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

NCT03941132 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: H19-00411
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 2

Brief Summary

In type 1 diabetes (T1D), immune defense cells in the body attack and destroy insulin-producing beta cells leaving affected people with a lifelong need for daily insulin injections. Even with insulin injections, blood glucose (sugar) control is imperfect and leads to many health complications and a shortened life span. Our pilot study (NCT02117765) has informed us that Ustekinumab is safe in the treatment of participants with recent-onset T1D. Ustekinumab is currently licensed for use in psoriasis where it has proven to be both highly effective and safe. The investigators hope that if the drug can block immune cells soon after the development of diabetes, any remaining insulin-producing cells may be protected, and regenerate, thus producing more insulin so that individuals may be insulin free, or require less insulin. This trial will assess the efficacy of Ustekinumab in decreasing C-peptide decline (proxy for endogenous insulin production) in participants with recent onset T1D.

Conditions

Type 1 Diabetes Mellitus

Keywords

T1D; Ustekinumab; new-onset; diabetes

Outcome Measures

Primary Outcomes (2)

• Baseline change in 2-hour mixed meal-stimulated C-peptide AUC at week 52.

  Week 52

• Rate, frequency and severity of all adverse events including; hypoglycemic episodes; injection reactions; hypersensitivity reactions; evidence of infection and posterior leukoencephalopathy syndrome.

  Week 52

Secondary Outcomes (13)

• 2-hour MMTT-stimulated C-peptide AUC at weeks 28 and 78)

  Weeks 28 and 78

• HbA1C and insulin use in units per kg body weight per day at weeks 0, 8, 16, 24, 28, 32, 40, 48, 52, 78.

  78 Weeks

• Immune phenotyping via flow cytometry of all IL-12, IL-23, IL-17, IFN-γ secreting immune subsets at weeks 0, 32, 52, 78).

  78 Weeks

• Basic immune phenotyping of WBC subsets

  78 Weeks

• HLA- A, B, C, DR, DP, DQ typing at weeks 0, 8 ,16, 32, 52, 78)

  78 Weeks

Study Arms (2)

Ustekinumab

EXPERIMENTAL

Week 0: Loading dose of 6mg/kg Ustekinumab Intravenously. Weeks 8, 16, 24, 32, 40, and 48 (6 visits): 90mg Ustekinumab subcutaneously. Weeks 28, 52, 78: Non-dosing visits where a Mixed Meal Tolerance Test will be administered. Total of 11 visits

Drug: Ustekinumab

Saline Solution - Placebo

PLACEBO COMPARATOR

Patients allocated to receive placebo will receive respective amounts of a saline-placebo at the same intervals. Week 0: Loading dose of 6mg/kg saline intravenously. Weeks 8, 16, 24, 32, 40, and 48 (6 visits): 90mg saline subcutaneously. Weeks 28, 52, 78: Non-dosing visits where a Mixed Meal Tolerance Test will be administered. Total of 11 visits

Drug: Placebo

Interventions

Ustekinumab DRUG

Week 0: Loading dose of 6mg/kg Ustekinumab Intravenously. Weeks 8, 16, 24, 32, 40, and 48 (6 visits): 90mg Ustekinumab subcutaneously.

Also known as: Stelara

Ustekinumab

Placebo DRUG

Patients allocated to receive placebo will receive respective amounts of a saline-placebo at the same intervals. Week 0: Loading dose of 6mg/kg saline intravenously. Weeks 8, 16, 24, 32, 40, and 48 (6 visits): 90mg saline subcutaneously.

Also known as: Saline solution

Saline Solution - Placebo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of British Columbia: lead
• Juvenile Diabetes Research Foundation: collaborator
• Janssen, LP: collaborator

Study Sites (2)

Mount Sinai Hospital/UHN

Toronto, British Columbia, M5T 3L9, Canada

Location

BCDiabetes

Vancouver, British Columbia, V5Y 3W2, Canada

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus

Interventions

Ustekinumab; Saline Solution

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Jan Dutz, MD FRCPC

  University of British Columbia

  PRINCIPAL INVESTIGATOR

• Betina F Rasmussen, MSc

  University of British Columbia

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: There will be a total of 60 patients enrolled in the study. The study participants will be enrolled at 2 centers (Vancouver and Toronto), and will be referred by adult or pediatric endocrinologists. This sample size estimation is based on results from week 52 C-peptide AUC values observed in the pilot UST1D study and the expected 1-year C-peptide decline in adult-onset T1D patients. Using a 2:1 Ustekinumab vs. placebo randomized assignment, a sample size of 60 yields 85% power to detect improvement in C-peptide function (alpha = 0.05) in the Ustekinumab group for an unstratified analysis at 12 months. Sixty-six participants (44 active: 22 placebo) will be recruited to allow for an approximate 10% loss to follow-up.

Study Record Dates

• First Submitted: May 3, 2019
• First Posted: May 7, 2019
• Study Start: January 4, 2021
• Primary Completion: February 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: February 24, 2025

Record last verified: 2025-02

Locations

CA (2)