Tocilizumab (TCZ) in New-onset Type 1 Diabetes
Condition: Type 1 Diabetes Mellitus; New-onset Type 1 Diabetes Mellitus; T1DM; T1D
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: Tocilizumab (TCZ); Placebo; Standard of Care
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.; 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.; Participants will also receive standard intensive diabetes management (in accordance with the American Diabetes Association guidelines [Standard of Care, SOC])
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 136.0
Sex: All
Minimum age: 6 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: interleukin-6 (IL-6) receptor inhibitor

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.
    

Eligibility criteria:

        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.