Clinical Phase II/III Trial of Ustekinumab to Treat Type 1 Diabetes (UST1D2)

This is a randomized, placebo-controlled, double-blinded, multi-centre phase II/II study to assess efficacy and safety of Ustekinumab (STELARA®) in patients with T1D. The investigators will perform a phase II/III clinical trial with a total of 66 adult (18-35 years old) subjects with recent-onset T1D. There will be two study cohorts, with a drug:placebo ratio of 2:1. Patients receiving the study drug will receive a loading dose of 6mg/kg Ustekinumab IV given at week 0. Thereafter, 90mg Ustekinumab subcutaneously given at weeks 8, 16, 24, 32, 40, 48 (total of 7 doses). Patients randomized to receive placebo will receive respective amounts of a saline-placebo. An additional non-dosing visit at the midpoint (week 28) is required to measure 2-hour C-peptide during a MMTT. Patients will be followed for 78 weeks following the first dose. There will be a total of 10 study visits over 78 weeks, three of which are non-dosing and follow-up visits. Recruitment and screening for the study will be completed within the first 24 months. The follow up period is 1 and 1.5 years from the first dose.

Inclusion criteria

• A diagnosis of type 1 diabetes mellitus in accordance with the ADA/CDA criteria.
• An interval of ≤100 days between the diagnosis and the first dose of the study drug.
• Ability to provide documented informed consent.
• Male or female, aged 18-35 years inclusive, at the time of the anticipated first dose of the study drug.
• Evidence of residual functioning β cells. This will be assessed by a C-peptide level over 0.2nmol/L in the MMTT test.
• Positive for at least one diabetes-related autoantibody.
• Willing to record all insulin taken and blood glucose levels that are required for monitoring during the study, including reporting any hypoglycaemic events.

Exclusion criteria

• No condition that, in the investigators' judgment, is likely to cause the subject to not be able to understand information in order to provide informed consent.
• History of malignancy.
• No significant and/or active disease in any body system that is likely to increase the risk to the subject or interfere with the subject's participation in the study.
• No significant systemic infection during the 6 weeks before the first dose of the study drug.
• No history of current or past active tuberculosis infection and no latent tuberculosis as per CDC guidelines.
• Have used any other investigational drug within the 3 months prior to the first dose and/or intend on using any investigational drug for the duration of the study.
• Prior or current treatment that is known to cause a significant, ongoing change in the course of T1D or immunological status.
• Current or prior (within 30 days prior to first study drug dose) use of medications known to influence glucose tolerance.
• No significant abnormal laboratory values during the screening period, other than those due to T1D.
• Not pregnant, breastfeeding or planning to become pregnant during the 60 days after the last dose of the study drug.
• Have not received any live vaccines within 30 days prior to the first study drug dose and are not expected to need to receive a vaccine during the study.
• No prior allergic reaction, including anaphylaxis, to any component of the study drug product.
• No prior allergic reaction, including anaphylaxis, to any human, humanized, chimeric or rodent antibody treatment.
• Have not undergone any major surgery within the 30 day period prior to the first drug dose and not anticipating requiring surgery during the study period.
• Negative results for Hepatitis B surface antigen and for antibodies to Hepatitis B core antigen, or evidence of Hepatitis B surface antibody > 10 IU, and negative for Hepatitis C. Negative results for HIV and not considered by the investigator to be at high risk for HIV infection.