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

Exclusion Criteria

• •1. Significant concomitant illness such as, but not limited to cardiac, renal, rheumatologic, gastrointestinal, hematological, skeletal/muscular, neurologic, psychiatric, endocrine, metabolic or immunological disease.
• •2. Evidence of malnutrition
• •3. Cachexia of any cause
• •4. Evidence or history of muscle diseases or weakness with the exception of age related muscle loss
• •5. Limb amputation
• •6. Immobilization, surgical procedure, fracture, or trauma to the upper or lower limb within 6 months
• •7. 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
• •8. Women of childbearing potential (not surgically sterile or amenorrheic for at least 12 months if postmenopausal)
• •9. 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
• •10. Asthmatic subjects with current or recurring symptoms within 1 year.
• •11. History of, COPD, chronic kidney disease, cancer except primary basal-cell skin cancer that has been adequately treated
• •12. Neurological injury (eg, stroke) within 1 year
• •13. 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
• •14. Hepatic transaminases (ALT and or AST) \> 2X ULN
• •15. Reduced renal function as defined by eGFR\<60 mL/min
• •16. Current smokers or previous smokers who stopped smoking within 6 months
• •17. Current or recent history (within 1 year of screen) of alcohol or drug abuse
• •18. History of hypersensitivity response to any biologics
• •19. History of hypersensitivity to doxycycline or other tetracycline antibiotics
• •20. Current or recent participation in any clinical trial (within 30 days of small molecular drugs or within 3 months of biologics)
• •21. Exposure within 3 months to approved biological drugs. (The name of the drug and duration of previous exposure will be recorded). Vaccines are allowed.
• •22. Sexually active men\* who are unwilling to practice adequate contraception during the study