Assessing the Impact of TQJ230 in reduction of cardiovascular risk in patients with established CVD and elevated Lp(a)
Scientific Title of Study
A randomized double-blind, placebo-controlled, multicenter
trial assessing the impact of lipoprotein (a) lowering with
TQJ230 on major cardiovascular events in patients with
established cardiovascular disease
6 & 7 floor, Inspire BKC, G Block, BKC Main Road, Bandra Kurla
Complex, Bandra (East), Mumbai – 400051,India
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
Argentina Australia Austria Belgium Brazil Bulgaria Canada Chile China Colombia Czech Republic Denmark Egypt Finland France Germany Greece Guatemala Hong Kong Hungary Iceland India Israel Italy Japan Jordan Lebanon Malaysia Mexico Netherlands Norway Peru Philippines Poland Portugal Republic of Korea Romania Russian Federation Saudi Arabia Singapore Slovakia South Africa Spain Sweden Switzerland Taiwan Thailand Turkey United Kingdom United States of America
Ground Floor, Dept. of Clinical Research
Near Dept. of Oncology
Kuttisahib Road Cheranalloor,
South Chittoor, Kochi, Kerala 682027 Ernakulam KERALA
9746980997
dranil.kumar@asterhospital.com
Dr Dhiman Kahali
B M Birla Heart Research Centre
1/1, National Library Ave, Alipore, Kolkata, West Bengal- 700027 Kolkata WEST BENGAL
9830048563
dhiman.kahali@gmail.com
Dr Hemant Konkane
B.J. Govt. Medical College & Sassoon General Hospital
Department of Cardiology, Main
Building, B.J. Govt.
Medical College and
Sassoon General
Hospital, Near Pune
Railway Station, Pune –
411001 Pune MAHARASHTRA
9619294398
hemantkokane@gmail.com
Dr Sandeep Patil
Bhaktivedanta Hospital and Research Institute
Bhaktivedanta Swami
Marg, Sector 6, Sector
1, Srishti Complex, Mira
Road East, Mira
Bhayandar,
Maharashtra 401107 Thane MAHARASHTRA
9324929490
drsandeep.patil@bhaktivedantahospital.com
Dr Manoj Chopda
Chopda Medicare & Research Centre Pvt. Ltd; Magnum Heart Institute
3/5, Patil Lane No. 1, Laxmi Nagar, Near K.B.H. Vidyalaya, Canada Corner, Nashik-422005, Maharashtra Nashik MAHARASHTRA
9823021613
rush_manoj@yahoo.com
Dr Urmil Shah
CIMS Hospital
Off Science City Rd, Panchamrut Bunglows II, Sola, Ahmedabad, Gujarat -380060 Ahmadabad GUJARAT
P.O Box No.3050, Kochi, Kerala-682018
Ernakulam KERALA
9447011773
drjabi@yahho.co.in
Dr Nagamalesh UM
M.S. Ramaiah Medical College and Hospitals
M.S. Ramaiah Clinical
Research Centre, 1st
floor, M.S. Ramaiah
Advanced Learning
Centre, M S Ramaiah
Nagar, MSRIT Post
Bangalore-560054,
Karnataka Bangalore KARNATAKA
9880135258
nmalesh@yahoo.co.in
Dr Ranjan Shetty
Manipal Hospital
#98, HAL Airport Road,
Bengaluru, Karnataka
560017 Bangalore KARNATAKA
Tikekar Rd, Congress Nagar, Square, Nagpur, Maharashtra 440012
Nagpur MAHARASHTRA
9823078146
maheshfulwani@yahoo.co.in
Dr Ashwani Mehta
Sir Ganga Ram Hospital
Sir Ganga Ram
Hospital Marg, Rajinder
Nagar, New Delhi –
110060 New Delhi DELHI
9811057384
drashwanimehta@gmail.com
Dr Vikrant Vinod Vijan
Vijan Hospital & Research Centre (Vijan Cardiac & Critical Care)
Dr Vijan Hospital Marg,
College Road, Nashik,
Maharashtra 422005,
India Nashik MAHARASHTRA
9822025353
vikrantvijan@hotmail.com
Dr K Sarat Chandra
Virinchi Hospitals
Virinchi Circle, Rd Number 1, Shyam Rao Nagar, Banjara Hills, Hyderabad, Telangana 500034 Hyderabad TELANGANA
9848012212
saratkoduganti@gmail.com
Dr A Ravikanth
Yashoda Hospital
Raj Bhavan Road,Som
ajiguda,Hyderabad-500
082,Telangana
State Hyderabad TELANGANA
9849646335
athuluri113@gmail.com
Dr Prashanth
Yenepoya Medical College Hospital
Dept. of Internal
Medicine, Yenepoya Medical College
Hospital, Yenepoya
University, University
Road, Deralakatte,
Mangalore - 575018,
Karnataka Dakshina Kannada KARNATAKA
Aakash Healthcare Super Seciality Institutional Ethics Committee, Dr. Ashish Agarwal
Approved
Artemis Health Sciences Institutional Ethics Committee, Dr. Manjindar Sandhu
Submittted/Under Review
Bhaktivedanta Hospital ethics Committee, Dr. Sandeep Patil
Approved
Epic Hospital Ethics Committee-Dr Anil Jain
Approved
Ethical Review Board-M.S. Ramaiah Clinical Research Centre,Dr. Nagamalesh UM
Submittted/Under Review
Ethics Committe of S.P Medical College, Dr. D K Agarwal
Submittted/Under Review
Ethics Committee of CIMS Hospital, Dr. Urmil Shah
Approved
Ethics Committee of Manipal Hospitals. Dr. Ranjan Shetty
Submittted/Under Review
Ethics Committee,Jehangir Clinical Developement Centre Pvt.Ltd, Dr. Ajit Mehta
Submittted/Under Review
G KUPPUSAMY NAIDU MEMORIAL HOSPITAL, Dr. Rajpal Abhaichand
Submittted/Under Review
Galaxy Hospital Ethics Committee, Dr. Ajay Kumar Pandey
Approved
IEC Columbia Asia Hospital, Dr. Keshavamurthy
Approved
Insititutional Ethics committee-Clinical Studies, Apollo Hospitals-Dr. Abraham Oommen
Approved
Institiutional Ethics Committee-Maxcure Hospitals. Dr. Sridhar Papani
Approved
INSTITUTIONAL COMMITTEE OF KOVAI DIABETES SPECIALITY CENTRE AND HOSPITAL, Dr. Balamurugan
Submittted/Under Review
Institutional Etghics Committee, Max Superspeciality Hospital, Dr. Gaurav Minocha
Approved
Institutional Ethics Commitee Niramaya Hospitals Private Ltd., Dr. Abhijeet Joshi
Approved
Institutional Ethics Committee Institutional Ethics Committee (IEC-I/II), Dr. Prafulla Kerkar
Submittted/Under Review
Institutional Ethics Committee, Amrita Institute of Medical Sciences, Dr. Rajiv C
Submittted/Under Review
INSTITUTIONAL ETHICS COMMITTEE, CLINICAL STUDIES, Dr. Vivek Bose
Submittted/Under Review
Institutional Ethics Committee, Datta Meghe Institute of Medical sciences, Dr. Gajendra Agarwal
Submittted/Under Review
Institutional Ethics Committee, Dr. Prasad MR
Approved
Institutional Ethics Committee, Dr. Sunil Karna
Approved
Institutional Ethics Committee, Governement Medical College, Dr, Sunil Washimkar
Approved
Institutional Ethics Committee, Governement Medical College, Dr. Neeraj Manikath
Approved
Institutional Ethics committee, LISIE hospital, Dr. Jabir Abdullakutty
Submittted/Under Review
Institutional Ethics Committee, Yashoda Academy of Medical Education and Research, Dr. Ravikanth
Approved
Institutional Ethics Committee-Aster Medcity Hospital, Dr. Anil KUmar
Approved
Institutional Ethics Committee-B M Birla Heart Research Centre, Dr. Dhiman Kahali
Approved
Institutional Ethics Committee-Clinical Studies (IEC-CS), Dr. A Sreenivas Kumar
Approved
Institutional Ethics Committee-Clinical Studies, Dr. Ghosh
Approved
Institutional Ethics Committee-DIVINE HEART & MULTISPECIALITY HOSPITAL, Dr. Nakul Sinha
Submittted/Under Review
Institutional Ethics Committee-Fortis Escorts Heart Institute, Dr. Vishal Rastogi
Submittted/Under Review
Institutional Ethics Committee-King Georges Medical University. Dr. S K Dwivedi
Approved
Institutional Ethics Committee-Shri Mahant Indiresh Hospital, Dr. Tanuj Bhatia
Submittted/Under Review
INSTITUTIONAL HUMAN ETHICS COMMITTEE, KIMS, DR RAMESH NATARAJA SHARMA
Approved
KIMS Ethics Committee, Dr. R K Premchand
Approved
Lalitha Superspecialities Hospital Ethics Committee, Dr. Raghava Sarma
Approved
Magna-Care Ethics Committee, Dr. Chopda
Approved
Manipal Academy of Higher Education Ethics Committee, DR. Tom Devasia
Approved
MGM Ethics Commitee for research omn human subjects (MGM-ECRHS), Dr. Prashant Udgire
Approved
New Era Hospital Ethics Committee, Dr. Nidheesh Mishra
Approved
Research Society B.J.M.C. Pune, Dr. Hemant Konkane
Approved
Rhythm Heart Institute Ethics Committee, Dr. NIrav Bhalani
Approved
Sahyadri Hospitals Ltd Ethics Commitee, Dr. Sathe
Approved
Samvedna Hospital Ethics Committee, Dr. Monica Gupta
Approved
Sengupta Hospital & Research Institute Ethics Committee, Dr. Shantanu Sengupta
Approved
Sir Ganga Ram Hospital Ethics Committee, Dr. Ashwani Mehta
Submittted/Under Review
Vijan Hospital Ethics committee, Dr. Vikrant Vijan
Approved
Virinchi Hospital Institutional Ethics Committee, Dr. K Sarat Chandra
Submittted/Under Review
Virtous Institutional Medical Research Ethics Committee, Dr. Mahesh Fulwani
Approved
Yenepoya Ethics Committee - 1, Dr. Prashanth
Submittted/Under Review
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: I998||Other disorder of circulatory system,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Placebo
Solution for injection, Subcutaneous injection, Solution for injection in prefilled syringe, treatment period 4.5 yrs
Intervention
TQJ230 80 mg
Solution for injection, Subcutaneous injection, Solution for injection in prefilled syringe, treatment period 4.5 yrs
Inclusion Criteria
Age From
18.00 Year(s)
Age To
80.00 Year(s)
Gender
Both
Details
1. Written informed consent must be obtained before any assessment is performed.
2. Male and female 18 to ≤ 80 years of age
3. Lp(a) ≥ 70 mg/dL at the screening visit, measured at the Central laboratory
4. LDL-cholesterol lowering treatment at Randomization as follows:
a. subjects must be on an optimal LDL-C lowering treatment to meet the target LDL-C
level according to local practice/guidelines, or
b. if subjects do not meet the target LDL-C level according to local practice/guidelines,
they should be treated with the highest tolerated doses of statins and/or with other
optimized LDL-lowering therapy (e.g. ezetimibe, cholesterol absorption inhibitor,
fibrate, PCSK9 inhibitor), or
c. if subjects have a contraindication or do not tolerate statin treatment, they must be
treated with other optimized LDL-lowering therapy (e.g. ezetimibe, cholesterol
absorption inhibitor, fibrate, PCSK9 inhibitor) according to local practice/guidelines
5. At the randomization visit subjects must be optimally treated for other CV risk factors
according to local practice/guidelines
ExclusionCriteria
Details
1. Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) ≥ 160 mmHg
and/ or diastolic blood pressure (DBP) ≥ 100 mmHg (mean of 3 measurements for each
SBP and DBP assessment) at the Screening visit.
2. Treatment with niacin in the 3 months before the screening visit; niacin in multi-vitamins
is allowed
3. Treatment with stable dose of a PCSK9 inhibitor (evolocumab, alirocumab) for less than
12 weeks before Randomization
4. Treatment with lipoprotein apheresis, or already planned to start lipoprotein apheresis
during the study
5. Within 3 months of screening and between Screening visit and Randomization visit (Day
1): myocardial infarction, stroke, coronary or lower limb re-vascularization, major cardiac
or non-cardiac surgery. The subjects can be re-screened 3 months after the relevant
event/procedure.
6. Planned or expected cardiac, cerebrovascular or peripheral artery surgery or coronary revascularization
after Randomization visit (Day 1)
7. Heart failure New York Heart Association (NYHA) class IV at Screening visit or
at Randomization visit (Day 1)
8. History of hemorrhagic stroke or other major bleeding, or if occurring between Screening
visit and Randomization visit
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Demonstrate the superiority of TQJ230 compared to placebo in reducing the risk of expanded MACE (cardiovascular
death, non-fatal MI, non-fatal stroke and urgent coronary re-vascularization
requiring hospitalization) in the overall study population with established CVD
and (Lp(a) ≥ 70 mg/dL) and/or Lp(a) ≥ 90 mg/dL.
Time to the first occurrence of CEC confirmed
expanded MACE (cardiovascular death, nonfatal
MI, non-fatal stroke and urgent coronary
re-vascularization requiring hospitalization) in a
population of patients with elevated Lp(a) ≥ 70
mg/dL and in a subpopulation of patients
with elevated Lp(a) ≥ 90 mg/dL
Secondary Outcome
Outcome
TimePoints
Time to the first occurrence of the clinical endpoint committee confirmed composite endpoint of major adverse cardiovascular events (CV death, non-fatal MI, and non-fatal stroke)
Demonstrate the superiority of TQJ230 compared to placebo in reducing the risk of the MACE composite of CV death, nonfatal MI and non-fatal stroke.
4 years
Time to the first occurrence of the clinical endpoint committee confirmed composite endpoint of coronary heart disease: coronary heart disease death, non-fatal MI, urgent coronary re-vascularization requiring hospitalization
Demonstrate the superiority of TQJ230 compared to placebo in reducing the risk of the composite of coronary heart disease (CHD) outcomes: death due to CHD, nonfatal MI and urgent coronary revascularization requiring hospitalization.
4 years
Number of participants with confirmed all-cause death
Evaluation by clinical endpoint committee the rate of all-cause death
4 years
Target Sample Size
Total Sample Size="7680" Sample Size from India="450" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a pivotal phase 3 study designed to support an indication for the reduction of cardiovascular risk in patients with established CVD and elevated Lp(a)