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

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

Sponsors

Lead Sponsor: Novo Nordisk A/S

Source Novo Nordisk A/S
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.

Overall Status Completed
Start Date November 10, 2015
Completion Date February 27, 2019
Primary Completion Date August 31, 2018
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Area under the curve (AUC)0-4h mixed meal tolerance test(MMTT) stimulated C-peptide concentration-time curve Day 0 to week 54
Secondary Outcome
Measure Time Frame
Number of treatment emergent episodes of diabetic ketoacidosis (DKA) Weeks 0-54
Number of treatment emergent hypoglycaemic episodes according to the American Diabetes Association (ADA) and Novo Nordisk definitions Weeks 0-54
Area under the curve 0-4h for MMTT (mixed meal tolerance test) stimulated C-peptide concentration time curve Week 0, Week 80
Area under the curve 0-2h for MMTT stimulated C-peptide concentration time curve Week 0, Week 54
Area under the curve 0-2h for MMTT stimulated C-peptide concentration time curve Week 0, Week 80
Maximum MMTT stimulated C-peptide concentration (Cmax, C-peptide) Week 0, Week 54
Maximum MMTT stimulated C-peptide concentration (Cmax, C-peptide) Week 0, Week 80
Change in fasting C-peptide Week 0, Week 54
Change in fasting C-peptide Week 0, Week 80
Change in HbA1c (Glycosylated haemoglobin)) Week 0, Week 54
Change in HbA1c (Glycosylated haemoglobin)) Week 0, Week 80
Change in fasting plasma glucose Week 0, Week 54
Change in fasting plasma glucose Week 0, Week 80
Total daily insulin dose in units per kg (three day average) Week 54, Week 80
Enrollment 308
Condition
Intervention

Intervention Type: Drug

Intervention Name: NNC0114-0006

Description: NNC0114-0006 12 mg/kg administered i.v (intravenously) every 6 weeks. Subjects will continue their pre-trial insulin treatment

Intervention Type: Drug

Intervention Name: liraglutide

Description: Liraglutide 1.8 mg administered s.c. (subcutaneously) daily. Subjects will continue their pre-trial insulin treatment

Intervention Type: Drug

Intervention Name: placebo

Description: Placebo administered s.c (subcutaneously) or i.v ( intravenously). Subjects will continue their pre-trial insulin treatment

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

Gender: All

Minimum Age: 18 Years

Maximum Age: 45 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Global Clinical Registry (GCR, 1452) Study Director Novo Nordisk A/S
Location
Facility:
Novo Nordisk Investigational Site | La Jolla, California, 92037, United States
Novo Nordisk Investigational Site | Northridge, California, 91325, United States
Novo Nordisk Investigational Site | Aurora, Colorado, 80045, United States
Novo Nordisk Investigational Site | Miami, Florida, 33136, United States
Novo Nordisk Investigational Site | Orlando, Florida, 32804, United States
Novo Nordisk Investigational Site | Atlanta, Georgia, 30339, United States
Novo Nordisk Investigational Site | Lexington, Kentucky, 40503, United States
Novo Nordisk Investigational Site | Las Vegas, Nevada, 89128, United States
Novo Nordisk Investigational Site | Teaneck, New Jersey, 07666, United States
Novo Nordisk Investigational Site | Chapel Hill, North Carolina, 27517, United States
Novo Nordisk Investigational Site | Nashville, Tennessee, 37203, United States
Novo Nordisk Investigational Site | Houston, Texas, 77079, United States
Novo Nordisk Investigational Site | Mesquite, Texas, 75149, United States
Novo Nordisk Investigational Site | Graz, 8036, Austria
Novo Nordisk Investigational Site | Innsbruck, 6020, Austria
Novo Nordisk Investigational Site | Salzburg, 5020, Austria
Novo Nordisk Investigational Site | Wien, 1030, Austria
Novo Nordisk Investigational Site | Wien, 1130, Austria
Novo Nordisk Investigational Site | Brussels, 1090, Belgium
Novo Nordisk Investigational Site | Edegem, 2650, Belgium
Novo Nordisk Investigational Site | Leuven, 3000, Belgium
Novo Nordisk Investigational Site | Edmonton, Alberta, T6G 2E1, Canada
Novo Nordisk Investigational Site | Vancouver, British Columbia, V5Z 1M9, Canada
Novo Nordisk Investigational Site | Winnipeg, Manitoba, R3E 3P4, Canada
Novo Nordisk Investigational Site | Halifax, Nova Scotia, B3H 2Y9, Canada
Novo Nordisk Investigational Site | Kingston, Ontario, K7L 2V7, Canada
Novo Nordisk Investigational Site | Toronto, Ontario, M4G 3E8, Canada
Novo Nordisk Investigational Site | Laval, Quebec, H7T 2P5, Canada
Novo Nordisk Investigational Site | Montreal, Quebec, H4A 3T2, Canada
Novo Nordisk Investigational Site | Sherbrooke, Quebec, J1H 5N4, Canada
Novo Nordisk Investigational Site | Quebec, G1V 4G2, Canada
Novo Nordisk Investigational Site | Aarhus N, 8200, Denmark
Novo Nordisk Investigational Site | Esbjerg, 6700, Denmark
Novo Nordisk Investigational Site | Hellerup, 2900, Denmark
Novo Nordisk Investigational Site | Helsinki, 00290, Finland
Novo Nordisk Investigational Site | Oulu, 90220, Finland
Novo Nordisk Investigational Site | Tampere, 33520, Finland
Novo Nordisk Investigational Site | Dublin, DUBLIN 15, Ireland
Novo Nordisk Investigational Site | Dublin, DUBLIN 4, Ireland
Novo Nordisk Investigational Site | Galway, H91 YR71, Ireland
Novo Nordisk Investigational Site | Holon, 58100, Israel
Novo Nordisk Investigational Site | Jerusalem, 91120, Israel
Novo Nordisk Investigational Site | Petah Tikva, 49202, Israel
Novo Nordisk Investigational Site | Rehovot, 76100, Israel
Novo Nordisk Investigational Site | Bergamo, 24127, Italy
Novo Nordisk Investigational Site | Catanzaro, 88100, Italy
Novo Nordisk Investigational Site | Milano, 20132, Italy
Novo Nordisk Investigational Site | Siena, 53100, Italy
Novo Nordisk Investigational Site | Oslo, 0586, Norway
Novo Nordisk Investigational Site | Stavanger, 4011, Norway
Novo Nordisk Investigational Site | Gdansk, 80-214, Poland
Novo Nordisk Investigational Site | Gdansk, 80-546, Poland
Novo Nordisk Investigational Site | Warszawa, 04-736, Poland
Novo Nordisk Investigational Site | Zabrze, 41-800, Poland
Novo Nordisk Investigational Site | Almada, 2805-267, Portugal
Novo Nordisk Investigational Site | Amadora, 2720-276, Portugal
Novo Nordisk Investigational Site | Braga, 4710-243, Portugal
Novo Nordisk Investigational Site | Matosinhos, 4464-513, Portugal
Novo Nordisk Investigational Site | Porto, 4200-319, Portugal
Novo Nordisk Investigational Site | Viana do Castelo, 4901-858, Portugal
Novo Nordisk Investigational Site | Arkhangelsk, 163001, Russian Federation
Novo Nordisk Investigational Site | Chelyabinsk, 454000, Russian Federation
Novo Nordisk Investigational Site | Dzerzhinskiy, 140091, Russian Federation
Novo Nordisk Investigational Site | Kazan, 420012, Russian Federation
Novo Nordisk Investigational Site | Moscow, 123423, Russian Federation
Novo Nordisk Investigational Site | Moscow, 125315, Russian Federation
Novo Nordisk Investigational Site | Novosibirsk, 630091, Russian Federation
Novo Nordisk Investigational Site | Penza, 440026, Russian Federation
Novo Nordisk Investigational Site | Saint-Petersburg, 199226, Russian Federation
Novo Nordisk Investigational Site | Saratov, 410031, Russian Federation
Novo Nordisk Investigational Site | Saratov, 410053, Russian Federation
Novo Nordisk Investigational Site | Syktyvkar, 167981, Russian Federation
Novo Nordisk Investigational Site | Ulianovsk, 432063, Russian Federation
Novo Nordisk Investigational Site | Yoshkar-Ola, 424004, Russian Federation
Novo Nordisk Investigational Site | Belgrade, 11000, Serbia
Novo Nordisk Investigational Site | Kragujevac, 34000, Serbia
Novo Nordisk Investigational Site | Barcelona, 08035, Spain
Novo Nordisk Investigational Site | Girona, 17007, Spain
Novo Nordisk Investigational Site | Málaga, 29010, Spain
Novo Nordisk Investigational Site | Palma de Mallorca, 07198, Spain
Novo Nordisk Investigational Site | Sabadell, 08208, Spain
Novo Nordisk Investigational Site | Sevilla, 41003, Spain
Novo Nordisk Investigational Site | Sevilla, 41009, Spain
Novo Nordisk Investigational Site | Valencia, 46026, Spain
Novo Nordisk Investigational Site | Göteborg, 413 45, Sweden
Novo Nordisk Investigational Site | Karlstad, 651 85, Sweden
Novo Nordisk Investigational Site | Lund, 221 85, Sweden
Novo Nordisk Investigational Site | Stockholm, 141 86, Sweden
Novo Nordisk Investigational Site | Kiev, 03049, Ukraine
Novo Nordisk Investigational Site | Kiev, 04053, Ukraine
Novo Nordisk Investigational Site | Kyiv, 02091, Ukraine
Novo Nordisk Investigational Site | Kyiv, 02232, Ukraine
Novo Nordisk Investigational Site | Kyiv, 04114, Ukraine
Novo Nordisk Investigational Site | Vinnytsia, 21010, Ukraine
Novo Nordisk Investigational Site | Zhytomyr, 10002, Ukraine
Novo Nordisk Investigational Site | Belfast, BT12 6BA, United Kingdom
Novo Nordisk Investigational Site | Blackburn, BB2 3HH, United Kingdom
Novo Nordisk Investigational Site | Bristol, BS10 5NB, United Kingdom
Novo Nordisk Investigational Site | Cardiff, CF14 4XW, United Kingdom
Novo Nordisk Investigational Site | Chester, CH2 1UL, United Kingdom
Novo Nordisk Investigational Site | Edgbaston, Birmingham, B15 2TH, United Kingdom
Novo Nordisk Investigational Site | London, E1 2AT, United Kingdom
Novo Nordisk Investigational Site | London, W2 1NY, United Kingdom
Novo Nordisk Investigational Site | Newcastle upon Tyne, NE1 4LP, United Kingdom
Novo Nordisk Investigational Site | Plymouth, PL8 8DQ, United Kingdom
Novo Nordisk Investigational Site | Sheffield, S5 7AU, United Kingdom
Novo Nordisk Investigational Site | Stevenage, SG1 4AB, United Kingdom
Novo Nordisk Investigational Site | Swansea, SA2 8PP, United Kingdom
Location Countries

Austria

Belgium

Canada

Denmark

Finland

Ireland

Israel

Italy

Norway

Poland

Portugal

Russian Federation

Serbia

Spain

Sweden

Ukraine

United Kingdom

United States

Verification Date

March 2020

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 4
Arm Group

Label: NNC0114-0006 + Liraglutide

Type: Experimental

Label: NNC0114-0006 + Placebo

Type: Experimental

Label: Liraglutide + Placebo

Type: Active Comparator

Label: Placebo

Type: Placebo Comparator

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Double (Participant, Investigator)

Source: ClinicalTrials.gov