CTRI/2024/01/061256 [Registered on: 09/01/2024] Trial Registered Prospectively
Last Modified On:
20/11/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Multiple Arm Trial
Public Title of Study
A research study to see how well CagriSema compared to semaglutide,cagrilintide and placebo lowers blood sugar and body weight 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) s.c. in doses 2.4/2.4 mg and 1.0/1.0 mg once weekly versus semaglutide 2.4 mg and 1.0 mg, cagrilintide 2.4 mg and placebo in participants with type 2 diabetes inadequately controlled on metformin with or without an SGLT2 inhibitor
Trial Acronym
REIMAGINE 2
Secondary IDs if Any
Secondary ID
Identifier
155796
Other
2022-502678-18-00
EudraCT
NN9388-4896, Version 1.0, Dated 24 Apr 2023
Protocol Number
U1111-1283-0427
UTN
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Nxt Tower - 2, Floor 1 & 2
Embassy Manyata Business Park,
Nagavara Village, Kasaba Hobli,
Bangalore - 560045. India
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
Argentina Australia Brazil Bulgaria Canada China Colombia Croatia Czech Republic Denmark Finland Germany Greece Hungary India Israel Italy Japan Mexico Poland Romania Serbia Slovakia Slovenia South Africa Spain Sweden Taiwan Turkey United Kingdom United States of America
Sites of Study
No of Sites = 15
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
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 Tirthankar Chaudhary
Apollo Multispeciality Hospitals Limited
Department of Clinical Trials,
6th floor
Day care building,
58, Canal Circular Road Kolkata -700054, West Bengal, India
Kolkata WEST BENGAL
9831322394
tirthankarc05@gmail.com
Dr Shrikant Vishnu Deshpande
Ashirwad Hospital and Research Centre
Clinical Research Department, 2nd Floor, 32 Maratha Section, Next to Jijamata Udyan, Ulhasnagar, Thane, Maharashtra – 421004 Thane MAHARASHTRA
9822017445
writetoshrikant@rediffmail.com
Dr Nikhil Bhagwat
BYL Nair Hospital and T N Medical College
Department of endocrinology, College building, 4th floor, room no. 19, Dr A L Nair Road, Mumbai Central,Mumbai, Maharashtra, 400008 Mumbai MAHARASHTRA
9820238399
bhagwatnik@yahoo.co.in
Dr Anjan Jyoti Talukdar
Gauhati Medical College
3rd floor, Department of Medicine,GUWAHATI ASSAM BHANGAGARH 781032 Kamrup ASSAM
1st Floor, Department of Medicine, K R Hospital attached to Mysore Medical College and Research Institute, Irwin Road, Mysuru- 570001 Mysore KARNATAKA
9448051046
sumi_anjum262@yahoo.com
Dr Girithara Gopalakrishnan Jayaram Naidu
KG Hospital
Department of Diabetology, A unit of K. Govindaswamy naidu medical Trust, No 5 Govt Arts College Road, Coimbatore 641018, Tamilnadu
Coimbatore TAMIL NADU
Room No. 114, Department of medicine, First Floor, Academic block,C-604, Shaeed Bhagat Singh Road,DIZ Area, Cannaught Place, New Delhi-110001,New Delhi New Delhi DELHI
9818626614
rameshlhmc@gmail.com
Dr L Sreenivasamurthy
Lifecare Hospital and Research Centre
1st floor, Department of Diabetes,2748/2152, MLN Enclave, 16th E Cross, 8th Main road, D Block, Next to Union bank, Sahakarnagar, Bangalore- 560092 Bangalore KARNATAKA
9448051046
drlsm@lcrc.in
Dr Rama Walia
Postgraduate institute of medical Education and Research (PGIMER)
Department of endocrinology, sector -12 PGIMER Chandigarh. Chandigarh CHANDIGARH
9872997438
ramawalia@rediffmail.com
Dr Abhishek Agrawal
SMS Hospital
Department of Medicine, Ground Floor, G-1 Dhanvantri OPD Block SMS Hospital Jaipur-302004 Jaipur RAJASTHAN
9829298691
drabhie@yahoo.com
Dr Mayur Patel
Swasthya Diabetes Care
Department of Diabetes and Endocrinology,Opp Jaymangal BRTS Bus Stop, 132 Feet
Ring Road, Naranpura, Ahmedabad, Gujarat
380013 Ahmadabad GUJARAT
Life Care Hospital tnstitutional Review Board. 2748-2152, M.L.N Enclave, 16th E Cross Road, 8th Main, D-Block Next to Corporation Bank, Sahakarnagar, Bangalore, Urban Karnataka
Approved
OM Institutional Ethics committee, Silver star complex, chandlodiya, Ahmedabad
(1) ICD-10 Condition: E119||Type 2 diabetes mellitus without complications,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
cagrilintide
(0.25/0.5/1.0/1.7/2.4mg)
Injections should be administered Subcutaneously (SC) in the thigh, abdomen, or upper arm, at any time of day
irrespective of meals. Rotation of the injection site within 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
CagriSema
(0.25/0.5/1.0mg)
Injections should be administered Subcutaneously (SC) in the thigh, abdomen, or upper arm, at any time of day
irrespective of meals. Rotation of the injection site within 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)
Intervention
CagriSema (0.25/0.5/1.0/1.7/2.4mg)
Injections should be administered Subcutaneously (SC) in the thigh, abdomen, or upper arm, at any time of day
irrespective of meals. Rotation of the injection site within 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
placebo
(0.25/0.5/1.0/1.7/2.4mg)
Injections should be administered Subcutaneously (SC) in the thigh, abdomen, or upper arm, at any time of day
irrespective of meals. Rotation of the injection site within 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
placebo
(0.25/0.5/1.0mg)
Injections should be administered Subcutaneously (SC) in the thigh, abdomen, or upper arm, at any time of day
irrespective of meals. Rotation of the injection site within 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
semaglutide
(0.25/0.5/1.0/1.7/2.4mg)
Injections should be administered Subcutaneously (SC) in the thigh, abdomen, or upper arm, at any time of day
irrespective of meals. Rotation of the injection site within 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
semaglutide
(0.25/0.5/1.0mg)
Injections should be administered Subcutaneously (SC) in the thigh, abdomen, or upper arm, at any time of day
irrespective of meals. Rotation of the injection site within 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)
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 18 years or above at the time of signing the informed consent. 4. Diagnosed with type 2 diabetes mellitus ≥ 180 days before screening. 5. Stable daily dose(s) ≥ 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. 6. HbA1c 7.0-10.5% (53-91 mmol/mol) (both inclusive) as determined by central laboratory at screening. 7. BMI ≥ 25 kg/m2 at screening. BMI will be calculated in the eCRF based on height and body weight at screening.
ExclusionCriteria
Details
1. Renal impairment with estimated Glomerular Filtration Rate (eGFR) < 30 ml/min/1.73 m2 as
determined by central laboratory at screening.
2. 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.
3. 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.
4. Anticipated initiation or change in concomitant medications (for more than 14 consecutive
days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid
hormones, or corticosteroids).
5. Previous or planned (during the study period) obesity treatment with surgery or a weight loss
device. However, the following are allowed: (1) liposuction and/or abdominoplasty, if
performed > 1 year before screening, (2) lap banding, if the band has been removed > 1 yearbefore screening, (3) intragastric balloon, if the balloon has been removed > 1 year before
screening or (4) duodenal-jejunal bypass sleeve, if the sleeve has been removed > 1 year before
screening.
6. A self-reported change in body weight > 5% within 90 days before screening irrespective of
medical records.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator and Outcome Assessor Blinded
To confirm superiority of CagriSema 2.4
mg/2.4 mg versus semaglutide 2.4 mg on
change in HbA1c in participants with T2D in
inadequate glycaemic control on stable dose of
metformin +/-SGLT2i
Change in HbA1c From baseline
(week 0) to end of
treatment (week 68)
%-points
Secondary Outcome
Outcome
TimePoints
To confirm superiority of CagriSema
2.4 mg/2.4 mg versus cagrilintide 2.4 mg on
change in HbA1c and/or change in body
weight
From baseline (week
0) to end of
treatment (week 68)
To confirm superiority of CagriSema
2.4 mg/2.4 mg versus semaglutide 1.0 mg
on change in HbA1c and/or change in body
weight
From baseline (week
0) to end of
treatment (week 68)
To confirm superiority of cagrilintide
2.4 mg versus placebo on change in
1) HbA1c
2) Body weight
From baseline (week
0) to end of
treatment (week 68)
To confirm superiority of CagriSema versus
semaglutide (2.4 mg/2.4 mg versus 2.4 mg
and 1.0 mg/1.0 mg vs 1.0 mg) on:
1) Achievement of ≥ 10% weight reduction
2) Achievement of ≥ 15% weight reduction
3) Achievement of ≥ 20% weight reduction
From baseline (week
0) to end of
treatment (week 68)
To confirm superiority of CagriSema versus
semaglutide (2.4 mg/2.4 mg versus 2.4 mg
and 1.0 mg/1.0 mg vs 1.0 mg, respectively)
on time in tight range (TITR)
From baseline (week
-3 to end of
treatment (week 68)
To confirm superiority of CagriSema versus
semaglutide (2.4 mg/2.4 mg versus 2.4 mg
and 1.0 mg/1.0 mg vs 1.0 mg, respectively)
on:
1) Systolic blood pressure
2) Triglycerides
3) Non-HDL cholesterol
From baseline (week
-3 to end of
treatment (week 68)
To confirm superiority of CagriSema versus
semaglutide (2.4 mg/2.4 mg versus 2.4 mg
and 1.0 mg/1.0 mg vs 1.0 mg, respectively)
on time in range (TIR)
From baseline (week
-3) to end of
treatment (week 68)
To confirm superiority of CagriSema versus
semaglutide (2.4 mg/2.4 mg versus 2.4 mg
and 1.0 mg/1.0 mg vs 1.0 mg, respectively)
on hsCRP
From baseline (week
0) to end of
treatment (week 68)
Target Sample Size
Total Sample Size="2700" Sample Size from India="110" 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
CagriSema versus semaglutide, cagrilintide and placebo. The study will be double-blind within dose
level.
Rationale:
The purpose of the present study is to compare the effect of CagriSema 2.4 mg/2.4 mg once weekly
versus semaglutide 2.4 mg once weekly and CagriSema 1.0 mg/1.0 mg once weekly versus
semaglutide 1.0 mg once weekly on glycaemic control, weight loss, as well as safety and
tolerability profile in people with T2D treated with metformin with or without an SGLT2 inhibitor.
Furthermore, the study will compare the effect of CagriSema 2.4 mg/2.4 mg once weekly versus
cagrilintide 2.4 mg once weekly and semaglutide 1.0 mg once weekly, as well as cagrilintide 2.4 mg
once weekly versus placebo once weekly on glycaemic control and weight loss.
Overall design:
The study consists of:
ï‚· up to 3-week screening period
ï‚· a 68-week intervention period which for participants randomised to the 1.0mg /1.0mg dose
includes an 8-week dose escalation followed by a 60-week maintenance period and for
participants randomised to the 2.4mg/2.4mg dose includes a 16-week escalation followed by
a 52-week maintenance period
ï‚· a 7-week follow-up period