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CTRI Number  CTRI/2022/01/039705 [Registered on: 25/01/2022] Trial Registered Prospectively
Last Modified On: 04/10/2024
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 the new weekly medicine IcoSema, which is a combination of insulin icodec and semaglutide, controls blood sugar level in people with type 2 diabetes compared to insulin glargine taken daily with insulin aspart (COMBINE 3) 
Scientific Title of Study   A 52 week study comparing the efficacy and safety of once weekly IcoSema and daily insulin glargine 100 units/mL combined with insulin aspart, both treatment arms with or without oral anti diabetic drugs, in participants with type 2 diabetes inadequately controlled with daily basal insulin. 
Trial Acronym   
Secondary IDs if Any
Modification(s)  
Secondary ID  Identifier 
2020-005309-18  EudraCT 
NN1535-4593 Protocol v7.0 dated 27 Oct 2022  Protocol Number 
U1111-1260-8295  UTN 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name   
Designation   
Affiliation   
Address 




 
Phone    
Fax    
Email    
 
Details of Contact Person
Scientific Query
Modification(s)  
Name  Dr Maya Sharma 
Designation  Vice President - CMR 
Affiliation  Novo Nordisk India Private Limited 
Address  Novo Nordisk India Private Limited, Nxt Tower - 2, Floor 1 & 2 Embassy Manyata Business Park, Nagavara Village, Kasaba Hobli, Bangalore, India

Bangalore
KARNATAKA
560045
India 
Phone  9911497869  
Fax    
Email  yrms@novonordisk.com  
 
Details of Contact Person
Public Query
Modification(s)  
Name  Dr Maya Sharma 
Designation  Vice President - CMR 
Affiliation  Novo Nordisk India Private Limited 
Address  Novo Nordisk India Private Limited, Nxt Tower - 2, Floor 1 & 2 Embassy Manyata Business Park, Nagavara Village, Kasaba Hobli, Bangalore, India

Bangalore
KARNATAKA
560045
India 
Phone  9911497869  
Fax    
Email  yrms@novonordisk.com  
 
Source of Monetary or Material Support  
Novo Nordisk A/S-Novo Allé, 2880 Bagsvaerd Denmark. 
 
Primary Sponsor
Modification(s)  
Name  Novo Nordisk 
Address  Novo Nordisk India Private Limited, 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     Czech Republic
France
Germany
Hungary
India
Italy
Japan
Malaysia
Poland
Slovenia
South Africa
Thailand
Turkey
United States of America  
Sites of Study
Modification(s)  
No of Sites = 13  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr AG Unnikrishnan  Chellaram Hospital – Diabetes care & Multispeciality  1st Floor, Lalani Quantum,"Pune-Bangalore highway NH4,oppsite calsoft building Bavdhan Budruk
Pune
MAHARASHTRA 		 020-66839830

uagcdi@cdi.org.in 
Dr Nihal Thomas  Christian Medical College  Room No 6, 810,Dept of Endocrinology Diabetes & Metabolism,
Vellore
TAMIL NADU 		 9843111996

nihal_thomas@yahoo.com 
Dr Jubbin Jacob  Christian Medical College & Hospital  Endocrine & Diabetes Unit, Christian Medical College & Hospital, Brown Road, Ludhiana
Ludhiana
PUNJAB 		 91-161-2115757

endocrinecmc@gmail.com 
Dr Ramesh Goyal  Department of Diabetology and Endocrinology Apollo Hospitals International Ltd,,   Bhat, Gandhinagar , Gujarat. 38242 8. India.
Gandhinagar
GUJARAT 		 9879512438

ramogoyal@yahoo.com 
Dr Surendra Kumar Sharma  Diabetes Thyroid & Endocrine Centre  A-1, Madrampur, Ajmerpur Road, Near 4 No ESI Hospital, Ajmer Road, Sodala– 302006
Jaipur
RAJASTHAN 		 9829010233

sksharmacr@gmail.com 
Dr SR Aravind  Diacon Hospital  Department of Endocrinology Diacon Hospital, 359-360, 19th Main,1st block, Rajajinagar
Bangalore
KARNATAKA 		 9008998367

draravind@hotmail.com 
Dr K P Singh  Fortis Hospital  Room Number – 603, Basement, Biomedical - Engineering Department, Sector 62, Phase VIII, Mohali – 160062
Rupnagar
PUNJAB 		 9815311711

drkp1292@gmail.com 
Dr V Mohan  MADRAS DIABETES RESEARCH FOUNDATION  Department of Endocrinology,#4 Conran Smith Road, Gopalapuram
Chennai
TAMIL NADU 		 91-44-43968888

drmohans@diabetes.ind.in 
Dr Manish Gutch  Medanta Hospital Lucknow  Sector A, Pocket 1, Sushant Golf City, Amar Shaheed Path -226030
Lucknow
UTTAR PRADESH 		 9453429252

Manish07gutch@gmail.com 
Dr Ashu Rastogi   Post Graduate Institute of Medical Education and Research(PGIMER)  Room no-16, Nehru Extension Block, PGIMER
Chandigarh
CHANDIGARH 		 09781001046

ashuendo@gmail.com 
Dr Uday Phadke  Sahyadri Super Speciality Hospital  30C, Erandwane, Karve Road, Pune
Pune
MAHARASHTRA 		 2067213000

uday@drudayphadke.com 
Dr Mayur Patel  Swasthya Diabetes Care   "Opp. Jaymangal BRTS Bus Stop, 132 ft. ring road, Naranpura, Ahmedabad.380013, India."
Ahmadabad
GUJARAT 		 9824602848

diabetes@swasthyaindia.com 
Dr Sunil M Jain  TOTALL Diabetes Hormone Institute  A Unit of Diabetes Thyroid Hormone Research Institute Pvt. Ltd., BCM Health Island, PU-4, Scheme No. 54, Near Bombay Hospital, Behind Prestige Institute of Management-452010
Indore
MADHYA PRADESH 		 9826023182

sunilmjain@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 13  
Name of Committee  Approval Status 
Chellaram Diabetes Institute-Institutional Ethics Committee  Approved 
Diacon Hospital Ethics Committee  Approved 
Ethics Committee of Diabetes Thyroid Hormone Research Institute  Approved 
Human Welfare Ethical committee for Human sciences and Research  Approved 
INSTITUTIONAL ETHICS COMMITTEEE OF MADRAS DIABETES RESEARCH FOUNDATION  Approved 
Institutional Ethics Committee Medanta lucknow  Approved 
Institutional Ethics Committee(PGIMR)  Approved 
Institutional Ethics Committee, Christian Medical College & Hospital, Ludhiana  Approved 
Institutional Ethics Committee, Fortis Hospital, Mohali  Approved 
Institutional Ethics Committee- Clinical Studies(Apollo)  Approved 
Institutional Review Board-CMC Vellore  Approved 
Rlddhi Medical Nursing Home IEC,  Approved 
Sahyadri Hospital Pvt Limited Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
No Objection Certificate 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: E119||Type 2 diabetes mellitus without complications,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  IcoSema  once weekly icosema subcutaneous Injection with Insulin Aspart with or without OADs 
Comparator Agent  Insulin Glargine  once daily insulin glargine subcutaneous injection with Insulin Aspart with or without OADs 
 
Inclusion Criteria
Modification(s)  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  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 18 years at the time of signing informed consent.
4. Diagnosed with type 2 diabetes mellitus ≥ 180 days before screening.
5. HbA1c of 7.0-10.0% (53.0-85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening.
6. Treated with once daily or twice-daily basal insulin (neutral protamine hagedorn insulin, insulin degludec, insulin detemir, insulin glargine 100 units/mL, or insulin glargine 300 units/mL) 20-80 units/day ≥ 90 days before screening. Short term bolus insulin treatment for a maximum of 14 days before screening is allowed, as is prior insulin treatment for gestational diabetes. The treatment can be with or without any of the following anti-diabetic drugs with stable doses ≥ 90 days before screening: ▪ Metformin ▪ Sulfonylureasa ▪ Meglitinides (glinides)a ▪ DPP4 inhibitorsa ▪ Sodium-glucose co-transporter 2 inhibitors ▪ Alpha-glucosidase-inhibitors ▪ Thiazolidinediones ▪ Marketed oral combination products only including the products listed above.
7. Body mass index (BMI) ≤ 40.0 kg/m2 .
8. Not currently using real time continuous or flash glucose monitoring.
 
 
ExclusionCriteria 
Details  1. Known or suspected hypersensitivity to randomised treatment or related products.
2. Previous participation in this study. Participation is defined as signed informed consent.
3. Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method, as defined in Appendix 4.
4. Participation (i.e., signed informed consent) in any interventional, clinical study within 90 days before screening. Note: Simultaneous participation in a study with the primary objective of evaluating an approved or non-approved investigational medicinal product for prevention or treatment of COVID-19 disease or postinfectious conditions is allowed if the last dose of the investigational medicinal product has been received more than 30 days before screening in the current study and if simultaneous participation is allowed by local authorities.
5. Any disorder, except for conditions associated with T2D, which in the investigator’s opinion might jeopardise participant’s safety or compliance with the protocol.
6. Anticipated initiation or change in concomitant medication (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or systemic corticosteroids).
7. Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening.
8. Any episodesa of diabetic ketoacidosis within 90 days before screening.
9. Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma.
10. Presence or history of pancreatitis (acute or chronic) within 180 days before screening.
11. Any of the following: Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days before screening.
12. Chronic heart failure classified as being in New York Heart Association Class IV at screening.
13. Planned coronary, carotid or peripheral artery revascularisation.
14. Renal impairment measured as estimated glomerular filtration rate value of < 30 ml/min/1.73 m2 at screening as defined by KDIGO 2012.27
15. Impaired liver function, defined as alanine aminotransferase ≥ 2.5 times or bilirubin > 1.5 times upper normal limit at screening.
16. Known hypoglycaemic unawareness as indicated by the investigator according to Clarke’s questionnaire question 8. 28 .
17. Recurrent severe hypoglycaemic episodes within the last year (12 months) as judged by the investigator.
18. Inadequately treated blood pressure defined as systolic ≥ 180 mmHg or diastolic ≥ 110 mmHg at screening.
19. Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 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, see 8.2.4. 20. Presence or history of malignant neoplasm (other than basal or squamous cell skin cancer, in-situ carcinomas of the cervix, or in situ prostate cancer) within 5 years before screening.
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Change in HbA1c - % point  From baseline week 0 (V2) to week 52 (V54) 
 
Secondary Outcome  
Outcome  TimePoints 
"Change in body weight - in KG
" 		 From baseline week 0 (V2) to week 52 (V54) 
Number of clinically significant hypoglycaemic episodes (level 2) (3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3)  From baseline week 0 (V2) to week 57 (V56) 
Weekly insulin dose (total)  From week 50 (V52) to week 52 (V54) 
Time in range 3.9-10.0 mmol/L (70-180 mg/dL)  From week 48 (V50) to week 52 (V54) 
Time spent 3.0 mmol/L (54 mg/dL)  From week 48 (V50) to week 52 (V54) 
Time spent 10.0 mmol/L (180 mg/dL)  From week 48 (V50) to week 52 (V54) 
Change in fasting plasma glucose (FPG) - in mmol/L  From baseline week 0 (V2) to week 52 (V54) 
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in total treatment satisfaction  From baseline week 0 (V2) to week 52 (V54) 
Number of clinically significant hypoglycaemic episodes (level 2) (3.0 mmol/L (54 mg/dL), confirmed by BG meter)  From baseline week 0 (V2) to week 57 (V56) 
Number of severe hypoglycaemic episodes (level 3)  From baseline week 0 (V2) to week 57 (V56) 
 
Target Sample Size   Total Sample Size="680"
Sample Size from India="120" 
Final Enrollment numbers achieved (Total)= "679"
Final Enrollment numbers achieved (India)="90" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)
Modification(s)  		 02/03/2022 
Date of Study Completion (India) Date Missing 
Date of First Enrollment (Global)  08/12/2021 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="1"
Months="1"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Completed 
Recruitment Status of Trial (India)  Completed 
Publication Details    
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary
Modification(s)  
This is an interventional, multi-national, multi-centre, randomised, 52-week, open label, parallel
group, treat-to-target, confirmatory study with two treatment arms.This study is designed to investigate the efficacy and safety of once weekly IcoSema, which is a combination product of insulin icodec and semaglutide. IcoSema will be compared to daily insulin glargine 100 units/mL combined with insulin aspart, both treatment arms with or without oral anti-diabetic drugs, in participants with type 2 diabetes inadequately controlled with daily basal insulin.
 
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