Study of Safety, Tolerability, and Pharmacokinetics of REGN3470-3471-3479 in Healthy Adult Volunteers

A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study Investigating the Safety, Tolerability, and Pharmacokinetics of Intravenously Administered REGN3470-3471-3479 in Healthy Adult Subjects

This is a Phase 1, randomized, double-blind, placebo-controlled, dose escalation study evaluating the safety, tolerability, pharmacokinetics (PK) and immunogenicity of REGN3470-3471-3479 in healthy adult volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: REGN3470-3471-3479

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Evansville, Indiana, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy man or woman between the ages of 18 and 60
2. Body mass index (BMI) between 18 and 30 kg/m2, inclusive
3. Willing and able to comply with clinic visits and study-related procedures
4. Provide signed informed consent
5. Able to understand and complete study-related questionnaires

Exclusion Criteria:

1. Use of any medications started within 30 days prior to the screening visit including, prescription medications, nutritional supplements, and over-the-counter medications except for vitamin supplements, and recommended doses of acetaminophen, aspirin or ibuprofen
2. Hospitalization for any reason within 60 days prior to the screening visit
3. History of or positive human immunodeficiency virus (HIV) screen result at the screening visit
4. History of or positive blood test for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) or hepatitis C virus (HCV) antibody at the screening visit
5. History of drug or alcohol abuse within 1 year prior to screening
6. Participation in any clinical research study evaluating another investigational drug or therapy within 30 days or at least 5 half-lives (whichever is longer), of the investigational drug prior to the screening visit
7. Any history of receiving treatment, vaccine or mAbs against the Ebola virus
8. Pregnant or breast-feeding women

9. Sexually active men* or women of childbearing potential** who are unwilling to practice adequate contraception during the study (adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device [IUD]; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly).

   • Contraception is not required for men with documented vasectomy.
   • Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of childbearing potential. A baseline follicle-stimulating hormone (FSH) test will be performed for confirmation of menopausal status. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort 1; REGN3470-3471-3479 dosing level 1 or placebo	Drug: Placebo; Drug: REGN3470-3471-3479
EXPERIMENTAL: Cohort 2; REGN3470-3471-3479 dosing level 2 or placebo	Drug: Placebo; Drug: REGN3470-3471-3479
EXPERIMENTAL: Cohort 3; REGN3470-3471-3479 dosing level 3 or placebo	Drug: Placebo; Drug: REGN3470-3471-3479
EXPERIMENTAL: Cohort 4; REGN3470-3471-3479 dosing level 4 or placebo	Drug: Placebo; Drug: REGN3470-3471-3479

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and severity of TEAEs through the end of the study visit in subjects treated with REGN3470-3471-3479 in a fixed dose combination	From baseline up to day 169

Secondary Outcome Measures

Outcome Measure	Time Frame
Concentration of REGN3479 in serum over time	From baseline up to day 169
Concentration of REGN3471 in serum over time	From baseline up to day 169
Concentration of REGN3470 in serum over time	From baseline up to day 169
The presence or absence of antibodies against REGN3470 over time	From baseline up to day 169
The presence or absence of antibodies against REGN3471 over time	From baseline up to day 169
The presence or absence of antibodies against REGN3479 over time	From baseline up to day 169

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Collaborators: Department of Health and Human Services

Publications and helpful links

General Publications

• Sivapalasingam S, Kamal M, Slim R, Hosain R, Shao W, Stoltz R, Yen J, Pologe LG, Cao Y, Partridge M, Sumner G, Lipsich L. Safety, pharmacokinetics, and immunogenicity of a co-formulated cocktail of three human monoclonal antibodies targeting Ebola virus glycoprotein in healthy adults: a randomised, first-in-human phase 1 study. Lancet Infect Dis. 2018 Aug;18(8):884-893. doi: 10.1016/S1473-3099(18)30397-9. Epub 2018 Jun 18.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 27, 2016
• Primary Completion (ACTUAL): April 26, 2017
• Study Completion (ACTUAL): April 26, 2017

Study Registration Dates

• First Submitted: May 17, 2016
• First Submitted That Met QC Criteria: May 17, 2016
• First Posted (ESTIMATE): May 19, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 5, 2018
• Last Update Submitted That Met QC Criteria: February 1, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Antiviral Agents; Atoltivimab, maftivimab, and odesivimab-ebgn drug combination; Atoltivimab
• Other Study ID Numbers: R3470-3471-3479-HV-1528

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO