A Comparison of Subject-administered Romosozumab With Healthcare Provider-administered Romosozumab for Osteoporosis
Condition: Post-Menopausal Osteoporosis
MeSH terms: Osteoporosis; Osteoporosis, Postmenopausal
Intervention: romosozumab HCP administration with PFS; romosozumab self-administration with AI/Pen
Intervention description: 210 mg romosozumab SC QM by HCP administration with 2 PFS; 210 mg romosozumab SC QM by self-administration with 2 AI/Pens
Intervention MeSH terms: Antibodies, Monoclonal
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
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.
Enrollment: 283.0
Sex: Female
Minimum age: 55 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: Post-Menopausal osteoporosis

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