A 40-Week Randomized Study Evaluating the Efficacy and Safety of Weekly Insulin Icodec/Semaglutide Versus Daily Insulin Glargine in Type 2 Diabetes Patients
- Trial ID
- 2022-502484-38-00
- Protocol
- NN1535-4988
- Sponsor
- Novo Nordisk A/S
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to confirm the **superiority** of once-weekly IcoSema compared with daily insulin glargine in terms of glycaemic control, as measured by the change in HbA1c from baseline after 40 weeks. This is clinically relevant for participants with type 2 diabetes (T2D) who are inadequately controlled with oral antidiabetic drugs (OADs), as it may offer a more effective treatment regimen.
Secondary objectives include:
- Confirming the superiority of once-weekly IcoSema compared with daily insulin glargine in terms of change in body weight from baseline after 40 weeks in participants with T2D inadequately controlled with OADs.
- Comparing parameters of glycaemic control, patient-reported outcomes, and safety of once-weekly IcoSema with daily insulin glargine in participants with T2D inadequately controlled with OADs.
Participants
The clinical trial involves a total of **347 participants** diagnosed with **type 2 diabetes**. The study population includes both male and female subjects, aged 18 years and above, who have been diagnosed with type 2 diabetes mellitus for at least 180 days prior to screening. Participants are insulin-naïve, although short-term insulin treatment for a maximum of 14 consecutive days before screening is permissible, as well as prior insulin treatment for gestational diabetes. They are currently treated with 1-3 oral antidiabetic drugs (OADs) with stable daily doses for at least 90 days before screening. The participants have a body mass index (BMI) of 40.0 kg/m² or less. The trial population was selected based on these criteria, ensuring that individuals have an HbA1c level of 8.0% (64.0 mmol/mol) or higher, as assessed by a central laboratory on the day of screening. The study does not exclude vulnerable populations, and lifestyle factors such as diet and physical activity are not specified as part of the selection criteria. The sponsor has not provided additional information regarding specific lifestyle considerations.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy and safety of a new weekly medication, IcoSema, compared to daily **insulin glargine** in participants with **type 2 diabetes** inadequately controlled on oral antidiabetic drugs. This study is a randomized, double-blind, controlled trial with a duration of 40 weeks. Participants will be randomly assigned to receive either IcoSema or insulin glargine, with or without oral antidiabetic drugs (OADs), to assess the primary endpoint of change in HbA1c from baseline to week 40. Secondary endpoints include changes in body weight, time in range using continuous glucose monitoring, and the number of hypoglycemic episodes.
The trial will commence with a screening visit to confirm eligibility based on criteria such as age, diagnosis of type 2 diabetes, and HbA1c levels. Participants must be insulin-naïve and currently treated with 1-3 OADs. Following the screening, eligible participants will undergo randomization and begin the treatment phase. Study visits will occur at regular intervals to monitor safety, efficacy, and adherence to the treatment regimen. These visits will include assessments of glycemic control, body weight, and other relevant health parameters.
The expected length of participant involvement is approximately 40 weeks, with the possibility of early termination if significant adverse events occur or if the participant withdraws consent. The end-of-study visit will involve a comprehensive evaluation of the participant's health status and the collection of final data for analysis. The trial aims to provide robust data to support the potential indication update for IcoSema, contributing to the advancement of treatment options for individuals with type 2 diabetes.
Treatment
The clinical trial involves the administration of several treatments to evaluate their efficacy and safety in participants with type 2 diabetes inadequately controlled on oral antidiabetic drugs. **Dapagliflozin** is one of the experimental medications used in this study. It is administered orally in a pharmaceutical form identified as PHF00082MIG. The specific dosage and frequency of administration are not detailed in the provided data. Dapagliflozin is classified under the ATC code A10BK01, which corresponds to sodium-glucose co-transporter 2 inhibitors, a class of blood glucose-lowering drugs excluding insulins.
Another experimental treatment is **IcoSema**, a combination of **insulin icodec** and **semaglutide**. This medication is provided as a solution for injection with a concentration of 700 U/mL of insulin icodec and 2 mg/mL of semaglutide. It is administered subcutaneously using a PDS290-C Icosema pen-injector, a prefilled, multidose disposable delivery device. The maximum daily dose is 350 U, with a total maximum dose of 14,000 U over a 40-week treatment period. The administration frequency is once weekly.
**Metformin** is also included in the trial as a comparator treatment. It is administered orally in the same pharmaceutical form as dapagliflozin, PHF00082MIG. The specific dosage and frequency of administration are not provided. Metformin is classified under the ATC code A10BA02, indicating its role as a blood glucose-lowering drug.
**Insulin glargine** is used as a comparator treatment in the form of Lantus SoloStar, a solution for injection in a pre-filled pen. It is administered subcutaneously, with the specific dosage and frequency not detailed in the data. The treatment period for insulin glargine is up to 40 weeks. It is classified under the ATC codes A10AE and A10AE04, representing long-acting insulins and analogues.
**Pioglitazone** is another comparator treatment, administered orally in a pharmaceutical form identified as PHF00245MIG. The specific dosage and frequency of administration are not provided. Pioglitazone is classified under the ATC code A10BG03, which corresponds to thiazolidinediones, a class of blood glucose-lowering drugs excluding insulins.
Participant compliance with the treatment regimen is monitored throughout the study, although specific methods of compliance monitoring are not detailed in the provided data. The trial aims to confirm the superiority of once-weekly IcoSema compared to daily insulin glargine, with or without oral antidiabetic drugs, in terms of glycemic control as measured by changes in HbA1c levels from baseline after 40 weeks.
Efficacy
The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoint is the change in **HbA1c** levels from baseline at week 0 to week 40. This will be measured to confirm the superiority of once-weekly IcoSema compared to daily insulin glargine in participants with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs).
Secondary endpoints include changes in body weight from baseline to week 40, and various metrics using the continuous glucose monitoring (CGM) system, Dexcom G6, such as time in range (3.9–10.0 mmol/L), time spent below 3.0 mmol/L, and time spent above 10.0 mmol/L, all measured from week 36 to week 40. Additionally, the weekly basal insulin dose will be assessed from week 38 to week 40. The Diabetes Treatment Satisfaction Questionnaire (DTSQs) will be used to evaluate changes in total treatment satisfaction from baseline to week 40. The number of clinically significant hypoglycemic episodes (level 2) and severe hypoglycemic episodes (level 3) will be recorded from baseline to week 45. Lastly, changes in fasting plasma glucose (FPG) from baseline to week 40 will also be evaluated.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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.
- Male or female.
- Age 18 years or above at the time of signing the informed consent.
- Diagnosed with type 2 diabetes mellitus ≥ 180 days before screening.
- HbA1c ≥ 8.0% (≥ 64.0 mmol/mol) as assessed by central laboratory on the day of screening.
- Insulin naïve. Short term insulin treatment for a maximum of 14 consecutive days before screening is allowed, as is prior insulin treatment for gestational diabetes.
- Currently treated with 1-3 OADs with stable daily doses ≥ 90 days before screening comprising any of the following anti‑diabetic drug(s) at effective or maximum tolerated dose (a): Metformin, Sulfonylureasa (b), Meglitinides (glinides) (b), DPP 4 inhibitors (b), Sodium glucose co transporter 2 inhibitors, Alpha glucosidase inhibitors, Thiazolidinediones, Marketed oral combination products only including the products listed above. a) As per investigator judgement participant is suitable for intensification with injectables. b) Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation."
- Body mass index (BMI) ≤ 40.0 kg/m2.
Exclusion Criteria
- Known or suspected hypersensitivity to study intervention(s) or related products.
- Previous participation in this study. Participation is defined as signed informed consent.
- Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using highly effective contraceptive method, as defined in Appendix 4 (Section 10.4).
- Participation (defined as 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.(a) a) not applicable for Japan and China
- Any disorder, except for conditions associated with T2D, which in the investigator’s opinion might jeopardise participant’s safety or compliance with the protocol.
- 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(b) of diabetic ketoacidosis within 90 days before screening. b) as declared by the participant or in the medical records.
- Personal or first‑degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma.
- Presence or history of pancreatitis (acute or chronic) within 180 days before screening.(c) c) For Turkey, stricter exclusion criteria applies “Presence or history of pancreatitis (acute or chronic)” , see Appendix 16 (Section 10.16)
- 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.
- Planned coronary, carotid or peripheral artery revascularisation.
- Renal impairment measured as estimated glomerular filtration rate value of < 30 ml/min/1.73 m2 at screening as defined by KDIGO 2012.
- Impaired liver function, defined as alanine aminotransferase ≥ 2.5 times or bilirubin > 1.5 times upper normal limit at screening.
- Known hypoglycaemic unawareness as indicated by the investigator according to Clarke’s questionnaire question 8.
- Recurrent severe hypoglycaemic episodes within the last year (12 months) as judged by the investigator.
- Inadequately treated blood pressure defined as systolic ≥ 180 mmHg or diastolic ≥ 110 mmHg 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, see Section 8.2.5.
- 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.
- For Italy, an additional exclusion criteria “known severe diabetic autonomic neuropathy as judged by the investigator” is applicable, please see protocol Appendix 16 (Section 10.16)
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Greece | Not Recruiting | 15 Feb 2024 | 35 |
 Italy | Not Recruiting | 15 Feb 2024 | 40 |
 Poland | Not Recruiting | 15 Feb 2024 | 61 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
IcoSema 700 U/mL + 2 mg/mL PDS290 | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS | 350 | 40 | PRD8960774 |
Lantus SoloStar 100 units/ml solution for injection in a pre-filled pen | Comparator | SOLUTION FOR INJECTION IN A PRE-FILLED PEN | SUBCUTANEOUS | 00 | 40 | PRD2905020 |
DAPAGLIFLOZIN | Other | PHF00082MIG | ORAL | 00 | 1 | SCP153586 |
METFORMIN | Other | PHF00082MIG | ORAL | 00 | 1 | SCP135808 |
PIOGLITAZONE | Other | PHF00245MIG | ORAL | 00 | 1 | SCP129581 |
- | Other | PHF00245MIG | ORAL | 00 | 1 | A10BF |