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
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 110
- 主要终点
- Percent change from baseline in lumbar spine Bone Mineral Density (BMD)
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 45 Years 至 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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.
研究组 & 干预措施
TST002 1200 mg Q12W
TST002 1200 mg D1(W0), W12, W24, W36, W48; placebo infusion at W12, W24, W36, W48
干预措施: Placebo (Drug)
Denosumab
Denosumab 60 mg subcutaneous injection at D1(W0) and W24 (open-label)
干预措施: Placebo (Drug)
TST002 400 mg Q12W
IV infusion 400 mg on D1(W0), W8, W16, W24, W32, W40, W48; placebo infusion at W12, W24, W36, W48
干预措施: Placebo (Drug)
TST002 800 mg Q12W
IV infusion 800 mg on D1(W0), W8, W16, W24, W32, W40, W48; placebo infusion at W12, W24, W36, W48
干预措施: Placebo (Drug)
Placebo
IV placebo on D1(W0), W12, W24, W36, W48; crosses over to open-label TST002 in extension phase (dose per primary analysis)
干预措施: Denosumab (Drug)
结局指标
主要结局
Percent change from baseline in lumbar spine Bone Mineral Density (BMD)
时间窗: Baseline to Week 24
Lumbar spine (L1-L4) bone mineral density, central imaging read (DXA)
次要结局
- TST002 Volume of Distribution(Out to 52 weeks)
- Percent change from baseline in lumbar spine Bone Mineral Density (BMD)(Weeks 12 and 52)
- Percent change from baseline in total hip Bone Mineral Density (BMD)(Weeks 12, 24, and 52)
- Percent change from baseline in femoral neck Bone Mineral Density (BMD)(Weeks 12, 24 and 52)
- TST002 plasma concentration(Up to 52 weeks)
- Percent change from baseline in bone turnover markers(Up to 52 weeks)
- Anti-drug antibody (ADA) positivity rate(Up to 52 weeks)
- Incidence of adverse events(Up to 52 weeks)
- TST002 Concentration-time(Up to 52 weeks)
- TST002 Peak Plasma Concentration(Up to 52 weeks)
- TST002 Trough Concentrations(Up to 52 weeks)
- TST002 Half-life(Up to 52 weeks)
- TST002 Systemic Clearance(Up to 52 weeks)
- TST002 Effects on total Sclerostin(Up to 52 weeks)
- TST002 Effects on total P1NP(Up to 52 weeks)
- TST002 Effects on total B-CTX(Out to 52 weeks)
- TST002 Effects on total OC(Out to 52 weeks)
- TST002 Effects on total BSAP(Up to 52 weeks)
- TST002 Effects on total TRACP-5b(Up to 52 weeks)