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)

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05013229
• Collaborator: (none)
• Enrollment: 680
• Locations: 101
• Arms: 2
• Anticipated Duration (Months): 22.4
• Patients Per Site: 6.7
• Patients Per Site Per Month: 0.3

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 insulin glargine taken daily with insulin aspart 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 insulin glargine taken with insulin aspart. Participants will either get IcoSema or insulin glargine taken with insulin aspart. Which treatment participants get is decided by chance. IcoSema is a new medicine that doctors cannot prescribe. Doctors can already prescribe insulin glargine and insulin aspart in many countries.

Participants will get IcoSema or insulin glargine together with insulin aspart. Participants must inject IcoSema once a week or inject insulin glargine once daily and insulin aspart 2-4 times a day. Participants will inject the medicines 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 be asked to wear a sensor that measures participants blood sugar level all the time during an 8 week period at the beginning of the study and a 4 week period at the end of the study.

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: Insulin glargine; Drug: insulin aspart	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 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. COMBINE 3
• Actual Study Start Date: Nov 30, 2021
• Anticipated Primary Completion Date: Sep 13, 2023
• Anticipated Study Completion Date: Oct 13, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IcoSema Participants will receive once weekly subcutaneous (s.c) injections of IcoSema during the 52-week treatment period.	Drug: IcoSema; Participants will receive a once weekly subcutanous (s.c.) injection of IcoSema, on the same day every week for 52 weeks.
Active Comparator: Insuling glargine/insulin aspart Participants will receive subcutaneous (s.c) injections of insulin glargine once daily combined with 2-4 times daily injections of insulin aspart.	Drug: Insulin glargine; Participants will receive a once daily subcutaneous (s.c.) injection of insulin glargine combined with Insulin aspart 2-4 times a day during mealtimes for 52 weeks.; Drug: insulin aspart; Participants will receive a once daily subcutaneous (s.c.) injection of insulin glargine combined with Insulin aspart 2-4 times a day during mealtimes for 52 weeks.

Outcome Measures

Primary Outcome Measures

1. Change in HbA1c [From baseline week 0 (V2) to week 52 (V54)]

   Percent-points

Secondary Outcome Measures

1. Change in body weight [From baseline week 0 (V2) to week 52 (V54)]

   Kg

2. Number of clinically significant hypoglycaemic episodes (level 2) (less than 3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3) [From week 0 (V52) to week 52 (V54)]

   Number of episodes

3. Time in range 3.9 - 10.0 mmol/L (70 - 180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 [From week 48 (V50) to week 52 (V54)]

   Percentage of readings

4. Time spent more than 10.0 mmol/L (180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 [From week 48 (V50) to week 52 (V54)]

   Percentage of readings

5. Time spent less than 3.0 mmol/L (54 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 [From week 48 (V50) to week 52 (V54)]

   Percentage of readings

6. Change in fasting plasma glucose (FPG) [From baseline week 0 (V2) to week 52 (V54)]

   mmol/L

7. Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in total treatment satisfaction [From baseline week 0 (V2) to week 52 (V54)]

   Score 0-36. The higher the score the greater the satisfaction with treatment.

8. Number of severe hypoglycaemic episodes (level 3) [From baseline week 0 (V2) to week 57 (V56)]

   Number of episodes

9. Number of clinically significant hypoglycaemic episodes (level 2) (less than 3.0 mmol/L (54 mg/dL), confirmed by BG meter) [From baseline week 0 (V2) to week 57 (V56)]

   Number of episodes

10. Weekly insulin dose (total) [From week 50 (V52) to week 52 (V54)]

    Units

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 percentage (53.- 85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening.

• 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 or more 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 or more before screening:

• Metformin

• Sulfonylureas(a)

• Meglitinides (glinides)(a)

• DPP-4 inhibitors(a)

• Sodium-glucose co-transporter 2 inhibitors

• Alpha-glucosidase-inhibitors

• Thiazolidinediones

• Marketed oral combination products only including the products listed above.

• Body mass index (BMI) less than or equal to 40.0 kg/m^2.

1. Sulfonylureas, meglitinides (glinides) and DPP-4 inhibitors must be discontinued at randomisation.

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 of diabetic ketoacidosis within 90 days before screening. As declared by the participant or in the medical records.

• 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.

• Recurrent severe hypoglycaemic episodes within the last year (12 months) as judged by the investigator.

• 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	La Jolla	California	United States	92037
2	Novo Nordisk Investigational Site	Los Angeles	California	United States	90017
3	Novo Nordisk Investigational Site	San Diego	California	United States	92111
4	Novo Nordisk Investigational Site	Denver	Colorado	United States	80209
5	Novo Nordisk Investigational Site	Fleming Island	Florida	United States	32003
6	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32204
7	Novo Nordisk Investigational Site	Mount Dora	Florida	United States	32757
8	Novo Nordisk Investigational Site	Orlando	Florida	United States	32825
9	Novo Nordisk Investigational Site	Pembroke Pines	Florida	United States	33027
10	Novo Nordisk Investigational Site	Roswell	Georgia	United States	30076
11	Novo Nordisk Investigational Site	Nampa	Idaho	United States	83686-6011
12	Novo Nordisk Investigational Site	Skokie	Illinois	United States	60077
13	Novo Nordisk Investigational Site	West Des Moines	Iowa	United States	50265
14	Novo Nordisk Investigational Site	Lexington	Kentucky	United States	40503
15	Novo Nordisk Investigational Site	Hyattsville	Maryland	United States	20782
16	Novo Nordisk Investigational Site	Methuen	Massachusetts	United States	01844
17	Novo Nordisk Investigational Site	Buckley	Michigan	United States	49620
18	Novo Nordisk Investigational Site	Las Vegas	Nevada	United States	89128
19	Novo Nordisk Investigational Site	Nashua	New Hampshire	United States	03060
20	Novo Nordisk Investigational Site	West Seneca	New York	United States	14224
21	Novo Nordisk Investigational Site	Statesville	North Carolina	United States	28625
22	Novo Nordisk Investigational Site	Wilmington	North Carolina	United States	28401
23	Novo Nordisk Investigational Site	Canton	Ohio	United States	44718
24	Novo Nordisk Investigational Site	Franklin	Ohio	United States	45005
25	Novo Nordisk Investigational Site	Wadsworth	Ohio	United States	44281
26	Novo Nordisk Investigational Site	Simpsonville	South Carolina	United States	29681-1538
27	Novo Nordisk Investigational Site	Bartlett	Tennessee	United States	38133
28	Novo Nordisk Investigational Site	Chattanooga	Tennessee	United States	37411
29	Novo Nordisk Investigational Site	Morristown	Tennessee	United States	37813
30	Novo Nordisk Investigational Site	Amarillo	Texas	United States	79106
31	Novo Nordisk Investigational Site	Dallas	Texas	United States	75230
32	Novo Nordisk Investigational Site	Houston	Texas	United States	77079
33	Novo Nordisk Investigational Site	Hurst	Texas	United States	76054
34	Novo Nordisk Investigational Site	Laredo	Texas	United States	78041
35	Novo Nordisk Investigational Site	Plano	Texas	United States	75075
36	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78224
37	Novo Nordisk Investigational Site	Schertz	Texas	United States	78154
38	Novo Nordisk Investigational Site	Sugar Land	Texas	United States	77478
39	Novo Nordisk Investigational Site	Saint George	Utah	United States	84790
40	Novo Nordisk Investigational Site	Renton	Washington	United States	98057
41	Novo Nordisk Investigational Site	Brno		Czechia	656 91
42	Novo Nordisk Investigational Site	Hradec Kralove		Czechia	500 05
43	Novo Nordisk Investigational Site	Plzen		Czechia	304 60
44	Novo Nordisk Investigational Site	Praha		Czechia	14021
45	Novo Nordisk Investigational Site	Praha		Czechia	160 00
46	Novo Nordisk Investigational Site	LA ROCHE-sur-YON cedex 9		France	85295
47	Novo Nordisk Investigational Site	Le Coudray		France	28630
48	Novo Nordisk Investigational Site	Le Creusot		France	71200
49	Novo Nordisk Investigational Site	Paris		France	75010
50	Novo Nordisk Investigational Site	Pessac		France	33600
51	Novo Nordisk Investigational Site	Venissieux		France	69200
52	Novo Nordisk Investigational Site	Essen		Germany	45136
53	Novo Nordisk Investigational Site	Essen		Germany	45359
54	Novo Nordisk Investigational Site	Hamburg		Germany	22607
55	Novo Nordisk Investigational Site	Münster		Germany	48145
56	Novo Nordisk Investigational Site	Oldenburg I. Holst		Germany	23758
57	Novo Nordisk Investigational Site	Saint Ingbert-Oberwürzbach		Germany	66386
58	Novo Nordisk Investigational Site	Budapest		Hungary	1033
59	Novo Nordisk Investigational Site	Budapest		Hungary	1088
60	Novo Nordisk Investigational Site	Békéscsaba		Hungary	5600
61	Novo Nordisk Investigational Site	Pécs		Hungary	7623
62	Novo Nordisk Investigational Site	Gandhinagar	Gujarat	India	382428
63	Novo Nordisk Investigational Site	Pune	Maharashtra	India	411004
64	Novo Nordisk Investigational Site	Pune	Maharashtra	India	411021
65	Novo Nordisk Investigational Site	Ludhiana	Punjab	India	141008
66	Novo Nordisk Investigational Site	Chennai	Tamil Nadu	India	600086
67	Novo Nordisk Investigational Site	Vellore	Tamil Nadu	India	632004
68	Novo Nordisk Investigational Site	Ahmedabad		India	390013
69	Novo Nordisk Investigational Site	Bangalore		India	560010
70	Novo Nordisk Investigational Site	Catanzaro		Italy	88100
71	Novo Nordisk Investigational Site	Aichi		Japan	468-0009
72	Novo Nordisk Investigational Site	Chiba-shi, Chiba		Japan	260-0804
73	Novo Nordisk Investigational Site	Chuo-ku, Tokyo		Japan	103-0002
74	Novo Nordisk Investigational Site	Ibaraki		Japan	311-0113
75	Novo Nordisk Investigational Site	Kawagoe-shi, Saitama		Japan	350-0851
76	Novo Nordisk Investigational Site	Mito-shi, Ibaraki		Japan	311-4153
77	Novo Nordisk Investigational Site	Miyazaki		Japan	880-0034
78	Novo Nordisk Investigational Site	Tokyo		Japan	103-0027
79	Novo Nordisk Investigational Site	Cheras		Malaysia	56000
80	Novo Nordisk Investigational Site	Kota Bharu, Kelantan		Malaysia	16150
81	Novo Nordisk Investigational Site	Kuala Lumpur		Malaysia	59100
82	Novo Nordisk Investigational Site	Sungai Buloh		Malaysia	47000
83	Novo Nordisk Investigational Site	Bialystok		Poland	15-404
84	Novo Nordisk Investigational Site	Bialystok		Poland	15-435
85	Novo Nordisk Investigational Site	Gdynia		Poland	81-338
86	Novo Nordisk Investigational Site	Lodz		Poland	90-132
87	Novo Nordisk Investigational Site	Lodz		Poland	90-242
88	Novo Nordisk Investigational Site	Warsaw		Poland	00-465
89	Novo Nordisk Investigational Site	Koper		Slovenia	SI-6000
90	Novo Nordisk Investigational Site	Ljubljana		Slovenia	1525
91	Novo Nordisk Investigational Site	Murska Sobota		Slovenia	SI-9000
92	Novo Nordisk Investigational Site	Nova Gorica		Slovenia	SI-5290
93	Novo Nordisk Investigational Site	Bloemfontein	Free State	South Africa	9301
94	Novo Nordisk Investigational Site	Lenasia	Gauteng	South Africa	1827
95	Novo Nordisk Investigational Site	Pretoria	Gauteng	South Africa	0181
96	Novo Nordisk Investigational Site	Cape Town	Western Cape	South Africa	7441
97	Novo Nordisk Investigational Site	Bangkoknoi, Bangkok		Thailand	10700
98	Novo Nordisk Investigational Site	Bangkok		Thailand	10400
99	Novo Nordisk Investigational Site	Chiang Mai		Thailand	50200
100	Novo Nordisk Investigational Site	Khon Kaen		Thailand	40002
101	Novo Nordisk Investigational Site	Nakhon Ratchasima		Thailand	30000

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: NCT05013229
• Other Study ID Numbers: NN1535-4593; U1111-1260-8295; 2020-005309-18; jRCT2051210127
• First Posted: Aug 19, 2021
• Last Update Posted: Mar 25, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin; Insulin, Globin Zinc; Insulin Glargine; Insulin Aspart

Study Results

No Results Posted as of Mar 25, 2022