Study to Assess the Safety and Tolerability of Multiple Ascending Doses of REGN1033 (SAR391786)

Study Overview
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Brief Summary
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This is a study to assess the safety and tolerability of subcutaneously administered REGN1033 (SAR391786) in healthy volunteers.

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: REGN1033 (SAR391786)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible subjects are males and females aged 60 years and older with no significant health issues or clinically significant abnormal laboratory values. A subject must meet the following criteria to be eligible for inclusion in the study: Sexually active males willing to use contraceptives during the study and through 4 months after the study. Female subjects not of child bearing potential (surgically sterile or postmenopausal for longer than 1 year) Body mass index (BMI) between 18.5 and 32 kg/m2 inclusive Willing to maintain current diet and exercise routine for the duration of the study Willing and able to return for all clinic visits and complete all study-related procedures Able to read and understand, and willing to sign the ICF Exclusion Criteria: Significant concomitant illness such as, but not limited to cardiac, renal, rheumatologic, gastrointestinal, hematological, skeletal/muscular, neurologic, psychiatric, endocrine, metabolic or immunological disease. Evidence of malnutrition Cachexia of any cause Evidence or history of muscle diseases or weakness with the exception of age related muscle loss Limb amputation Immobilization, surgical procedure, fracture, or trauma to the upper or lower limb within 6 months History or evidence of heart diseases including but not limited to coronary heart disease with/without history of myocardial infarction, chronic or acute heart failure (New York Heart Association [NYHA] stage 2-4), cardiac arrhythmia with clinical symptoms, valvular heart disease, and cardiac hypertrophy of clinical significance Women of childbearing potential (not surgically sterile or amenorrheic for at least 12 months if postmenopausal) Uncontrolled diabetes defined as HbA1C > 7.5 at screening; if taking oral hypoglycemic drugs, have to be on stable doses of medication for more than 3 months. Diabetics using insulin are excluded Asthmatic subjects with current or recurring symptoms within 1 year. History of, COPD, chronic kidney disease, cancer except primary basal-cell skin cancer that has been adequately treated Neurological injury (eg, stroke) within 1 year Abnormal or uncontrolled blood pressure at screening visit defined as diastolic BP >95 and/or systolic BP >160 mm Hg; if taking hypertensive medication, have to be on stable doses of medication for more than 3 months Hepatic transaminases (ALT and or AST) > 2X ULN Reduced renal function as defined by eGFR<60 mL/min Current smokers or previous smokers who stopped smoking within 6 months Current or recent history (within 1 year of screen) of alcohol or drug abuse History of hypersensitivity response to any biologics History of hypersensitivity to doxycycline or other tetracycline antibiotics Current or recent participation in any clinical trial (within 30 days of small molecular drugs or within 3 months of biologics) Exposure within 3 months to approved biological drugs. (The name of the drug and duration of previous exposure will be recorded). Vaccines are allowed. Sexually active men* who are unwilling to practice adequate contraception during the study

Ages Eligible for Study
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Minimum Age: 60 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: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Dose 1 of REGN1033 (SAR391786) or Placebo | Drug: REGN1033 (SAR391786)<br> <br> Drug: Placebo<br> <br> |
| Experimental: Cohort 2<br>Dose 2 of REGN1033 (SAR391786) or Placebo | Drug: REGN1033 (SAR391786)<br> <br> Drug: Placebo<br> <br> |
| Experimental: Cohort 3<br>Dose 3 of REGN1033 (SAR391786) or Placebo | Drug: REGN1033 (SAR391786)<br> <br> Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of TEAEs | The primary endpoint in the study is the incidence and severity of TEAEs (Treatment Emergent Adverse Events) in participants treated with REGN1033 (SAR391786) or placebo, reported from the time of administration of study drug on day 1 (baseline) to day 141 (end of study). | Day 1 to Day 141 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum concentration of REGN1033 (SAR391786) | Serum concentration of REGN1033 (SAR391786) over time | Day 1 to Day 141 | 
| immunogenicity | Presence or absence of anti-REGN1033 (SAR391786) antibodies over time (immunogenicity ) | Day 1 to Day 141 |