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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Other: Placebo; Drug: REGN1033; Drug: REGN2477

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand
  • Christchurch, New Zealand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Panel A; REGN1033 + REGN2477 (Regimen 1) or placebo	Other: Placebo; Placebo; Drug: REGN1033; REGN1033; Drug: REGN2477; REGN2477
Experimental: Panel B; Panel B - REGN1033 + REGN2477 (Regimen 2) or Placebo	Other: Placebo; Placebo; Drug: REGN1033; REGN1033; Drug: REGN2477; REGN2477
Experimental: Panel C; Panel C - Patients will receive either REGN1033 + REGN2477 (Regimen 3) or Placebo	Other: Placebo; Placebo; Drug: REGN1033; REGN1033; Drug: REGN2477; REGN2477
Experimental: Panel D; Panel D - Patients will receive either REGN1033 + REGN2477 (Regimen 4), REGN1033, REGN2477 (high dose) or Placebo	Other: Placebo; Placebo; Drug: REGN1033; REGN1033; Drug: REGN2477; REGN2477
Experimental: Panel E; REGN2477 (Regimen 5) or placebo	Other: Placebo; Placebo; Drug: REGN2477; REGN2477
Experimental: Panel F; REGN2477 + REGN1033 (Regimen 6) or placebo	Other: Placebo; Placebo; Drug: REGN1033; REGN1033; Drug: REGN2477; REGN2477
Experimental: Panel G; REGN2477 (Regimen 7) or placebo	Other: Placebo; Placebo; Drug: REGN2477; REGN2477

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2016
• Primary Completion (Actual): April 30, 2019
• Study Completion (Actual): April 30, 2019

Study Registration Dates

• First Submitted: October 19, 2016
• First Submitted That Met QC Criteria: October 21, 2016
• First Posted (Estimated): October 24, 2016

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: August 8, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: R2477-1033-HV-1621; 2016-002979-95 (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
• product manufactured in and exported from the U.S.: No