Table 5 Bone-derived factors in the clinical trials
From: Bone-derived factors mediate crosstalk between skeletal and extra-skeletal organs
Target Protein | Conditions | Drug | Location | Ages and sex | Treatment method | Primary outcome | Phase | Clinical study ID |
|---|---|---|---|---|---|---|---|---|
RANKL | Fibrous dysplasia | Denosumab | USA | Over 18, all | 120 mg s.c. Q4W | CTX, PINP | II | NCT03571191 |
RANKL | Osteopenia, Spine fusion, Denosumab allergy | Denosumab | China | 40–85, all | 60 mg s.c. plus intravenous placebo Q6M plus calcium supplementation 1200 mg/D and vitamin D 800 IU/D | BMD, P1NP, CTX, VAS score | II | NCT05419050 |
RANKL | Osteoporotic vertebral compression fracture | Denosumab | China | 50–90, all | 60 mg s.c. Q6M | BMD, P1NP, CTX, VAS score | II/III | NCT05058443 |
RANKL | Denosumab allergy, zoledronic acid allergy | Denosumab | China | 50–90, all | 60 mg s.c. plus intravenous placebo Q6M | BMD, P1NP, CTX, VAS score | IV | NCT05598606 |
RANKL | Osteoporosis, lumbar fusion | Denosumab | China | Over 50, all | 60 mg s.c., on week1 and 26 | lumbar fusion rate | IV | NCT05203588 |
RANKL | Healthy subjects | AVT03 | Poland, UK, South Africa | 28–55, male | 120 mg s.c., single dose | Cmax, AUClast | I | NCT05876949 |
RANKL | Healthy subjects | AVT03 | Australia, New Zealand, South Africa | 28–55, male | 60 mg s.c., single dose | AUCinf, AUClast, Cmax, CTX-1 | I | NCT05126784 |
RANKL | Healthy subjects | Bmab 1000 | USA | 28–55, all | 60 mg s.c., single dose | AUCinf, AUClast, Cmax | I | NCT05323708 |
RANKL | Healthy subjects | MW031 | China | 18–65, male | 60 mg s.c., single dose | AUC, Cmax | I | NCT04798313 |
RANKL | Healthy subjects | LY06006 | China | 28–65, male | 60 mg s.c., single dose | AUCinf, AUClast, Cmax, Tmax | I | NCT04973722 |
RANKL | Healthy subjects | HS-20090-2 | China | 18–50, male | 60 mg s.c., single dose | AUCinf, Cmax | I | NCT04940845 |
RANKL | Healthy subjects | CT-P41 | Korea | 28–55, male | 60 mg s.c., single dose | AUCinf, AUClast, Cmax | I | NCT06037395 |
RANKL | Healthy subjects | HLX14 | China | 28–65, male | 60 mg s.c., single dose | AUCinf, AUClast, Cmax | I | NCT04534582 |
RANKL | Healthy subjects | CT-P41 | Australia | 28–55, male | 60 mg s.c., single dose | Treatment-emergent adverse events | I | NCT04512872 |
RANKL | Healthy subjects | MB09 | Poland | 28–55, male | 35 mg s.c., single dose | AUClast, Cmax | I | NCT05299073 |
RANKL | Healthy subjects | CMAB807 | China | 18–65, male | 60 mg s.c., single dose | AUClast, Cmax | I | NCT03925051 |
RANKL | Women with osteoporosis | Bmab 1000 | UK | 55–80, female | 60 mg s.c. Q6M | BMD | III | NCT05345691 |
RANKL | Bone metastases from solid tumors | LY01011 | China | 18–80, all | 120 mg s.c. Q4W | Urinary type I collagen cross-linked N-telopeptides corrected for urine creatinine | III | NCT04859569 |
RANKL | Bone metastases | MW032 | China | over 18, all | 120 mg s.c. Q4W | Bone conversion index | III | NCT04812509 |
RANKL | Postmenopausal osteoporosis | FKS518 | Bulgaria, Czechia, Estonia, Georgia, Hungary, Poland | 55–85, female | 60 mg s.c. every 26 weeks | BMD, P1NP, CTX, Adverse Event | III | NCT04934072 |
RANKL | Postmenopausal osteoporosis | TVB-009P | USA, Bulgaria, Czechia, Georgia, Hungary, Poland, Russian Federation, Slovakia | 60–90, female | 60 mg s.c. on various time point | BMD | III | NCT04729621 |
RANKL | Postmenopausal osteoporosis | CT-P41 | Estonia, Latvia, Poland, Ukraine | 50–80, female | 60 mg s.c., single dose | BMD | III | NCT04757376 |
RANKL | Postmenopausal osteoporosis | SB16 | Poland | 55–80, female | 60 mg s.c. Q6M | BMD | III | NCT04664959 |
RANKL | Bone metastases | QL1206 | China | 18–80, all | 120 mg s.c. Q4W | uNTx/uCr | III | NCT04550949 |
RANKL | Postmenopausal osteoporosis | HLX14 | China | 60–90, female | 60 mg s.c. Q6M | BMD, CTX | III | NCT05352516 |
RANKL | Postmenopausal osteoporosis | MB09 | Bulgaria, Estonia, Georgia, Hungary, Latvia, Mexico, Poland, Serbia | 55–80, female | 60 mg s.c. Q6M | BMD | III | NCT05338086 |
RANKL | Postmenopausal osteoporosis | GP2411 | USA, Bulgaria, Czechia, Japan, Poland, Spain | 55–80, female | 60 mg s.c. Q6M | BMD, AUCinf, AUClast, Cmax | III | NCT03974100 |
RANKL | Postmenopausal osteoporosis | RGB-14-P | USA, Bulgaria, Czechia, Hungary, Italy, Poland, Spain, Ukraine | 60–90, female | 60 mg s.c. on various time point | BMD, CTX | III | NCT05087030 |
RANKL | Postmenopausal osteoporosis | ENZ215 | Czechia | 55–85, female | 60 mg s.c., single dose | BMD, CTX | III | NCT05405725 |
Sclerostin | Osteogenesis imperfecta | Romosozumab | USA, Australia, Germany, Greece, Hungary, Italy, Spain, Turkey | 5–17, all | Multiple doses, s.c. | Cmax, Tmax | I | NCT04545554 |
Sclerostin | Multiple myeloma | Romosozumab | USA | Over 18, all | 210 mg s.c., Q4W for 12 months | P1NP, Incidence and Severity of adverse events | I | NCT05775094 |
Sclerostin | Chronic spinal cord injury and osteoporosis | Romosozumab | USA | Over 18, female | 60 mg s.c., monthly | BMD | II | NCT04708886 |
Sclerostin | Premenopausal idiopathic osteoporosis | Romosozumab | USA | 18–45, female | 210 mg s.c., once a month for 12 months | Lumbar spine BMD | II | NCT04800367 |
Sclerostin | Osteoporosis | Romosozumab | China | 55–90, female | In a specified sequence | BMD, treatment-emergent adverse events | III | NCT05067335 |
Sclerostin | Osteogenesis imperfecta | Romosozumab | USA, Australia, Belgium, Canada, France, Germany, Hungary, Japan, Poland, Slovakia, Spain, Switzerland, Turkey, UK | 5–17, all | Once a month for 12 months | Number of Clinical fractures/any fractures, lumbar spine BMD | III | NCT05972551 |
Sclerostin | Osteoporosis | Romosozumab | Denmark | Over 50, female | 210 mg/2.34 ml | BMD | IV | NCT06059222 |
Sclerostin | Spinal cord injuries | Romosozumab | USA | 18–55, all | 210 mg s.c. every month | BMD | IV | NCT05101018 |
Sclerostin | Postmenopausal osteoporosis | Romosozumab | India | Over 18, all | 210 mg s.c., once a month for 12 months | Treatment-emergent adverse events, clinically significant changes | IV | NCT06079476 |
Sclerostin | Glucocorticoid-induced osteoporosis | Romosozumab | China | Over 18, all | 60 mg s.c. Q6M | BMD | IV | NCT04091243 |
DKK1 | Prostate cancer | DKN-01 | USA | 18–100, male | Start with 300 mg and be escalated to 600 mg or de-escalated to 150 mg | Number of dose limiting toxicities, number of participants with a best overall response | Ib, IIa | NCT03837353 |
DKK1 | Endometrial cancer | DKN-01 | USA | Over 18, all | i.v. over about 30 minutes to 2 hours on Day 1 of each cycle, as well as on Day 15 of Cycle 1. | Incidence of adverse events | II | NCT05761951 |
DKK1 | Colorectal cancer | DKN-01 | USA, Germany, Korea, | Over 18, all | i.v. (400 mg) every two weeks with an additional loading dose in the first cycle of treatment | Progression free survival | II | NCT05480306 |
DKK1 | Gastric cancer | USA, Germany, Korea, | Over 18, all | i.v. (300 mg) on Days 1 and 15 | Safety and tolerability, Progression free survival | II | NCT04363801 |
