The cardiovascular safety of cagrilintide 2.4 mg s.c. in combination with semaglutide 2.4 mg s.c. (CagriSema 2.4 mg/2.4 mg s.c.) once-weekly in participants with established cardiovascular disease
Poland Argentina Australia Brazil Bulgaria Canada Colombia Denmark France Germany India Ireland Italy Japan Mexico Netherlands Serbia South Africa Spain Turkey United Kingdom United States of America
Chellaram Diabetes Institute, 1st floor,Lalani Quantum, Bavdhan (Budruk), Pune-Bangalore National
Highway No. 4. Pune-411021, Maharashtra, India.
Pune MAHARASHTRA
919689287337
uagcdi@cdi.org.in
Dr Manojkumar Bhavarilal Chopada
Chopda Medicare and Research Centre Pvt Ltd
Ground floor OPD, Department of Cardiology, 3-5, Patil Lane No. 1, Laxmi Nagar, Near K.B.H. Vidyalaya, Canada Corner, Nashik-422005, Maharashtra, India Nashik MAHARASHTRA
9823021613
drchopdamanoj@gmail.com
Dr Jubbin Jagan Jacob
Christian Medical College & Hospital
Department of Medicine, Brown Road, Ludhiana, Punjab, India – 141008 Ludhiana PUNJAB
9915281219
jubbin.jacob@gmail.com
Dr Nitin Kapoor
Christian Medical College Hospital, Vellore
810, Department of Endocrinology
Diabetes and Metabolism, Christian Medical College
Vellore, Tamil Nadu, 632004 Vellore TAMIL NADU
9500249665
nitin.endocrine@gmail.com
Dr Rupam Borgohain
Citi Neuro Center, Hyderabad Institute of Neurosciences, Pvt.Ltd
MLA Colony,
Road No.12, Banjara Hills, Hyderabad-500034,
Telangana, India.
Hyderabad TELANGANA
9866191476
b_rupam@hotmail.com
Dr Sunil Gupta
Diabetes Care N’ Research Centre Pvt Ltd
42 Lendhra Park, Ramdaspeth, Nagpur, Maharashtra 44001 Nagpur MAHARASHTRA
A-1 Ajmer Road
Near 4 No. E.S.I. Hospital
Jaipur, Rajasthan,302006
India Jaipur RAJASTHAN
9829010233
sksharmacr@gmail.com
Dr Satbir Singh
Dr B L Kapur Memorial Hospital
7th floor B block, Clinical Research Department, Pusa Road, New Delhi-110005, India New Delhi DELHI
9717456667
drsatbir9717456667@gmail.com
Dr Kongara Srikanth
Endolife Speciality Hospitals Pvt ltd
D.no 12-12-94, old club road, kothapet , Guntur A P - 522001, India. Guntur ANDHRA PRADESH
9849945577
srikanthendo@gmail.com
DrSharvil Gadve
Excel Endocrine Centre
Excel Endocrine Centre, Diabetes Corner 1758, E Ward 4th Lane Rajarampuri Kolhapur, Maharasthra -416008 India Kolhapur MAHARASHTRA
9552365977
sharvilgadve@gmail.com
Dr Kiran Pal Singh
Fortis Heart Institute and Multispeciality Hospital
Endocrinology Research Room, Ground Floor, Fortis Inn, Behind Reception, Fortis Heart Institute and Multispeciality Hospital,Mohali – 160062, Punjab, India Fatehgarh Sahib PUNJAB
919815311711
drkp1292@gmail.com
Dr Mohit Dayal Gupta
G.B PANT INSTITUTE OF POST GRADUATE MEDICAL EDUCATION AND RESEARCH
Department of Cardiology, 1, Jawaharlal Nehru Marg, 64 Khamba, Raj Ghat, New Delhi - 110002, India New Delhi DELHI
9810121311
drmohitgupta@yahoo.com
DrChandni R
Government (Calicut) Medical College
Government (Calicut) Medical College, Clinical Research room, Department of General Medicine, opposite OP pharmacy, Medical College junction, 17, Mavoor road, near police station, Calicut Medical College, Kozhikode, Kerela- 673008 Kozhikode KERALA
Department of Clinical Research
4th floor, 1-4-908/7/1
Bakaram, musheerabad main road
Musheerabad-500020 Hyderabad TELANGANA
9701445011
johann1403@gmail.com
Dr Hitendra M Bhagwatkar
Hrudayaa Cardiac And Vascular Care Centre
Unit of NKP Salve Institute of Medical Science & Research Centre and Lata Mangeshkar Hospital, Hingna Road, Digdoh Hills, Police Nagar, Nagpur, Maharashtra 440019 Nagpur MAHARASHTRA
9096115922
hitendrabhagwatkar@gmail.com
Dr Rajeeve Kumar Rajput
Indraprastha Apollo Hospital
Room No. 1038, Cardiology Department, Sarita Vihar, Mathura Road, New Delhi - 110076, India New Delhi DELHI
9810013417
rajeevekumar64@gmail.com
Dr Sujoy Ghosh
IPGMER and SSKM HOSPITAL
244, AJC BOSE ROAD, RONALD ROSS BUILDING, 3rd Floor, KOLKATA-700020 Kolkata WEST BENGAL
9674625823
drsujoyghosh2000@gmail.com
Dr Ashish Kumar Agarwal
JAWAHAR LAL NEHRU GOVT. MEDICAL COLLEGE
Clinical Research Department, Medicine College Building, Kala Bagh, Ajmer, Rajasthan, 305001
India Ajmer RAJASTHAN
9636016718
dr.ashish.jln@gmail.com
Dr Ajit Raghunath Bhagwat
Kamalnayan Bajaj Hospital
Gut no. 43, Satara Parisar, Beed bypass road, Aurangabad-431010, Maharashtra, India Aurangabad MAHARASHTRA
9822050817
drbhagwat.knb@gmail.com
Dr Girithara G Naidu
KG Hospital
A Unit Of K Govindaswamy Naidu Medical Trust, 1st floor, Old Block, Department of Diabetology, No 5 Arts College Road, Coimbatore 641018, Tamil Nadu, India Coimbatore TAMIL NADU
9443170088
drgirimd@yahoo.com
Dr Shudhanshu Kumar Dwivedi
King Georges Medical College
Dept Of Cardiology, Lucknow - 226003 Uttar Pradesh, India Lucknow UTTAR PRADESH
9935037620
drskdwivedi60@gmail.com
Dr Abhijeet Bhausaheb Shelke
Krishna Vishwa Vidyapeeth
Deemed to be University Karad, Pune-Bangalore highway-4, malkapur road Karad ,Dist-Satara, Maharashtra-415539 Satara MAHARASHTRA
8978623010
abhijeetshelke5757@gmail.com
Dr Raghava Sharma
Lalitha super specialities hospital
New building,4th Floor,Clinical Research Department, Kothapet, Near Gowri Shankar theatre,Guntur ,Pincode- 522001,Andhra Pradesh Guntur ANDHRA PRADESH
9866391141
drpvr.lssh@gmail.com
Dr L Sreenivasa Murty
Life Care Hospitals and research center
Clinical research department,M.L.N Enclave,16th E Cross Road,Sahakarnagar,Banglore-560092, Karnataka Bangalore KARNATAKA
9448051046
drlsm@lcrc.in
Dr Pramila Kalra
M S Ramiah Clinical Research center
M S Ramaiah Medical College and Hospitals, M S R Nagar, MSRIT Post, Bangalore-560054, Karnataka, India Bangalore KARNATAKA
9243257161
kalrapramila@gmail.com
Dr V Mohan
Madras Diabetes Research Foundation
Department of Diabetes, Utsav flat, 1st floor, 4 Conran Smith Road, Gopalapuram, Chennai- 600086 Chennai TAMIL NADU
4443968888
drmohans@diabetes.ind.in
Dr Urmil Girishbhai Shah
Marengo CIMS Hospital Pvt Ltd
Plot no 67-1, 2nd floor, west wing, Research Department, Opp. Panchamrut Bunglows, Near Shukan Mall, Off. Science city Road, Sola, Ahmedabad - 380060, Gujarat, India Ahmadabad GUJARAT
9825066848
urmil.shah@cims.me
Dr Mohit Bhandari
Mohak Hi-Tech Speciality Hospital, (Unit of Bhandari Hospital & Research center)
Department of Endocrinology & Metabolism, room no F40, 1st floor, OPD, Sir Ganga Ram Hospital Marg, Rajinder Nagar, New Delhi - 110060, India New Delhi DELHI
9811126165
sudhirtrip@gmail.com
Dr Muffazal Lakdawala
Sir H N Reliance Foundation Hospital and Research centre
Raja Ram Mohan Roy Road, Mumbai 400004 india Mumbai MAHARASHTRA
9769162040
muffazal.lakdawala@rfhospital.org
Dr Satish C Suryavanshi
SMC Heart Institute and IVF Research Centre
Department of Cardiology In front of BSNL Office, Vidhan Sabha Road, Khamardih, Raipur – 492007 ( C.G. ) Raipur CHHATTISGARH
9826334404
drsatish_suryavanshi@yahoo.co.in
Dr Abhishek Agarwal
SMS Hospital
SMS Medical College & Attached Hospitals, Department of Medicine G-1. Dhanvantri OPD Block SMS Hospital, Jaipur - 302004 Rajasthan Jaipur RAJASTHAN
9829298691
drabhie@yahoo.com
Dr Krishna M V S
Sunrise Hospitals (A Unit of NS Health Care Services Pvt Ltd)
33-25-35 Near Pushpa Hotel Centre, Opp. Corporation Bank, Bellapu Sobhanadri Road, Vijayawada - 520002, Andhra Pradesh, India Krishna ANDHRA PRADESH
9848148967
drsaikrishnamaddi@gmail.com
Dr Devang Desai
UNICARE HEART INSTITUTE AND RESEARCH CENTRE
Surat , Clinical research Department, Basement floor, Acme plaza,B-wing, Near sosyo circle,Surat-395002,Gujarat,India. Surat GUJARAT
9825145738
heartfirst.surat@gmail.com
Dr Hemanth Kokane
WMFs Villoo Poonawalla Memorial Hospital
Department of Cardiology S.No. 156, Pune-Solapur Road Soli Poonawalla Road, Hadapsar, Pune 411028, India Pune MAHARASHTRA
9619284398
drhemantkokane@gmail.com
Dr Ramen Goel
Wockhardt Hospital Ltd
1877, Dr. Anandrao Nair Marg,Mumbai- 400011, Maharashtra Mumbai MAHARASHTRA
Institutional Ethics Committee,Jawahar Lal Nehru Medical College
Approved
Institutional Ethics Committee- CARE Hospital
Approved
Institutional Ethics Committee- Diabetes Research Center
Approved
Institutional Ethics Committee-l
Approved
Institutional Human Ethics Committee, All India Institute of Medical Sciences Jodhpur
Approved
Institutional Resarch Committee Govt. Medical College , KoziKode
Approved
IPGME&R Research Oversight Committee,
Approved
Lalitha Super Specialities Hospital Ethics Committee
Approved
Life Care Hospital Institutional Review Board
Approved
Magna-Care Ethics Committee
Approved
Narayana Health Medical Ethics Committee
Approved
Nirmal Hospital Private Limited Etics Committee
Approved
Office of Ethics Committee SMS Medical College & Attached Hospitals
Approved
Omega Ethical Committee
Approved
Rhythm Heart Institute Ethics Committee
Approved
Sengupta Hospital and Research Institute
Approved
SMC Heart Institute Institutional Ethics Committe
Approved
SMHRC-Ethics committe
Approved
UNITY HOSPITAL ETHICS COMMITTEE
Approved
Wockhardt Hospital Ltd
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: E669||Obesity, unspecified,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Cagrilintide and Semaglutide
Participants will be treated with CagriSema 2.4 mg by 2.4 mg s.c. or placebo s.c. administered once weekly, both on top of standard of care. For 156-week
Comparator Agent
Placebo cagrilintide and placebo
semaglutide
Participants will be treated with CagriSema 2.4 mg by 2.4mg s.c. or placebo s.c. administered once weekly, both on top of standard of care. For 156-week
1.Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study
2. Male or female
3. Age above or equal to 55 years at the time of signing informed consent
4. Body mass index (BMI) ≥ 30.0 kg/m2
5. Have established CVD as evidenced by at least one of the following:
Prior myocardial infarction
Prior stroke (ischemic or haemorrhagic stroke)
6.Symptomatic peripheral arterial disease (PAD) defined as at least one of the following:
Intermittent claudication with an Ankle-brachial index (ABI) greater than 0.85 at rest, Intermittent claudication with a less than or equal to 50% stenosis in a lower extremity peripheral artery documented by X-ray angiography, MR angiography, CT angiography or Doppler ultrasound
Prior revascularization procedure of a lower extremity peripheral artery
d.Lower extremity amputation at or above ankle due to atherosclerotic disease(excluding e.g., trauma or osteomyelitis)For participants with T2D at screening:
7.Diagnosed with type 2 diabetes mellitus ≥ 180 days before screening
8.HbA1c 7%-10% (53-86 mmol/mol) (both inclusive), as measured by central laboratory at screening.
9. Treatment with either:Lifestyle intervention alone ,1-3 marketed oral antidiabetic drugs (OAD)s (metformin, α-glucosidase inhibitors (AGI), glinides, sodium-glucose co-transporter 2 inhibitor (SGLT2i), DPP4-inhibitors, thiazolidinediones, or sulphonylureas (SU) as a single agent or in combination) according to local label Treatment with oral antidiabetic drugs should be stable (same drug(s), dose and
dosing frequency) for at least 90 days before screening Basal insulin alone or in combination with up to two marketed OADs, all according to local label
ExclusionCriteria
Details
All exclusion criteria are based on declaration by the participant or the participants’ medical
records, except for exclusion criteria #8 (diabetic retinopathy or maculopathy) and #18 (eGFR)
which is assessed at the screening visit. Participants are excluded from the study if any of the
following criteria apply:
Cardiovascular related:
1. Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic
attack within 60 days before screening
2. Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
3. Heart failure classified as being in New York Heart Association (NYHA) Class IV at screening
Glycaemia related:
4. Severe hypoglycaemia, as defined in Appendix 7 (Section 10.7), within 6 months before
screening
5. History of hypoglycaemia unawareness as indicated by the Investigator according to Clarke’s
questionnaire question 8
6. History of type 1 diabetes mellitus
7. Treatment with any medication for the indication of diabetes other than stated in the inclusion
criteria within 90 days before screening
8. Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus
examination performed within 90 days before screening or in the period between screening and
randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus
photography camera specified for non-dilated examination
Obesity related:
9. Treatment with any GLP-1 RA or a medication with GLP-1 activity within 90 days before
screening
Mental health related:
10. History of major depressive disorder within 2 years before screening
11. Diagnosis of other severe psychiatric disorder (e.g., schizophrenia, bipolar disorder)
12. A lifetime history of a suicidal attempt
13. Suicidal behaviour within 30 days before screening
General safety:
14. History or presence of chronic pancreatitis
15. Presence of acute pancreatitis within the past 180 days before screening
16. Personal or first degree relative(s) history of multiple endocrine neoplasia type 2 or medullary
thyroid carcinoma
17. Presence or history of malignant neoplasms (other than basal and squamous cell skin cancer,
in situ carcinomas of the cervix, or in situ prostate cancer) within 5 years before screening
18. End stage renal disease defined as eGFR < 15 mL/min/1.73 m2, as measured by the central
laboratory at screening48
19. Chronic or intermittent haemodialysis or peritoneal dialysis
20. Known or suspected abuse of alcohol or recreational drugs
21. Known or suspected hypersensitivity to IMP(s) or related products
22. Previous participation in this study. Participation is defined as randomisation
23. Participation (i.e., signed informed consent) in any interventional, clinical study of an approved
or non-approved investigational medicinal product within 90 days before screening
24. Other participant(s) from the same household participating in any CagriSema study
25. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing
potential and not using a highly effective contraceptive method as defined in
Appendix 4 (Section 10.4)
26. Any disorder, unwillingness or inability, not covered by any of the other exclusion criteria,
which in the investigator’s opinion, might jeopardise the participant’s safety or compliance with
the protocol
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome
Outcome
TimePoints
Time to first occurrence of
MACE, a composite
endpoint consisting of:
ï‚· CV death,
ï‚· non-fatal myocardial
infarction,
non-fatal stroke
Time frame:From baseline (week 0) to end of study (up to 163 weeks or more).
Unit: Month(s)
Secondary Outcome
Outcome
TimePoints
Time to first occurrence of
MACE, a composite
endpoint consisting of:
ï‚· CV death
ï‚· non-fatal
myocardial
infarction,
ï‚· non-fatal stroke
Time frame:From baseline (week 0) to
end of study (up to 163
weeks or more).
Unit: Month(s)
Time to first occurrence of
an expanded MACE composite endpoint consisting of:
CV death
non-fatal myocardial infarction,
non-fatal stroke
coronary
revascularisation
unstable angina
requiring hospitalisation
Time Frame: From baseline (week 0) to end of study (up to 163 weeks or more).
Unit: Month(s)
Time to first occurrence of a
composite heart failure
endpoint consisting of:
CV death
heart failure
hospitalisation
urgent heart failure
visit
Time Frame : From baseline (week 0) to end of study (up to 163 weeks or more).
Unit : Month(s)
Time to first occurrence of a
composite endpoint
consisting of:
all-cause death
non-fatal
myocardial infarction
non-fatal stroke
Time Frame: From baseline (week 0) to end of study(up to 163 weeks or more)
Time to occurrence of CV death
Time Frame: From baseline (week 0) to end of study (up to 163 weeks or more).
Unit: Month(s)
Time to first occurrence of non-fatal stroke
Time frame:From baseline (week 0) to end of study (up to 163 weeks or more).
Unit: Month(s)
Relative change in body weight
Time frame:From baseline (week 0) to end of treatment(week 156).
Unit: percentage
Change in waist circumference
Time frame:From baseline (week 0) to end of treatment(week 156).
Unit:cm
Change in systolic blood pressure(SBP)
Time frame:From baseline (week 0) to end of treatment(week 156).
Unit: mmHg
Change in diastolic blood pressure(DBP)
Time frame:From baseline (week 0) to end of treatment(week 156).
Unit:mmHg
Relative change in lipids:ï‚·Total cholesterolï‚·HDL cholesterolï‚·LDL cholesterolï‚·VLDL cholesterolï‚·Triglyceridesï‚·Free fatty acids
Time frame:From baseline (week 0) to end of treatment(week 156).
Unit: percentage
Change in HbA1c
Time frame:From baseline (week 0) to end of treatment(week 156).
Unit: Percentage-points
Change in SF-36v2:ï‚·Physical Component Summary scoreï‚·Mental Component Summary score
Time frame:From baseline (week 0) to end of treatment(week 156).
Unit: Score points
Number of TESAEs
Time frame:From baseline (week 0) to end of study (up to163 weeks or more).
Unit: Count of events
Number of event adjudication committee (EAC)-confirmed malignant neoplasms
Time frame:From baseline (week 0) to end of study (up to 163 weeks or more).
Unit: Count of events
Number of severe hypoglycaemic episodes (level 3) (only forparticipants with T2D at screening)
Time frame:From baseline (week 0) to end of study (up to 163 weeks or more).
Unit : Count of events
Target Sample Size
Total Sample Size="4000" Sample Size from India="264" Final Enrollment numbers achieved (Total)= "0" Final Enrollment numbers achieved (India)="0"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is an interventional 156-week, randomised, double-blind,
placebo-controlled, two-armed, parallel-group, multicentre, multinational
clinical study primarily intended to assess the cardiovascular (CV) safety of
CagriSema 2.4 mg/2.4 mg versus placebo, both administered subcutaneously (s.c.)
once-weekly and both added to standard of care in individuals with obesity and
established cardiovascular disease (CVD). The study design will also allow for
evaluation of neoplasm safety, due to the 3-year treatment duration.