Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of REGN3918 in Healthy Volunteers

A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose and Multiple Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenously and Subcutaneously Administered Human Monoclonal Antibody REGN3918 in Healthy Volunteers.

To evaluate the safety and tolerability of single ascending intravenous (IV) and subcutaneous (SC) doses and a multiple dose regimen.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: REGN3918

Detailed Description

Participants will be randomized to single IV or SC or multiple dose treatment with REGN3918 or matched placebo.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS2 9LH
    • Covance Clinical Research Unit (CRU) Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

A subject must meet the follow criteria to be eligible for inclusion in the study:

1. Males and females from 18 to 50 years of age.
2. Subject is judged to be in good health based on medical history, physical examination, vital sign measurements and laboratory safety tests performed at screening and/or prior to administration of initial dose of study drug
3. The subject has a body mass index less than 30 kg/m2
4. Willingness to undergo vaccination and antibiotic prophylaxis against N. meningitides.

Key Exclusion Criteria:

A subject who meets any of the following criteria will be excluded from the study:

1. Any clinically significant physical examination abnormalities observed during the screening visit.
2. Hospitalization for any reason within 30 days of the screening visit
3. Persistent chronic or active recurring infection requiring treatment with antibiotics, antivirals, or antifungals.
4. Subject has a history of meningococcal infection.
5. Carriers of Neisseria meningitides based on cultures from naso-pharyngeal swabs during screening.
6. Subject has had a splenectomy.
7. Known allergy to penicillin class antibiotics
8. Known or suspected complement deficiency, or abnormal complement C3, C4 or CH50 during screening.
9. Recent (within the previous 2 months) bacterial, protozoal, viral or parasite infection requiring systemic treatment.
10. History of tuberculosis or systemic fungal diseases
11. HIV infection or HIV seropositivity at the screening visit
12. Positive HBsAg, HBcAb, or hepatitis C antibody at the screening visit
13. History of malignancy (except non-melanoma skin cancer or cervical in-situ)
14. Pregnant or breastfeeding women
15. Women of childbearing potential and men who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: REGN3918 (Cohorts 1-4 & 6a); Cohorts 1-4 and 6a will receive sequential ascending doses of REGN3918	Drug: REGN3918; Intravenous (IV) or Subcutaneous (SC)
Experimental: Placebo (Cohorts 1-4 & 6a); Cohorts 1-4 and 6a will receive placebo	Drug: Placebo; Matching Placebo
Experimental: REGN3918 (Cohort 5 & 6b); Cohort 5 and 6b will receive multiple doses of REGN3918	Drug: REGN3918; Intravenous (IV) or Subcutaneous (SC)
Experimental: Placebo (Cohort 5 & 6b); Cohort 5 and 6b will receive placebo	Drug: Placebo; Matching Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of treatment emergent adverse events (TEAEs)	Up to 20 weeks
Severity of TEAEs	Up to 20 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic profile of REGN3918; single dose IV and SC	Assessed via serum concentrations of REGN3918 over time; Area under the Curve (AUC)	Up to 20 weeks
Pharmacokinetic profile of REGN3918; single dose IV and repeated SC doses	Assessed via serum concentrations of REGN3918 over time; peak concentration Cmax	Up to 20 weeks
Pharmacodynamics profile of REGN3918	Assessed by CH50 assay over time	Up to 20 weeks
Pharmacokinetic exploratory analysis	Peak concentration Cmax	Up to 20 weeks
Immunogenicity of REGN3918	Assessed by measurement of anti-drug antibodies (ADA)	Up to 20 weeks

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2017
• Primary Completion (Actual): August 31, 2018
• Study Completion (Actual): August 31, 2018

Study Registration Dates

• First Submitted: April 5, 2017
• First Submitted That Met QC Criteria: April 12, 2017
• First Posted (Actual): April 14, 2017

Study Record Updates

• Last Update Posted (Actual): September 26, 2018
• Last Update Submitted That Met QC Criteria: September 25, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: R3918-HV-1659; 2016-004208-70 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No