Clinical Trials List
Protocol NumberNN1535-4592
NCT Number(ClinicalTrials.gov Identfier)NCT05259033
Completed
2022-04-05 - 2024-09-30
Phase III
Not yet recruiting4
Terminated1
ICD-10E11.65
Type 2 diabetes mellitus with hyperglycemia
ICD-10E11.8
Type 2 diabetes mellitus with unspecified complications
ICD-9250.92
Diabetes with unspecified complication, Type II [non-insulin dependent type][NIDDM type][adult-onset type] or unspecified type, uncontrolled
A 52-week study comparing the efficacy and safety of once weekly IcoSema and once weekly semaglutide, both treatment arms with or without oral anti-diabetic drugs, in participants with type 2 diabetes inadequately controlled with a GLP-1 receptor agonist. COMBINE 2
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Trial Applicant
NOVO NORDISK PHARMA (TAIWAN) LTD.
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Sponsor
Novo Nordisk A/S
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Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- 洪士淵 無
- Jia-Hong Lin 無
- 黃瓊慧 無
- Chih-Yiu Tsai Division of Endocrinology
- 陳怡文 無
- 林承緯 無
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- Chii-Min Hwu Division of Endocrinology
- Liang-Yu Lin Division of Endocrinology
- Harn-Shen Chen Division of Endocrinology
- Chun-Jui Huang Division of Endocrinology
- Chin-Sung Kuo Division of Endocrinology
- 許惠恒 Division of Endocrinology
- 陳涵栩 Division of Endocrinology
The Actual Total Number of Participants Enrolled
0 Completed
Condition/Disease
Type 2 Diabetes
Objectives
To confirm superiority of once weekly IcoSema compared with once weekly semaglutide, both
treatment arms with or without oral anti-diabetic drugs, in terms of glycaemic control measured by
change in HbA1c from baseline after 52 weeks in participants with type 2 diabetes inadequately
controlled with a GLP-1 receptor agonist.
Test Drug
IcoSema
Active Ingredient
IcoSema
Semaglutide
Semaglutide
Dosage Form
Solution for injection
Dosage
Insulin icodec 700 units/mL + Semaglutide 2 mg/mL
1.34 mg/m
1.34 mg/m
Endpoints
Change in HbA1c
Inclution Criteria
Inclusion Criteria:
1. Male or female and age above or equal to 18 years at the time of signing informed consent.
2. Diagnosed with type 2 diabetes mellitus 180 days or more before screening.
3. HbA1c of 7.0 - 10.0% (53.0 - 85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening.
4. Insulin naïve. The following exceptions are permitted: short term insulin treatment for a maximum of 14 days before screening and/or prior insulin treatment for gestational diabetes.
5. Treated with stable doses of daily or weekly GLP-1 receptor agonist (excluding once weekly semaglutide with doses higher than 1.0 mg) according to local label for the treatment of diabetes for 90 days or more before screening. The treatment can be with or without any of the following anti diabetic drugs with stable doses for 90 days or more before screening: Metformin - Sulfonylureas (Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation) - Meglitinides (glinides)(Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation) - DPP 4 inhibitors (Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation) - Sodium glucose co transporter 2 inhibitors - Alpha-glucosidase inhibitors - Thiazolidinediones - Marketed oral combination products only including the products listed above.
6. Body mass index (BMI) below or equal to 40.0 kg/m^2.
1. Male or female and age above or equal to 18 years at the time of signing informed consent.
2. Diagnosed with type 2 diabetes mellitus 180 days or more before screening.
3. HbA1c of 7.0 - 10.0% (53.0 - 85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening.
4. Insulin naïve. The following exceptions are permitted: short term insulin treatment for a maximum of 14 days before screening and/or prior insulin treatment for gestational diabetes.
5. Treated with stable doses of daily or weekly GLP-1 receptor agonist (excluding once weekly semaglutide with doses higher than 1.0 mg) according to local label for the treatment of diabetes for 90 days or more before screening. The treatment can be with or without any of the following anti diabetic drugs with stable doses for 90 days or more before screening: Metformin - Sulfonylureas (Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation) - Meglitinides (glinides)(Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation) - DPP 4 inhibitors (Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation) - Sodium glucose co transporter 2 inhibitors - Alpha-glucosidase inhibitors - Thiazolidinediones - Marketed oral combination products only including the products listed above.
6. Body mass index (BMI) below or equal to 40.0 kg/m^2.
Exclusion Criteria
Exclusion Criteria:
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. Insulin naïve. The following exceptions are permitted: short term insulin treatment for a
maximum of 14 days before screening and/or prior insulin treatment for gestational diabetes.
7. Treated with stable doses of daily or weekly GLP-1 receptor agonist (excluding once weekly
semaglutide with doses higher than 1.0 mg) according to local label for the treatment of diabetes
≥ 90 days before screening. 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
▪ DPP-4 inhibitorsa
▪ Sodium-glucose co-transporter 2 inhibitors
▪ Alpha-glucosidase-inhibitors
▪ Thiazolidinediones
▪ Marketed oral combination products only including the products listed above.
8. Body mass index (BMI) ≤ 40.0 kg/m2
.
9. Not currently using real time continuous or flash glucose monitoring.
a Sulfonylureas, meglitinides (glinides) and DPP-4 inhibitors must be discontinued at randomisation.
5.2 Exclusion criteria
Participants are excluded from the study if any of the following criteria apply:
1. Known or suspected hypersensitivity to randomised treatment or related products.
2. Previous participation in this study. Participation is defined as signed informed consent.
Protocol
CONFIDENTIAL
Date: 10 August 2021 Novo Nordisk
Study ID: NN1535-4592 Version: 4.0
Status: Final
Page: 29 of 103
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 2012.20
15. Impaired liver function, defined as alanine aminotransferase ≥ 2.5 times or bilirubin > 1.5 times
upper normal limit at screening.
16. Inadequately treated blood pressure defined as systolic ≥ 180 mmHg or diastolic ≥ 110 mmHg
at screening.
17. 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.
18. 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.
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. Insulin naïve. The following exceptions are permitted: short term insulin treatment for a
maximum of 14 days before screening and/or prior insulin treatment for gestational diabetes.
7. Treated with stable doses of daily or weekly GLP-1 receptor agonist (excluding once weekly
semaglutide with doses higher than 1.0 mg) according to local label for the treatment of diabetes
≥ 90 days before screening. 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
▪ DPP-4 inhibitorsa
▪ Sodium-glucose co-transporter 2 inhibitors
▪ Alpha-glucosidase-inhibitors
▪ Thiazolidinediones
▪ Marketed oral combination products only including the products listed above.
8. Body mass index (BMI) ≤ 40.0 kg/m2
.
9. Not currently using real time continuous or flash glucose monitoring.
a Sulfonylureas, meglitinides (glinides) and DPP-4 inhibitors must be discontinued at randomisation.
5.2 Exclusion criteria
Participants are excluded from the study if any of the following criteria apply:
1. Known or suspected hypersensitivity to randomised treatment or related products.
2. Previous participation in this study. Participation is defined as signed informed consent.
Protocol
CONFIDENTIAL
Date: 10 August 2021 Novo Nordisk
Study ID: NN1535-4592 Version: 4.0
Status: Final
Page: 29 of 103
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 2012.20
15. Impaired liver function, defined as alanine aminotransferase ≥ 2.5 times or bilirubin > 1.5 times
upper normal limit at screening.
16. Inadequately treated blood pressure defined as systolic ≥ 180 mmHg or diastolic ≥ 110 mmHg
at screening.
17. 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.
18. 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.
The Estimated Number of Participants
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Taiwan
20 participants
-
Global
680 participants
