Corona Virus Infection
Conditions
Keywords
Adults, Evaluate, Healthy, Immunogenicity, MERS-CoV, Pharmacokinetics, Phase I, Placebo, REGN MERS, Safety, Tolerability
Brief summary
This is a Phase 1, first-in-human (FIH), single site, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of single ascending doses of a co-administered (1:1, w/w) combination of REGN3048 and REGN3051 mAb's, administered IV in healthy adult volunteers. Study duration of approximately 16 months. Approximately 48 evaluable subjects will be enrolled in the study, eight (8) subjects in each one of 6 sequential ascending IV dose cohorts. In each cohort, subjects will be randomized to receive mAb's REGN3048 and REGN3051 (6 subjects) or placebo (2 subjects). Primary Objective: To assess the safety and tolerability of REGN3048 and REGN3051 following co-administration of single, ascending IV doses of 1.5, 5, 15, 25, 50, and 75 mg/kg of each of the two mAb's.
Detailed description
This is a Phase 1, first-in-human (FIH), single site, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of single ascending doses of a co-administered (1:1, w/w) combination of REGN3048 and REGN3051 mAb's, administered IV in healthy adult volunteers. Study duration of approximately 16 months. Approximately 48 evaluable subjects will be enrolled in the study, eight (8) subjects in each one of 6 sequential ascending IV dose cohorts. In each cohort, subjects will be randomized to receive mAb's REGN3048 and REGN3051 (6 subjects) or placebo (2 subjects). Primary Objective: To assess the safety and tolerability of REGN3048 and REGN3051 following co-administration of single, ascending IV doses of 1.5, 5, 15, 25, 50, and 75 mg/kg of each of the two mAb's. Secondary Objectives: 1) To assess the pharmacokinetic (PK) profiles of REGN3048 and REGN3051 following co-administration of single IV doses (1.5, 5, 15, 25, 50, and 75 mg/kg of each of the two mAb's); 2) To assess the immunogenicity of REGN3048 and REGN3051 following co-administration of single IV doses (1.5, 5, 15, 25, 50, and 75 mg/kg of each of the two mAb's)
Interventions
BIOLOGICALREGN3048
REGN3048 is a fully monoclonal antibody (mAbs) which binds to the S protein of MERS-CoV.
OTHERPlacebo
Placebo
BIOLOGICALREGN3051
REGN3051 is a fully human monoclonal antibody (mAb) which binds to the S protein of MERS-CoV. It can reduce virus titers and ameliorate MERS-CoV-induced lung pathology when given post infection.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
All must be answered yes for the subject to be eligible for study participation 1. Informed consent understood and signed prior to initiation of any study procedures 2. Healthy male or healthy, non-pregnant, non-lactating female, meeting eligibility criteria as assessed by the clinicians listed on the FDA Form 1572 3. Willingness to comply and be available for all protocol procedures including inpatient confinement for about 3 days 4. Age between 18 and 45 years, inclusive on the day of infusion 5. Body Mass Index (BMI) of \> or =18.5 and \>or =30 kg/m2 and Weight \> or = 50 kg (110 lbs) and \< or = 100 kg (220 lbs) 6. In female subject of childbearing potential, a negative serum pregnancy test at screening and negative serum test within 24 hours prior to infusion Note: A woman is considered of childbearing potential unless post-menopausal (\> or = 1 year without menses without other known or suspected cause and appropriately elevated FSH) or surgically sterilized via bilateral oophorectomy or hysterectomy 7. Females of childbearing potential and males agree to use acceptable contraception for the duration of the study Note: A highly effective method of birth control is defined as one that results in a low failure rate (i.e., less than 1 percent per year) according to the CDC criteria.30. These include progestin implants, intrauterine devices (IUDs), surgical (hysterectomy or tubal ligation; vasectomy) or abstinence. Use of methods with higher failure rate (such as progestin injectables, combined oral hormonal contraceptives, condoms, and diaphragms) will not be acceptable when used alone, but they could be considered, if used in combination with another method (for example, a female using combined oral contraceptives if her male partner is sterile, or if she and her non-sterile male partner use a double-barrier method), after consultation with the DMID MM. All males will be required to use a barrier method (condoms) for the duration of the study 8. Screening laboratory tests, are in the normal reference range with acceptable exceptions Notes: 1. If urinalysis by dipstick is abnormal, a complete urinalysis with microscopic evaluation will be performed and the results will supersede the results of the dipstick for blood, glucose and protein. 2. Menstruating females failing inclusion criteria due to a positive blood on urine test (dipstick or microscopic urinalysis) may be retested following cessation of menses. Do not exclude subjects with \<5 RBC/HPF. 3. Other laboratory values that are outside the range of eligibility but are thought to be due to an acute condition or due to collection or laboratory error may be repeated once. 9. Vital signs are within the acceptable range 10. Has adequate venous access for the infusion and blood collection 11. The urine drug screen is negative 12. Willing to abstain from alcohol consumption for a period of 2 days prior to and during the study 13. Available for follow-up for the duration of the study
Exclusion criteria
Subjects meeting any of the following
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Changes from baseline in abbreviated physical examination | Days 1-2 |
| Changes from baseline in clinical safety laboratory values | From Day 2 up to Day 121 |
| Changes from baseline in Electrocardiogram (ECG) parameters | 15 mins after infusion |
| Changes from baseline in symptom-directed physical examination | From Day 1 up to Day 121 |
| Changes from baseline in vital signs | From Day 1 up to Day 121 |
| The incidence of Adverse Events | From Day 1 up to Day 121 |
| The incidence of treatment-emergent Serious Adverse Events | From Day 1 up to Day 121 |
| The severity of Adverse Events assessed by toxicity grading criteria | From Day 1 up to Day 121 |
| The severity of treatment-emergent Serious Adverse Events assessed by toxicity grading criteria | From Day 1 up to Day 121 |
| The type of treatment-emergent Serious Adverse Events | From Day 1 up to Day 121 |
Secondary
| Measure | Time frame |
|---|---|
| t(1/2) for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs) | From Day 1 up to Day 121 |
| t(1/2) for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs) | From Day 1 up to Day 121 |
| The change from baseline of antibodies against REGN3048 and REGN3051 (anti-drug antibodies, ADA), as measured in serum using validated bridging assays | Day 121 |
| AUC for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs) | From Day 1 up to Day 121 |
| TMAX for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs) | From Day 1 up to Day 121 |
| V(ss) for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs) | From Day 1 up to Day 121 |
| V(ss) for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs) | From Day 1 up to Day 121 |
| TMAX for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs) | From Day 1 up to Day 121 |
| AUC for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs) | From Day 1 up to Day 121 |
| AUC(0-infinity) for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs) | From Day 1 up to Day 121 |
| AUC(0-infinity) for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs) | From Day 1 up to Day 121 |
| CL for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs) | From Day 1 up to Day 121 |
| CL for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs) | From Day 1 up to Day 121 |
| CMAX for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs) | From Day 1 up to Day 121 |
| CMAX for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs) | From Day 1 up to Day 121 |
| K(e) for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs) | From Day 1 up to Day 121 |
| K(e) for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs) | From Day 1 up to Day 121 |
Countries
United States
Outcome results
None listed