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 Weekly Semaglutide (COMBINE 2)

Sponsor

Novo Nordisk A/S (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05259033

Collaborator

(none)

680

Enrollment

Locations

Arms

22.2

Anticipated Duration (Months)

8.3

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will compare the new medicine IcoSema, which is a combination of insulin icodec and semaglutide, taken once a week, to semaglutide taken once a week in people with type 2 diabetes.

The study will look at how well IcoSema controls blood sugar level in people with type 2 diabetes compared to semaglutide.

Participants will either get IcoSema or semaglutide. Which treatment participants get is decided by chance. IcoSema is a new medicine that doctors cannot prescribe. Doctors can already prescribe semaglutide in many countries.

Participants will get IcoSema or semaglutide, which they must inject once a week with a pen, which has a small needle, in a skin fold in the thigh, upper arm, or stomach.

The study will last for about 1 year and 1 month. Participants will have 18 clinic visits, 34 phone/video calls with the study doctor, and 4 contacts with the site that can either be clinic visits or phone/video calls.

At 11 clinic visits participants will have blood samples taken. At 7 clinic visits participants cannot eat or drink (except for water) for 8 hours before the visit.

Women cannot take part if pregnant, breast-feeding or plan to get pregnant during the study period.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: IcoSema Drug: Semaglutide 1 mg	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

680 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 11, 2022

Anticipated Primary Completion Date :

Jan 12, 2024

Anticipated Study Completion Date :

Feb 17, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IcoSema Participants will get once weekly dose	Drug: IcoSema IcoSema once weekly subcutaneously (s.c., under the skin) using a needle and a pen. For about 1 year and 1 month.
Experimental: Semaglutide Participants will get once weekly dose	Drug: Semaglutide 1 mg Semaglutide once weekly subcutaneously (s.c., under the skin). Dose titrated to 1mg over 8 weeks (0.25 mg for 4 weeks, 0.5 mg for 4 weeks). For about 1 year and 1 month.

Arm

Intervention/Treatment

Experimental: IcoSema

Participants will get once weekly dose

Drug: IcoSema

IcoSema once weekly subcutaneously (s.c., under the skin) using a needle and a pen. For about 1 year and 1 month.

Experimental: Semaglutide

Participants will get once weekly dose

Drug: Semaglutide 1 mg

Semaglutide once weekly subcutaneously (s.c., under the skin). Dose titrated to 1mg over 8 weeks (0.25 mg for 4 weeks, 0.5 mg for 4 weeks). For about 1 year and 1 month.

Outcome Measures

Primary Outcome Measures

Change in glycated haemoglobin (HbA1c) [From baseline week 0 (V2) to week 52 (V54)]
Percentage-point

Secondary Outcome Measures

Change in fasting plasma glucose (FPG) [From baseline week 0 (V2) to week 52 (V54)]
Measured in mmol/L
Change in body weight [From baseline week 0 (V2) to week 52 (V54)]
Measured in Kg
Number of clinically significant hypoglycaemic episodes (level 2) (below 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)]
Number of episodes
Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 mmol/L (54 mg/dL), confirmed by BG meter) [From baseline week 0 (V2) to week 57 (V56)]
Number of episodes
Number of severe hypoglycaemic episodes (level 3) [From baseline week 0 (V2) to week 57 (V56)]
Number of episodes

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female and age above or equal to 18 years at the time of signing informed consent.
Diagnosed with type 2 diabetes mellitus 180 days or more before screening.
HbA1c of 7.0 - 10.0% (53.0 - 85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening.
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.
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.
Body mass index (BMI) below or equal to 40.0 kg/m^2.

Exclusion Criteria:

Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method.
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).
Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening.
Any episodes (as declared by the participant or in the medical records) of diabetic ketoacidosis within 90 days before screening.
Presence or history of pancreatitis (acute or chronic) within 180 days before screening.
Any of the following: Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days before screening.
Chronic heart failure classified as being in New York Heart Association Class IV at screening.
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Birmingham	Alabama	United States	35294
2	Novo Nordisk Investigational Site	Gilbert	Arizona	United States	85296
3	Novo Nordisk Investigational Site	Sun City West	Arizona	United States	85375
4	Novo Nordisk Investigational Site	Concord	California	United States	94520
5	Novo Nordisk Investigational Site	Los Angeles	California	United States	90017
6	Novo Nordisk Investigational Site	Los Angeles	California	United States	90057
7	Novo Nordisk Investigational Site	Northridge	California	United States	91325
8	Novo Nordisk Investigational Site	Sacramento	California	United States	95821
9	Novo Nordisk Investigational Site	Toluca Lake	California	United States	91602
10	Novo Nordisk Investigational Site	Fleming Island	Florida	United States	32003
11	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32204
12	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32216
13	Novo Nordisk Investigational Site	Mount Dora	Florida	United States	32757
14	Novo Nordisk Investigational Site	Orlando	Florida	United States	32825
15	Novo Nordisk Investigational Site	Oviedo	Florida	United States	32765
16	Novo Nordisk Investigational Site	Pembroke Pines	Florida	United States	33027
17	Novo Nordisk Investigational Site	West Palm Beach	Florida	United States	33401
18	Novo Nordisk Investigational Site	Roswell	Georgia	United States	30076
19	Novo Nordisk Investigational Site	Honolulu	Hawaii	United States	96814
20	Novo Nordisk Investigational Site	Nampa	Idaho	United States	83686-6011
21	Novo Nordisk Investigational Site	Carlinville	Illinois	United States	62626
22	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60607
23	Novo Nordisk Investigational Site	Skokie	Illinois	United States	60077
24	Novo Nordisk Investigational Site	Slidell	Louisiana	United States	70461-4231
25	Novo Nordisk Investigational Site	Hyattsville	Maryland	United States	20782
26	Novo Nordisk Investigational Site	Buckley	Michigan	United States	49620
27	Novo Nordisk Investigational Site	Las Vegas	Nevada	United States	89148
28	Novo Nordisk Investigational Site	Nashua	New Hampshire	United States	03063
29	Novo Nordisk Investigational Site	Lawrenceville	New Jersey	United States	08648
30	Novo Nordisk Investigational Site	Albuquerque	New Mexico	United States	87102
31	Novo Nordisk Investigational Site	West Seneca	New York	United States	14224
32	Novo Nordisk Investigational Site	Greensboro	North Carolina	United States	27408
33	Novo Nordisk Investigational Site	Canton	Ohio	United States	44718
34	Novo Nordisk Investigational Site	Wadsworth	Ohio	United States	44281
35	Novo Nordisk Investigational Site	Summerville	South Carolina	United States	29485
36	Novo Nordisk Investigational Site	Bartlett	Tennessee	United States	38133
37	Novo Nordisk Investigational Site	Chattanooga	Tennessee	United States	37404
38	Novo Nordisk Investigational Site	Amarillo	Texas	United States	79106
39	Novo Nordisk Investigational Site	Austin	Texas	United States	78731
40	Novo Nordisk Investigational Site	Austin	Texas	United States	78749
41	Novo Nordisk Investigational Site	Corpus Christi	Texas	United States	78414
42	Novo Nordisk Investigational Site	Dallas	Texas	United States	75231
43	Novo Nordisk Investigational Site	Fort Worth	Texas	United States	76132
44	Novo Nordisk Investigational Site	Live Oak	Texas	United States	78233
45	Novo Nordisk Investigational Site	Longview	Texas	United States	75605
46	Novo Nordisk Investigational Site	Round Rock	Texas	United States	78681
47	Novo Nordisk Investigational Site	Sugar Land	Texas	United States	77479
48	Novo Nordisk Investigational Site	Saint George	Utah	United States	84790
49	Novo Nordisk Investigational Site	Forest	Virginia	United States	24551
50	Novo Nordisk Investigational Site	Curitiba	Parana	Brazil	80810-040
51	Novo Nordisk Investigational Site	Concord	Ontario	Canada	L4K 4M2
52	Novo Nordisk Investigational Site	Hamilton	Ontario	Canada	L8L 5G8
53	Novo Nordisk Investigational Site	Oshawa	Ontario	Canada	L1G4T3
54	Novo Nordisk Investigational Site	Sarnia	Ontario	Canada	N7T 4X3
55	Novo Nordisk Investigational Site	Toronto	Ontario	Canada	M4G 3E8
56	Novo Nordisk Investigational Site	Montreal	Quebec	Canada	H1M 1B1
57	Novo Nordisk Investigational Site	Montreal	Quebec	Canada	H4T 1Z9
58	Novo Nordisk Investigational Site	Quebec		Canada	G1G 3Y8
59	Novo Nordisk Investigational Site	Quebec		Canada	G1N 4V3
60	Novo Nordisk Investigational Site	Beijing	Beijing	China	100044
61	Novo Nordisk Investigational Site	Huizhou	Guangdong	China	516001
62	Novo Nordisk Investigational Site	Changzhou	Jiangsu	China	213003
63	Novo Nordisk Investigational Site	Nanjing	Jiangsu	China	210011
64	Novo Nordisk Investigational Site	Jinan	Shandong	China	250013
65	Novo Nordisk Investigational Site	Shanghai	Shanghai	China	200240
66	Novo Nordisk Investigational Site	Athens		Greece	115 25
67	Novo Nordisk Investigational Site	Athens		Greece	GR-115 27
68	Novo Nordisk Investigational Site	Larissa		Greece	GR-41110
69	Novo Nordisk Investigational Site	Thessaloniki		Greece	GR-54635
70	Novo Nordisk Investigational Site	Thessaloniki		Greece	GR-54642
71	Novo Nordisk Investigational Site	Thessaloniki		Greece	GR-57010
72	Novo Nordisk Investigational Site	Haifa		Israel	35152
73	Novo Nordisk Investigational Site	Herzlia		Israel	4630945
74	Novo Nordisk Investigational Site	Holon		Israel	58100
75	Novo Nordisk Investigational Site	Jerusalem		Israel	91120
76	Novo Nordisk Investigational Site	Tel Hashomer		Israel	52621
77	Novo Nordisk Investigational Site	Kosice		Slovakia	04001
78	Novo Nordisk Investigational Site	Kosice		Slovakia	04011
79	Novo Nordisk Investigational Site	Kosice		Slovakia	04190
80	Novo Nordisk Investigational Site	Levice		Slovakia	93401
81	Novo Nordisk Investigational Site	Turcianske Teplice		Slovakia	039 01
82	Novo Nordisk Investigational Site	Tainan City		Taiwan	704

Sponsors and Collaborators

Novo Nordisk A/S

Investigators

Study Director: Clinical Transparency (dept. 1452), Novo Nordisk A/S

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Novo Nordisk A/S

ClinicalTrials.gov Identifier:

NCT05259033

Other Study ID Numbers:

NN1535-4592
U1111 1260 8268
2020 005308 21

First Posted:

Feb 28, 2022

Last Update Posted:

Jun 30, 2022

Last Verified:

Jun 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Diabetes Mellitus

Diabetes Mellitus, Type 2

Study Results

No Results Posted as of Jun 30, 2022