Clinical Trials/NCT02443155

NCT02443155

Completed

Phase 2

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

Novo Nordisk A/S1 site in 1 country308 target enrollmentNovember 10, 2015

ConditionsDiabetes Diabetes Mellitus, Type 1

InterventionsNNC0114-0006 liraglutide placebo

Drugsplacebo NNC0114-0006 liraglutide

Overview

Phase: Phase 2
Intervention: NNC0114-0006
Conditions: Diabetes
Sponsor: Novo Nordisk A/S
Enrollment: 308
Locations: 1
Primary Endpoint: Area Under the Concentration-time Curve (AUC) 0-4h of Mixed Meal Tolerance Test (MMTT) Stimulated C-peptide at Week 54 Relative to Baseline
Status: Completed
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

November 10, 2015

End Date

February 27, 2019

Last Updated

5 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Novo Nordisk A/S

Responsible Party

Sponsor

Eligibility Criteria

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

Arms & Interventions

NNC0114-0006 + Liraglutide

Intervention: NNC0114-0006

NNC0114-0006 + Liraglutide

Intervention: liraglutide

NNC0114-0006 + Placebo

Intervention: NNC0114-0006

NNC0114-0006 + Placebo

Intervention: placebo

Liraglutide + Placebo

Intervention: liraglutide

Liraglutide + Placebo

Intervention: placebo

Placebo

Intervention: placebo

Outcomes

Primary Outcomes

Area Under the Concentration-time Curve (AUC) 0-4h of Mixed Meal Tolerance Test (MMTT) Stimulated C-peptide at Week 54 Relative to Baseline

Time Frame: 0 - 4 hours post-dose on week 0 and week 54

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).

Secondary Outcomes

Estimated Glomerular Filtration Rate (eGFR)- Ratio to Baseline((Week 0, week 54) and (week 0, week 80))
Change in Haematology: Mean Corpuscular Hemoglobin((Week 0, week 54) and (week 0, week 80))
AUC0-4h of Glucose at Week 54 Relative to Baseline(0 - 4 hours post-dose on week 0 and week 54)
Cmax of Glucose at Week 54 Relative to Baseline(0-4 hours post-dose on week 0 and week 54)
Number of Participants Experiencing Treatment Emergent Injection/Infusion Site Reactions Caused by NNC0114-0006/Liraglutide/Placebo Injection/Infusion(Week 0-54)
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association (ADA)(Weeks 0-54; Weeks 54-80)
Number of Treatment Emergent Hypoglycaemic Episodes According to Novo Nordisk Definitions(Weeks 0-54; Weeks 54-80)
Change in Haematology: Mean Corpuscular Volume((Week 0, week 54) and (week 0, week 80))
Change in Haematology: Thrombocytes((Week 0, week 54) and (week 0, week 80))
Change in Haematology: Eosinophil((Week 0, week 54) and (week 0, week 80))
Change in Haematology: Neutrophils((Week 0, week 54) and (week 0, week 80))
Cmax of C-peptide at Week 54 Relative to Baseline(0-4 hours post-dose on week 0 and week 54)
Change in Haematology: Erythrocytes((Week 0, week 54) and (week 0, week 80))
AUC0-2h of C-peptide at Week 54 Relative to Baseline(0-2 hours post-dose on week 0 and week 54)
Number of Treatment Emergent Adverse Events(Week 0-54; Week 54-80)
Number of Treatment Emergent Hyperglycaemic Episodes(Week 0-54; Week 54-80)
Number of Treatment Emergent Episodes of Diabetic Ketoacidosis(Weeks 0-54; Weeks 54-80)
Change in Body Weight (kg)((Week 0, week 54) and (week 0, week 80))
Diabetes Retinopathy(Baseline, week 54 and week 80)
Change in Haematology: Haematocrit((Week 0, week 54) and (week 0, week 80))
Change in Haematology: Haemoglobin((Week 0, week 54) and (week 0, week 80))
Change in Haematology: Leukocytes((Week 0, week 54) and (week 0, week 80))
AUC0-2h of Glucose at Week 54 Relative to Baseline(0-2 hours post-dose on week 0 and week 54)
Change in Haematology: Mean Corpuscular Hemoglobin Concentration((Week 0, week 54) and (week 0, week 80))
Change in Haematology: Basophils((Week 0, week 54) and (week 0, week 80))
Change in Haematology: Lymphocytes((Week 0, week 54) and (week 0, week 80))
Change in Haematology: Monocytes((Week 0, week 54) and (week 0, week 80))
Change in Biochemistry: Alanine Aminotransferase (ALAT)((Week 0, week 54) and (week 0, week 80))
Change in Biochemistry: Albumin((Week 0, week 54) and (week 0, week 80))
Change in Biochemistry: Amylase((Week 0, week 54) and (week 0, week 80))
Change in Biochemistry: Alkaline Phosphatase (ALP)((Week 0, week 54) and (week 0, week 80))
Change in Biochemistry: Aspartate Aminotransferase (ASAT)((Week 0, week 54) and (week 0, week 80))
Change in Biochemistry: Total Bilirubin((Week 0, week 54) and (week 0, week 80))
Change in Biochemistry: Calcium Corrected((Week 0, week 54) and (week 0, week 80))
Change in Biochemistry: Chloride((Week 0, week 54) and (week 0, week 80))
Change in Biochemistry: Creatine Kinase((Week 0, week 54) and (week 0, week 80))
Change in Biochemistry: Creatinine((Week 0, week 54) and (week 0, week 80))
Change in Biochemistry: Gamma-glutamyl Transferase (GGT)((Week 0, week 54) and (week 0, week 80))
Change in Biochemistry: C-reactive Protein Serum((Week 0, week 54) and (week 0, week 80))
Change in Biochemistry: Lactate Dehydrogenase((Week 0, week 54) and (week 0, week 80))
Change in Biochemistry: Lipase((Week 0, week 54) and (week 0, week 80))
Change in Biochemistry: Magnesium((Week 0, week 54) and (week 0, week 80))
Change in Biochemistry: Phosphate((Week 0, week 54) and (week 0, week 80))
Change in Biochemistry: Potassium((Week 0, week 54) and (week 0, week 80))
Change in Biochemistry: Sodium((Week 0, week 54) and (week 0, week 80))
Change in Biochemistry: Total Protein((Week 0, week 54) and (week 0, week 80))
Change in Biochemistry: Blood Urea Nitrogen Serum((Week 0, week 54) and (week 0, week 80))
Change in Biochemistry: Uric Acid((Week 0, week 54) and (week 0, week 80))
Change in International Normalised Ratio (INR)((Week 0, week 54) and (week 0, week 80))
Change in D-Dimer((Week 0, week 54) and (week 0, week 80))
Change in Lipids: Total Cholesterol (Ratio to Baseline)((Week 0, week 54) and (week 0, week 80))
Change in Lipids: Free Fatty Acids (Ratio to Baseline)((Week 0, week 54) and (week 0, week 80))
Change in Lipids: HDL Cholesterol (Ratio to Baseline)((Week 0, week 54) and (week 0, week 80))
Change in Lipids: LDL Cholesterol (Ratio to Baseline)((Week 0, week 54) and (week 0, week 80))
Change in Lipids: Triglycerides (TG) (Ratio to Baseline)((Week 0, week 54) and (week 0, week 80))
Change in Total Immunoglobulin E (IgE)((Week 0, week 54) and (week 0, week 80))
Change in Urinalysis: Urine Dipsticks(Week 0, week 54 and week 80)
Change in Cytokines: Interleukin (IL)-6(Week 0, week 54 and week 80)
Change in Cytokines- Interleukin (IL)-10(Week 0, week 54 and week 80)
Change in Cytokines: Interleukin (IL)-17(Week 0, week 54 and week 80)
Change in Cytokines: Interferon (IFN) Gamma(Week 0, week 54 and week 80)
Change in Cytokines: TNF-alpha(Week 0, week 54 and week 80)
Change in Hormone Level: Thyroid Stimulating Hormone (TSH)((Week 0, week 54) and (week 0, week 80))
Change in Hormone Level: Calcitonin((Week 0, week 54) and (week 0, week 80))
Change in Systolic and Diastolic Blood Pressure((Week 0, week 54) and (week 0, week 80))
Change in Pulse((Week 0, week 54) and (week 0, week 80))
Change in Body Temperature(Week 0, week 54) and (week 0, week 80))
Change in Respiratory Rate((Week 0, week 54) and (week 0, week 80))
Change in Electrocardiogram (ECG)(Week 0, week 54 and week 80)
Change in Eye-examination(Week 0, week 54 and week 80)
Change in Physical Examination(Week 0, week 54 and week 80)
Occurrence of Anti-NNC0114-0006 Antibodies(Week 0, week 54 and week 80)
Occurrence of Anti-liraglutide Antibodies(Week 0, week 54 and week 80)
Change in Insulin Dose((Week 0, week 54) and (week 0, week 80))
Change in Number of Insulin Injections((Week 0, week 54) and (week 0, week 80))
Number of Weeks Off Bolus Insulin((Week 0 to week 54) and (week 0 to week 80))
Change in HbA1c((Week 0, week 54) and (week 0, week 80))
Change in Fasting Plasma Glucose((Week 0, week 54) and (week 0, week 80))
Change in Fasting C-peptide- Ratio to Baseline((Week 0, week 54) and (week 0, week 80))
Change in Fasting Glucagon- Ratio to Baseline((Week 0, week 54) and (week 0, week 80))
7-point SMPG Profiles(Week 54 and Week 80)
Change in 7- Points Self-measured Plasma Glucose (SMPG) Postprandial Glucose /Prandial Increment: Breakfast, Lunch, Dinner((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)((Week 0, week 54) and (week 0, week 80))
Change in Mean of 7-point Profiles((Week 0, week 54) and (week 0, week 80))
Before Breakfast 7- Points Self Measured Plasma Glucose (SMPG)(Week 54 and week 80)
Area Under the NNC0114-0006 Concentration-time Curve Over a Dosing Interval at Steady State (AUCtau, NNC0114-0006)(Pre-dose and 1 hour post-dose during week 48 to week 54)
Terminal Half-life (t½) After Last Dose of NNC0114-0006(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)(Pre-dose and 1 hour post-dose during week 48 to week 80)
Clearance of NNC0114-0006 at Steady State (CLss, NNC0114-0006)(Pre-dose and 1 hour post-dose during week 48 to week 54)
Mean Residence Time of NNC0114-0006 (MRT, NNC0114-0006)(Pre-dose and 1 hour post-dose during week 48 to week 80)
Accumulation Ratio of NNC114-0006 (RA,AUC, NNC0114-0006)(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)(Week 48 (predose))
Observed NNC0114-0006 Concentration 1 Hour After Dosing of NNC0114-0006 at Steady State (C1h, NNC0114-0006)(Week 48 (1 hour post-dose))
Liraglutide Concentration at Steady State (C Liraglutide)(Week 54 (post-dose))
Change in Biomarker: Immune Phenotyping- B Cell Panel(Week 0, week 54 and week 80)
Change in Biomarker: Immune Phenotyping- Natural Killer (NK) Cell Panel(Week 0, week 54 and week 80)
Change in Biomarker: Immune Phenotyping- T Cell Panel(Week 0, week 54 and week 80)
Change in Biomarker: Immune Phenotyping- T Follicular Helper (TfH) Cell Panel(Week 0, week 54 and week 80)
Change in Biomarker: Immune Phenotyping- Myeloid Cell Panel(Week 0, week 54 and week 80)
Autoantibodies Against Glutamic Acid Decarboxylase (GAD)(Week 0, week 54 and week 80)
Autoantibodies Against Zinc-transporter 8 (ZnT8)(Week 0, week 54 and week 80)
Autoantibodies Against Islet Antigen-2 (IA2)(Week 0, week 54 and week 80)
Autoantibodies Against Insulin Autoantibodies (IAA)(Week 0, week 54 and week 80)
Change in Biomarker: Total Interleukin-21 (IL-21)(Week 0, week 54 and week 80)
Change in Biomarker: Serum Vitamin D (1,25 Dehydroxy-calciferol)(Week 0, week 54 and week 80)
Change in Short Form 36 Health Survey (SF-36)((Week 0, week 54) and (week 0, week 80))
Change in Experience of Treatment Benefits and Barriers (ETBB)((Week 0, week 54) and (week 0, week 80))
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ)((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(0 - 4 hours post-dose on week 0 and week 80)
AUC0-2h of C-peptide at Week 80 Relative to Baseline(0-2 hours post-dose on week 0 and week 80)
Cmax of C-peptide at Week 80 Relative to Baseline(0-4 hours post-dose on week 0 and week 80)
AUC0-4h of Glucose at Week 80 Relative to Baseline(0 - 4 hours post-dose on week 0 and week 80)
AUC0-2h of Glucose at Week 80 Relative to Baseline(0-2 hours post-dose on week 0 and week 80)
Cmax of Glucose at Week 80 Relative to Baseline(0-4 hours post-dose on week 0 and week 80)