A Randomized Phase 3 Study to Evaluate Two Formulations of Romosozumab in Postmenopausal Women With Osteoporosis

A Multicenter, Randomized, Multiple-dose Phase 3 Study to Evaluate the Noninferiority of Romosozumab at a 90 mg/mL Concentration Compared With a 70 mg/mL Concentration in Postmenopausal Women With Osteoporosis

The purpose of this study is to compare 2 formulations of romosozumab (AMG 785) on bone mineral density (BMD) in postmenopausal women with osteoporosis.

Study Overview

• Status: Completed
• Conditions: Postmenopausal Osteoporosis
• Intervention / Treatment: Drug: Romosozumab 90 mg/mL; Drug: Placebo 90 mg/mL; Drug: Romosozumab 70 mg/mL; Drug: Placebo 70 mg/mL

Detailed Description

Upon confirmation of eligibility, participants were randomized in a 22:5:22:5 ratio to the following treatment groups:

• Romosozumab 90 mg/mL
• Placebo 90 mg/mL
• Romosozumab 70 mg/mL
• Placebo 70 mg/mL

After completing a 6-month treatment period, participants entered a 3-month follow-up period with an end of study (EOS) at month 9.

For the analysis of efficacy endpoints, the 2 placebo groups were combined into a single placebo group. For safety analyses, the data for placebo were presented separately for each group.

• Study Type: Interventional
• Enrollment (Actual): 294
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia, 602 00
    • Research Site
  • Klatovy, Czechia, 339 01
    • Research Site
  • Uherske Hradiste, Czechia, 686 01
    • Research Site
• Poland
  • Gdynia, Poland, 81-384
    • Research Site
  • Gliwice, Poland, 44-100
    • Research Site
  • Katowice, Poland, 40-040
    • Research Site
  • Kraków, Poland, 31-501
    • Research Site
  • Swidnik, Poland, 21-040
    • Research Site
  • Warszawa, Poland, 01-192
    • Research Site
  • Wroclaw, Poland, 50-088
    • Research Site
• United States
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Research Site
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

Postmenopausal women with osteoporosis at high risk for fracture defined as

• BMD T-score ≤ -2.50 at the lumbar spine, total hip, or femoral neck AND
• a history of fragility fracture or at least 2 other risk factors

Exclusion Criteria:

• BMD T score < -3.50 at the total hip or femoral neck.
• History of hip fracture.
• History of metabolic or bone disease (except osteoporosis).
• Use of agents affecting bone metabolism.
• Vitamin D insufficiency.
• History of solid organ or bone marrow transplants.
• Hyper- or hypocalcemia.
• Hyper- or hypothyroidism.
• Hyper- or hypoparathyroidism.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Romosozumab 90 mg/mL; Participants received 210 mg romosozumab monthly, administered as 2 subcutaneous (SC) 1.17 mL injections of a 90 mg/mL solution, for 6 months.	Drug: Romosozumab 90 mg/mL; Administered as 2 SC injections of a 90 mg/mL concentration in a 1.17 mL crystal zenith resin prefilled syringe (PFS).; Other Names: AMG 785; EVENITY™
Experimental: Placebo 90 mg/mL; Participants received matching placebo administered as 2 subcutaneous injections of 1.17 mL every month for 6 months.	Drug: Placebo 90 mg/mL; Placebo administered as 2 SC injections with the 1.17 mL crystal zenith resin PFS.
Experimental: Romosozumab 70 mg/mL; Participants received 210 mg romosozumab monthly, administered as 3 subcutaneous 1.0 mL injections of a 70 mg/mL solution, for 6 months.	Drug: Romosozumab 70 mg/mL; Administered as 3 SC injections of a 70 mg/mL concentration in a 1.0 mL glass PFS.; Other Names: AMG 785; EVENITY™
Placebo Comparator: Placebo 70 mg/mL; Participants received matching placebo administered as 3 subcutaneous injections of 1.0 mL every month for 6 months.	Drug: Placebo 70 mg/mL; Placebo administered as 3 SC injections with the 1.0 mL glass PFS.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine	Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA).	Baseline and month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Total Hip BMD	Total hip BMD was measured using DXA. The analysis was based on an ANCOVA model adjusted for treatment and baseline total hip BMD T-score.	Baseline and month 6
Percent Change From Baseline in Femoral Neck BMD	Femoral neck BMD was measured using DXA. The analysis was based on an ANCOVA model adjusted for treatment and baseline femoral neck BMD T-score.	Baseline and month 6
Percent Change From Baseline in N-Terminal Propeptide Type 1 Procollagen (P1NP)		Baseline, month 1, month 3, and month 6
Percent Change From Baseline in Serum C-Telopeptide (CTX)		Baseline, month 1, month 3, and month 6

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2013
• Primary Completion (Actual): September 8, 2014
• Study Completion (Actual): December 8, 2014

Study Registration Dates

• First Submitted: December 10, 2013
• First Submitted That Met QC Criteria: December 16, 2013
• First Posted (Estimate): December 20, 2013

Study Record Updates

• Last Update Posted (Actual): November 8, 2018
• Last Update Submitted That Met QC Criteria: October 11, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Postmenopausal Osteoporosis
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Osteoporosis, Postmenopausal; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: 20120156; 2013-000434-35 (EudraCT Number)