Evaluation of a Sirolimus Eluting Bioadaptor as Compared to a Zotarolimus Eluting Stent in De Novo Native Coronary Arteries ELX-CL-1805
Phase: NA
Conditions: Coronary Artery Disease, Coronary Artery Stenosis, Coronary Disease, Coronary Stenosis
Sponsor: Elixir Medical Corporation

 
 
BIOADAPTOR RCT Protocol Synopsis 
NCT04192747 
 
 
 
Study Title: Evaluation of a Sirolimus Eluting Bioadaptor as Compared to a Zotarolimus Eluting 
Stent in De novo Native Coronary Arteries 
NCT Number: NCT04192747 
Protocol Number: ELX-CL-1805 
Date: 20 July 2022 
Revision: 1.4 (Japan) and 1.4.1 (Europe) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confidential – This document is property of Elixir Medical Corporation 

 
 
BIOADAPTOR RCT Protocol Synopsis 
NCT04192747 
 
 
Title 
Evaluation of a Sirolimus Eluting Bioadaptor as Compared to a 
Zotarolimus Eluting Stent in De novo Native Coronary Arteries (referred to 
as “Bioadaptor RCT”) 
Objective 
The objective of this study is to verify the safety and efficacy of the 
investigational device (ELX1805J) for the treatment of ischemic heart 
disease due to de novo, native coronary artery lesions 
Study design 
A prospective, multicenter, randomized (1:1; DynamX Bioadaptor 
(ELX1805J): Resolute Onyx), single-blind study, registering approximately 
444 subjects at approximately 35 sites within Japan, Europe, and New 
Zealand to be conducted in two parallel cohorts. The combined Japan 
Bioadaptor RCT data and European Bioadaptor RCT data are intended to 
serve as the pivotal trial to support the regulatory approval in Japan with 
the Pharmaceuticals and Medical Devices Agency (PMDA). 
 
Up to 2 de novo lesions located in 2 separate native coronary arteries 
designated as target lesions may be treated. The target lesion(s) must 
measure between 2.25 mm and 4.0 mm in diameter and ≤ 34 mm in length, 
to be covered by a single ELX1805J Bioadaptor or a single control device. 
Patients should not be randomized until after satisfactory pre-dilatation of 
the target lesion has been performed.   
 
A non-target lesion may be treated if located in separate epicardial vessel 
(RCA, LCX or LAD) using an approved ‘olimus drug eluting stent 
provided the treatment of this non-target lesion is done prior to the 
treatment of the target lesion(s), and the treatment of the non-target lesion 
is considered successful. The segment should be located such that any 
injury that might occur during intervention can be clearly attributable to 
that treated segment. 
 
Japanese Cohort (222 subjects) & European/New Zealand Cohort (222 
subjects) The study is composed of two cohorts, i.e., the Japanese cohort 
and the European/New Zealand cohort. For each cohort, at least 222 
subjects are randomly allocated in a 1:1 ratio to either the test or control 
arm. All subjects will receive follow-up clinical assessments at 1, 6 and 12 
months and every year for 5 years thereafter. Additionally, imaging follow-
up with IVUS and IVUS + OCT are collected in the following imaging 
subsets. Data from the Bioadaptor RCT European Cohort will be pooled with 
the data from the Bioadaptor RCT Japan Cohort to support primary and 
secondary endpoints. The primary endpoint analysis will be performed using 
the Intent-to-Treat (ITT) population on all subjects at the point of 
randomization. 
 

 
 
BIOADAPTOR RCT Protocol Synopsis 
NCT04192747 
 
 
IVUS Imaging Subset (80 subjects in the Japanese cohort) 
The IVUS imaging subset of approximately 80 subjects undergo 
angiography and IVUS assessments at baseline and 12 month follow-up. 
IVUS + OCT Imaging Subset (20 subjects in the Japanese cohort) 
The IVUS + OCT imaging subset of approximately 20 subjects undergo 
angiography, IVUS + OCT assessments at baseline and 12 month follow-
up. 
 
Single-group study (referred to as PK substudy)  
Up to 2 de novo lesions located in 2 separate native coronary arteries 
designated as target lesions may be treated.  The PK study will enroll 8 
Japanese subjects and is being conducted to assess the blood 
pharmacokinetics of Sirolimus eluted from the ELX1805J Bioadaptor 
implanted in patients. PK measurement will be conducted at pre-treatment, 
10 minutes, 30 minutes, 1, 2, 4, 6, 12, 24, 72 hours, and 7 days. In addition, 
all subjects will undergo clinical follow-up assessments at 1, 6 and 12 
months and every year for 5 years thereafter. 
Enrollment/ 
Number of Sites 
Approximately 444 subjects will be enrolled at up to 35 centers in Japan and 
Europe/New Zealand. 
Planned:  
Japanese cohort: 222 
European/New Zealand cohort: 222  
PK substudy: 8 
Study Devices 
Investigational device: ELX1805J (Japan); DynamX Sirolimus Eluting 
Coronary Bioadaptor System (Europe/NZ) 
 
Control device: Resolute Onyx Zotarolimus Eluting Coronary Stent System 
(Medtronic Japan Co., Ltd. or Medtronic per the applicable geography) 
 
PK study: Subjects are to receive the ELX1805J device 
 
Clinical 
Endpoints:   
 
Primary Endpoint:  Target lesion failure (TLF) assessed at 12 months.  
TLF is a composite endpoint defined as cardiovascular death, target-
vessel MI, and clinically-indicated target lesion revascularization (CI-
TLR) 
 
Secondary Endpoints:  
Efficacy endpoints 
• Acute success rates: 
Lesion success rate, device success rate, procedure success rate 
 
 

 
 
BIOADAPTOR RCT Protocol Synopsis 
NCT04192747 
 
 
Clinical endpoints 
Measured at 30 days, 6 months, 12 months, 2, 3, 4 and 5 years: 
• 
TLF 
• 
Patient Oriented Clinical Endpoint: Overall cardiovascular 
outcomes from the patient’s perspective.  This endpoint is a 
composite endpoint that includes all-cause mortality (cardiac and 
non-cardiac), stroke, MI (target vessel and non-target vessel) and 
revascularization (target vessel and non-target vessel) 
• 
A composite of all-cause mortality, MI (target vessel or non-target 
vessel) and revascularization (target vessel or non-target vessel) 
• 
Composite of cardiovascular death, target vessel myocardial 
infarction (TV-MI)*, or clinically-indicated target vessel 
revascularization (CI-TVR) 
• 
Composite of cardiovascular death, stroke, MI (target vessel or 
non-target vessel) and revascularization (target vessel or non-
target vessel) 
• 
Composite of cardiovascular death, MI (target vessel or non-target 
vessel) and revascularization (target vessel or non-target vessel) 
• 
Clinically-indicated target lesion revascularization (CI-TLR)TLR 
• 
Target vessel revascularization (TVR) 
• 
Clinically-indicated TVR (CI-TVR) 
• 
Revascularization (target vessel or non-target vessel) 
• 
Q-wave MI 
• 
Non Q-wave MI 
• 
MI (target vessel or non-target vessel) 
• 
Target vessel MI 
• 
Cardiovascular death 
• 
All-cause death 
• 
Composite of cardiovascular death or target vessel MI 
• 
Composite of all-cause death or MI(target vessel or non-target 
vessel) 
• 
Composite of all-cause death, MI(target vessel or non-target 
vessel), or TVR 
• 
Composite of probable or definite stent thrombosis‡ 
• 
Probable stent thrombosis‡ 
• 
Definite stent thrombosis‡ 
* Defined as myocardial infarction not clearly attributed to a non-target 
vessel  
‡ Defined as per the Academic Research Consortium (ARC-2) criteria 
 
Imaging 
Endpoints 
QCA endpoints: 
• Acute recoil  
• Late lumen loss (in-stent and in-segment) at 12-month follow-up 

 
 
BIOADAPTOR RCT Protocol Synopsis 
NCT04192747 
 
 
QCA , IVUS, 
and OCT 
• Change in vessel angulation from baseline, post-stent and 12-
month follow-up 
• MLD  post-procedure and 12 months 
• % DS post-procedure and 12 months 
 
IVUS endpoints: 
• Change in mean lumen area from post-procedure to 12-month 
follow-up 
• In-stent % neointimal obstruction at 12-month follow-up 
• In-stent late lumen loss at 12-month follow-up 
• Acute, persistent and late stent malapposition 
 
OCT Endpoints:  
• % Strut coverage 
• Neointimal thickness 
• Vessel Pulsatility - % change in Lumen Area and Device Area 
during systole and diastole by stationary OCT 
• Additional parameters may be assessed 
 
Key Inclusion 
Criteria 
 
Patients who meet all of the following criteria are eligible: 
• Patient must be ≥ 20 years of age. 
• Patient must have evidence of myocardial ischemia (e.g., stable or 
unstable angina, silent ischemia, positive functional study or 
electrocardiogram (ECG) changes consistent with ischemia) 
• Patients who are able to take dual anti-platelet therapy for 1 year 
following the index procedure and anticoagulants prior to/during 
the index procedure 
• The subject is an acceptable candidate for Percutaneous 
Transluminal Coronary Angioplasty (PTCA), stenting, and 
emergent Coronary Artery Bypass Graft (CABG) surgery. 
• The subject or subject’s legally authorized representative has been 
informed of the nature of the study and agrees to its provisions and 
has provided written informed consent as approved by the 
Institutional Review Board or Ethics Committee of the respective 
clinical site. 
• Women of childbearing potential with a negative pregnancy test 
within 7 days and women who are not pregnant or nursing  
• Patient must agree to undergo all clinical study required follow up 
visits, angiograms, and imaging testing  
• Patient must agree not to participate in any other clinical research 
study for a period of one year following the index procedure 
 
 

 
 
BIOADAPTOR RCT Protocol Synopsis 
NCT04192747 
 
 
Angiographic inclusion criteria- Target Lesion/Vessel 
 
Confirmed in QCA assessment: 
• Target lesion(s) must be de novo and located in a native coronary 
artery with a vessel mean diameter of ≥ 2.25 and ≤ 4.0 mm assessed  
Confirmed by visual assessment: 
• Target lesion(s) must be in a major artery or branch with a visually 
estimated stenosis of ≥ 50% and < 100% with a TIMI flow of >1. 
When two target lesions are treated, they must be located in separate 
major epicardial vessels 
• The visually estimated target lesion length is ≤ 34 mm and must be 
able to be covered by a single 14/15/18/23/28/32/38 mm ELX1805J 
stent and have at least 2 mm of healthy vessel on either side, OR 
• The visually estimated target lesion length is ≤ 34 mm and must be 
able to be covered by a single 15/18/22/30/34/38 mm ZES stent 
respectively and have at least 2 mm of healthy vessel on either side 
• The lesion(s) must be successfully pre-dilated prior to enrollment 
• Mandatory pre-dilatation includes the use of 2 orthogonal views to 
confirm lesion inclusion and exclusion criteria. Successful pre-
dilatation of a minimum of 1 Target Lesion, defined as no waist in 
the inflated pre-dilatation balloon (using two orthogonal views) 
with a pre-dilatation balloon diameter size approximately 0.25 mm 
smaller than reference vessel diameter but not more than 0.5 mm 
smaller than the reference vessel diameter. A residual diameter 
stenosis prior to study device implantation by visual estimate is 
recommended to be <30%. 
• Percutaneous intervention of lesions in a non-target vessel if: 
o Not part of another clinical investigation 
o ≥ 30 days prior to the study index procedure 
o ≥ 6 months after the study index procedure (planned) 
• Percutaneous intervention of lesions located in the target vessel if: 
o Not part of a clinical investigation 
o ≥ 6 months prior to the study index procedure 
o ≥ 12 months after the study index procedure (planned) 
o Previous intervention was distal to and >10 mm from the 
target lesion 
 
Additional inclusion Criteria for PK study 
Patients participating in PK study may be treated with only ELX1805J 
Key Exclusion 
Criteria 
 
Patients must not have any of the following:  
• The patient was diagnosed with an acute myocardial infarction 
within the past 72 hours and the CK and CKMB have not returned 
to normal (or cTn >15x ULN) and the patient is experiencing 
clinical symptoms indicative of ongoing ischemia  

 
 
BIOADAPTOR RCT Protocol Synopsis 
NCT04192747 
 
 
• Patient has a known hypersensitivity or contraindication to aspirin, 
both heparin and bivalirudin, clopidogrel, prasugrel or ticagrelor, 
cobalt, nickel, chromium, molybdenum, PLLA polymers or 
contrast sensitivity that cannot be adequately pre-medicated 
• Patients with a history of allergic reaction or serious 
hypersensitivity to drugs exhibiting interactions with sirolimus, 
zotarolimus, everolimus, tacrolimus, temsirolimus, biolimus and 
other rapamycin, derivatives or analogues) or similar drugs 
• Elective surgery is planned within the first 6 months after the 
procedure that will require discontinuing either aspirin or 
clopidogrel or other P2Y12 inhibitors 
• Patient presenting with chronic (permanent) atrial or ventricular 
arrhythmia or current unstable ventricular arrhythmias 
• Patient has a known left ventricular ejection fraction (LVEF) < 
30% 
• Patient has received a heart or other organ transplant or is on a 
waiting list for any organ transplant 
• Patient has a malignancy that is not in remission. 
• Patient is receiving immunosuppression therapy other than 
steroids and has known immunosuppressive or autoimmune 
disease (e.g. human immunodeficiency virus, systemic lupus 
erythematosus etc.) 
• Patient is receiving chronic anticoagulation therapy (e.g., heparin, 
coumadin) that cannot be stopped and restarted according to local 
hospital standard procedures 
• Patient has a platelet count < 100,000 cells/mm3 or > 700,000 
cells/mm3, a WBC of < 3,000 cells/mm3, or documented or 
suspected to have cirrhosis of Child-Pugh ≥ Class B within 7 days 
before study procedure  
• Patient has known renal insufficiency (e.g., serum creatinine level 
of more than 2.5 mg/dL within 7 days before study procedure, or 
patient on dialysis) 
• Patient has a history of bleeding diathesis or coagulopathy or will 
refuse blood transfusions 
• Patient has had a cerebrovascular accident (CVA) or transient 
ischemic neurological attack (TIA) within the past six months 
• Patient has had a significant GI or urinary bleed within the past six 
months 
• Patient has severe symptomatic heart failure (i.e., NYHA class IV) 
• Patient has a medical condition that precludes safe 6 French sheath 
insertion 
• Patient has other medical illness or known history of substance 
abuse (alcohol, cocaine, heroin etc.) that may cause non-

 
 
BIOADAPTOR RCT Protocol Synopsis 
NCT04192747 
 
 
compliance with the clinical study plan, confound the data 
interpretation or is associated with a limited life expectancy (i.e., 
less than one year) 
• Patient is already participating in another clinical research study 
which has not reached the primary endpoint (long-term follow-up 
is not an exclusion) 
• Other patients whom primary investigator or sub-investigator 
determined to be ineligible for this clinical study 
 
Angiographic exclusion criteria 
• Patients with bypass graft to the target vessel or lesion is located in 
a bypass graft 
• Patients with stent implanted within 10 mm of proximal or distal 
end of target lesion 
• Patients with a target lesion involving a bifurcation of which the 
side branch will be jailed by the struts and: 
• Side branch > 2.5 mm in diameter 
• Side branch requires planned predilatation (including Kissing 
Balloon Technique), or Side branch has an ostial lesion or lesion 
with > 50% stenosis 
• Patients suspected or confirmed with the QCA analysis of having 
stenotic lesion of more than 50% in target vessel in addition to 
target lesion 
• Patients with target lesion in ostia located within 5 mm of origin of 
LAD, LCX or RCA 
• Patients with stenotic lesion in left main trunk 
• Patients with target lesion that is a chronic total occlusion (CTO) 
or ≤ TIMI 1 coronary flow in the target vessel 
• Patients with target vessel that contains thrombus as indicated in 
pre-procedure angiographic, IVUS or OCT images 
• Excessive tortuosity ≥ two 45° angles or extreme angulation (≥ 
90°) proximal to or within the target lesion 
• Patients with target vessel that has moderate to severe calcification 
that prevents complete angioplasty balloon (POBA with non-
compliant balloon, or scoring balloon,) inflation or requires other 
devices such as rotational atherectomy, rotablator. 
• Patients with dissection of Grade A or B that cannot be covered 
(including 2 mm distal to the dissection) with a single study device 
or with dissection of Grade C or higher  
• Patients with 2 or more target lesions on 1 branch or target lesions 
on 3 branches that need to be treated during study procedure 
• Target lesion involves a myocardial bridge 

 
 
BIOADAPTOR RCT Protocol Synopsis 
NCT04192747 
 
 
Additional Exclusion Criteria for PK study 
• Patients with following criteria 
o 
Patient with PCI within 180 days before study procedure 
o 
Patient with plan to have staged PCI within 90 days after 
study procedure 
o 
Patients who have non-target lesion 
 
Statistical 
Methods 
The analysis of primary endpoint and secondary endpoints are performed 
using the Intention-To-Treat (ITT) population. The analysis of secondary 
clinical endpoints are conducted with the Per-Treatment Evaluable (PTE) 
population in addition to the ITT population. 
Analysis of the Primary Endpoint 
Study success is defined as successful rejection of the null 
hypothesis for the primary endpoint. The primary endpoint for 
the study is TLF at 12 months post treatment. The primary 
endpoint will be evaluated using the ITT population for study 
success and may also be carried out on the PTE population. The 
null hypothesis for this study is that the ELX1805J arm will have a 
12-month TLF rate that exceeds that of the control device arm by at 
least a pre-specified margin of 6 (delta). The alternative hypothesis 
is that the ELX1805J arm will have a 12-month TLF rate that is 
no more than that of the control device, or exceeds that of the 
control device but by less than 6. Rejection of the null hypothesis 
will signify that the ELX1805J is non-inferior to the control device 
with regard to 12-month TLF. The null hypothesis (Ho) and the 
alternative hypothesis (Ha) can be expressed as below: 
Ho: πA≥πC + 8.6%  
Ha: πA <πC + 8.6% 
Here, πA is a true TLF Rate of investigational device, and πC is a true 
TLF Rate of control device. 
Based on non-inferiority test for an endpoint that follows 
binomial distribution, in addition to difference between TLF rates 
at 12 months for 2 groups (investigational device - control device), 
one-sided 95% confidence interval of the difference in TLF is 

 
 
BIOADAPTOR RCT Protocol Synopsis 
NCT04192747 
 
 
calculated. Tests are conducted using normal approximation of 
binomial distribution. When the upper limit of this confidence 
interval is less than 8.6% (delta of non-inferiority), the null 
hypothesis is rejected, confirming non-inferiority of 
investigational device compared to control device for TLF rate at 
12 months. This primary analysis will be conducted using the ITT 
population. Handling of missing data is described in section 3.4.1. 
In addition, Kaplan-Meier curve for time till first event considered 
to be TLF will be done. If multiple TLF occurred in same case, 
occurrence date of the first TLF is the occurrence date of TLF. 
During study procedure, up to 2 lesions in different epicardial vessels 
may be treated with the assigned study device. When there are 
multiple TLF, in a single case, it is counted per case (counted as 
single incidence). 
Analysis of the Secondary Endpoints 
Time-dependent response variables can be expressed using Kaplan-
Meier curve, and differences in these variables between groups are 
tested using log-rank test. Data for all categorical endpoints (e.g., 
TLF rate at a specific time point, etc.) are shown with number of 
patients, percentage and Clopper-Pearson's exact 95% confidence 
interval. Differences between treatment groups are shown using 
95% confidence interval of the difference. Comparison of imaging 
corelab endpoints (QCA, IVUS and OCT) in the Japanese cohort 
will also use the difference between treatment groups and the 95% 
confidence interval of the difference. Analyses of clinical 
secondary endpoints are conducted with the PTE population in 
addition to the ITT population. 
Sponsor 
Elixir Medical Corporation 
920 N McCarthy Blvd, Suite 100  
Milpitas, CA 95035 
USA