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.

Study Overview

• Status: Not yet recruiting
• Conditions: Postmenopausal Osteoporosis; Low Bone Mass
• Intervention / Treatment: Drug: Placebo; Drug: Denosumab

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Vicky Zhong; Phone Number: +86-0571-28279502; Email: vicky.zhong@transcenta.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TST002 400 mg Q8W; IV infusion 400 mg on D1(W0), W8, W16, W24, W32, W40, W48; placebo infusion at W12, W36	Drug: Placebo; Vehicle Placebo
Experimental: TST002 800 mg Q8W; IV infusion 800 mg on D1(W0), W8, W16, W24, W32, W40, W48; placebo infusion at W12, W36	Drug: Placebo; Vehicle Placebo
Experimental: TST002 1200 mg Q12W	Drug: Placebo; Vehicle Placebo
Placebo Comparator: Placebo; IV placebo on D1(W0), W8, W12, W16; crosses over to open-label TST002 in extension phase (dose per primary analysis)	Drug: Placebo; Vehicle Placebo
Active Comparator: Denosumab; Denosumab 60 mg subcutaneous injection at D1(W0) and W24 (open-label)	Drug: Denosumab; Active comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change from baseline in lumbar spine Bone Mineral Density (BMD)	Lumbar spine (L1-L4) bone mineral density, central imaging read (DXA)	Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change from baseline in lumbar spine Bone Mineral Density (BMD)	Central imaging read (DXA)	Weeks 12 and 52
Percent change from baseline in total hip Bone Mineral Density (BMD)	Central imaging read (DXA)	Weeks 12, 24, and 52
Percent change from baseline in femoral neck Bone Mineral Density (BMD)	Central imaging DXA	Weeks 12, 24 and 52
TST002 plasma concentration	Plasma concentrations at each dosing timepoint	Up to 52 weeks
Percent change from baseline in bone turnover markers	P1NP, β-CTX, OC, BSAP, TRACP-5b, and total sclerostin	Up to 52 weeks
Anti-drug antibody (ADA) positivity rate	Immunogenicity - proportion positive and time to first positive	Up to 52 weeks
Incidence of adverse events	AEs, vital signs, physical exam, and clinically significant lab abnormalities (CTCAE v6.0 graded)	Up to 52 weeks
TST002 Concentration-time	Area under curve (AUC)	Up to 52 weeks
TST002 Peak Plasma Concentration	Cmax	Up to 52 weeks
TST002 Trough Concentrations	Ctrough	Up to 52 weeks
TST002 Half-life	T1/2	Up to 52 weeks
TST002 Systemic Clearance	CL	Up to 52 weeks
TST002 Volume of Distribution	Vd	Out to 52 weeks
TST002 Effects on total Sclerostin	Pharmacodynamic effects	Up to 52 weeks
TST002 Effects on total P1NP	Pharmacodynamic effects of Serum N-terminal propeptide of procollagen type 1	Up to 52 weeks
TST002 Effects on total B-CTX	Pharmacodynamic effects of Beta-C-terminal telopeptide	Out to 52 weeks
TST002 Effects on total OC	Pharmacodynamic effects of osteocalcin	Out to 52 weeks
TST002 Effects on total BSAP	Pharmacodynamic effects of Bone-specific alkaline phosphatase	Up to 52 weeks
TST002 Effects on total TRACP-5b	Pharmacodynamic effects of Tartrate-Resistant Acid Phosphatase 5b	Up to 52 weeks

Collaborators and Investigators

• Sponsor: Suzhou Transcenta Therapeutics Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): October 31, 2026
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): October 31, 2028

Study Registration Dates

• First Submitted: August 20, 2026
• First Submitted That Met QC Criteria: September 1, 2026
• First Posted (Actual): September 8, 2026

Study Record Updates

• Last Update Posted (Actual): September 8, 2026
• Last Update Submitted That Met QC Criteria: September 1, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: monoclonal antibody; DXA; bone mineral density; postmenopausal osteoporosis; sclerostin; low bone mass; TST002
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Bone Diseases, Metabolic; Osteoporosis; Nutritional and Metabolic Diseases; Osteoporosis, Postmenopausal; Sclerosteosis; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Denosumab
• Other Study ID Numbers: TST002-1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Original informed consent forms for trial participants do not explicitly cover secondary research use or broad data sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No