Abaloparatide Added to Ongoing Denosumab vs Continued Denosumab Alone

NCT04467983 | Active Not Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 2022-1296
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized open label clinical trial will evaluate the effect of continued denosumab alone over 18 months versus denosumab with added abaloparatide for 18 months. 70 postmenopausal women will be enrolled over a period of 18 months. The co-primary outcomes will be group differences in bone mineral density (BMD) of the total hip and lumbar spine at 18 months. Secondary outcomes will include group differences in bone mineral density (BMD) at the femoral neck, trochanter and wrist sites at 6, 12 and 18 months, spine and total hip bone mineral density (BMD) at 6 and 12 months and trabecular bone score (TBS) at 18 months. Secondary outcomes will also include within group changes from baseline for each of these variables. Bone turnover markers will also be measured to demonstrate that PINP levels will increase with administration of abaloparatide even in the setting of ongoing denosumab, while CTX levels will remain low.

Conditions

Osteoporosis, Postmenopausal

Keywords

denosumab; abaloparatide

Outcome Measures

Primary Outcomes (1)

• Bone mineral density changes at total hip and lumbar spine

  Group differences in BMD increment at total hip and lumbar spine at 18 months.

  18 months

Secondary Outcomes (4)

• Bone mineral density changes in increments

  6, 12, 18 months

• Trabecular Bone Score changes

  18 months

• Within Group Increments in bone mineral density (vs baseline)

  6, 12, 18 months

• Differences in biochemical bone turnover markers

  3, 6, 12, 18 months

Study Arms (2)

Denosumab alone

ACTIVE COMPARATOR

3 injections of Denosumab at appropriate times, separated by no more than 7 months from the last treatment.

Drug: Denosumab Injection

Combination therapy

ACTIVE COMPARATOR

3 injections of Denosumab at appropriate times, separated by no more than 7 months from the last treatment, with added abaloparatide 80 mcg subcutaneously daily, started within 6 months of the last denosumab treatment, for a total of 18 months.

Drug: Denosumab Injection; Drug: Abaloparatide

Interventions

Denosumab Injection DRUG

Denosumab alone: 3 injections of Denosumab at appropriate times, separated by no more than 7 months from the last treatment.

Also known as: Prolia

Combination therapy; Denosumab alone

Abaloparatide DRUG

Combination therapy: 3 injections of Denosumab at appropriate times, separated by no more than 7 months from the last treatment, with added abaloparatide 80 mcg subcutaneously daily, started within 6 months of the last denosumab treatment, for a total of 18 months.

Also known as: Tymlos

Combination therapy

Eligibility Criteria

• Age: 45 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• postmenopausal woman \>age 45 of any racial origin
• Participants will have received at least 4 prior denosumab treatments and be within 7 months from their last denosumab injection
• Participants are willing to participate for the duration of the study and have no physical or psychological illness that would prohibit them from participating.
• Diagnosis of osteoporosis based on bone mineral density and/or fracture criteria. Osteoporosis will be defined by bone mineral density T-Score \< -2.5 at lumbar spine (at least 2 evaluable vertebrae between L1 and L4), total hip or femoral neck. Osteoporosis will also be defined clinically in women with osteoporotic fractures within the preceding 5 years, including clinical vertebral or nonvertebral fractures or vertebral fracture confirmed by radiograph or lateral DXA VFA image, along with a DXA BMD T-Score \< -1.5 at one or more skeletal sites.

You may not qualify if:

• Use of drugs other than denosumab (within the preceding 3 months) known to affect skeletal or calcium homeostasis.
• Fewer than 2 evaluable lumbar vertebrae
• A history of a symptomatic renal stone within the past 2 years or history of multiple symptomatic renal stones within the preceding 10 years
• Skeletal Disorders other than osteoporosis, including hypercalcemia, hyperparathyroidism, or Paget's Disease
• History of external or internal radiation therapy
• Estimated GFR below 30 ml/min
• Any contraindications to receipt of Abaloparatide or Denosumab
• History of any cancer in past 5 years (except basal/squamous skin cancer)
• Unexplained elevation of Serum Alkaline Phosphatase
• History of atypical femoral fracture

Sponsors & Collaborators

• Hospital for Special Surgery, New York: lead
• Radius Health, Inc.: collaborator
• Crozer-Keystone Health System: collaborator

Study Sites (1)

Hospital for Special Surgery

New York, New York, 10021, United States

Location

Related Publications (5)

• Leder BZ, Tsai JN, Uihlein AV, Wallace PM, Lee H, Neer RM, Burnett-Bowie SA. Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial. Lancet. 2015 Sep 19;386(9999):1147-55. doi: 10.1016/S0140-6736(15)61120-5. Epub 2015 Jul 2.

  PMID: 26144908 BACKGROUND

• Cosman F, Wermers RA, Recknor C, Mauck KF, Xie L, Glass EV, Krege JH. Effects of teriparatide in postmenopausal women with osteoporosis on prior alendronate or raloxifene: differences between stopping and continuing the antiresorptive agent. J Clin Endocrinol Metab. 2009 Oct;94(10):3772-80. doi: 10.1210/jc.2008-2719. Epub 2009 Jul 7.

  PMID: 19584192 BACKGROUND

• Cosman F, Keaveny TM, Kopperdahl D, Wermers RA, Wan X, Krohn KD, Krege JH. Hip and spine strength effects of adding versus switching to teriparatide in postmenopausal women with osteoporosis treated with prior alendronate or raloxifene. J Bone Miner Res. 2013 Jun;28(6):1328-36. doi: 10.1002/jbmr.1853.

  PMID: 23281041 BACKGROUND

• Leder BZ, O'Dea LS, Zanchetta JR, Kumar P, Banks K, McKay K, Lyttle CR, Hattersley G. Effects of abaloparatide, a human parathyroid hormone-related peptide analog, on bone mineral density in postmenopausal women with osteoporosis. J Clin Endocrinol Metab. 2015 Feb;100(2):697-706. doi: 10.1210/jc.2014-3718. Epub 2014 Nov 13.

  PMID: 25393645 BACKGROUND

• Leder BZ, Tsai JN, Uihlein AV, Burnett-Bowie SA, Zhu Y, Foley K, Lee H, Neer RM. Two years of Denosumab and teriparatide administration in postmenopausal women with osteoporosis (The DATA Extension Study): a randomized controlled trial. J Clin Endocrinol Metab. 2014 May;99(5):1694-700. doi: 10.1210/jc.2013-4440. Epub 2014 Feb 11.

  PMID: 24517156 BACKGROUND

MeSH Terms

Conditions

Osteoporosis, Postmenopausal

Interventions

Denosumab; abaloparatide

Condition Hierarchy (Ancestors)

Osteoporosis; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jeri W Nieves, PhD

  Hospital for Special Surgery, New York

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 8, 2020
• First Posted: July 13, 2020
• Study Start: February 1, 2021
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 2, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)