Study to Evaluate the Safety and Efficacy of BA058 (Abaloparatide) for Prevention of Fracture in Postmenopausal Women

Conditions

Osteoporosis, Postmenopausal Osteoporosis

Keywords

BA058, abaloparatide, Abaloparatide-SC, osteoporosis, postmenopausal, bone loss, ACTIVE, fracture

Brief summary

The purpose of this study is to determine whether BA058 (abaloparatide), a parathyroid hormone-related peptide, is effective in preventing fractures in postmenopausal women with severe osteoporosis who are at risk of fractures.

Detailed description

This is a randomized, double-blind, placebo-controlled, comparative Phase 3, multicenter international study to evaluate the efficacy and safety of BA058 (abaloparatide) 80 µg in the prevention of fracture in otherwise healthy ambulatory postmenopausal women with severe osteoporosis.

Sheth NP, Krohn K, Torkelson J, Winzenrieth R, Humbert L, Pearman L, Wang Y, Boxberger JI, Bostrom MP.

2025-07-19

10.1016/j.bonr.2025.101858

Effect of abaloparatide on fracture incidence and bone mineral density in postmenopausal women with osteoporosis at highest risk for fracture

Kristi Tough DeSapri, B.L. Clarke, Paul Kostenuik, Yamei Wang, Bruce Mitlak

Menopause The Journal of The North American Menopause Society2025-02-252 citations

10.1097/gme.0000000000002516

Bone turnover markers predict changes in bone mineral density in men treated with abaloparatide: results from the abaloparatide for the treatment of men with osteoporosis (ATOM) study

Richard Eastell, Jacques P. Brown, Robert A. Adler, E. Michael Lewiecki, Neil Binkley et al. (9 authors)

Journal of Bone and Mineral Research2025-01-101 citations

10.1093/jbmr/zjaf003

Effects of Abaloparatide on Bone Mineral Density in Proximal Femoral Regions Corresponding to Arthroplasty Gruen Zones

Neil P. Sheth, J Smith, Renaud Winzenrieth, Ludovic Humbert, Yamei Wang et al. (7 authors)

Journal of Bone and Joint Surgery2024-05-016 citations

10.2106/jbjs.23.01334

Response rates for lumbar spine, total hip, and femoral neck bone mineral density in men treated with abaloparatide: results from the ATOM study

Ruban Dhaliwal, David L. Kendler, Kenneth G. Saag, Steven Ing, Andrea Singer et al. (9 authors)

JBMR Plus2024-01-274 citations

10.1093/jbmrpl/ziae009

Proximal Femur Responses to Sequential Therapy With Abaloparatide Followed by Alendronate in Postmenopausal Women With Osteoporosis by <scp>3D</scp> Modeling of Hip Dual‐Energy X‐Ray Absorptiometry (<scp>DXA)</scp>

Renaud Winzenrieth, Paul J. Kostenuik, John Boxberger, Yamei Wang, Ludovic Humbert

JBMR Plus2022-02-146 citations

10.1002/jbm4.10612

Phase 1b Evaluation of Abaloparatide Solid Microstructured Transdermal System (Abaloparatide-sMTS) in Postmenopausal Women with Low Bone Mineral Density.

Miller PD, Troy S, Weiss RJ, Annett M, Schense J, Williams SA, Mitlak B.

2021-02-2716 citations

10.1007/s40261-021-01008-7

Cardiovascular Safety of Abaloparatide in Postmenopausal Women With Osteoporosis: Analysis From the ACTIVE Phase 3 Trial

Felicia Cosman, Linda R. Peterson, Dwight A. Towler, Bruce Mitlak, Yamei Wang et al. (6 authors)

The Journal of Clinical Endocrinology & Metabolism2020-07-1344 citations

10.1210/clinem/dgaa450

Effect of Abaloparatide on Bone Mineral Density and Fracture Incidence in a Subset of Younger Postmenopausal Women with Osteoporosis at High Risk for Fracture

Kenneth G. Saag, Setareh A. Williams, Yamei Wang, R. J. Weiss, Jane A. Cauley

Clinical Therapeutics2020-06-0114 citations

10.1016/j.clinthera.2020.04.012

Fracture and Bone Mineral Density Response by Baseline Risk in Patients Treated With Abaloparatide Followed by Alendronate: Results From the Phase 3 ACTIVExtend Trial

Benjamin Z. Leder, Carol Zapalowski, Ming-Yi Hu, Gary Hattersley, Nancy E. Lane et al. (7 authors)

Journal of Bone and Mineral Research2019-08-1417 citations

10.1002/jbmr.3848

SAT-519 Effect of Abaloparatide on Bone Mineral Density and Fracture Incidence in a Subset of Younger Postmenopausal Women with Osteoporosis at High Risk for Fracture Representative of Covered Commercial Insurance Enrollees

Kenneth G. Saag, Setareh A. Williams, Yamei Wang, R. J. Weiss, Jane A. Cauley

Journal of the Endocrine Society2019-04-01

10.1210/js.2019-sat-519

OR03-1 The Effect of Abaloparatide on Bone Mineral Density and Fracture Incidence in Postmenopausal Women with Osteoporosis and Osteoarthritis

Nancy E. Lane, Bruce Mitlak, R. J. Weiss, Yamei Wang, Guillermo Valenzuela et al. (6 authors)

Journal of the Endocrine Society2019-04-01

10.1210/js.2019-or03-1

Bone mineral density response rates are greater in patients treated with abaloparatide compared with those treated with placebo or teriparatide: Results from the ACTIVE phase 3 trial.

Miller PD, Hattersley G, Lau E, Fitzpatrick LA, Harris AG, Williams GC, Hu MY, Riis BJ, Russo L, Christiansen C.

2018-10-2250 citations

10.1016/j.bone.2018.10.015

Effects of abaloparatide-SC (BA058) on bone histology and histomorphometry: The ACTIVE phase 3 trial

Carolina Aguiar Moreira, Lorraine A. Fitzpatrick, Yamei Wang, Robert R. Recker

Bone2016-11-0580 citations

10.1016/j.bone.2016.11.004

Effects of Abaloparatide-SC on Fractures and Bone Mineral Density in Subgroups of Postmenopausal Women With Osteoporosis and Varying Baseline Risk Factors

Felicia Cosman, Gary Hattersley, Ming‐yi Hu, Gregory C. Williams, Lorraine A. Fitzpatrick et al. (6 authors)

Journal of Bone and Mineral Research2016-09-0992 citations

10.1002/jbmr.2991

Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis

Paul D. Miller, Gary Hattersley, Bente Juel Riis, Gregory C. Williams, Edith Lau et al. (14 authors)

JAMA2016-08-16824 citations

10.1001/jama.2016.11136

Interventions

DRUGPlacebo

Placebo 0 mcg subcutaneous daily

DRUGBA058 80 mcg

BA058 80 mcg subcutaneous daily

DRUGteriparatide

teriparatide 20 mcg subcutaneous daily

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

FEMALE

Age

50 Years to 85 Years

Healthy volunteers

No

Inclusion criteria

* Healthy ambulatory postmenopausal (≥ 5 years) women from 50 to 85 years of age (inclusive) with a diagnosis of osteoporosis * The women are to have a bone mineral density (BMD) T score ≤ -2.5 and \> -5.0 at the lumbar spine or hip (femoral neck) by dual energy x-ray absorptiometry (DXA) and radiological evidence of 2 or more mild or one or more moderate lumbar or thoracic vertebral fractures, or history of low trauma forearm, humerus, sacral, pelvic, hip, femoral, or tibial fracture within the past 5 years. Postmenopausal women older than 65 who meet the above fracture criteria but have a T score ≤ -2.0 and \> -5.0 may be enrolled. Women older than 65 who do not meet the fracture criteria may also be enrolled if their T score is ≤ -3.0 and \> -5.0 * Normal physical exam, vital signs, electrocardiogram (ECG) and medical history * Laboratory tests within the normal range including serum calcium, PTH(1-84), serum phosphorus and alkaline phosphatase

Exclusion criteria

* History of more than 4 mild or moderate spine fractures or any severe fracture * Abnormality of the spine or hip that would prohibit assessment of bone mineral density (BMD) * Unexplained elevation of serum alkaline phosphatase, history of bone disorders (such as Paget's disease) or a diagnosis of cancer within the last 5 years (with the exception of basal cell or squamous cancer of the skin) * History of thyroid, parathyroid, or adrenal disorders, or malabsorptive syndromes or any chronic or recurrent diseases or disturbances that would interfere with the interpretation of study data or compromise the safety of the patient * Prior treatment with parathyroid hormone (PTH) or parathyroid hormone-related peptid (PTHrP) * Prior treatment with bisphosphonates, fluoride, or strontium within the past five years or treatment with androgens, anabolic steroids, corticosteroids or selective estrogen receptor modulators within the past 12 months (except hormone replacement therapy) * Prior treatment with an investigational drug within the past 12 months * History of nephrolithiasis or urolithiasis within the past five years, or history of osteosarcoma at any time

Design outcomes

Primary

Measure	Time frame
Number of Participants With New Vertebral Fractures at 18 Months	18 months

Secondary

Measure	Time frame
Percent Change in Bone Mineral Density (BMD) of Lumbar Spine From Baseline to 18 Months	Basline and 18 months
Percent Change in Bone Mineral Density (BMD) of Total Hip From Baseline to Month 18	Baseline and 18 months
Percent Change in Bone Mineral Density (BMD) of Femoral Neck From Baseline to Month 18	Baseline and 18 months
Number of Participants With Non-vertebral Fractures at 18 Months	18 months
Number of Treatment-Emergent Adverse Events Associated With Hypercalcemia at 18 Months	18 months

Countries

Argentina, Brazil, Czechia, Denmark, Estonia, Hong Kong, Lithuania, Poland, Romania, United States

Participant flow

Participants by arm

Arm	Count
Placebo Placebo identical in appearance to BA058 study drug Placebo: Placebo 0 mcg subcutaneous daily	821
BA058 80 mcg (Abaloparatide) BA058 80 mcg: BA058 80 mcg subcutaneous daily	824
Teriparatide Blinded until after randomization, then open-label teriparatide: teriparatide 20 mcg subcutaneous daily	818
Total	2,463

Baseline characteristics

Characteristic	Placebo	BA058 80 mcg (Abaloparatide)	Teriparatide	Total
Age, Continuous	68.7 years STANDARD_DEVIATION 6.5	68.9 years STANDARD_DEVIATION 6.5	68.8 years STANDARD_DEVIATION 6.6	68.8 years STANDARD_DEVIATION 6.5
Gender Female	821 Participants	824 Participants	818 Participants	2463 Participants
Gender Male	0 Participants	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	447 / 820	492 / 822	456 / 818
serious Total, serious adverse events	90 / 820	80 / 822	82 / 818

Outcome results

Primary

Number of Participants With New Vertebral Fractures at 18 Months

Time frame: 18 months

Population: Modified intent-to-treat (MITT) population included all patients with pre-treatment and end-of-treatment evaluable radiologic assessment (spine X-ray).

Arm	Measure	Value (NUMBER)
Placebo	Number of Participants With New Vertebral Fractures at 18 Months	30 participants
BA058 80 mcg (Abaloparatide)	Number of Participants With New Vertebral Fractures at 18 Months	4 participants
Teriparatide	Number of Participants With New Vertebral Fractures at 18 Months	6 participants

p-value: <0.0001Fisher Exact

Secondary

Number of Participants With Non-vertebral Fractures at 18 Months

Time frame: 18 months

Population: Intent-to-treat population included all patients who were randomized into the study by assigning the randomized study medication kit on Day 1.

Arm	Measure	Value (NUMBER)
Placebo	Number of Participants With Non-vertebral Fractures at 18 Months	33 Participants
BA058 80 mcg (Abaloparatide)	Number of Participants With Non-vertebral Fractures at 18 Months	18 Participants
Teriparatide	Number of Participants With Non-vertebral Fractures at 18 Months	24 Participants

p-value: 0.0318Chi-squared

p-value: 0.2304Chi-squared

p-value: 0.3361Chi-squared

Secondary

Number of Treatment-Emergent Adverse Events Associated With Hypercalcemia at 18 Months

Time frame: 18 months

Population: Safety population included all patients who received 1 or more doses of study medication

Arm	Measure	Value (NUMBER)
Placebo	Number of Treatment-Emergent Adverse Events Associated With Hypercalcemia at 18 Months	5 Hypercalcemic events
BA058 80 mcg (Abaloparatide)	Number of Treatment-Emergent Adverse Events Associated With Hypercalcemia at 18 Months	15 Hypercalcemic events
Teriparatide	Number of Treatment-Emergent Adverse Events Associated With Hypercalcemia at 18 Months	34 Hypercalcemic events

Secondary

Percent Change in Bone Mineral Density (BMD) of Femoral Neck From Baseline to Month 18

Time frame: Baseline and 18 months

Population: Intent-to-treat population included all patients who were randomized into the study by assigning the randomized study medication kit on Day 1. Baseline BMD data were missing for some patients; the method of last observation carried forward (LOCF) was used to impute missing data.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Percent Change in Bone Mineral Density (BMD) of Femoral Neck From Baseline to Month 18	-0.44 percent change	Standard Deviation 3.57
BA058 80 mcg (Abaloparatide)	Percent Change in Bone Mineral Density (BMD) of Femoral Neck From Baseline to Month 18	2.90 percent change	Standard Deviation 4.21
Teriparatide	Percent Change in Bone Mineral Density (BMD) of Femoral Neck From Baseline to Month 18	2.26 percent change	Standard Deviation 3.57

p-value: <0.0001ANCOVA

p-value: 0.0004ANCOVA

Secondary

Percent Change in Bone Mineral Density (BMD) of Lumbar Spine From Baseline to 18 Months

Time frame: Basline and 18 months

Population: Intent-to-treat population included all patients who were randomized into the study by assigning the randomized study medication kit on Day 1. Baseline BMD data were missing for some patients; the method of last observation carried forward (LOCF) was used to impute missing data.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Percent Change in Bone Mineral Density (BMD) of Lumbar Spine From Baseline to 18 Months	0.48 percent change from baseline	Standard Deviation 3.82
BA058 80 mcg (Abaloparatide)	Percent Change in Bone Mineral Density (BMD) of Lumbar Spine From Baseline to 18 Months	9.20 percent change from baseline	Standard Deviation 7.54
Teriparatide	Percent Change in Bone Mineral Density (BMD) of Lumbar Spine From Baseline to 18 Months	9.12 percent change from baseline	Standard Deviation 6.28

p-value: <0.0001ANCOVA

p-value: 0.8155ANCOVA

Secondary

Percent Change in Bone Mineral Density (BMD) of Total Hip From Baseline to Month 18

Time frame: Baseline and 18 months

Population: Intent-to-treat population included all patients who were randomized into the study by assigning the randomized study medication kit on Day 1. Baseline BMD data were missing for some patients; the method of last observation carried forward (LOCF) was used to impute missing data.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Percent Change in Bone Mineral Density (BMD) of Total Hip From Baseline to Month 18	-0.08 percent change	Standard Deviation 2.77
BA058 80 mcg (Abaloparatide)	Percent Change in Bone Mineral Density (BMD) of Total Hip From Baseline to Month 18	3.44 percent change	Standard Deviation 3.51
Teriparatide	Percent Change in Bone Mineral Density (BMD) of Total Hip From Baseline to Month 18	2.81 percent change	Standard Deviation 3.33

p-value: <0.0001ANCOVA

Study to Evaluate the Safety and Efficacy of BA058 (Abaloparatide) for Prevention of Fracture in Postmenopausal Women

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Baseline characteristics

Adverse events

Outcome results

Number of Participants With New Vertebral Fractures at 18 Months

Number of Participants With Non-vertebral Fractures at 18 Months

Number of Treatment-Emergent Adverse Events Associated With Hypercalcemia at 18 Months

Percent Change in Bone Mineral Density (BMD) of Femoral Neck From Baseline to Month 18

Percent Change in Bone Mineral Density (BMD) of Lumbar Spine From Baseline to 18 Months

Percent Change in Bone Mineral Density (BMD) of Total Hip From Baseline to Month 18