Study of TST002 Injection in Postmenopausal Women With Osteoporosis or Low Bone Mass

Primary Purpose: Efficacy and safety evaluation of TST002 in postmenopausal osteoporosis and low bone mass.

Design: 5-arm, randomized, double-blind (denosumab arm open-label), placebo- and active-comparator (denosumab)-controlled, parallel-group study with stratified block randomization by screening BMD T-score (Stratum 1: T-score ≥ -2.00; Stratum 2: T-score < -2.00 at all sites). Enrollment capped at <20% Stratum 1 participants per arm.

All participants receive daily calcium (600-1200 mg elemental) and vitamin D (725-1450 IU) supplementation from screening through study end, with an optional vitamin D loading dose for those with baseline 25(OH)D 20-40 ng/mL.

Unblinding: Primary analysis after all participants complete Week 24 is performed by an unblinded CRO team; investigators, participants, and the CRO study team (except for the open-label denosumab arm) remain blinded until final study unblinding

Inclusion criteria

• Voluntary signed informed consent; able to walk freely; willing/able to complete all study procedures.
• BMI 18.0-30.0 kg/m² (inclusive); body weight ≥45 kg.
• Postmenopausal women aged 45-80 years (inclusive) at screening, postmenopausal ≥2 years (≥12 consecutive months without spontaneous vaginal bleeding/spotting).
• BMD T-score <-2.00 at lumbar spine (L1-L4 total), total hip, or femoral neck at screening; OR history of fragility fracture with T-score <-1.00 at one of these sites (central imaging read).
• At least 2 contiguous evaluable vertebrae (L1-L4) and at least one evaluable hip for DXA assessment.
• No disease, per investigator history/exam/workup, likely to significantly affect the study or increase health risk (documented exceptions permitted with justification).

Exclusion criteria

• BMD T-score ≤-3.50 at lumbar spine, total hip, or femoral neck at screening.
• Prior hip fracture.
• ≥2 vertebral fractures on screening lateral spine X-ray (investigator-assessed).
• Known skeletal, endocrine, or rheumatic disease that could confound results (e.g., Paget's disease, osteomalacia, osteopetrosis, osteogenesis imperfecta, sclerosteosis, rheumatoid arthritis, ankylosing spondylitis, Cushing's disease, hyperprolactinemia, uncontrolled thyroid disease, hyper-/hypoparathyroidism, or CN VIII compression hearing loss).
• Prior osteoporosis therapy (incl. trial participation) within protocol-specified washout windows (IV bisphosphonates, oral bisphosphonates, denosumab/cathepsin K inhibitors, tibolone/cinacalcet/calcitonin, teriparatide/PTH analogs, systemic estrogen/SERMs, strontium ranelate/fluoride, hormonal castration therapy, systemic glucocorticoids ≥5 mg/day prednisone-equivalent for >14 days) - see protocol for exact windows per agent.
• History of TMJ disorder, TMJ osteonecrosis, or atypical fracture.
• Hypercalcemia or hypocalcemia (albumin-corrected) at screening.
• Serum 25(OH)D <20 ng/mL at screening.
• History of MI, or serious cardiac disease (CAD, NYHA class II-IV heart failure) within 6 months before screening.
• History of stroke (cerebral infarction, ischemic or hemorrhagic).
• ALT/AST >3× ULN; ALP >2.5× ULN; total bilirubin or creatinine >1.5× ULN at screening.
• Multiple myeloma, primary/metastatic bone malignancy, or history of skeletal radiotherapy.
• Malignancy within 5 years before screening (except cured skin squamous/basal cell carcinoma or documented cured in situ cervical cancer, no recurrence ≥3 months before dosing).
• Known hypersensitivity to study drug.
• History of solid organ or bone marrow transplant.
• Positive HIV, syphilis, HCV antibody, or HBsAg at screening; or HBcAb-positive with detectable HBV DNA.
• Active tuberculosis within 6 months before screening.
• Participation in another clinical trial within 30 days or 5 half-lives of the investigational product (whichever longer) before screening.
• Any other condition the investigator judges unsuitable for participation, a safety risk, or interfering with study assessments/completion.