A Study for the Evaluation of Efficacy and Safety of Prolia® in Participants With Glucocorticoid-induced Osteoporosis in Mainland China

A Phase 4 Single-arm Open-label Study for the Efficacy and Safety of Prolia® in Participants With Glucocorticoid-induced Osteoporosis in Mainland China

The main objective of this study is to evaluate the efficacy of Prolia® in improving bone mass density (BMD) of lumbar spine at month 12.

Inclusion Criteria

• Participant has provided informed consent prior to initiation of any study-specific activities/procedures.

• Male and female participants aged ≥ 18 years at the time of signing the informed consent.

• Participants are receiving glucocorticoid treatment at screening.

• Participants who are ≥ 50 years of age at the time of screening will be required to have a T-score with:

  - a BMD value equivalent to a T-score ≤ -2.5 at the lumbar spine or total hip or femoral neck; OR

  - a BMD value equivalent to a T-score ≤ -1.0 at the lumbar spine or total hip or femoral neck AND a history of osteoporotic fracture.

• Participants who are < 50 years of age at the time of screening will be required to have a T-score with a BMD value equivalent to a T-score ≤ -1.0 at the lumbar spine or total hip or femoral neck AND have a history of osteoporotic fracture.

• At least 2 lumbar vertebrae from L1 through L4 and 1 hip must be evaluable by dual-energy x-ray absorptiometry (DXA).

• Adequate organ function, defined as follows:

  • Hematological function:

    1. Absolute neutrophil count ≥ 1 x 10^9 /L
    2. Platelet count ≥ 100 x 10^9 /L
    3. Hemoglobin > 9 g/dL (90 g/L).

  • Coagulation function:

    1 Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time or activated partial thromboplastin time ≤ 1.5 x upper limit of normal (ULN). Participants on chronic anticoagulation therapy who do not meet the criteria above may be eligible to enroll at the investigator's discretion per local standard of care.

  • Renal function:

    1 Estimated glomerular filtration rate based on Modification of Diet in Renal Disease (MDRD) calculation > 30 mL/min/1.73 m^2.

  • Hepatic function:

    1. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase < 3 x ULN
    2. Total bilirubin (TBL) < 1.5 x ULN.

Exclusion Criteria

Disease Related

• Received other osteoporosis treatment or bone-active treatment with:

  - prior use of bisphosphonate:

  1. bisphosphonate use within 1 year unless duration of oral bisphosphonates treatment < 3 months use prior to screening

  2. administration of intravenous zoledronate within 2 years or intravenous bisphosphonate other than zoledronate within the last year.

     • fluoride or strontium for osteoporosis within the last 5 years
     • anabolic agents to include PTH or PTH derivatives within the last year
     • any prior use of products containing denosumab

• Administration of any of the following treatments within 3 months of screening:

  - any selective estrogen receptor modulator (estrogen agonist antagonist)

  • tibolone
  • anabolic steroids
  • testosterone above normal replacement doses not on stable dose
  • systemic hormone replacement therapy not on stable dose
  • systemic hormonal contraception not specified in the protocol or not on stable dose
  • calcitonin.

• Other bone-active drugs including:

  • anti-convulsants (except benzodiazepines) and heparin (low molecular weight heparin is allowed)
  • chronic systemic ketoconazole, androgens, adrenocorticotropic hormone (ACTH), cinacalcet, aluminum, lithium, protease inhibitors, gonadotropin-releasing hormone agonists.

• Any pretrial initiation of anti-inflammatory disease-modifying anti-rheumatic drug (DMARD) that is not consistent with the local Chinese label or guidelines.

• Participant has an active infection or history of infections as follows:

  • any active infection for which systemic anti-infectives were used within 4 weeks prior to screening
  • a serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to screening
  • recurrent or chronic infections or other active infection that, in the opinion of the investigator, might compromise the safety of the participant.

Other Medical Conditions

• History of hyperthyroidism (stable on antithyroid therapy is allowed) when suggested by medical history
• History of hypothyroidism (stable on thyroid replacement therapy is allowed) when suggested by medical history
• History of hypo- or hyperparathyroidism
• History of Addison's disease
• History of osteomalacia
• History of osteonecrosis of the jaw (ONJ)
• History of tooth extraction or other dental surgery within the prior 6 months
• Invasive dental work (per local oral surgeon's assessment) planned in the next 12 months
• History of Paget's disease of bone
• Other bone diseases which affect bone metabolism (e.g., osteopetrosis, osteogenesis imperfecta) (chart review)
• Received any solid organ or bone marrow transplant
• Known to have tested positive for human immunodeficiency virus, hepatitis C virus, hepatitis B surface antigen
• Participants with a history of any cancer (cured basal cell or squamous cell cancers are allowed)

Prior/Concurrent Clinical Study Experience • Currently receiving treatment in another investigational device or drug study, or less than 30 days or 5 half-lives, whichever is longer, since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.

Diagnostic Assessments

• Abnormalities of the following per central laboratory reference ranges:

  - Vitamin D deficiency (25[OH] vitamin D level < 20 ng/mL [< 49.9 nmol/L]). Vitamin D replenishment will be permitted, and participants may be re-screened once.

  - Hypercalcemia.

  - Elevated transaminases ≥ 3.0 x ULN.

  • Elevated TBL > 1.5 x ULN.
  • Albumin-adjusted serum calcium levels < 8.5 mg/dL or > 10.5 mg/dL.

Other Exclusions

• Female participants of childbearing potential unwilling to use protocol-specified method of contraception (see Appendix 5, Section 11.5) during treatment and for an additional 5 months after the last dose of Prolia®.
• Female participants who are breastfeeding or who plan to breastfeed while on study through 5 months after the last dose of Prolia®.
• Female participants planning to become pregnant while on study through 5 months after the last dose of Prolia®.
• Female participants of childbearing potential with a positive pregnancy test assessed at Screening by a serum pregnancy test.
• Participant has known sensitivity to any of the products or components to be administered during dosing.
• Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the participant's and investigator's knowledge.
• History or evidence of any other clinically significant disorder, condition, or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion.