Healthy Adult Immune Responses to VaccinePhase 1NCT03478891
Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-EBOMAB092-00-AB (MAb114), Administered Intravenously to Healthy Adults
A Phase 1 study testing VRC-EBOMAB092-00-AB (MAb114) in people with Healthy Adult Immune Responses to Vaccine, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: Ebola is a virus that has infected and killed people mostly in West Africa. There is no treatment or prevention for it, but several drugs are being studied. Researchers want to test the drug MAb114 in healthy people not exposed to Ebola to see whether it can be used for Ebola treatment in people who are… Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Adult Immune Responses to Vaccine
- What is being tested?
- VRC-EBOMAB092-00-AB (MAb114)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 16 May 2018to 20 Mar 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Show all 20Show fewer
- 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.
Who cannot join
- 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.
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: 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
Background:
Ebola is a virus that has infected and killed people mostly in West Africa. There is no treatment or prevention for it, but several drugs are being studied. Researchers want to test the drug MAb114 in healthy people not exposed to Ebola to see whether it can be used for Ebola treatment in people who are infected in the future. This trial will not expose volunteers to the Ebola virus.
Read more
Objectives:
To see if MAb114 is safe and how a person's body responds to it.
Eligibility:
Healthy adults ages 18-60 who weigh 220.5 pounds or less
Design:
Participants will be screened under protocol NIH 11-I-0164 with:
- Medical history
- Physical exam
- Blood or urine tests
Participants will have a first 8- to10-hour visit. They will get MAb114 by IV infusion. For this, a thin tube will be placed in an arm vein. They may get an IV line in their other arm to collect blood. Blood will be taken many times before and after the infusion. Participants may have a urine test.
Participants will get a thermometer to check their temperature for 3 days after they get MAb114. They will record their highest temperature and any symptoms.
Participants will have about 14 more study visits over 6 months. At each visit, they will have blood taken and be checked for any health changes. They will talk about how they are feeling and if they have taken any medications.
At the end of the 6 months, participants may be invited to take part in another study for follow-up sample collection.
Read the 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.
- Being tested
- VRC-EBOMAB092-00-AB (MAb114)
- Keywords
- Ebola Virus, Immune Response, Filovirus, Ebola Hemorrhagic Fever, First in Human
- Medical subject headings
- Hemorrhagic Fever, Ebola
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Biological: VRC-EBOMAB092-00-AB (MAb114) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 7 days after product administration
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.
Measured: Through 24 weeks after product administration
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.
Measured: Through 24 weeks after product administration
Secondary outcomes (8)
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.
Measured: Pre-infusion (baseline), end of infusion (0h), 1 hr, 3 hr, 6 hr, 24 hr, 48 hr and 7-28 days post-infusion
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.
Measured: Pre-infusion (baseline), end of infusion (0h), 1 hr, 3 hr, 6 hr, 24 hr, 48 hr and 7-28 days post-infusion
Mean Serum Concentration of MAb114
The mean of individual subject MAb114 serum concentrations by administered dose group
Measured: Pre-infusion (baseline), end of infusion (0h), 1 hr, 3 hr, 6 hr, 24 hr, 48 hr and 7-28 days post-infusion
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.
Measured: Pre-infusion (baseline), end of infusion (0h), 1 hr, 3 hr, 6 hr, 24 hr, 48 hr and 7-56 days post-infusion
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.
Measured: Pre-infusion (baseline), end of infusion (0h), 1 hr, 3 hr, 6 hr, 24 hr, 48 hr and 7-28 days post-infusion
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.
Measured: Pre-infusion (baseline), end of infusion (0h), 1 hr, 3 hr, 6 hr, 24 hr, 48 hr and 7-28 days post-infusion
MAb114 Clearance Rate
Rate of MAb114 elimination divided by the plasma MAb114 concentration; determined based on the summary PK curve for each study group.
Measured: Pre-infusion (baseline), end of infusion (0h), 1 hr, 3 hr, 6 hr, 24 hr, 48 hr and 7-28 days post-infusion
Number of Subjects Who Produced Anti-drug Antibodies to MAb114
Serum samples collected 28 days and 56 days after MAb114 administration
Measured: Days 28 and 56 post-infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2018
- Study start16 May 2018
- Primary completion20 Mar 2019
- Study completion20 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Healthy Adult Immune Responses to VaccineStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Martin R Gaudinski, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03478891
- Sponsor's protocol ID
- 180069
- Other IDs
- 18-I-0069
- Status last verified
- Oct 2020
- First submitted
- 21 Mar 2018
- Last updated
- 26 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
- Expanded access
- Available
Publications
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.
PubMed 26917593Misasi J, Gilman MS, Kanekiyo M, Gui M, Cagigi A, Mulangu S, Corti D, Ledgerwood JE, Lanzavecchia A, Cunningham J, Muyembe-Tamfun JJ, Baxa U, Graham BS, Xiang Y, Sullivan NJ, McLellan JS. Structural and molecular basis for Ebola virus neutralization by protective human antibodies. Science. 2016 Mar 18;351(6279):1343-6. doi: 10.1126/science.aad6117. Epub 2016 Feb 25.
PubMed 26917592Gaudinski MR, Coates EE, Novik L, Widge A, Houser KV, Burch E, Holman LA, Gordon IJ, Chen GL, Carter C, Nason M, Sitar S, Yamshchikov G, Berkowitz N, Andrews C, Vazquez S, Laurencot C, Misasi J, Arnold F, Carlton K, Lawlor H, Gall J, Bailer RT, McDermott A, Capparelli E, Koup RA, Mascola JR, Graham BS, Sullivan NJ, Ledgerwood JE; VRC 608 Study team. 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 Mar 2;393(10174):889-898. doi: 10.1016/S0140-6736(19)30036-4. Epub 2019 Jan 24.
PubMed 30686586
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03478891
- Acronym / sponsor ID
- 180069
- Keywords
- Ebola Virus, Immune Response, Filovirus, Ebola Hemorrhagic Fever, First in Human
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 16 May 2018 (actual)
- Primary completion
- 20 Mar 2019 (actual)
- Study completion
- 20 Mar 2019 (actual)
- First posted
- 27 Mar 2018 (actual)
- Results
- Posted 11 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Ebola is a virus that has infected and killed people mostly in West Africa. There is no treatment or prevention for it, but several drugs are being studied. Researchers want to test the drug MAb114 in healthy people not exposed to Ebola to see whether it can be used for Ebola treatment in people who are infected in the future. This trial will not expose volunteers to the Ebola virus.
Objectives:
To see if MAb114 is safe and how a person's body responds to it.
Eligibility:
Healthy adults ages 18-60 who weigh 220.5 pounds or less
Design:
Participants will be screened under protocol NIH 11-I-0164 with:
- Medical history
- Physical exam
- Blood or urine tests
Participants will have a first 8- to10-hour visit. They will get MAb114 by IV infusion. For this, a thin tube will be placed in an arm vein. They may get an IV line in their other arm to collect blood. Blood will be taken many times before and after the infusion. Participants may have a urine test.
Participants will get a thermometer to check their temperature for 3 days after they get MAb114. They will record their highest temperature and any symptoms.
Participants will have about 14 more study visits over 6 months. At each visit, they will have blood taken and be checked for any health changes. They will talk about how they are feeling and if they have taken any medications.
At the end of the 6 months, participants may be invited to take part in another study for follow-up sample collection.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1: 5 mg/kg IV | Experimental | Biological: VRC-EBOMAB092-00-AB (MAb114)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. |
| Group 2: 25 mg/kg IV | Experimental | Biological: VRC-EBOMAB092-00-AB (MAb114)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. |
| Group 3: 50 mg/kg IV | Experimental | Biological: VRC-EBOMAB092-00-AB (MAb114)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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (20 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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). | Biological | Group 1: 5 mg/kg IV, Group 2: 25 mg/kg IV, Group 3: 50 mg/kg IV |
Primary outcome
Number of Subjects Experiencing Infusion Reaction During Product Administration
Time frame: About 30 minutes of 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.
Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of Product Administration
Time frame: 3 days after 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.
Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Product Administration
Time frame: 7 days after 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.
Number of Subjects Reporting 1 or More Unsolicited Non-Serious Adverse Events
Time frame: Through 24 weeks after product administration
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.
Number of Subjects Reporting Serious Adverse Events
Time frame: Through 24 weeks after product administration
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.
8 secondary outcomes
Maximum Observed Serum Concentration (Cmax) of MAb114
Time frame: Pre-infusion (baseline), end of infusion (0h), 1 hr, 3 hr, 6 hr, 24 hr, 48 hr and 7-28 days post-infusion
Time to Reach Maximum Observed Serum Concentration (Tmax) of MAb114
Time frame: Pre-infusion (baseline), end of infusion (0h), 1 hr, 3 hr, 6 hr, 24 hr, 48 hr and 7-28 days post-infusion
Mean Serum Concentration of MAb114
Time frame: Pre-infusion (baseline), end of infusion (0h), 1 hr, 3 hr, 6 hr, 24 hr, 48 hr and 7-28 days post-infusion
Overall IV Half-life (T1/2) of MAb114
Time frame: Pre-infusion (baseline), end of infusion (0h), 1 hr, 3 hr, 6 hr, 24 hr, 48 hr and 7-56 days post-infusion
Area Under the Curve (AUC0-28D)
Time frame: Pre-infusion (baseline), end of infusion (0h), 1 hr, 3 hr, 6 hr, 24 hr, 48 hr and 7-28 days post-infusion
Volume of Distribution (Vd) at Steady-state
Time frame: Pre-infusion (baseline), end of infusion (0h), 1 hr, 3 hr, 6 hr, 24 hr, 48 hr and 7-28 days post-infusion
MAb114 Clearance Rate
Time frame: Pre-infusion (baseline), end of infusion (0h), 1 hr, 3 hr, 6 hr, 24 hr, 48 hr and 7-28 days post-infusion
Number of Subjects Who Produced Anti-drug Antibodies to MAb114
Time frame: Days 28 and 56 post-infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26917593Corti 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.
- Background: PubMed 26917592Misasi J, Gilman MS, Kanekiyo M, Gui M, Cagigi A, Mulangu S, Corti D, Ledgerwood JE, Lanzavecchia A, Cunningham J, Muyembe-Tamfun JJ, Baxa U, Graham BS, Xiang Y, Sullivan NJ, McLellan JS. Structural and molecular basis for Ebola virus neutralization by protective human antibodies. Science. 2016 Mar 18;351(6279):1343-6. doi: 10.1126/science.aad6117. Epub 2016 Feb 25.
- Results publication: PubMed 30686586Gaudinski MR, Coates EE, Novik L, Widge A, Houser KV, Burch E, Holman LA, Gordon IJ, Chen GL, Carter C, Nason M, Sitar S, Yamshchikov G, Berkowitz N, Andrews C, Vazquez S, Laurencot C, Misasi J, Arnold F, Carlton K, Lawlor H, Gall J, Bailer RT, McDermott A, Capparelli E, Koup RA, Mascola JR, Graham BS, Sullivan NJ, Ledgerwood JE; VRC 608 Study team. 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 Mar 2;393(10174):889-898. doi: 10.1016/S0140-6736(19)30036-4. Epub 2019 Jan 24.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- NIH Press ReleaseLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin R Gaudinski, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing VRC-EBOMAB092-00-AB (MAb114) in people with Healthy Adult Immune Responses to Vaccine, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects Experiencing Infusion Reaction During Product Administration (time frame: About 30 minutes of product administration). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03478891, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2020.