Tocilizumab (TCZ) in New-onset Type 1 Diabetes (EXTEND)
Type 1 Diabetes Mellitus, New-onset Type 1 Diabetes Mellitus, T1DM
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
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.
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
Experimental
Placebo Comparator
Tocilizumab (TCZ) + SOC
Tocilizumab Placebo Group + SOC
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])