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

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Completed; Phase 2

Conditions: Type 1 Diabetes Mellitus; T1D; New-onset Type 1 Diabetes Mellitus; T1DM

Treatments: Drug: Placebo; Drug: Tocilizumab (TCZ); Other: Standard of Care

Study type: Interventional

Funder types: NETWORK; Industry; NIH

Identifiers

NCT02293837

DAIT ITN058AI

Details and patient eligibility

About

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.

Full 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.

Enrollment: 136 patients

Sex: All

Ages: 6 to 17 years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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136 participants in 2 patient groups, including a placebo group

Tocilizumab (TCZ) + SOC

Experimental group

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 \[Standard of Care, SOC\])

Treatment:

Other: Standard of Care

Drug: Tocilizumab (TCZ)

Tocilizumab Placebo Group + SOC

Placebo Comparator group

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 \[Standard of Care, SOC\])

Treatment:

Other: Standard of Care

Drug: Placebo