Tocilizumab (TCZ) in New-onset Type 1 Diabetes

NCT ID: NCT02293837

Last Updated: 2021-09-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 136 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-12
• Study Completion Date: 2020-08-31

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Tocilizumab (TCZ) + 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 \[Standard of Care, SOC\])

Group Type: EXPERIMENTAL

Tocilizumab (TCZ)

Intervention Type: DRUG

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.

Standard of Care

Intervention Type: OTHER

Participants will also receive standard intensive diabetes management (in accordance with the American Diabetes Association guidelines \[Standard of Care, SOC\])

Tocilizumab Placebo Group + 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 \[Standard of Care, SOC\])

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Standard of Care

Intervention Type: OTHER

Participants will also receive standard intensive diabetes management (in accordance with the American Diabetes Association guidelines \[Standard of Care, SOC\])

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Standard of Care

Participants will also receive standard intensive diabetes management (in accordance with the American Diabetes Association guidelines \[Standard of Care, SOC\])

Intervention Type: OTHER

Other Intervention Names

Actemra®; Placebo for Tocilizumab; SOC

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Immune Tolerance Network (ITN)

NETWORK

Sponsor Role: collaborator

PPD Development, LP

INDUSTRY

Sponsor Role: collaborator

Rho Federal Systems Division, Inc.

INDUSTRY

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carla Greenbaum

Role: STUDY_CHAIR

Benaroya Research Institute at Virginia Mason: Diabetes Research Program

Jane Buckner, M.D.

Role: STUDY_CHAIR

Benaroya Research Institute at Virginia Mason: Diabetes Research Program

Locations

University of California San Francisco

San Francisco, California, United States

Stanford University

Stanford, California, United States

Yale University School of Medicine: Diabetes Endocrinology Research Center

New Haven, Connecticut, United States

University of Florida

Gainesville, Florida, United States

University of Miami: Diabetes Research Institute

Miami, Florida, United States

University of South Florida: Diabetes Center

Tampa, Florida, United States

Indiana University Health - Riley Hospital for Children

Indianapolis, Indiana, United States

University of Iowa

Iowa City, Iowa, United States

Harvard University, Joslin Diabetes Center

Boston, Massachusetts, United States

University of Minnesota

Minneapolis, Minnesota, United States

Children's Mercy Hospital

Kansas City, Missouri, United States

Columbia University, Naomi Berrie Diabetes Center

New York, New York, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Sanford Research

Sioux Falls, South Dakota, United States

Vanderbilt University

Nashville, Tennessee, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Benaroya Research Institute

Seattle, Washington, United States

The Children's Hospital at Westmead: Kids Research Institute

Westmead, New South Wales, Australia

Lady Cilento Children's Hospital: Department of Endocrinology

South Brisbane, Queensland, Australia

Countries

United States; Australia

References

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.

Reference Type: DERIVED

PMID: 34747368 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27629486 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases (NIAID) website

https://www.niaid.nih.gov/about/dait

Division of Allergy, Immunology, and Transplantation (DAIT) website

http://www.immunetolerance.org/

Immune Tolerance Network (ITN) website

http://www.extendstudy.org/about-extend

EXTEND's study-specific ITN website

Other Identifiers

DAIT ITN058AI

Identifier Type: -

Identifier Source: org_study_id