Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-EBOMAB092-00-AB (MAb114), Administered Intravenously to Healthy Adults

NCT03478891 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 18006918-I-0069
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Healthy Adult Immune Responses to Vaccine

Keywords

Ebola Virus; Immune Response; Filovirus; Ebola Hemorrhagic Fever; First in Human

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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.

  Through 24 weeks after product administration

Secondary Outcomes (8)

• Maximum Observed Serum Concentration (Cmax) of MAb114

  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

  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

  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

  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)

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

Study Arms (3)

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

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).

Group 1: 5 mg/kg IV; Group 2: 25 mg/kg IV; Group 3: 50 mg/kg IV

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 26917593 BACKGROUND

• Misasi 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.

  PMID: 26917592 BACKGROUND

• Gaudinski 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.

  PMID: 30686586 RESULT

Related Links

• NIH Clinical Center Detailed Web Page
• NIH Press Release

MeSH Terms

Conditions

Hemorrhagic Fever, Ebola

Interventions

ansuvimab

Condition Hierarchy (Ancestors)

Hemorrhagic Fevers, Viral; RNA Virus Infections; Virus Diseases; Infections; Filoviridae Infections; Mononegavirales Infections

Results Point of Contact

• Title: Martin Gaudinski, MD
• Organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health

martin.gaudinski@nih.gov

301-451-8715

Study Officials

• Martin R Gaudinski, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: March 21, 2018
• First Posted: March 27, 2018
• Study Start: May 16, 2018
• Primary Completion: March 20, 2019
• Study Completion: March 20, 2019
• Last Updated: October 26, 2020
• Results First Posted: October 11, 2018

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)