Safety and Pharmacokinetics of a Human Monoclonal Antibod... | NCT03478891

NCT03478891

ID	Type	Description	Link
18-I-0069

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Detailed Description

VRC 608: A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-EBOMAB092-00-AB (MAb114), Administered Intravenously to Healthy Adults

Study Design: VRC 608 is the first-in-human Phase I study to examine safety, tolerability and pharmacokinetics of the monoclonal antibody (MAb), VRC-EBOMAB092-00-AB (MAb114). MAb114 will be administered as a single dose. The hypotheses are: 1) MAb114 administration to healthy adults will be safe by the intravenous (IV) route; and 2) MAb114 will be detectable in human sera with a definable half-life. The primary objectives are to evaluate the safety and tolerability of MAb114 in healthy adults. Secondary objectives will evaluate the pharmacokinetics of MAb114 and the potential to detect an anti-drug antibody response to MAb114.

Product Description: MAb114 is a human IgG1 MAb targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP). It was developed by the VRC/NIAID/NIH and manufactured at Cook Pharmica LLC d.b.a. Catalent Indiana, LLC (Bloomington, IN) under current Good Manufacturing Practice (cGMP) regulations. MAb114 is supplied as a lyophilized product in a glass vial at 400 mg per vial with target overfill to 425 mg per vial.

Subjects: Up to 30 healthy adults, 18-60 years of age.

Study Plan: This is an open-label, dose-escalation study of MAb114 administered by IV infusion at dosages of 5, 25 and 50 mg/kg (Groups 1-3). Enrollment will begin with the lowest dose group. Following the first product administration in each group, the study team will wait at least 3 days before administering MAb114 to a second subject within the same group. Dose-escalation evaluations will occur to ensure the safety data support proceeding to the higher doses. Solicited reactogenicity following product administration will be evaluated using a 3-day diary. Assessment of safety will include clinical observation and monitoring of serum hematological and chemical parameters at defined timepoints throughout the study.

Group 1: 3 subjects; 5 mg/kg IV
Group 2: 5 subjects; 25 mg/kg IV
Group 3: 10 subjects; 50 mg/kg IV
Total* 18 subjects
- A minimum of 18 subjects will be enrolled. Enrollment up to a total of 30 subjects is permitted if additional subjects are necessary for safety or pharmacokinetic (PK) evaluations.

Study Duration: Subjects will be followed for 24 weeks after the study product administration.

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Group 1: 5 mg/kg IV	Experimental	Group 1 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 5 mg/kg.	Biological: VRC-EBOMAB092-00-AB (MAb114)
Group 2: 25 mg/kg IV	Experimental	Group 2 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 25 mg/kg.	Biological: VRC-EBOMAB092-00-AB (MAb114)
Group 3: 50 mg/kg IV	Experimental	Group 3 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 50 mg/kg.	Biological: VRC-EBOMAB092-00-AB (MAb114)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
VRC-EBOMAB092-00-AB (MAb114)	Biological	VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Subjects Experiencing Infusion Reaction During Product Administration	Possible infusion reaction symptoms: unusually tired/feeling unwell, muscles aches, headache, chills, rigors, nausea, fever, joint pain, urticaria/rash, and pruritus. Also information was collected if administration was slowed down or stopped for reactogenicity reasons.	About 30 minutes of product administration
Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of Product Administration	Subjects recorded 3-day systemic reactogenicity symptoms in a diary after study product administration. Solicited systemic symptoms include: unusually tired/feeling unwell, muscles aches, headache, chills, nausea, fever and joint pain. Subjects recorded highest measured temperature daily. Clinicians reviewed the diary with the subject and collected resolution information for any symptoms that were not resolved within 3 days. Subjects were counted once for each symptom at the worst severity if they indicated experiencing the symptom at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of subjects experiencing any systemic symptom as reported at the worst severity. Solicited reactogenicity was recorded without an attribution assessment. Grading was done by Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 2.1.	3 days after product administration
Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Product Administration	Local reactogenicity symptoms were assessed and recorded by clinicians. Solicited local symptoms include pain/tenderness, swelling, redness, bruising, and pruritus (itchiness) at the product administration site. Clinicians assessed the study product administration site for local symptoms on the day of product administration after completion of the administration and on Days 1, 2 and 7 post administration. Subjects were counted once for each symptom at the worst severity if they experienced the symptom at any severity during the reporting period. If symptoms were experienced, clinicians collected resolution information for any symptom that wasn't resolved within 7 days. The number reported for "Any Local Symptom" is the number of subjects reporting any local symptom as reported at the worst severity. Solicited reactogenicity was recorded without attribution assessment. Grading was done by Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 2.1.

Secondary Outcomes

Measure	Description	Time Frame
Maximum Observed Serum Concentration (Cmax) of MAb114	Cmax is the peak serum concentration that MAb114 achieves after it has been administered; it is determined as a maximum value on the summary pharmacokinetic (PK) curve for each study group.	Pre-infusion (baseline), end of infusion (0h), 1 hr, 3 hr, 6 hr, 24 hr, 48 hr and 7-28 days post-infusion

Eligibility Module

Eligibility Criteria

INCLUSION CRITERIA:

A volunteer must meet all of the following criteria:

Able and willing to complete the informed consent process.
Available for clinical follow-up through the last study visit.
18 to 60 years of age.
In good general health without clinically significant medical history.
Willing to have blood samples collected, stored indefinitely, and used for research purposes.
Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
Physical examination without clinically significant findings within the 84 days prior to enrollment.
Have screening laboratory values within 84 days prior to enrollment that meet the following criteria:
- White Blood Cell (WBC) 2,500-12,000/mm^3
- WBC differential either within institutional normal range or accompanied by the Principal Investigator (PI) or designee approval
- Platelets = 125,000 - 400,000/mm^3
- Hemoglobin within institutional normal range or accompanied by the PI or designee approval
- Creatinine less than or equal to 1.1 x upper limit of normal (ULN)
- Alanine aminotransferase (ALT) less than or equal to 1.25 x ULN
- Negative for human immunodeficiency virus (HIV) infection by a Food and Drug Administration (FDA) approved method of detection
- Negative for Hepatitis B core antibody (HBcAb) and Hepatitis C virus antibody (HCV Ab)
Criteria applicable to women of childbearing potential:
- If a woman is of reproductive potential and sexually active with a male partner, then she agrees to use an effective means of birth control from the time of study enrollment until the last study visit, or to be monogamous with a partner who has had a vasectomy.
- Negative human chorionic gonadotropin (beta-HCG) pregnancy test (urine or serum) on day of enrollment and product administration.

EXCLUSION CRITERIA:

A volunteer will be excluded from study participation if one or more of the following conditions apply:

Previous receipt of a licensed or investigational monoclonal antibody or Ebola vaccine.
Weight >100 kg.
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.
Hypertension that is not well controlled.
Woman who is breast-feeding, or planning to become pregnant during study participation.
Receipt of any investigational study product within 28 days prior to enrollment.
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, psychiatric disorders, heart disease, or cancer.
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 (IM) injections or blood draws.
Use of angiotensin-converting enzyme (ACE) inhibitors or other potential nephrotoxins.

Contacts/Locations Module

Name	Affiliation	Role
Martin R Gaudinski, M.D.	National Institute of Allergy and Infectious Diseases (NIAID)	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
National Institutes of Health Clinical Center		Bethesda	Maryland	20892	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
26917593	Background	Corti D, Misasi J, Mulangu S, Stanley DA, Kanekiyo M, Wollen S, Ploquin A, Doria-Rose NA, Staupe RP, Bailey M, Shi W, Choe M, Marcus H, Thompson EA, Cagigi A, Silacci C, Fernandez-Rodriguez B, Perez L, Sallusto F, Vanzetta F, Agatic G, Cameroni E, Kisalu N, Gordon I, Ledgerwood JE, Mascola JR, Graham BS, Muyembe-Tamfun JJ, Trefry JC, Lanzavecchia A, Sullivan NJ. Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody. Science. 2016 Mar 18;351(6279):1339-42. doi: 10.1126/science.aad5224. Epub 2016 Feb 25.
26917592

Label	URL
NIH Clinical Center Detailed Web Page	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Group 1: 5 mg/kg IV	Group 1 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 5 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP_ICF	Yes	Yes	Yes	Study Protocol, Statistical Analysis Plan, and Informed Consent Form	Jan 14, 2019

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Group 2: 25 mg/kg IV

Group 3: 50 mg/kg IV

All enrolled subjects

Arm/Group Information

ID	Title	Description
BG000	Group 1: 5 mg/kg IV	Group 1 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 5 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
BG001	Group 2: 25 mg/kg IV	Group 2 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 25 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
BG002	Group 3: 50 mg/kg IV	Group 3 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 50 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG0003 BG0015 BG00211 BG00319

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00039.7± 7.4 BG00136.4± 9.8 BG00239.0± 13.9 BG003

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

21-30 years

Title	Measurements
	BG0000 BG0011 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0001 BG0014 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0011 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

United States

Title	Measurements
	BG0003 BG0015 BG002

Weight

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00088± 8.8 BG00166.3± 12.6 BG002

Education

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
College or University	BG0002 BG0013 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Subjects Experiencing Infusion Reaction During Product Administration

Possible infusion reaction symptoms: unusually tired/feeling unwell, muscles aches, headache, chills, rigors, nausea, fever, joint pain, urticaria/rash, and pruritus. Also information was collected if administration was slowed down or stopped for reactogenicity reasons.

Subjects who received MAb114 (N=18), where "N" signifies number of subjects analyzed for this outcome measure.

Posted

Count of Participants

Participants

About 30 minutes of product administration

ID	Title	Description
OG000	Group 1: 5 mg/kg IV (n=3)	Group 1 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 5 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
OG001	Group 2: 25 mg/kg IV (n=5)	Group 2 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 25 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
OG002	Group 3: 50 mg/kg IV (n=10)	Group 3 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 50 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).

Units	Counts
Participants	OG0003 OG0015 OG00210

Title

Denominators

Categories

Number who experienced infusion reaction

Title	Measurements
	OG0000 OG0010 OG0020

Number who completed infusion in about 30 min

Primary

Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of Product Administration

Subjects recorded 3-day systemic reactogenicity symptoms in a diary after study product administration. Solicited systemic symptoms include: unusually tired/feeling unwell, muscles aches, headache, chills, nausea, fever and joint pain. Subjects recorded highest measured temperature daily. Clinicians reviewed the diary with the subject and collected resolution information for any symptoms that were not resolved within 3 days. Subjects were counted once for each symptom at the worst severity if they indicated experiencing the symptom at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of subjects experiencing any systemic symptom as reported at the worst severity. Solicited reactogenicity was recorded without an attribution assessment. Grading was done by Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 2.1.

Subjects who received MAb114 (N=18), where "N" signifies number of subjects analyzed for this outcome measure.

Posted

Count of Participants

Participants

3 days after product administration

ID	Title	Description
OG000	Group 1: 5 mg/kg IV (n=3)	Group 1 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 5 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
OG001

Primary

Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Product Administration

Local reactogenicity symptoms were assessed and recorded by clinicians. Solicited local symptoms include pain/tenderness, swelling, redness, bruising, and pruritus (itchiness) at the product administration site. Clinicians assessed the study product administration site for local symptoms on the day of product administration after completion of the administration and on Days 1, 2 and 7 post administration. Subjects were counted once for each symptom at the worst severity if they experienced the symptom at any severity during the reporting period. If symptoms were experienced, clinicians collected resolution information for any symptom that wasn't resolved within 7 days. The number reported for "Any Local Symptom" is the number of subjects reporting any local symptom as reported at the worst severity. Solicited reactogenicity was recorded without attribution assessment. Grading was done by Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 2.1.

Subjects who received MAb114 (N=18), where "N" signifies number of subjects analyzed for this outcome measure.

Posted

Count of Participants

Participants

7 days after product administration

ID	Title	Description
OG000	Group 1: 5 mg/kg IV (n=3)	Group 1 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 5 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).

Primary

Number of Subjects Reporting 1 or More Unsolicited Non-Serious Adverse Events

Unsolicited adverse events (AEs) collected during the period from study product administration at Day 0 through 28 days after product administration. After the indicated time period through the last expected study visit at 24 weeks after product administration, only new chronic medical conditions collected as unsolicited AEs.

The number reported is the number of subjects who experienced at least one AE in the reporting period. A subject with multiple experiences of the same event is counted once using the event of worst severity. The relationship between an AE and the product was assessed by the investigator on the basis of his or her clinical judgment and the protocol-specific definitions of Related - There is a reasonable possibility that the AE may be related to the study product and Not Related - There is not a reasonable possibility that the AE is related to the study product.

Subjects who received MAb114 (N=18), where "N" signifies number of subjects analyzed for this outcome measure.

Posted

Count of Participants

Participants

Through 24 weeks after product administration

ID	Title	Description
OG000	Group 1: 5 mg/kg IV (n=3)	Group 1 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 5 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
OG001	Group 2: 25 mg/kg IV (n=5)

Primary

Number of Subjects Reporting Serious Adverse Events

Serious adverse events (SAEs) collected during the period from study product administration at Day 0 through 24 weeks after product administration. Grading done by Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 2.1. The relationship between a SAE and the product was assessed by the investigator on the basis of his or her clinical judgment and the protocol-specific definitions of Related - There is a reasonable possibility that the SAE may be related to the study product and Not Related - There is not a reasonable possibility that the SAE is related to the study product.

Subjects who received MAb114 (N=18), where "N" signifies number of subjects analyzed for this outcome measure.

Posted

Count of Participants

Participants

Through 24 weeks after product administration

ID	Title	Description
OG000	Group 1: 5 mg/kg IV (n=3)	Group 1 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 5 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
OG001	Group 2: 25 mg/kg IV (n=5)	Group 2 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 25 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).

Secondary

Maximum Observed Serum Concentration (Cmax) of MAb114

Cmax is the peak serum concentration that MAb114 achieves after it has been administered; it is determined as a maximum value on the summary pharmacokinetic (PK) curve for each study group.

Subjects with 28 days of pharmacokinetic data.

Posted

Mean

Standard Deviation

µg/mL

Pre-infusion (baseline), end of infusion (0h), 1 hr, 3 hr, 6 hr, 24 hr, 48 hr and 7-28 days post-infusion

ID	Title	Description
OG000	Group 1: 5 mg/kg IV (n=3)	Group 1 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 5 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
OG001	Group 2: 25 mg/kg IV (n=5)	Group 2 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 25 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
OG002	Group 3: 50 mg/kg IV (n=5)

Secondary

Time to Reach Maximum Observed Serum Concentration (Tmax) of MAb114

Tmax is the time it takes to reach Cmax of MAb114 after it has been administered; it is determined based on the summary PK curve for each study group.

Subjects with 28 days of pharmacokinetic data.

Posted

Mean

Standard Deviation

hours

Pre-infusion (baseline), end of infusion (0h), 1 hr, 3 hr, 6 hr, 24 hr, 48 hr and 7-28 days post-infusion

ID	Title	Description
OG000	Group 1: 5 mg/kg IV (n=3)	Group 1 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 5 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
OG001	Group 2: 25 mg/kg IV (n=5)	Group 2 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 25 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
OG002	Group 3: 50 mg/kg IV (n=5)	Group 3 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 50 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).

Secondary

Mean Serum Concentration of MAb114

The mean of individual subject MAb114 serum concentrations by administered dose group

Subjects with 28 days of pharmacokinetic data.

Posted

Mean

Standard Deviation

µg/mL

Pre-infusion (baseline), end of infusion (0h), 1 hr, 3 hr, 6 hr, 24 hr, 48 hr and 7-28 days post-infusion

ID	Title	Description
OG000	Group 1: 5 mg/kg IV (n=3)	Group 1 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 5 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
OG001	Group 2: 25 mg/kg IV (n=5)	Group 2 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 25 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
OG002	Group 3: 50 mg/kg IV (n=5)	Group 3 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 50 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).

Secondary

Overall IV Half-life (T1/2) of MAb114

Half-life (T1/2) is the time required for half of the drug to be eliminated from the serum.

Subjects with 56 days of pharmacokinetic data. No standard deviation reported for a Group 3 single subject data.

Posted

Mean

Standard Deviation

days

Pre-infusion (baseline), end of infusion (0h), 1 hr, 3 hr, 6 hr, 24 hr, 48 hr and 7-56 days post-infusion

ID	Title	Description
OG000	Group 1: 5 mg/kg IV (n=3)	Group 1 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 5 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
OG001	Group 2: 25 mg/kg IV (n=5)	Group 2 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 25 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
OG002	Group 3: 50 mg/kg IV (n=1)	Group 3 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 50 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).

Secondary

Area Under the Curve (AUC0-28D)

The AUC0-28D represents the total drug exposure in 28 days after MAb114 administration; it is determined based on the summary PK curve for each group.

Subjects with 28 days of pharmacokinetic data.

Posted

Mean

Standard Deviation

µg x day/mL

Pre-infusion (baseline), end of infusion (0h), 1 hr, 3 hr, 6 hr, 24 hr, 48 hr and 7-28 days post-infusion

ID	Title	Description
OG000	Group 1: 5 mg/kg IV (n=3)	Group 1 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 5 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
OG001	Group 2: 25 mg/kg IV (n=5)	Group 2 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 25 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
OG002	Group 3: 50 mg/kg IV (n=5)	Group 3 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 50 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).

Secondary

Volume of Distribution (Vd) at Steady-state

Theoretical volume that would be necessary to contain the total amount of administered drug at the same concentration as observed in plasma. It represents the degree to which a drug is distributed in body tissue rather than the plasma and calculated based in the PK curve for each study group.

Subjects with 28 days of pharmacokinetic data.

Posted

Mean

Standard Deviation

Liters

Pre-infusion (baseline), end of infusion (0h), 1 hr, 3 hr, 6 hr, 24 hr, 48 hr and 7-28 days post-infusion

ID	Title	Description
OG000	Group 1: 5 mg/kg IV (n=3)	Group 1 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 5 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
OG001	Group 2: 25 mg/kg IV (n=5)	Group 2 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 25 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
OG002	Group 3: 50 mg/kg IV (n=5)

Secondary

MAb114 Clearance Rate

Rate of MAb114 elimination divided by the plasma MAb114 concentration; determined based on the summary PK curve for each study group.

Subjects with 28 days of pharmacokinetic data.

Posted

Mean

Standard Deviation

mL/day

Pre-infusion (baseline), end of infusion (0h), 1 hr, 3 hr, 6 hr, 24 hr, 48 hr and 7-28 days post-infusion

ID	Title	Description
OG000	Group 1: 5 mg/kg IV (n=3)	Group 1 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 5 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
OG001	Group 2: 25 mg/kg IV (n=5)	Group 2 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 25 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
OG002	Group 3: 50 mg/kg IV (n=5)	Group 3 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 50 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).

Secondary

Number of Subjects Who Produced Anti-drug Antibodies to MAb114

Serum samples collected 28 days and 56 days after MAb114 administration

Subjects with serum samples collected at 28 days and 56 days.

Posted

Count of Participants

Participants

Days 28 and 56 post-infusion

ID	Title	Description
OG000	Group 1: 5 mg/kg IV (n=3)	Group 1 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 5 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
OG001	Group 2: 25 mg/kg IV (n=5)	Group 2 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 25 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
OG002	Group 3: 50 mg/kg IV (n=5)	Group 3 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 50 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Group 1: 5 mg/kg IV	Group 1 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 5 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).	3	0	3	0	3
EG001	Group 2: 25 mg/kg IV	Group 2 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 25 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).	5	0	5	3	5
EG002	Group 3: 50 mg/kg IV	Group 3 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 50 mg/kg. VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).	10	1	10	5	10

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Syncope	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment		EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected10 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hordeolum	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected10 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected10 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected10 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected10 at risk
Alanine aminotransferase increased	Investigations	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected10 at risk
Hypertension	Vascular disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected10 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0023 affected10 at risk
Malaise	General disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0022 affected10 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0021 affected10 at risk
Headache	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected5 at risk EG0022 affected10 at risk
Chills	General disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0021 affected10 at risk
Nausea	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0021 affected10 at risk
Joint Pain	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0021 affected10 at risk

Point of Contact

Title	Organization	Phone	Extension	Email
Martin Gaudinski, MD	Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health	301-451-8715		martin.gaudinski@nih.gov

ID	Term
D019142	Hemorrhagic Fever, Ebola

ID	Term
C000711947	ansuvimab

Group 3 subjects received a single IV infusion of a Human Monoclonal Antibody (MAb), VRC-EBOMAB092-00-AB (MAb114), on Day 0 at a dose of 50 mg/kg.

VRC-EBOMAB092-00-AB (MAb114): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).

ID	Term
D006482	Hemorrhagic Fevers, Viral
D012327	RNA Virus Infections
D014777	Virus Diseases
D007239	Infections
D018702	Filoviridae Infections
D018701	Mononegavirales Infections