RESTORE - Study of AGN1 LOEP to Prevent Secondary Hip Fractures

Not Applicable

Recruiting

• Conditions: Fragility Fracture; Hip Fractures; Osteoporosis

• Registration Number: NCT04796350
• Lead Sponsor: AgNovos Healthcare, LLC

Brief Summary

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

This is an event driven, randomized, controlled, prospective, single blinded (non-blinded in Canada), 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:

1. Treated Group - receives standard of care to repair the index hip fracture and AGN1 LOEP treatment on the target unfractured contralateral hip

2. 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.

Study Timeline

• Study First Submitted: 2021-03-08
• Study First Submitted QC: 2021-03-11
• Study First Posted: 2021-03-12
• Study Start: 2021-04-24
• Status Verified: 2024-07
• Last Update Submitted: 2025-01-29
• Last Update Posted: 2025-01-31
• Primary Completion: 2027-04-01
• Study Completion: 2029-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 2400

Inclusion Criteria

1. Subject is a postmenopausal female at least 1-year post menses and at least 65 years of age.

2. Subject presents with a low-energy index fragility hip fracture in one hip and will undergo surgical repair of the fractured hip.

3. 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

4. Subject is expected to be ambulatory after the hip fracture repair procedure.

5. Informed consent is provided by the subject or the subject's LAR.

6. 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

1. Subject hospital admission is > 24 hours from the time of the index hip fracture.
2. Subject was dependent on the use of a wheelchair or was bedridden prior to the index hip fracture.
3. Subject is currently enrolled in another clinical study.
4. Subject has a history of hip surgery or previous hip fracture on the target unfractured hip contralateral to the index hip fracture.
5. Subject has one or more new fractures in addition to the index hip fracture at admission that, in the opinion of the investigator, would further compromise patient mobility, rehabilitation, and/or recovery or subject has three or more new fractures in addition to the index hip fracture.
6. 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.
7. 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.
8. 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.
9. Subject is at ASA Class IV, V, or VI.
10. Subject has a history of metabolic bone disease other than osteoporosis (e.g., Paget's disease, renal osteodystrophy, or osteomalacia).
11. Subject has a history of Pott's disease.
12. 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.
13. 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.
14. 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.
15. Subject is on oral or parenteral immuno-suppressive drugs.
16. Subject has uncontrolled diabetes mellitus.
17. Subject has Hb ≤ 9 g/dL at admission.
18. Subject has severe renal insufficiency defined as an estimated glomerular filtration rate (eGFR) ≤ 30 mL/min.
19. Subject has a diagnosed and ongoing calcium metabolism disorder.
20. Subject has a Parker Mobility Score ≤ 5.
21. Subject has severe cognitive impairment as assessed by SPMSQ.
22. Subject has known allergies to calcium-based bone void fillers.
23. 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).
24. Subject fails pre-operative or intraoperative eligibility criteria as specified in section 7.4.2. of the clinical investigation plan.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (54)

University Hospital of Duesseldorf; 🇩🇪 Düsseldorf, Germany

Justus Liebig Universitat Gießen; 🇩🇪 Gießen, Germany

Medizinische Hochschule Hannover; 🇩🇪 Hannover, Germany

Innsbruck Hospital; 🇦🇹 Innsbruck, Austria

Health Sciences Centre - Eastern Health; 🇨🇦 Saint John's, Newfoundland and Labrador, Canada

Aarhus University Hospital; 🇩🇰 Aarhus, Denmark

CHU Grenoble-Alpes; 🇫🇷 Grenoble, France

CHU Lyon; 🇫🇷 Lyon, France

CHU Toulouse; 🇫🇷 Toulouse, France

Universitatsklinikum Schleswig-Holstein; 🇩🇪 Kiel, Germany

Klinikum der Universität München; 🇩🇪 München, Germany

University Hospital of Münster; 🇩🇪 Münster, Germany

Universitätsklinikum Regensburg; 🇩🇪 Regensburg, Germany

BG Klinik Tuebingen; 🇩🇪 Tuebingen, Germany

Helios Wuppertal; 🇩🇪 Wuppertal, Germany

Azienda Ospedaliero Universitaria Careggi; 🇮🇹 Firenze, Italy

ASST Gaetano Pini CTO; 🇮🇹 Milano, Italy

University Hospital San Raffaele Milano; 🇮🇹 Milano, Italy

Policlinico Tor Vergata; 🇮🇹 Rome, Italy

CTO Torino; 🇮🇹 Torino, Italy

Akita City Hospital; 🇯🇵 Akita-shi, Akita, Japan

Southern Tohoku General Hospital; 🇯🇵 Kōriyama, Fukushima, Japan

Hyogo Prefectural Nishinomiya Hospital; 🇯🇵 Nishinomiya, Hyogo, Japan

Kagawa Rosai Hospital; 🇯🇵 Marugame, Kagawa, Japan

Kanto Rosai Hospital; 🇯🇵 Kawasaki City, Kanagawa, Japan

Shin-yurigaoka General Hospital; 🇯🇵 Kawasaki-Shi, Kanagawa, Japan

Chikamori Hospital; 🇯🇵 Kouchi City, Kochi, Japan

Okayama Medical Center; 🇯🇵 Okayama City, Okayama, Japan

Jutendo University Shizuoka Hospital; 🇯🇵 Izunokuni City, Shizuoka, Japan

The University of Tokyo Hospital; 🇯🇵 Bunkyō-Ku, Tokyo, Japan

St. Mary's Hospital; 🇯🇵 Fukuoka, Japan

Iwata City Hospital; 🇯🇵 Iwata, Japan

Shin-Yurigaoka General Hospital; 🇯🇵 Kawasaki-shi, Japan

National Hospital Organization Kumamoto Medical Center; 🇯🇵 Kumamoto, Japan

Saga-Ken Medical Centre Koseikan; 🇯🇵 Saga, Japan

Japanese Red Cross Shizuoka Hospital; 🇯🇵 Shizuoka, Japan

Deventer Hospital; 🇳🇱 Deventer, Netherlands

Saint Anna Ziekenhuis; 🇳🇱 Geldrop, Netherlands

Maastricht UMC; 🇳🇱 Maastricht, Netherlands

Isala Hospital; 🇳🇱 Zwolle, Netherlands

Vall d'Hebron University Hospital; 🇪🇸 Barcelona, Spain

Clinic de Barcelona; 🇪🇸 Barcelona, Spain

Hospital Universitario de Basurto; 🇪🇸 Bilbao, Spain

Galdakao-Usansolo Hospital; 🇪🇸 Galdakao, Spain

Hospital Neuro-Traumatológico de Jaén; 🇪🇸 Jaén, Spain

Hospital Clínico San Carlos; 🇪🇸 Madrid, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

PARC Tauli; 🇪🇸 Sabadell, Spain

Mutua de Terrassa University Hospital; 🇪🇸 Terrassa, Spain

Valladolid University Clinic Hospital; 🇪🇸 Valladolid, Spain

Birmingham Heartlands Hospital; 🇬🇧 Birmingham, England, United Kingdom

Leicester Royal Infirmary; 🇬🇧 Leicester, England, United Kingdom

Royal Infirmary of Edinburgh; 🇬🇧 Edinburgh, Scotland, United Kingdom

Nottingham University Hospitals, Queen's Medical Center; 🇬🇧 Nottingham, United Kingdom