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

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

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

Official Title
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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.

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: REGN3918
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: A subject must meet the follow criteria to be eligible for inclusion in the study: Males and females from 18 to 50 years of age. 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 The subject has a body mass index less than 30 kg/m2 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: Any clinically significant physical examination abnormalities observed during the screening visit. Hospitalization for any reason within 30 days of the screening visit Persistent chronic or active recurring infection requiring treatment with antibiotics, antivirals, or antifungals. Subject has a history of meningococcal infection. Carriers of Neisseria meningitides based on cultures from naso-pharyngeal swabs during screening. Subject has had a splenectomy. Known allergy to penicillin class antibiotics Known or suspected complement deficiency, or abnormal complement C3, C4 or CH50 during screening. Recent (within the previous 2 months) bacterial, protozoal, viral or parasite infection requiring systemic treatment. History of tuberculosis or systemic fungal diseases HIV infection or HIV seropositivity at the screening visit Positive HBsAg, HBcAb, or hepatitis C antibody at the screening visit History of malignancy (except non-melanoma skin cancer or cervical in-situ) Pregnant or breastfeeding women 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |