Phase 2
N=307
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
Diabetes · Diabetes Mellitus, Type 1
Bottom Line
View on ClinicalTrials.gov: NCT02443155 ↗Enrolled (actual)
307
Serious AEs
10.4%
Results posted
Jan 2021
Primary outcome: Primary: Area Under the Concentration-time Curve (AUC) 0-4h of Mixed Meal Tolerance Test (MMTT) Stimulated C-peptide at Week 54 Relative to Baseline — 0.934; 0.783; 0.709; 0.660 Ratio of AUC — p==0.0017
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- NNC0114-0006 (Drug); liraglutide (Drug); placebo (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novo Nordisk A/S
- Primary completion
- Aug 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Concentration-time Curve (AUC) 0-4h of Mixed Meal Tolerance Test (MMTT) Stimulated C-peptide at Week 54 Relative to Baseline |
0.934; 0.783; 0.709; 0.660 | =0.0017 sig |
| SECONDARY AUC0-2h of C-peptide at Week 54 Relative to Baseline |
0.961; 0.824; 0.646; 0.655 | — |
| SECONDARY Cmax of C-peptide at Week 54 Relative to Baseline |
0.978; 0.779; 0.733; 0.644 | — |
| SECONDARY AUC0-4h of Glucose at Week 54 Relative to Baseline |
0.904; 1.078; 0.993; 1.089 | — |
| SECONDARY AUC0-2h of Glucose at Week 54 Relative to Baseline |
0.939; 1.066; 0.978; 1.057 | — |
| SECONDARY Cmax of Glucose at Week 54 Relative to Baseline |
0.937; 1.068; 1.004; 1.057 | — |
| SECONDARY Number of Treatment Emergent Adverse Events |
434; 327; 410; 364; 70; 73 | — |
| SECONDARY Number of Treatment Emergent Hyperglycaemic Episodes |
302; 256; 217; 291; 306; 74 | — |
| SECONDARY Number of Treatment Emergent Episodes of Diabetic Ketoacidosis |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants Experiencing Treatment Emergent Injection/Infusion Site Reactions Caused by NNC0114-0006/Liraglutide/Placebo Injection/Infusion |
2; 0; 0; 1 | — |
| SECONDARY Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association (ADA) |
1; 2; 0; 0; 2038; 1956 | — |
| SECONDARY Number of Treatment Emergent Hypoglycaemic Episodes According to Novo Nordisk Definitions |
396; 394; 315; 503; 576; 616 | — |
| SECONDARY Change in Body Weight (kg) |
-1.8; 1.2; -2.5; 1.1; 1.9; 1.6 | — |
| SECONDARY Diabetes Retinopathy |
4; 2; 1; 1; 73; 75 | — |
| SECONDARY Estimated Glomerular Filtration Rate (eGFR)- Ratio to Baseline |
0.98; 0.95; 0.97; 1.00; 0.97; 0.94 | — |
| SECONDARY Change in Haematology: Erythrocytes |
0.99; 1.01; 0.99; 1.00; 0.99; 1.00 | — |
| SECONDARY Change in Haematology: Haematocrit |
0.99; 1.00; 0.99; 1.00; 0.98; 1.00 | — |
| SECONDARY Change in Haematology: Haemoglobin |
1.01; 1.02; 1.00; 1.01; 1.00; 1.02 | — |
| SECONDARY Change in Haematology: Leukocytes |
0.96; 0.98; 0.97; 1.02; 0.99; 0.95 | — |
| SECONDARY Change in Haematology: Mean Corpuscular Hemoglobin |
1.02; 1.01; 1.01; 1.01; 1.02; 1.01 | — |
| SECONDARY Change in Haematology: Mean Corpuscular Hemoglobin Concentration |
1.02; 1.01; 1.02; 1.02; 1.02; 1.02 | — |
| SECONDARY Change in Haematology: Mean Corpuscular Volume |
1.00; 0.99; 1.00; 0.99; 1.00; 1.00 | — |
| SECONDARY Change in Haematology: Thrombocytes |
0.98; 0.98; 1.03; 0.98; 1.00; 1.03 | — |
| SECONDARY Change in Haematology: Eosinophil |
1.15; 1.30; 3.10; 1.37; 1.31; 1.23 | — |
| SECONDARY Change in Haematology: Neutrophils |
0.98; 0.99; 0.97; 1.04; 0.97; 0.99 | — |
| SECONDARY Change in Haematology: Basophils |
1.73; 1.58; 1.52; 1.43; 2.17; 1.73 | — |
| SECONDARY Change in Haematology: Lymphocytes |
1.00; 1.00; 1.02; 0.91; 1.01; 0.98 | — |
| SECONDARY Change in Haematology: Monocytes |
1.05; 1.02; 1.01; 1.01; 1.12; 1.07 | — |
| SECONDARY Change in Biochemistry: Alanine Aminotransferase (ALAT) |
0.96; 0.98; 0.97; 0.90; 0.95; 0.98 | — |
| SECONDARY Change in Biochemistry: Albumin |
0.99; 1.00; 1.02; 0.99; 1.00; 1.01 | — |
| SECONDARY Change in Biochemistry: Amylase |
1.07; 0.98; 1.04; 1.01; 1.04; 0.99 | — |
| SECONDARY Change in Biochemistry: Alkaline Phosphatase (ALP) |
1.03; 0.99; 0.99; 1.03; 1.07; 1.05 | — |
| SECONDARY Change in Biochemistry: Aspartate Aminotransferase (ASAT) |
0.99; 0.99; 1.00; 0.98; 0.98; 0.98 | — |
| SECONDARY Change in Biochemistry: Total Bilirubin |
0.81; 1.10; 0.99; 1.01; 0.91; 1.04 | — |
| SECONDARY Change in Biochemistry: Calcium Corrected |
0.99; 0.98; 0.98; 0.99; 0.96; 0.97 | — |
| SECONDARY Change in Biochemistry: Chloride |
1.01; 1.00; 1.00; 1.00; 1.00; 1.01 | — |
| SECONDARY Change in Biochemistry: Creatine Kinase |
1.16; 1.17; 1.08; 1.02; 1.11; 1.09 | — |
| SECONDARY Change in Biochemistry: Creatinine |
1.01; 1.05; 1.04; 1.01; 1.02; 1.05 | — |
| SECONDARY Change in Biochemistry: Gamma-glutamyl Transferase (GGT) |
1.02; 1.08; 1.03; 1.02; 1.05; 1.13 | — |
| SECONDARY Change in Biochemistry: C-reactive Protein Serum |
0.92; 1.04; 0.89; 1.06; 1.08; 0.94 | — |
| SECONDARY Change in Biochemistry: Lactate Dehydrogenase |
0.99; 1.03; 1.04; 1.03; 1.02; 1.04 | — |
| SECONDARY Change in Biochemistry: Lipase |
1.49; 1.00; 1.34; 1.01; 1.05; 0.94 | — |
| SECONDARY Change in Biochemistry: Magnesium |
1.02; 1.01; 1.02; 0.99; 1.01; 1.03 | — |
| SECONDARY Change in Biochemistry: Phosphate |
0.99; 0.99; 1.02; 0.96; 1.02; 1.01 | — |
| SECONDARY Change in Biochemistry: Potassium |
1.01; 0.98; 0.99; 0.98; 0.99; 0.99 | — |
| SECONDARY Change in Biochemistry: Sodium |
1.00; 1.00; 1.00; 1.00; 0.99; 1.00 | — |
| SECONDARY Change in Biochemistry: Total Protein |
0.99; 1.00; 1.01; 1.00; 0.99; 1.00 | — |
| SECONDARY Change in Biochemistry: Blood Urea Nitrogen Serum |
1.00; 1.05; 0.98; 0.94; 0.97; 0.97 | — |
| SECONDARY Change in Biochemistry: Uric Acid |
0.93; 0.98; 0.98; 0.96; 0.95; 0.94 | — |
| SECONDARY Change in International Normalised Ratio (INR) |
0.97; 0.96; 0.95; 0.96; 0.98; 0.99 | — |
| SECONDARY Change in D-Dimer |
0.96; 0.98; 0.98; 1.15; 0.96; 0.92 | — |
| SECONDARY Change in Lipids: Total Cholesterol (Ratio to Baseline) |
1.00; 1.02; 1.03; 1.04; 1.02; 1.03 | — |
| SECONDARY Change in Lipids: Free Fatty Acids (Ratio to Baseline) |
0.86; 1.01; 1.18; 0.97; 0.89; 1.06 | — |
| SECONDARY Change in Lipids: HDL Cholesterol (Ratio to Baseline) |
1.04; 1.08; 1.12; 1.10; 1.04; 1.06 | — |
| SECONDARY Change in Lipids: LDL Cholesterol (Ratio to Baseline) |
0.96; 0.97; 0.98; 1.01; 0.99; 1.02 | — |
| SECONDARY Change in Lipids: Triglycerides (TG) (Ratio to Baseline) |
1.03; 0.96; 1.03; 1.02; 1.08; 0.94 | — |
| SECONDARY Change in Total Immunoglobulin E (IgE) |
1.31; 1.05; 1.08; 1.02; 1.32; 1.18 | — |
| SECONDARY Change in Urinalysis: Urine Dipsticks |
72; 71; 67; 71; 5; 6 | — |
| SECONDARY Change in Cytokines: Interleukin (IL)-6 |
0.9; 0.8; 1.2; 0.8; 0.8; 0.8 | — |
| SECONDARY Change in Cytokines- Interleukin (IL)-10 |
0.7; 0.5; 0.4; 0.4; 0.4; 0.4 | — |
| SECONDARY Change in Cytokines: Interleukin (IL)-17 |
4.9; 4.7; 4.7; 4.8; 4.9; 4.8 | — |
| SECONDARY Change in Cytokines: Interferon (IFN) Gamma |
7.3; 7.8; 5.8; 4.3; 4.6; 7.5 | — |
| SECONDARY Change in Cytokines: TNF-alpha |
2.60; 2.32; 2.70; 3.06; 2.36; 2.33 | — |
| SECONDARY Change in Hormone Level: Thyroid Stimulating Hormone (TSH) |
1.00; 1.12; 0.89; 0.91; 1.04; 0.99 | — |
| SECONDARY Change in Hormone Level: Calcitonin |
1.00; 0.90; 0.89; 0.88; 0.85; 0.93 | — |
| SECONDARY Change in Systolic and Diastolic Blood Pressure |
-3; 3; -2; 1; -1; 2 | — |
| SECONDARY Change in Pulse |
3; 0; 6; 2; -1; -1 | — |
| SECONDARY Change in Body Temperature |
-0.1; 0.0; -0.1; -0.0; -0.0; 0.1 | — |
| SECONDARY Change in Respiratory Rate |
-0.3; 0.1; 0.1; 0.6; -0.3; -0.2 | — |
| SECONDARY Change in Electrocardiogram (ECG) |
62; 65; 60; 63; 15; 12 | — |
| SECONDARY Change in Eye-examination |
64; 68; 70; 66; 13; 9 | — |
| SECONDARY Change in Physical Examination |
76; 77; 76; 76; 1; 0 | — |
| SECONDARY Occurrence of Anti-NNC0114-0006 Antibodies |
68; 62; 9; 14; 4; 7 | — |
| SECONDARY Occurrence of Anti-liraglutide Antibodies |
77; 75; 0; 0; 0; 0 | — |
| SECONDARY Change in Insulin Dose |
-0.05; 0.02; 0.01; 0.09; 0.10; 0.05 | — |
| SECONDARY Change in Number of Insulin Injections |
-0.3; -0.1; -0.5; 0.2; 0.2; -0.3 | — |
| SECONDARY Number of Weeks Off Bolus Insulin |
10; 5; 9; 4; 14; 9 | — |
| SECONDARY Change in HbA1c |
-0.7; -0.5; -0.3; -0.3; -0.1; -0.2 | — |
| SECONDARY Change in Fasting Plasma Glucose |
0.5; 0.2; -0.3; 0.5; 1.1; 0.3 | — |
| SECONDARY Change in Fasting C-peptide- Ratio to Baseline |
1.01; 0.70; 0.65; 0.66; 0.58; 0.53 | — |
| SECONDARY Change in Fasting Glucagon- Ratio to Baseline |
1.01; 0.95; 0.96; 1.00; 0.89; 0.85 | — |
| SECONDARY 7-point SMPG Profiles |
6.8; 6.8; 6.4; 6.3; 8.9; 7.5 | — |
| SECONDARY Change in 7- Points Self-measured Plasma Glucose (SMPG) Postprandial Glucose /Prandial Increment: Breakfast, Lunch, Dinner |
1.3; 0.4; -0.1; -0.6; 1.9; 0.5 | — |
| SECONDARY Change in 7- Points Self-measured Plasma Glucose (SMPG) Postprandial Glucose /Prandial Increment (Average Over the Three Meals) |
0.9; 0.6; 0.2; -0.1; 0.8; 0.4 | — |
| SECONDARY Change in Mean of 7-point Profiles |
0.5; 0.3; -0.1; 0.0; 0.1; 0.0 | — |
| SECONDARY Before Breakfast 7- Points Self Measured Plasma Glucose (SMPG) |
6.8; 6.8; 6.4; 6.3; 6.5; 6.4 | — |
| SECONDARY Area Under the NNC0114-0006 Concentration-time Curve Over a Dosing Interval at Steady State (AUCtau, NNC0114-0006) |
3969; 4115 | — |
| SECONDARY Terminal Half-life (t½) After Last Dose of NNC0114-0006 |
22.3; 22.2 | — |
| SECONDARY Apparent Volume of Distribution of NNC0114-0006 at Steadystate (Vss, NNC0114-0006) |
83.7; 79.3 | — |
| SECONDARY Clearance of NNC0114-0006 at Steady State (CLss, NNC0114-0006) |
3.02; 2.92 | — |
| SECONDARY Mean Residence Time of NNC0114-0006 (MRT, NNC0114-0006) |
27.7; 27.2 | — |
| SECONDARY Accumulation Ratio of NNC114-0006 (RA,AUC, NNC0114-0006) |
1.24; 1.26 | — |
| SECONDARY Observed NNC0114-0006 Concentration Prior to Dosing of NNC0114-0006 at Steady State (Ctrough, NNC0114-0006) |
34.7; 36.7 | — |
| SECONDARY Observed NNC0114-0006 Concentration 1 Hour After Dosing of NNC0114-0006 at Steady State (C1h, NNC0114-0006) |
298.6; 282.6 | — |
| SECONDARY Liraglutide Concentration at Steady State (C Liraglutide) |
16287; 15920 | — |
| SECONDARY Change in Biomarker: Immune Phenotyping- B Cell Panel |
1.3; 1.4; 1.6; 1.5; 1.2; 1.1 | — |
| SECONDARY Change in Biomarker: Immune Phenotyping- Natural Killer (NK) Cell Panel |
39.5; 36.3; 36.0; 34.7; 37.1; 32.5 | — |
| SECONDARY Change in Biomarker: Immune Phenotyping- T Cell Panel |
10.1; 9.7; 10.8; 9.7; 10.3; 8.7 | — |
| SECONDARY Change in Biomarker: Immune Phenotyping- T Follicular Helper (TfH) Cell Panel |
0.8; 1.0; 0.8; 0.6; 0.6; 0.4 | — |
| SECONDARY Change in Biomarker: Immune Phenotyping- Myeloid Cell Panel |
1.1; 1.0; 0.9; 1.0; 1.1; 0.7 | — |
| SECONDARY Autoantibodies Against Glutamic Acid Decarboxylase (GAD) |
3; 1; 5; 3; 74; 76 | — |
| SECONDARY Autoantibodies Against Zinc-transporter 8 (ZnT8) |
29; 30; 30; 36; 48; 47 | — |
| SECONDARY Autoantibodies Against Islet Antigen-2 (IA2) |
38; 37; 31; 45; 39; 40 | — |
| SECONDARY Autoantibodies Against Insulin Autoantibodies (IAA) |
35; 28; 26; 36; 42; 48 | — |
| SECONDARY Change in Biomarker: Total Interleukin-21 (IL-21) |
28.8; 31.1; 30.9; 30.2; 3993.5; 4368.2 | — |
| SECONDARY Change in Biomarker: Serum Vitamin D (1,25 Dehydroxy-calciferol) |
123; 122; 122; 120; 117; 125 | — |
| SECONDARY Change in Short Form 36 Health Survey (SF-36) |
-0.8; -2.2; 0.1; 0.6; 0.8; -1.4 | — |
| SECONDARY Change in Experience of Treatment Benefits and Barriers (ETBB) |
-1.2; -1.8; -0.2; -0.3; -2.0; -2.0 | — |
| SECONDARY Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ) |
0.6; 0.0; 0.0; 0.5; 0.9; 0.5 | — |
| SECONDARY Area Under the Concentration-time Curve (AUC) 0-4h of Mixed Meal Tolerance Test (MMTT) Stimulated C-peptide at Week 80 Relative to Baseline |
0.566; 0.598; 0.373; 0.571 | — |
| SECONDARY AUC0-2h of C-peptide at Week 80 Relative to Baseline |
0.590; 0.619; 0.370; 0.540 | — |
| SECONDARY Cmax of C-peptide at Week 80 Relative to Baseline |
0.580; 0.592; 0.389; 0.568 | — |
| SECONDARY AUC0-4h of Glucose at Week 80 Relative to Baseline |
1.129; 1.115; 1.136; 1.221 | — |
| SECONDARY AUC0-2h of Glucose at Week 80 Relative to Baseline |
1.119; 1.086; 1.070; 1.166 | — |
| SECONDARY Cmax of Glucose at Week 80 Relative to Baseline |
1.114; 1.074; 1.104; 1.155 | — |
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.
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
Data sourced from ClinicalTrials.gov (NCT02443155). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.