Clinical trial NCT01343004: Study to Evaluate the Safety and Efficacy of BA058 (Abaloparatide) for Prevention of Fracture in Postmenopausal Women
Official title: A Randomized, Double-blind, Placebo-Controlled, Comparative Multicenter Phase 3 Study to Evaluate the Safety and Efficacy of BA058 (Abaloparatide) for Injection for Prevention of Fracture in Ambulatory Postmenopausal Women With Severe Osteoporosis and at Risk of Fracture
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoporosis
Postmenopausal Osteoporosis
Keywords: BA058
abaloparatide
Abaloparatide-SC
osteoporosis
postmenopausal
bone loss
ACTIVE
fracture
Lead sponsor: Radius Health, Inc.
Sponsor class: INDUSTRY
First posted: 2011-04-27
Enrollment: 2463
Sex: FEMALE
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With New Vertebral Fractures at 18 Months
timeFrame: 18 months
Secondary outcomes:
measure: Percent Change in Bone Mineral Density (BMD) of Lumbar Spine From Baseline to 18 Months
timeFrame: Basline and 18 months
measure: Percent Change in Bone Mineral Density (BMD) of Total Hip From Baseline to Month 18
timeFrame: Baseline and 18 months
measure: Percent Change in Bone Mineral Density (BMD) of Femoral Neck From Baseline to Month 18
timeFrame: Baseline and 18 months
measure: Number of Participants With Non-vertebral Fractures at 18 Months
timeFrame: 18 months
measure: Number of Treatment-Emergent Adverse Events Associated With Hypercalcemia at 18 Months
timeFrame: 18 months
Other outcomes:
Locations:
city: Lakewood
country: United States
state: Colorado
city: Miami
country: United States
state: Florida
city: N. Miami
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Bethesda
country: United States
state: Maryland
city: Buenos Aires
country: Argentina
city: Brasilia
country: Brazil
city: Curitiba
country: Brazil
city: Rio de Janeiro
country: Brazil
city: Sao Paolo
country: Brazil
city: Vitoria
country: Brazil
city: Brno
country: Czech Republic
city: Pardubice
country: Czech Republic
city: Prague
country: Czech Republic
city: Aalborg
country: Denmark
city: Ballerup
country: Denmark
city: Vejle
country: Denmark
city: Tallinn
country: Estonia
city: Tartu
country: Estonia
city: Hong Kong
country: Hong Kong
city: Vilnius
country: Lithuania
city: Bialystok
country: Poland
city: Katowice
country: Poland
city: Kielce
country: Poland
city: Lodz
country: Poland
city: Warszaw
country: Poland
city: Zgierz
country: Poland
city: Bucharest
country: Romania
Study officials:
affiliation: Radius Health, Inc.
name: Radius Health, Inc.
role: STUDY_DIRECTOR
References:
citation: Hara T, Hijikata Y, Matsubara Y, Watanabe N. Pharmacological interventions versus placebo, no treatment or usual care for osteoporosis in people with chronic kidney disease stages 3-5D. Cochrane Database Syst Rev. 2021 Jul 7;7(7):CD013424. doi: 10.1002/14651858.CD013424.pub2.
citation: Cosman F, Peterson LR, Towler DA, Mitlak B, Wang Y, Cummings SR. Cardiovascular Safety of Abaloparatide in Postmenopausal Women With Osteoporosis: Analysis From the ACTIVE Phase 3 Trial. J Clin Endocrinol Metab. 2020 Nov 1;105(11):3384-95. doi: 10.1210/clinem/dgaa450.
citation: Saag KG, Williams SA, Wang Y, Weiss RJ, Cauley JA. Effect of Abaloparatide on Bone Mineral Density and Fracture Incidence in a Subset of Younger Postmenopausal Women with Osteoporosis at High Risk for Fracture. Clin Ther. 2020 Jun;42(6):1099-1107.e1. doi: 10.1016/j.clinthera.2020.04.012. Epub 2020 Jun 6.
citation: Leder BZ, Mitlak B, Hu MY, Hattersley G, Bockman RS. Effect of Abaloparatide vs Alendronate on Fracture Risk Reduction in Postmenopausal Women With Osteoporosis. J Clin Endocrinol Metab. 2020 Mar 1;105(3):938-43. doi: 10.1210/clinem/dgz162.
citation: Leder BZ, Zapalowski C, Hu MY, Hattersley G, Lane NE, Singer AJ, Dore RK. Fracture and Bone Mineral Density Response by Baseline Risk in Patients Treated With Abaloparatide Followed by Alendronate: Results From the Phase 3 ACTIVExtend Trial. J Bone Miner Res. 2019 Dec;34(12):2213-2219. doi: 10.1002/jbmr.3848. Epub 2019 Sep 11.
citation: Moreira CA, Fitzpatrick LA, Wang Y, Recker RR. Effects of abaloparatide-SC (BA058) on bone histology and histomorphometry: The ACTIVE phase 3 trial. Bone. 2017 Apr;97:314-319. doi: 10.1016/j.bone.2016.11.004. Epub 2016 Nov 5.
citation: Cosman F, Hattersley G, Hu MY, Williams GC, Fitzpatrick LA, Black DM. Effects of Abaloparatide-SC on Fractures and Bone Mineral Density in Subgroups of Postmenopausal Women With Osteoporosis and Varying Baseline Risk Factors. J Bone Miner Res. 2017 Jan;32(1):17-23. doi: 10.1002/jbmr.2991. Epub 2016 Sep 28.
citation: Miller PD, Hattersley G, Riis BJ, Williams GC, Lau E, Russo LA, Alexandersen P, Zerbini CA, Hu MY, Harris AG, Fitzpatrick LA, Cosman F, Christiansen C; ACTIVE Study Investigators. Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial. JAMA. 2016 Aug 16;316(7):722-33. doi: 10.1001/jama.2016.11136.