Clinical trial NCT06951672: The AMEND TS Early Feasibility Study is a Prospective, Single-arm, Multi-center Study to Evaluate the Safety and Function of the AMEND(TM) Trans-Septal System for MR Reduction: Up to 15 Subjects Will be Enrolled in up to 7 Investigational Centers in the U.S. and Canada With a 30d Safety Endpoint
Official title: AMEND TS Early Feasibility Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Mitral Regurgitation Functional
Mitral Incompetence
Annuloplasty
Lead sponsor: Valcare Medical Ltd.
Sponsor class: INDUSTRY
First posted: 2025-04-30
Enrollment: 15
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this clinical investigation, the AMEND TS Early Feasibility Study is to evaluate the safety and functionality of the AMEND Trans-Septal System for annuloplasty as treatment of mitral regurgitation.

Protocol Design Rationale The investigational device under this protocol consists of a "D"-shaped semi-rigid ring that is implanted using a transseptal approach. The ability to deploy the annuloplasty ring in a percutaneous fashion affords an improved safety profile for surgical candidates, as well as surgical style solution for those patients that are at elevated risk for surgery due to comorbidities and advanced age. This early feasibility study allows treatment of higher risk surgical candidates with a surgical- level annuloplasty repair therapy by the AMEND™ Implant. This clinical investigation is intended to evaluate the safety and functionality of the AMEND™ Trans-Septal System. Study results are expected to provide information that cannot be obtained through non-clinical testing, due to the limitations of in-vivo and in-vitro test models. The AMEND™ Trans-septal System has previously undergone extensive preclinical and bench testing as well as initial OUS clinical experience. The results of these tests and clinical data obtained so far, justify the use of the device in the EFS IDE study as proposed in this study protocol.

DEVICE DESCRIPTION Valcare Medical AMENDTM Trans-Septal System is a mitral valve repair annuloplasty ring implanted in a trans-catheter method intended for correction of mitral regurgitation. It is designed to be used as standalone therapy or in combination with other repair treatments. The device is delivered through a catheter using a trans-septal approach and implanted in the beating heart on the atrial surface of the mitral valve annulus similar to surgical annuloplasty rings.

The AMENDTM Trans-Septal System consists of a semi-rigid annuloplasty ring (implant), a delivery system (catheter), and accessories (Stage, Introducer sheath). The implant delivered under fluoroscopic and echocardiographic guidance, is placed and fixed to achieve an anatomic outcome that is consistent with standard open surgical annuloplasty procedures. The system is a single-use device, supplied sterile, non-pyrogenic and ready-for-use.

Indications for Use The Valcare Medical AMEND™ Trans-Septal System is intended for correction of mitral insufficiency in adult male and female patients. It is indicated to treat patients with mitral regurgitation using a percutaneous direct annuloplasty approach. The decision to use an annuloplasty ring is made by the heart center team after reviewing the risks and benefits of alternative procedures and evaluating the patient's mitral valve disease.

Detailed description: The purpose of this clinical investigation, the AMEND TS Early Feasibility Study is to evaluate the safety and functionality of the AMEND Trans-Septal System for annuloplasty as treatment of mitral regurgitation.

Protocol Design Rationale The investigational device under this protocol consists of a "D"-shaped semi-rigid ring that is implanted using a transseptal approach. The ability to deploy the annuloplasty ring in a percutaneous fashion affords an improved safety profile for surgical candidates, as well as surgical style solution for those patients that are at elevated risk for surgery due to comorbidities and advanced age. This early feasibility study allows treatment of higher risk surgical candidates with a surgical- level annuloplasty repair therapy by the AMEND™ Implant. This clinical investigation is intended to evaluate the safety and functionality of the AMEND™ Trans-Septal System. Study results are expected to provide information that cannot be obtained through non-clinical testing, due to the limitations of in-vivo and in-vitro test models. The AMEND™ Trans-septal System has previously undergone extensive preclinical and bench testing as well as initial OUS clinical experience. The results of these tests and clinical data obtained so far, justify the use of the device in the EFS IDE study as proposed in this study protocol.

DEVICE DESCRIPTION Valcare Medical AMENDTM Trans-Septal System is a mitral valve repair annuloplasty ring implanted in a trans-catheter method intended for correction of mitral regurgitation. It is designed to be used as standalone therapy or in combination with other repair treatments. The device is delivered through a catheter using a trans-septal approach and implanted in the beating heart on the atrial surface of the mitral valve annulus similar to surgical annuloplasty rings.

The AMENDTM Trans-Septal System consists of a semi-rigid annuloplasty ring (implant), a delivery system (catheter), and accessories (Stage, Introducer sheath). The implant delivered under fluoroscopic and echocardiographic guidance, is placed and fixed to achieve an anatomic outcome that is consistent with standard open surgical annuloplasty procedures. The system is a single-use device, supplied sterile, non-pyrogenic and ready-for-use.

Indications for Use The Valcare Medical AMEND™ Trans-Septal System is intended for correction of mitral insufficiency in adult male and female patients. It is indicated to treat patients with mitral regurgitation using a percutaneous direct annuloplasty approach. The decision to use an annuloplasty ring is made by the heart center team after reviewing the risks and benefits of alternative procedures and evaluating the patient's mitral valve disease.

AMEND™ Mode of Action

The current standard of care for repair of the mitral valve is open heart surgery that involves a sternotomy, cardioplegia and the use of cardiopulmonary bypass. Surgical repair of the mitral valve is aimed at improving the leaflet coaptation. One of the key changes occurring to the mitral valve resulting in mitral incompetence is the dilation of the valve annulus with the posterior annular segment stretching further posteriorly. This results in an increased anterior- posterior dimension and subsequent reduction of anterior-posterior leaflet coaptation. Ring annuloplasty aims to reduce the enlarged anterior-posterior dimension thereby restoring the native D-shaped annular geometry. The principle of operation for the AMEND™ System is based on this surgical remodeling concept. The rigidity, shape, and attachment mechanism of the AMEND™ implant enables restoration of the native geometry of the mitral annulus and stabilization of its structure. In order to achieve this dimensional reduction, the posterior ring zones are apposed and then attached to the posterior annulus. The entire system is then translated anteriorly to the anterior annulus using the delivery system steering mechanism. Once adequate apposition is achieved anteriorly, the anterior zones are anchored to the anterior annulus. The AMEND™ implant enables restoration of the geometry of the mitral annulus by reducing the mitral valve annulus anterior-posterior distance in order to increase mitral valve leaflet coaptation and reduce regurgitation. After anchoring the posterior side of the implant to the posterior side of the native annulus, the implant is pulled towards the anterior annulus using the Delivery System. The implant is then fixed to the anterior section of the native annulus using the anterior anchors. This results in the reduction of the native valve's anterior- posterior dimension aimed at improving leaflets coaptation and reducing mitral regurgitation.

Benefits It is expected that the Valcare Medical AMENDTM Trans Septal System, while providing a surgical style solution for mitral incompetence with the implantation of annuloplasty ring, it will provide the potential for fewer clinical complications due to the less invasive technique of implantation in comparison with standard open-heart surgery The potential benefits associated with the AMEND™ Trans-Septal System may include a reduction in heart failure symptoms, reduced hospitalizations due to heart failure, improvement in quality of life and potentially improved survival. The potential benefits of the AMENDTM procedure compared to open-heart surgery for mitral valve repair include:

* Decreased surgical risk: bleeding, infection, stroke etc.
* Shorter recovery and hospital stay.
* Reduced mortality and morbidity The potential benefits of the AMENDTM procedure compared to leaflet therapies for mitral valve repair include:
* Annular stabilization as achieved with a surgical annuloplasty ring
* Treatment of annular circularization
* Improved coaptation due to antero-posterior annular dimension reduction
* Allowance of additional therapies to be added acutely or at a later date such as edge to edge, chordal therapies or valve in ring with limited elevation of transvalvular gradient
* Improved reduction of MR due to the ability to replicate the surgical techniques (primarily annuloplasty with secondary therapies as necessary) and not being limited by a single therapeutic mechanism 4.2 Potential Risks During the development of the AMENDTM Trans-Septal System, an extensive Risk Management process has been carried out to identify and control potential risks, in accordance with ISO 14971 Medical devices - Application of risk management to medical devices.

Potential risks associated with the specific design features of the AMENDTM Trans-Septal System have been mitigated and the likelihood of their occurrence has been minimized, as summarized in company's Risk Analysis documentation. In addition, to reduce potential risks related to the study procedure, the following risk mitigations will be implemented in this clinical investigation:

1. Investigators will be selected based on their experience in treating patients with mitral incompetence. CIP- 0001762, Rev. 3.0, 08Jan2025 Page 25 of 70 This document contains information that is the confidential property of Valcare medical Ltd. Neither this document nor the information therein may be reproduced, used or distributed to or for the benefit of any third party without the prior written consent of Valcare Medical Ltd.
2. Investigators will receive extensive training and hands-on experience on the AMENDTM Trans-Septal System.
3. Subjects will be selected based on well- and detailed-defined inclusion/exclusion criteria
4. Enrolment Committee will review patient information and determine the subject's eligibility for the study procedure
5. 6. Echocardiography core lab will evaluate the echocardiograms Safety Monitoring Board will monitor device- and procedure-related serious adverse events

7. Ongoing clinical monitoring. Most of the diagnostic procedures required with respect to the AMENDTM Trans-Septal System are similar to those required for other commercial annuloplasty rings, with the exception of cardiac CT scan that is required for annulus sizing and ring model selection prior to AMEND implantation and involves radiation. The potential risks associated with the AMEND™ procedure can be grouped into two categories: First, potential risks associated with standard cardiac catheterization, including transseptal catheterization, the transesophageal echocardiogram (TEE) probe and administration of general anesthesia. Second, there are potential risks uniquely associated with the use of the AMEND™ Trans Septal System or the presence of the AMEND™ Implant in the body. Potential risks associated with standard cardiac catheterization, TEE probe, and anesthesia, include but are not limited to the following:

* Air embolus
* Allergic reaction (anesthesia, contrast media, nickel alloy, latex)
* Anemia
* Aneurysm or pseudo-aneurysm
* Arrhythmia
* Arterio-venous fistula
* Atrial fibrillation
* Bleeding complications
* Bleeding/haemorrage requiring transfusion
* Cardiac Arrest
* Cardiac perforation
* Cardiac tamponade
* Coagulopathy
* Conversion to standard valve surgery
* Damage to Aortic Valve
* Dizziness
* Emboli (air or thrombus)
* Endocarditis
* Death
* Deep Venous thrombus (DVT)
* Dyspnea
* Edema
* Esophagus irritation;
* Esophagus perforation or stricture;
* Infection
* Infection or hematoma at access site
* Injury of the coronary arteries
* Lymphatic complications
* Low cardiac output
* Mesenteric ischemia
* Multi-system organ failure
* Myocardial infarction
* Nausea/vomiting/digestive discomfort
* Pacemaker dysfunction
* Pain
* Peripheral ischemia
* Pleural effusion
* Pericardial effusion
* Prolonged angina
* Prolonged ventilation
* Pulmonary Congestion
* Pulmonary thrombo-embolism
* Renal insufficiency or failure
* Respiratory failure/atelectasis/pneumonia
* Septicemia
* Skin injury or tissue changes due to exposure to ionizing radiation
* Fever or hyperthermia
* Gastrointestinal bleeding or infarct
* Headache
* Heart arrhythmia
* Heart block
* Heart failure, new or worsening
* Hematoma
* Hemolysis
* Hypotension or hypertension
* Stroke or transient ischemic attack (TIA)
* Thrombosis
* Thromboembolism
* Urinary tract infection
* Vascular trauma, damage, dissection or occlusion
* Vessel spasm Potential risks associated with the use of AMEND™ Trans-Septal System include, but are not limited to, the following:
* Atrial Septal Defect requiring surgical intervention
* Arterio-venous fistula
* Chordal entanglement / rupture
* Damage to Aortic Valve
* Damage to mitral apparatus (valve, leaflets, chordae)
* Device breakage
* Device malfunction
* Device components embolization
* Device thrombosis
* Device dehiscence
* Dislodgement of previously implanted device
* Drug reaction to anti- platelet/anticoagulation agents/contrast media
* Dyskinesia
* Emergency cardiac surgery
* Failure of the anchors over time
* Failure to deliver the device to the intended site
* Irregular leaflet motion (SAM or LVOTO)
* Injury to mitral valve complicating or preventing later surgical repair
* Inappropriate annular remodeling
* Low cardiac output
* Malfunction of the ring due to distortion or fracture of the ring or physical or chemical deterioration of ring components
* Migration, erosion or malposition of the device
* Mitral stenosis
* Perforation or laceration of vessels or damage to tissue
* Recurrent or worsening of Mitral Regurgitation
* Requirement for additional mitral procedure
* Shock, Anaphylactic or Cardiogenic
* Single leaflet device attachment (SLDA)
* Wound dehiscence
* Failure to retrieve system components
* Infection and pain at incision site As with any device undergoing clinical investigation, there may be unforeseeable risks, which are not known at this time. Medical and/or surgical intervention may be required to correct clinical complications associated with the investigational device procedure. All participants will be closely monitored and followed for adverse events at all follow-up visits.

Eligibility criteria: Inclusion Criteria:

1. Patient age \>21
2. The patient will benefit from isolated mitral valve annuloplasty for mitral regurgitation without the need for concomitant cardiovascular surgical procedures such as coronary artery bypass or another valve reconstruction or replacement
3. Symptomatic functional MR≥3+
4. NYHA functional capacity ≥2
5. LV Ejection Fraction \> 30%, LVEDD \< 68 mm
6. The subject meets the anatomical eligibility criteria for available implant size(s)
7. The subject is at high risk for mitral valve surgery as assessed by the center's heart team for mitral procedures.
8. The subject has been stable and on a stable pharmacological regimen for heart failure for at least 1 month prior to inclusion
9. Femoral vein access and transseptal device access is determined to be feasible by the implanting investigator
10. The patient is willing to comply with study procedures and is available to return to the implant center for follow-up visits
11. Informed consent documentation signed and dated confirming that the patient has been adequately informed of all aspects related to his/her participation in the clinical study and is willing to participate.

Exclusion Criteria:

1. The patient has mitral incompetence where an annuloplasty ring will not contribute to its repair 2. Cardiac or non-cardiac major or progressive disease, which in the investigator's discretion produces an unacceptable increased risk to the patient. 3. Life expectancy of less than 12 months 4. The subject is non-operable and is not eligible for TEER, to allow bailout 5. Heavily calcified mitral annulus or leaflets 6. Previous or active endocarditis. 7. Active infection 8. A previously implanted prosthetic aortic valve or mitral intervention 9. Cardiovascular intervention within 30 days prior to study procedure 10. GFR \<30 ml/min 11. The patient has had an ischemic coronary event within 30 days prior to study procedure 12. The patient has clinically significant coronary artery disease requiring re- vascularization 13. The subject is contraindicated to general anesthesia 14. The subject is unable to take anti-platelet or anti-coagulant medications 15. A known allergy to nickel 16. Severe allergy to contrast media 17. Significant right ventricle dysfunction 18. Left atrial thrombus 19. A cerebral vascular event (CVA or TIA) within the past 12 months 20. A mitral valve anatomy which may preclude proper AMEND™ treatment 21. Pulmonary systolic h1. The patient has mitral incompetence where an annuloplasty ring will not contribute to its repair 2. Cardiac or non-cardiac major or progressive disease, which in the investigator's discretion produces an unacceptable increased risk to the patient.

3. Life expectancy of less than 12 months 4. The subject is non-operable and is not eligible for TEER, to allow bailout 5. Heavily calcified mitral annulus or leaflets 6. Previous or active endocarditis. 7. Active infection 8. A previously implanted prosthetic aortic valve or mitral intervention 9. Cardiovascular intervention within 30 days prior to study procedure 10. GFR \<30 ml/min 11. The patient has had an ischemic coronary event within 30 days prior to study procedure 12. The patient has clinically significant coronary artery disease requiring re- vascularization 13. The subject is contraindicated to general anesthesia 14. The subject is unable to take anti-platelet or anti-coagulant medications 15. A known allergy to nickel 16. Severe allergy to contrast media 17. Significant right ventricle dysfunction 18. Left atrial thrombus 19. A cerebral vascular event (CVA or TIA) within the past 12 months 20. A mitral valve anatomy which may preclude proper AMEND™ treatment 21. Pulmonary systolic hypertension (estimated SPAP \> 70 mmHg at rest), determined by echocardiography 22. Pregnant (for women in the reproductive age, blood HCG test result positive) or lactating patient 23. Drug or alcohol abuse 24. Participation in concomitant research studies of investigational products 25. Any planned cardiac surgery or intervention within the next 7 months. 26. Implant or revision of any rhythm management device (cardiac resynchronization therapy (CRT) or cardiac resynchronization therapy device (CRT-D) ) or implantable cardioverter defibrillator within the prior month.

27. Hypotension (systolic pressure \<90 mm Hg) or requirement for inotropic support or mechanical hemodynamic support 28. Status 1 heart transplantation or prior orthotopic heart transplantation 29. Subjects in whom transesophageal echocardiography is contraindicated or high risk

Primary outcomes:
measure: Safety Endpoint: Composite of death (all-cause), stroke, myocardial infarction (MI), or non-elective cardiovascular surgery for device related complications at 30 days.
timeFrame: 30 days
Secondary outcomes:
measure: Secondary Endpoint: Performance Endpoint
timeFrame: 30 days
Other outcomes:
measure: Additional Endpoints
timeFrame: 6 months and 1 year
Locations:
city: Wilmington
country: United States
facility: Valcare Medical Inc.
state: Delaware
Study officials:
affiliation: Valcare Medical
name: Dr. David Meerkin, CMO, MD
role: STUDY_DIRECTOR
References: