Abaloparatide for Spinal Fusion

(FAST-Healing Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Emily Stein, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Hospital for Special Surgery, New York

Must not be taking: Chronic oral steroids, Forteo, Tymlos, Bisphosphonates

Disqualifiers: Hypersensitivity to abaloparatide, Osteosarcoma risk, Hypercalcemia, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a prospective randomized, double-blinded, placebo-controlled, phase 2, 12-month pilot to study the efficacy of abaloparatide in postmenopausal women needing lumbar spinal fusion surgery. A total of 72 women with low bone mass who are scheduled to undergo spinal fusion surgery will be randomized 2:1 in a blinded fashion to receive either 80 mcg of abaloparatide subcutaneously (SC) every day or an identical-appearing placebo SC for 6 months. As well as a total of 24 men in an open-label design will be enrolled as an extension to this study. The total anticipated enrollment updated to 97. Outcomes include surgical outcomes at one year, pain, and fusion bone mass volume (FBMV) as a marker of bone union at 6 months and 1 year.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on chronic oral steroids or have used certain bone medications like Forteo or Tymlos recently, you may not be eligible to participate.

What data supports the effectiveness of the drug Abaloparatide for spinal fusion?

Research on similar drugs like teriparatide, which is used to treat osteoporosis, suggests it can help improve spinal fusion rates. Studies have shown that teriparatide can enhance bone formation and reduce complications in spinal fusion surgeries, indicating potential benefits for similar drugs like Abaloparatide. ^{1 2 3 4 5}

Is abaloparatide safe for humans?

Abaloparatide has been studied for treating osteoporosis in postmenopausal women and is generally considered safe, with common side effects being mild skin reactions at the injection site. Serious side effects were similar to those of a placebo, indicating it is generally well-tolerated. ^{6 7 8 9 10}

How does the drug Abaloparatide differ from other treatments for spinal fusion?

Abaloparatide is unique because it is a synthetic peptide that selectively activates a specific receptor involved in bone growth, which can increase bone mass and strength without increasing bone breakdown. This makes it potentially beneficial for spinal fusion by promoting bone formation and improving bone quality, unlike other treatments that may not specifically target these pathways. ^{6 7 11 12 13}

Research Team

Emily Stein, MD

Principal Investigator

Hospital for Special Surgery, New York

Eligibility Criteria

This trial is for postmenopausal women over 50 needing lumbar spinal fusion surgery, with low bone mass and specific degenerative conditions. Excluded are those unwilling to take placebo or abaloparatide, unable to consent, with recent kidney stones, prior lumbar surgery revisions, bisphosphonate treatment history, hypersensitivity to abaloparatide, risk of osteosarcoma, smokers, certain medical conditions like hypercalcemia or chronic steroid use.

Inclusion Criteria

I need spine surgery for a lower back condition.

I have not had a menstrual cycle for over 12 months.

I am 50 years old or older.

Exclusion Criteria

I have high calcium levels or an active parathyroid disorder.

My cancer has spread to other parts of my body or I have multiple myeloma.

I have had kidney stones multiple times or within the last 2 years.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 80 mcg of abaloparatide or placebo subcutaneously every day for 6 months

6 months

Follow-up

Participants are monitored for surgical outcomes, pain, and fusion bone mass volume at 6 months and 1 year

6 months to 1 year

Open-label extension (Men)

Men receive open-label treatment with abaloparatide for 6 months

6 months

Treatment Details

Interventions

• Abaloparatide (Osteoporosis Agent)
• Placebo (Other)
• Spinal Fusion Surgery (Procedure)

Trial Overview The study tests if abaloparatide can improve surgical outcomes in these women compared to a placebo. Participants will be randomly assigned in a 2:1 ratio to receive either the drug or placebo daily for six months. The main measures are pain relief and bone mass volume at the fusion site after six months and one year.

Participant Groups

Group I: Abaloparatide (Men) Experimental Treatment 1 Intervention

Open-label treatment with Abaloparatide 80 mcg dose administered subcutaneously with a pen once daily for 6 months

Group II: Abaloparatide (PM Women) Active Control 1 Intervention

Abaloparatide 80 mcg dose administered subcutaneously with a pen once daily for 6 months

Group III: Placebo (PM Women) Placebo Group 1 Intervention

Placebo administered subcutaneously with a pen once daily for 6 months

Abaloparatide is already approved in Japan for the following indications:

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+

Dr. Douglas E. Padgett

Hospital for Special Surgery, New York

Chief Medical Officer since 2023

MD from Cornell University Medical College

Dr. Bryan T. Kelly

Hospital for Special Surgery, New York

Chief Executive Officer since 2023

MD, MBA

Findings from Research

Osteoporotic patients treated with teriparatide showed significantly lower rates of reoperation (11.5% vs. 23.1%) and pseudarthrosis (6.4% vs. 21.8%) compared to osteopenic patients after 2 years of spinal fusion surgery, indicating teriparatide's efficacy in improving surgical outcomes.

When compared to patients with normal bone mineral density, those on teriparatide had similar rates of reoperation and pseudarthrosis, suggesting that teriparatide can help osteoporotic patients achieve outcomes comparable to those with healthier bones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Teriparatide on Complications and Patient-Reported Outcomes of Patients Undergoing Long Spinal Fusion According to Bone Density. Mohanty, S., Sardar, ZM., Hassan, FM., et al.[2023]

In a study involving 32 New Zealand rabbits, a single dose of pamidronate (PA) administered at the time of spinal fusion surgery resulted in a higher spinal fusion rate (50%) compared to the control group (25%), although this difference was not statistically significant (p = 0.137).

The findings suggest that while pamidronate did not negatively impact spinal fusion rates, its effect on enhancing fusion rates remains inconclusive, indicating the need for further research to clarify its role in spinal fusion procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of a single dose of pamidronate administered at the time of surgery in a rabbit posterolateral spinal fusion model. Urrutia, J., Briceno, J., Carmona, M., et al.[2021]

In a study involving 676 patients from eight randomized clinical trials and three prospective studies, teriparatide combined with Denosumab significantly increased the fusion rate in spinal surgery compared to placebo and bisphosphonate treatments.

This network meta-analysis suggests that teriparatide is a promising option for enhancing spinal fusion outcomes, highlighting its potential effectiveness in peri-operative care for patients undergoing thoracic and lumbar spine surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of teriparatide and bisphosphonate on spinal fusion procedure: A systematic review and network meta-analysis. Cheng, SH., Kuo, YJ., Chen, C., et al.[2020]

In a study involving 67 patients with osteoporosis undergoing spinal fusion, teriparatide (TPTD) therapy significantly improved bone mineral density (BMD) and bone formation markers compared to zoledronic acid (ZOL) after 12 months.

TPTD also demonstrated a higher spinal fusion rate at 12 months (86%) compared to ZOL (70%), indicating its greater efficacy in promoting bone healing in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Daily Teriparatide versus One-Time Annually Zoledronic Acid Administration After Transforaminal Lumbar Interbody Fusion in Osteoporotic Patients. Wang, Z., Zhuang, C., Chen, W., et al.[2022]

In a study of 77 postmenopausal women with osteoporosis undergoing spinal fusion, teriparatide led to a higher rate of bone union at 6 months compared to zoledronate, indicating its potential effectiveness in enhancing early recovery after surgery.

Both teriparatide and zoledronate improved bone mineral density (BMD) over 2 years, but teriparatide showed greater BMD increases at 12 months and resulted in lower disability scores, suggesting it may offer additional benefits in functional recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Teriparatide Versus Zoledronate on Posterior Lumbar Interbody Fusion in Postmenopausal Women with Osteoporosis. Xiong, Y., Li, L., Liu, P., 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]

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]

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]

In the Phase 3 ACTIVE trial, abaloparatide-SC significantly reduced new vertebral fractures by 86% and nonvertebral fractures by 43% in postmenopausal women with osteoporosis, demonstrating its efficacy in fracture prevention.

Abaloparatide-SC also increased bone mineral density at key sites (3.4% at the hip, 2.9% at the femoral neck, and 9.2% at the lumbar spine) after 18 months, and its protective effects against fractures were consistent across various baseline risk factors, making it a suitable treatment for a broad range of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Abaloparatide-SC on Fractures and Bone Mineral Density in Subgroups of Postmenopausal Women With Osteoporosis and Varying Baseline Risk Factors. Cosman, F., Hattersley, G., Hu, MY., et al.[2018]

In a phase 3 study involving 511 postmenopausal women with osteoporosis, the transdermal system for abaloparatide showed clinically meaningful increases in lumbar spine and total hip bone mineral density (BMD) after 12 months, but it did not demonstrate noninferiority compared to the subcutaneous (SC) formulation.

Both treatment methods had similar safety profiles, with the most common adverse events being administration site reactions; however, the transdermal system had a higher incidence of these reactions (94.4% vs. 70.5% for SC).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Transdermal Abaloparatide in Postmenopausal Women with Osteoporosis: A Randomized Study. Lewiecki, EM., Czerwinski, E., Recknor, C., et al.[2023]

Abaloparatide is a synthetic peptide approved for treating postmenopausal women with osteoporosis, showing strong anabolic effects that help increase bone density and reduce fracture risk.

Clinical trials indicate that abaloparatide significantly lowers the risk of both vertebral and nonvertebral fractures while improving bone mineral density in key areas like the femoral neck and lumbar spine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abaloparatide for the treatment of postmenopausal osteoporosis. Pietrogrande, L., Raimondo, E.[2018]

Abaloparatide, a selective activator of the parathyroid hormone receptor 1, significantly improved bone mass and strength in osteopenic ovariectomized rats over a 12-month treatment period, with dose-dependent effects observed at various skeletal sites.

The study found that increases in bone mass were correlated with enhanced bone strength and quality, indicating that abaloparatide not only increases bone density but also improves the structural integrity of bones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One year of abaloparatide, a selective peptide activator of the PTH1 receptor, increased bone mass and strength in ovariectomized rats. Varela, A., Chouinard, L., Lesage, E., et al.[2017]

In a 12-month study with osteopenic ovariectomized rats, abaloparatide significantly increased bone mass and density without causing bone resorption or hypercalcemia, indicating its safety and efficacy as a bone anabolic agent.

The treatment led to a 25% increase in whole-body bone mineral density and improved trabecular microarchitecture, demonstrating that abaloparatide selectively stimulates bone formation through the parathyroid hormone receptor signaling pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One Year of Abaloparatide, a Selective Activator of the PTH1 Receptor, Increased Bone Formation and Bone Mass in Osteopenic Ovariectomized Rats Without Increasing Bone Resorption. Varela, A., Chouinard, L., Lesage, E., et al.[2018]

References

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

Impact of Teriparatide on Complications and Patient-Reported Outcomes of Patients Undergoing Long Spinal Fusion According to Bone Density. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Effect of a single dose of pamidronate administered at the time of surgery in a rabbit posterolateral spinal fusion model. [2021]

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

Effects of teriparatide and bisphosphonate on spinal fusion procedure: A systematic review and network meta-analysis. [2020]

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

The Effect of Daily Teriparatide versus One-Time Annually Zoledronic Acid Administration After Transforaminal Lumbar Interbody Fusion in Osteoporotic Patients. [2022]

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

Effect of Teriparatide Versus Zoledronate on Posterior Lumbar Interbody Fusion in Postmenopausal Women with Osteoporosis. [2023]

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

Abaloparatide: First Global Approval. [2018]

7. 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]

8. 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]

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

Effects of Abaloparatide-SC on Fractures and Bone Mineral Density in Subgroups of Postmenopausal Women With Osteoporosis and Varying Baseline Risk Factors. [2018]

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

Efficacy and Safety of Transdermal Abaloparatide in Postmenopausal Women with Osteoporosis: A Randomized Study. [2023]

11. Spain pubmed.ncbi.nlm.nih.gov

Abaloparatide for the treatment of postmenopausal osteoporosis. [2018]

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

One year of abaloparatide, a selective peptide activator of the PTH1 receptor, increased bone mass and strength in ovariectomized rats. [2017]

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

One Year of Abaloparatide, a Selective Activator of the PTH1 Receptor, Increased Bone Formation and Bone Mass in Osteopenic Ovariectomized Rats Without Increasing Bone Resorption. [2018]