AGN1 LOEP SV Kit for VCFs

(STAND Trial)

Recruiting at 17 trial locations

Overseen By Charles Raymond

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: AgNovos Healthcare, LLC

Must not be taking: Opioids, Immune-suppressive drugs

Disqualifiers: Unstable VCF, Bleeding disorder, Infection, others

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

Compensation: Varies

Number of Visits: 6

Duration: 1 day

408 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called the AGN1 LOEP SV Kit for individuals with painful vertebral compression fractures (VCFs) due to osteoporosis. The goal is to determine if this treatment is as effective and safe as the usual method, which uses PMMA bone cement. Participants will receive either the new treatment or the standard bone cement treatment. Those who have experienced painful VCFs for six months or less, caused by osteoporosis, and have not found success with other treatments, may be suitable for this study. As an unphased trial, this study allows patients to contribute to the development of innovative treatments for osteoporosis-related fractures.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you require daily opioid medication for pain not related to the target fractures, you may not be eligible to participate.

What prior data suggests that the AGN1 LOEP SV Kit is safe for treating vertebral compression fragility fractures?

Research has shown that the AGN1 LOEP SV Kit is designed to strengthen bones and assist with vertebral compression fractures (VCFs). This treatment remains under study, so limited safety information is currently available. However, the FDA has recognized it as a breakthrough device, indicating its potential for treating VCFs.

For PMMA bone cement, studies have demonstrated that many patients tolerate it well. This cement is already a common treatment for stabilizing bones in these fractures and has been used for years, with its safety well-established.

Both treatments aim to alleviate painful spine fractures. While more is known about PMMA bone cement, the AGN1 LOEP SV Kit is still undergoing testing, and additional safety information will emerge as research progresses. ^{1 2 3 4 5}

Why are researchers excited about this trial?

The AGN1 LOEP SV Kit is unique because it not only stabilizes fractures in the vertebral body but also encourages the growth of new bone. Unlike the PMMA bone cement, which is commonly used to simply fill and stabilize fractures, the AGN1 implant material is injected, hardens, and then is gradually replaced by natural bone. Researchers are excited about the AGN1 Kit because it offers the potential for a more natural and long-term healing process compared to traditional methods, which primarily focus on immediate stabilization without bone regrowth. This new approach could lead to better outcomes for patients with vertebral compression fractures by restoring bone integrity over time.

What evidence suggests that the AGN1 LOEP SV Kit is effective for treating vertebral compression fragility fractures?

Research has shown that the AGN1 LOEP SV Kit, a treatment in this trial, can strengthen bones in weakened areas, enhancing overall bone strength. This treatment involves injecting a special material that hardens and supports broken vertebrae. Over time, new bone replaces this material. Early results suggest it might be as effective as PMMA bone cement, another treatment option in this trial, for treating vertebral compression fractures. The goal is to relieve pain and improve mobility. ^{1 3 4 6 7}

Who Is on the Research Team?

Kern Singh

Principal Investigator

Midwest Orthopedics at Rush

Are You a Good Fit for This Trial?

This trial is for men and women aged 55 to 85 with a single painful vertebral compression fracture (VCF) that hasn't healed within 6 months despite conservative treatments. Participants must have significant disability from the VCF, no high-energy trauma or tumor-related fractures, not be severely overweight, and have no major health issues like uncontrolled diabetes or severe heart/lung problems.

Inclusion Criteria

I am between 55 and 85 years old.

My pain from vertebral compression fractures has been for 6 months or less.

My spine is tender at the site of my vertebral fracture, confirmed by an exam.

Exclusion Criteria

I have severe heart or lung problems.

Subject is currently enrolled in another interventional clinical study.

Target VCF is due to high-energy trauma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vertebral augmentation using either the AGN1 LOEP SV Kit or PMMA bone cement

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

5 visits (in-person) at 7 days, 28 days, 3 months, 12 months, and 24 months

What Are the Treatments Tested in This Trial?

Interventions

• AGN1 LOEP SV Kit
• PMMA bone cement

Trial Overview The STAND trial is testing the AGN1 LOEP SV Kit against PMMA bone cement in treating vertebral compression fractures. It's a multicenter study where participants are randomly assigned to one of these treatments to see if AGN1 is just as safe and effective as the standard PMMA treatment.

How Is the Trial Designed?

Group I: Treatment with AGN1 LOEP SV Kit Experimental Treatment 1 Intervention

The AGN1 LOEP SV Kit is intended for fixation of pathological fractures of the vertebral body using vertebral augmentation. Following saline lavage to create space, the AGN1 implant material is injected and hardens in situ to augment the fractured vertebral body. The AGN1 implant material is then resorbed and replaced with new bone.

Group II: Treatment with PMMA bone cement Active Control 1 Intervention

High viscosity PMMA bone cement will be used for vertebral augmentation.

AGN1 LOEP SV Kit is already approved in European Union, United States for the following indications:

Approved in European Union as AGN1 LOEP SV Kit for:

• Bone loss in higher volume applications at other anatomical sites

Approved in United States as AGN1 LOEP SV Kit for:

• Investigational device for stable but painful vertebral compression fractures

Who Is Running the Clinical Trial?

AgNovos Healthcare, LLC

Lead Sponsor

Trials

9

Recruited

3,200+

Published Research Related to This Trial

In a study of 160 elderly patients with osteoporotic vertebral compression fractures, types I, II, and III bone cement distributions during percutaneous vertebroplasty (PVP) resulted in significantly better pain relief and functional outcomes compared to types IV and V, both three days and one year post-surgery.

Patients with types I, II, and III distributions experienced lower rates of refractures and adjacent vertebral fractures, indicating that even distribution of bone cement is crucial for long-term clinical efficacy following PVP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of cement distribution type on clinical outcome after percutaneous vertebroplasty for osteoporotic vertebral compression fractures in the aging population. Zhou, C., Liao, Y., Huang, S., et al.[2022]

The Confidence high viscosity bone cement system, combined with postural reduction, effectively treated acute severe osteoporotic vertebral compression fractures in 34 patients, achieving complete pain relief in 31 cases and significant improvements in vertebral height and alignment.

The procedure demonstrated a low complication rate, with only 8.8% experiencing cement leakage, none of which resulted in clinical symptoms, indicating a safe intervention for elderly patients with osteoporosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Confidence high viscosity bone cement system and postural reduction in treating acute severe osteoporotic vertebral compression fractures]. Li, B., Wang, Q., Yu, Y., et al.[2019]

A new mixing regimen for bone cement and iodinated contrast used in percutaneous vertebroplasty (PVP) was developed, allowing for proper fluoroscopic visualization during procedures without major complications in 125 patients.

While the addition of contrast reduced the ultimate compressive strength of the cement mixture by 38%, this change did not significantly impact clinical outcomes, with 64% of patients achieving complete response and no vertebral collapse during follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A simplified method of opacifying and mixing acrylic cement for percutaneous vertebroplasty: a clinical and in vitro study. Teng, GJ., He, SC., Deng, G., et al.[2019]

In a study of 191 patients with osteoporotic vertebral fractures treated with percutaneous kyphoplasty, using acrylic cement (PMMA) mixed with calcium sulfate showed equivalent pain relief and functional improvement compared to pure PMMA.

The combination of PMMA and calcium sulfate significantly reduced the risk of cement leakage during the procedure, enhancing the safety of the treatment without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of acrylic bone cement mixed with calcium sulfate combined with percutaneous kyphoplasty in the treatment of osteoporotic fractures]. Fu, Y., Yan, YC., Ru, XL., et al.[2023]

Using subject-specific planning and computer-assisted techniques to augment osteoporotic femora with PMMA bone cement significantly increased bone strength, with yield load increasing by 33% and maximum load by 30%.

The method minimized the amount of cement used (average of 9.5 ml) while effectively reducing the risk of hip fractures, demonstrating a promising approach to enhance bone stability without the common side effects associated with excessive cement use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subject-specific planning of femoroplasty: an experimental verification study. Basafa, E., Murphy, RJ., Otake, Y., et al.[2022]

In a study of 56 elderly patients with osteoporotic vertebral compression fractures, the use of high viscosity bone cement for targeted sealing followed by low viscosity cement injection significantly reduced pain, with VAS scores dropping from an average of 7.21 to 2.81 within three days post-operation.

The technique demonstrated a low incidence of bone cement leakage (3.57%), with no significant clinical symptoms reported, indicating improved safety during vertebroplasty procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical application of targeted sealing with high viscosity bone cement and secondary injection of low viscosity bone cement in vertebroplasty]. Liu, CZ., Jia, BX., Gao, XQ., et al.[2023]

In a study of 98 patients with osteoporosis, the extent of polymethylmethacrylate cement used in vertebroplasty was found to correlate with the risk of new fractures in adjacent vertebral bodies, with a follow-up period averaging about 2 years.

Specifically, the risk of adjacent vertebral fractures was highest when the cement was placed at the disc level (44% of cases), compared to 29% at the endplate level and only 7% at the trabecula level, suggesting that careful placement of cement could help reduce fracture risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of post-vertebroplasty fracture in adjacent vertebral bodies appears correlated with the morphologic extent of bone cement. Sun, YC., Teng, MM., Yuan, WS., et al.[2019]

In a study of 63 patients over 80 years old with osteoporotic vertebral compression fractures, the new bone cement made from mineralized collagen and PMMA (MC-PMMA) showed comparable short-term outcomes to traditional PMMA cement in terms of pain relief and functional improvement.

However, 12 months post-surgery, the MC-PMMA group demonstrated superior long-term benefits, suggesting that this new bone cement may provide better overall clinical outcomes for elderly patients with these types of fractures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poly(methyl methacrylate) bone cement composited with mineralized collagen for osteoporotic vertebral compression fractures in extremely old patients. Luo, K., Jiang, G., Zhu, J., et al.[2020]

In a study of 62 osteoporosis patients undergoing anterior lumbar interbody fusion (ALIF), the use of PMMA cement augmentation significantly reduced cage subsidence (5.2% in the PMMA group vs. 19.6% in the control group) and vertebral body height loss (3.9% vs. 10.7%).

The addition of PMMA augmentation did not increase the rates of nonunion or adjacent-segment degeneration, suggesting it is a safe and effective method to enhance the stability of ALIF in osteoporotic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anterior bone cement augmentation in anterior lumbar interbody fusion and percutaneous pedicle screw fixation in patients with osteoporosis. Kim, KH., Lee, SH., Lee, DY., et al.[2022]

Cement augmentation during posterior spinal fusion (PSF) significantly reduces the incidence of screw loosening and other complications in patients with low bone density, with only 5.41% experiencing screw loosening compared to higher rates in unaugmented patients.

Patients with low bone density who received cement augmentation (Group II-B) showed similar pain relief and clinical outcomes as those with normal bone density, indicating that cement augmentation is an effective strategy for improving surgical outcomes in low-density bones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pedicle Screw Fixation With Cement Augmentation Versus Without in the Treatment of Spinal Stenosis Following Posterior Spinal Fusion Surgery, Superiority According to Bone Mineral Density: A Three-Arm Randomized Clinical Trial. Shafiekhani, P., Darabi, M., Jajin, EA., et al.[2023]

In a study involving 32 lumbar vertebral levels, it was found that latex or air injected into the lumbar vertebrae could flow into the inferior vena cava, highlighting the risk of cement extrusion during procedures involving polymethylmethacrylate for stabilizing osteoporotic fractures.

The research confirmed that while latex or air could enter the inferior vena cava, it did not enter the spinal canal, emphasizing the importance of understanding lumbar vertebral venous anatomy to prevent complications during surgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venous Drainage of Lumbar Vertebral Bodies: Anatomic Study with Application to Kyphoplasty, Vertebroplasty, and Pedicle Screw Complications. Iwanaga, J., Rustagi, T., Ishak, B., et al.[2020]

In a review of 13 randomized controlled trials with 1949 participants, bone cement augmentation for osteoporotic vertebral compression fractures did not significantly increase the incidence of new vertebral fractures during short-term follow-ups (6 and 12 months).

However, over a longer follow-up period of 24 months or more, patients receiving bone cement augmentation had a significantly lower incidence of new vertebral fractures compared to non-bone cement treatments, although they experienced a higher risk of new adjacent vertebral fractures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Bone Cement Augmentation and New Vertebral Fractures in Patients with Osteoporotic Vertebral Compression Fractures: A Systematic Review and Meta-Analysis. Xiao, Q., Zhao, Y., Qu, Z., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04835428

NCT04835428 | STAND - Study of the AGN1 LOEP SV Kit ... The objective of this study is to demonstrate non-inferiority of the AGN1 LOEP SV Kit for the treatment of VCFs to standard of care vertebroplasty treatment ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40297188/

AGN1 local osteo-enhancement procedure increases ... The AGN1 LOEP treatment can locally increase trabecular bone density in weakened areas of the proximal femur where strength increase is most needed.

3. mayo.edu mayo.edu/research/clinical-trials/cls-20548780

Study of the AGN1 LOEP SV Kit Compared to PMMA in ... The purpose of this trial is to evaluate the safety and effectiveness of the AGN1 LOEP SV Kit for the treatment of painful vertebral compression fragility ...

4. my.clevelandclinic.org my.clevelandclinic.org/clinical-trials/1667-a-randomized-single-blinded-non-inferiority-study-comparing-agn1-local-osteo-enhancement-procedure-loep-sv-kit-treatment-of-vertebral-compression-fragility-fractures-to-pmma-bone-cement-treatment

Clinical Trials The objective of this study is to demonstrate non-inferiority of the AGN1 LOEP SV Kit for the treatment of VCFs to standard of care vertebroplasty treatment.

5. odtmag.com odtmag.com/breaking-news/agnovos-healthcares-agn1-loep-sv-kit-obtains-ide/

AgNovos Healthcare's AGN1 LOEP SV Kit Obtains IDE - ODT The IDE will allow studying the device's ability to reduce pain and support mobility in vertebral compression fracture patients. “We are pleased ...

6. agnovos.com agnovos.com/en/news-events/agn1-loep-sv-kit-receives-an-investigational-device-exemption-ide-from-the-u-s-fda/

AGN1 LOEP SV Kit Receives an Investigational Device ... AGN1 LOEP SV Kit Receives an Investigational Device Exemption (IDE) from the U.S. FDA ... The IDE for the AGN1 LOEP SV kit will enable the study of the ...

7. bioworld.com bioworld.com/articles/506090-fda-oks-ide-trial-of-agnovos-healthcares-breakthrough-spine-device

FDA OKs IDE trial of Agnovos Healthcare's breakthrough ... The AGN1 LEOP SV kit won breakthrough device designation from the FDA in March of 2020 for the treatment of stable VCFs.