A Comparison of Subject-administered Romosozumab With Healthcare Provider-administered Romosozumab for Osteoporosis

A Randomized, Multicenter, Open-label, Parallel Group Study in Postmenopausal Women With Osteoporosis to Evaluate the Noninferiority of Subject-administered Romosozumab Via Autoinjector/Pen vs Healthcare Provider-administered Romosozumab Via Prefilled Syringe

To evaluate the noninferiority of a 6-month treatment with 210 mg romosozumab at 90 mg/mL administered subcutaneously (SC) once a month (QM) in postmenopausal women with osteoporosis either by healthcare provider (HCP) administration with prefilled syringe (PFS) or by subject self-administration with autoinjector/pen (AI/Pen)

Study Overview

• Status: Completed
• Conditions: Post-Menopausal Osteoporosis
• Intervention / Treatment: Drug: romosozumab HCP administration with PFS; Device: romosozumab self-administration with AI/Pen

• Study Type: Interventional
• Enrollment (Actual): 283
• Phase: Phase 3

Contacts and Locations

Study Locations

• Poland
  • Bialystok, Poland, 15-351
    • Research Site
  • Lodz, Poland, 90-558
    • Research Site
  • Swidnik, Poland, 21-040
    • Research Site
  • Warszawa, Poland, 01-192
    • Research Site
• United Kingdom
  • Chorley, United Kingdom, PR7 7NA
    • Research Site
  • Edinburgh, United Kingdom, EH4 2XU
    • Research Site
  • Liverpool, United Kingdom, L22 0LG
    • Research Site
  • London, United Kingdom, DA14 6LT
    • Research Site
  • Manchester, United Kingdom, M15 6SX
    • Research Site
  • Northwood, United Kingdom, HA6 2RN
    • Research Site
  • Romford, United Kingdom, RM1 3PJ
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Research Site
    • Birmingham, Alabama, United States, 35205
      • Research Site
    • Huntsville, Alabama, United States, 35801
      • Research Site
    • Tuscaloosa, Alabama, United States, 35406
      • Research Site
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Research Site
    • Mesa, Arizona, United States, 85213
      • Research Site
  • California
    • Cypress, California, United States, 90630
      • Research Site
    • Fullerton, California, United States, 92835
      • Research Site
    • Glendale, California, United States, 91206
      • Research Site
    • Laguna Hills, California, United States, 92653
      • Research Site
    • Santa Maria, California, United States, 93454
      • Research Site
    • Tustin, California, United States, 92780
      • Research Site
  • Colorado
    • Denver, Colorado, United States, 80230
      • Research Site
    • Golden, Colorado, United States, 80401
      • Research Site
  • Florida
    • Delray Beach, Florida, United States, 33446
      • Research Site
    • South Miami, Florida, United States, 33143
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Research Site
    • Atlanta, Georgia, United States, 30319
      • Research Site
  • Missouri
    • Bridgeton, Missouri, United States, 63044
      • Research Site
    • Springfield, Missouri, United States, 65802
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Research Site
  • New York
    • Great Neck, New York, United States, 11021
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Research Site
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Research Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Research Site
    • Wyomissing, Pennsylvania, United States, 19610
      • Research Site
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Research Site
    • Summerville, South Carolina, United States, 29486
      • Research Site
  • Texas
    • San Antonio, Texas, United States, 78209
      • Research Site
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Research Site
  • Virginia
    • Chesapeake, Virginia, United States, 23320
      • Research Site
    • Danville, Virginia, United States, 24541
      • Research Site
  • Washington
    • Renton, Washington, United States, 98057
      • Research Site
  • Wisconsin
    • Franklin, Wisconsin, United States, 53132
      • 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:

• Subject has provided informed consent/assent prior to initiation of any studyspecific activities/procedures, or subject's legally acceptable representative has provided informed consent prior to any study-specific activities/procedures being initiated when the subject has any kind of condition that, in the opinion of the Investigator, may compromise the ability of the subject to give written informed consent.

• Postmenopausal female (postmenopausal status is defined as no vaginal bleeding or spotting for 12 consecutive months prior to screening)

  -≥ 55 to ≤ 90 years of age at the time of informed consent

• Ambulatory
• BMD T-score ≤ -2.50 at the lumbar spine, total hip, or femoral neck, as assessed by the central imaging vendor at the time of screening, based on DXA scans -Subject has at least 2 vertebrae in the L1-L4 region evaluable by DXA, as assessed by the principal investigator or designee
• Subject has at least 1 hip evaluable by DXA, as assessed by the principal investigator or designee

• Subject has history of fragility (ie, osteoporosis-related fracture) or subject meets at least 2 of the following clinical risk factors for fracture

  • ≥ 70 years of age at the time of informed consent
  • BMD T-score ≤ -3.00 at the lumbar spine, total hip, or femoral neck, as assessed by the central imaging vendor at the time of screening, based on DXA scans
  • current smoker
  • consumption of ≥ 3 glasses of alcohol a day
  • parental history of fragility (ie, osteoporosis-related) fracture
  • body weight ≤ 125 pounds/56 kilogram
• Ability to follow and understand instructions and the ability to self-inject, per investigator judgement

Exclusion Criteria:

• History of osteonecrosis of the jaw and/or atypical femoral fracture
• History of metabolic or bone disease (except osteoporosis) that may interfere with the interpretation of the results, such as sclerosteosis, Paget's disease, rheumatoid arthritis, osteomalacia, osteogenesis imperfecta, osteopetrosis, ankylosing spondylitis, Cushing's disease, hyperprolactinemia, and malabsorption syndrome
• Subject with reported history of hearing loss associated with cranial nerve VIII compression due to excessive bone growth (eg, as seen in conditions such as Paget's disease, sclerosteosis and osteopetrosis)
• Vitamin D insufficiency [defined as serum 25 (OH) vitamin D levels < 20 ng/mL], as determined by the central laboratory. Vitamin D repletion will be permitted a nd subjects may be rescreened
• Current hyperthyroidism (unless well controlled on stable antithyroid therapy) by subject report or by chart review, per principal investigator evaluation
• Current clinical hypothyroidism (unless well controlled on stable thyroid replacement therapy) by subject report or by chart review, per principal investigator evaluation normal range, per subject medical history. Uncontrolled hyperparathyroidism is defined as: parathyroid hormone (PTH) outside the normal range in subjects with concurrent hypercalcemia; or PTH values > 20% above the upper limit of normal (ULN) in normocalcemic subjects.
• Current hyper- or hypocalcemia, defined as albumin-adjusted serum calcium outside the normal range, as assessed by the central laboratory. Serum calcium levels may be retested once in case of an elevated serum calcium level within 1.1x the ULN as assessed by the central laboratory

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Romosozumab 210 mg QM: PFS; During the open-label treatment period, participants receive 210 mg romosozumab SC QM by HCP administration with PFS.	Drug: romosozumab HCP administration with PFS; 210 mg romosozumab SC QM by HCP administration with 2 PFS; Other Names: Evenity; AMG785
ACTIVE_COMPARATOR: Romosozumab 210 mg QM: AI/Pen; During the open-label treatment period, participants receive 210 mg romosozumab SC QM by self-administration with AI/pen.	Device: romosozumab self-administration with AI/Pen; 210 mg romosozumab SC QM by self-administration with 2 AI/Pens; Other Names: Evenity; AMG785

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Lumbar Spine BMD at Month 6	Percent change from baseline in BMD at the lumbar spine as measured by dual-energy x-ray absorptiometry (DXA).	Baseline, Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Total Hip BMD at Month 6	Percent change from baseline in BMD for total hip as measured by DXA.	Baseline, Month 6
Percent Change From Baseline in Femoral Neck BMD at Month 6	Percent change from baseline in BMD at femoral neck as measured by DXA.	Baseline, Month 6
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths	AE: any untoward medical occurrence irrespective of a causal relationship with the study treatment. SAE: any untoward medical occurrence that meets at least 1 of the following criteria: results in death; is immediately life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a medically important serious event. Adverse device effect: any AE related to the use of a combination product or medical device. TEAEs are those AEs occurring after first dose of study drug.	up to Month 9 (-7/+3 days)
Number of Participants Developing Anti-Romosozumab Antibodies	Participants with a negative or no result at baseline (BL) developing anti-romosozumab antibodies postbaseline, including those who were binding antibody-positive or neutralizing antibody-positive postbaseline. 'Transient' positive results are those with a negative result at the participant's last time point tested within the study period.	up to Month 9 (-7/+3 days)

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 6, 2018
• Primary Completion (ACTUAL): April 11, 2019
• Study Completion (ACTUAL): January 8, 2020

Study Registration Dates

• First Submitted: January 30, 2018
• First Submitted That Met QC Criteria: February 12, 2018
• First Posted (ACTUAL): February 14, 2018

Study Record Updates

• Last Update Posted (ACTUAL): November 23, 2020
• Last Update Submitted That Met QC Criteria: November 5, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Post-Menopausal 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: 20150120; 2017-003512-40 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes