A Clinical Proof-of-principle Trial in Adult Subjects With Newly Diagnosed Type 1 Diabetes Mellitus Investigating the Effect of NNC0114-0006 and Liraglutide on Preservation of Beta-cell Function

Study Overview
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Brief Summary
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This trial is conducted globally. The aim of this trial is to assess the clinical proof-of-principle of NNC0114-0006 and liraglutide on preservation of beta-cell function in adult subjects with newly diagnosed type 1 diabetes mellitus.

Official Title
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A Randomised, Double-blind, Double-dummy, Placebo-controlled, Parallel-group Multi-centre Clinical Proof-of-principle Trial in Adult Subjects With Newly Diagnosed Type 1 Diabetes Mellitus Investigating the Effect of NNC0114-0006 and Liraglutide on Preservation of Beta-cell Function

Conditions
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Diabetes, Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: NNC0114-0006
* Drug: liraglutide
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial T1DM (type 1 diabetes mellitus) (as diagnosed clinically) for not more than 20 weeks prior to screening - Male or female, aged 18-45 (both inclusive) at the time of signing the informed consent form Non-fasting peak C-peptide higher or equal to 0.2 nmol/l at visit 2 BMI (body mass index) higher or equal to 18.5 kg/m^2 Presence of one or more islet specific auto antibodies (glutamic acid decarboxylase (GAD), islet antigen-2 (IA2) or zinc-transporter 8 (ZnT8)) at screening Insulin dependence unless in temporary spontaneous remission (honeymoon period) Exclusion Criteria: Daily insulin usage above 1 U/kg per day at screening or use of continuous subcutaneous insulin infusion (CSII) History of recurrent (e.g. several times a year) of severe (e.g. pneumonia) or chronic infections or conditions predisposing to chronic infections (e.g., bronchiectasis and chronic osteomyelitis) History of severe systemic fungal infection within the past 12 months prior to screening unless treated and resolved with appropriate documented therapy Vaccination within 4 weeks before randomisation, Visit 3 (V3) Receipt of any other concomitant medications or herbal products that can influence the immune system within 90 days prior to screening (V1) History of pancreatitis (acute or chronic) Family or personal history of Multiple Endocrine Neoplasia Type 2 (MEN2) or Medullary Thyroid Carcinoma (MTC) Any past or current diagnosis of malignant neoplasms Known impairment of the immune system, except for T1DM, coeliac disease, alopecia, autoimmune antibodies not considered clinical important (e.g. thyroid antibodies without any clinically important thyroid disease), and vitiligo

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NNC0114-0006 + Liraglutide<br> | Drug: NNC0114-0006<br>* NNC0114-0006 12 mg/kg administered i.v (intravenously) every 6 weeks. Subjects will continue their pre-trial insulin treatment<br>Drug: liraglutide<br>* Liraglutide 1.8 mg administered s.c. (subcutaneously) daily. Subjects will continue their pre-trial insulin treatment<br>|
| Experimental: NNC0114-0006 + Placebo<br> | Drug: NNC0114-0006<br>* NNC0114-0006 12 mg/kg administered i.v (intravenously) every 6 weeks. Subjects will continue their pre-trial insulin treatment<br>Drug: placebo<br>* Placebo administered s.c (subcutaneously) or i.v ( intravenously). Subjects will continue their pre-trial insulin treatment<br>|
| Active Comparator: Liraglutide + Placebo<br> | Drug: liraglutide<br>* Liraglutide 1.8 mg administered s.c. (subcutaneously) daily. Subjects will continue their pre-trial insulin treatment<br>Drug: placebo<br>* Placebo administered s.c (subcutaneously) or i.v ( intravenously). Subjects will continue their pre-trial insulin treatment<br>|
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* Placebo administered s.c (subcutaneously) or i.v ( intravenously). Subjects will continue their pre-trial insulin treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-time Curve (AUC) 0-4h of Mixed Meal Tolerance Test (MMTT) Stimulated C-peptide at Week 54 Relative to Baseline | Area under the concentration-time curve, from 0 to 4 hours (AUC0-4h) of a mixed meal tolerance test (MMTT) stimulated C-peptide at week 54 is presented as ratio to baseline. AUC of C-peptide was measured as Nano moles*hour per liter (nmol*h/L). | 0 - 4 hours post-dose on week 0 and week 54 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-2h of C-peptide at Week 54 Relative to Baseline | Area under the concentration-time curve, from 0 to 2 hours (AUC0-2h) of a MMTT stimulated C-peptide at week 54 is presented as ratio to baseline. AUC of C-peptide was measured as 'nmol*h/L'. | 0-2 hours post-dose on week 0 and week 54 | 
| Cmax of C-peptide at Week 54 Relative to Baseline | Maximum observed concentration (Cmax) of a MMTT stimulated C-peptide at week 54 is presented as ratio to baseline. Cmax of C-peptide was measured as nanomoles per liter (nmol/L). | 0-4 hours post-dose on week 0 and week 54 | 
| AUC0-4h of Glucose at Week 54 Relative to Baseline | Area under the concentration-time curve, from 0 to 4 hours (AUC0-4h) of a MMTT stimulated glucose at week 54 is presented as ratio to baseline. AUC of glucose was measured as Milli moles*hour per liter (mmol*h/L). | 0 - 4 hours post-dose on week 0 and week 54 | 
| AUC0-2h of Glucose at Week 54 Relative to Baseline | Area under the concentration-time curve, from 0 to 2 hours (AUC0-2h) of a MMTT stimulated glucose at week 54 is presented as ratio to baseline. AUC of glucose is measured as 'mmol*h/L'. | 0-2 hours post-dose on week 0 and week 54 | 
| Cmax of Glucose at Week 54 Relative to Baseline | Maximum observed concentration (Cmax) of a MMTT stimulated glucose at week 54 is presented as ratio to baseline. Cmax of C-peptide was measured as 'mmol/L'. | 0-4 hours post-dose on week 0 and week 54 | 
| Number of Treatment Emergent Adverse Events | An adverse event was any untoward medical occurrence in a participants administered a product, and which did not necessarily have a causal relationship with this treatment. An adverse event was defined as treatment emergent if the onset of the adverse event occurs on or after the first day of trial product administration. Number of treatment emergent adverse events from first dose of trial product to week 54 and week 80 are presented. Results are based on the on-treatment and on-observation period. On-treatment period: From the day of first trial product administration to the day of the visit at week 54. On-observation: From the day after the visit at week 54 to the day of the last visit. | Week 0-54; Week 54-80 | 
| Number of Treatment Emergent Hyperglycaemic Episodes | Hyperglycaemic episodes were defined as treatment-emergent if the onset occurred on or after the first day of trial product administration. Number of treatment emergent episodes of hyperglycaemic episodes from first dose of trial product to week 54 and from week 54 to week 80 are presented. Results are based on the on-treatment and on-observation period. On-treatment period: From the day of first trial product administration to the day of the visit at week 54. On-observation: From the day after the visit at week 54 to the day of the last visit. | Week 0-54; Week 54-80 | 
| Number of Treatment Emergent Episodes of Diabetic Ketoacidosis | Diabetic ketoacidosis episodes were defined as treatment-emergent if the onset occurred on or after the first day of trial product administration. Number of treatment emergent episodes of hyperglycaemic episodes from first dose of trial product to week 54 and from week 54 to week 80 are presented. Results are based on the on-treatment and on-observation period. On-treatment period: From the day of first trial product administration to the day of the visit at week 54. On-observation: From the day after the visit at week 54 to the day of the last visit. | Weeks 0-54; Weeks 54-80 | 
| Number of Participants Experiencing Treatment Emergent Injection/Infusion Site Reactions Caused by NNC0114-0006/Liraglutide/Placebo Injection/Infusion | Injection/infusion site reactions episodes were defined as treatment-emergent if the onset occurred on or after the first day of trial product administration. Number of participants experiencing treatment emergent episodes of injection/infusion site reactions episodes from first dose of trial product to week 54 (treatment period) is presented. | Week 0-54 | 
| Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association (ADA) | Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 1 day after the date of last contact. Number of treatment-emergent hypoglycaemic episodes according to American Diabetes Association (ADA) classification from first dose of trial product to week 54 and from week 54 to week 80 are presented. Results presented hypoglycaemia episodes were recorded as per ADA definition: Severe hypoglycaemia, Documented symptomatic hypoglycaemia, Asymptomatic hypoglycaemia, Probable symptomatic hypoglycaemia and Pseudo-hypoglycaemia. | Weeks 0-54; Weeks 54-80 | 
| Number of Treatment Emergent Hypoglycaemic Episodes According to Novo Nordisk Definitions | Hypoglycaemia episodes were recorded as per Novo Nordisk definition: Symptomatic BG-confirmed: An episode that is blood glucose (BG) confirmed by plasma glucose (PG) value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Asymptomatic BG-confirmed: An episode that is BG-confirmed by PG value <3.1 mmol/L without symptoms consistent with hypoglycaemia. Severe or BG-confirmed symptomatic: An episode that is severe according to the ISPAD classification or BG-confirmed by a PG value <3.1 mmol/L with symptoms consistent with hypoglycaemia. BG-confirmed: An episode that is BG-confirmed by a PG value <3.1 mmol/L with or without symptoms consistent with hypoglycaemia. Severe or BG-confirmed: An episode that is severe according to the International Society for Pediatric and Adolescent Diabetes (ISPAD) classification or BG-confirmed by a PG value <3.1 mmol/L with or without symptoms consistent with hypoglycaemia. | Weeks 0-54; Weeks 54-80 | 
| Change in Body Weight (kg) | Change in body weight is measured at week 54 and week 80 respective to baseline. Body weight was measured in unit 'Kg'. | (Week 0, week 54) and (week 0, week 80) | 
| Diabetes Retinopathy | Number of participants evaluated for diabetic retinopathy at baseline (Day -28 to -14), week 54 and week 80 are presented as 'yes', 'no' or 'unknown'. | Baseline, week 54 and week 80 | 
| Estimated Glomerular Filtration Rate (eGFR)- Ratio to Baseline | The eGFR was measured using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Change in eGFR (measured in milliliters per minute per 1.73 square meters) from baseline (week 0) at week 54 and week 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Haematology: Erythrocytes | Change in erythrocytes (measured in 10^12 cells per liter) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Haematology: Haematocrit | Change in haematocrit (measured in percentage '%') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Haematology: Haemoglobin | Change in haemoglobin (measured in millimoles per liter 'mmol/L') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Haematology: Leukocytes | Change in leukocytes (measured in 10^9 cells/L) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Haematology: Mean Corpuscular Hemoglobin | Change in mean Corpuscular hemoglobin (measured in femtomole 'fmol') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Haematology: Mean Corpuscular Hemoglobin Concentration | Change in mean corpuscular hemoglobin concentration (MCHC) (measured in gram per liter 'g/L') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Haematology: Mean Corpuscular Volume | Change in Mean Corpuscular volume (measured in femtoliter 'fL') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Haematology: Thrombocytes | Change in thrombocytes (measured in 10^9 cells per liter) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Haematology: Eosinophil | Change in eosinophil (measured in percentage '%') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Haematology: Neutrophils | Change in neutrophils (measured in percentage '%') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Haematology: Basophils | Change in basophils (measured in percentage '%') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Haematology: Lymphocytes | Change in lymphocytes (measured in percentage '%') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Haematology: Monocytes | Change in monocytes (measured in percentage '%') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Biochemistry: Alanine Aminotransferase (ALAT) | Change in ALAT (measured in units per liter [U/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Biochemistry: Albumin | Change in albumin (measured in gram per deciliter [g/dL]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Biochemistry: Amylase | Change in amylase (measured in units per liter [U/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Biochemistry: Alkaline Phosphatase (ALP) | Change in ALP (measured in units per liter [U/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Biochemistry: Aspartate Aminotransferase (ASAT) | Change in ASAT (measured in units per liter [U/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Biochemistry: Total Bilirubin | Change in Total bilirubin (measured in micromole per liter [umol/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Biochemistry: Calcium Corrected | Change in calcium corrected (measured in millimole per liter [mmol/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Biochemistry: Chloride | Change in chloride (measured in millimole per liter [mmol/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Biochemistry: Creatine Kinase | Change in creatine kinase (measured in units per liter [U/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Biochemistry: Creatinine | Change in creatinine (measured in micromole per liter [umol/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Biochemistry: Gamma-glutamyl Transferase (GGT) | Change in GGT (measured in units per liter [U/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Biochemistry: C-reactive Protein Serum | Change in C-reactive protein serum (measured in milligrams per liter [mg/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Biochemistry: Lactate Dehydrogenase | Change in Lactate Dehydrogenase (measured in units per liter [U/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Biochemistry: Lipase | Change in lipase (measured in units per liter [U/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Biochemistry: Magnesium | Change in magnesium (measured in millimole per liter [mmol/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Biochemistry: Phosphate | Change in phosphate (measured in millimole per liter [mmol/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Biochemistry: Potassium | Change in potassium (measured in millimole per liter [mmol/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Biochemistry: Sodium | Change in sodium (measured in millimole per liter [mmol/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Biochemistry: Total Protein | Change in total protein (measured in gram per liter [g/dL]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Biochemistry: Blood Urea Nitrogen Serum | Change in blood urea nitrogen serum (measured in milligram per deciliter [mg/dL]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Biochemistry: Uric Acid | Change in Uric Acid (measured in milligram per deciliter [mg/dL]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in International Normalised Ratio (INR) | Change in INR (measured in ratio]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in D-Dimer | Change in D-Dimer (measured in mg/L) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Lipids: Total Cholesterol (Ratio to Baseline) | Change in total cholesterol (measured in mmol/L) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Lipids: Free Fatty Acids (Ratio to Baseline) | Change in total free fatty acids (measured in mmol/L) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Lipids: HDL Cholesterol (Ratio to Baseline) | Change in HDL cholesterol (measured in mmol/L) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Lipids: LDL Cholesterol (Ratio to Baseline) | Change in LDL cholesterol (measured in mmol/L) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Lipids: Triglycerides (TG) (Ratio to Baseline) | Change in Triglycerides (measured in mmol/L) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Total Immunoglobulin E (IgE) | Change in IgE (measured in kilo international units per liter [kIU/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Urinalysis: Urine Dipsticks | Urinalysis was performed by urine dipsticks for protein, glucose, erythrocytes, ketones leukocytes, nitrite, pH and specific gravity and categorised as normal, abnormal not clinically significant (NCS) and abnormal clinially significant (CS). Number of participants in each category at baseline (week 0), week 54 and 80 are presented. | Week 0, week 54 and week 80 | 
| Change in Cytokines: Interleukin (IL)-6 | IL-6 levels at baseline (week 0), weeks 54 and 80 are evaluated and presented. | Week 0, week 54 and week 80 | 
| Change in Cytokines- Interleukin (IL)-10 | IL-10 levels at baseline (week 0), weeks 54 and 80 are evaluated and presented. | Week 0, week 54 and week 80 | 
| Change in Cytokines: Interleukin (IL)-17 | IL-17 levels at baseline (week 0), weeks 54 and 80 are evaluated and presented. | Week 0, week 54 and week 80 | 
| Change in Cytokines: Interferon (IFN) Gamma | IFN gamma levels at baseline (week 0), weeks 54 and 80 are evaluated and presented. | Week 0, week 54 and week 80 | 
| Change in Cytokines: TNF-alpha | TNF-alpha levels at baseline (week 0), weeks 54 and 80 are evaluated and presented. | Week 0, week 54 and week 80 | 
| Change in Hormone Level: Thyroid Stimulating Hormone (TSH) | Change in TSH (measured in milli international units per liter [mIU/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Hormone Level: Calcitonin | Change in Calcitonin (measured in nanogram per liter [ng/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Systolic and Diastolic Blood Pressure | Change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) are evaluated from baseline (week 0) to weeks 54 and 80. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Pulse | Change in pulse is evaluated from baseline (week 0) to weeks 54 and 80 | (Week 0, week 54) and (week 0, week 80) | 
| Change in Body Temperature | Change in body temperature is evaluated from baseline (week 0) to weeks 54 and 80. | Week 0, week 54) and (week 0, week 80) | 
| Change in Respiratory Rate | Change in respiratory rate is evaluated from baseline (week 0) to weeks 54 and 80. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Electrocardiogram (ECG) | The ECG was assessed by the investigator at baseline (week 0), week 54 and week 80 and categorised as normal, abnormal NCS or abnormal CS. Number of participants in each ECG category at baseline, week 54 and week 80 are presented. | Week 0, week 54 and week 80 | 
| Change in Eye-examination | Dilated fundoscopy or fundus photography was performed by the investigator at week 0, week 54 and week 80. The results of the examination were interpreted for each eye (left/right) are categorised as normal, abnormal NCS or abnormal CS. Number of participants in each category at week 0, week 54 and week 80 are presented. | Week 0, week 54 and week 80 | 
| Change in Physical Examination | Physical examination parameters are categorised as general appearance; head, ears, eyes, nose, throat, neck; respiratory system;cardiovascular system; gastrointestinal system including mouth; musculoskeletal system; central and peripheral nervous system; skin; lymph node palpation and thyroid gland. Investigator assessed the participants with normal, abnormal not clinically significant (NCS) and abnormal clinically significant (CS) findings at week 0, week 54 and week 80 are presented. | Week 0, week 54 and week 80 | 
| Occurrence of Anti-NNC0114-0006 Antibodies | This outcome measure was applicable for NNC0114-0006 + Liraglutide treatment arm and NNC0114-0006 treatment arm. Participants was assessed for anti-NNC0114-0006 antibodies. Participant who reported anti-NNC0114-0006 antibodies were further analyzed for cross-reactivity. Number of participants who measured with anti-NNC0114-0006 antibodies at week 54 and week 80 are presented. | Week 0, week 54 and week 80 | 
| Occurrence of Anti-liraglutide Antibodies | This outcome measure is applicable for NNC0114-0006 + Liraglutide treatment arm and Liraglutide treatment arm. Participants was assessed for anti-liraglutide antibodies. Participant who reported anti-liraglutide antibodies were further analyzed for cross-reactivity. Number of participants who measured with anti-liraglutide antibodies at week 54 and week 80 are presented. | Week 0, week 54 and week 80 | 
| Change in Insulin Dose | The total daily insulin dose was derived as the average of the doses reported on the three days prior to the visit. Change in daily total insulin dose from baseline (week 0) after 54 weeks of treatment and week 80 are presented. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Number of Insulin Injections | The number of insulin injections was derived as the average of the reported number on the three days prior to the visit. The change in number of insulin injections per day (count) from baseline (week 0) after 54 weeks of treatment and week 80 are presented. | (Week 0, week 54) and (week 0, week 80) | 
| Number of Weeks Off Bolus Insulin | The number of weeks off bolus insulin after 54 weeks of treatment and week 80 are presented. | (Week 0 to week 54) and (week 0 to week 80) | 
| Change in HbA1c | Change in glycosylated haemoglobin (HbA1c) is evaluated from baseline (week 0) to weeks 54 and 80. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Fasting Plasma Glucose | Change in fasting plasma glucose is evaluated from baseline (week 0) to weeks 54 and 80. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Fasting C-peptide- Ratio to Baseline | Change in fasting C-peptide (measured in nanomole per liter [nmol/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Fasting Glucagon- Ratio to Baseline | Change in fasting glucagon (measured in picogram per milliliter [pg/mL]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline. | (Week 0, week 54) and (week 0, week 80) | 
| 7-point SMPG Profiles | Participants measured plasma glucose values using the blood glucose meter at 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime. 7-point SMPG profile values are presented for week 54 and week 80. | Week 54 and Week 80 | 
| Change in 7- Points Self-measured Plasma Glucose (SMPG) Postprandial Glucose /Prandial Increment: Breakfast, Lunch, Dinner | Participants measured plasma glucose values using the blood glucose meter at 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner and at bedtime. Change from baseline (week 0) to week 54 and week 80 in 7-point SMPG postprandial glucose /prandial increment (breakfast, lunch and dinner) value are presented. | (Week 0, week 54) and (week 0, week 80) | 
| Change in 7- Points Self-measured Plasma Glucose (SMPG) Postprandial Glucose /Prandial Increment (Average Over the Three Meals) | Participants measured plasma glucose values using the blood glucose meter at 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime. Change from baseline (week 0) to week 54 and week 80 in 7-point self-measured plasma glucose (SMPG) postprandial glucose /prandial increment (average over the three meals) value is presented. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Mean of 7-point Profiles | Participants measured plasma glucose values using the blood glucose meter at 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime. Change from baseline (week 0) to week 54 and week 80 in mean of 7-point profiles value is presented. | (Week 0, week 54) and (week 0, week 80) | 
| Before Breakfast 7- Points Self Measured Plasma Glucose (SMPG) | Participants measured plasma glucose values using the blood glucose meter at 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner and at bedtime. Before breakfast 7-point self-measured plasma glucose (SMPG) profile values are presented at week 54 and week 80. | Week 54 and week 80 | 
| Area Under the NNC0114-0006 Concentration-time Curve Over a Dosing Interval at Steady State (AUCtau, NNC0114-0006) | AUCtau, NNC0114-0006 was derived as the area under the concentration-time curve using the linear trapezoidal technique based on observed values and actual measurement times between 0 and 6 weeks (after the last dose). This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms. | Pre-dose and 1 hour post-dose during week 48 to week 54 | 
| Terminal Half-life (t½) After Last Dose of NNC0114-0006 | Terminal half life was calculated as log(2)/λz. The terminal rate constant λz was determined through linear regression with the logarithm to concentration as the response variable and actual measurement time as the explanatory variable. Valid observations from the terminal part of the curve, which is approximately linear, were used for the determination. This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms. | Pre-dose and 1 hour post-dose during week 48 to week 80 | 
| Apparent Volume of Distribution of NNC0114-0006 at Steadystate (Vss, NNC0114-0006) | The apparent volume of distribution of NNC0114-0006 at steady-state was calculated as mean residence time of (MRT) of NNC0114-0006 multiplied by clearance of NNC0114-0006 at steady state. This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms. | Pre-dose and 1 hour post-dose during week 48 to week 80 | 
| Clearance of NNC0114-0006 at Steady State (CLss, NNC0114-0006) | Clearance of NNC0114-0006 at steady state was calculated as dose/AUCtau, NNC0114-0006. This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms. | Pre-dose and 1 hour post-dose during week 48 to week 54 | 
| Mean Residence Time of NNC0114-0006 (MRT, NNC0114-0006) | This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms. Mean residence time of NNC0114-0006 is presented. | Pre-dose and 1 hour post-dose during week 48 to week 80 | 
| Accumulation Ratio of NNC114-0006 (RA,AUC, NNC0114-0006) | Accumulation ratio of NNC114-0006 was defined as AUC48-54 weeks/AUC0-6 weeks. This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms. | Pre-dose and 1 hour post-dose during (week 0 to week 6) and (week 48 to week 54) | 
| Observed NNC0114-0006 Concentration Prior to Dosing of NNC0114-0006 at Steady State (Ctrough, NNC0114-0006) | Ctrough of NNC0114-0006 was defined as concentration prior to dosing of NNC0114-0006 at steady state. This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms. | Week 48 (predose) | 
| Observed NNC0114-0006 Concentration 1 Hour After Dosing of NNC0114-0006 at Steady State (C1h, NNC0114-0006) | C1h, NNC0114-0006 was defined as concentration of NNC0114-0006 at 1 hour after dosing of NNC0114-0006 at steady state. This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms. | Week 48 (1 hour post-dose) | 
| Liraglutide Concentration at Steady State (C Liraglutide) | C liraglutide was defined as the liraglutide concentration at steady state. This outcome measure was applicable for NNC0114-0006 + Liraglutide and Liraglutide treatment arms. | Week 54 (post-dose) | 
| Change in Biomarker: Immune Phenotyping- B Cell Panel | B cell panel is evaluated by Immune phenotyping of peripheral blood mononuclear cells (PBMC) at baseline (week 0), week 54 and week 80. In below table CD refer to Cluster of Differentiation; IgMNeg refers to Immunoglobulin M negative; IgDNeg refers to Immunoglobulin D negative. | Week 0, week 54 and week 80 | 
| Change in Biomarker: Immune Phenotyping- Natural Killer (NK) Cell Panel | NK cell panel is evaluated by Immune phenotyping of peripheral blood mononuclear cells (PBMC) at baseline (week 0), week 54 and week 80. In below table ADCC refer to Antibody-dependent cellular cytotoxicity; CD refer to Cluster of Differentiation. | Week 0, week 54 and week 80 | 
| Change in Biomarker: Immune Phenotyping- T Cell Panel | T cell panel is evaluated by Immune phenotyping of peripheral blood mononuclear cells (PBMC) at baseline (week 0), week 54 and week 80. In below table CD refer to Cluster of Differentiation; TEMRA refers to terminally differentiated effector memory cells re-expressing CD45RA; CCR refers to C-C chemokine receptor; TREG refers to Regulatory T cells. | Week 0, week 54 and week 80 | 
| Change in Biomarker: Immune Phenotyping- T Follicular Helper (TfH) Cell Panel | TfH cell panel is evaluated by Immune phenotyping of peripheral blood mononuclear cells (PBMC) at baseline (week 0), week 54 and week 80. In below table CTFH refer to Circulating T follicular helper; ICOS refers to inducible T-cell co-stimulator; PD refers to Programmed cell death protein; CCR refers to C-C chemokine receptor; CXCR refers to C-X-C chemokine receptor; CD refer to Cluster of Differentiation; CM refers to central memory; EM refers to effector memory, TIGIT refers to T cell immunoreceptor with Ig and ITIM domains. | Week 0, week 54 and week 80 | 
| Change in Biomarker: Immune Phenotyping- Myeloid Cell Panel | Myeloid panel is evaluated by Immune phenotyping of peripheral blood mononuclear cells (PBMC) at baseline (week 0), week 54 and week 80. In below table HLA refers to Human Leukocyte Antigen; MDSC refers to myeloid-derived suppressor cell; DC refers to Dendritic cells; MYDC refers to Myeloid Dendritic Cells; IMMYE_MDSC refers to Immature myeloid cells & a subset of myeloid suppressor cells within the CD14-HLA class II- myeloid cell population. | Week 0, week 54 and week 80 | 
| Autoantibodies Against Glutamic Acid Decarboxylase (GAD) | Participants were analyzed for autoantibodies against Glutamic acid decarboxylase (GAD) and were categorized as negative and positive. | Week 0, week 54 and week 80 | 
| Autoantibodies Against Zinc-transporter 8 (ZnT8) | Participants were analyzed for autoantibodies against Zinc-transporter 8 (ZnT8) and were categorized as negative and positive. | Week 0, week 54 and week 80 | 
| Autoantibodies Against Islet Antigen-2 (IA2) | Participants were analyzed for autoantibodies against Islet antigen-2 (IA2) and were categorized as negative and positive. | Week 0, week 54 and week 80 | 
| Autoantibodies Against Insulin Autoantibodies (IAA) | Participants were analyzed for autoantibodies against Insulin autoantibodies (IAA) and were categorized as negative and positive. | Week 0, week 54 and week 80 | 
| Change in Biomarker: Total Interleukin-21 (IL-21) | IL-21 is evaluated at baseline (week 0), week 54 and week 80. | Week 0, week 54 and week 80 | 
| Change in Biomarker: Serum Vitamin D (1,25 Dehydroxy-calciferol) | Serum vitamin D is evaluated at baseline (week 0), week 54 and week 80. | Week 0, week 54 and week 80 | 
| Change in Short Form 36 Health Survey (SF-36) | SF-36v2™ questionnaire measured the HRQoL on 8 domains (Bodily Pain, General Health, Mental Health, Physical Functioning, Role Emotion, Physical Health, Social Functioning and Vitality) on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. Change from baseline (week 0) to week 54 and week 80 in SF-36 score is presented.The MCS measure is derived from domain scales of vitality, social functioning, role emotional and mental health. The PCS measure is derived from domain scales of physical functioning, role-physical, bodily pain, and general health. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. A positive change score indicate an improvement since baseline. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Experience of Treatment Benefits and Barriers (ETBB) | Treatment Benefits and Barriers (ETBB) questionnaire measured diabetes-specific health beliefs on 2 categories: Total Score for Perceived Barriers and Perceived Benefits. The measurement of perceived benefits of, and barriers to, treatment was achieved by creating a pool 28 statements each with a 7-point scale ranging from strongly agree (6) to strongly disagree (0). ETBB benefits score was calculated using the responses from questions 1, 4, 7, 8, 10, and 12 and ETBB barriers score was calculated using the responses from questions 2, 3, 5, 6, 9, and 11. Both was calculated as the sum of responses divided by number of responses received multiplied by the maximum number of responses. Based on the responses used the maximum responses available was 6. The higher score indicates more perceived benefits or more perceived barrier. | (Week 0, week 54) and (week 0, week 80) | 
| Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ) | Change from baseline (week 0) in DTSQ is evaluated at week 54 and 80. The DTSQs items are scored on a 7-point graded response scale ranging from 6 to 0. Higher score indicates a higher level of glycaemia/treatment satisfaction. | (Week 0, week 54) and (week 0, week 80) | 
| Area Under the Concentration-time Curve (AUC) 0-4h of Mixed Meal Tolerance Test (MMTT) Stimulated C-peptide at Week 80 Relative to Baseline | Area under the concentration-time curve, from 0 to 4 hours (AUC0-4h) of a mixed meal tolerance test (MMTT) stimulated C-peptide at week 80 is presented as ratio to baseline. AUC of C-peptide was measured as Nano moles*hour per liter (nmol*h/L). | 0 - 4 hours post-dose on week 0 and week 80 | 
| AUC0-2h of C-peptide at Week 80 Relative to Baseline | Area under the concentration-time curve, from 0 to 2 hours (AUC0-2h) of a MMTT stimulated C-peptide at week 80 is presented as ratio to baseline. AUC of C-peptide was measured as 'nmol*h/L'. | 0-2 hours post-dose on week 0 and week 80 | 
| Cmax of C-peptide at Week 80 Relative to Baseline | Maximum observed concentration (Cmax) of a MMTT stimulated C-peptide at week 80 is presented as ratio to baseline. Cmax of C-peptide was measured as nanomoles per liter (nmol/L). | 0-4 hours post-dose on week 0 and week 80 | 
| AUC0-4h of Glucose at Week 80 Relative to Baseline | Area under the concentration-time curve, from 0 to 4 hours (AUC0-4h) of a MMTT stimulated glucose at week 80 is presented as ratio to baseline. AUC of glucose was measured as Milli moles*hour per liter (mmol*h/L). | 0 - 4 hours post-dose on week 0 and week 80 | 
| AUC0-2h of Glucose at Week 80 Relative to Baseline | Area under the concentration-time curve, from 0 to 2 hours (AUC0-2h) of a MMTT stimulated glucose at week 80 is presented as ratio to baseline. AUC of glucose was measured as 'mmol*h/L'. | 0-2 hours post-dose on week 0 and week 80 | 
| Cmax of Glucose at Week 80 Relative to Baseline | Maximum observed concentration (Cmax) of a MMTT stimulated glucose at week 80 is presented as ratio to baseline. Cmax of C-peptide was measured as 'mmol/L'. | 0-4 hours post-dose on week 0 and week 80 |