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Tocilizumab (TCZ) in New-onset Type 1 Diabetes (EXTEND)

Primary Purpose

Type 1 Diabetes Mellitus, New-onset Type 1 Diabetes Mellitus, T1DM

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Tocilizumab (TCZ)
Placebo
Standard of Care
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 1 Diabetes Mellitus focused on measuring interleukin-6 (IL-6) receptor inhibitor

Eligibility Criteria

6 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of California San Francisco
  • Stanford University
  • Yale University School of Medicine: Diabetes Endocrinology Research Center
  • University of Florida
  • University of Miami: Diabetes Research Institute
  • University of South Florida: Diabetes Center
  • Indiana University Health - Riley Hospital for Children
  • University of Iowa
  • Harvard University, Joslin Diabetes Center
  • University of Minnesota
  • Children's Mercy Hospital
  • Columbia University, Naomi Berrie Diabetes Center
  • Children's Hospital of Philadelphia
  • Sanford Research
  • Vanderbilt University
  • University of Texas Southwestern Medical Center
  • Benaroya Research Institute
  • The Children's Hospital at Westmead: Kids Research Institute
  • Lady Cilento Children's Hospital: Department of Endocrinology

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Tocilizumab (TCZ) + SOC

Tocilizumab Placebo Group + SOC

Arm Description

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 (in accordance with the American Diabetes Association guidelines [Standard of Care, SOC])

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 (in accordance with the American Diabetes Association guidelines [Standard of Care, SOC])

Outcomes

Primary Outcome Measures

Change From Baseline in 2-Hour C-peptide Mean Area Under the Curve (mAUC) in Pediatric Participants
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes post-meal. C-peptide mAUC was calculated using the trapezoidal rule over the 2-hour time period. Larger numbers are preferable (better) in these mAUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., mAUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint.

Secondary Outcome Measures

Change From Baseline in 2-Hour C-peptide Mean Area Under the Curve (mAUC)
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes post-meal. C-peptide mAUC was calculated using the trapezoidal rule over the 2-hour time period. Larger numbers are preferable (better) in these mAUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., mAUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint.
2-Hour C-peptide Mean Area Under the Curve (mAUC), Mixed Model
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes post-meal. C-peptide mAUC was calculated using the trapezoidal rule over the 2-hour time period. Larger numbers are preferable (better) in these mAUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., mAUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint.
Change From Baseline in 4-Hour C-peptide Mean Area Under the Curve (mAUC)
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes post-meal. C-peptide mAUC was calculated using the trapezoidal rule over the 4-hour time period. Larger numbers are preferable (better) in these mAUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., mAUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint.
Change From Baseline in Average Insulin Use in Units Per Kilogram Body Weight Per Day
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. Insulin use was collected each day for 5 days prior to the visit. Average insulin use per kg is the average insulin use over the 5 days prior to the visit divided by the participant's weight in kg.
Change From Baseline in Average Insulin Use Per Kg, Mixed Model
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. Insulin use was collected each day for 5 days prior to the visit. Average insulin use per kg is the average insulin use over the 5 days prior to the visit divided by the participant's weight in kg.
Change From Baseline in Hemoglobin A1c
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. An HbA1c of 5.6% or less is considered normal. HbA1c of 6.5% or higher is typical for individuals with Type 1 Diabetes mellitus (T1DM). The closer HbA1c levels are to normal, the better controlled the disease is.
Change From Baseline in Hemoglobin A1C (HbA1c) Level in Participants, Mixed Model
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. An HbA1c of 5.6% or less is considered normal. HbA1c of 6.5% or higher is typical for individuals with Type 1 Diabetes mellitus (T1DM). The closer HbA1c levels are to normal, the better controlled the disease is.
Number of Participants Who Experienced at Least One Major Hypoglycemic Event After Treatment Initiation
Major hypoglycemic adverse events are defined as: Blood glucose concentration < 40 mg/dL (Grades 3-5, NCI-CTCAE version 4.03*), or hypoglycemic events involving seizure or loss of consciousness (coma) or requiring assistance from another individual in order to recover. *NCI-CTCAE: National Cancer Institute Common Terminology Criteria for Adverse Events
Number of Participants Who Experienced Infusion-Related Adverse Events
An infusion/dose reaction is defined as an adverse event occurring during and within 24 hours after the infusion or subcutaneous injection of tocilizumab. This may include hypersensitivity reactions or anaphylactic reactions.
Number of Participants Who Experienced Hypersensitivity Adverse Events
Signs of a possible hypersensitivity reaction to the study drug include but are not limited to: Fever, chills, pruritus, urticaria, angioedema, and skin rash Cardiopulmonary reactions, including chest pain, dyspnea, hypotension or hypertension

Full Information

First Posted
November 13, 2014
Last Updated
August 16, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Immune Tolerance Network (ITN), PPD, Rho Federal Systems Division, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02293837
Brief Title
Tocilizumab (TCZ) in New-onset Type 1 Diabetes
Acronym
EXTEND
Official Title
Preserving Beta-Cell Function With Tocilizumab in New-onset Type 1 Diabetes (ITN058AI)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
March 12, 2015 (Actual)
Primary Completion Date
July 10, 2019 (Actual)
Study Completion Date
August 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Immune Tolerance Network (ITN), PPD, Rho Federal Systems Division, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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 limited to participants ages 6 to 17 years inclusive.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes Mellitus, New-onset Type 1 Diabetes Mellitus, T1DM, T1D
Keywords
interleukin-6 (IL-6) receptor inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
136 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tocilizumab (TCZ) + SOC
Arm Type
Experimental
Arm Description
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 (in accordance with the American Diabetes Association guidelines [Standard of Care, SOC])
Arm Title
Tocilizumab Placebo Group + SOC
Arm Type
Placebo Comparator
Arm Description
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 (in accordance with the American Diabetes Association guidelines [Standard of Care, SOC])
Intervention Type
Drug
Intervention Name(s)
Tocilizumab (TCZ)
Other Intervention Name(s)
Actemra®
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo for Tocilizumab
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Standard of Care
Other Intervention Name(s)
SOC
Intervention Description
Participants will also receive standard intensive diabetes management (in accordance with the American Diabetes Association guidelines [Standard of Care, SOC])
Primary Outcome Measure Information:
Title
Change From Baseline in 2-Hour C-peptide Mean Area Under the Curve (mAUC) in Pediatric Participants
Description
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes post-meal. C-peptide mAUC was calculated using the trapezoidal rule over the 2-hour time period. Larger numbers are preferable (better) in these mAUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., mAUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint.
Time Frame
Baseline (Pre-treatment) to Week 52
Secondary Outcome Measure Information:
Title
Change From Baseline in 2-Hour C-peptide Mean Area Under the Curve (mAUC)
Description
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes post-meal. C-peptide mAUC was calculated using the trapezoidal rule over the 2-hour time period. Larger numbers are preferable (better) in these mAUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., mAUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint.
Time Frame
Baseline (Pre-treatment) to Weeks 24, 52, and 104
Title
2-Hour C-peptide Mean Area Under the Curve (mAUC), Mixed Model
Description
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes post-meal. C-peptide mAUC was calculated using the trapezoidal rule over the 2-hour time period. Larger numbers are preferable (better) in these mAUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., mAUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint.
Time Frame
Baseline (Pre-treatment), Weeks 12, 24, 39, 52, 78, and 104
Title
Change From Baseline in 4-Hour C-peptide Mean Area Under the Curve (mAUC)
Description
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes post-meal. C-peptide mAUC was calculated using the trapezoidal rule over the 4-hour time period. Larger numbers are preferable (better) in these mAUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., mAUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint.
Time Frame
Baseline (Pre-treatment) to Weeks 52 and 104
Title
Change From Baseline in Average Insulin Use in Units Per Kilogram Body Weight Per Day
Description
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. Insulin use was collected each day for 5 days prior to the visit. Average insulin use per kg is the average insulin use over the 5 days prior to the visit divided by the participant's weight in kg.
Time Frame
Baseline (Pre-treatment) to Weeks 24, 52, and 104
Title
Change From Baseline in Average Insulin Use Per Kg, Mixed Model
Description
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. Insulin use was collected each day for 5 days prior to the visit. Average insulin use per kg is the average insulin use over the 5 days prior to the visit divided by the participant's weight in kg.
Time Frame
Baseline (Pre-treatment) to Weeks 12, 24, 39, 52, 78, and 104
Title
Change From Baseline in Hemoglobin A1c
Description
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. An HbA1c of 5.6% or less is considered normal. HbA1c of 6.5% or higher is typical for individuals with Type 1 Diabetes mellitus (T1DM). The closer HbA1c levels are to normal, the better controlled the disease is.
Time Frame
Baseline (Pre-treatment) to Weeks 24, 52, and 104
Title
Change From Baseline in Hemoglobin A1C (HbA1c) Level in Participants, Mixed Model
Description
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. An HbA1c of 5.6% or less is considered normal. HbA1c of 6.5% or higher is typical for individuals with Type 1 Diabetes mellitus (T1DM). The closer HbA1c levels are to normal, the better controlled the disease is.
Time Frame
Baseline (Pre-treatment) to Weeks 12, 24, 39, 52, 78, and 104
Title
Number of Participants Who Experienced at Least One Major Hypoglycemic Event After Treatment Initiation
Description
Major hypoglycemic adverse events are defined as: Blood glucose concentration < 40 mg/dL (Grades 3-5, NCI-CTCAE version 4.03*), or hypoglycemic events involving seizure or loss of consciousness (coma) or requiring assistance from another individual in order to recover. *NCI-CTCAE: National Cancer Institute Common Terminology Criteria for Adverse Events
Time Frame
Day 0 (Treatment Initiation) to Weeks 52 and 104
Title
Number of Participants Who Experienced Infusion-Related Adverse Events
Description
An infusion/dose reaction is defined as an adverse event occurring during and within 24 hours after the infusion or subcutaneous injection of tocilizumab. This may include hypersensitivity reactions or anaphylactic reactions.
Time Frame
Day 0 (Treatment Initiation) to Week 52
Title
Number of Participants Who Experienced Hypersensitivity Adverse Events
Description
Signs of a possible hypersensitivity reaction to the study drug include but are not limited to: Fever, chills, pruritus, urticaria, angioedema, and skin rash Cardiopulmonary reactions, including chest pain, dyspnea, hypotension or hypertension
Time Frame
Day 0 (Treatment Initiation) to Week 52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Diagnosis of type 1 diabetes mellitus (T1DM), using the American Diabetes Association T1DM criteria, within 100 days of study enrollment Positive for at least one diabetes-related autoantibody, including but not limited to: Glutamate decarboxylase (GAD-65) Insulin, if obtained within 10 days of the onset of exogenous insulin therapy Insulinoma antigen-2 (IA-2) Zinc transporter-8 (ZnT8) 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) Signed informed consent (and informed assent of minor, if applicable). Exclusion Criteria: Severe reaction or anaphylaxis to human, humanized or murine monoclonal antibodies History of malignancy or serious uncontrolled cardiovascular, nervous system, pulmonary, renal, or gastrointestinal disease, or significant dyslipidemia Any history of recent serious bacterial, viral, fungal, or other opportunistic infections Have serologic evidence of current or past HIV (Human immunodeficiency virus), Hepatitis B, or Hepatitis C Positive QuantiFERON Tuberculosis (TB) test, history of TB, or active TB infection Active infection with Epstein-Barr virus (EBV) as defined by EBV viral load ≥10,000 copies per mL of whole blood Active infection with Cytomegalovirus (CMV) as defined by CMV viral load ≥10,000 copies per mL of whole blood 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 Current or prior treatment that is known to cause a significant, ongoing change in the course of T1D or immunologic status 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) Current use of any medication known to significantly influence glucose tolerance (e.g., atypical antipsychotics, diphenylhydantoin, niacin) Any of the following hematologic abnormalities, confirmed by repeat tests: White blood count <3,000/microL or >14,000/microL Lymphocyte count <500/microL Platelet count <150,000 /microL Hemoglobin <8.5 g/dL . Neutrophil count <2,000 cells/microL. Females who are pregnant, lactating, or planning on pregnancy during the 2- year study period History or diagnoses of other autoimmune diseases with the exception of stable thyroid or celiac disease History of alcohol, drug or chemical abuse within 1 year prior to study eligibility screening evaluation Any medical or psychological condition that in the opinion of the principal investigator would interfere with safe completion of the trial Prior participation in a clinical trial that could increase risks associated with this clinical trial 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 High lipid levels (fasting Low-density lipoprotein (LDL) cholesterol ≥160 mg/dL) History of significant allergy (e.g. anaphylaxis) to milk or soy proteins.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carla Greenbaum
Organizational Affiliation
Benaroya Research Institute at Virginia Mason: Diabetes Research Program
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Jane Buckner, M.D.
Organizational Affiliation
Benaroya Research Institute at Virginia Mason: Diabetes Research Program
Official's Role
Study Chair
Facility Information:
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Yale University School of Medicine: Diabetes Endocrinology Research Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
University of Miami: Diabetes Research Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
University of South Florida: Diabetes Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Indiana University Health - Riley Hospital for Children
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Harvard University, Joslin Diabetes Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
002215
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64111
Country
United States
Facility Name
Columbia University, Naomi Berrie Diabetes Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Sanford Research
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57104
Country
United States
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Benaroya Research Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
Facility Name
The Children's Hospital at Westmead: Kids Research Institute
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
Westmead 2145
Country
Australia
Facility Name
Lady Cilento Children's Hospital: Department of Endocrinology
City
South Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
IPD Sharing Time Frame
On average, within 24 months after database lock for the trial.
IPD Sharing Access Criteria
Open access.
IPD Sharing URL
https://www.immport.org/home
Citations:
PubMed Identifier
34747368
Citation
Greenbaum CJ, Serti E, Lambert K, Weiner LJ, Kanaparthi S, Lord S, Gitelman SE, Wilson DM, Gaglia JL, Griffin KJ, Russell WE, Raskin P, Moran A, Willi SM, Tsalikian E, DiMeglio LA, Herold KC, Moore WV, Goland R, Harris M, Craig ME, Schatz DA, Baidal DA, Rodriguez H, Utzschneider KM, Nel HJ, Soppe CL, Boyle KD, Cerosaletti K, Keyes-Elstein L, Long SA, Thomas R, McNamara JG, Buckner JH, Sanda S; ITN058AI EXTEND Study Team. IL-6 receptor blockade does not slow beta cell loss in new-onset type 1 diabetes. JCI Insight. 2021 Nov 8;6(21):e150074. doi: 10.1172/jci.insight.150074.
Results Reference
derived
PubMed Identifier
27629486
Citation
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.
Results Reference
derived
Links:
URL
https://www.niaid.nih.gov/
Description
National Institute of Allergy and Infectious Diseases (NIAID) website
URL
https://www.niaid.nih.gov/about/dait
Description
Division of Allergy, Immunology, and Transplantation (DAIT) website
URL
http://www.immunetolerance.org/
Description
Immune Tolerance Network (ITN) website
URL
http://www.extendstudy.org/about-extend
Description
EXTEND's study-specific ITN website
URL
http://www.diabetes.org/diabetes-basics/type-1/?loc=util-header_type1
Description
American Diabetes Association information on Type 1 Diabetes

Learn more about this trial

Tocilizumab (TCZ) in New-onset Type 1 Diabetes

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