RESTORE - Study of AGN1 LOEP to Prevent Secondary Hip Fractures

Study Overview
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Brief Summary
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A randomized controlled trial to evaluate AGN1 to prevent secondary hip fractures in osteoporotic women undergoing treatment of index hip fractures. Up to 2400 subjects will be randomized between a treatment group and a control group. Subjects will be followed for a minimum of 5 years after undergoing hip fracture repair surgery.

Detailed Description
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This is an event driven, randomized, controlled, prospective, single blinded, multi-national study. 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 fracture and undergoing hip fracture repair surgery. Subjects presenting with an index fragility hip fracture who will undergo hip fracture repair will be enrolled. Subjects will be randomized 1:1 into the following two study groups: Treated Group - receives standard of care to repair the index hip fracture and AGN1 LOEP treatment on the target unfractured contralateral hip Control Group - receives standard of care to repair the index hip fracture and no AGN1 LOEP treatment on the target unfractured contralateral hip AGN1 LOEP is an elective procedure that will be performed immediately following hip fracture repair. Subjects will be followed through scheduled visits conducted at 6 weeks, 6 months, and every 6 months thereafter for a minimum of 5 years.

Official Title
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Randomized Controlled Study of a Local Osteo-Enhancement Procedure (LOEP) to Prevent Secondary Hip Fractures in Osteoporotic Women Undergoing Treatment of Index Hip Fractures

Conditions
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Fragility Fracture, Hip Fractures, Osteoporosis

Intervention / Treatment
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* Device: AGN1 LOEP treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is a postmenopausal female at least 1-year post menses and at least 65 years of age. Subject presents with a low-energy index fragility hip fracture in one hip and will undergo surgical repair of the fractured hip. Subject has at least one of the following additional risk factors for a secondary hip fracture (as determined by subject or legally authorized representative (LAR) interview or medical record review): Documented falls assessment indicating subject is at moderate or high risk of falls Falls history (2 or more falls in the previous 12 months) History of vertigo, dizziness, or postural hypotension Documented T-score < -2.5 at the hip Taking more than 3 daily prescription medications Visual impairment as confirmed by one of the following: Subject reports difficulty seeing Lack of depth perception or vision loss in one eye Macular degeneration Cataracts Prior non-hip fragility fracture Cognitive frailty as assessed by SPMSQ (mild or moderate cognitive impairment) or delirium Parkinson's disease stage 3 or 4 10-year hip fracture probability >15% using the FRAX® Fracture Risk Assessment Tool of the clinical site country Subject is expected to be ambulatory after the hip fracture repair procedure. Informed consent is provided by the subject or the subject's LAR. The subject's willingness, ability, and commitment to participate in screening, treatment, and all follow-up evaluations for the full duration of the study has been documented. Exclusion Criteria: Subject hospital admission is > 24 hours from the time of the index hip fracture. Subject was dependent on the use of a wheelchair or was bedridden prior to the index hip fracture. Subject is currently enrolled in another clinical study. Subject has a history of hip surgery or previous hip fracture on the target unfractured hip contralateral to the index hip fracture. Subject has one or more new fractures in addition to the index hip fracture at admission. Subject has an infection at the LOEP intended treatment site or has non-intact skin or acute traumatic injuries with open wounds close to the area of intended LOEP treatment. Subject has a progressive increase in undiagnosed pain in the target hip contralateral to the index fractured hip over the previous 3 months that in the opinion of the Investigator may suggest underlying bone or joint pathology on the unfractured side. Subject has radiological evidence of gross bony or joint pathology of the hip, including signs predictive of atypical femoral fractures (e.g. cortical beaking), or has been diagnosed and/or treated for atypical femoral fractures. Subject is at ASA Class IV, V, or VI. Subject has a history of metabolic bone disease other than osteoporosis (e.g., Paget's disease, renal osteodystrophy, or osteomalacia). Subject has a history of Pott's disease. Subject has a history of any invasive malignancy (except nonmelanoma skin cancer), unless treated with curative intent and with no clinical signs or symptoms of the malignancy for 5 years. Subject has chronic cardiac insufficiency or severe cardiovascular disease as assessed by a subject or LAR interview to be NYHA Class III or IV or has an implanted pacemaker. Subject has a history of cardiovascular events (e.g. stroke, transient ischemic attack, myocardial infarction, unstable angina, pulmonary embolus, deep vein thrombosis, ventricular tachycardia, or atrial fibrillation) in the last 3 months. Subject is on oral or parenteral immuno-suppressive drugs. Subject has uncontrolled diabetes mellitus. Subject has Hb ≤ 9 g/dL at admission. Subject has severe renal insufficiency defined as an estimated glomerular filtration rate (eGFR) ≤ 30 mL/min. Subject has albumin corrected serum calcium levels outside the normal laboratory range or has a pre-existing calcium metabolism disorder (e.g. hypercalcemia). Subject has a Parker Mobility Score ≤ 5. Subject has severe cognitive impairment as assessed by SPMSQ. Subject has known allergies to calcium-based bone void fillers. In the judgement of the Investigator, the subject is not a good study candidate (e.g., inability to maintain follow-up schedule, comorbidity or poor general physical/mental health, or drug or alcohol abuse issues). Subject fails pre-operative or intraoperative eligibility criteria as specified in section 7.4.2. of the clinical investigation plan.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treated group<br>Subject receives standard of care to repair the index hip fracture and AGN1 LOEP treatment on the target unfractured contralateral hip | Device: AGN1 LOEP treatment<br>* the implantation site is injected with the AGN1 implant material<br>|
| No Intervention: Control group<br>Subject receives standard of care to repair the index hip fracture and no AGN1 LOEP treatment on the target unfractured contralateral hip | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of secondary fragility hip fractures | Comparison of incidence of secondary fragility hip fractures in the target hip among the Treated Group vs. Control Group. | Interim Analysis, approximately 30 Months | 
| Cumulative Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Comparison of incidence of AEs and SAEs among the Treated Group vs. Control Group. | Interim Analysis, approximately 30 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Areal bone mineral density (aBMD) | Total hip areal bone mineral density in target hips of the Treated Group compared to the Control Group | 12 months and 24 months | 
| Trabecular Bone Score (TBS) | Continuous densitometry measure of the target hip bone of the Treated Group compared to the Control Group | 12 months and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoporosis, Hip Fracture, Fragility Fracture