Pilot Clinical Trial of Ustekinumab in Patients With New-onset T1D

NCT02117765 | Unknown Phase 1 DMC

• 1 other identifier: H14-00939
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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. This is a pilot clinical trial to test the safety of a drug, ustekinumab, in 20 adult subjects with recent-onset T1D. Ustekinumab is currently licensed for use in psoriasis where it has proven to be both highly effective and safe and so the investigators hope to see a similar effect in T1D. This trial will also be used to determine the best dosage and frequency of the drug to be given to people with T1D to help design future studies on the drug's effectiveness. 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.

Conditions

Type 1 Diabetes

Keywords

T1D; ustekinumab; new-onset; diabetes

Outcome Measures

Primary Outcomes (1)

• Primary Safety Endpoints (composite outcome measure)

  1. Rate, frequency and severity of all adverse events including; hypoglycemic episodes; injection reactions; hypersensitivity reactions; evidence of infection and posterior leukoencephalopathy syndrome. 2. Vital signs, standard hematology and chemistry tests, physical examinations.

  12 months

Secondary Outcomes (2)

• Immunological Endpoints (composite outcome measure)

  12 months

• Exploratory (composite outcome measure)

  12 months

Study Arms (1)

Treatment

EXPERIMENTAL

Four cohorts of 5 subjects will be recruited: Group 1: Five subjects will be given Ustekinumab 45mg SC at 0, 4, 16, 28 and 40 weeks. Group 2: Five subjects will be given Ustekinumab 90mg SC at 0, 4, 16, 28 and 40 weeks. Group 3: Five subjects will be given Ustekinumab 45 mg SC at 0,4 and 16 weeks. Group 4: Five subjects will be given Ustekinumab 90mg SC at 0, 4 and 16 weeks.

Drug: Ustekinumab

Interventions

Ustekinumab DRUG

Also known as: Stelara

Treatment

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 canadian diabetes association 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.
• 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

Study Sites (1)

BC Diabetes

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Related Publications (1)

• Marwaha AK, Chow S, Pesenacker AM, Cook L, Sun A, Long SA, Yang JHM, Ward-Hartstonge KA, Williams E, Domingo-Vila C, Halani K, Harris KM, Tree TIM, Levings MK, Elliott T, Tan R, Dutz JP. A phase 1b open-label dose-finding study of ustekinumab in young adults with type 1 diabetes. Immunother Adv. 2021 Nov 13;2(1):ltab022. doi: 10.1093/immadv/ltab022. eCollection 2022.

  PMID: 35072168 DERIVED

Related Links

• Website for study centre.

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus

Interventions

Ustekinumab

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

Study Officials

• Jan Dutz, MD FRCPC

  Professor Department of Dermatology and Skin Science University of British Columbia

  PRINCIPAL INVESTIGATOR

• Ashish Marwaha, BMBCh PhD

  University of British Columbia

  STUDY DIRECTOR

• Annika Sun, MSc

  University of British Columbia

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2014
• First Posted: April 21, 2014
• Study Start: March 1, 2015
• Primary Completion: February 1, 2017
• Study Completion: June 1, 2017
• Last Updated: May 25, 2016

Record last verified: 2016-05

Locations

CA (1)