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Pilot Clinical Trial of Ustekinumab in Patients With New-onset T1D (UST1D)

Primary Purpose

Type 1 Diabetes

Status
Unknown status
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Ustekinumab
Sponsored by
University of British Columbia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 1 Diabetes focused on measuring T1D, ustekinumab, new-onset, diabetes

Eligibility Criteria

18 Years - 35 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. A diagnosis of type 1 diabetes mellitus in accordance with the canadian diabetes association criteria.
  2. An interval of ≤100 days between the diagnosis and the first dose of the study drug
  3. Ability to provide documented informed consent.
  4. Male or female, aged 18-35 years inclusive, at the time of the anticipated first dose of the study drug.
  5. Evidence of residual functioning β cells. This will be assessed by a C-peptide level over 0.2nmol/L in the MMTT test.
  6. Positive for at least one diabetes-related autoantibody.
  7. 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:

  1. 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.
  2. History of malignancy.
  3. 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.
  4. No significant systemic infection during the 6 weeks before the first dose of the study drug.
  5. No history of current or past active tuberculosis infection and no latent tuberculosis.
  6. 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.
  7. Prior or current treatment that is known to cause a significant, ongoing change in the course of T1D or immunological status.
  8. Current or prior (within 30 days prior to first study drug dose) use of medications known to influence glucose tolerance.
  9. No significant abnormal laboratory values during the screening period, other than those due to T1D.
  10. Not pregnant, breastfeeding or planning to become pregnant during the 60 days after the last dose of the study drug.
  11. 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.
  12. No prior allergic reaction, including anaphylaxis, to any component of the study drug product.
  13. No prior allergic reaction, including anaphylaxis, to any human, humanized, chimeric or rodent antibody treatment.
  14. 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.
  15. 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.

Sites / Locations

  • BC Diabetes

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

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.

Outcomes

Primary Outcome Measures

Primary Safety Endpoints (composite outcome measure)
Rate, frequency and severity of all adverse events including; hypoglycemic episodes; injection reactions; hypersensitivity reactions; evidence of infection and posterior leukoencephalopathy syndrome. Vital signs, standard hematology and chemistry tests, physical examinations.

Secondary Outcome Measures

Immunological Endpoints (composite outcome measure)
Immune phenotyping via flow cytometry of all Interleukin (IL)-12, IL-23, IL-17, Interferon(IFN)-γ secreting immune subsets. Basic immune phenotyping of white blood cell subsets. Human leukocyte antigen(HLA)- A, B, C, DR, DP, DQ typing. Fluorospot (ELISpot) analysis for IL-17 and IFN-γ secretion in response to whole insulin and antigens for Cluster of differentiation (CD)8+ and CD4+ T cells . Luminex assessment of serum cytokines IL-17, IFN-γ, IL-12 and IL-23. Regulatory T cell : Effector T cell ratio CD154 based assays to determine diabetogenic antigen specific responses of T helper cells. Epigenetic assessment of Treg phenotype and function.
Exploratory (composite outcome measure)
Mixed-meal tolerance test (MMTT) - stimulated 2-hour C-peptide area under the curve (AUC) at weeks 4, 28 and 52. Insulin use in units per kg body weight per day at weeks 4, 16, 28, 40 and 52. HbA1C levels at weeks 4, 16, 28, 40 and 52.

Full Information

First Posted
April 7, 2014
Last Updated
May 24, 2016
Sponsor
University of British Columbia
Collaborators
Juvenile Diabetes Research Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT02117765
Brief Title
Pilot Clinical Trial of Ustekinumab in Patients With New-onset T1D
Acronym
UST1D
Official Title
Phase I/II Study of Ustekinumab in Patients With New-onset Type 1 Diabetes
Study Type
Interventional

2. Study Status

Record Verification Date
May 2016
Overall Recruitment Status
Unknown status
Study Start Date
March 2015 (undefined)
Primary Completion Date
February 2017 (Anticipated)
Study Completion Date
June 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of British Columbia
Collaborators
Juvenile Diabetes Research Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
The investigators will perform an open-label pilot safety study (Phase I/II clinical trial) with a total of 20 adult (18-35 years old) subjects with recent-onset T1D. There will be four study cohorts, which will be recruited sequentially all to the treatment arm: five subjects will be given ustekinumab, 45mg subcutaneously (SC) at 0, 4, 16, 28 and 40weeks, five subjects will be given ustekinumab, 90mg SC at weeks 0, 4, 16, 28 and 40, five subjects will be given 45mg SC at weeks 0, 4 and 16 and five subjects will be given 90mg subcutaneously (SC) at weeks 0, 4 and 16. Recruitment and screening for the pilot study will be completed within the first 6 months. The follow up period is 1 year from the first dose.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes
Keywords
T1D, ustekinumab, new-onset, diabetes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ustekinumab
Other Intervention Name(s)
Stelara
Primary Outcome Measure Information:
Title
Primary Safety Endpoints (composite outcome measure)
Description
Rate, frequency and severity of all adverse events including; hypoglycemic episodes; injection reactions; hypersensitivity reactions; evidence of infection and posterior leukoencephalopathy syndrome. Vital signs, standard hematology and chemistry tests, physical examinations.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Immunological Endpoints (composite outcome measure)
Description
Immune phenotyping via flow cytometry of all Interleukin (IL)-12, IL-23, IL-17, Interferon(IFN)-γ secreting immune subsets. Basic immune phenotyping of white blood cell subsets. Human leukocyte antigen(HLA)- A, B, C, DR, DP, DQ typing. Fluorospot (ELISpot) analysis for IL-17 and IFN-γ secretion in response to whole insulin and antigens for Cluster of differentiation (CD)8+ and CD4+ T cells . Luminex assessment of serum cytokines IL-17, IFN-γ, IL-12 and IL-23. Regulatory T cell : Effector T cell ratio CD154 based assays to determine diabetogenic antigen specific responses of T helper cells. Epigenetic assessment of Treg phenotype and function.
Time Frame
12 months
Title
Exploratory (composite outcome measure)
Description
Mixed-meal tolerance test (MMTT) - stimulated 2-hour C-peptide area under the curve (AUC) at weeks 4, 28 and 52. Insulin use in units per kg body weight per day at weeks 4, 16, 28, 40 and 52. HbA1C levels at weeks 4, 16, 28, 40 and 52.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 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. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jan Dutz, MD FRCPC
Organizational Affiliation
Professor Department of Dermatology and Skin Science University of British Columbia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ashish Marwaha, BMBCh PhD
Organizational Affiliation
University of British Columbia
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Annika Sun, MSc
Organizational Affiliation
University of British Columbia
Official's Role
Study Director
Facility Information:
Facility Name
BC Diabetes
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1M9
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
35072168
Citation
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.
Results Reference
derived
Links:
URL
http://www.bcdiabetes.ca/
Description
Website for study centre.

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

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