IonMAN II Trial- Early Feasibility Study of the IoNIR Ridaforolimus-Eluting Coronary Stent System

This is a prospective, multi-center, single-arm, open-label, early feasibility study to provide preliminary evidence for the safety and efficacy of the novel IoNIR stent system

Study Overview

• Status: Not yet recruiting
• Conditions: Coronary Artery Disease; Coronary Stenosis
• Intervention / Treatment: Device: IoNIR Ridaforolimus-Eluting Coronary Stent System

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Brenda Koltun Reuven; Phone Number: +972542666688; Email: brendak@medinol.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years.
2. Patient with an indication for PCI including NSTEMI (biomarkers have peaked or are falling), angina (stable or unstable), silent ischemia (in absence of symptoms a visually estimated target lesion diameter stenosis of ≥70%, a positive non-invasive stress test, or FFR ≤0.80, Pd/Pa≤0.91or iFR, RFR, DFR, DPR≤0.89 must be present).
3. Non-target vessel PCIs are allowed if performed >30 days prior to index procedure.
4. Patient or legal guardian is willing and able to provide informed written consent and comply with follow-up visits and testing schedule.
5. Staged procedures are allowed as long as the IoNIR stent is implanted in the last procedure and at least 30 days have elapsed between the previous procedure and the IoNIR PCI.
6. A maximum of two vessels and up to two lesions may be treated (two lesions separated by up to 10mm that can be covered by a single stent are considered as one lesion).
7. Lesions requiring scoring/cutting and/or rotational/orbital atherectomy and/or intra-vascular lithotripsy are allowed.
8. Overlapping stents are allowed.
9. Target lesion must be in a major native coronary artery with visually estimated diameter of ≥2.5 mm to ≤4.0 mm and lesion length of up to 40 mm, and appropriate size IoNIR stents are available.

Exclusion Criteria:

• 1. ST Segment Elevation MI within past 30 days. 2. NSTEMI with biomarkers that have not peaked. 3. Significant valvular disease or planned valvular intervention. 4. PCI within the 30 days preceding the baseline procedure. 5. PCI in the target vessel within 12 months of the baseline procedure. 6. Planned staged procedures (coronary or valvular), where the study stent is implanted in the first stage.

  7. Brachytherapy in conjunction with the baseline procedure. 8. Known history of stent thrombosis. 9. Cardiogenic shock (defined as persistent hypotension (systolic blood pressure <90 mm/Hg for more than 30 minutes) or requiring pressors or hemodynamic support, including IABP.

  10. Subject is intubated. 11. Known LVEF <30%. 12. Contraindication to DAPT for 6 months in non-ACS patients and 12 months in ACS patients (including planned surgeries that cannot be delayed).

  13. Subject has an indication such as atrial fibrillation for oral anticoagulation/prolonged heparinization (i.e., use of coumadin/DOAC (NOAC) or prolonged enoxaparin/heparin therapy is not allowed).

  14. eGFR <60 mL/min. 15. Hemoglobin <10 g/dL. 16. Platelet count <100,000 cells/mm3 or >700,000 cells/mm3. 17. White blood cell (WBC) count <3,000 cells/mm3. 18. Clinically significant liver disease. 19. Active peptic ulcer or active bleeding from any site. 20. Bleeding from any site within the previous 8 weeks requiring active medical or surgical attention.

  21. If femoral access is planned, significant peripheral arterial disease which precludes safe insertion of a 6F sheath.

  22. History of bleeding diathesis or coagulopathy and patients that refuse blood transfusions.

  23. Cerebrovascular accident or transient ischemic attack within the past 6 months, or any permanent neurologic defect attributed to CVA.

  24. Known allergy to the study stent components (cobalt, nickel, chromium, molybdenum, platinum, PDLG, PLC, or limus drugs (ridaforolimus, zotarolimus, tacrolimus, sirolimus, everolimus, or similar drugs or any other analogue or derivative or similar compounds).

  25. Known allergy to protocol-required concomitant medications such as aspirin, or P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor), heparin and bivalirudin, or iodinated contrast allergy that cannot be adequately pre-medicated.

  26. Any co-morbid condition that may cause non-compliance with the protocol (e.g., dementia, substance abuse, etc.) or reduced life expectancy to <24 months (e.g., cancer, severe heart failure, severe lung disease).

  27. Patient is participating in or plans to participate in any other investigational drug or device clinical trial that has not reached its primary endpoint.

  28. Women who are pregnant or breastfeeding. 29. Women who intend to become pregnant within 12 months after the baseline procedure (women of child-bearing potential who are sexually active must agree to use a reliable method of contraception from the time of screening through 12 months after the baseline procedure).

  30. Patient has received an organ transplant or is on a waiting list for an organ transplant.

  31. Patient is receiving or scheduled to receive chemotherapy within 30 days before or any time after the baseline procedure.

  32. Patient is receiving oral or intravenous immunosuppressive therapy or has known life-limiting immunosuppressive or autoimmune disease (e.g., HIV). Corticosteroids are allowed.

  33. Complex lesions including severely calcified lesions, presence of visible thrombus, chronic total occlusions, bifurcation lesions (side branch diameter ≥2.0 mm), tortuous lesions, restenotic lesions, left main lesions, ectasia, aneurysm and any bypass graft lesions.

  34. Another lesion in a target or non-target vessel (including all side branches) is present that requires or has a high probability of requiring PCI within 12 months after the baseline procedure.

  35. Ostial lesions within 3 mm of origin of LAD, LCx, lesions in the LM.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IoNIR Ridaforolimus-Eluting Coronary Stent; IoNIR Ridaforolimus-Eluting Coronary Stent System	Device: IoNIR Ridaforolimus-Eluting Coronary Stent System; The IoNIR Ridaforolimus-Eluting Coronary Stent System is a sterile single-use device/drug combination product, comprised of a cobalt chromium (CoCr) alloybased stent coated with a bioresorbable polymer mesh which is embedded with drug, mounted on a Rapid Exchange (RX) delivery system.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In-stent Late Loss (LL)	In-stent Late Loss (LL) at 13 months assessed by quantitative coronary angiography (QCA) (Minimal Lumen Diameter (MLD) post-procedure - MLD follow-up (US patients only))	13 months
Target Lesion Failure	Target Lesion Failure (composite of cardiovascular death, target vessel-related myocardial infarction, or ischemia-driven target lesion revascularization)	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse cardiac events	Major adverse cardiac events (MACE; the composite rate of cardiovascular death, any MI or ischemia-driven target lesion revascularization (TLR)).	30 days, 6 months, 1,2,3,4,5 years
All-cause mortality	All-cause mortality	30 days, 6 months, 1,2,3,4,5 years
Cardiovascular death	Cardiovascular death	30 days, 6 months, 1,2,3,4,5 years
Myocardial infarction	Myocardial infarction	30 days, 6 months, 1,2,3,4,5 years
Target vessel related MI	Target vessel related MI	30 days, 6 months, 1,2,3,4,5 years
Target Lesion Failure	Target Lesion Failure	6 months, 2, 3, 4, 5 years
Ischemia-driven TLR	Ischemia-driven TLR	30 days, 6 months, 1, 2, 3, 4, 5 years
Ischemia-driven Target Vessel Revascularization	Ischemia-driven Target Vessel Revascularization	30 days, 6 months, 1, 2, 3, 4, 5 years
Stent thrombosis	Stent thrombosis (ARC-2 definite and probable).	30 days, 6 months, 1, 2, 3, 4, 5 years
Acute Device Success	Acute Device Success (successful crossing and deployment with residual QCA DS <30%)	index procedure
Luminal gain	Luminal gain (MLD post-procedure - MLD pre-procedure)	13 months - US patients only
In-stent MLD	In-stent MLD	13 months - US patients only
In-segment MLD	In-segment (+5mm from the stent edges) MLD	13 months - US patients only
In-segment late loss	In-segment (+5mm from the stent edges) late loss	13 months - US patients only
Proximal late loss	Proximal late loss (+5 mm from proximal stent edge)	13 months - US patients only
Distal late loss	Distal late loss (+5 mm from proximal stent edge)	13 months - US patients only
In-stent and in-segment Binary Restenosis	In-stent and in-segment Binary Restenosis	13 months - US patients only
OCT-determined inner layer percent neointimal hyperplasia volume	OCT-determined inner layer percent neointimal hyperplasia volume	13 months - US patients only
In-stent MLA	In-stent MLA	13 months - US patients only
In-segment minimum lumen area (MLA)	In-segment minimum lumen area (MLA)	13 months - US patients only
Minimal stent area (MSA)	Minimal stent area (MSA)	13 months - US patients only
Stent expansion	Stent expansion	13 months - US patients only
Edge dissection	Edge dissection	13 months - US patients only
% NIH at the MLA	% NIH at the MLA	13 months - US patients only
% Area stenosis at the MLA	% Area stenosis at the MLA	13 months - US patients only
Luminal gain (MLA post-procedure - MLA pre-procedure)	Luminal gain (MLA post-procedure - MLA pre-procedure)	13 months - US patients only
In-stent late loss MLA	In-stent late loss MLA	13 months - US patients only
In-segment (+5 mm from the stent edges) late loss (MLA).	In-segment (+5 mm from the stent edges) late loss (MLA).	13 months - US patients only
Proximal late loss (+5 mm from proximal stent edge) (MLA)	Proximal late loss (+5 mm from proximal stent edge) (MLA)	13 months - US patients only
Distal late loss (+5 mm from distal stent edge) (MLA)	Distal late loss (+5 mm from distal stent edge) (MLA)	13 months - US patients only
Intraluminal mass at least 0.2 mm beyond the luminal edge of a strut	Intraluminal mass at least 0.2 mm beyond the luminal edge of a strut (Intraluminal mass attached to the vessel is defined as an irregularly shaped structure in contact with the luminal contour, a free intraluminal mass is defined as an isolated structure in the lumen without contact to the vessel wall)	13 months - US patients only
Malapposition	Malapposition (stent struts clearly separated from the vessel wall (lumen border/plaque surface) without tissue behind the struts with a distance from the adjacent intima of ≥0.2 mm not associated with any side branch)	13 months - US patients only
% Covered strut	% Covered strut (NIH thickness of >0 μm).	13 months - US patients only
% Healthy covered strut	% Healthy covered strut (NIH thickness≥40 μm).	13 months - US patients only
Peri-strut low intensity area	Peri-strut low intensity area (peri-strut region of homogeneous lower intensity observed without signal attenuation).	13 months - US patients only
Healing score	Healing score (defined as % intraluminal mass [=intraluminal mass volume/stent volume] ×4 + % malposed and uncovered struts ×3 + (% uncovered struts alone ×2 + % malposed struts alone ×1) at 13 months.; Intraluminal mass (+4).; Malposed and uncovered struts (+3).; Uncovered struts alone (+2).; Malposed struts alone (+1).	13 months - US patients only

Collaborators and Investigators

• Sponsor: Medinol Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: October 1, 2023
• First Submitted That Met QC Criteria: October 1, 2023
• First Posted (Actual): October 6, 2023

Study Record Updates

• Last Update Posted (Actual): October 13, 2023
• Last Update Submitted That Met QC Criteria: October 11, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Coronary Stenosis
• Other Study ID Numbers: IoNIR-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes