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

A Randomized, Double-Blind, Parallel-Controlled Phase II Clinical Trial to Evaluate the Efficacy and Safety of TST002 Injection in Postmenopausal Osteoporosis Patients and Middle-Aged to Older Women With Low Bone Mass

This is a randomized, double-blind, placebo- and active-controlled Phase II study evaluating the efficacy and safety of TST002 injection (a humanized monoclonal antibody) in postmenopausal women with osteoporosis or low bone mass, aged 45-80 years.

Approximately 110 participants will be randomized 1:1:1:1:1 (stratified by baseline BMD T-score) to one of five arms: TST002 400 mg every 8 weeks (Q8W), TST002 800 mg Q8W, TST002 1200 mg every 12 weeks (Q12W), placebo, or open-label denosumab 60 mg subcutaneously every 24 weeks. The study includes a screening period (Day -28 to Day -1), a main study period (Week 0-24), and an extension period (Week 25-52), with all participants followed through Week 52 (Day 365).

The primary objective is to evaluate the effect of repeated IV TST002 infusions on lumbar spine bone mineral density (BMD). Secondary objectives include characterization of pharmacokinetics, pharmacodynamics, immunogenicity, safety, and tolerability.

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:

1. Voluntary signed informed consent; able to walk freely; willing/able to complete all study procedures.
2. BMI 18.0-30.0 kg/m² (inclusive); body weight ≥45 kg.
3. Postmenopausal women aged 45-80 years (inclusive) at screening, postmenopausal ≥2 years (≥12 consecutive months without spontaneous vaginal bleeding/spotting).
4. 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).
5. At least 2 contiguous evaluable vertebrae (L1-L4) and at least one evaluable hip for DXA assessment.
6. No disease, per investigator history/exam/workup, likely to significantly affect the study or increase health risk (documented exceptions permitted with justification).

Exclusion Criteria:

1. BMD T-score ≤-3.50 at lumbar spine, total hip, or femoral neck at screening.
2. Prior hip fracture.
3. ≥2 vertebral fractures on screening lateral spine X-ray (investigator-assessed).
4. 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).
5. 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.
6. History of TMJ disorder, TMJ osteonecrosis, or atypical fracture.
7. Hypercalcemia or hypocalcemia (albumin-corrected) at screening.
8. Serum 25(OH)D <20 ng/mL at screening.
9. History of MI, or serious cardiac disease (CAD, NYHA class II-IV heart failure) within 6 months before screening.
10. History of stroke (cerebral infarction, ischemic or hemorrhagic).
11. ALT/AST >3× ULN; ALP >2.5× ULN; total bilirubin or creatinine >1.5× ULN at screening.
12. Multiple myeloma, primary/metastatic bone malignancy, or history of skeletal radiotherapy.
13. 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).
14. Known hypersensitivity to study drug.
15. History of solid organ or bone marrow transplant.
16. Positive HIV, syphilis, HCV antibody, or HBsAg at screening; or HBcAb-positive with detectable HBV DNA.
17. Active tuberculosis within 6 months before screening.
18. Participation in another clinical trial within 30 days or 5 half-lives of the investigational product (whichever longer) before screening.
19. Any other condition the investigator judges unsuitable for participation, a safety risk, or interfering with study assessments/completion.