| CTRI Number |
CTRI/2024/03/064047 [Registered on: 12/03/2024] Trial Registered Prospectively |
| Last Modified On: |
12/11/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
A research study to see how much CagriSema lowers blood sugar and body weight compared to tirzepatide in people with type 2 diabetes treated with metformin with or without an SGLT2 inhibitor |
|
Scientific Title of Study
|
Efficacy and safety of co-administered cagrilintide and semaglutide (CagriSema)
2.4 mg/2.4 mg s.c. once weekly versus tirzepatide 15 mg s.c. once weekly in participants with type
2 diabetes inadequately controlled on metformin with or without an SGLT2 inhibitor |
| Trial Acronym |
REIMAGINE 4 (NN9388-4894) |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 155796 |
Other |
| 2023-503789-21-00 |
EudraCT |
| U1111-1282-5561 |
UTN |
| Version 1.0, Global dated 21 June 2023 |
Protocol Number |
|
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
|
| Designation |
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| Affiliation |
|
| Address |
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| Phone |
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| Fax |
|
| Email |
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Details of Contact Person
Scientific Query
|
| Name |
Dr Maya Sharma |
| Designation |
Vice President - Clinical, Medical, Regulatory & Pharmacovigilance |
| Affiliation |
Novo Nordisk India Pvt. Ltd. |
| Address |
Novo Nordisk India Private Limited,
Nxt Tower 2, Floor 1 and 2 Embassy Manyata Business Park, Nagavara Village, Kasaba Hobli
Bangalore
KARNATAKA
560045
India |
| Phone |
9911497869 |
| Fax |
|
| Email |
yrms@novonordisk.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Maya Sharma |
| Designation |
Vice President - Clinical, Medical, Regulatory & Pharmacovigilance |
| Affiliation |
Novo Nordisk India Pvt. Ltd. |
| Address |
Novo Nordisk India Private Limited,
Nxt Tower 2, Floor 1 and 2 Embassy Manyata Business Park, Nagavara Village, Kasaba Hobli
Bangalore
KARNATAKA
560045
India |
| Phone |
9911497869 |
| Fax |
|
| Email |
yrms@novonordisk.com |
|
|
Source of Monetary or Material Support
|
| Novo Nordisk India Private Limited,
Nxt Tower - 2, Floor 1 & 2 Embassy Manyata Business Park, Nagavara Village, Kasaba Hobli, Bangalore - 560045. India |
|
|
Primary Sponsor
|
| Name |
Novo Nordisk |
| Address |
Novo Nordisk India Private Limited,
Nxt Tower - 2, Floor 1 and 2 Embassy Manyata Business Park, Nagavara Village, Kasaba Hobli, Bangalore - 560045. India |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
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Details of Secondary Sponsor
|
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Countries of Recruitment
|
Argentina
Australia
Canada
Colombia
India
South Africa
Taiwan
United States of America |
|
Sites of Study
|
| No of Sites = 17 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Neeta Deshpande |
Belgaum Diabetes Centre |
Belgaum Diabetes Centre, second floor Maruti Street, Belgaum 590001
Belgaum
KARNATAKA |
9880271313
neetarohit@gmail.com |
| Dr Debaditya Das |
BP Poddar Hospital |
BP Poddar Hospital, 71-1, Humayun Kabir Sarani, Durgapur Colony, Block G, New Alipore, Kolkata
Kolkata
WEST BENGAL |
9038789365
dasdebaditya@gmail.com |
| Dr Manoj Chawla |
BSES MG Hospital |
BSES MG Hospital, Opp. Railway Station, SV Road, 7th floor, inside waiting area, Andheri West, Mumbai - 400058
Mumbai
MAHARASHTRA |
9820002333
linadiabetesresearch@gmail.com |
| Dr Unnikrishnan A G |
Chellaram Diabetes Institute |
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 Nitin Kapoor |
Christian Medical College |
Christian Medical College,
810, Department of Endocrinology Diabetes & Metabolism, Christian Medical College, Vellore, Tamil Nadu, India- 632002
Chennai
TAMIL NADU |
9500249665
nitin.endocrine@gmail.com |
| Dr Surendra Sharma |
ESI Hospital |
Diabetes, Thyroid and Endocrine centre. A-1, Madrampura, THIRD FLOOR, DEPARTMENT OF CLICIAL RESEARCH Near 4 no. ESI Hospital, Ajmer road, Jaipur-302006 Rajasthan, India
Jaipur
RAJASTHAN |
9829010233
sksharmacr@gmail.com |
| Dr Chandni 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 |
9447202748
drchandni2019@gmail.com |
| Dr Sanjay Agarwal |
Grant Medical Foundation Ruby Hall Clinic |
Grant Medical Foundation Ruby Hall Clinic, Clinical Research Department E4- C to E4- F, 4th floor, Grant Medical Foundation Ruby Hall Clinic, Fifth Avenue Condominium, Dhole Patil Road, Pune, Maharashtra- 411001
Pune
MAHARASHTRA |
919822091220
agarwalclinic@gmail.com |
| Dr P K Jabbar |
Indian Institute of Diabetes |
Indian Institute of Diabetes,
Pulayanarkotta, Thiruvananthapuram, Kerala- 695033
Thiruvananthapuram
KERALA |
9446828766
drjabbar10@gmail.com |
| Dr Jothydev Kesavadev |
Jothydevs Diabetes Research Centre |
Jothydevs Diabetes Research Centre, JDC Junction, Konkalam Road, Department of research, Room no 25, second floor, Mudavanmugal, Poojappura, Trivandrum-695032
Thiruvananthapuram
KERALA |
9895040055
jothydev@gmail.com |
| Dr Sandeep Garg |
Maualana Azad Medical College |
Room No 103-104. Department of Medicine, BL Taneja Block, Maualana Azad Medical College, New Delhi 110002
New Delhi
DELHI |
9968604280
drsandeepgargmamc@gmail.com |
| Dr Piyush Desai |
Nirmal Hospitals Pvt. Ltd. |
Nirmal Hospitals Pvt. Ltd., 5th Floor, Clinical Research Room, Wing A, Sagrampura, Surat - 395002, Gujarat
Surat
GUJARAT |
9825144453
drpiyushdesai@gmail.com |
| Dr Hamid Ashraf |
Rajiv Gandhi Centre for Diabetes and Endocrinology, J.N Medical College |
Rajiv Gandhi Centre for Diabetes and Endocrinology, J.N Medical College, Aligarh Muslim University, Aligarh, U.P
Aligarh
UTTAR PRADESH |
918986376271
hamid2k3@gmail.com |
| Dr Saba Memon |
Seth GS Medical College and KEM Hospital |
Seth GS Medical College and KEM Hospital, Room 6, 1st Floor, Clinical Research Department, Mumbai, Maharashtra- 400012
Mumbai
MAHARASHTRA |
9971247224
sabasamadmemon@gmail.com |
| Dr Balram Sharma |
SMS HOSPITAL |
DEPARTMENT OF ENDOCRINOLOGY ROOM NO 43 A FOURTH FLOOR DHANVANTRI OPD BLOCK SMS HOSPITAL JAIPUR -302004
Jaipur
RAJASTHAN |
9660226666
drbalramendo@gmail.com |
| Dr J S Kumar |
SRM Medical College Hospital and Research Centre |
SRM Centre for Clinical Trials & Research, 3rd Floor, SRM Medical College Hospital and Research Centre, Kattankulathur - 603203
Kancheepuram
TAMIL NADU |
9840047678
kumarj1@srmist.edu.in |
| Dr Keyur Brahme |
SSG Hospital |
SSG Hospital, Baroda, Sayajigunj, Jail Road, Vadodara, Gujarat- 390006
Vadodara
GUJARAT |
9727729105
keyurbrahme@gmail.com |
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Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 17 |
| Name of Committee |
Approval Status |
| B P Poddar and Parvati Devi Foundation For Education |
Approved |
| BSES Municipal General Hospital Ethics Committee |
Approved |
| Chellaram Diabetes Institute-Institutional Ethics Committee |
Approved |
| ETHICS COMMITTEE |
Approved |
| Ethics Committee SMS Medical college and Attached Hospitals |
Approved |
| Human Welfare Ethical Committee for Human Sciences and Research |
Approved |
| Institutional Ethic Committee (IEC), |
Not Applicable |
| Institutional Ethic Committee, Indian Institute of Diabetes |
Approved |
| Institutional Ethics Committee Government Medical College |
Approved |
| Institutional Ethics Committee for Human Research |
Approved |
| Institutional Ethics Committee MAMC |
Approved |
| Institutional Ethics Committee Poona Medical Research Foundation |
Approved |
| Institutional Review Board-Silver, Christian Medical College |
Approved |
| Jothydev s Diabetes Research Centre |
Approved |
| KEM Hospital Research And Ethics committee |
Approved |
| Lakeview Ethics Committee |
Approved |
| Nirmal Hospital Pvt Ltd, |
Approved |
|
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Regulatory Clearance Status from DCGI
|
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Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: E11||Type 2 diabetes mellitus, |
|
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Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
CagriSema |
Cagrilintide B, semaglutide I,
DV3384 pen-injector. Route of administration-Subcutaneous. Product strength:
A1: Cagrilintide B 1.0 mg/mL
and semaglutide I 0.5 mg/mL
A2: Cagrilintide B 2.0 mg/mL
and semaglutide I 1.0 mg/mL
A3: Cagrilintide B 4.0 mg/mL
and semaglutide I 2.0 mg/mL
A4: Cagrilintide B 6.8 mg/mL
and semaglutide I 3.4 mg/mL
A5: Cagrilintide B 9.6 mg/mL
and semaglutide I 4.8 mg/mL. Injections should be administered in the thigh, abdomen, or upper arm,
at any time of day irrespective of meals. Rotation of the injection sitewithin the same body region is recommended. The IMP should be
injected once weekly on the same day of the week throughout the
treatment period (scheduled dosing day) |
| Comparator Agent |
Tirzepatide |
Tirzepatide
Mounjaro® a pen. Route of administration-Subcutaneous. Strength:
B1: Tirzepatide 2.5 mg
B2: Tirzepatide 5 mg
B3: Tirzepatide 7.5 mg
B4: Tirzepatide 10 mg
B5: Tirzepatide 12.5 mg
B6: Tirzepatide 15 mg.
Injections should be administered in the thigh, abdomen, or upper arm,
at any time of day irrespective of meals. Rotation of the injection sitewithin the same body region is recommended. The IMP should be
injected once weekly on the same day of the week throughout the
treatment period (scheduled dosing day) |
|
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Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
1. Male or female.
2. Age 18 years or above at the time of signing the informed consent.
3. Diagnosed with type 2 diabetes more than or equal to 180 days before screening.
4. Stable daily dose(s) more than or equal to 90 days before screening of any of the following antidiabetic drug(s)
or combination regimen(s) at effective or maximum tolerated dose as judged by the
investigator: metformin with or without an SGLT2 inhibitor.
5. HbA1c 7.0-10.5 percent (53-91 mmol per mol) (both inclusive) as determined by central laboratory at
screening.
6. BMI more than or equal to 30 kg per m2 at screening. BMI will be calculated in the eCRF based on height and body
weight at screening. |
|
| ExclusionCriteria |
| Details |
1.Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing
potential and not using a highly effective contraceptive method.
2.Renal impairment with estimated Glomerular Filtration Rate more than 30 ml per min per 1.73 m2 as determined by central laboratory at screening.
3.Treatment with any medication for the indication of diabetes or obesity other than stated in
the inclusion criteria within 90 days before screening. However, short term insulin treatment for a maximum of 14 consecutive days and prior insulin treatment for gestational diabetes
are allowed.
4. 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 |
|
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Method of Generating Random Sequence
|
Stratified randomization |
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Method of Concealment
|
Centralized |
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Blinding/Masking
|
Open Label |
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Primary Outcome
|
| Outcome |
TimePoints |
1) Change in HbA1c
2) Relative change in body
weight |
1) From baseline
(week 0) to end of
treatment (week
68)
2) From baseline
(week 0) to end of
treatment (week
68) |
|
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Secondary Outcome
|
| Outcome |
TimePoints |
To confirm superiority of CagriSema 2.4 mg per 2.4 mg versus tirzepatide 15 mg on
change in HbA1c |
From baseline
(week 0) to end of
treatment (week
68) |
| To compare the effect of CagriSema 2.4 mg per 2.4 mg versus tirzepatide 15 mg on Change in FPG |
From baseline
(week 0) to end of
treatment (week
68) |
To compare the effect of CagriSema 2.4 mg per 2.4 mg versus tirzepatide 15 mg on Achievement of more than or equal to 5 percent weight
reduction |
From baseline
(week 0) to end of
treatment (week
68) |
Achievement of HbA1c target
values of less than 7.0 percent(less than 53 mmol per mol) |
At end of treatment
(week 68) |
Achievement of HbA1c target
values of less than 6.5 percent (less than 48 mmol per mol) |
At end of treatment
(week 68) |
| Achievement of more than 10 percent weight reduction |
From baseline
(week 0) to end of
treatment (week
68) |
| Achievement of more than 15 percent weight reduction |
From baseline
(week 0) to end of
treatment (week
68) |
| Achievement of more than 20 percent weight reduction |
From baseline (week 0) to end of treatment (week 68) |
Change in systolic blood
pressure |
From baseline
(week 0) to end of
treatment (week
68) |
Change in diastolic blood
pressure |
From baseline
(week 0) to end of
treatment (week
68) |
Change in waist
circumference |
From baseline
(week 0) to end of
treatment (week
68) |
Ratio to baseline in lipids
Total cholesterol
HDL cholesterol
LDL cholesterol
VLDL cholesterol
Triglycerides
non-HDL cholesterol |
From baseline
(week 0) to end of
treatment (week
68) |
Change in SF-36v2 score
Physical Component
Summary score
Mental Component
Summary score |
From baseline
(week 0) to end of
treatment (week
68) |
Change in IWQOL-Lite-CT:
Physical Function score
Total score |
From baseline
(week 0) to end of
treatment (week
68) |
To compare the safety and tolerability of
CagriSema 2.4 mg per 2.4 mg versus tirzepatide
15 mg -Number of TEAEs |
From baseline
(week 0) to end of
study (week 74) |
To compare the safety and tolerability of
CagriSema 2.4 mg per 2.4 mg versus tirzepatide
15 mg- Count of events
Number of clinically
significant hypoglycaemic
episodes (level 2) |
From baseline
(week 0) to end of
study (week 74) |
Score points
To compare the safety and tolerability of
CagriSema 2.4 mg Per 2.4 mg versus tirzepatide
15 mg-Count of episodes
Number of severe
hypoglycaemic episodes
(level 3): hypoglycaemia
associated with severe
cognitive impairment
requiring external assistance
for recovery, with no specific
glucose threshold |
From baseline
(week 0) to end of
study (week 74) |
|
|
Target Sample Size
|
Total Sample Size="1000"
Sample Size from India="200"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
16/04/2024 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
16/01/2024 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="1"
Days="21" |
Recruitment Status of Trial (Global)
Modification(s)
|
Closed to Recruitment of Participants |
| Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
|
Publication Details
|
N/A |
|
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, multi-national, multi-centre, randomised, parallel-group, open-label study comparing CagriSema versus tirzepatide. Rationale: The purpose of the present study is to compare the effect of CagriSema 2.4 mg/2.4 mg versus tirzepatide 15 mg on glycaemic control and weight loss as well as safety and tolerability in people with type 2 diabetes treated with metformin with or without a sodium glucose transporter type 2 inhibitor (SGLT2i). |