Abaloparatide + Denosumab for Osteoporosis

Recruiting at 2 trial locations

Overseen By William Friedman

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Hospital for Special Surgery, New York

Must be taking: Denosumab

Must not be taking: Calcium homeostasis drugs

Disqualifiers: Renal stones, Cancer, Hypercalcemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 18 months

70 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you have not used any drugs other than denosumab that affect bone or calcium levels in the last 3 months. If you are taking such medications, you may need to stop them before joining the trial.

What data supports the effectiveness of the drug Abaloparatide for osteoporosis?

Research shows that Abaloparatide increases bone mineral density and improves hip structure in patients with osteoporosis, reducing the risk of fractures. ^{1 2 3 4 5}

Is the combination of Abaloparatide and Denosumab safe for treating osteoporosis?

Abaloparatide has been approved for treating osteoporosis in postmenopausal women and has been studied for safety, but long-term safety data in large populations is still incomplete. There is no specific safety data available for the combination of Abaloparatide and Denosumab. ^{1 2 5 6 7}

How is the drug combination of Abaloparatide and Denosumab unique for treating osteoporosis?

The combination of Abaloparatide and Denosumab is unique because it combines two different mechanisms: Abaloparatide, which builds bone by activating a specific receptor related to parathyroid hormone, and Denosumab, which prevents bone breakdown by inhibiting a protein involved in bone resorption. This dual approach may offer enhanced benefits for increasing bone density and reducing fracture risk compared to using either drug alone. ^{1 2 3 8 9}

What is the purpose of this trial?

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.

Research Team

Jeri W Nieves, PhD

Principal Investigator

Hospital for Special Surgery, New York

Eligibility Criteria

This trial is for postmenopausal women over 45 who have osteoporosis, defined by a bone density T-Score < -2.5 or fractures in the last 5 years with a T-Score < -1.5. They must have had at least 4 prior denosumab injections and be within 7 months of their last shot, willing to participate throughout the study without any condition that would prevent them.

Inclusion Criteria

Participants are willing to participate for the duration of the study and have no physical or psychological illness that would prohibit them from participating

I am a woman over 45 and have gone through menopause.

I have had at least 4 denosumab injections and my last one was within the past 7 months.

Exclusion Criteria

I do not have bone disorders like hypercalcemia, hyperparathyroidism, or Paget's Disease.

I have undergone radiation therapy before.

I have had a painful kidney stone in the last 2 years or multiple ones in the last 10 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either continued denosumab alone or denosumab with added abaloparatide for 18 months

18 months

3 injections of Denosumab, separated by no more than 7 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Abaloparatide
• Denosumab Injection

Trial Overview The trial compares two treatments: continued denosumab alone versus adding abaloparatide to denosumab for 18 months among 70 participants. It will measure changes in bone mineral density at various sites and times, as well as bone turnover markers like PINP and CTX levels.

Participant Groups

Group I: Denosumab alone Active Control 1 Intervention

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

Group II: Combination therapy Active Control 2 Interventions

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.

Abaloparatide is already approved in United States, European Union, Japan for the following indications:

Approved in United States as Tymlos for:

• Osteoporosis in postmenopausal women at high risk of fracture
• Osteoporosis in men at high risk of fracture

Approved in European Union as Eladynos for:

• Osteoporosis in postmenopausal women at increased risk of fracture

Approved in Japan as Tymlos for:

• Osteoporosis in patients at high risk of fracture

Who Is Running the Clinical Trial?

Hospital for Special Surgery, New York

Lead Sponsor

Trials

257

Recruited

61,800+

Felicia Cosman, MD

Lead Sponsor

Trials

1

Recruited

70+

Crozer-Keystone Health System

Collaborator

Trials

5

Recruited

290+

Radius Health, Inc.

Industry Sponsor

Trials

15

Recruited

27,200+

Findings from Research

In the ACTIVE-J trial, daily subcutaneous injections of 80 μg abaloparatide significantly increased bone mineral density and improved hip geometry in Japanese patients with osteoporosis at high fracture risk, with 128 participants receiving abaloparatide and 65 receiving placebo over 78 weeks.

Abaloparatide treatment led to notable improvements in various hip structural analysis parameters, including increased cortical thickness and cross-sectional area, and a decrease in the buckling ratio, indicating enhanced biomechanical properties compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of abaloparatide on hip geometry and biomechanical properties in Japanese osteoporotic patients assessed using DXA-based hip structural analysis: results of the Japanese phase 3 ACTIVE-J trial. Sone, T., Ohnaru, K., Sugai, T., et al.[2023]

Abaloparatide (Tymlos™) is a synthetic peptide that effectively treats postmenopausal osteoporosis by activating the parathyroid hormone type 1 receptor, promoting bone formation and reducing fracture risk.

Approved in the USA in April 2017 for women at high risk of fractures, abaloparatide is also undergoing review in Europe and has a transdermal formulation in development for easier administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abaloparatide: First Global Approval. Shirley, M.[2018]

Abaloparatide, used for treating osteoporosis in postmenopausal women, caused a temporary increase in heart rate and slight decreases in blood pressure, but did not increase the risk of serious cardiovascular events.

In fact, abaloparatide was associated with a longer time to the first incidence of major adverse cardiovascular events and heart failure compared to placebo, suggesting a favorable cardiovascular safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular Safety of Abaloparatide in Postmenopausal Women With Osteoporosis: Analysis From the ACTIVE Phase 3 Trial. Cosman, F., Peterson, LR., Towler, DA., et al.[2021]

In a randomized, double-blind, placebo-controlled study of 78 weeks involving postmenopausal women and men with osteoporosis, abaloparatide significantly increased bone mineral density (BMD) in the lumbar spine by 12.5%, and by 4.3% in both the total hip and femoral neck compared to placebo.

The treatment was safe, with no new vertebral fractures occurring in the abaloparatide group, while three participants in the placebo group experienced new fractures, indicating a strong safety profile similar to previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abaloparatide Increases Lumbar Spine and Hip BMD in Japanese Patients With Osteoporosis: The Phase 3 ACTIVE-J Study. Matsumoto, T., Sone, T., Soen, S., et al.[2022]

Abaloparatide (ABL) is a cost-effective treatment for postmenopausal osteoporosis (PMO) in women at high risk of fracture, showing better quality-adjusted life-years (QALYs) and lower costs compared to teriparatide (TPTD) over a 10-year period.

In a simulation model based on the ACTIVE trial, ABL/ALN treatment resulted in 6.792 QALYs at an average cost of $26,837, making it a dominant strategy over TPTD/ALN, which had 6.781 QALYs at a cost of $46,783.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness Analysis of Sequential Treatment of Abaloparatide Followed by Alendronate Versus Teriparatide Followed by Alendronate in Postmenopausal Women With Osteoporosis in the United States. Le, QA., Hay, JW., Becker, R., et al.[2023]

A comprehensive analysis of 33,480 adverse events related to abaloparatide (ABL) from the FDA database revealed 99 safety signals, including 35 unexpected adverse events, indicating the need for ongoing monitoring of its safety profile.

The study highlighted that patient age may influence the severity of adverse events, with most reported issues occurring within the first week of treatment, providing valuable insights for healthcare professionals in managing potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real-world pharmacovigilance study of abaloparatide based on the FDA Adverse Event Reporting System (FAERS). Shi, X., Cheng, Q., Zhao, YZ., et al.[2023]

Abaloparatide is effective in reducing the risk of new vertebral and nonvertebral fractures in postmenopausal women with osteoporosis, while also significantly increasing bone mineral density (BMD) at key sites like the hip and spine.

It has a mild adverse effect profile, with fewer instances of hypercalcemia compared to teriparatide, making it a well-tolerated option for improving bone health in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abaloparatide: A new pharmacological option for osteoporosis. Sleeman, A., Clements, JN.[2022]

In a study involving 22 healthy postmenopausal women, abaloparatide delivered via a microstructured transdermal system (abaloparatide-sMTS) was successfully self-administered, showing a consistent pharmacokinetic profile over 29 days.

The treatment led to significant increases in serum procollagen type I N-terminal propeptide (s-PINP), indicating effective bone formation, with high patient acceptability and minimal adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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., et al.[2021]

In an 18-month phase 3 study, abaloparatide significantly increased bone mineral density (BMD) in postmenopausal women with osteoporosis, showing greater improvements compared to both placebo and teriparatide.

At 18 months, 44.5% of patients treated with abaloparatide experienced over a 3% increase in BMD, compared to only 1.9% for placebo and 32.0% for teriparatide, indicating its superior efficacy in enhancing bone health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

The effects of abaloparatide on hip geometry and biomechanical properties in Japanese osteoporotic patients assessed using DXA-based hip structural analysis: results of the Japanese phase 3 ACTIVE-J trial. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Abaloparatide: First Global Approval. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Cardiovascular Safety of Abaloparatide in Postmenopausal Women With Osteoporosis: Analysis From the ACTIVE Phase 3 Trial. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Abaloparatide Increases Lumbar Spine and Hip BMD in Japanese Patients With Osteoporosis: The Phase 3 ACTIVE-J Study. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Cost-effectiveness Analysis of Sequential Treatment of Abaloparatide Followed by Alendronate Versus Teriparatide Followed by Alendronate in Postmenopausal Women With Osteoporosis in the United States. [2023]

6. England pubmed.ncbi.nlm.nih.gov

A real-world pharmacovigilance study of abaloparatide based on the FDA Adverse Event Reporting System (FAERS). [2023]

7. England pubmed.ncbi.nlm.nih.gov

Abaloparatide: A new pharmacological option for osteoporosis. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Phase 1b Evaluation of Abaloparatide Solid Microstructured Transdermal System (Abaloparatide-sMTS) in Postmenopausal Women with Low Bone Mineral Density. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

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. [2020]