AGN1 LOEP for Preventing Secondary Hip Fractures

(RESTORE Trial)

Recruiting at 59 trial locations

Overseen By Charles Raymond

Age: 65+

Sex: Female

Trial Phase: Academic

Sponsor: AgNovos Healthcare, LLC

Must not be taking: Immuno-suppressive drugs

Disqualifiers: Wheelchair dependent, Metabolic bone disease, Invasive malignancy, Severe cardiovascular disease, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: Immediate post-surgery

2400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether AGN1 LOEP, a new potential therapy, can prevent a second hip fracture in women with osteoporosis who have already experienced one. The study will compare two groups: one receiving standard hip repair and the other receiving standard repair plus AGN1 LOEP treatment on the opposite, unbroken hip. It is suitable for postmenopausal women who have had a low-energy hip fracture and face issues like frequent falls or vision problems that increase fracture risk. Researchers will follow participants for at least five years after surgery to determine if the treatment makes a difference. As an unphased trial, this study allows participants to contribute to important research that could lead to new preventive treatments for hip fractures.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on oral or parenteral immuno-suppressive drugs, you may not be eligible to participate.

What prior data suggests that AGN1 LOEP treatment is safe for preventing secondary hip fractures?

Research shows that the AGN1 LOEP treatment is generally well-tolerated. Studies have found that this treatment can help increase bone strength in the hip where it's needed most. In previous cases using the AGN1 material, no major safety problems occurred. The material in AGN1 LOEP resembles that used in approved bone implants, suggesting its safety. While more information is always useful, current evidence indicates that AGN1 LOEP is safe for people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard care for hip fractures, which typically involves surgery and rehabilitation, AGN1 LOEP is unique because it targets the unfractured hip to prevent a future break. This treatment introduces a novel preventive approach by strengthening the contralateral hip, potentially reducing the risk of a secondary fracture. Researchers are excited about AGN1 LOEP because it shifts the focus from reactive care to proactive prevention, possibly offering better long-term outcomes for patients prone to hip fractures.

What evidence suggests that AGN1 LOEP treatment might be effective for preventing secondary hip fractures?

Research has shown that AGN1 LOEP treatment, which participants in this trial may receive, can help prevent another hip fracture. It rebuilds lost bone in the thigh, making it stronger. Stronger bones are less likely to break. Some studies suggest that AGN1 LOEP could lower the risk of another hip fracture by about 80%. This treatment targets bone loss, a major issue in osteoporosis, a condition that weakens bones and makes them prone to fractures. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for postmenopausal women aged 65 or older with osteoporosis who have had a low-energy hip fracture and are at moderate to high risk of falls. They must be undergoing surgery for the hip fracture, have a history of multiple falls, issues with dizziness or blood pressure changes when standing, poor bone density scores, take several prescription meds daily, and may have vision problems including macular degeneration.

Inclusion Criteria

Informed consent provided by the subject or the subject's legally authorized representative

Has at least one additional risk factor for a secondary hip fracture

Willingness, ability, and commitment to participate in screening, treatment, and all follow-up evaluations for the full duration of the study documented

Exclusion Criteria

I have a diagnosed disorder affecting my calcium levels.

Currently enrolled in another clinical study

I have multiple new fractures besides my hip fracture that affect my mobility or recovery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo hip fracture repair surgery and receive AGN1 LOEP treatment or standard care

Immediate post-surgery

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Visits at 6 weeks, 6 months, and every 6 months thereafter

What Are the Treatments Tested in This Trial?

Interventions

• AGN1 LOEP treatment

Trial Overview The RESTORE study is testing AGN1 LOEP treatment's effectiveness in preventing secondary hip fractures in women after their initial surgical repair. Participants will either receive this new treatment or be part of a control group not receiving it. The study involves up to 2400 subjects followed over at least five years.

How Is the Trial Designed?

Group I: Treated group Experimental Treatment 1 Intervention

Subject receives standard of care to repair the index hip fracture and AGN1 LOEP treatment on the target unfractured contralateral hip

Group II: Control group Active Control 1 Intervention

Subject receives standard of care to repair the index hip fracture and no AGN1 LOEP treatment on the target unfractured contralateral hip

AGN1 LOEP treatment is already approved in European Union for the following indications:

Approved in European Union as OSSURE LOEP Kit for:

• Prevention of secondary hip fractures in osteoporotic women undergoing treatment of index hip fractures

Who Is Running the Clinical Trial?

AgNovos Healthcare, LLC

Lead Sponsor

Trials

9

Recruited

3,200+

BioClinica, Inc.

Industry Sponsor

Trials

8

Recruited

3,000+

Emergent Clinical Consulting, LLC

Industry Sponsor

Trials

6

Recruited

2,900+

CMIC Co, Ltd. Japan

Industry Sponsor

Trials

11

Recruited

3,800+

Baim Institute for Clinical Research

Collaborator

Trials

29

Recruited

55,700+

Avania

Industry Sponsor

Trials

59

Recruited

10,000+

Published Research Related to This Trial

In a study of 91 patients with early osteonecrosis of the femoral head (ONFH), those who underwent multiple small-diameter drilling decompression combined with hip arthroscopy (group A) showed significantly better improvement in hip function and pain relief compared to those who had drilling decompression alone (group B), with Harris scores of 83.34 versus 76.61.

The combined treatment also resulted in a lower rate of femoral head collapse (11.3% in group A vs. 21.6% in group B), indicating that this approach may slow the progression of ONFH and delay the need for total hip arthroplasty.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness of multiple small-diameter drilling decompression combined with hip arthroscopy for early osteonecrosis of the femoral head]. Li, J., Li, Z., Su, X., et al.[2021]

The modified Advanced Core Decompression (ACD) technique, which includes the use of autologous bone from the femoral neck, showed a 75.9% success rate in preventing collapse of the femoral head in patients with osteonecrosis of the femoral head over an average follow-up of 30 months.

Success rates varied by stage of the disease, with a 100% success rate for stage 2a lesions, and 84.6% and 61.5% for stages 2b and 2c, respectively, indicating that the addition of autologous bone significantly improves outcomes compared to previous ACD methods without it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modifications to advanced Core decompression for treatment of Avascular necrosis of the femoral head. Landgraeber, S., Warwas, S., Claßen, T., et al.[2018]

In a study of 60 patients with avascular necrosis (AVN) of the hip, treatment with alendronate significantly reduced pain and disability while improving walking and standing times over a follow-up period of up to 5 years.

Alendronate was well tolerated and led to stabilization or improvement in hip condition, allowing most patients to avoid early surgical intervention, indicating its efficacy in managing AVN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of alendronate, a bisphosphonate, in the treatment of AVN of the hip. A prospective open-label study. Agarwala, S., Jain, D., Joshi, VR., et al.[2016]

Recent literature suggests that bisphosphonates, anticoagulants, and vasodilators can effectively reduce pain and slow the progression of early-stage osteonecrosis, although their routine use is not yet supported.

Core decompression remains one of the safest and most effective procedures for treating pre-collapse osteonecrosis, and combining it with bone morphogenic protein and stem cells may further improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of avascular necrosis of femoral head at pre-collapse stage. Sen, RK.[2022]

In a study of 18 patients with early-stage non-femoral avascular necrosis (AVN), treatment with oral alendronate and intravenous zoledronic acid resulted in significant pain relief and a 50% reduction in analgesic use within the first 6 weeks.

MRI results showed that 94.4% of patients experienced complete resolution of bone marrow edema after 1 year, and only one patient required surgery, indicating that this treatment may effectively manage early AVN and prevent disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bisphosphonate combination therapy for non-femoral avascular necrosis. Agarwala, S., Vijayvargiya, M.[2020]

The AGN1 local osteo-enhancement procedure (LOEP) significantly increased the failure load of treated femurs by an average of 20.5%, indicating a strong immediate biomechanical benefit for bones affected by osteoporosis.

In osteoporotic femurs specifically, the treatment resulted in a 26% increase in failure load and a 45% increase in work to failure, suggesting that this approach could effectively reduce the risk of hip fractures in vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro injection of osteoporotic cadaveric femurs with a triphasic calcium-based implant confers immediate biomechanical integrity. Stroncek, JD., Shaul, JL., Favell, D., et al.[2023]

The AGN1 local osteo-enhancement procedure (LOEP) significantly increased areal bone mineral density (aBMD) in the femurs of 12 postmenopausal women with osteoporosis, showing improvements of 68% at 12 weeks and sustained increases of 58% after 5-7 years.

No serious adverse events were reported, indicating that AGN1 LOEP is a safe and effective minimally-invasive treatment that enhances bone strength and could help prevent hip fractures in osteoporotic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of bone loss in proximal femurs of postmenopausal osteoporotic women with AGN1 local osteo-enhancement procedure (LOEP) increases hip bone mineral density and hip strength: a long-term prospective cohort study. Howe, JG., Hill, RS., Stroncek, JD., et al.[2021]

The Local Osteo-Enhancement Procedure (LOEP) using AGN1 material effectively promotes the replacement of the implant with normal bone in a canine model, showing significant bone volume and strength improvements by 52 weeks post-surgery.

Alendronate treatment did not negatively affect the resorption of AGN1 or the formation of new bone, indicating that AGN1 can be safely used alongside this common osteoporosis medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AGN1 implant material to treat bone loss: Resorbable implant forms normal bone with and without alendronate in a canine critical size humeral defect model. Shaul, JL., Hill, RS., Bouxsein, ML., et al.[2022]

In a study of over 31,000 patients, there was no significant difference in fracture risk between those who discontinued alendronate (ALN) treatment and those who continued after 5 years, indicating that stopping the medication may not increase fracture risk.

The study highlighted that less than 50% of patients continued ALN treatment for 5 years, and older age was identified as a significant factor influencing fracture risk among those who discontinued the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fracture rates in patients discontinuing alendronate treatment in real life: a population-based cohort study. Sølling, AS., Christensen, DH., Darvalics, B., et al.[2021]

Sequential therapy using abaloparatide followed by alendronate is cost-effective compared to alendronate monotherapy for women aged 60 and older with low bone mineral density, indicating it can be a beneficial treatment strategy for reducing fracture risk.

The study found that sequential ABL/ALN therapy not only costs less but also provides more quality-adjusted life years (QALYs) than the alternative sequential treatment starting with alendronate, highlighting its superior efficacy in patients not previously treated with antiresorptive agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of sequential treatment with abaloparatide followed by alendronate vs. alendronate monotherapy in women at increased risk of fracture: A US payer perspective. Hiligsmann, M., Williams, SA., Fitzpatrick, LA., et al.[2021]

Only 21.5% of patients were receiving anti-osteoporotic treatment (OT) at the time of hip fracture, despite 88.5% being recommended for treatment based on risk assessments, highlighting a significant gap in care.

One year after the hip fracture, only 12.1% of patients who survived were prescribed OT, and 5.5% experienced new fractures, indicating a critical need for improved adherence to treatment guidelines to prevent further complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to the recommended prevention strategies before and after a hip fragility fracture: what makes us go blind? Daniel, A., Marques, ML., Brites, L., et al.[2019]

A study of 244 hip fracture patients revealed that many are over 80 years old and face barriers to osteoporosis treatment, such as dementia and multiple medical conditions, highlighting the need for tailored care.

Implementing coordinator-facilitated programs in hospitals can effectively identify and treat osteoporosis in hip fracture patients, ensuring they receive necessary medications and education to improve adherence and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overcoming barriers to osteoporosis care in vulnerable elderly patients with hip fractures. Switzer, JA., Jaglal, S., Bogoch, ER.[2022]

Osteoporosis is a serious condition that leads to over 2 million fragility fractures annually, including 300,000 hip fractures, which significantly increase the risk of future fractures and mortality within the first year.

Orthopaedic surgeons play a crucial role in managing osteoporosis by coordinating care for patients with fragility fractures, and administering treatments like zoledronic acid, which has been shown to effectively reduce the risk of subsequent fractures after a low-energy hip fracture.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of the orthopaedic surgeon in minimizing mortality and morbidity associated with fragility fractures. Ekman, EF.[2022]

The Comprehensive Fragility Fracture Management Program (CFFMP) significantly reduced the re-fracture rate in elderly hip fracture patients, with only 1.32% in the intervention group compared to 10.39% in the control group, indicating its effectiveness in preventing secondary fractures.

Patients in the CFFMP group showed significant improvements in functional performance measures after one year, while also incurring lower overall healthcare costs ($22,450 vs. $25,313), suggesting that this multi-disciplinary approach not only enhances recovery but is also cost-effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a multidisciplinary rehabilitation programme for elderly patients with hip fracture: A prospective cohort study. Cheung, WH., Shen, WY., Dai, DL., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04796350

NCT04796350 | RESTORE - Study of AGN1 LOEP to ... This study is designed to demonstrate that the AGN1 LOEP treatment can reduce the incidence of secondary hip fractures in subjects presenting with an index hip ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12035697/

AGN1 local osteo-enhancement procedure increases ... These results suggest that AGN1 LOEP provides a treatment option that can help to locally restore lost trabecular bone to strengthen the femur, and therefore, ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S8756328221004129

AGN1 implant material to treat bone loss: Resorbable ... This study suggests that the AGN1 implant material demonstrates potential for local restoration of bone in critical-size core defects.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05202678

NCT05202678 | RECONFIRM - Study of AGN1 LOEP in ... The study will collect procedural, short- and long-term data on the safety and clinical performance of AGN1 LOEP in the post-market setting in European ...

5. onderzoekmetmensen.nl onderzoekmetmensen.nl/en/node/54786/pdf

Randomized Controlled Study of a Local Osteo- ... We estimate that the AGN1 LOEP device effect in reducing the incidence of secondary hip fracture in the intended patient population will be. 80% ...

6. withpower.com withpower.com/trial/phase-osteoporosis-3-2021-27fcf

AGN1 LOEP for Preventing Secondary Hip Fractures A randomized controlled trial to evaluate AGN1 to prevent secondary hip fractures in osteoporotic women undergoing treatment of index hip fractures.

7. accessdata.fda.gov accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/detail.cfm?mdrfoi__id=8200086&pc=MQV

AGNOVOS HEALTHCARE USA, LLC OSSURE LOEP KIT The implant material in the ossure loep kit is equivalent to the implant material identified in 510(k)# k181342. Event Description. Patient underwent cemented ...