Study of Safety, Tolerability, and Pharmacokinetics of REGN2477 Alone and in Combination With REGN1033 in Healthy Postmenopausal Women and Healthy Adult Men

Study Overview
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Brief Summary
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The primary objective is to assess the safety and tolerability of REGN2477 alone and combined with REGN1033. The secondary objectives are to: Assess the effect of REGN2477 alone, REGN1033 alone, and REGN2477 + REGN1033 in combination on thigh muscle volume Assess the effects of REGN2477 alone, REGN1033 alone, and REGN2477 + REGN1033 in combination on total and regional body composition Evaluate the Pharmacokinetic (PK) profile of REGN2477 and REGN1033 Assess immunogenicity of REGN2477 or REGN1033 Assess REGN2477 or REGN1033 target engagement

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacodynamic Effects of REGN2477 Alone and in Combination With REGN1033 in Healthy Postmenopausal Women and Healthy Adult Men

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: REGN1033
* Drug: REGN2477
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Postmenopausal women age 45 to 70 years and age 35 to 60 years inclusive for men not intending to father children BMI between 18 to 32 kg/m2, inclusive Willing and able to maintain current diet, supplements and physical activity level throughout the study Provides signed informed consent Key Exclusion Criteria: Significant illness or history of significant illness Contraindication to MRI History of human immunodeficiency virus (HIV); hepatitis B or hepatitis C virus (HCV) History of immobilization, major surgical procedure, fracture, or major trauma within 9 months prior to screening History of significant gynecological disorders or malignancies; history of breast malignancies (uterine fibroids or dysfunctional uterine bleeding is acceptable) Inconsistent vigorous physical activity (on fewer than 5 days per week), such as intermittent weight lifting History of hypersensitivity reactions to tetracycline antibiotics (includes doxycycline), vaccines, or biologics Use of agents that alter muscle mass that have not been at a stable dose for 3 months prior to screening (includes protein supplements), or use of any weight altering or anabolic steroid drugs (includes drugs for obesity, diuretics, testosterone) Participants treated with a biologic therapy or biologic immunotherapy in the previous 12 weeks prior to screening and during the study Note: Other protocol Inclusion/Exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 70 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: Panel A<br>REGN1033 + REGN2477 (Regimen 1) or placebo | Drug: REGN1033<br>* REGN1033<br>Drug: REGN2477<br>* REGN2477<br>Other: Placebo<br>* Placebo<br>|
| Experimental: Panel B<br>Panel B - REGN1033 + REGN2477 (Regimen 2) or Placebo | Drug: REGN1033<br>* REGN1033<br>Drug: REGN2477<br>* REGN2477<br>Other: Placebo<br>* Placebo<br>|
| Experimental: Panel C<br>Panel C - Patients will receive either REGN1033 + REGN2477 (Regimen 3) or Placebo | Drug: REGN1033<br>* REGN1033<br>Drug: REGN2477<br>* REGN2477<br>Other: Placebo<br>* Placebo<br>|
| Experimental: Panel D<br>Panel D - Patients will receive either REGN1033 + REGN2477 (Regimen 4), REGN1033, REGN2477 (high dose) or Placebo | Drug: REGN1033<br>* REGN1033<br>Drug: REGN2477<br>* REGN2477<br>Other: Placebo<br>* Placebo<br>|
| Experimental: Panel E<br>REGN2477 (Regimen 5) or placebo | Drug: REGN2477<br>* REGN2477<br>Other: Placebo<br>* Placebo<br>|
| Experimental: Panel F<br>REGN2477 + REGN1033 (Regimen 6) or placebo | Drug: REGN1033<br>* REGN1033<br>Drug: REGN2477<br>* REGN2477<br>Other: Placebo<br>* Placebo<br>|
| Experimental: Panel G<br>REGN2477 (Regimen 7) or placebo | Drug: REGN2477<br>* REGN2477<br>Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of treatment-emergent adverse events (TEAEs) |  | Up to 40 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in thigh muscle volume as measured by MRI |  | Up to 28 weeks | 
| Change in thigh muscle volume as measured by MRI |  | Up to 28 weeks | 
| Percent change in total and regional body composition as measured by Dual X-ray absorptiometry (DXA) |  | Up to 28 weeks | 
| Change in total body composition as measured by DXA |  | Up to 28 weeks | 
| Change in regional body composition as measured by DXA |  | Up to 28 weeks | 
| Pharmacokinetic profile of REGN2477 assessed via measurement of concentrations of REGN2477 in serum over time |  | Up to 40 weeks | 
| Pharmacokinetic profile of REGN1033 assessed via measurement of concentrations of REGN1033 in serum overtime |  | Up to 40 weeks | 
| Change in total Activin A levels in blood |  | Up to 40 weeks | 
| Change in total GDF8 levels in blood |  | Up to 32 weeks | 
| Presence or absence of antibodies against REGN2477 and REGN1033 |  | Up to 40 weeks |