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

• ClinicalTrials.gov Identifier: NCT01343004
• Recruitment Status: Completed
• First Posted: April 27, 2011
• Results First Posted: March 1, 2017
• Last Update Posted: March 1, 2017
• Sponsor: Radius Health, Inc.
• Information provided by (Responsible Party): Radius Health, Inc.

Tracking Information

• First Submitted Date: April 26, 2011
• First Posted Date: April 27, 2011
• Results First Submitted Date: October 25, 2016
• Results First Posted Date: March 1, 2017
• Last Update Posted Date: March 1, 2017
• Study Start Date: April 2011
• Actual Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 10, 2017): Number of Participants With New Vertebral Fractures at 18 Months [ Time Frame: 18 months ]

Original Primary Outcome Measures (submitted: April 26, 2011)

New vertebral fractures [ Time Frame: 18 months ]

Number of BA058-treated patients showing new vertebral fractures by X-ray at End-of-Treatment when compared to Placebo in postmenopausal women

Current Secondary Outcome Measures (submitted: January 10, 2017)

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

Original Secondary Outcome Measures (submitted: April 26, 2011)

• Bone mineral density of lumbar spine, hip, and femoral neck [ Time Frame: 18 months ]
  Efficacy of BA058 on lumbar spine, hip, and femoral neck bone mineral density at End-of-Treatment when compared to teriparatide in postmenopausal women
• Non-vertebral fractures [ Time Frame: 18 months ]
  Efficacy of BA058 on incidence of non-vertebral fractures at End-of-Treatment when compared to Placebo in postmenopausal women
• Number of hypercalcemic events [ Time Frame: 18 months ]
  Number of hypercalcemic events in BA058 treated patients at End-of-Treatment when compared to teriparatide in postmenopausal women

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Osteoporosis
• Postmenopausal Osteoporosis

Intervention

• Drug: Placebo
  Placebo 0 mcg subcutaneous daily
• Drug: BA058 80 mcg
  BA058 80 mcg subcutaneous daily
  Other Name: abaloparatide, Abaloparatide-SC
• Drug: teriparatide
  teriparatide 20 mcg subcutaneous daily
  Other Names:

  • Forteo
  • Forsteo

Study Arms

• Placebo Comparator: Placebo
  Placebo identical in appearance to BA058 study drug
  Intervention: Drug: Placebo
• Experimental: BA058 80 mcg (abaloparatide)
  Intervention: Drug: BA058 80 mcg
• Active Comparator: teriparatide
  Blinded until after randomization, then open-label
  Intervention: Drug: teriparatide

Publications *

• 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:CD013424. doi: 10.1002/14651858.CD013424.pub2.
• 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). pii: dgaa450. doi: 10.1210/clinem/dgaa450.
• 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. Erratum in: Clin Ther. 2020 Oct;42(10):2117.
• 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). pii: dgz162. doi: 10.1210/clinem/dgz162. Erratum in: J Clin Endocrinol Metab. 2020 Aug 1;105(8):.
• 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.
• 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.
• 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.
• 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. Erratum in: JAMA. 2017 Jan 24;317(4):442.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 14, 2015): 2463
• Original Estimated Enrollment (submitted: April 26, 2011): 2400
• Actual Study Completion Date: October 2014
• Actual Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 50 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Brazil, Czech Republic, Denmark, Estonia, Hong Kong, Lithuania, Poland, Romania, United States

Administrative Information

• NCT Number: NCT01343004
• Other Study ID Numbers: BA058-05-003; ACTIVE Trial ( Other Identifier: Radius Health, Inc. )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Radius Health, Inc.
• Original Responsible Party: Program Director, Radius Health, Inc.
• Current Study Sponsor: Radius Health, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Radius Health, Inc.; Radius Health, Inc.

• PRS Account: Radius Health, Inc.
• Verification Date: January 2017