Phase 1
N=19
Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-EBOMAB092-00-AB (MAb114), Administered Intravenously to Healthy Adults
Healthy Adult Immune Responses to Vaccine
Bottom Line
View on ClinicalTrials.gov: NCT03478891 ↗Enrolled (actual)
19
Serious AEs
5.6%
Results posted
Oct 2018
Primary outcome: Primary: Number of Subjects Experiencing Infusion Reaction During Product Administration — 0; 0; 0; 3 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- VRC-EBOMAB092-00-AB (MAb114) (Biological)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Primary completion
- Mar 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Subjects Experiencing Infusion Reaction During Product Administration |
0; 0; 0; 3; 5; 10 | — |
| PRIMARY Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of Product Administration |
3; 4; 8; 15; 0; 1 | — |
| PRIMARY Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Product Administration |
3; 5; 10; 18; 0; 0 | — |
| PRIMARY Number of Subjects Reporting 1 or More Unsolicited Non-Serious Adverse Events |
0; 0; 0; 0; 0; 2 | — |
| PRIMARY Number of Subjects Reporting Serious Adverse Events |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Maximum Observed Serum Concentration (Cmax) of MAb114 |
198.45; 829.38; 1961.21 | — |
| SECONDARY Time to Reach Maximum Observed Serum Concentration (Tmax) of MAb114 |
3.21; 2.99; 2.75 | — |
| SECONDARY Mean Serum Concentration of MAb114 |
52.60; 373.12; 692.64; 42.90; 272.91; 629.34 | — |
| SECONDARY Overall IV Half-life (T1/2) of MAb114 |
20.1; 26.7; 23.6; 24.2 | — |
| SECONDARY Area Under the Curve (AUC0-28D) |
1480; 8586; 18588 | — |
| SECONDARY Volume of Distribution (Vd) at Steady-state |
5.08; 3.93; 4.16 | — |
| SECONDARY MAb114 Clearance Rate |
199; 108; 115 | — |
| SECONDARY Number of Subjects Who Produced Anti-drug Antibodies to MAb114 |
0; 0; 0; 0; 0; 0 | — |
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.
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.
Data sourced from ClinicalTrials.gov (NCT03478891). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.