Clinical trial NCT03432533: A Comparison of Subject-administered Romosozumab With Healthcare Provider-administered Romosozumab for Osteoporosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Post-Menopausal Osteoporosis
Keywords: Post-Menopausal osteoporosis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2018-02-14
Enrollment: 283
Sex: FEMALE
Minimum age (years): 55
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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)


Eligibility 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

Primary outcomes:
measure: Percent Change From Baseline in Lumbar Spine BMD at Month 6
timeFrame: Baseline, Month 6
Secondary outcomes:
measure: Percent Change From Baseline in Total Hip BMD at Month 6
timeFrame: Baseline, Month 6
measure: Percent Change From Baseline in Femoral Neck BMD at Month 6
timeFrame: Baseline, Month 6
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths
timeFrame: up to Month 9 (-7/+3 days)
measure: Number of Participants Developing Anti-Romosozumab Antibodies
timeFrame: up to Month 9 (-7/+3 days)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Huntsville
country: United States
facility: Research Site
state: Alabama
city: Tuscaloosa
country: United States
facility: Research Site
state: Alabama
city: Chandler
country: United States
facility: Research Site
state: Arizona
city: Mesa
country: United States
facility: Research Site
state: Arizona
city: Cypress
country: United States
facility: Research Site
state: California
city: Fullerton
country: United States
facility: Research Site
state: California
city: Glendale
country: United States
facility: Research Site
state: California
city: Laguna Hills
country: United States
facility: Research Site
state: California
city: Santa Maria
country: United States
facility: Research Site
state: California
city: Tustin
country: United States
facility: Research Site
state: California
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Golden
country: United States
facility: Research Site
state: Colorado
city: Delray Beach
country: United States
facility: Research Site
state: Florida
city: South Miami
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Bridgeton
country: United States
facility: Research Site
state: Missouri
city: Springfield
country: United States
facility: Research Site
state: Missouri
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Great Neck
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Fargo
country: United States
facility: Research Site
state: North Dakota
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Duncansville
country: United States
facility: Research Site
state: Pennsylvania
city: Wyomissing
country: United States
facility: Research Site
state: Pennsylvania
city: Spartanburg
country: United States
facility: Research Site
state: South Carolina
city: Summerville
country: United States
facility: Research Site
state: South Carolina
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Chesapeake
country: United States
facility: Research Site
state: Virginia
city: Danville
country: United States
facility: Research Site
state: Virginia
city: Renton
country: United States
facility: Research Site
state: Washington
city: Franklin
country: United States
facility: Research Site
state: Wisconsin
city: Bialystok
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Swidnik
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Chorley
country: United Kingdom
facility: Research Site
city: Edinburgh
country: United Kingdom
facility: Research Site
city: Liverpool
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Northwood
country: United Kingdom
facility: Research Site
city: Romford
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: