Canakinumab Study in Individuals With Newly Diagnosed Type 1 Diabetes (TN14)

Effects of Canakinumab On The Progression of Type 1 Diabetes In New Onset Subjects

Canakinumab is a fully human anti-interleukin-1β (anti-IL-1β) monoclonal antibody (IgG-1 class). Canakinumab is designed to bind to human IL-1β and to functionally neutralize the bioactivity of this pro-inflammatory cytokine.

The study is a two-arm, multicenter, randomized, double-masked, placebo-controlled clinical trial. 66 subjects will be randomly assigned to receive either monthly subcutaneous injections of 2.0 mg/kg Canakinumab, or placebo for 12 months. All groups will receive standard intensive diabetes treatment with insulin and dietary management.

Participants randomly assigned to Canakinumab treatment or placebo will receive a total of 12 injections over one year.

All subjects will be followed for 1 year of treatment plus 1- 3 years of additional follow-up until study end. Enrollment is expected to occur over two years.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes; Preservation of Insulin Secretion; Newly Diagnosed Type 1 Diabetes; Canakinumab in Type 1 Diabetes
• Intervention / Treatment: Drug: Placebo; Drug: canakinumab (anti IL-1beta)

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Hospital for Sick Children
• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California-San Francisco
    • Stanford, California, United States, 94305
      • Stanford University
  • Connecticut
    • New Haven, Connecticut, United States
      • Yale Medical School
  • Florida
    • Gainesville, Florida, United States, 32610-
      • University of Florida
    • Miami, Florida, United States, 33136
      • University of Miami School of Medicine
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University-Riley Hospital for Children
  • Minnesota
    • Minneapolis, Minnesota, United States, 57931
      • University of Minnesota
  • New York
    • New York, New York, United States
      • Columbia University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas-Southwestern Medical School
  • Washington
    • Seattle, Washington, United States, 98101
      • Benaroya Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Between the ages of 6-45 years
• Be within 3-months (100 days) of diagnosis of type 1 diabetes
• Must have at least one diabetes-related autoantibody present
• Must have stimulated C-peptide levels >0.2 pmol/ml measured during a mixed meal tolerance test (MMTT) conducted at least 21 days from diagnosis and within 37 days of randomization
• If participant is female with reproductive potential, she must be willing to avoid pregnancy and have a negative pregnancy test during the 12 months of treatment and for an additional 3 months after completing treatment
• Be at least one month from time of last live immunization received
• Willing to forgo live vaccinations for 24 months
• Must be willing to comply with intensive diabetes management
• Must weigh at least 20 kg (44 lbs) at study entry

Exclusion Criteria:

• Are immunodeficient or have clinically significant chronic lymphopenia (low white blood cell count)
• Have an active infection
• Have a positive PPD test result
• Be currently pregnant or lactating, or anticipate getting pregnant
• Ongoing use of medications known to influence glucose tolerance
• Require use of other immunosuppressive agents
• Have serologic evidence of current or past HIV, Hepatitis B, or Hepatitis C infection
• Have any complicating medical issues or abnormal clinical laboratory blood counts or results that interfere with study conduct; history of malignancies
• Be currently participating in another type 1 diabetes treatment study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo solution given by subcutaneous injection on monthly basis for 12 months	Drug: Placebo; Placebo subcutaneous injections
Experimental: Canakinumab; Subcutaneous injection of canakinumab at dose of 2.0 mg/kg given monthly of 12 months	Drug: canakinumab (anti IL-1beta); canakinumab subcutaneous injections given at 2.0mg/kg dose on monthly basis for 12 months; Other Names: canakinumab; anti IL-1beta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
C-peptide Response to Mixed Meal Glucose Tolerance Test (MMTT) at One Year for Subjects Given Canakinumab Compared to Placebo	The primary outcome is the area under the stimulated C-peptide curve (AUC) based on data collected at time 0 to 2 hours of a 4-hour mixed meal glucose tolerance test (MMTT) conducted at the primary endpoint visit. The timed measurements are done at: 0, 15, 30 60, 90, and 120 minutes. The calculation for the concentration of c-peptide is a weighted average of the 6 timed measurements of c-peptide in nano-moles/Liter. We try to distinguish this calculation from the AUC by referring to it as the "AUC mean" and may be expressed algebraically as the AUC/(120 min.); thus, the units are the same as the y-axis.	12 months

Collaborators and Investigators

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

General Publications

• Moran A, Bundy B, Becker DJ, DiMeglio LA, Gitelman SE, Goland R, Greenbaum CJ, Herold KC, Marks JB, Raskin P, Sanda S, Schatz D, Wherrett DK, Wilson DM, Krischer JP, Skyler JS; Type 1 Diabetes TrialNet Canakinumab Study Group, Pickersgill L, de Koning E, Ziegler AG, Boehm B, Badenhoop K, Schloot N, Bak JF, Pozzilli P, Mauricio D, Donath MY, Castano L, Wagner A, Lervang HH, Perrild H, Mandrup-Poulsen T; AIDA Study Group. Interleukin-1 antagonism in type 1 diabetes of recent onset: two multicentre, randomised, double-blind, placebo-controlled trials. Lancet. 2013 Jun 1;381(9881):1905-15. doi: 10.1016/S0140-6736(13)60023-9. Epub 2013 Apr 5.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: July 24, 2009
• First Submitted That Met QC Criteria: July 24, 2009
• First Posted (Estimate): July 28, 2009

Study Record Updates

• Last Update Posted (Actual): May 6, 2020
• Last Update Submitted That Met QC Criteria: April 27, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: T1D; type 1 diabetes; canakinumab; newly diagnosed T1D; anti IL-1
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: TN14 Cana; UC4DK097835 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data are available at the NIDDK Central Repository:https://repository.niddk.nih.gov/studies/tn14-anti-il-1-beta/?query=TN14

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No