Abaloparatide + Denosumab for Osteoporosis

Recruiting in Palo Alto (17 mi)

+1 other location

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

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

Prior Safety Data

Trial Summary

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.

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}

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.

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Osteoporosis Center of Delaware County Broomall, PA

Hospital for Special Surgery New York, NY

Who Is Running the Clinical Trial?

Hospital for Special Surgery, New York Lead Sponsor

Felicia Cosman, MD Lead Sponsor

Crozer-Keystone Health System Collaborator

Radius Health, Inc. Industry Sponsor

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] Daily subcutaneous injection of 80 μg abaloparatide increased bone mineral density in Japanese patients with osteoporosis at high fracture risk in the ACTIVE-J trial. Dual-energy X-ray absorptiometry-based hip structural analysis from ACTIVE-J data showed improved hip geometry and biomechanical properties with abaloparatide compared with placebo.

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

Abaloparatide: First Global Approval. [2018] Abaloparatide (Tymlos™) is a synthetic peptide analogue of human parathyroid hormone-related protein that was developed by Radius Health as an osteoanabolic agent for the treatment of postmenopausal osteoporosis. Abaloparatide acts through selective activation of the parathyroid hormone type 1 receptor signalling pathway. In April 2017, subcutaneous abaloparatide received its first global approval, in the USA, for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. A Marketing Authorization Application for subcutaneous abaloparatide for the treatment of postmenopausal women with osteoporosis was accepted by the European Medicines Agency and is currently under review. Radius is also developing a transdermal formulation of abaloparatide, with administration via a microneedle patch. This article summarizes the milestones in the development of abaloparatide leading to this first approval for the treatment of women with postmenopausal osteoporosis.

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] Abaloparatide is a US Food and Drug Administration-approved parathyroid hormone-related peptide analog for treatment of osteoporosis in postmenopausal women at high risk of fracture.

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] Abaloparatide reduced fracture risk in postmenopausal women with osteoporosis in the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE). Its effect in Japanese patients remains unexamined.

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] The US Food and Drug Administration has recently approved abaloparatide (ABL) for treatment of women with postmenopausal osteoporosis (PMO) at high risk of fracture. With increasing health care spending and drug prices, it is important to quantify the value of newly available treatment options for PMO.

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

A real-world pharmacovigilance study of abaloparatide based on the FDA Adverse Event Reporting System (FAERS). [2023] Abaloparatide (ABL) is a US Food and Drug Administration-approved parathyroid hormone-related peptide analog for treatment of osteoporosis in postmenopausal women at high risk of fracture. However, real-world data regarding its long-term safety and tolerability in large sample population are incomplete. We evaluated abaloparatide-associated safety signals by data mining of the FDA pharmacovigilance database.

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

Abaloparatide: A new pharmacological option for osteoporosis. [2022] The efficacy and safety of abaloparatide, a parathyroid hormone-related protein analog for the treatment of osteoporosis in postmenopausal women at high fracture risk, is reviewed.

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] Abaloparatide, an anabolic osteoporosis treatment administered by subcutaneous (SC) injection, increases bone mineral density (BMD) and reduces fracture risk in postmenopausal women with osteoporosis. The abaloparatide-solid Microstructured Transdermal System [abaloparatide-sMTS (Kindeva, St Paul, MN, USA)], which delivers abaloparatide intradermally, is in development to provide an alternative method for abaloparatide delivery. The objective of this study was to evaluate the ability of subjects to self-administer abaloparatide-sMTS, based on pharmacokinetic and pharmacodynamic markers.

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] Abaloparatide is a 34-amino acid peptide that selectively binds to the RG conformation of the parathyroid hormone receptor type 1. It was developed for the treatment of women with postmenopausal osteoporosis at high risk of fracture. In ACTIVE, an 18-month phase 3 study (NCT01343004), abaloparatide increased bone mineral density (BMD), decreased the risk of vertebral and nonvertebral fractures compared with placebo, and decreased the risk of major osteoporotic fractures compared with placebo and teriparatide. Here, we report a prospective, exploratory BMD responder analysis from ACTIVE.