 
• Two (or more) subjects experience the same Grade 3 or higher AE that is assessed as 
related (possibly, probably or definitely) to the study product (other than self-limited 
Grade 3 solicited reactogenicity). 
4.7.1. 
Plan for Review of Pauses and Resuming Rules   
In the event of a pause, the IND Sponsor Medical Officer (MO) and the PSRT will be promptly 
notified.  The IND Sponsor MO and PI, in consultation with the PSRT, will conduct a review of 
available information, including the events that lead to the pause, and will make the decision to 
resume, amend or close the study.  As part of the pause review, the reviewers may also advise on 
whether the study needs to be paused again for any subsequent events of the same type.   
Study product administrations and new enrollments would resume only if review of the AEs that 
caused the pause results in a recommendation to permit further study product administrations and 
study enrollments.  Safety data reports and changes in study status will be submitted to relevant 
regulatory authorities in accordance with Section 5 and institutional policy. 


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5. 
SAFETY AND ADVERSE EVENTS  
5.1. 
Adverse Events 
An adverse event (AE) 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 research, whether or not 
considered related to the subject’s participation in the research.  In the context of FDA-required 
reporting, an AE means any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related.  
• Solicited AEs (i.e., reactogenicity parameters as defined in Section 4.3.6) will be 
recorded without attribution assessments by the subject on paper or an electronic diary 
for 7 days after each product administration. 
• Unsolicited AEs will be recorded in the study database with attribution assessments 
during the following periods:  
1) from product administration through the Day 28 post-product administration visit; and  
2) from CHMI through the Day 28 post-CHMI visit.   
After and between the indicated time periods, only SAEs (as detailed in Section 5.3) and new 
chronic medical conditions will be recorded as AEs through the last expected study visit or 
contact.   
Malaria and the associated signs and symptoms of parasitemia events occurring at any time 
during the study will be recorded on a Malaria Endpoint CRF and will not be recorded as an AE. 
APPENDIX II describes how attribution assessments, the relationship between an AE and the 
study product, CHMI or both, will be determined.  Also available in APPENDIX II is the link to 
the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse 
Events, Corrected Version 2.1 [July 2017], which will be used to determine the severity grades 
of AEs in this protocol with several modifications as noted.  
5.2. 
Serious Adverse Events 
The term “Serious Adverse Event” (SAE) is defined in 21 CFR 312.32 as follows:  “An adverse 
event or suspected adverse reaction is considered serious if, in the view of either the investigator 
or the sponsor, it results in any of the following outcomes:  Death, a life-threatening adverse 
event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or 
significant incapacity or substantial disruption of the ability to conduct normal life functions, or a 
congenital anomaly/birth defect.  Important medical events that may not result in death, be life-
threatening, or require hospitalization may be considered serious when, based upon appropriate 
medical judgment, they may jeopardize the patient or subject and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition.  Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an emergency 
room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, 
or the development of drug dependency or drug abuse.” 


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“Life threatening” refers to an AE or suspected adverse reaction that represents an immediate 
risk of death to the subject.  It does not include an AE or suspected adverse reaction that, had it 
occurred in a more severe form, might have caused death.  Similarly, a hospital admission for an 
elective procedure is not considered a SAE. 
5.3. 
Adverse Event Reporting to the IND Sponsor 
AEs that meet SAE criteria must be reported and submitted by the clinical site on an expedited 
basis to the IND Sponsor, VRC/NIAID/NIH, according to sponsor guidelines as follows: 
• Results in death; 
• Is life threatening (places the subject at immediate risk of death from the event as it 
occurred); 
• Results in inpatient hospitalization or prolongation of existing hospitalization; 
• Results in a persistent or significant disability/incapacity; 
• Results in a congenital anomaly/birth defect in the offspring of a study subject; OR 
• Based upon appropriate medical judgment, may jeopardize the subject’s health and may 
require medical or surgical intervention to prevent one of the other outcomes listed in this 
definition (examples of such events include allergic bronchospasm requiring intensive 
treatment in the emergency room or at home, blood dyscrasias or convulsions that do not 
result in inpatient hospitalization, or the development of drug dependency or drug abuse). 
In addition, any event, regardless of severity, which in the judgment of an investigator represents 
a SAE, may be reported on an expedited basis. 
An investigator will communicate an initial SAE report within 24 hours of site awareness of 
occurrence to the IND Sponsor by data entry into the database, which triggers an alert to the IND 
Sponsor MO.  Within 3 working days, a written summary by the investigator should be 
submitted to the IND Sponsor.   
In order for the IND Sponsor to comply with regulations mandating sponsor notification of 
specified SAEs to the FDA within 7 and/or 15 calendar days, the investigator must submit 
additional information as soon as it is available. 
5.4. 
IND Sponsor Reporting to the FDA  
The IND Sponsor is responsible for making the determination of which SAEs are “serious and 
unexpected suspected adverse reactions” (SUSARs) as defined in 21 CFR 312.32.  
• Suspected Adverse Reaction means any AE for which there is a reasonable possibility that 
the drug caused the AE.  
• Unexpected Adverse Event means an AE that is not listed at the specificity or severity that 
has been observed.  
All SUSARs (as determined by the IND Sponsor) will be reported to the FDA as IND Safety 
Reports per 21 CFR 312.32 as soon as possible but not exceeding 7 calendar days for unexpected 


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fatal or life-threatening events, and not exceeding 15 calendar days for other qualifying events. 
IND Safety Reports will also be provided to the IRB.  
The IND Sponsor will also submit an IND Annual Report of the progress of the investigation to 
the FDA as defined in 21 CFR 312.33. 
5.5. 
Reporting to the Institutional Review Board 
The following information is consistent with NIH IRB Policy 801: Reporting Research Events, 
Version 1, effective July 1, 2019.  
Reportable Event:  An event that occurs during the course of human subject research that 
requires notification to the IRB. 
For the purposes of this policy, reportable events include the following: 
• Unanticipated Problems (UPs) involving risks to subjects or others 
• Non-compliance (including major protocol deviations and noncompliance that is not 
related to a protocol deviation) 
• Deaths related or possibly related to research activities 
• New information that might affect the willingness of subjects to enroll or continue 
participation in the study 
5.5.1. 
Unanticipated Problem 
An Unanticipated Problem (UP) is defined as any incident, experience, or outcome that meets all 
the following criteria: 
• Unexpected (in terms of nature, severity, or frequency) given (a) the research procedures 
that are described in the protocol-related documents, such as the IRB approved research 
protocol and informed consent document; and (b) the characteristics of the subject 
population being studied; and 
• Related or possibly related to participation in the research (possibly related means there is 
a reasonable possibility that the incident, experience, or outcome may have been caused 
by the procedures involved in the research); and 
• Suggests that the research places subjects, or others (which may include research staff, 
family members or other individuals not directly participating in the research) at a greater 
risk of harm (including physical, psychological, economic, or social harm) related to the 
research than was previously known or expected. 
A UP must be reported within 7 calendar days of an investigator becoming aware of the actual or 
suspected UP. 
5.5.2. 
Non-Compliance  
Non-compliance is the failure of investigator(s) to follow the applicable laws, regulations, or 
institutional policies governing the protection of human subjects in research, or the requirements 
or determinations of the IRB, whether intentional or not.   


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Non-compliance may be unintentional (e.g. due to lack of understanding, knowledge, or 
commitment), or intentional (e.g. due to deliberate choice to ignore or compromise the 
requirements of any applicable regulation, organizational policy, or determination of the IRB). 
Non-compliance is further characterized as serious or continuing as follows: 
• Serious non-compliance – Non-compliance, whether intentional or not, that results in 
harm or otherwise materially compromises the rights, welfare and/or safety of the subject. 
Non-compliance that materially effects the scientific integrity or validity of the research 
may be considered serious non-compliance, even if it does not result in direct harm to 
research subjects. 
• Continuing non-compliance – A pattern of recurring non-compliance that either has 
resulted, or, if continued, may result in harm to subjects or otherwise materially 
compromise the rights, welfare and/or safety of subjects, affect the scientific integrity of 
the study or validity of the results.  The pattern may comprise repetition of the same non-
compliant action(s), or different noncompliant events.   
Any actual or suspected non-compliance by any investigator or entity associated with the 
protocol must be reported to the IRB by the PI/designee within 7 calendar days of any 
investigator or individual associated with the protocol first becoming aware. 
5.5.3. 
Protocol Deviation  
A Protocol Deviation (PD) is defined as any change, divergence, or departure from the IRB-
approved research protocol and are further characterized as major and minor as follows:  
• Major Deviations – Deviations from the IRB approved protocol that have, or may have the 
potential to, negatively impact, the rights, welfare or safety of the subject, or to 
substantially negatively impact the scientific integrity or validity of the study.  
• Minor Deviations – Deviations that do not have the potential to negatively impact the 
rights, safety, or welfare of subjects or others, or the scientific integrity or validity of the 
study.   
For the reporting purposes, failure of subjects to comply with the research protocol does not 
represent non-compliance unless that failure is due to an action or omission of a member of the 
research team, for example, the failure to give adequate instruction to the subject. 
A major deviation must be reported within 7 calendar days of an investigator becoming aware of 
an actual or suspected deviation.  Although PDs are also non-compliance, these should only be 
reported once as deviations.  Major deviations resulting in death must be reported within 24 
hours of the occurrence of the event or of any member of the study team becoming aware of the 
death.   
Researchers are responsible for monitoring their studies throughout the year for adherence to the 
IRB approved protocol.  The purpose of this monitoring is to identify major deviations and to 
look for trends in minor deviations that may indicate a systemic issue in how the study is being 
conducted that could potentially negatively impact the rights, safety, or welfare of participants or 
the study’s ability to produce scientifically valid results.  A series of minor deviations pointing 
toward a more global issue that could affect the rights, safety or welfare of the participant or 


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affect the validity of the study should be reported as a major deviation.  In all other instances, a 
summary of minor deviations should be provided to the IRB at the time of continuing review.   
5.5.4. 
Death 
Any death of a research subject that is possibly, probably or definitely related to the research 
must be reported within 24 hours of an investigator becoming aware of the death. 
5.5.5. 
New Information  
New information that might affect the willingness of a subject to enroll or remain in the study 
should be reported within 7 calendar days of an investigator first becoming aware.  
5.5.6. 
Suspension or Termination of Research Activities 
Any suspension or termination of research activities, including holds on new enrollment, placed 
upon the research by the study sponsor, NIH or IC leadership, or any regulatory agency must be 
reported within 7 calendar days of an investigator becoming aware. 
5.5.7. 
Expedited Reporting to the IRB 
Death related to research must be reported within 24 hours. 
The following will be reported within 7 calendar days of investigator awareness:  
• Actual or suspected UPs; 
• Actual or suspected non-compliance; 
• Actual or suspected Major PDs; 
• SAEs that are actual or suspected UPs; 
• New information that might affect the willingness of a subject to enroll or remain in the 
study; 
• Suspension or termination of research activities, including holds on new enrollment, 
placed upon the research by the study sponsor, NIH or IC leadership, or any regulatory 
agency. 
5.5.8. 
Annual Reporting to the IRB 
The following will be reported to the IRB in summary at the time of Continuing Review: 
• Summary of UPs and non-compliance; 
• AEs, including SAEs, that are not UPs, as a narrative summary statement indicating 
whether these events were within the expected range; 
• Minor PDs (aggregate summary); 
• Any trends or events which in the opinion of the investigator should be reported. 


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6. 
STATISTICAL CONSIDERATIONS 
6.1. 
Overview 
This study is a Phase 1, dose-escalation study in healthy adults to assess the safety, PK and 
protective efficacy of L9LS, an investigational human antimalarial mAb.   
6.2. 
Sample Size and Accrual 
Trial recruitment will target about 29 healthy adults, ages 18 to 50 years, as shown in Table 1.  
This includes 18 subjects that receive study product and then undergo CHMI and 6 controls who 
will only undergo the CHMI and do not receive study product and 5 subjects who will receive 
study product but not take part in the CHMI.  The permitted accrual is 40 subjects in total 
(inclusive of 2 subjects who will serve as back-ups to the control) to allow for additional 
enrollments to meet the minimum number of subject evaluations needed for a dose-escalation 
evaluation or CHMI per protocol criteria.  Dose escalation rules are described in Section 4.5.  
Specifically, if a subject enrolls into a study product group but does not receive a product 
administration or withdraws before the challenge for reasons that are not safety related, or a 
control group subject withdraws before the malaria challenge occurs, then additional subjects 
may be enrolled to achieve the accrual target.  Following a withdrawal from a study product 
group, additional enrollments may be made if there is sufficient time to complete product 
administration prior to the scheduled CHMI. 
The primary goal of this study is to identify safety concerns associated with L9LS at different 
doses.  Primary sample size considerations are expressed in terms of the ability to detect serious 
adverse experiences.  The ability of the study to identify SAEs will be expressed in terms of the 
probability of observing a certain number of serious adverse events.  With a sample size of n=5, 
there is over 90% chance to observe at least 1 SAE if the true rate is at least 0.370 and over 90% 
chance to observe no SAE if the true rate is no more than 0.020.  With a sample size of n=23, 
there is over 90% chance to observe at least 1 SAE if the true rate is no less than 0.096 and over 
90% chance of observing no SAE if the true rate is no more than 0.004.  Probabilities of 
observing 0 or more than 1 SAE within a group are presented in Table 2 for a range of possible 
true event rates.  
Table 2: 
Probability of Events for Different Safety Scenarios (n=5 or 23) 
True Event 
Rate 
n=5 
n=23 
Pr(0) 
Pr(>1) 
Pr(0) 
Pr(>1) 
0.005 
0.975 
0.000 
0.891 
0.006 
0.01 
0.951 
0.001 
0.794 
0.022 
0.02 
0.904 
0.004 
0.628 
0.077 
0.035 
0.837 
0.011 
0.441 
0.192 
0.05 
0.774 
0.023 
0.307 
0.321 
0.1 
0.590 
0.081 
0.089 
0.685 
0.15 
0.444 
0.165 
0.024 
0.88 
0.2 
0.328 
0.263 
0.006 
0.96 
0.3 
0.168 
0.472 
0.000 
0.997 
 


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Table 3 gives the upper and lower bounds for 95% exact binomial confidence intervals of the 
true SAE rate at possible numbers of events within a group.  Within a group size of n=5, if none 
experience an SAE, the 95% exact confidence interval has an upper bound of 0.522. With a 
group size of n=23, if 2 subjects experience an SAE, the exact 95% confidence interval has a 
lower and upper bound of 0.011 and 0.28, respectively. 
Table 3: 
95% Confidence Intervals for the True Rate at Possible Observed Number of 
Events (n=5 or n=23) 
Observed 
Number of 
Events 
95% Confidence Interval 
(n=5) 
95% Confidence Interval 
(n=23) 
Lower 
Bound 
Upper 
Bound 
Lower 
Bound 
Upper 
Bound 
0 
0.000 
0.522 
0.000 
0.148 
1 
0.005 
0.716 
0.001 
0.219 
2 
0.053 
0.853 
0.011 
0.28 
3 
0.147 
0.947 
0.028 
0.336 
4 
0.284 
0.995 
0.05 
0.388 
5 
0.478 
1.000 
0.075 
0.437 
6 
 
 
0.102 
0.484 
7 
 
 
0.132 
0.529 
8 
 
 
0.164 
0.573 
9 
 
 
0.197 
0.615 
 
6.3. 
Statistical Analysis  
Enrollment of L9LS recipients may occur on the same day as product administration at Visit 02 
(Day 0) or in advance of product administration at Visit 01R (Day -28 to Day 0), except in the 
case of controls.  All subjects who receive product administration will provide safety data.  
Three analysis cohorts are involved in the statistical analysis: 
• Intent-to-treat (ITT) - This cohort will include all enrolled subjects who receive product 
administration and will be analyzed according to the assigned group.   
• As-treated - This cohort will include all enrolled subjects who receive product administration 
and will be analyzed according to the actual dose they receive.  
• Modified intent-to-treat (mITT) – This cohort will include all enrolled subjects who 
participate in the CHMI challenge and will be analyzed according to the assigned group.   
All statistical analyses will be performed using SAS and R statistical software. 
6.3.1. 
Analysis Variables 
The analysis variables consist of baseline, safety parameters, PK, and presence or absence of 
malaria infection after CHMI.  Descriptive statistics will be used to summarize baseline 
characteristics, inclusive of demographics and safety laboratory measurements. 


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6.3.2. 
Safety Analysis 
Safety evaluation will be performed using the as-treated cohort.  The number and percentage of 
subjects with one or more AEs will be summarized by dose group along with the exact 95% 
confidence intervals of the AE rate.  For subjects experiencing more than one AE, they will be 
counted once under the event of highest severity.  In addition, a complete listing of AEs for each 
subject will provide details such as severity, duration, and relationship to study product.  
Summaries will be provided for any solicited or unsolicited AEs.  
a. Solicited Reactogenicity 
Solicited AE data will be collected after product administration.  The number and percentage of 
subjects experiencing each type of solicited sign or symptom will be tabulated by severity and by 
dose group and overall (i.e., pooled IV dose groups and pooled SC and IV dose groups).  
Subjects with multiple occurrences of the same event will be counted once using the event of 
highest severity.  
b. Adverse Events 
All reportable AEs will be recorded and coded by Medical Dictionary for Regulatory Activities 
(MedDRA) system organ class (SOC) and preferred term (PT).  The number and percentages of 
subjects with each unsolicited AE will be tabulated by severity and relationship to the study 
product, and by dose group and overall (i.e., pooled IV dose groups and pooled SC and IV dose 
groups).  Subjects with multiple occurrences of the same event will be counted once using the 
event of highest severity or strongest relationship to the study treatment.  
A by-subject listing of all unsolicited AEs will provide details including severity, relationship to 
treatment type, seriousness, new medical condition status, onset and end date, duration, and 
outcome.  
c. Local Laboratory Values 
Boxplots of local laboratory values will be generated for baseline values and for values measured 
during the course of the study.  Each boxplot will show the 1st quartile, the median, and the 3rd 
quartile.  Outliers, or values outside the boxplot, will also be plotted.  If appropriate, horizontal 
lines representing boundaries for abnormal values will be plotted. 
6.3.3. 
Pharmacokinetics Analysis  
PK analysis will be performed using the as-treated  cohort.  Blood samples for PK evaluations 
will be collected at defined time-points as listed in APPENDIX I.   
Individual Subject Pharmacokinetic Analysis:  A non-compartmental (NC) PK analysis will 
be performed using Phoenix 7.0 (CertaraR), PKPlus or a similar program on the L9LS 
concentration data generated from each subject.  Individual subject and dosing group 
concentration vs time profiles will be constructed in linear and semi-log scales.  In the NC 
analysis the maximum concentration (Cmax) and time of maximal concentration (Tmax) will be 
taken directly from the observed data.  The area under the concentrations vs. time curve (AUC) 
will be calculated using the trapezoidal method and determined out to the final concentration 
collected.  If a subjects L9LS concentration falls below the quantitative limit (QL) of the assay 
before the final of PK sample collection, the sample with concentration below the QL will be 
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initial concentration below the QL sample will be ignored in AUC calculations because partial 
AUC is not contributory to the total AUC.  In addition to calculation of the total AUC from 
Time=0 to the last L9LS concentration (AUC0-last), Time= 0 to the CHMI challenge (AUC0-CHMI) 
and Time of CHMI to 21 Days post CHMI (AUCCHMI-21DCHMI) will be determined.  The time 
weighted average concentrations (Cave) during these intervals will be calculated as the AUC 
divided by the AUC collection interval, e.g. CaveCHMI-21DCHMI = (AUCCMHI-21DCHMI) / 3weeks.  
The terminal slope, λz will be determined by regression of the terminal, log-linear portion of the 
concentration vs. time profile.  If the final PK sample has measurable L9LS concentrations 
greater than the assay QL, the AUC post final PK collection (AUClast-infinity) will be estimated as 
Clast/λz and AUC0-infinity will be calculated as sum AUC0-last + AUClast-infinity.  
Population Pharmacokinetic Analyses:  Population PK analyses will be performed on the PK 
data following IV and SC administration to determine compartmental PK parameters with the 
PK program NONMEM 7.3 or later (ICONR).  Based on preclinical PK results for L9LS and 
known PK behavior studies of mAbs, two-compartment model will be used (subroutine 
ADVAN4 TRANS4).  Both zero order and first order absorption following SC administration 
will be evaluated and a lag time included if a delay is seen in the raw data figures.  The First 
Order Conditional Estimation Method with Interaction (FOCEI) will be used.  The population 
analysis will generate estimates for clearance (CL) central and peripheral volumes of distribution 
(Vd1 and Vd2), inter-compartmental clearance (Q), CL and SC bioavailability (F).  Total volume 
of distribution at steady-state (Vdss), will be calculated as the sum of Vd1 + Vd2.  Alpha and beta 
half-lives will be calculated from CL, Q, Vd1 and Vd2 using standard equations [24].  While the 
number of subjects is expected to be sufficient to characterize the typical PK parameters and 
their between-subject variabilities (BSVs), the sample number is too small for a robust broad 
population PK covariate analysis. Therefore, the impact of subjects’ size will be accounted for 
using allometric scaling normalized to 70 kg with dose level and CHMI response being the only 
covariates explored.  Individual subjects’ empiric Bayesian PK parameter estimates will be 
generated using the posthoc subroutine and may be used to estimate individual participant L9LS 
concentration-time profiles.   
Final model selection will be based on changes in the objective function, a goodness-of-fit 
statistic generated by NONMEM, and graphically by goodness of fit plots. The final population 
PK model will be assessed using bootstrap analysis.  Dosing strategies and their ability to 
achieve and maintain target L9LS concentrations will be performed using the final population 
PK model and Monte Carlo simulations with at least 1000 replicates. 
6.3.4. 
Efficacy Analysis 
Efficacy analysis will be performed using the mITT cohort.  The primary efficacy analysis will 
be based on a two-sided Barnard test on the proportion of infected subjects who receive L9LS 
compared to the controls who undergo CHMI concurrently.  The secondary efficacy analyses 
will be based on time-to-parasitemia, where L9LS recipients will be compared with the control 
participants via a log-rank test.  Kaplan-Meier curves will also be provided for each group.  
To assess how L9LS concentration impacts protection against infection, a logistic regression 
may be performed to estimate the infection risk as a function of the L9LS concentration at the 
time of challenge.  For the same reason, a Cox proportional hazards regression may be 


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performed to estimate the hazard function with the L9LS concentration at the time of challenge 
and CaveCHMI-28DCHMI, as a regressor. 
In addition to the above efficacy analyses, descriptive statistics will be provided which include 
the proportion of infection post CHMI in each dose group and the control group.  To assess the 
comparability of challenge, salivary gland score (related to the quantity of sporozoites in each 
mosquito) will be listed for each participant and the summary statistics, such as the median and 
interquartile range of the salivary gland score, will be reported for each dose group as well as the 
control group.  
6.3.5. 
Interim Analyses 
PK data may be analyzed for each dose group.  Preliminary PK analyses may be performed per 
dose level prior to CHMI which may only generate a subset of the final PK parameters.   


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7. 
PHARMACY PROCEDURES 
The study groups are shown in Table 1. 
7.1. 
Study Product  
VRC-MALMAB0114-00-AB (L9LS) is a sterile, aqueous, buffered solution filled into single 
dose vials at 150 + 15 mg/mL in a formulation buffer composed of 10 mM Acetate Phosphate, 
10 mM Sodium Chloride, 250 mM Proline, 0.02% Polysorbate 80 at pH 5.6; and to a target fill 
volume of 2.25 ml in a 3 ml vial. The drug product container closure system consists of Type I 
glass vials, chlorobutyl rubber stoppers, and seals purchased from approved manufacturers.   
7.2. 
Storage and Temperature Excursions 
Filled product must be stored at -35°C to -15°C, in a qualified, continuously-monitored, 
temperature-controlled freezer.   
The site pharmacist must promptly report any storage temperature excursions outside of the 
normal allowance to the IND Sponsor.  The affected product must be quarantined in a separate 
area under protocol-specific temperature ranges until further notice from the Sponsor.  If the 
excursion results in thawed material, DO NOT REFREEZE; store the thawed, vialed material at 
2°C to 8°C.   
When a storage/shipping/handling excursion occurs, the IND Sponsor designee must send a 
notification of the occurrence of an excursion to VRCProductinquiries@nih.gov.  An automatic 
email reply will be sent to the notifier, including (as an attachment) the Clinical Excursion 
Reporting Form, which can be filled electronically (or manually and scanned, if needed). The 
completed form and relevant attachments (e.g. temperature charts) must be emailed to the VRC 
via the same email address (VRCProductinquiries@nih.gov) using the “reply” function.  The 
IND Sponsor will notify the site pharmacist if continued clinical use of the product is acceptable 
or will provide further instructions. 
7.3. 
Labeling of Study Product Vial 
Vials of study product 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. 
7.4. 
Preparation of Study Product for Administration 
This section describes how to prepare study injections and will be updated when information is 
available. For complete and detailed instructions for the preparation of the product please see 
Appendix III. 
7.4.1. 
Preparation for IV Administration  
For each IV infusion order, the subject’s weight, dose level, and study group code will be 
included in the pharmacy order.  To prepare an IV infusion, the pharmacist will: 1) calculate the 
total milligrams of L9LS needed, 2) retrieve the minimum number of thawed vials required to 
prepare the full dose, 3) withdraw the necessary amount of L9LS, and 4) add this volume to a 


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normal saline IV bag using sterile compounding techniques to maintain sterility.  Overfill may be 
added to the IV bag to ensure proper IV administration via a volumetric pump when the total 
volume to be administered is low (e.g. less than 50 mL). The ideal L9LS concentration in the 
final product to be infused is greater than 2 mg/mL in order to maintain appropriate formulation. 
Thaw and equilibrate vials for a minimum of 1 hour and 30 minutes at ambient temperature. If 
thawed vials are removed from 2°C to 8°C, equilibrate at ambient temperature for a minimum of 
30 minutes.  Prior to preparation for administration in the IV bag, vials should be gently swirled 
for approximately 30 seconds while avoiding foaming.  DO NOT SHAKE THE VIALS. 
An in-line filter infusion set must be used for IV product administrations and MUST comply 
with the following specifications: 1.2-micron PES (polyethersulfone) filter membrane, DEHP-
free, latex-free (equivalent to B.Braun #473994 filter extension set).  When the in-line filter is 
added to the tubing, the administration set must then be primed.   
The study product solution will typically be administered IV over about 15-30 minutes using a 
volumetric pump.  The total time needed to administer the dose may be longer than 30 minutes 
based on factors such as subject tolerance.  The mL/hr infusion rate may vary based on the total 
volume needed to administer a full dose.   
At the end of product administration, the IV administration set must be flushed with about 30 mL 
(or appropriate volume) of normal saline unless the IV bag was prepared with overfill.  
7.4.2. 
Preparation for SC or IM Administration  
For each SC or IM administration order, the subject’s weight, dose level, and study group code 
will be included in the pharmacy order.  To prepare a SC or IM administration dose, the 
pharmacist will calculate the total mg needed and retrieve the minimum number of vials needed 
to prepare the full dose.  Thaw and equilibrate vials for a minimum of 1 hour and 30 minutes at 
ambient temperature. If thawed vials are removed from 2°C to 8°C, equilibrate at ambient 
temperature for a minimum of 30 minutes.  Prior to preparation for administration, vials should 
be gently swirled for approximately 30 seconds while avoiding foaming.  DO NOT SHAKE 
THE VIALS.   
The needed volume of L9LS must be withdrawn from the vial into 1 to 4 syringes using a 5-
micron filter needle.  A new filter needle must be used for each syringe.  The filter needle must 
be discarded prior to dispensing and replaced with a needle suitable for SC or IM injection at the 
time of administration.  The product may be administered by direct SC or IM injection with 
needle and syringe.  The clinician will use proper SC or IM technique to ensure administration 
into SC fatty layer or the IM injection into muscle and a slow push to minimize discomfort or the 
excessive distention of overlying skin. 
7.4.3. 
Handling of Prepared Product for IV, SC, or IM Administration  
After product preparation in an IV bag, the prepared L9LS may be stored at 2°C to 8°C for a 
maximum of 24 hours and/or at ambient temperature for a maximum of 4 hours total including 
the infusion time.  Product may not be stored in direct sunlight.   
After preparation in syringes for SC or IM administration, the prepared L9LS may be stored at 
2°C to 8°C up to 24 hours and/or at ambient temperature up to 4 hours.  Product may not be 
stored in direct sunlight. 


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7.5. 
Study Product Accountability 
The study pharmacist or designee will be responsible for maintaining an accurate record of the 
study group codes, inventory, and an accountability record of study agent supplies.  Electronic 
documentation as well as paper copies may be used.  
7.6. 
Study Product Disposition 
The empty vials and the unused portion of a vial will be discarded in a biohazard containment 
bag and incinerated or autoclaved in accordance with the institutional or pharmacy policy.  Any 
unopened vials that remain at the end of the study will be returned to the production facility or 
discarded at the discretion of the sponsor in accordance with policies that apply to investigational 
agents.  Partially used vials will not be administered to other subjects or used for in vitro 
experimental studies.  These vials will be disposed of in accordance with institutional or 
pharmacy policy.  


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8. 
HUMAN SUBJECT PROTECTIONS AND ETHICAL 
OBLIGATIONS 
This research will be conducted in compliance with the protocol, International Conference on 
Harmonisation (ICH) Good Clinical Practice (GCP) guidelines and all applicable regulatory 
requirements. 
8.1. 
Institutional Review Board 
The protocol, proposed informed consent form, other written subject information, and any 
proposed advertising material will be submitted to the IRB for review and written approval. 
The investigator must submit and, where necessary, obtain approval from the IRB for all 
subsequent protocol amendments and changes to the informed consent document.  The 
investigator will notify the IRB of research events that occur on study as described in Section 
5.5. 
The investigator will be responsible for obtaining IRB approval of the annual Continuing Review 
throughout the duration of the study. 
8.2. 
Informed Consent 
The study informed consent form (ICF) is provided as a separate hard copy and describes the 
investigational product to be used and all aspects involved in protocol participation. 
The PI or designee is responsible for obtaining written informed consent from the subject after 
adequate explanation of the aims, methods, anticipated risks and benefits of the study and before 
any protocol-specific procedures or study product is administered.  The AoU will be completed 
before the study ICF is signed. 
The acquisition of informed consent will be documented in the subject’s medical records, as 
required by 21 CFR 312.62, and the ICF will be signed and personally dated by the subject and 
the person who conducted the informed consent discussion.  The signed ICF will be retained in 
the medical chart and a copy of the ICF will be provided to the subject. 
During the consent process, participants and investigators will view the same approved consent 
document simultaneously in their respective locations.   
8.3. 
Study Discontinuation and Closure 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause.  Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to study participants, the 
investigators, the Investigational New Drug (IND) and regulatory authorities as appropriate.  If 
the study is prematurely terminated or suspended, the Principal Investigator (PI) will promptly 
inform study participants, the Institutional Review Board (IRB), and Sponsor and will provide 
the reason(s) for the termination or suspension.  Study participants will be contacted, as 
applicable, and be informed of changes to study visit schedule. 
 Circumstances that may warrant termination or suspension include, but are not limited to: 
• Determination of unexpected, significant, or unacceptable risk to participants 


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• Demonstration of efficacy that would warrant stopping    
• Insufficient compliance to protocol requirements 
• Data that are not sufficiently complete and/or evaluable 
• Determination that the primary endpoint has been met 
• Determination of futility 
The study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the Sponsor, IRB and/or FDA. 
8.4. 
Confidentiality and Privacy 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, 
their staff, and the Sponsor(s) and their interventions.  This confidentiality is extended to cover 
testing of biological samples in addition to the clinical information relating to participants.  
Therefore, the study protocol, documentation, data, and all other information generated will be 
held in strict confidence.  No information concerning the study or the data will be released to any 
unauthorized third-party without prior written approval of the sponsor.  
All research activities will be conducted in as private a setting as possible. 
The study monitor, other authorized representatives of the Sponsor, representatives of the 
Institutional Review Board (IRB), and/or regulatory agencies may inspect all documents and 
records required to be maintained by the investigator, including but not limited to, medical 
records (office, clinic, or hospital) and pharmacy records for the participants in this study.  The 
clinical study site will permit access to such records. 
The study participant’s contact information will be securely stored at the clinical site for internal 
use during the study.  At the end of the study, all records will continue to be kept in a secure 
location for as long a period as dictated by the reviewing IRB, Institutional policies, or Sponsor 
requirements. 
Study participant research data, which is for purposes of statistical analysis and scientific 
reporting, will be transmitted to and stored by Emmes, the Data Coordinating Center.  This will 
not include the participant’s contact or identifying information.  Rather, individual participants 
and their research data will be identified by a unique study identification number.  The study data 
entry and study management systems used by the clinical site and by Emmes research staff will 
be secured and password protected.  At the end of the study, all study databases will be de-
identified and archived. 
To further protect the privacy of study participants, a Certificate of Confidentiality has been 
issued by the National Institutes of Health (NIH).  This certificate protects identifiable research 
information from forced disclosure.  It allows the investigator and others who have access to 
research records to refuse to disclose identifying information on research participation in any 
civil, criminal, administrative, legislative, or other proceeding, whether at the federal, state, or 
local level.  By protecting researchers and institutions from being compelled to disclose 
information that would identify research participants, Certificates of Confidentiality help achieve 
the research objectives and promote participation in studies by helping assure confidentiality and 
privacy to participants. 


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8.5. 
Risk/Benefit Assessment  
8.5.1. 
Potential Risks 
Risk of L9LS: The risk of L9LS is not yet known as this is the first in human study.  A similar 
malaria antibody, CIS43LS, was evaluated as safe and well-tolerated in the VRC 612 study[7]. 
Investigational monoclonal antibody, L9LS, exhibited scattered membrane binding which 
localized to the epithelial cells lining the human salivary gland ducts and acini in a preclinical 
tissue cross-reactivity study. Binding was rare at an antibody concentration of 1.15 µg/ml, and 
rare to occasional at 11.5 µg/ml. These findings are of unclear clinical significance. Any effect 
on the salivary glands from L9LS, if present, is expected to be transient due to clearance of the 
passively transferred antibody over time. Additionally, salivary gland epithelium turns over 
rapidly which would likewise be expected to decrease any potential complications.  
To address these findings, the trial will exclude individuals at an increased risk for salivary gland 
dysfunction and will prospectively monitor for signs and symptoms that may be indicative of 
salivary gland abnormality.  Subject matter experts in salivary gland disorders at the National 
Institute of Dental and Craniofacial Research, who are board-certified by the American Board of 
Oral and Maxillofacial Pathology, have assisted the study team in developing a risk mitigation 
strategy and have agreed to participate in eligibility or adverse event evaluations as needed by 
the study team. Evidence of clinically significant salivary gland toxicity will be considered at 
each dose escalation review and dose escalation would not proceed if clinical toxicity is 
identified.  
Risks of mAb Administration:  Administration of mAbs may cause immune reactions such as 
acute anaphylaxis, serum sickness and the generation of antibodies.  However, these reactions 
are rare and more often associated with mAbs targeted to human proteins or with the use of 
mouse mAbs that would have a risk of human anti-mouse antibodies [25].  In this regard, 
because L9LS is targeted to a malaria parasite antigen and is a human mAb, it is expected to 
have a low risk of such side effects.  
Typically, the side effects of mAbs are mild to moderate and may include local reactions at the 
injection site (including pain, redness, bruising, swelling) and systemic reactions such as fever, 
chills, rigors, nausea, vomiting, pain, headache, dizziness, shortness of breath, bronchospasm, 
hypotension, hypertension, pruritus, rash, urticaria, angioedema, diarrhea, tachycardia or chest 
pain.  Clinical use of mAbs that are targeted to cytokines or antigens associated with human cells 
may be associated with an increased risk of infections [25]; however, this is not expected to be a 
risk for a mAb targeted to a parasite antigen.  
Severe reactions, such as anaphylaxis, angioedema, bronchospasm, hypotension and hypoxia, are 
infrequent and more often associated with mAbs targeted to human proteins or with non-human 
mAb, such as a mouse mAb [25].  Most infusion-related events occur within the first 24 hours 
after initiation of mAb administration. 
Published experience with human mAbs directed against cell surface targets on lymphocytes 
shows that infusion of a mAb may be associated with cytokine release, causing a reaction known 
as cytokine release syndrome (CRS) [26].  CRS reactions commonly occur within the first few 
hours of infusion start and with the first mAb infusion received.  This is because the cytokine 
release is associated with lysis of the cells targeted by the mAb and the burden of target cells is 


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greatest at the time of the first mAb treatment.  With licensed therapeutic mAbs, CRS is 
managed by temporarily stopping the infusion, administering histamine blockers and restarting 
the infusion at a slower rate [27].  Supportive treatment may also be indicated for some signs and 
symptoms.   
Delayed allergic reactions that include a serum sickness type of reaction characterized by 
urticaria, fever, lymph node enlargement, and joint pains, typically occur several days after mAb 
exposure and are more commonly associated with chimeric types of mAbs [25].  In general, and 
with due consideration of the needs dictated by individual subject symptoms and treating 
clinician discretion, immediate and delayed reactions to study product would be managed 
according to the principles of the American Academy of Allergy, Asthma, and Immunology 
guidelines established in the Drug Allergy: Practice Parameters (2010).  
Participation in this study may limit a subject’s eligibility for future mAb studies.  
Risks of Blood Drawing:  Blood drawing may cause pain, bruising, and a feeling of 
lightheadedness or fainting. Rarely, it may cause infection at the site where blood is taken. In this 
study, an IV line that can be used for blood collection may be placed in the arm and left in place 
for several hours on days when there is product administration for frequent PK blood draws.  
Problems from use of an IV for blood drawing are generally mild and may include pain, bruising, 
minor swelling or bleeding at the IV site and rarely, infection, vein irritation (phlebitis), or blood 
clot. 
Risks of Mosquito Bites for CHMI:  Risks associated with CHMI include local inflammatory 
reactions, lymphadenitis, persistent local pruritus and larger local reactions involving the whole 
forearm, allergic reactions to mosquito bites.  Another remotely possible risk includes a systemic 
allergic reaction to the mosquitoes. 
Risks of Acquiring Malaria Infection:  There is also the possibility of complications of 
malaria, which are seen during naturally acquired malaria when diagnosis and treatment are 
delayed and high levels of parasitemia develop.  Under the carefully controlled conditions of this 
study that supports early diagnosis and treatment, the chance of such complications is unlikely 
and the risk of death from malaria infection is very small.  Transient abnormalities, e.g. fever, 
headache, myalgia, shaking chills, abdominal discomfort, nausea, vomiting, mild anemia, 
leukopenia, thrombocytopenia, hepatosplenomegaly, hepatic tenderness and fatigue, are expected 
consequences of malaria.  In uncontrolled circumstances, malaria infections can lead to kidney, 
liver or brain injury (seizures, coma) and death.  
Risks of Antimalarial Medication:  Additional risks include possible side effects of the 
antimalarial medication taken (chloroquine) following challenge with chloroquine-sensitive Pf. 
These side effects include nausea, vomiting, diarrhea, abdominal pain, dizziness, headaches, 
sleep disturbances, blurred vision, pruritus, skin rash, exacerbation of psoriasis or porphyria, 
tinnitus, and photosensitivity.  Rarely, there may be changes in electrocardiograms and 
hypotension.  Side effects of atovaquone/proguanil (Malarone®) include nausea, vomiting, 
abdominal pain, anorexia, diarrhea, headache, cough and rarely, anemia, oral ulcerations, 
insomnia, fever, edema, rash and alopecia.  Another remotely possible risk includes a systemic 
allergic reaction to chloroquine (or Malarone®).  The study team will discuss these medications 
and their possible side effects in detail both as part of the informed consent process, prior to 
CHMI, and prior to initiation of treatment for diagnosed malaria infections. 


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Risks of Screening Procedures: The risks of screening procedures can be found in the VRC-
sponsored screening protocol VRC 500 (NIH 11-I-0164, NCT01375530) used for all VRC IND 
studies conducted at the NIH Clinical Center. 
8.5.2. 
Potential Benefits 
Study subjects will not receive direct health benefit from study participation.  Others may benefit 
from knowledge gained in this study that may aid in the development of malaria prevention. 
8.5.3. 
Assessment of Potential Risks and Benefits 
This research study will be conducted in compliance with the protocol, GCP guidance, and all 
applicable regulatory requirements.   
The plan for reduction of known and unknown risks to participants includes appropriate training 
of study personnel; education of study subjects for participation in care throughout the study; 
monitoring of study subject’s health status and experiences; withdrawal from study procedures 
upon evidence of difficulty, contraindication, or a significant adverse event; and referral for 
treatment, counseling or other necessary follow-up.  The VRC CTP Risk Management Plan 
guides the reduction and mitigation strategies applied to the known and unknown risks 
associated with study participation and trial management/operations.  
As study subjects will not receive direct health benefit from study participation or product 
administration, no alternative procedures are planned. The alternative course of action is to 
choose not to participate. 
8.6. 
Plan for Use and Storage of Biological Samples 
The plan for use and storage of biological samples from this protocol is outlined in the following 
sections. 
8.6.1. 
Use of Samples, Specimens and Data 
Samples, specimens and data collected under this protocol may be used to conduct protocol-
related safety, parasitology and immunogenicity evaluations, exploratory laboratory evaluations 
related to malaria, exploratory laboratory evaluations related to mAb, vaccine or infectious 
disease research in general and for research assay validation.   
Stored samples may also be used later for exploratory genetic factors that may influence the 
immune response. No specific results will be provided to participants or their health care 
providers because we will not be investigating genetic analyses that have known medical 
diagnoses (e.g. Huntington’s disease) or other medically actionable genetic information. 
8.6.2. 
Storage and Tracking of Blood Samples and Other Specimens  
All research samples use coded labels that only the VRC VEC can link to the subject. Samples 
are stored at VIP or VRC laboratories in Building 40, Bethesda, MD, which are both secure 
facilities with limited access.  Data will be kept in password-protected computers.  Only 
investigators or their designees will have access to the samples and data.  Samples will be 
tracked in the Laboratory Information Management System (LIMS) database or using another 
software designed for this purpose (e.g., Freezerworks). 


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8.6.3. 
Disposition of Samples, Specimens and Data at Completion of the Protocol  
In the future, other investigators (both at NIH and outside) may wish to study these samples 
and/or data.  IRB approval must be sought prior to any sharing of samples with non-NIH 
investigators and any clinical information shared about those samples would similarly require 
prior IRB approval.  The research use of stored, unlinked or unidentified samples will be exempt 
from the need for prospective IRB review and approval.  Exemption requests will be submitted 
in writing to the NIH Office of Human Subjects Research, which is authorized to determine 
whether a research activity is exempt.  
At the time of protocol termination, samples will remain in the VIP facility or VRC laboratories 
or, after IRB approval, will be transferred to another repository.  Regulatory oversight of the 
stored samples and data may be transferred to a stored samples protocol as part of the IRB 
approved termination plan.  Data will be archived by the VRC in compliance with requirements 
for retention of research records, or after IRB and study sponsor approval, it may be either 
destroyed or transferred to another repository. 
8.6.4. 
Loss or Destruction of Samples, Specimens or Data   
Any loss or unanticipated destruction of samples (for example, due to freezer malfunction) or 
data (for example, misplacing a printout of data with identifiers) will be reported to the IRB.  
The Protocol Chair or PI will also notify the IRB if the decision is made to destroy the remaining 
samples. 
Neither participation nor refusal to participate will have an effect, either beneficial or adverse, on 
the participant’s employment or work situation.  The NIH information sheet regarding NIH 
employee research participation will be distributed to all potential subjects who are NIH 
employees.  The employee subject’s privacy and confidentiality will be preserved in accordance 
with applicable policies at the study site.  For any employee subjects, consent will be obtained by 
an individual who is independent of the employee’s team.  At NIH, if the individual obtaining 
consent is a co-worker to the subject, independent monitoring of the consent process will be 
included through the Bioethics Consultation Service.  Protocol study staff will be trained on 
obtaining potentially sensitive and private information from co-workers or subordinates.  
8.7. 
Safety Oversight 
Close cooperation between the designated members of the Protocol Team will occur to evaluate 
and respond to individual AEs in a timely manner.  The VRC clinic designated Safety Officer 
(SO) for the day conducts a daily safety review of clinical data per VRC Standard Operating 
Procedures. A Protocol Safety Review Team (PSRT) comprised of the Principal Investigator 
(PI), Associate Investigators, Study Coordinator, Protocol Specialists, other study clinicians, and 
the IND MO, will review the summary study safety data reports per the protocol-defined 
frequency. In addition, an Independent Safety Monitor (ISM), who is not associated with the 
VRC will provide safety oversight. 
The designated ISM will receive safety reports that contains a line listing of all adverse events 
that occurred to date. The ISM will meet with the PSRT during the weekly protocol safety 
meeting to clarify, discuss, and provide an impression of the safety data acquired to date. 
Meetings and safety report distribution will transition to a monthly schedule beginning 4 weeks 
after the last product administration to the final subject. Weekly safety meetings will resume for 


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4 weeks after CHMI. All adverse events, including those that are expected, will be contained in 
the weekly safety reports and will be available for independent review by the ISM. The overall 
findings and recommendations that result from the safety meetings will be documented in a 
protocol interim safety review form that will document adverse events that have occurred, 
including specifically any that may trigger pause criteria, serious adverse events, and comments 
from the group related to the adverse events. Attendance by the PI or designee, Medical Officer 
and/or ISM is documented on the form and officially signed by the PI or designee.  The signed 
interim safety review form will be sent to the ISM and the PSRT so that all are aware of any 
emerging safety signals even if unable to attend a PSRT meeting. 


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9. 
ADMINISTRATIVE AND OPERATIONAL OBLIGATIONS 
9.1. 
Protocol Amendments and Study Termination 
Protocol amendments must be made only with prior approval of the IND Sponsor and with 
agreement from the PI and MO.  All study amendments will be submitted to the IRB for 
approval. 
The IND Sponsor, the IRB, OHRP, the PI, Protocol Chairs, and/or the FDA reserve the right to 
terminate the study.  The PI will notify the IRB in writing of the study’s completion or early 
termination. 
9.2. 
Study Documentation and Storage 
The PI will delegate the study responsibilities to the study team, and a list of appropriately 
qualified persons to whom trial duties have been delegated will be maintained. 
Source documents are original documents, data, and records from which the subject’s data are 
obtained.  These include but are not limited to hospital records, clinical and office charts, 
laboratory and pharmacy records, and correspondence.  Long-term storage of source documents 
may be in the form of electronic files. 
The PI and staff are responsible for maintaining a comprehensive and centralized filing system of 
all study-related (essential) documentation, suitable for inspection at any time by representatives 
from the IND Sponsor, VRC/NIAID/NIH, IRB, NIH, FDA, and/or applicable regulatory 
authorities.  Elements include: 
• Subject files containing completed informed consent forms, and supporting copies of 
source documentation. 
• Study files containing the protocol with all amendments, IBs, copies of all correspondence 
with the IRB. 
In addition, all original source documentation must be maintained and be readily available.  
All essential documentation should be retained by the institution for the same period of time 
required for medical records retention.  The FDA requires study records to be retained for up to 
two years after marketing approval (21 CFR 312.62).  If no marketing application is filed, or if 
the application is not approved, the records will be retained for two years after the investigation 
is discontinued and the FDA is notified.  The HHS protection of human subjects’ regulations 
require that institutions retain records of IRB/EC activities and documentation of informed 
consent of subjects for at least 3 years after study completion (45 CFR 46). 
No study document should be destroyed without prior written agreement between the VRC and 
the investigator.  Should the investigator wish to assign the study records to another party or 
move them to another location, they must notify the VRC in writing of the new responsible 
person and/or the new location. 
9.3. 
Clinical Monitoring  
Clinical site monitoring is conducted to ensure that the rights and well-being of trial participants 
are protected, that the reported trial data are accurate, complete, and verifiable, and that the 


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conduct of the trial is in compliance with the currently approved protocol/amendment(s), with 
ICH GCP, and with applicable regulatory requirement(s).  
Monitoring for this study will be performed by a designated contract research organization 
(CRO). Details of clinical site monitoring are documented in a Clinical Monitoring Plan.  The 
Clinical Monitoring Plan describes in detail who will conduct the monitoring, at what frequency 
monitoring will be done, at what level of detail monitoring will be performed, and the 
distribution of monitoring reports. 
9.4. 
Data Collection and Sharing 
9.4.1. 
Data Collection 
Clinical research data will be collected in a secure electronic web-based clinical data 
management system (CDMS) through a CRO, Emmes (Rockville, MD). Extracted, anonymized 
data will be sent to the PSRT for safety review and to the Protocol Statistician for statistical 
analysis. 
9.4.2. 
Source Documents  
The site will maintain appropriate medical and research records for this trial, in compliance with 
ICH E6(R2) GCP, applicable regulations, and institutional requirements for the protection of 
confidentiality of subjects.  Source data are all information, original records of clinical findings, 
observations, or other activities in a clinical trial necessary for the reconstruction and evaluation 
of the trial.  Examples of these original documents and data records include, but are not limited 
to, medical records, laboratory reports, pharmacy records and other research records maintained 
for the clinical trial. 
9.4.3. 
Data Sharing 
Data generated in this study will be shared as de-identified data in the government-funded public 
repository, www.clinicaltrials.gov.  Data may be shared prior to publication at approved public 
presentations or for collaborative development and will be shared at the time of publication or 
within one year of the primary completion date. 
9.5. 
Quality Assurance and Quality Control 
The clinical site will perform internal quality management of study conduct, data and biological 
specimen collection, documentation and completion.  The VEC’s Quality Management Plan will 
be used to perform quality management for this trial. 
Quality control (QC) procedures will be implemented beginning with the data entry system and 
data QC checks that will be run on the database will be generated.  Any missing data or data 
anomalies will be communicated to the site for clarification/resolution. 
The monitors will verify that the clinical trial is conducted, and data are generated, and 
biological specimens are collected, documented (recorded), and reported in compliance with the 
protocol, ICH GCP, and applicable regulatory requirements. 


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The site will provide direct access to all trial related sites, source data/documents, and reports for 
the purpose of monitoring and auditing by the sponsor, and inspection by local and regulatory 
authorities. 
9.6. 
Language 
All written information and other material to be used by subjects and investigative staff must use 
vocabulary and language that are clearly understood.  
9.7. 
Research-Related Injuries 
9.7.1. 
NIH 
The NIH Clinical Center will provide short-term medical care for any injury resulting from 
participation in research here. In general, no long-term medical care or financial compensation 
for research-related injuries will be provided by the NIH, the NIH Clinical Center, or the Federal 
Government. However, subjects have the right to pursue legal remedy if they believe that their 
injury justifies such action. 
9.7.2. 
WRAIR  
If subjects are injured because of participation in this research during the CHMI and they are a 
DOD healthcare beneficiary (e.g., active duty in the military, military spouse or dependent, 
retiree), they are entitled to medical care for their injury within the DOD healthcare system, as 
long as they remain a DOD healthcare beneficiary.  
If subjects are injured because of participation in this research during the CHMI and they are not 
a DOD healthcare beneficiary, they are entitled to medical care for their injury at a DOD hospital 
or clinic, but such care for the injury at DOD hospitals or clinics may be time-limited, and the 
subject’s insurance may be billed. It cannot be determined in advance which DOD hospital or 
clinic will provide care. If subjects obtain care for research-related injuries outside of a DOD 
hospital or clinic, they or their insurance will be responsible for medical expenses.  
For DOD healthcare beneficiaries and non-DOD healthcare beneficiaries: Transportation to and 
from hospitals or clinics will not be provided. No reimbursement is available if subjects incur 
medical expenses to treat research-related injuries. No compensation is available for research-
related injuries. Subjects are not waiving any legal rights. If subjects believe they have sustained 
a research-related injury, they may contact the PI. If subjects have any questions, they can 
contact the PI. 
9.8. 
WRAIR Facility and CHMI Management  
The VRC, NIAID, NIH is the coordinating center as well as the only clinical site for this 
protocol.  Dr. Richard Wu, VRC, NIAID, NIH, is the site PI overseeing the management and 
monitoring of the protocol conduct overall.  
Investigators from WRAIR, the facility that will be administering the CHMI, will have limited 
interaction with study subjects during the administration of the CHMI.  Certain immediate pre- 
and post-CHMI assessments of subjects will take place in the CHMI facility with some 


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participation by CHMI facility personnel and NIH staff. All other post-CHMI clinical visits for 
subjects will take place at the NIH clinical site. 
A Reliance Agreement will be established with the collaborating CHMI facility such that the 
NIH IRB is the IRB of Record for the conduct of the VRC 614 protocol.  Referring to Section 5 
of the VRC 614 protocol, any Serious Adverse Events, Unanticipated Problems or Protocol 
Deviation which are reportable to the NIH IRB which are in relation to the conduct of the CHMI 
will also be communicated to the collaborating CHMI facility within the same reporting period 
specified in the protocol.   
9.8.1. 
Roles and Responsibilities for the CHMI 
The PI will delegate responsibility for overseeing the administration of the CHMI at the 
collaborating CHMI facility (i.e., application of and assessment of the mosquito bites) to 
designated Associate Investigators from those facilities.  Follow-up and medical care of the study 
subjects after the CHMI is administered remains the responsibility of the site PI and the 
designated personnel at the clinical site.  
The Authorized Representative from the CHMI facility may review research records related to 
the CHMI conducted at their own facility.   
The roles and responsibilities for this collaborating institution and facility personnel for the 
conduct of CHMI as described above are delineated in the corresponding VRC 614 Study 
Personnel Page.   
9.8.2. 
WRAIR Protocol Review and Reporting Requirements 
Initial Protocol Review 
WRAIR will defer their IRB review to the NIH IRB once a reliance agreement is in place. 
WRAIR Human Subjects Protection Branch (HSPB) will still perform an administrative review 
of the protocol to ensure that the WRAIR reporting requirements are met.  WRAIR Commander 
Approval Authorization will be issued once the NIH IRB approval has been submitted to the 
WRAIR HSPB and the administrative WRAIR comments have been adequately addressed. 
Headquarters level review will be conducted as appropriate.  
Protocol Modifications/Amendments 
All amendments/modifications to the protocol and supporting documents (informed consent, 
recruitment materials, etc.) must be reviewed by the WRAIR HSPB and a WRAIR Commander 
Authorization Approval issued prior to WRAIR participation on the amended/modified protocol.  
Continuing Reviews and Closeout Report  
The WRAIR Point of Contact will be responsible for preparing and submitting continuing review 
reports as per UWS-HP-618.03 and a closeout report as per WRAIR Policy #30. The WRAIR 
HSPB will review and acknowledge the reports in order for WRAIR personnel to continue their 
participation on the study.  Once all study activities have been completed, to include data 
analysis, a closeout report will need to be submitted to the WRAIR HSPB to close the study.  


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The following reporting requirements apply: 
Unanticipated Problems Involving Risks to Subjects or Others  
Unanticipated problems, as defined in Section 5.5.1, should be promptly reported (48 hours) by 
telephone, email, or fax to the WRAIR HSPB.  A complete written report should follow the 
initial notification within 10 working days.  All unanticipated problems occurring within the 
reporting period should also be summarized in the continuing review reports submitted to the 
WRAIR HSPB (contact information is below at end of section).   
Serious Adverse Events  
All related SAEs and deaths, as defined in Section 5.2, should be reported to the WRAIR HSPB 
within 48 hours by telephone, email, or fax.  A complete written report should follow the initial 
notification within 10 working days.  All SAEs occurring within the reporting period should also 
be summarized in the continuing review reports submitted to the WRAIR HSPB.   
Protocol Deviations  
All major protocol deviations that adversely affect the safety or rights of a subject or scientific 
integrity of the study, as defined in Section 5.5.3, will be reported to the WRAIR HSPB within 
48 hours and a written report should be submitted within 10 working days.  All protocol 
deviations occurring within the reporting period should be summarized in the continuing review 
reports that are submitted to the WRAIR HSPB.  
Pending Inspections/Issuance of Reports  
The knowledge of any pending compliance inspection/visit by the FDA, Office for Human 
Research Protections (Department of Health and Human Services), or other government agency 
concerning clinical investigation or research, the issuance of Inspection Reports, FDA Form 483, 
warning letters, or actions taken by any regulatory agency including legal or medical actions and 
any instances of serious or continuing noncompliance with the regulations or requirements will 
be reported immediately to the WRAIR HSPB. 
WRAIR HSPB Contact Information  
Director, Human Subjects Protection Branch  
 
503 Robert Grant Avenue  
Silver Spring, MD 20910  
Telephone: 301-319-9940 Fax: 301-319-9961  
E-mail: usarmy.detrick.medcom-wrair.mbx.hspb@mail.mil  
 


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10. 
REFERENCES  
 
1. 
Sachs, J. and P. Malaney, The economic and social burden of malaria. Nature, 2002. 
415(6872): p. 680-5. 
2. 
Roll Back Malaria. Global Malaria Action Plan 2008 2008; Available from: 
http://www.rbm.who.int/keyfacts.html. 
3. 
Breman, J.G., Eradicating malaria. Sci Prog, 2009. 92(Pt 1): p. 1-38. 
4. 
Rts, S.C.T.P., Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a 
booster dose in infants and children in Africa: final results of a phase 3, individually 
randomised, controlled trial. Lancet, 2015. 386(9988): p. 31-45. 
5. 
Mahmoudi, S. and H. Keshavarz, Efficacy of phase 3 trial of RTS, S/AS01 malaria 
vaccine: The need for an alternative development plan. Hum Vaccin Immunother, 2017. 
13(9): p. 2098-2101. 
6. 
Wang, L.T., et al., A Potent Anti-Malarial Human Monoclonal Antibody Targets 
Circumsporozoite Protein Minor Repeats and Neutralizes Sporozoites in the Liver. 
Immunity, 2020. 53(4): p. 733-744 e8. 
7. 
Gaudinski, M.R., et al., A Monoclonal Antibody for Malaria Prevention. New England 
Journal of Medicine, 2021. 385(9): p. 803-814. 
8. 
Gaudinski, M.R., et al., Safety and pharmacokinetics of the Fc-modified HIV-1 human 
monoclonal antibody VRC01LS: A Phase 1 open-label clinical trial in healthy adults. 
PLoS Med, 2018. 15(1): p. e1002493. 
9. 
Ledgerwood, J.E., et al., Safety, pharmacokinetics and neutralization of the broadly 
neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults. Clin Exp 
Immunol, 2015. 182(3): p. 289-301. 
10. 
Gaudinski, M.R., et al., Safety, tolerability, pharmacokinetics, and immunogenicity of the 
therapeutic monoclonal antibody mAb114 targeting Ebola virus glycoprotein (VRC 608): 
an open-label phase 1 study. Lancet, 2019. 393(10174): p. 889-898. 
11. 
Gaudinski, M.R., et al., Safety and pharmacokinetics of broadly neutralising human 
monoclonal antibody VRC07-523LS in healthy adults: a phase 1 dose-escalation clinical 
trial. Lancet HIV, 2019. 6(10): p. e667-e679. 
12. 
Chulay, J.D., et al., Malaria transmitted to humans by mosquitoes infected from cultured 
Plasmodium falciparum. Am J Trop Med Hyg, 1986. 35(1): p. 66-8. 
13. 
Seder, R.A., et al., Protection against malaria by intravenous immunization with a 
nonreplicating sporozoite vaccine. Science, 2013. 341(6152): p. 1359-65. 
14. 
Lyke, K.E., et al., Attenuated PfSPZ Vaccine induces strain-transcending T cells and 
durable protection against heterologous controlled human malaria infection. Proc Natl 
Acad Sci U S A, 2017. 114(10): p. 2711-2716. 
15. 
Roestenberg, M., et al., Experimental infection of human volunteers. Lancet Infect Dis, 
2018. 18(10): p. e312-e322. 
16. 
Nieman, A.E., et al., Cardiac complication after experimental human malaria infection: 
a case report. Malar J, 2009. 8: p. 277. 
17. 
Moorthy, V.S., et al., Report of a consultation on the optimization of clinical challenge 
trials for evaluation of candidate blood stage malaria vaccines, 18-19 March 2009, 
Bethesda, MD, USA. Vaccine, 2009. 27(42): p. 5719-25. 
18. 
van Meer, M.P., et al., Idiopathic acute myocarditis during treatment for controlled 
human malaria infection: a case report. Malar J, 2014. 13: p. 38. 


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19. 
Deye, G.A., et al., Prolonged protection provided by a single dose of atovaquone-
proguanil for the chemoprophylaxis of Plasmodium falciparum malaria in a human 
challenge model. Clin Infect Dis, 2012. 54(2): p. 232-9. 
20. 
Stanisic, D.I., et al., Development of cultured Plasmodium falciparum blood-stage 
malaria cell banks for early phase in vivo clinical trial assessment of anti-malaria drugs 
and vaccines. Malar J, 2015. 14: p. 143. 
21. 
Mejia, R., et al., Peripheral blood stem cell transplant-related Plasmodium falciparum 
infection in a patient with sickle cell disease. Transfusion, 2012. 52(12): p. 2677-82. 
22. 
Shokoples, S.E., et al., Multiplexed real-time PCR assay for discrimination of 
Plasmodium species with improved sensitivity for mixed infections. J Clin Microbiol, 
2009. 47(4): p. 975-80. 
23. 
Gaziano, T.A., et al., Laboratory-based versus non-laboratory-based method for 
assessment of cardiovascular disease risk: the NHANES I Follow-up Study cohort. 
Lancet, 2008. 371(9616): p. 923-31. 
24. 
Ammon, H., Drugs and the Pharmaceutical Sciences, Vol. 1: PHARMACOKINETICS, 
von M. Gibaldi und D. Perrier, 360 S., Preis $. 19,50, Marcel Dekker Verlag, New York 
1975. Archiv der Pharmazie, 1976. 309. 
25. 
Hansel, T.T., et al., The safety and side effects of monoclonal antibodies. Nat Rev Drug 
Discov, 2010. 9(4): p. 325-38. 
26. 
Bugelski, P.J., et al., Monoclonal antibody-induced cytokine-release syndrome. Expert 
Rev Clin Immunol, 2009. 5(5): p. 499-521. 
27. 
Vogel, W.H., Infusion reactions: diagnosis, assessment, and management. Clin J Oncol 
Nurs, 2010. 14(2): p. E10-21. 


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APPENDIX I: SCHEDULE OF EVALUATIONS 
 
 
 
 


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Schedule of Evaluations: IV Groups (Groups 1, 2, 4) 
Visit Number 
01 
1 01R 
1 02 
02A 
02B 
02C 
02D 
03 
04 
06 
07 
08 
09 
10 
11 
12 
13 
14 
Time After Infusion 
 
 
Pre 
EOI 
1hr 
3h 
6h 
24hr 
48hr 
Wk1 Wk2 Wk3 Wk4 Wk8 Wk12 Wk16 Wk20 Wk24 
Day of Study -56 to -1 -28 to 0 
D0 
D0 
D0 
D0 
D0 
D1 
D2 
D7 
D14 
D21 
D28 
D56 
D84 D112 D140 D168 
Study Procedures 
Tube 
Screen 
Enroll 
Day of infusion 
 
 
 
 
 
 
 
 
 
 
 
VRC 500 Screening Consent 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
VRC 614 Informed Consent, AoU 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 Physical Exam 
 
X 
X 
X 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
3 Medical History  
 
X 
X 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
EKG 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medications 
 
X 
X 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Product Administration 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Begin 7-day Diary Card 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4 Pregnancy Prevention Counseling 
 
X 
X 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
Clinical Evaluations 
4 Pregnancy Test (urine or serum) 
 
X 
X 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
CBC with differential 
EDTA 
3 
 
3 
 
 
 
 
3 
 
3 
3 
 
3 
 
3 
 
 
 
ALT, creatinine 
GLT 
X 
 
X 
 
 
 
 
4 
 
4 
4 
 
4 
 
4 
 
 
 
5 CMP 
GLT 
4 
 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV Ag/Ab Combo 
EDTA 
3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sickle Cell Test 
EDTA 
3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Parasitemia Evaluation (PCR) 
EDTA 
3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Research Samples 
6 PK  
SST 
 
 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
PBMC 
EDTA 
20 
 
 
 
 
 
 
 
 
 
40 
 
 
 
 
 
 
 
Serum 
SST 
8 
 
16† 
 
 
 
 
 
8 
8† 
8 
8 
8† 
8 
8† 
8 
8 
8† 
Daily Volume (mL) 
 
44 
0 
27 
4 
4 
4 
4 
11 
12 
19 
59 
12 
19 
12 
19 
12 
12 
12 
Cumulative Volume (mL) 
 
44 
44 
71 
75 
79 
83 
87 
98 
110 
129 
188 
200 
219 
231 
250 
262 
274 
286 
Visit windows:  Schedule Visits 02A–14 with respect to Visit 02.  Visit 02A (within 10 min of EOI); Visits 02B, 02C (±10 min); Visit 02D (-2 hrs); Visits 03, 04 
(±6 hrs); Visits 06, 07, 08, 09 (±2 days); Visits 10, 11, 12, 13, 14 (±7 days). Visit 05 is not applicable to this schedule. 
Footnotes (continue to next page): 
1 Visit 01R is the day of enrollment and may be done on the same day as Day 0. V02/Day 0 is day of product administration and preferably scheduled 
within 14 days after enrollment at Visit 01R but may be scheduled up to 28 days after Visit 01R.  
2 Screening includes physical exam, vital signs (blood pressure (BP), temperature, pulse, respiratory rate (RR)), height, weight.  Day 0 includes vital signs 
and weight (for ordering study product dose).  At other visits, perform a targeted exam if medically indicated, otherwise only vital signs are required. 
3 Perform full medical history at screening.  At other visits, perform interim medical history  


L9LS in Healthy Adults 
 
VRC 614, Version 2.0 
                      
October 13, 2021 
Page 59 of 73 
4 Pregnancy test results must be negative for women of reproductive potential before product administration. Complete Pregnancy Prevention Counseling 
Form when pregnancy test is done.  
5 CMP includes sodium, potassium, chloride, total CO2, creatinine, glucose, urea nitrogen, albumin, alanine aminotransferase, alkaline phosphatase, 
aspartate aminotransferase, total bilirubin, calcium, total protein 
6 PK blood draws, defined by time after an infusion, are relative to the exact time of the end of infusion (EOI).  Record the exact start / end times of product 
administration and of blood draw to ensure accurate PK analysis.   
† Anti-drug antibodies (ADA) assessed from serum samples at timepoints as indicated. 


L9LS in Healthy Adults 
 
VRC 614, Version 2.0 
                      
October 13, 2021 
Page 60 of 73 
Schedule of Evaluations: SC Group (Group 3) 
Visit Number 
01 
1 01R 
1 02 
02A 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
Time after Infusion 
 
 
Pre 
EOI 
24hr 
48hr 
72hr 
Wk1 
Wk2 
Wk3 
Wk4 
Wk8 
Wk12 Wk16 Wk20 Wk24 
Study Day 
-56 to -1 -28 to 0 
D0 
D0 
D1 
D2 
D3 
D7 
D14 
D21 
D28 
D56 
D84 
D112 
D140 
D168 
Study Procedures 
Tube 
Screen 
Enroll Day of injection 
 
 
 
 
 
 
 
 
 
 
 
 
VRC 500 Screening Consent 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
VRC 614 Informed Consent, AoU 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 Physical Exam 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
3 Medical History  
 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
EKG 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medications 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Product Administration 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Begin 7-day Diary Card 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
4 Pregnancy Prevention Counseling 
 
X 
X 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
Clinical Evaluations 
4 Pregnancy Test (urine or serum) 
 
X 
X 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
CBC with differential 
EDTA 
3 
 
3 
 
3 
 
 
3 
3 
 
3 
 
3 
 
 
 
ALT, creatinine 
GLT 
X 
 
X 
 
4 
 
 
4 
4 
 
4 
 
4 
 
 
 
5 CMP 
GLT 
4 
 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV Ag/Ab Combo 
EDTA 
3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sickle Cell Test 
EDTA 
3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Parasitemia Evaluation (PCR) 
EDTA 
3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Research Samples 
6 PK  
SST 
 
 
4 
 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
PBMC 
EDTA 
20 
 
 
 
 
 
 
 
40 
 
 
 
 
 
 
 
Serum 
SST 
8 
 
16† 
 
 
8 
8 
8† 
8 
8 
8† 
8 
8† 
8 
8 
8† 
Daily Volume (mL) 
 
44 
0 
27 
0 
11 
12 
12 
19 
59 
12 
19 
12 
19 
12 
12 
12 
Cumulative Volume (mL) 
 
44 
44 
71 
71 
82 
94 
106 
125 
184 
196 
215 
227 
246 
258 
270 
28 
Visit windows:  Schedule Visits 02A –14 with respect to Visit 02. Visit 02A (within 10 min of EOI); Visits 03, 04, 05 (±6 hrs); Visits 06, 07, 08, 09 (±2 days); 
Visits 10, 11, 12, 13, 14 (±7 days).  
Footnotes (continue to next page):  
1 Visit 01R is the day of enrollment and may be done on the same day as Day 0. V02/Day 0 is day of product administration and preferably scheduled within 
14 days after enrollment at Visit 01R but may be scheduled up to 28 days after Visit 01R.  
2 Screening includes physical exam, vital signs (BP, temperature, pulse, RR), height, weight.  Day 0 includes vital signs and weight (for ordering study product 
dose).  At other visits, perform a targeted exam if medically indicated, otherwise only vital signs are required. 
3 Perform full medical history at screening.  At other visits, perform interim medical history.  
4 Pregnancy test results must be negative for women of reproductive potential before product administration. Complete Pregnancy Prevention Counseling Form 
when pregnancy test is done.  


L9LS in Healthy Adults 
 
VRC 614, Version 2.0 
                      
October 13, 2021 
Page 61 of 73 
5 CMP includes sodium, potassium, chloride, total CO2, creatinine, glucose, urea nitrogen, albumin, alanine aminotransferase, alkaline phosphatase, aspartate 
aminotransferase, total bilirubin, calcium, total protein. 
6 PK blood draws, defined by time after infusion, are relative to the exact time of the end of infusion (EOI).  Record exact start / end times of product 
administration and of blood draw to ensure accurate analysis.  
† ADA assessed from serum samples at timepoints as indicated. 


L9LS in Healthy Adults 
 
VRC 614, Version 2.0 
                      
October 13, 2021 
Page 62 of 73 
Schedule of Evaluations: IM Group (Group 6) 
Visit Number 
01 
1 01R 
1 02 
02A 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
Time after Infusion 
 
 
Pre 
EOI 
24hr 
48hr 
72hr 
Wk1 
Wk2 
Wk3 
Wk4 
Wk8 
Wk12 Wk16 Wk20 Wk24 
Study Day 
-56 to -1 -28 to 0 
D0 
D0 
D1 
D2 
D3 
D7 
D14 
D21 
D28 
D56 
D84 
D112 
D140 
D168 
Study Procedures 
Tube 
Screen 
Enroll Day of injection 
 
 
 
 
 
 
 
 
 
 
 
 
VRC 500 Screening Consent 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
VRC 614 Informed Consent, AoU 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 Physical Exam 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
3 Medical History  
 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medications 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Product Administration 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Begin 7-day Diary Card 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
4 Pregnancy Prevention Counseling 
 
X 
X 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
Clinical Evaluations 
4 Pregnancy Test (urine or serum) 
 
X 
X 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
CBC with differential 
EDTA 
3 
 
3 
 
3 
 
 
3 
3 
 
3 
 
3 
 
 
 
ALT, creatinine 
GLT 
X 
 
X 
 
4 
 
 
4 
4 
 
4 
 
4 
 
 
 
5 CMP 
GLT 
4 
 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV Ag/Ab Combo 
EDTA 
3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Research Samples 
6 PK  
SST 
 
 
4 
 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
PBMC 
EDTA 
20 
 
 
 
 
 
 
 
40 
 
 
 
 
 
 
 
Serum 
SST 
8 
 
16† 
 
 
8 
8 
8† 
8 
8 
8† 
8 
8† 
8 
8 
8† 
Daily Volume (mL) 
 
44 
0 
27 
0 
11 
12 
12 
19 
59 
12 
19 
12 
19 
12 
12 
12 
Cumulative Volume (mL) 
 
44 
44 
71 
71 
82 
94 
106 
125 
184 
196 
215 
227 
246 
258 
270 
28 
Visit windows:  Schedule Visits 02A –14 with respect to Visit 02. Visit 02A (within 10 min of EOI); Visits 03, 04, 05 (±6 hrs); Visits 06, 07, 08, 09 (±2 days); 
Visits 10, 11, 12, 13, 14 (±7 days).  
Footnotes (continue to next page):  
1 Visit 01R is the day of enrollment and may be done on the same day as Day 0. V02/Day 0 is day of product administration and preferably scheduled within 
14 days after enrollment at Visit 01R but may be scheduled up to 28 days after Visit 01R.  
2 Screening includes physical exam, vital signs (BP, temperature, pulse, RR), height, weight.  Day 0 includes vital signs and weight (for ordering study product 
dose).  At other visits, perform a targeted exam if medically indicated, otherwise only vital signs are required. 
3 Perform full medical history at screening.  At other visits, perform interim medical history.  
4 Pregnancy test results must be negative for women of reproductive potential before product administration. Complete Pregnancy Prevention Counseling Form 
when pregnancy test is done.  
5 CMP includes sodium, potassium, chloride, total CO2, creatinine, glucose, urea nitrogen, albumin, alanine aminotransferase, alkaline phosphatase, aspartate 
aminotransferase, total bilirubin, calcium, total protein. 


L9LS in Healthy Adults 
 
VRC 614, Version 2.0 
                      
October 13, 2021 
Page 63 of 73 
6 PK blood draws, defined by time after infusion, are relative to the exact time of the end of infusion (EOI).  Record exact start / end times of product 
administration and of blood draw to ensure accurate analysis.  
 
          † ADA assessed from serum samples at timepoints as indicated


L9LS in Healthy Adults 
 
VRC 614, Version 2.0 
                      
October 13, 2021 
Page 64 of 73 
 
Schedule of Evaluations: CHMI for Groups 1-4 
Visit Number 
C01 
C02 
1 C02A 
1 C02B 
C03 
C04 
C05 
C06 
C07 
C08 
C09 
C10 
Time after CHMI 
 
 
24hr 
72hr 
Wk1 
Wk1 
Wk1 
Wk1 
Wk1 
Wk1 
Wk1 
Wk2 
CHMI Day 
-1 
D0 
D1 
D3 
D7 
D8 
D9 
D10 
D11 
D12 
D13 
D14 
Study Procedures 
Tube 
 
CHMI 
 
 
Parasitemia Check (daily checks until treatment criteria met) 
2 Physical Exam, Vital Signs 
 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Interim Medical History 
 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
CHMI 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Phone Contact 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
Pregnancy Prevention Counseling 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Clinical Evaluations 
3 Pregnancy Test (urine or serum) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
CBC with differential 
EDTA 
3 
 
 
 
3 
 
 
 
 
 
 
 
ALT, creatinine 
GLT 
4 
 
 
 
 
 
 
 
 
 
 
 
4 Parasitemia Evaluation (PCR) 
EDTA 
 
 
 
 
3 
3 
[3] 
[3] 
[3] 
[3] 
[3] 
[3] 
Research Samples 
PK 
SST 
4 
 
 
 
4 
 
 
 
 
 
 
4 
PBMC 
EDTA  
 
 
 
 
40 
 
 
 
 
 
 
*60 
Serum 
SST 
 
 
 
 
16† 
 
 
 
 
 
 
*16 
Daily Volume (mL) 
 
11 
0 
0 
0 
66 
3 
3 
3 
3 
3 
3 
83 
Cumulative Volume (mL) 
 
11 
11 
11 
11 
77 
80 
83 
86 
89 
92 
95 
178 
1 After CHMI, schedule Visit C02A on Day 1 or 2, Visit C02B on Day 3 or 4. 
2 Perform a targeted physical exam if medically indicated, otherwise only vital signs (BP, temperature, pulse, RR) are required. 
3 Pregnancy test results must be negative for women of reproductive potential within 2 days prior to CHMI.  Complete a Pregnancy Prevention 
Counseling Form when pregnancy test is done.  
4 Parasitemia evaluations should continue daily until a subject has one positive PCR or blood smear; brackets [3] indicate optional draw as needed.  A 
positive result prior to Day 21 is required for initiation of antimalarial directly observed therapy (DOT).  
* Research blood will be drawn at 14 days post-CHMI (Visit C10) from all subjects. 
† ADA assessed from serum samples at timepoints as indicated.  
 


L9LS in Healthy Adults 
 
VRC 614, Version 2.0 
                      
October 13, 2021 
Page 65 of 73 
Schedule of Evaluations: CHMI for Groups 1-4 (continued) 
1 Visit Number 
C11 
C12 
C13 
1 C14 
C15 
C16 
C17 
2 C18 
Time after CHMI 
Wk2 
Wk2 
Wk2 
Wk3 
Wk3 
Wk3 
Wk4 
Wk7 
CHMI Day 
D15 
D16 
D17 
D21 
D22 
D23 
D28 
D49 
Study Procedures 
Tube 
Parasitemia Check 
(daily until treatment criteria met) 
 
 
 
 
 
3 Physical Exam, Vital Signs 
 
X 
X 
X 
X 
X 
X 
 
[X] 
Interim Medical History 
 
X 
X 
X 
X 
X 
X 
 
[X] 
Phone Contact  
 
 
 
 
 
 
 
X 
[X] 
Clinical Evaluations 
CBC with differential 
EDTA 
 
 
 
*3 
 
*3 
 
[3] 
ALT, creatinine 
GLT 
 
 
 
*4 
 
*4 
 
[4] 
4 Parasitemia Evaluation (PCR) 
EDTA 
[3] 
[3] 
[3] 
[3] 
 
 
 
[3] 
Anti-Malarial Treatment 
 
 
 
 
[X] 
[X] 
[X] 
 
 
Research Samples 
PK 
SST 
 
 
 
4 
 
 
 
[4] 
PBMC 
EDTA 
 
 
 
 
 
 
 
[60] 
Serum 
SST 
 
 
 
8† 
 
 
 
[16] 
Daily Volume (mL) 
 
3 
3 
3 
22 
0 
7 
0 
90 
Cumulative Volume (mL) 
 
181 
184 
187 
209 
209 
216 
216 
306 
1 Visit C14 is only required for CHMI participants not previously diagnosed with malaria parasitemia to rule out a delayed case. At Visit C14 (Day 21), any subject 
who has not already started antimalarial treatment will be given definitive DOT.  Subjects must return for DOT for 2 more days after initiation.  Brackets [X] 
indicate optional as needed per subject treatment status.  
2 Visit C18 is only required for subjects who had a positive PCR or blood smear to document test of cure. It is scheduled to occur 26±5 days after DOT completion 
and is shown at Day 49 for convenience.  Visit C18 may be completed via phone for subjects who remain malaria negative, brackets [X] indicate optional as 
needed per subject infection status. 
3 Perform a targeted physical exam if medically indicated, otherwise only vital signs (BP, temperature, pulse, RR) are required. 
4 Parasitemia evaluations should continue daily until a subject has one positive PCR or blood smear; brackets [3] indicate optional draw as needed.  A positive result 
prior to Day 21 is required for initiation of antimalarial DOT.  Otherwise, initiate DOT at C14.  
* Blood for CBC, ALT, and creatinine will be drawn at onset of DOT and about 2 days later; shown at visits C14 and C16 to account for blood draw.  Parasitemia 
evaluations are not performed during treatment through to test of cure. 
† ADA assessed from serum samples at timepoints as indicated. 
 
 


L9LS in Healthy Adults 
 
VRC 614, Version 2.0 
                      
October 13, 2021 
Page 66 of 73 
Schedule of Evaluations: CHMI for Group 5 
Visit Number 
01 
01R 
C01 
C02 
1 C02A 
1 C02B 
C03 
C04 
C05 
C06 
C07 
C08 
C09 
C10 
Time after CHMI 
 
 
 
 
24hr 
72hr 
Wk1 
Wk1 
Wk1 
Wk1 
Wk1 
Wk1 
Wk1 
Wk2 
CHMI Day -56 to -1 -56 to -1 
-1 
D0 
D1 
D3 
D7 
D8 
D9 
D10 
D11 
D12 
D13 
D14 
Study Procedures 
Tube 
 
 
 
CHMI 
 
 
Parasitemia Check (daily checks until treatment criteria met) 
VRC 500 Screening Consent 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
VRC 614 Informed Consent, AoU 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
2 Physical Exam, Vital Signs 
 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
3 Medical History 
 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
EKG 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medications 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
CHMI 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Phone Contact 
 
 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
4 Pregnancy Prevention Counseling 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Clinical Evaluations 
4 Pregnancy Test (urine or serum) 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
CBC with differential 
EDTA 
3 
 
3 
 
 
 
3 
 
 
 
 
 
 
 
ALT, creatinine 
GLT 
X 
 
4 
 
 
 
 
 
 
 
 
 
 
 
5 CMP 
GLT 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV Ag/Ab Combo 
EDTA 
3 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sickle Cell Test 
EDTA 
3 
 
 
 
 
 
 
 
 
 
 
 
 
 
6 Parasitemia Evaluation (PCR) 
EDTA 
3 
 
 
 
 
 
3 
3 
[3] 
[3] 
[3] 
[3] 
[3] 
[3] 
Research Samples 
PBMC 
EDTA 
20 
 
 
 
 
 
20 
 
 
 
 
 
 
*20 
Serum 
SST 
8 
 
 
 
 
 
8 
 
 
 
 
 
 
*8 
Daily Volume (mL) 
 
44 
0 
7 
0 
0 
0 
34 
3 
3 
3 
3 
3 
3 
31 
Cumulative Volume (mL) 
 
44 
44 
51 
51 
51 
51 
85 
88 
91 
94 
97 
100 
103 
134 
Footnotes (continue to next page):  
1 After CHMI, schedule Visit C02A on Day 1 or 2, Visit C02B on Day 3 or 4. 
2 Screening includes physical exam, vital signs (BP, temperature, pulse, RR), height, weight.  Day 0 includes vital signs and weight (for ordering study product 
dose).  At other visits, perform a targeted exam if medically indicated, otherwise only vital signs are required. 
3 Perform full medical history at screening.  At other visits, perform interim medical history.  
4 Pregnancy test results must be negative for women of reproductive potential within 2 days prior to CHMI.  Complete a Pregnancy Prevention Counseling Form 
when pregnancy test is done.  


L9LS in Healthy Adults 
 
VRC 614, Version 2.0 
                      
October 13, 2021 
Page 67 of 73 
5 CMP includes sodium, potassium, chloride, total CO2, creatinine, glucose, urea nitrogen, albumin, alanine aminotransferase, alkaline phosphatase, aspartate 
aminotransferase, total bilirubin, calcium, total protein. 
6 Parasitemia evaluations should continue daily until a subject has one positive PCR or blood smear; brackets [3] indicate optional draw as needed.  A positive 
result prior to Day 21 is required for initiation of antimalarial directly observed therapy (DOT).  
* Research blood will be drawn at 14 days post-CHMI (Visit C10) from all subjects. 
 
 


L9LS in Healthy Adults 
 
VRC 614, Version 2.0 
                      
October 13, 2021 
Page 68 of 73 
Schedule of Evaluations: CHMI for Group 5 (continued) 
1 Visit Number 
C11 
C12 
C13 
1 C14 
C15 
C16 
C17 
2 C18 
Time after CHMI 
Wk2 
Wk2 
Wk2 
Wk3 
Wk3 
Wk3 
Wk4 
Wk7 
CHMI Day 
D15 
D16 
D17 
D21 
D22 
D23 
D28 
D49 
Study Procedures 
Tube 
Parasitemia Check 
(daily until treatment criteria met) 
 
 
 
 
 
3 Physical Exam, Vital Signs 
 
X 
X 
X 
X 
X 
X 
 
[X] 
Interim Medical History 
 
X 
X 
X 
X 
X 
X 
 
[X] 
Phone Contact  
 
 
 
 
 
 
 
X 
[X] 
Clinical Evaluations 
CBC with differential 
EDTA 
 
 
 
*3 
 
*3 
 
[3] 
ALT, creatinine 
GLT 
 
 
 
*4 
 
*4 
 
[4] 
4 Parasitemia Evaluation (PCR) 
EDTA 
[3] 
[3] 
[3] 
[3] 
 
 
 
[3] 
Anti-Malarial Treatment 
 
 
 
 
[X] 
[X] 
[X] 
 
 
Research Samples 
PBMC 
EDTA 
 
 
 
 
 
 
 
[20] 
Serum 
SST 
 
 
 
 
 
 
 
[8] 
Daily Volume (mL) 
 
3 
3 
3 
10 
0 
7 
0 
38 
Cumulative Volume (mL) 
 
137 
140 
143 
153 
153 
160 
160 
198 
1 Visit C14 is only required for CHMI participants not previously diagnosed with malaria parasitemia to rule out a delayed case.  At Visit C14 (Day 21), any subject 
who has not already started antimalarial treatment will be given definitive DOT.  Subjects must return for DOT for 2 more days after initiation.  Brackets [X] 
indicate optional as needed per subject treatment status.  
2 Visit C18 is only required for subjects who had a positive PCR or blood smear to document test of cure.  It is scheduled to occur 26±5 days after DOT completion 
and is shown at Day 49 for convenience.  Visit C18 may be completed via phone for subjects who remain malaria negative, brackets [X] indicate optional as 
needed per subject infection status. 
3 Perform a targeted physical exam if medically indicated, otherwise only vital signs (BP, temperature, pulse, RR) are required. 
4 Parasitemia evaluations should continue daily until a subject has one positive PCR or blood smear; brackets [3] indicate optional draw as needed.  A positive result 
prior to Day 21 is required for initiation of antimalarial DOT.  Otherwise, initiate DOT at C14.  
* Blood for CBC, ALT, and creatinine will be drawn at onset of DOT and about 2 days later; shown at visits C14 and C16 to account for blood draw.  Parasitemia 
evaluations are not performed during treatment through to test of cure. 


L9LS in Healthy Adults 
 
VRC 614, Version 2.0 
                      
October 13, 2021 
Page 69 of 73 
APPENDIX II: ASSESSMENT OF AE RELATIONSHIP AND SEVERITY 
GRADING


L9LS in Healthy Adults 
 
VRC 614, Version 2.0 
                      
October 13, 2021 
Page 70 of 73 
Assessment of Relationship of an Adverse Event  
The relationship between an AE and the study product or CHMI will be assessed by the 
investigator on the basis of clinical judgment and the definitions below. 
• Definitely Related:  The AE and administration of study product and/or CHMI are 
related in time, and a direct association can be demonstrated. 
• Probably Related:  The AE and administration of study product and/or CHMI are 
reasonably related in time, and the AE is more likely explained by study agent or CHMI 
than other causes. 
• Possibly Related:  The AE and administration of study product and/or CHMI are 
reasonably related in time, but the AE can be explained equally well by causes other than 
study agent or CHMI. 
• Not Related:  The AE is clearly explained by another cause not related to the study 
product or CHMI. 
For purposes of preparing summary data reports in which AE attributions are simplified to 
“Related” or “Not Related”, in this protocol, the “Definitely, Probably and Possibly” attributions 
above will be mapped to the “Related” category, while the “Unlikely/Probably Not Related” and 
“Not Related” attributions above will be mapped to the “Not Related” category.  The definitions 
that apply when these two attribution categories alone are used are as follows: 
• Related:  There is a reasonable possibility that the AE may be related to the study 
product or CHMI. 
• Not Related:  There is not a reasonable possibility that the AE is related to the study 
product or CHMI.  
 
Grading the Severity of an Adverse Event 
The Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse 
Events, Corrected Version 2.1 [July 2017] will be used to determine the severity grades of AEs 
in this protocol and is available from: https://rsc.niaid.nih.gov/clinical-research-sites/daids-
adverse-event-grading-tables. 
 
Several modifications were made to the table as follows: 
• Weight loss will be recorded as an AE only if it is considered deleterious to the 
participant’s health. 
• 
For severity grading of the solicited bruising parameter at the product administration site, 
the definitions based on size of the largest diameter and listed for the “Injection Site 
Erythema or Redness” will be used.  The severity grade definition for “Bruising” 
provided under the Dermatologic Clinical Conditions will be used only for unsolicited 
AEs involving bruising at other body locations. 
• Creatinine changes will be graded on the basis of the upper limit of normal provided by 
the grading table and not change from baseline. 
• Creatinine clearance changes will be graded according to ml/min provided by the grading 
table and not change from baseline. 
• Subclinical CMP results for sodium, potassium, chloride, bicarbonate, BUN, and glucose 
will not be considered an AE unless Grade 2 or higher. 


L9LS in Healthy Adults 
 
VRC 614, Version 2.0 
                      
October 13, 2021 
Page 71 of 73 
APPENDIX III: STUDY PRODUCT PREPARATION


L9LS in Healthy Adults 
 
VRC 614, Version 2.0 
                      
October 13, 2021 
Page 72 of 73 
1. 
Preparation for IV Administration 
To prepare an IV infusion, the pharmacist will complete the sequence of steps outlined below.   
1. Obtain a pre-filled, DEHP-free, 100 mL IV bag of 0.9% saline.   
2. Remove the air from the IV bag.  
3. Calculate the total dose needed to prepare L9LS in the 0.9% saline bag in order to achieve 
the ideal concentration of  ≥2mg/mL.   
The IV bag may be prepared with a higher volume than required (i.e. overfill) to ensure 
proper administration via volumetric pump.   
Maintaining infusible volume of L9LS at the minimum concentration of 2 mg/mL may cause 
the total L9LS dose in the bag to exceed the lower weight-based dose (e.g., 1 mg/kg).  
Do not infuse the entire volume of the IV bag if the total amount exceeds the weight-based 
dose of the subject.  
4. Thaw and equilibrate vials on the bench at room temperature for 90 minutes. If vials are 
stored at 5°C ± 3°C, equilibrate for approximately 30 min at room temperature before use.  
5. Gently swirl the vials for 30 seconds to mix while avoiding foaming. Vials should never be 
shaken.   
6. Withdraw the necessary amount of L9LS and add it to the IV bag so that final concentration 
in bag is ≥ 2 mg/mL.   
7. Add the syringe contents to the sterile bag of saline using good sterile compounding 
technique.   
8.  An in-line filter infusion set is required for IV product administrations and must comply with 
the following specifications: 1.2 micron polyethersulfone filter membrane, DEHP-free, latex-
free (equivalent to B. Braun #473994 filter extension set). After the in-line filter is added to 
the tubing, the administration set must be primed.   
Note: If the compounded IV preparation has been stored at 5°C ± 3°C, equilibrate for 
approximately 30 min at room temperature before use.  The study product solution will typically 
be administered IV over about 15-30 minutes using a volumetric pump.  The total time needed to 
administer the dose may be longer than 30 minutes based on factors such as subject 
tolerance.  The mL/hr infusion rate may vary based on the total volume needed to administer a 
full dose.   
IV bag prepared without overfill:   
At the end of product administration, the IV administration set must be flushed with about 30 
mL (or appropriate volume) of normal saline.  
IV bag prepared with overfill:  
At the end of product administration, the IV administration set should not be flushed with saline.  
  
 


L9LS in Healthy Adults 
 
VRC 614, Version 2.0 
                      
October 13, 2021 
Page 73 of 73 
2. 
Preparation for SC or IM Administration   
To prepare a SC or IM administration dose, the pharmacist will complete the sequence of steps 
as outlined in this section.  
1. Calculate the total mg DP needed. 
2. Thaw and equilibrate vials on the bench at room temperature for 90 minutes. If vials are 
stored at 5°C ± 3°C, equilibrate for approximately 30 min at room temperature before use.  
3. Gently swirl the vials for 30 seconds to mix while avoiding foaming. Vials should never be 
shaken.   
4. Withdraw the necessary amount of L9LS using a 5-micron filter needle (maximum syringe 
fill volume of 2.5 ml for SC and 1.0 mL for IM). Use a new filter needle for each syringe. 
5. Prior to dispensing, discard the filter needle and replace it with a needle suitable for SC or IM 
injection.  
Note:  If SC or IM preparations have been stored at 5°C ± 3°C, equilibrate for approximately 30 
min at room temperature before use.  
 


PATIENTIDENTIFICATION
ConsenttoParticipateinaClinicalResearchStudy
NIH-2977(4-17)
FileinSection4:ProtocolConsent(1)
VersionDate:11/03/2021V2.0
Page1 of19
CCICFtemplatev904.13.2021
MEDICALRECORD
CONSENTTOPARTICIPATEINANNIHCLINICALRESEARCHSTUDY
PRINCIPALINVESTIGATOR:RichardWu,MD
STUDYTITLE:VRC614(000536):APhase1,DoseEscalation,Open-LabelClinicalTrialwith
ExperimentalControlledHumanMalariaInfections(CHMI)toEvaluateSafetyandProtective
EfficacyofanAnti-MalariaHumanMonoclonalAntibody,VRC-MALMAB0114-00-AB(L9LS),
inHealthy,Malaria-NaiveAdults
STUDYSITE:NIH/NIAID/VRC/VaccineEvaluationClinic(VEC)
Cohort:Healthyvolunteer
ConsentVersion:Version2.0,November3,2021
WHODOYOUCONTACTABOUTTHISSTUDY?
PrincipalInvestigator:RichardWu,MD,
StudyCoordinator:FlorelizMendoza,RN,
KEYINFORMATIONABOUTTHISRESEARCH
Thepurposeofthisconsentformistogiveyouinformationtohelpyoudecideifyouwouldlike
to be part of a research study at the National Institutes of Health (NIH). The decision to
participateisyourchoice.Thissectionprovidesinformationwebelieveismosthelpfuland
importanttoyouinmakingyourdecision.Additionalinformationthatmayhelpyoudecidecan
befoundinothersectionsofthedocument.
Thisisastudyofanexperimentaldrugcalled“L9LS”.L9LSisamonoclonalantibodythat
targetsmalaria. L9LShasnotbeentestedinhumansbeforethisstudy. Wedonotknowif
L9LSwillprotectyoufrommalariainfection.ThereisnomalariainL9LS,soyoucannotget
theinfectionjustbytakingtheexperimentaldrug.YoushouldnotassumeL9LSwillprotect
youfrommalariaifyoutraveltoaplacewherethereisariskofinfection.
ThemainpurposeofthisstudyistoseeifL9LSissafeandhowyourbodyrespondstothe
antibody.ThisisthefirsttimethatL9LSwillbegiventopeople,andwedonotknowhowyour
bodywillrespond.WewillfolloweveryonewhogetsL9LSforabout24weeks.
IfyouhavesideeffectsfromL9LS,weexpectthemtobelikethosethatoccurwithother
antibodyproducts.Thesesideeffectsincludefever,chills,shaking,nausea,diarrhea,vomiting,
pain,headache,dizziness,andtiredness.Theyusuallyoccurwithinthefirst24hoursafterthe
antibodyisgiven.Someantibodyproductshaveariskofseriousallergicreactionsthatcanbe
lifethreatening.Althoughrare,othersideeffectsthatmayoccuraretroublebreathing,itchiness,
rash,hives,swelling,orchestpain,andyoumustreachouttothestudycliniciansrightawayif
youhaveanyoftheseserioussideeffects.
AnotherpurposeofthisstudyistotestifL9LSpreventsyoufromgettingmalariawhenyouare
bittenbymosquitoesthatcarrylivemalariaparasites.Thisiscalleda“malariachallenge”ora
	0003
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PATIENTIDENTIFICATION
ConsenttoParticipateinaClinicalResearchStudy
NIH-2977(4-17)
FileinSection4:ProtocolConsent(1)
VersionDate:11/03/2021V2.0
Page2 of19
CCICFtemplatev904.13.2021
MEDICALRECORD
CONSENTTOPARTICIPATEINANNIHCLINICALRESEARCHSTUDY
controlledhumanmalariainfection(CHMI).YoumustbeavailableonthedayoftheCHMIif
youareinagrouptakingpartintheCHMI.EachpersonwhotakespartintheCHMImayget
malariainfection,andwewillfolloweveryoneafterwardforabout7weeks.TheCHMIwill
includeparticipantswhogetadoseofL9LSand“control”participantswhodonotgetL9LS.
Starting7daysaftertheCHMI,youmustcometothecliniceverydayfor11daystobechecked
formalariaparasitesthroughabloodtest.Testingisdoneeverydaysothatthelevelofmalaria
inyourblooddoesnotgettodangerouslevels.AftertheCHMI,itisimportantthatyoucome
totheclinicforyourscheduledvisitssothatthelevelofmalariaparasitesinyourblood
doesnotincreasetodangerouslevels.
Atthefirstsignofmalariainfectioninyourblood,wewilltreatyouwithamedicationthatwill
cureyou.Evenifthebloodtestisneverpositive,allwhotakepartwillgettreatedwithamalaria
medicationatDay21afterCHMI.Wetakethissteptomakesurethateveryoneiscuredof
malaria.Thedrugsthattreatmalariamaycausesomesideeffects.Onceyouaretreated,you
willnotbeatriskforrecurrence/reactivationoftheinfectionfromtheCHMI.Ifyoudonottake
partintheCHMI,youwillnotbeatgreaterriskofgettingmalariainfectionandwillnotneed
drugsthattreatmalaria.
Duringthestudy,wewillcollectbloodsamplesfromyou.Someofyourbloodwillbestored
forfutureresearch.Youwillbecompensatedforyourtimeandinconveniencefortakingpart
inthisstudy.
Thestudywilllastabout2to6months,dependingonyourstudygroup.Duringthistime,you
mustuseaneffectiveformofbirthcontrolifabletobecomepregnant,mustnottraveltoa
malariaregion,mustnottakeantibioticdrugsstarting4weeksbeforethebeginningoftheCHMI
andduringtheCHMI(unlessprescribedbyaphysician,inwhichcasethestudyteammustbe
notified)ordonatebloodfor3yearsfollowingparticipationinCHMI.Thesesafetymeasures
arefurtherdescribedbelow.AllclinicalstudyvisitswilltakeplaceattheNIHClinicalCenter
in Bethesda, Maryland.  The CHMI will take place at the Walter Reed Army Institute of
ResearchfacilityinSilverSpring,Maryland,andisalsosupportedbytheU.S.Departmentof
Defense(DOD).
Theremainingdocumentwillnowdescribetheresearchstudyinmoredetail.Thisinformation
shouldbeconsideredbeforeyoumakeyourchoice.Membersofthestudyteamwilltalkwithyou
abouttheinformationinthisdocument.Somepeoplehavepersonal,religious,orethicalbeliefs
that may limit the kinds of medical or research interventions in which they would want to
participate.TakethetimeyouneedtoaskanyquestionsanddiscussthisstudywithNIHstaff,
andwithyourfamily,friends,andpersonalhealthcareproviders.
ITISYOURCHOICETOTAKEPARTINTHESTUDY
Youmaychoosenottotakepartinthisstudyforanyreason.Ifyoujointhisstudy,youmay
changeyourmindandstopparticipatinginthestudyatanytimeandforanyreason.Ineithercase,
youwillnotloseanybenefitstowhichyouareotherwiseentitled.However,tobeseenattheNIH,
youmustbetakingpartinastudyorarebeingconsideredforastudy.Ifyoudochoosetoleave
thestudy,pleaseinformyourstudyteamtoensureasafewithdrawalfromtheresearch.
	0003
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PATIENTIDENTIFICATION
ConsenttoParticipateinaClinicalResearchStudy
NIH-2977(4-17)
FileinSection4:ProtocolConsent(1)
VersionDate:11/03/2021V2.0
Page3 of19
CCICFtemplatev904.13.2021
MEDICALRECORD
CONSENTTOPARTICIPATEINANNIHCLINICALRESEARCHSTUDY
WHYISTHISSTUDYBEINGDONE?
Malariaisadiseasethataffectsmorethan250millionpeoplethroughouttheworld.Theparasites
thatcausemalariaareknownasPlasmodium.Theyliveinthemosquitosalivaandareinjected
intotheskinwhenamosquitobitesahuman.Thiscancausemalariainfection.Malariaoccursin
mosttropicalpartsoftheworldincludingAfrica,SoutheastAsiaandSouthAmerica.Itisaserious
threattothelocalpopulations,totravelersandtomilitarypersonnelstationedoverseas.Although
therearemedicinestotreatmalaria,thereisnovaccinethatfullypreventsinfectionandtreatment
isnoteasytogetinmanyareasoftheworld.Ifmalariaisnottreatedrightaway,itcanbecomea
seriousandsometimesdeadlydisease.Ifitistreatedrightaway,itcanbecompletelycured.
Thepurposeofthisresearchstudyistotestadrugthatcouldpreventmalariainfectioninhumans
calledL9LS.L9LSisconsideredinvestigational,whichmeansthatithasnotbeenapprovedby
theU.S.FoodandDrugAdministration(FDA)topreventmalariainfection.Itisamonoclonal
antibody(mAb)thattargetstheparasitesthatcausemalaria.Antibodiesarenaturallymadebythe
immune system to fight infection by blocking germs (bacteria and parasites) like malaria.
MonoclonalmeansthatalltheantibodiesinL9LSareexactlythesame.
L9LSwasdevelopedattheVaccineResearchCenter(VRC)atNIH.Itwasmadeinalaboratory
andlookslikeanantibodythatyourownbodycouldmake.Ithasshownpromiseforprevention
ofmalariainlaboratoryandanimalstudies,butithasnotyetbeenstudiedinhumans.
ThisisthefirststudytogiveL9LStohumans.WedonotknowifL9LSwillprotectyoufrom
malariainfection.YoucannotgetmalariafromL9LSbecausethereisnomalariainit.Youshould
notassumeL9LSwillprotectyoufrommalaria.
ThepurposeofthisresearchstudyistoseeifL9LSissafeandhowyourbodyrespondstoit.We
willgiveyouadoseofL9LSandmeasurehowmuchofitstaysinyourbodyovertime.Wealso
want to see the differences between getting L9LS as an infusion in a vein in your arm
(intravenously,IV)asaninjectionundertheskin(subcutaneously,SC)orasaninjectionintoa
muscle(intramuscularly,IM).
Inthisstudy,youwillbeexposedtomalariathroughbitesfrommosquitosinfectedwithmalaria
parasites,ifyouareinGroups1-5. Thisiscalleda“malariachallenge”ora“ControlledHuman
MalariaInfection”(CHMI).WedothistofindoutifL9LSpreventsyoufromgettingmalariaafter
youarebittenbytheinfectedmosquitoesinacontrolledsetting.Wewillmonitoryoucloselyand
testyourbloodeverydayformanydaystoseeifyougetinfectedwithmalaria.Evenifyourtest
isnegative,wewillgiveeveryonemalariatreatmentby21daysafterCHMI.
Weareaskingyoutojointhisresearchstudybecauseyouareahealthyadultbetweentheagesof
18and50whohasneverbeeninfectedwithmalaria.IfyouareinGroups1-5,youmustbewilling
totakepartintheCHMIandcomplywithfollow-uprequirementsafterCHMItobeinthisstudy.
IfyoutakepartintheCHMI,youmustalsoagreenottotraveltoamalariaendemicregionduring
thewholestudyandnottodonatebloodtoabloodbankfor3yearsafterCHMI.
WHATWILLHAPPENDURINGTHESTUDY?
Thisstudyhas6groupsasshownintheStudySchematablebelow.Groups1,2,3,4,and6will
getdifferentdosesand/orroutesofL9LS.MostpeoplewhogetL9LSwillgetitbyinfusioninto
avein(IV).SomepeoplewillgetL9LSintothefatundertheskin(SC)orintothemuscle(IM).
	0003
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PATIENTIDENTIFICATION
ConsenttoParticipateinaClinicalResearchStudy
NIH-2977(4-17)
FileinSection4:ProtocolConsent(1)
VersionDate:11/03/2021V2.0
Page4 of19
CCICFtemplatev904.13.2021
MEDICALRECORD
CONSENTTOPARTICIPATEINANNIHCLINICALRESEARCHSTUDY
Agroupofpeoplecalled“control”participantswillnotgetthestudyproductbutwilltakepartin
theCHMI.Thisgrouphelpsusmakesurethemosquitoscaninfectpeople.
Ifyoudecidetotakepartinthisstudy,youwillbeaskedtoreviewandagreetothisinformed
consentformandtheproceduresoutlinedwithinit.Youwillhavecompletedthescreeningprocess
whichincludesaphysicalexamandreviewofyourmedicalhistory,vitalsignsandlaboratory
results.Youmustbehealthyandqualifyforenrollmentbeforeyoucantakepartinthisstudy.
ThestudywillstartwithenrollmentsofpeopletothelowestdoseofL9LSbyIVandSCroutes(1
mg/kgIV(Group1)and5mg/kgSC(Group3)).Thenextgroups,5mg/kgIV(Group2)and20
mg/kgIV(Group4),willopenafterthestudyteamreviewsavailablesafetydataandagreesthat
therearenosafetyconcernsatthelowerIVdoses.Group5canbeenrolledatanytime.Group6
willenrollaftertheIVandSCgroupshavereceivedthestudyproductandhaveundergoneCHMI.
Groups1-5willtakepartintheCHMI.
IfyouareinGroup5,youwillbeacontrolparticipantandwillnotgetadoseofL9LS.After
enrollment,wewillcheckyourhealthanddrawyourbloodbeforetheCHMI.
Ifyouarefemaleandabletobecomepregnant,youmustuseaneffectivemethodofbirthcontrol
fortheentirestudy.YouwillbegivenapregnancytestbeforeyougetanydoseofL9LSand
beforetheCHMI.Ifyouarepregnant,wewillnotgiveyouL9LSandyoucannottakepartinthe
CHMI.
L9LSADMINISTRATION
Youwillbeintheclinicforabout8hoursonthedayL9LSisgiven.
·
Intravenous(IV)Dosing(Groups1,2,4):WewillplaceanIVline(thintube)inavein
inyourarm.TheIVlinewillbeattachedtoabagthathasL9LSmixedwithaliquid
called“normalsaline”orsaltwater.Itwillflowintoyourveinforabout30minutes.
Ifyouhavesideeffectsduringtheinfusion,itmaybesloweddownorstoppedasneeded.
Attheendofyourinfusion,wewillmonitoryouforanysideeffects.Ifyouarethe
firstpersontogetthefirstofanewdoselevel,youwillbemonitoredforatleast2
hours.Everyoneelsewillbemonitoredforatleast1houraftergettingL9LS.
WewillalsoplaceanIVlineinyourotherarmforbloodcollectionduringthevisitto
avoidstickingyouwithaneedlemultipletimes.Wewilldrawyourbloodbeforeand
rightaftertheinfusion,andthen3moretimesduringthe4-6hoursaftertheinfusion.
VRC614StudySchema
L9LSAdministration
Group
Subjects
Dose(mg/kg)
Route
CHMI
1
5
1
IV
X
2
4
5
IV
X
3
5
5
SC
X
4
4
20
IV
X
5
61
Control
X
6
5
5
IM
N/A
Total
29
1Two(2)additionalcontrolsubjectswillbeenrolledasCHMIback-ups
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PATIENTIDENTIFICATION
ConsenttoParticipateinaClinicalResearchStudy
NIH-2977(4-17)
FileinSection4:ProtocolConsent(1)
VersionDate:11/03/2021V2.0
Page5 of19
CCICFtemplatev904.13.2021
MEDICALRECORD
CONSENTTOPARTICIPATEINANNIHCLINICALRESEARCHSTUDY
Youwillbeallowedtogohomeabout4-6hoursaftertheinfusion,aslongasyoudo
nothaveconcerningsideeffects.Ifyouhavesideeffects,wewilltreatthem.Youwill
needtocomebacktotheclinic2timesduringthesameweekforblooddraws.
·
Subcutaneous(SC)Dosing(Group3): WewilluseasmallneedletoinjectL9LSinto
thefattytissueofyourbelly.Wemayuseyourarmorthighareainsteadofyourbelly
ifthosesitesaremoreappropriateforyourbody.Youwillget1or2injectionstoget
thefulldoseofL9LS. IfyouarethefirstpersontogetL9LSinthisgroup,youwillbe
monitoredforatleast2hours.Everyoneelsewillbemonitoredforatleast1hourafter
gettingL9LS.Iftherearenosafetyconcerns,youwillbeallowedtoleavetheclinic
afterthesafetycheck.Youwillneedtocomebacktotheclinic3timesduringthesame
weekforblooddraws.
·
Intramuscular(IM)Dosing(Group6):WewilluseaneedletoinjectL9LSintothe
muscleofyourupperarmand/orthigh.Youwillget2to4injectionstogetthefull
dose of L9LS. If you are the first person to get L9LS in this group, you will be
monitoredforatleast2hours.Everyoneelsewillbemonitoredforatleast1hourafter
gettingL9LS.Iftherearenosafetyconcerns,youwillbeallowedtoleavetheclinic
afterthesafetycheck.Youwillneedtocomebacktotheclinic3timesduringthesame
weekforblooddraws.
Wewillgiveyouathermometersothatyoucancheckyourtemperatureeverydayfor7daysafter
yougetL9LS.You will need torecord your highest temperature daily and tell usabout any
symptomsyouhave.Wewillalsogiveyouameasuringtoolsothatyoucanmeasureanyredness,
swelling,orbruisingyoumayhaveattheinjectionsite.Youwillgetapasswordtoasecurewebsite
torecordthisinformation. Ifyoudonothaveinternetaccess,youmayuseapaperdiarythatwe
giveyouinstead.
IfyouhaveanysideeffectsorfeelunwellafteryougetL9LS,youshouldtellaVRCnurseor
doctorassoonaspossible.Youcanreachtheclinicstaffbyphone24hoursaday.Ifyouhave
symptoms,youmaybeaskedtocomeintotheclinicforanexaminationbeforeyournextscheduled
visit.Youmayalsostayovernightinthehospital,ifneeded.Itisveryimportantthatyoufollow
theinstructionsfromtheclinicstaff
FOLLOW-UPAFTERL9LSADMINISTRATION
Thefollow-upvisitswilllast30minutesto2hoursandallowustocheckyouforanyhealth
changesorproblems.Wewillaskyouhowyouarefeelingandifyouhavetakenanymedications.
Wewillmeasureyourvitalsigns,andmayperformatargetedphysicalexambasedonhowyou
arefeeling.Wewilltakeabout1–11tubesofblood(~lessthanonehalfupto6tablespoonsat
eachvisitforsafetyand/orresearchtests.BlooddrawvolumeswillbewithinNIHClinicalCenter
limits. Wewilltellyourightawayifanyofyourtestresultsshowahealthproblem.Youmight
needtohaveextraclinicvisitsandlaboratorytestsifyouhavehealthchangesthatneedtobe
checked.
Clinical studies followa set schedule. This helpsus answer the research questions. The visit
scheduleisalittleflexible,butitisimportantthatyoufollowthescheduleascloselyaspossible.
Youshouldtrytonotmissanyvisits.Youshouldcontacttheclinicstaffassoonaspossibleif
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PATIENTIDENTIFICATION
ConsenttoParticipateinaClinicalResearchStudy
NIH-2977(4-17)
FileinSection4:ProtocolConsent(1)
VersionDate:11/03/2021V2.0
Page6 of19
CCICFtemplatev904.13.2021
MEDICALRECORD
CONSENTTOPARTICIPATEINANNIHCLINICALRESEARCHSTUDY
youneedtochangethedateortimeofanystudyvisit.Whenyoucompletethisstudy,wemay
inviteyoutotakepartinanotherstudyforfollow-upsamplecollection.
CONTROLLEDHUMANMALARIACHALLENGE(CHMI)–GROUPS1-5ONLY
TolearnifL9LScanpreventmalariainfection,wewillconductaCHMI.TheCHMIwillbe
performedbyU.S.Militaryscientists,physiciansandothertrainedpersonnelwhoareexperienced
inconductingaCHMIundercontrolledconditions. ItwilltakeplaceattheWalterReedArmy
InstituteofResearch(WRAIR)facilityinSilverSpring,Maryland.TheCHMIvisitwilllastabout
4to6hoursandbeginsveryearlyinthemorning.
DuringtheCHMI,wewillputmosquitoescarryingthemalariaparasitesintoacup.Thecupis
coveredwithnylontullenettingandallowsthemosquitoestobiteyouundercontrolledconditions.
Theycannotescapefromthecup.Nomorethan5mosquitoesareputinthecupatonetime.You
willholdthecupagainstyourarmfor5minutesandthenthemosquitoswillbecheckedforblood
feedingandpresenceofmalariaparasites.Ifneeded,moremosquitoesmaybeaddeduntilweare
surethatatotalof5mosquitoeshavefedonyourblood.
FollowupaftertheCHMIisveryimportantsowecancheckyourhealth.Weknowthatittakes
anywherefrom7-15daystofindmalariaparasitesintheblood.So,aftertheCHMI,wewillcall
youbyphonetocheckonyou2timesinthefirstweek.Then,startingonday7,youmustcometo
theNIHClinicalCentereverydayforabout30-minutevisitsthroughday17sowecancollect
bloodfordiagnosticandresearchpurposes. Thevisitsmaybelongerifmedicalevaluationis
needed. If you test positive for malaria, you will be treated right away with anti-malarial
medication.Wewillalsobringyoubackabout8weeksaftertheCHMItomakesureyouare
cured. At day 21, anyone who still has a negative malaria test will be given antimalarial
medication.Thiswaywecanmakesurethatanyonewhomighthavemalariainfectionistreated,
evenifyourtestsarenegative.Ifyouarenegativeformalaria,wewillcallyoubyphonetocheck
onyouabout8weeksaftertheCHMI
ThistypeofCHMIhasbeendoneforover35yearsformanymalariastudies.Themosquitoes
thatwillbeusedareraisedinalaboratoryforCHMIs.Theyareinfectedwithaspecificstrainof
themalariaparasite(Plasmodiumfalciparum)thatisknowntobetreatablewiththeanti-malaria
medicationwewillgiveyou.Whilethemosquitosarebeinggrown,theyfeedontransfusion-
qualityhumandonorbloodthathasbeenscreenedfollowingFDArequirementstomakesurethat
the blood is not carrying any other infectious diseases. This type of malaria does not cause
recurrentinfectionsafteryouaretreated.
HOWLONGWILLTHESTUDYTAKE?
Thestudywilllastforabout24weeksifyouareinGroups1,2,3,4,and6thatgetL9LS.Youwill
visittheNIHClinicalCenterforabout11or12studyvisitsbasedonifyougetL9LSbyIVor
SC/IM,respectively,andupto15visitsfortheCHMIfollow-upifyouaretakingpartinthe
CHMI.IfyouareinGroup5,whichdoesnotreceiveL9LS,thestudywilllastforabout7weeks
aftertheCHMI.Wewilldiscusstheexactscheduleandlocationofthesevisitswithyou.
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PATIENTIDENTIFICATION
ConsenttoParticipateinaClinicalResearchStudy
NIH-2977(4-17)
FileinSection4:ProtocolConsent(1)
VersionDate:11/03/2021V2.0
Page7 of19
CCICFtemplatev904.13.2021
MEDICALRECORD
CONSENTTOPARTICIPATEINANNIHCLINICALRESEARCHSTUDY
HOWMANYPEOPLEWILLPARTICIPATEINTHISSTUDY?
Weplantoenrollabout29people. Thisincludesabout23peoplewhowillgetL9LSandabout6
controlparticipants.Wemayenrollupto40peopleifneededtocompletethestudyandthis
includes2back-upcontrolparticipantsfortheCHMI.
WHATARETHERISKSANDDISCOMFORTSOFBEINGINTHESTUDY?
POSSIBLERISKSOFL9LS
ThisstudyisthefirsttimethatL9LSwillbegiventopeople. Theinformationdescribedbelowis
takenfromstudieswithotherantibodiesthatarelikeL9LSandmayworkthesame.Someofthose
antibodiesareapprovedforuseinpeople.Likeotherdrugs,monoclonalantibodiescancauseside
effects,someofwhichcanbeserious.Mostsideeffectsoccurwithinthefirst24hoursafteran
antibodyisgiven.
·
Sideeffects to antibodies given by IV may include: fever, chills, shaking, nausea,
vomiting,pain,headache,dizziness. Moreseriousbutraresideeffectsmayoccur,
includingtroublebreathing,highorlowbloodpressure,itchiness,rash,hives,lipor
faceswelling,diarrhea,racingheart,orchestpain. Thesesymptomsusuallygoaway
withinafewminutestohoursaftertheproductisgiven. WearegivingL9LSata
controlledrate.IfyoudevelopsymptomswhilegettingL9LS,tellthenurserightaway.
Slowingorstoppingtheflowratemayhelpimprovethesymptoms.
·
Sideeffectsto antibodiesgivenby SCmayinclude:milditchiness,rednessand/or
swellingatthesiteofinjection.Tiredness,musclepain,andheadachehavealsobeen
reported.Thesesymptomsusuallygoawaywithin1to2days.
·
SideeffectstoantibodiesgivenIMinclude:milditchiness,rednessand/orswellingat
thesiteofinjection.Tiredness,musclepain,andheadachehavealsobeenreported.
Thesesymptomsusuallygoawaywithin1to2days.
Someantibodieshaveariskofseriousallergicreactionsthatcanbelifethreateningincluding:
·
Anaphylaxisisonetypeofallergicreactionthatmayhappensoonafteranantibodyis
given.Thisreactioncanincludedifficultybreathing,lowbloodpressure,hives,rash,
orswellinginthemouthandface. Thisreactionisrarebutcanbelifethreatening.
Participantswillremainunderobservationinthetimeframethatthisusuallyoccurs.
·
Serumsicknessisatypeofallergicreactionthatmayhappenseveraldaystoweeks
afteranantibodyisgiven.Thisreactionmayincludehives,rash,fever,enlargedlymph
nodes,musclepains,jointpains,chestdiscomfortorshortnessofbreath.
Someantibody productscan increase therisk of seriousinfections. L9LS isnotexpectedto
increasetheriskofseriousinfectionsbecauseitattacksaparasiteanddoesnottargetthehuman
immunesystem.
Inalabstudy,L9LSattachedtothesalivaryglandsthatproducesaliva.Thiswasararefinding.
WedonotknowifL9LSaffectsyoursalivaryglands.Wewillbecheckingforanypossible
problemswithyoursalivaryglandsduringthestudy. Ifthereisaconcernforsalivarygland
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PATIENTIDENTIFICATION
ConsenttoParticipateinaClinicalResearchStudy
NIH-2977(4-17)
FileinSection4:ProtocolConsent(1)
VersionDate:11/03/2021V2.0
Page8 of19
CCICFtemplatev904.13.2021
MEDICALRECORD
CONSENTTOPARTICIPATEINANNIHCLINICALRESEARCHSTUDY
problems,wemayaskanoralspecialisttoexamineyouandprovidearecommendationforyour
care.
UNKNOWNRISKS
L9LSmayhaveothersideeffectsthatarenotyetknown.Takingpartinthisstudymayaffect
youreligibilityforfuturemonoclonalantibodyormalariastudies.Wewillgiveyouanynew
informationaboutrisksorotherinformationthatmayaffectyourdecisiontocontinueinthestudy
asitbecomesavailable.Youmaynotdonatebloodwhiletakingpartinthisstudyandyoumay
notdonatebloodforoneyearafterthedateofyourlastdoseofL9LSorthreeyearsafteryourlast
CHMI.
POSSIBLERISKSOFIV,IM,ORSCDOSING
Generalrisksofmethodsthatuseaneedleincludestinging,discomfort,pain,soreness,redness,
bruising,swellingoratinycutattheneedleinsertionsite.
POSSIBLERISKSOFBLOODDRAWING
Blooddrawingmaycausepain,bruising,andmaycauseafeelingoflightheadednessorfainting.
Rarely,itmaycauseinfectionatthesitewherethebloodistaken.AnIVlinewillbeplacedin
yourveinforafewhoursonadayL9LSisgivenbyIV.ProblemsattheIVsiteareusuallymild
andmayincludepain,bruising,minorswelling,orbleeding.Rarely,theremaybeaninfection,
veinirritation,nerveproblem,orbloodclot.
POSSIBLERISKSOFCHMI–GROUPS1-5ONLY
DuringtheCHMI,youwillbebittenbymosquitoesthatcarrylivemalariaparasiteswhichcause
malariainfection.WedonotknowifL9LSwillprotectpeoplefrommalaria.Ifyoudidnot
receiveanyL9LSandareinthecontrolgroup,youareexpectedtogetmalaria. Ifyougetmalaria,
youmayexperiencethefollowingsymptoms:
·
Fever,chills,headache,dizziness,muscleaches,sweats,fatigue,insomnia
·
Nausea,vomiting,stomachcramps,diarrhea
·
Decreaseinnumbersofredbloodcells,whitebloodcells,andplatelets
·
Enlargedliverorspleen
Symptomsareusuallymildtomoderate,butyoumayhavesomeseveresymptoms.Youmayhave
feversfor1to3days.Youmaymisstimefromworkorschoolduetoyourillness.Youwillnot
becompensatedforanylossofincomeformissingwork.Ifmalariaisnottreatedrightaway,it
canleadtokidney,liver,heartorbraindamageanddeath.TheCHMIisconsideredtobesafe
because people are closely monitored and treated as soon as they are found to have malaria
infection,buttheymustremaininclosecontactwiththestudyteam.
AftertheCHMI,itisimportantthatyoucometotheclinicforyourscheduledvisitssothat
thelevelofmalariaparasitesinyourblooddoesnotincreasetodangerouslevels. Frompast
studiesweknowthatmalariaparasitescanbefoundinthebloodanywherefromabout7to15
daysaftermosquitoexposure.Abouthalfofthepeopleinfectedwithmalariaparasitesdevelop
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PATIENTIDENTIFICATION
ConsenttoParticipateinaClinicalResearchStudy
NIH-2977(4-17)
FileinSection4:ProtocolConsent(1)
VersionDate:11/03/2021V2.0
Page9 of19
CCICFtemplatev904.13.2021
MEDICALRECORD
CONSENTTOPARTICIPATEINANNIHCLINICALRESEARCHSTUDY
feverthatusuallylastslessthan12hours.Oncetreatmentformalariaisstarted,thefeverdoesnot
lastlongerthan48hours.
Othersymptomsofheadache,nausea,vomiting,andlossofappetitemayoccur.Thesesymptoms
maylastanaverageof3days,witharangeof1to6dayswhentreatmentisstartedsoonafter
malariaparasitesareidentifiedbybloodtests.Failuretoreturnfortestingortreatmentafter
aCHMIcanresultinaseriouscaseofmalariathatislife-threatening.Forthisreason,you
mustgivethenamesandphonenumbersofatleasttwoemergencycontactstothestudystaff.We
willcontactthembeforetheCHMItoconfirmcommunicationwiththemincasewearenotable
toreachyoubyphone,text,oremailafterCHMI.
Amongthe2,700+participantswhohaveparticipatedinaCHMIsince1971,twoseriousevents
havebeenreported.Bothwerecardiacevents(chestpain)andoccurredinpeoplewhogotan
investigationalmalariavaccine.Thepainwasthoughttobeduetomyocarditis(inflammationof
theheartmuscle).Myocarditisisareportedcomplicationfromvaccinations.Rarely,myocarditis
hasalsobeenreportedinassociationwithnaturally-acquiredmalariainfection.
ThesearetheonlytwocasesweknowaboutinwhichacardiaceventoccurredafterCHMI.In
the unlikely event that you develop myocarditis, you will be evaluated and followed by a
cardiologistuntilresolution.
IfyoufeelunwellatanytimeaftertheCHMI,youmaybeaskedtoremainintheclinicuntilyou
arecheckedbyastudydoctor. Youmightstayinthehospitalovernightifneeded.
POSSIBLERISKSFROMTREATMENTFORMALARIA–GROUPS1-5ONLY
EveryonewhotakespartintheCHMIwillgetantimalarialtreatmentbyDay21afterCHMI.
Standardtreatmentformalariatakes72hourstocomplete. Wewillgiveyouthemedicationatthe
firstsignofinfectioninyourblood.Youshouldexpecttohavemalariasymptomsforabout3
days.OnlydrugsapprovedbytheU.S.FDAwillbeusedfortreatmentofmalaria.Wewilltreat
youwithMalarone unlessyou have aknown allergy. Inthat case,wewould treat youwith
chloroquineoranothersuitablealternative.Anydrugsgivenareeffectiveintreatingthetypeof
malariaparasiteusedfortheCHMI.
Thedrugsthattreatmalariamayalsocausesomesideeffects.Treatmentsandtheirsideeffects
aredescribedbelow:
1.
ThefirstlineoftreatmentwillbeMalarone.IfyougetMalarone,youmayhavethe
followingsideeffects:
·
Nausea,vomiting,abdominalpain,lossofappetite,diarrhea
·
Temporaryelevationofliverfunctiontests
·
Headacheandcoughing
·
Rarely,lowbloodcount,oralirritationorulcers,insomnia,fever,
swelling,rashandhairloss
2.
Anotherbackuptreatmentoptionwillbechloroquine.Ifyougetchloroquine,you
mayhavethefollowingsideeffects:
·
Nausea, vomiting, abdominal pain, diarrhea, dizziness, sleep
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PATIENTIDENTIFICATION
ConsenttoParticipateinaClinicalResearchStudy
NIH-2977(4-17)
FileinSection4:ProtocolConsent(1)
VersionDate:11/03/2021V2.0
Page10 of19
CCICFtemplatev904.13.2021
MEDICALRECORD
CONSENTTOPARTICIPATEINANNIHCLINICALRESEARCHSTUDY
disturbances andphotosensitivity
·
Headache,blurredvision,ringinginears
·
Itching,skinrash,andmakeconditionsofpsoriasis(itchyskinrash)and
porphyria(raredisturbanceofmetabolismthatcanbeseenasdisordersof
theskinorotherorgans)worse
·
Longtermusecancausepermanenteyedamageordeafness,butyouwill
onlybereceivingashortcourseoftreatment
·
Rarely,theremaybechangesinelectrocardiograms(testofheart’selectrical
activity)andlowbloodpressure
Ifyouneedtreatmentwithanyotherantimalarialdrug,wewillgiveyouinformationaboutthe
side effects of that drug. You can also take over-the-counter medicine, like acetaminophen
(Tylenol)and/oribuprofenforfever,headacheorothersymptomsofmalaria.
MOSQUITOBITESITEREACTIONS–GROUPS1-5ONLY
Local,allergicreactionsarecommonaftermosquitobites.Youmayhaveitchingandraised,red
swellingatthesitesofthebites.Thesereactionsusuallydevelopquickly,goaway1to4days
afteramosquitobite,anddonotneedtreatment.Sofar,nosevereallergicreactionstomosquito
biteshavebeenreportedinpriorCHMIstudies. Youwillbeobservedfor30minutesafterthelast
mosquitobite.Wewillcheckthebiteareaandwatchforanysevereallergicsigns.Wemaygive
youasteroidcreamtouseontheskinreactions.
POSSIBLERISKSFROMSTOREDSAMPLES
Thereisasmallchancethatinformationfromyourmedicalrecordscouldbegiventosomeone
whoshouldnotgetitwithoutyourpermission.Itispossibleforsomeonetousethatinformation
todiscriminateagainstyouwhenyouapplyforinsuranceoremployment.Similarproblemsmay
occurifyougiveinformationaboutyourselforagreetohaveyourmedicalrecordsreleased.
POSSIBLERISKSOFDATASHARING
Informationintheshareddatabasescouldbelinkedbacktoyouandusedtodiscriminateagainst
you or your family.  State and federal laws provide some protections against genetic and
preexistingconditionsdiscrimination.
POSSIBLERISKSRELATEDTOPREGNANCY
Ifyouareabletobecomepregnant,wewilldoapregnancytestbeforebeginningthisstudy.We
willalsogiveyouapregnancytestbeforeyougetL9LSandbeforeCHMI.Youmustuseeffective
birthcontrolmethodsandtrynottobecomepregnantwhiletakingpartinthisstudy.Ifyoubecome
pregnant, there may be unknown risks to the fetus or unborn child, or risks that we did not
anticipate.Theremaybelong-termeffectsofthetreatmentbeingstudiedthatcouldincreasethe
riskofharmtoafetus.Youmusttellthestudydoctorifyourbirthcontrolmethodfailswhileyou
areinthestudy. Ifyouthinkorknowyouhavebecomepregnantwhiletakingpartinthisresearch
study,pleasecontacttheresearchteammemberidentifiedatthetopofthisdocumentassoonas
possible.Youshouldnotplantobecomepregnantuntilyouhavecompletedparticipationinthis
study.
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PATIENTIDENTIFICATION
ConsenttoParticipateinaClinicalResearchStudy
NIH-2977(4-17)
FileinSection4:ProtocolConsent(1)
VersionDate:11/03/2021V2.0
Page11 of19
CCICFtemplatev904.13.2021
MEDICALRECORD
CONSENTTOPARTICIPATEINANNIHCLINICALRESEARCHSTUDY
SAFETYMEASURESYOUSHOULDUSEASAPARTICIPANTINTHESTUDY
YoushouldnotexpectL9LStoprotectyoufrommalariainthefuture.Youshouldassumethat
youarenotprotectedfrommalaria.Afterleavingthestudy,youshouldfollowyourphysician’s
instructionstopreventmalariainfection.Wealsoaskthatyoufollowourinstructionsbelow:
·
Travel:DonottraveloutsidethelocalareafromtheCHMIthrough28daysafter.
Beforeorafterthispoint,pleaseletthestudystaffknowaboutplannedtravelssowe
canscheduleyourvisitsandhavecontactinformationbeforeyoutravel.Weaskthat
you not travel to any areas with malaria during the entire period of the study.
Country-specificinformationcanbeprovided.ThisdoesnotapplytoGroup6.
·
UseofAntibiotics:Avoidtakingantibioticsstarting4weeksbeforetheCHMIand
duringtheCHMIunlessprescribedbyaphysician.Pleasenotifythestudyteam
immediately if an antibiotic is prescribed for you or if you consider taking an
antibioticduringthecourseofthestudy.ThisdoesnotapplytoGroup6.
·
BloodDonation: Youwillnotbepermittedtodonatebloodfortransfusionpurposes
whileinthestudy,for1yearafteryourL9LSadministrationandfor3yearsafterthe
CHMI.Tomakesurethatbloodissafefordonation,bloodbankswillnotaccept
blooddonationsfor1yearafterexposuretoaninvestigationalproduct(L9LS)and
for3yearsfromanyonewhoisinfectedwithortreatedformalaria.
·
MosquitoAvoidance:FortwoweeksaftertheCHMIyoushouldpracticemosquito
avoidant behaviors. This includes covering your skin when outside, avoiding
outdoorsattimesmosquitoesareactive(dusk,evening,dawn),usinginsectrepellants
appropriately on yourself and your clothes, and maintaining effective mosquito
barriersinyourhomesuchasscreendoorsandwindows.Clinicalstaffwillcover
thesewithyouagainindetailduringtheCHMIprocess.ThisdoesnotapplytoGroup
6.
WHATARETHEBENEFITSOFBEINGINTHESTUDY?
Youwillnotbenefitfrombeinginthisstudy.
Arethereanypotentialbenefitstoothersthatmightresultfromthestudy?
Inthefuture,otherpeoplemightbenefitfromthisstudybecausetheinformationmayhelpuslearn
moreaboutpreventingandtreatingmalariainfection.Resultsfromthisstudymayalsobeusedto
helpdevelopnewproductsthattargetmalariaorotherinfectiousdiseasesinthefuture.
WHATOTHEROPTIONSARETHEREFORYOU?
Beforeyoudecidewhetherornottobeinthisstudy,wewilldiscussotheroptions thatare
availabletoyou.Insteadofbeinginthisstudy,youcouldchoosenottotakepart.Youmaybe
eligibleforotherVRCstudies.
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PATIENTIDENTIFICATION
ConsenttoParticipateinaClinicalResearchStudy
NIH-2977(4-17)
FileinSection4:ProtocolConsent(1)
VersionDate:11/03/2021V2.0
Page12 of19
CCICFtemplatev904.13.2021
MEDICALRECORD
CONSENTTOPARTICIPATEINANNIHCLINICALRESEARCHSTUDY
DISCUSSIONOFFINDINGS
Newinformationaboutthestudy
Ifwefindoutanynewinformationthatmayaffectyourchoicetoparticipateinthisstudy,we
willgetintouchwithyoutoexplainwhatwehavelearned.Thismaybeinformationwehave
learned while doing this study here at the NIH or information we have learned fromother
scientistsdoingsimilarresearchinotherplaces.
Returnofresearchresults
Ateachvisityouwillbecheckedforanyhealthchangesorproblems.Bloodwillbedrawnat
almosteverystudyvisittoeithercheckonyourhealthorcollectsamplesforresearch.Youwillbe
toldrightawaybyphonecall,text,orinpersonintheclinicifanyofyourtestresultsshowahealth
problem.
AftertheCHMI,wewilldrawyourbloodtotestformalariaparasites. Youwillbetoldrightaway
byphone,orinpersonintheclinicifwefindthatyouhavemalariainfection.
WewillusesomeofthebloodsamplestostudyhowlongL9LSremainsinyourbodyandifyour
bodydevelopsanimmuneresponsetoL9LSandtotheCHMI.Wewillalsostudythemalaria
parasitesthatwemayfindinyourbloodstreamaftertheCHMIifyougetmalariainfection.These
testsareforresearchpurposesonlyandarenotforcheckingonyourhealth.Wewillnotgiveyou
theseresults.
The results of this study may be reported inmedical journals,on the internet orat scientific
meetings.Wewillgiveyouinformationabouthowtofindthestudyresultsoncetheyareavailable.
EARLYWITHDRAWALFROMTHESTUDY
Youmayberemovedfromtheresearchstudybytheresearcherforanyofthefollowingreasons:
·
Notkeepingappointmentsorfollowingstudyprocedures;
·
Gettingaseriousillnessthatneedsongoingmedicalcare;
·
Enrollinginanotherresearchstudyatthesametimeyouareinthisstudy;
·
Becomingpregnant;
·
Thestudyisstoppedorcancelled;
·
Theresearcherbelievesthatitisinyourbestinteresttoremoveyoufromthestudy.
·
Thestudyisstoppedbyregulatoryagencies,thestudysponsororstudy
investigators.Ifthishappens,wewilltellyouwhy.
Youcanstoptakingpartinthestudyatanytime.However,ifyoudecidetostoptakingpartin
thisstudy,youwillbeaskedtokeepfollowupvisitssowecancheckyourhealth,especiallyif
yougotadoseofL9LSortakepartintheCHMI. Wemaystopcollectingsamplesthatarefor
researchpurposesonly.
Wedon’tknowifyouwillgetmalariaaftertheCHMI.Ifyouchoosetostopthestudyafterthe
CHMIandbeforecompletionofmonitoringformalariainfection,youwillneedtobetreatedfor
malariabythestudydoctorregardlessofwhetheryoudevelopsymptomsofmalariaorparasites
inyourblood.
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PATIENTIDENTIFICATION
ConsenttoParticipateinaClinicalResearchStudy
NIH-2977(4-17)
FileinSection4:ProtocolConsent(1)
VersionDate:11/03/2021V2.0
Page13 of19
CCICFtemplatev904.13.2021
MEDICALRECORD
CONSENTTOPARTICIPATEINANNIHCLINICALRESEARCHSTUDY
STORAGE,SHARINGANDFUTURERESEARCHUSINGYOURSPECIMENSAND
DATA
Willyourspecimensordatabesavedforuseinotherresearchstudies?
Aspartofthisstudy,weareobtainingspecimensanddatafromyou.Wewillremoveallthe
identifiers,suchasyourname,dateofbirth,address,ormedicalrecordnumberandlabelyour
specimensanddatawithacodesothatyoucannoteasilybeidentified.However,thecodewill
belinkedthroughakeytoinformationthatcanidentifyyou.Weplantostoreandusethese
specimensanddataforstudiesotherthantheonesdescribedinthisconsentformthataregoing
onrightnow,aswellasstudiesthatmaybeconductedinthefuture.Thesestudiesmayprovide
additional information that will be helpful in understanding malaria, or other diseases or
conditions. This could include studies to develop other research tests, treatments, drugs, or
devices,thatmayleadtothedevelopmentofacommercialproductbytheNIHand/oritsresearch
orcommercialpartners.Therearenoplanstoprovidefinancialcompensationtoyouifthis
happens.Also,itisunlikelythatwewilllearnanythingfromthesestudiesthatmaydirectly
benefityou.
Byagreeingtotakepartinthisstudy,yougivepermissionforyourcodedspecimensanddatato
bestoredandusedforfutureresearchasdescribedabove.
Willyourspecimensordatabesharedforuseinotherresearchstudies?
Wemayshareyourcodedspecimensanddatawithotherresearchers.Ifwedo,whilewewill
maintainthecodekey,wewillnotshareit,sotheotherresearcherswillnotbeabletoidentify
you.Theymaybedoingresearchinareasthataresimilartothisstudyorinotherunrelated
areas.TheseresearchersmaybeatNIH,otherresearchcentersandinstitutions,orcommercial
entities.
Byagreeingtotakepartinthisstudy,yougivepermissionforyourcodedspecimensanddatato
besharedwithotherresearchersandusedbytheseresearchersforfutureresearchasdescribed
above.
Ifyouchangeyourmindanddonotwantustostoreanduseyourspecimensanddataforfuture
research,youshouldcontacttheresearchteammemberidentifiedatthetopofthisdocument.
Wewilldoourbesttocomplywithyourrequestbutcannotguaranteethatwewillalwaysbe
abletodestroyyourspecimensanddata.Forexample,ifsomeresearchwithyourspecimens
anddatahasalreadybeencompleted,theinformationfromthatresearchmaystillbeused.Also,
forexample,ifthespecimensanddatahavebeensharedalreadywithotherresearchers,itmight
notbepossibletowithdrawthem.
Inadditiontotheplanneduseandsharingdescribedabove,wemightremoveallidentifiersand
codesfromyourspecimensanddataanduseorsharethemwithotherresearchersforfuture
researchattheNIHorotherplaces.Whenweortheotherresearchersaccessyouranonymized
data,therewillbenowaytolinkthespecimensordatabacktoyou.Wewillnotcontactyouto
askyourpermissionorotherwiseinformyoubeforewedothis.Wemightdothisevenifyou
answered"no"totheabovequestions.Ifwedothis,wewouldnotbeabletoremoveyour
specimensordatatopreventtheiruseinfutureresearchstudies,evenifyouasked,becausewe
willnotbeabletotellwhichareyourspecimensordata.
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PATIENTIDENTIFICATION
ConsenttoParticipateinaClinicalResearchStudy
NIH-2977(4-17)
FileinSection4:ProtocolConsent(1)
VersionDate:11/03/2021V2.0
Page14 of19
CCICFtemplatev904.13.2021
MEDICALRECORD
CONSENTTOPARTICIPATEINANNIHCLINICALRESEARCHSTUDY
NIHpoliciesrequirethatyourclinicalandotherstudydatabeplacedinaninternalNIHdatabase
thatisaccessibletootherNIHresearchersforfutureresearch.Usually,theseresearcherswillnot
haveaccesstoanyofyouridentifiers,suchasyourname,dateofbirth,address,ormedical
recordnumber;andyourdatawillbelabeledwithonlyacode.Wecannotofferyouachoiceof
whetheryourdatatobeplacedinthisdatabaseornot.Ifyoudonotwishtohaveyourdata
placedinthisdatabase,youshouldnotenrollinthisstudy.
GENETICTESTING
Someoftheblooddrawnfromyouduringthisstudywillbeusedforgenetictests.Somegenetic
testsaredoneinresearchstudiestoseeiftherearegeneticdifferenceinimmuneresponses.Your
bloodsampleusedinthesegenetictestswillnothaveyournameonit,andtheresultswillnot
beinyourmedicalrecord.
HowlongwillyourspecimensanddatabestoredbytheNIH?
YourspecimensanddatamaybestoredbytheNIHindefinitely.
Risksofstorageandsharingofspecimensanddata
Whenwestoreyourspecimensanddata,wetakeprecautionstoprotectyourinformationfrom
othersthatshouldnothaveaccesstoit.Whenweshareyourspecimensanddata,wewilldo
everythingwecantoprotectyouridentity,forexample,whenappropriate,weremoveinformation
thatcanidentifyyou.Evenwiththesafeguardsweputinplace,wecannotguaranteethatyour
identitywillneverbecomeknown,orsomeonemaygainunauthorizedaccesstoyourinformation.
Newmethodsmaybecreatedinthefuturethatcouldmakeitpossibletore-identifyyourspecimens
anddata.
PAYMENT
Willyoureceiveanytypeofpaymentfortakingpartinthisstudy?
YouwillbecompensatedforyourtimeandinconveniencebytheNIHClinicalResearchVolunteer
ProgramperNIHpoliciesandguidelines.Itispossiblethatyoumayhavesomeexpensesthatare
notcoveredbythecompensationprovided.
Thecompensationforspecificstudyvisitsisasfollows:
·
$430forthestudyvisitthatincludesIVadministrationofL9LS
·
$375forthestudyvisitthatincludesSCorIMadministrationofL9LS$455
forthemalariachallenge(CHMI)withpre-CHMIclinicvisitandactivities
·
$25totalforthetimelycompletionofall7daysofanelectronicdiary
·
$200forascheduledfollow-upvisitthatincludesblooddraw
·
$85forallotherclinicvisitsthatdonotincludeblooddraws
TotalcompensationforcompletionofallstudyvisitsincludingCHMIisbetween$4195and$5950
ifyougetL9LSbyIVandbetween$4340and$6140ifyougetL9LSbySC.Compensationfor
theIMgroupisaround$2800.CompensationforCHMIvisitsforthecontrolgroupisbetween
about$1625and$3425.Thetotalcompensationyougetisbasedonthenumberandtypeofstudy
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PATIENTIDENTIFICATION
ConsenttoParticipateinaClinicalResearchStudy
NIH-2977(4-17)
FileinSection4:ProtocolConsent(1)
VersionDate:11/03/2021V2.0
Page15 of19
CCICFtemplatev904.13.2021
MEDICALRECORD
CONSENTTOPARTICIPATEINANNIHCLINICALRESEARCHSTUDY
visitsyoucomplete.Ifyouareunabletofinishthestudy,youwillgetcompensationonlyforthe
studyvisitsyoucompleted.
Youwillgetthecompensationabout2weeksaftereachcompletedvisitbydirectdepositintoa
bankaccountthatyouspecifytotheVolunteerPaymentOffice.
Thestudyteamwillcollectsocialsecuritynumbersfromresearchparticipantsforpurposesof
compensation.Participantscanwithholdtheirsocialsecuritynumbersandstillparticipateinthe
researchstudy;howeveryoumaynotbeabletoreceivecompensationifyoudoso.
Withfewexceptions,studycompensationisconsideredtaxableincomethatisreportabletothe
InternalRevenueService(IRS).A“Form1099-OtherIncome”willbesenttoyouifyourtotal
paymentsforresearchparticipationare$600ormoreinacalendaryear.Ifyouhaveunpaiddebt
to the federal government, please be aware that some or all of your compensation may be
automaticallyreducedtorepaythatdebtonyourbehalf.
REIMBURSEMENT
WillyoureceivereimbursementordirectpaymentbyNIHaspartofyourparticipation?
Thisstudydoesnotofferreimbursementforparticipants,orpaymentof,hotel,travel,ormeals.
COSTS
Willtakingpartinthisresearchstudycostyouanything?
NIHdoesnotbillhealthinsurancecompaniesorparticipantsforanyresearchorrelatedclinical
carethatyoureceiveattheNIHClinicalCenter.
CONFLICTOFINTEREST(COI)
TheNIHreviewsNIHstaffresearchersatleastyearlyforconflictsofinterest.Thisprocessis
detailedinaCOIGuide.YoumayaskyourresearchteamforacopyoftheCOIGuideorformore
information.MembersoftheresearchteamwhodonotworkforNIHareexpectedtofollowthese
guidelinesortheguidelinesoftheirhomeinstitution,buttheydonotneedtoreporttheirpersonal
financestotheNIH.
TheNIHandtheresearchteamforthisstudyhavedevelopedtheinvestigationalproduct,L9LS,
being usedinthisstudy.Thismeansitis possiblethattheresultsofthisstudy couldleadto
paymentstoNIH.Bylaw,thegovernmentisrequiredtosharesuchpaymentswiththeemployee
inventors.YouwillnotreceiveanymoneyfromthedevelopmentofL9LS.
CLINICALTRIALREGISTRATIONANDRESULTSREPORTING
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,oncetheyareavailable.Youcansearchthiswebsiteatany
time.
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PATIENTIDENTIFICATION
ConsenttoParticipateinaClinicalResearchStudy
NIH-2977(4-17)
FileinSection4:ProtocolConsent(1)
VersionDate:11/03/2021V2.0
Page16 of19
CCICFtemplatev904.13.2021
MEDICALRECORD
CONSENTTOPARTICIPATEINANNIHCLINICALRESEARCHSTUDY
CONFIDENTIALITYPROTECTIONSPROVIDEDINTHISSTUDY
Willyourmedicalinformationbekeptprivate?
Wewilldoourbesttomakesurethatthepersonalinformationinyourmedicalrecordwillbekept
private.However,wecannotguaranteetotalprivacy.Organizationsthatmaylookatand/orcopy
yourmedicalrecordsforresearch,qualityassurance,anddataanalysisinclude:
·
TheNIHandothergovernmentagencies,liketheFoodandDrugAdministration(FDA),
whichareinvolvedinkeepingresearchsafeforpeople.
·
NIHIntramuralInstitutionalReviewBoard
·
ThestudySponsor(VRC)ortheiragent(s)
·
United States Army Medical Research and Development Command (USAMRDC)
representatives
TheresearchersconductingthisstudyandtheNIHfollowapplicablelawsandpoliciestokeep
youridentifyinginformationprivatetotheextentpossible.However,thereisalwaysachance
that,despiteourbest efforts,youridentity and/orinformationabout yourparticipationinthis
researchmaybeinadvertentlyreleasedorimproperlyaccessedbyunauthorizedpersons.
Inmostcases,theNIHwillnotreleaseanyidentifiableinformationcollectedaboutyouwithout
yourwrittenpermission.However,yourinformationmaybesharedasdescribedinthesectionof
thisdocumentonsharingofspecimensanddata,andasfurtheroutlinedinthefollowingsections.
Further, the information collected for this study is protected by NIH under a Certificate of
ConfidentialityandthePrivacyAct.
CertificateofConfidentiality
To help us protect your privacy, the NIH Intramural Program has received a Certificate of
Confidentiality(Certificate).Withthiscertificate,researchersmaynotreleaseorusedataor
informationaboutyouexceptincertaincircumstances.
NIHresearchersmustnotshareinformationthatmayidentifyyouinanyfederal,state,orlocal
civil,criminal,administrative,legislative,orotherproceedings,forexample,ifrequestedbya
court.
TheCertificatedoesnotprotectyourinformationwhenit:
1. isdisclosedtopeopleconnectedwiththeresearch,forexample,informationmaybeused
forauditingorprogramevaluationinternallybytheNIH;or
2. isrequiredtobedisclosedbyFederal,State,orlocallaws,forexample,wheninformation
must be disclosed to meet the legal requirements of the federal Food and Drug
Administration(FDA);
3. isforotherresearch;
4. isdisclosedwithyourconsent.
TheCertificatedoesnotpreventyoufromvoluntarilyreleasinginformationaboutyourselforyour
involvementinthisresearch.
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PATIENTIDENTIFICATION
ConsenttoParticipateinaClinicalResearchStudy
NIH-2977(4-17)
FileinSection4:ProtocolConsent(1)
VersionDate:11/03/2021V2.0
Page17 of19
CCICFtemplatev904.13.2021
MEDICALRECORD
CONSENTTOPARTICIPATEINANNIHCLINICALRESEARCHSTUDY
TheCertificatewillnotbeusedtopreventdisclosuretostateorlocalauthoritiesofharmtoselfor
othersincluding,forexample,childabuseandneglect,andbysigningbelowyouconsenttothose
disclosures.OtherpermissionsforreleasemaybemadebysigningNIHforms,suchastheNotice
andAcknowledgementofInformationPracticesconsent.
PrivacyAct
TheFederalPrivacyActgenerallyprotectstheconfidentialityofyourNIHmedicalinformation
thatwecollectundertheauthorityofthePublicHealthServiceAct.Insomecases,thePrivacy
ActprotectionsdifferfromtheCertificateofConfidentiality.Forexample,sometimesthePrivacy
Actallowsreleaseofinformationfromyourrecordwithoutyourpermission,forexample,ifitis
requestedbyCongress.Informationmayalsobereleasedforcertainresearchpurposeswithdue
considerationandprotection,tothoseengagedbytheagencyforresearchpurposes,tocertain
federalandstateagencies,forHIVpartnernotification,forinfectiousdiseaseorabuseorneglect
reporting,totumorregistries,forqualityassessmentandmedicalaudits,orwhentheNIHis
involvedinalawsuit.However,NIHwillonlyreleaseinformationfromyourmedicalrecordifit
ispermittedbyboththeCertificateofConfidentialityandthePrivacyAct.
POLICYREGARDINGRESEARCH-RELATEDINJURIES
TheNIHClinicalCenterwillprovideshort-termmedicalcareforanyinjuryresultingfromyour
participationinresearchhere.Ingeneral,nolong-termmedicalcareorfinancialcompensationfor
research-relatedinjurieswillbeprovidedbytheNIH,theNIHClinicalCenter,ortheFederal
Government.However,youhavetherighttopursuelegalremedyifyoubelievethatyourinjury
justifiessuchaction.
FORINJURIESRELATEDTOCHMI
IfyouareinjuredbecauseofyourparticipationinthisresearchduringtheCHMIandyouarea
DOD healthcare beneficiary (e.g., active duty in the military, military spouse or dependent,
retiree),youareentitledtomedicalcareforyourinjurywithintheDODhealthcaresystem,aslong
asyouremainaDODhealthcarebeneficiary.
IfyouareinjuredbecauseofyourparticipationinthisresearchduringtheCHMIandyouarenot
aDODhealthcarebeneficiary,youareentitledtomedicalcareforyourinjuryataDODhospital
orclinic,butsuchcareforyourinjuryatDODhospitalsorclinicsmaybetime-limited,andyour
insurancemaybebilled.ItcannotbedeterminedinadvancewhichDODhospitalorclinicwill
providecare.Ifyouobtaincareforresearch-relatedinjuriesoutsideofaDODhospitalorclinic,
youoryourinsurancewillberesponsibleformedicalexpenses.
ForDODhealthcarebeneficiariesandnon-DODhealthcarebeneficiaries:Transportationtoand
fromhospitalsorclinicswillnotbeprovided.Noreimbursementisavailableifyouincurmedical
expenses to treat research-related injuries. No compensation is available for research-related
injuries.Youarenotwaivinganylegalrights.Ifyoubelieveyouhavesustainedaresearch-related
injury,pleasecontactthePrincipalInvestigator(PI).Ifyouhaveanyquestions,pleasecontactthe
PI.
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PATIENTIDENTIFICATION
ConsenttoParticipateinaClinicalResearchStudy
NIH-2977(4-17)
FileinSection4:ProtocolConsent(1)
VersionDate:11/03/2021V2.0
Page18 of19
CCICFtemplatev904.13.2021
MEDICALRECORD
CONSENTTOPARTICIPATEINANNIHCLINICALRESEARCHSTUDY
PROBLEMSORQUESTIONS
If you have any problems or questions about this study, or about your rights as a research
participant,oraboutanyresearch-relatedinjury,contactthePrincipalInvestigator,RichardWu,
MD at
 Other researchers you may call are: Floreliz
Mendoza,RNorLasonjiHolman,FNPat
YoumayalsocalltheNIHClinical
CenterPatientRepresentativeat
ortheNIHOfficeofIRBOperationsat
ifyouhavearesearch-relatedcomplaintorconcern.
CONSENTDOCUMENT
Pleasekeepacopyofthisdocumentincaseyouwanttoreaditagain.
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PATIENTIDENTIFICATION
ConsenttoParticipateinaClinicalResearchStudy
NIH-2977(4-17)
FileinSection4:ProtocolConsent(1)
VersionDate:11/03/2021V2.0
Page19 of19
CCICFtemplatev904.13.2021
MEDICALRECORD
CONSENTTOPARTICIPATEINANNIHCLINICALRESEARCHSTUDY
AdultResearchParticipant:Ihavereadtheexplanationaboutthisstudyandhavebeengiventheopportunity
todiscussitandtoaskquestions.Iconsenttoparticipateinthisstudy.
SignatureofResearchParticipant
PrintNameofResearchParticipant
Date
Investigator:
SignatureofInvestigator
PrintNameofInvestigator
Date
Witnessshouldsignbelowifeither:
1. Ashortformconsentprocesshasbeenusedtoenrollanon-Englishspeakingsubjector
2. Anoralpresentationofthefullconsenthasbeenusedtoenrollablindorilliteratesubject
SignatureofWitness
PrintNameofWitness
Date
NIH ADMINISTRATIVE SECTION TO BE COMPLETED REGARDING THE USE OF AN
INTERPRETER:
Aninterpreter,orotherindividual,whospeaksEnglishandtheparticipant’spreferredlanguagefacilitated
theadministrationofinformedconsentandservedasawitness.Theinvestigatorobtainingconsentmaynot
alsoserveasthewitness.
Aninterpreter,orotherindividual,whospeaksEnglishandtheparticipant’spreferredlanguagefacilitated
theadministrationofinformedconsentbutdidnotserveasawitness.ThenameorIDcodeoftheperson
providinginterpretivesupportis:
.
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