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A Phase I Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Immunogenicity of Co-administered MERS-CoV Antibodies REGN3048 and REGN3051 vs. Placebo in Healthy Adults

Trial Profile

A Phase I Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Immunogenicity of Co-administered MERS-CoV Antibodies REGN3048 and REGN3051 vs. Placebo in Healthy Adults

Status: Completed
Phase of Trial: Phase I

Latest Information Update: 08 Feb 2019

At a glance

  • Drugs REGN-3048 (Primary) ; REGN-3051 (Primary)
  • Indications Middle East respiratory syndrome coronavirus
  • Focus Adverse reactions; First in man
  • Most Recent Events

    • 30 Jan 2019 Status changed from active, no longer recruiting to completed.
    • 03 Jan 2019 Planned End Date changed from 15 Jun 2019 to 19 Jan 2019.
    • 03 Jan 2019 Planned primary completion date changed from 15 Dec 2018 to 19 Jan 2019.

Trial Overview

Purpose

This study is evaluating the safety, tolerability, Pharmacokinetics, 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.

Primary Endpoints

Changes from baseline in abbreviated physical examination

time_frame: Days 1-2

Changes from baseline in clinical safety laboratory values

time_frame: From Day 2 up to Day 121

Changes from baseline in Electrocardiogram (ECG) parameters

time_frame: 15 mins after infusion
time_frame: 24 hrs after infusion

Changes from baseline in symptom-directed physical examination

time_frame: From Day 1 up to Day 121

Changes from baseline in vital signs

time_frame: From Day 1 up to Day 121

The incidence of Adverse Events

time_frame: From Day 1 up to Day 121

The incidence of treatment-emergent Serious Adverse Events

time_frame: From Day 1 up to Day 121

The severity of Adverse Events assessed by toxicity grading criteria

time_frame: From Day 1 up to Day 121

The severity of treatment-emergent Serious Adverse Events assessed by toxicity grading criteria

time_frame: From Day 1 up to Day 121

The type of treatment-emergent Serious Adverse Events

time_frame: From Day 1 up to Day 121

Other Endpoints

AUC for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

time_frame: From Day 1 up to Day 121

AUC for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

time_frame: From Day 1 up to Day 121

AUC(0-infinity) for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

time_frame: From Day 1 up to Day 121

AUC(0-infinity) for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

time_frame: From Day 1 up to Day 121

CL for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

time_frame: From Day 1 up to Day 121

CL for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

time_frame: From Day 1 up to Day 121

CMAX for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

time_frame: From Day 1 up to Day 121

CMAX for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

time_frame: From Day 1 up to Day 121

K(e) for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

time_frame: From Day 1 up to Day 121

K(e) for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

time_frame: From Day 1 up to Day 121

t(1/2) for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

time_frame: From Day 1 up to Day 121

t(1/2) for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

time_frame: 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

time_frame: Day 121
time_frame: Day 57

TMAX for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

time_frame: From Day 1 up to Day 121

TMAX for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

time_frame: From Day 1 up to Day 121

V(ss) for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

time_frame: From Day 1 up to Day 121

V(ss) for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

time_frame: From Day 1 up to Day 121 [1]

Diseases Treated

Indication Qualifiers Patient Segments
Middle East respiratory syndrome coronavirus treatment -

Subjects

  • Subject Type volunteers
  • Number

    Planned: 48

    Actual: 48

  • Sex male & female
  • Age Group 18-45 years; adult

Patient 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

Patient Exclusion Criteria

Subjects meeting any of the following exclusion criteria are not eligible for participation. All must be answered no for the subject to be eligible for study participation 1. History of a chronic medical condition that would either interfere with the accurate assessment of the objectives of the study or increase the risk profile of the subject. Note: Chronic medical conditions include diabetes; Asthma requiring use of medication in the year before screening; Autoimmune disorder such as lupus, Wegener's, rheumatoid arthritis, thyroid disease; Coronary artery disease; Chronic hypertension; History of malignancy except low-grade (squamous and basal cell) skin cancer thought to be cured; chronic renal, hepatic, pulmonary, or endocrine disease; myopathy, and neuropathy 2. History of severe allergic reaction of any type to medications, bee stings, food, or environmental factors or hypersensitivity or reaction to immunoglobulins. Note: Severe allergic reaction is defined as any of the following: anaphylaxis, urticaria, or angioedema 3. A marked baseline prolongation of QT/QTcF interval (e.g., repeated demonstration of a QTcF interval >450 milliseconds) 4. Clinically significant abnormal electrocardiogram at screening Note: Clinically significant abnormal ECG results include: complete left or right bundle branch block; other ventricular conduction block; 2nd degree or 3rd degree atrioventricular (AV) block; sustained ventricular arrhythmia; sustained atrial arrhythmia; two Premature Ventricular Contractions in a row; pattern of ST elevation felt consistent with cardiac ischemia; or any condition deemed clinically significant by a study investigator 5. Positive serology results for HIV, HBsAg, or HCV antibodies 6. Febrile illness with temperature >37.6°C 7 days prior to dosing 7. Pregnant or breastfeeding 8. Donated whole blood or blood products within 56 days prior to dosing or plans to donate blood prior to the last scheduled visit in the study (Day 121) Note: Blood products are defined as red blood cells, white blood cells, platelets or plasma) 9. Known allergic reactions to doxycycline or to any of the study product components present in the formulation or in the processing, as listed in the Investigator Brochure 10. Treatment with another investigational product within 30 days of dosing, including a drug, vaccine, biologic, device or blood product 11. Treatment with a monoclonal antibody at any time in the past or planned use during the study period 12. Receipt of antibody* or blood transfusion within 6 months of dosing or within 5 half-lives of the specific product given - Note: Tetanus Immune Globulin [TIG], Varicella-Zoster Immune Globulin [VZIG], Intravenous Immunoglobulin [IVIG], Intramuscular [IM] gamma globulin 13. Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements 14. Use of H1 antihistamines or beta-blockers within 5 days of dosing 15. Use of any prohibited medication within 30 days prior to study dosing or planned use during the study period Note: Prohibited medications include immunosuppressives (except nonsteroidal antiinflammatory drugs [NSAIDS]); immune modulators; oral corticosteroids (topical/intranasal steroids are acceptable); anti-neoplastic agents; any licensed biologic including monoclonal antibody or vaccine with the exception of licensed influenza vaccine during the flu season, which is allowed 7 days prior to dosing or 7 days after dosing 16. Any specific condition that in the judgment of the investigator precludes participation because it could affect subject safety 17. Plans to enroll or is already enrolled in another clinical trial that could interfere with safety assessment of the investigational product at any time during the study period Note: Includes trials that have a study intervention such as a drug, biologic, or device 18. Is a study site employee or staff who are paid entirely or partially by the NIAID Office of Clinical Research Resources (OCRR) contract for the DMID-funded trial Note: Site employees or staff include the PIs and sub-investigators or staff who are supervised by the PI or Sub-Investigators

Trial Details

Identifiers

Identifier Owner
NCT03301090 ClinicalTrials.gov: US National Institutes of Health
15-0109 -
HHSN272201500005I -

Trial Dates

  • Initiation Dates

    Actual : 12 Feb 2018

  • Primary Completion Dates

    Planned : 19 Jan 2019

    Actual : 19 Jan 2019

  • End Dates

    Planned : 19 Jan 2019

    Actual : 19 Jan 2019

Other Details

  • Design double-blind; parallel; prospective; randomised
  • Phase of Trial Phase I
  • Location USA
  • Focus Adverse reactions; First in man

Interventions

Drugs Route Formulation
REGN-3048Primary Drug Intravenous Infusion
REGN-3051Primary Drug Intravenous Infusion

Cohort A

REGN3048+REGN3051 3 mg/kg (1.5 mg/kg of each mAb) single infusion IV, n=6; placebo IV, n=2
Other: Placebo (Placebo)
Biological: REGN3048 (REGN3048 is a fully monoclonal antibody (mAbs) which binds to the S protein of MERS-CoV.)
Biological: REGN3051 (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.)

Cohort B

REGN3048+REGN3051 10 mg/kg (5 mg/kg of each mAb) single infusion IV, n=6; placebo IV, n=2
Other: Placebo (Placebo)
Biological: REGN3048 (REGN3048 is a fully monoclonal antibody (mAbs) which binds to the S protein of MERS-CoV.)
Biological: REGN3051 (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.)

Cohort C

REGN3048+REGN3051 30 mg/kg (15 mg/kg of each mAb) single infusion IV, n=6; placebo IV, n=2
Other: Placebo (Placebo)
Biological: REGN3048 (REGN3048 is a fully monoclonal antibody (mAbs) which binds to the S protein of MERS-CoV.)
Biological: REGN3051 (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.)

Cohort D

REGN3048+REGN3051 50 mg/kg (25 mg/kg of each mAb) single infusion IV, n=6; placebo IV, n=2
Other: Placebo (Placebo)
Biological: REGN3048 (REGN3048 is a fully monoclonal antibody (mAbs) which binds to the S protein of MERS-CoV.)
Biological: REGN3051 (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.)

Cohort E

REGN3048+REGN3051 100 mg/kg (50 mg/kg of each mAb) single infusion IV, n=6; placebo IV, n=2
Other: Placebo (Placebo)
Biological: REGN3048 (REGN3048 is a fully monoclonal antibody (mAbs) which binds to the S protein of MERS-CoV.)
Biological: REGN3051 (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.)

Cohort F

REGN3048+REGN3051 150 mg/kg (75 mg/kg of each mAb) single infusion IV, n=6; placebo IV, n=2
Other: Placebo (Placebo)
Biological: REGN3048 (REGN3048 is a fully monoclonal antibody (mAbs) which binds to the S protein of MERS-CoV.)
Biological: REGN3051 (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.)

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Dana Yee
17142520700 Ext: 1221
Dana.Yee@wcct.com
show details
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Centres

Centre Name Location Trial Centre Country
-
-
-
National Institute of Allergy and Infectious Diseases (NIAID)
-
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WCCT Global Cypress Clinical Pharmacology Unit Cypress, California USA

Trial History

Event Date Event Type Comment
08 Feb 2019 Other trial event Last checked against the ClinicalTrials.gov record. Updated 08 Feb 2019
30 Jan 2019 Status change - completed Status changed from active, no longer recruiting to completed. Updated 08 Feb 2019
03 Jan 2019 Completion date Planned End Date changed from 15 Jun 2019 to 19 Jan 2019. Updated 09 Jan 2019
03 Jan 2019 Other trial event Planned primary completion date changed from 15 Dec 2018 to 19 Jan 2019. Updated 09 Jan 2019
25 Oct 2018 Status change - active, no longer recruiting Status changed from recruiting to active, no longer recruiting. Updated 05 Nov 2018
03 May 2018 New trial record New trial record Updated 03 May 2018

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
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