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Trial record 1 of 1 for:    tocilizumab | Type 1 Diabetes
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Tocilizumab (TCZ) in New-onset Type 1 Diabetes (EXTEND)

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ClinicalTrials.gov Identifier: NCT02293837
Recruitment Status : Active, not recruiting
First Posted : November 18, 2014
Last Update Posted : May 3, 2019
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE November 13, 2014
First Posted Date  ICMJE November 18, 2014
Last Update Posted Date May 3, 2019
Actual Study Start Date  ICMJE March 12, 2015
Estimated Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 27, 2015)
2-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) [ Time Frame: Week 52 ]
The mean 2-hour C-peptide AUC, measured in pmol/mL, computed by dividing the total AUC by 120 minutes
Original Primary Outcome Measures  ICMJE
 (submitted: November 17, 2014)
Mixed-Meal Tolerance Test (MMTT)-stimulated mean 2-hour C-peptide AUC. [ Time Frame: Week 52 ]
The mean 2-hour C-peptide AUC, measured in pmol/ml, is computed by dividing the total AUC by 120 minutes.
Change History Complete list of historical versions of study NCT02293837 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 18, 2017)
  • MMTT-stimulated mean 2-hour C-peptide AUC [ Time Frame: At weeks 12, 24, and 104 ]
    Mixed-meal tolerance test (MMTT) area under the curve (AUC) computation per protocol.
  • MMTT-stimulated mean 2-hour C-peptide AUC assessed longitudinally [ Time Frame: At weeks 12, 24, 39, 52, 78, and 104 ]
    Mixed-meal tolerance test (MMTT) area under the curve (AUC) computation per protocol.
  • MMTT-stimulated peak and 4-hour C-peptide AUC for subjects ≥12 years old [ Time Frame: At weeks 52 and 104 ]
    Mixed-meal tolerance test (MMTT) area under the curve (AUC) computation per protocol.
  • Insulin Use in Units Per Kilogram Body Weight Per Day [ Time Frame: At weeks 12, 24, 39, 52, 78, and 104 ]
    The need to use exogenous insulin is an indication that the body is not producing enough endogenous insulin. Higher amounts of insulin use indicate higher disease activity.
  • Glycemic Control [ Time Frame: At weeks 12, 24, 39, 52, 78 and 104 ]
    As determined by blood glucose levels over time.
  • Hemoglobin A1c levels [ Time Frame: At weeks 12, 24, 39, 52, 78 and 104 ]
    Glycosylated hemoglobin (HbA1c) is a measure of the average plasma concentration of blood sugar (glucose) over the previous three months and measures the level of optimal management of underlying disease.
  • Rate of Adverse Events (AEs) related to infusion reactions and hypersensitivity [ Time Frame: Baseline [pre-treatment initiation] to 104 Weeks ]
    As defined per protocol.
  • Frequency of all AEs [ Time Frame: Baseline [pre-treatment initiation] to 104 weeks ]
    As defined per protocol.
  • Severity of all AEs. [ Time Frame: Baseline [pre-treatment initiation] to 104 weeks ]
    As defined per protocol.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 17, 2014)
  • Efficacy: MMTT-stimulated mean 2-hour C-peptide AUC. [ Time Frame: At weeks 12, 24, and 104 ]
  • Efficacy: MMTT-stimulated mean 2-hour C-peptide AUC assessed longitudinally [ Time Frame: At weeks 12, 24, 39, 52, 78, and 104 ]
  • Efficacy: MMTT-stimulated peak and 4-hour C-peptide AUC for subjects >=12 years old. [ Time Frame: At weeks 52 and 104 ]
  • Efficacy: Insulin use (U/kg/day). [ Time Frame: At weeks 12, 24, 39, 52, 78 and 104 ]
  • Efficacy: HbA1c levels [ Time Frame: At weeks 12, 24, 39, 52, 78 and 104 ]
  • Safety: Rate of AEs related to infusion reactions and hypersensitivity. [ Time Frame: Baseline to 104 Weeks ]
  • Safety: Frequency of all AEs. [ Time Frame: Baseline to 104 weeks ]
  • Safety: Severity of all AEs. [ Time Frame: Baseline to 104 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tocilizumab (TCZ) in New-onset Type 1 Diabetes
Official Title  ICMJE Preserving Beta-Cell Function With Tocilizumab in New-onset Type 1 Diabetes (ITN058AI)
Brief Summary

Type 1 diabetes mellitus (T1DM) is an autoimmune disease. Based on previous research, study doctors think that giving medicines to affect the immune system soon after diabetes is diagnosed may stop, delay or decrease the destruction of beta cells, resulting in better glucose control.

Researchers believe that tocilizumab could have some effect on the cells in the immune system that are thought to be involved in the development of type 1 diabetes. This study will test whether tocilizumab can help preserve or delay destruction of remaining beta cells in people recently diagnosed type 1 diabetes.

Detailed Description

Staggered enrollment is planned for this trial.

Prior to initiating the study in the pediatric age group (6-17 years old), 30-99 eligible adults (ages 18-45 years) will be randomized 2:1 to tocilizumab or placebo, respectively. Once the first thirty adult participants have completed 12 weeks of treatment, the FDA and Data and Safety Monitoring Board (DSMB) will review available data (e.g., interim analysis) to weigh potential risks and benefits before opening the trial to pediatric participants.

As of ≥ May 15, 2017: Study enrollment is limited to participants ages 6 to 17 years inclusive.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Type 1 Diabetes Mellitus
  • New-onset Type 1 Diabetes Mellitus
  • T1DM
  • T1D
Intervention  ICMJE
  • Drug: Tocilizumab (TCZ)
    Subjects assigned to this group will receive tocilizumab intravenous (IV) infusions of either 8.0 mg/kg (body weight ≥ 30kg) or 10.0 mg/kg (body weight <30kg) every 4 weeks for 24 weeks.
    Other Name: Actemra®
  • Drug: Placebo
    Subjects assigned to this group will receive placebo intravenous (IV) infusions of either 8.0 mg/kg (body weight ≥ 30kg) or 10.0 mg/kg (body weight <30kg) every 4 weeks for 24 weeks.
    Other Name: Placebo for Tocilizumab
Study Arms  ICMJE
  • Experimental: Tocilizumab (TCZ)
    Subjects will receive intravenous (IV) infusions of either 8.0 mg/kg (body weight ≥30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. Participants will also receive standard intensive diabetes management.
    Intervention: Drug: Tocilizumab (TCZ)
  • Placebo Comparator: Tocilizumab Placebo Group
    Subjects will receive IV infusions of either 8.0 mg/kg (body weight ≥ 30kg) or 10.0 mg/kg (body weight <30kg) placebo every 4 weeks for 24 weeks. Participants will also receive standard intensive diabetes management.
    Intervention: Drug: Placebo
Publications * Hundhausen C, Roth A, Whalen E, Chen J, Schneider A, Long SA, Wei S, Rawlings R, Kinsman M, Evanko SP, Wight TN, Greenbaum CJ, Cerosaletti K, Buckner JH. Enhanced T cell responses to IL-6 in type 1 diabetes are associated with early clinical disease and increased IL-6 receptor expression. Sci Transl Med. 2016 Sep 14;8(356):356ra119. doi: 10.1126/scitranslmed.aad9943.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 18, 2018)
136
Original Estimated Enrollment  ICMJE
 (submitted: November 17, 2014)
108
Estimated Study Completion Date  ICMJE August 2020
Estimated Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female aged 6-45 years*

    -*Current Institutional Review Board (IRB)-approved age eligibility criteria is restricted to subjects 6 to 17 years of age at time of study enrollment

  2. Diagnosis of type 1 diabetes mellitus (T1DM), using the American Diabetes Association T1DM criteria, within 100 days of study enrollment
  3. Positive for at least one diabetes-related autoantibody, including but not limited to:

    1. Glutamate decarboxylase (GAD-65)
    2. Insulin, if obtained within 10 days of the onset of exogenous insulin therapy
    3. Insulinoma antigen-2 (IA-2)
    4. Zinc transporter-8 (ZnT8)
  4. Peak stimulated C-peptide level ≥ 0.2 pmol/mL following a mixed-meal tolerance test (MMTT) conducted at least 21 days from diagnosis and within 37 days of randomization (V0)
  5. Signed informed consent (and informed assent of minor, if applicable).

Exclusion Criteria:

  1. Severe reaction or anaphylaxis to human, humanized or murine monoclonal antibodies
  2. History of malignancy or serious uncontrolled cardiovascular, nervous system, pulmonary, renal, or gastrointestinal disease, or significant dyslipidemia
  3. Any history of recent serious bacterial, viral, fungal, or other opportunistic infections
  4. Have serologic evidence of current or past HIV (Human immunodeficiency virus), Hepatitis B, or Hepatitis C
  5. Positive QuantiFERON Tuberculosis (TB) test, history of TB, or active TB infection
  6. Active infection with Epstein-Barr virus (EBV) as defined by EBV viral load ≥10,000 copies per mL of whole blood
  7. Active infection with Cytomegalovirus (CMV) as defined by CMV viral load ≥10,000 copies per mL of whole blood
  8. Diagnosis of liver disease or elevated hepatic enzymes, as defined by Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), or both > 1.5 x the upper limit of age-determined normal (ULN) or total bilirubin > ULN
  9. Current or prior treatment that is known to cause a significant, ongoing change in the course of T1D or immunologic status
  10. Current or prior (within last 30 days) use of drugs other than insulin to treat hyperglycemia (e.g. metformin, sulfonylureas, glinides, thiazolidinediones, exenatide, liraglutide, Dipeptidyl peptidase-4 Intravenous (DPP-IV) inhibitors, or amylin)
  11. Current use of any medication known to significantly influence glucose tolerance (e.g., atypical antipsychotics, diphenylhydantoin, niacin)
  12. Any of the following hematologic abnormalities, confirmed by repeat tests:

    1. White blood count <3,000/microL or >14,000/microL
    2. Lymphocyte count <500/microL
    3. Platelet count <150,000 /microL
    4. Hemoglobin <8.5 g/dL
    5. . Neutrophil count <2,000 cells/microL.
  13. Females who are pregnant, lactating, or planning on pregnancy during the 2- year study period
  14. History or diagnoses of other autoimmune diseases with the exception of stable thyroid or celiac disease
  15. History of alcohol, drug or chemical abuse within 1 year prior to study eligibility screening evaluation
  16. Any medical or psychological condition that in the opinion of the principal investigator would interfere with safe completion of the trial
  17. Prior participation in a clinical trial that could increase risks associated with this clinical trial
  18. Receipt of live vaccine (e.g. varicella, measles, mumps, rubella, cold-attenuated intranasal influenza vaccine, bacillus Calmette-Guérin, and small pox) in the 6 weeks before randomization
  19. High lipid levels (fasting Low-density lipoprotein (LDL) cholesterol ≥160 mg/dL)
  20. History of significant allergy (e.g. anaphylaxis) to milk or soy proteins.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   United States
Removed Location Countries Canada
 
Administrative Information
NCT Number  ICMJE NCT02293837
Other Study ID Numbers  ICMJE DAIT ITN058AI
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: The plan is to share data upon completion of the study in: 1.)ImmPort, a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts; and 2.)TrialShare, a clinical trials research portal developed by the Immune Tolerance Network that makes data from the consortium's clinical trials publicly available.
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Immune Tolerance Network (ITN)
Investigators  ICMJE
Study Chair: Carla Greenbaum Benaroya Research Institute at Virginia Mason: Diabetes Research Program
Study Chair: Jane Buckner, M.D. Benaroya Research Institute at Virginia Mason: Diabetes Research Program
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP