Abaloparatide + Denosumab for Osteoporosis

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments for osteoporosis, a condition that weakens bones, in postmenopausal women. It compares the effects of continuing with only denosumab injections versus adding abaloparatide, a daily medication, to denosumab over 18 months. Researchers aim to determine which approach more effectively improves bone density, particularly in the hip and spine. Women who have been using denosumab for some time and have been diagnosed with osteoporosis might be suitable candidates for this study. As a Phase 4 trial, it involves treatments already FDA-approved and proven effective, seeking to understand how they can benefit more patients.

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 is the safety track record for these treatments?

Research shows that both abaloparatide and denosumab are generally well-tolerated treatments. Earlier studies found abaloparatide to be safer than a placebo concerning heart-related issues. Denosumab, compared to other osteoporosis treatments, may not reduce fractures as effectively but remains safe for use.

When used together, abaloparatide and denosumab have demonstrated significant improvements in bone strength at critical areas like the lower spine and the top of the thigh bone, without major safety concerns. Various studies have tested this combination, supporting its safe use.

Overall, both treatments have a strong safety record, making them promising options for managing osteoporosis. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the combination of abaloparatide and denosumab for treating osteoporosis because it offers a unique dual approach. Unlike standard treatments that often target just one pathway, this combination uses abaloparatide to stimulate new bone formation, while denosumab helps prevent bone breakdown. This dual action has the potential to increase bone density more effectively than treatments like bisphosphonates or denosumab alone. Additionally, combining these two treatments could provide faster and more robust improvements, which is particularly promising for those at high risk of fractures.

What evidence suggests that this trial's treatments could be effective for osteoporosis?

Research has shown that abaloparatide and denosumab effectively treat osteoporosis by increasing bone strength. Abaloparatide, in particular, improves bone density in the spine and neck more effectively than some other treatments. Studies indicate that abaloparatide reduces fracture risk more effectively than similar drugs. Denosumab has been proven to lower fracture risk, especially in the hip and spine, compared to other treatments. In this trial, some participants will receive denosumab alone, while others will receive a combination of denosumab and abaloparatide. Together, these medications are expected to strengthen bones and reduce fracture risks in postmenopausal women with osteoporosis. ^{1 4 5 6 7}

Who Is on the Research Team?

Jeri W Nieves, PhD

Principal Investigator

Hospital for Special Surgery, New York

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 (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]

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]

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]

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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12040664/

Efficacy and safety of abaloparatide, denosumab ... The results indicate that abaloparatide and teriparatide are significantly superior to other drugs in improving lumbar spine and femoral neck BMD.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10118815/

Anabolic therapy for osteoporosis: update on efficacy and ... Anabolic agents for the treatment of osteoporosis increase bone density, improve bone strength, and reduce fracture risk.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1530891X24008279

Comparative Effectiveness of Abaloparatide and ... There were significantly lower rates of hip and nonvertebral fractures with abaloparatide compared to teriparatide, which were consistent across subgroups.

4. academic.oup.com academic.oup.com/jbmr/article/39/7/826/7675442

Comparative effectiveness of denosumab vs alendronate ... Overall, denosumab reduced the risk of MOP by 39%, hip by 36%, NV by 43%, NHNV by 50%, and HV fractures by 30% compared with alendronate.

5. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00004-X/fulltext

a network meta-analysis of randomised controlled trials The main outcomes included vertebral fracture risk, the percentage change in bone mineral density (BMD) in different body parts, and all safety ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S8756328222002873

Evidence for the cardiovascular effects of osteoporosis ... 75 trials with 27 providing cardiovascular safety event rates for analysis · Abaloparatide, oral bisphosphonates, teriparatide & MHT 'safer' than placebo.

7. bmj.com bmj.com/content/381/bmj-2021-068033

Fracture risk reduction and safety by osteoporosis ... Compared with parathyroid hormone receptor agonists and romosozumab, denosumab was less effective in reducing clinical fractures (odds ratios ...