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

• ClinicalTrials.gov Identifier: NCT03432533
• Recruitment Status: Completed
• First Posted: February 14, 2018
• Results First Posted: April 10, 2020
• Last Update Posted: November 23, 2020
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Study Description

Brief Summary:

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)

Condition or disease	Intervention/treatment	Phase
Post-Menopausal Osteoporosis	Drug: romosozumab HCP administration with PFS; Device: romosozumab self-administration with AI/Pen	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 283 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment

Intervention Model Description

After signing the informed consent form (ICF), subjects will undergo the following periods:

• Screening period (35 days) to complete eligibility assessments
• Open-label treatment period (6 months)
• Follow-up period (3 months) During the open-label treatment period, subjects will be randomized to receive romosozumab either via HCP administration with PFS or via self-administration withAI/Pen.

During the follow-up period, subjects will be followed for an additional 3 months to ensure appropriate follow-up for anti-romosozumab antibody formation and adverse events.

The primary analysis will be performed after all subjects have had the opportunity to complete the Month 6 visit. The final analysis will be performed after all subjects have had the opportunity to complete the Month 9 visit.

• Masking: None (Open Label)
• Masking Description: This is an open-label study; blinding procedures are not applicable.
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: February 6, 2018
• Actual Primary Completion Date: April 11, 2019
• Actual Study Completion Date: January 8, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Percent Change From Baseline in Total Hip BMD at Month 6 [ Time Frame: Baseline, Month 6 ]
   Percent change from baseline in BMD for total hip as measured by DXA.
2. Percent Change From Baseline in Femoral Neck BMD at Month 6 [ Time Frame: Baseline, Month 6 ]
   Percent change from baseline in BMD at femoral neck as measured by DXA.
3. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths [ Time Frame: up to Month 9 (-7/+3 days) ]
   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.
4. Number of Participants Developing Anti-Romosozumab Antibodies [ Time Frame: up to Month 9 (-7/+3 days) ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Alabama

Research Site

Birmingham, Alabama, United States, 35205

Research Site

Birmingham, Alabama, United States, 35294

Research Site

Huntsville, Alabama, United States, 35801

Research Site

Tuscaloosa, Alabama, United States, 35406

United States, Arizona

Research Site

Chandler, Arizona, United States, 85224

Research Site

Mesa, Arizona, United States, 85213

United States, California

Research Site

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

United States, Colorado

Research Site

Denver, Colorado, United States, 80230

Research Site

Golden, Colorado, United States, 80401

United States, Florida

Research Site

Delray Beach, Florida, United States, 33446

Research Site

South Miami, Florida, United States, 33143

United States, Georgia

Research Site

Atlanta, Georgia, United States, 30319

Research Site

Atlanta, Georgia, United States, 30342

United States, Missouri

Research Site

Bridgeton, Missouri, United States, 63044

Research Site

Springfield, Missouri, United States, 65802

United States, Nevada

Research Site

Las Vegas, Nevada, United States, 89148

United States, New York

Research Site

Great Neck, New York, United States, 11021

United States, North Carolina

Research Site

Charlotte, North Carolina, United States, 28204

United States, North Dakota

Research Site

Fargo, North Dakota, United States, 58103

United States, Ohio

Research Site

Cincinnati, Ohio, United States, 45242

United States, Pennsylvania

Research Site

Duncansville, Pennsylvania, United States, 16635

Research Site

Wyomissing, Pennsylvania, United States, 19610

United States, South Carolina

Research Site

Spartanburg, South Carolina, United States, 29303

Research Site

Summerville, South Carolina, United States, 29486

United States, Texas

Research Site

San Antonio, Texas, United States, 78209

United States, Utah

Research Site

Salt Lake City, Utah, United States, 84107

United States, Virginia

Research Site

Chesapeake, Virginia, United States, 23320

Research Site

Danville, Virginia, United States, 24541

United States, Washington

Research Site

Renton, Washington, United States, 98057

United States, Wisconsin

Research Site

Franklin, Wisconsin, United States, 53132

Poland

Research Site

Bialystok, Poland, 15-351

Research Site

Lodz, Poland, 90-558

Research Site

Swidnik, Poland, 21-040

Research Site

Warszawa, Poland, 01-192

United Kingdom

Research Site

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

Sponsors and Collaborators

Amgen

Investigators

• Study Director: MD; Amgen

  Study Documents (Full-Text)

Documents provided by Amgen:

Study Protocol  [PDF] August 10, 2017

Statistical Analysis Plan  [PDF] May 8, 2019

More Information

Additional Information:

AmgenTrials clinical trials website 

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT03432533
• Other Study ID Numbers: 20150120; 2017-003512-40 ( EudraCT Number )
• First Posted: February 14, 2018
• Results First Posted: April 10, 2020
• Last Update Posted: November 23, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• 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.
• 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.
• URL: https://www.amgen.com/datasharing

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by Amgen:

Post-Menopausal osteoporosis

Additional relevant MeSH terms:

Osteoporosis; Osteoporosis, Postmenopausal; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs