Ustekinumab for Type 1 Diabetes

(UST1D2 Trial)

Recruiting at 1 trial location

Overseen By Marla Inducil, Pharm, MD, CCRP

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: University of British Columbia

Must not be taking: Investigational drugs, Glucose tolerance drugs

Disqualifiers: Malignancy, Active tuberculosis, Significant infection, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: 48 weeks

66 Participants Needed

Trial Summary

Do I need to stop my current medications for this trial?

Yes, you may need to stop certain medications. The trial excludes participants who have used medications known to influence glucose tolerance within 30 days prior to the first study drug dose. It also excludes those with prior or current treatment affecting T1D or immunological status.

Will I have to stop taking my current medications?

The trial requires that you stop using medications known to influence glucose tolerance at least 30 days before the first dose. If you're on such medications, you may need to stop them before participating.

What data supports the idea that Ustekinumab for Type 1 Diabetes is an effective treatment?

The available research does not provide any data on Ustekinumab for Type 1 Diabetes. Instead, the studies focus on other drugs like adalimumab, golimumab, tocilizumab, anakinra, and infliximab for conditions such as juvenile idiopathic arthritis and rheumatoid arthritis. Therefore, there is no information here to support the effectiveness of Ustekinumab for Type 1 Diabetes. ^{1 2 3 4 5}

What safety data is available for Ustekinumab (Stelara)?

Ustekinumab (Stelara) has been studied for various conditions, including psoriasis, Crohn's disease, and inflammatory bowel diseases. Safety data indicates it is generally safe, but some adverse effects have been reported, such as eosinophilic pneumonia in psoriasis treatment. It is considered a safe and effective option for treating cutaneous manifestations of inflammatory bowel diseases and paradoxical skin reactions. However, more studies are needed to determine optimal dosing for conditions beyond psoriasis. In Crohn's disease, it has a favorable safety profile, though data in elderly patients is limited. ^{6 7 8 9 10}

Is Ustekinumab generally safe for humans?

Ustekinumab (Stelara) is generally considered safe for treating conditions like psoriasis, Crohn's disease, and ulcerative colitis, though some side effects like eosinophilic pneumonia (a lung condition) have been reported. It is effective for skin and gastrointestinal issues related to inflammatory bowel diseases, and its safety profile is favorable, even in elderly patients with Crohn's disease. ^{6 7 8 9 10}

Is the drug Ustekinumab a promising treatment for Type 1 Diabetes?

Ustekinumab, known as Stelara, is a drug that has shown promise in treating several conditions like psoriasis and psoriatic arthritis. It works by targeting specific proteins in the immune system, which can help reduce inflammation. While it is not yet proven for Type 1 Diabetes, its success in other immune-related conditions suggests it could be a promising option. ^{7 11 12 13 14}

How is the drug ustekinumab unique for treating type 1 diabetes?

Ustekinumab is unique because it targets specific proteins (interleukins-12 and -23) involved in immune system regulation, which is different from traditional treatments for type 1 diabetes that focus on insulin management. This approach is novel as it aims to address the underlying immune response rather than just managing blood sugar levels. ^{7 11 12 13 14}

What is the purpose of this trial?

This trial tests Ustekinumab, a drug used for psoriasis, in adults aged 18-35 with recent-onset type 1 diabetes. The drug aims to protect and regenerate insulin-producing cells by blocking harmful immune cells. This could reduce the need for insulin injections.

Research Team

Betina F Rasmussen, MSc

Principal Investigator

University of British Columbia

Jan Dutz, MD FRCPC

Principal Investigator

University of British Columbia

Eligibility Criteria

This trial is for 18-35 year olds recently diagnosed with Type 1 Diabetes, who still produce some insulin and have not used medications affecting glucose tolerance in the last month. Participants must be free from significant diseases, HIV, Hepatitis B/C, tuberculosis, and cannot be pregnant or planning pregnancy soon.

Inclusion Criteria

Ability to provide documented informed consent

The patient must have received the study drug within the last 100 days of the study.

Your body still makes insulin, as shown by a C-peptide level over 0.2nmol/L in a special test.

Exclusion Criteria

Use of any other investigational drug within the 3 months prior to the first dose and/or intent to use any investigational drug for the duration of the study

I have used medication that affects blood sugar levels in the last 30 days.

I do not have, nor have I ever had, an active tuberculosis infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a loading dose of Ustekinumab at week 0, followed by subcutaneous doses at weeks 8, 16, 24, 32, 40, and 48

48 weeks

7 dosing visits (in-person), 3 non-dosing visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including non-dosing visits at weeks 52 and 78

30 weeks

2 visits (in-person)

Treatment Details

Interventions

• Ustekinumab

Trial Overview The study tests Ustekinumab's ability to preserve insulin-producing cells in newly diagnosed Type 1 Diabetics against a placebo. The goal is to see if patients can become insulin-free or need less insulin by protecting these cells.

Participant Groups

Group I: Ustekinumab Experimental Treatment 1 Intervention

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

Group II: Saline Solution - Placebo Placebo Group 1 Intervention

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

Ustekinumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Stelara for:

• Moderate to severe plaque psoriasis
• Psoriatic arthritis
• Crohn's disease
• Ulcerative colitis

Approved in United States as Stelara for:

• Moderate to severe plaque psoriasis
• Active psoriatic arthritis
• Moderately to severely active Crohn's disease
• Moderately to severely active ulcerative colitis

Approved in Canada as Stelara for:

• Moderate to severe plaque psoriasis
• Active psoriatic arthritis
• Moderately to severely active Crohn's disease
• Moderately to severely active ulcerative colitis

Approved in Japan as Stelara for:

• Plaque psoriasis
• Psoriatic arthritis
• Crohn's disease
• Ulcerative colitis

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Janssen, LP

Industry Sponsor

Trials

169

Recruited

329,000+

Founded

1953

Headquarters

Beerse, Belgium

Known For

Mental Health Therapies

Top Products

Imodium, Remicade, Invega, Procrit

Joaquin Duato

Janssen, LP

Chief Executive Officer since 2022

MBA from ESADE Business School

Biljana Naumovic

Janssen, LP

Chief Medical Officer since 2023

MD from Belgrade University Medical School

Juvenile Diabetes Research Foundation

Collaborator

Trials

237

Recruited

142,000+

Findings from Research

In a study of 11 juvenile idiopathic arthritis (JIA) patients with uveitis, adalimumab was effective as a first-line treatment, with 63.64% achieving complete remission after two years.

No relapses of uveitis were observed during the treatment, and patients were able to taper off topical steroids, indicating both safety and efficacy of adalimumab in managing JIA with associated uveitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of Juvenile Idiopathic Arthritis Associated Uveitis in Two Disease Subtypes. Lazarević, D., Nikolić, I., Ratković-Janković, M., et al.[2022]

In a study of 39 patients with juvenile idiopathic arthritis (JIA) and refractory uveitis, adalimumab significantly reduced inflammation in both the anterior and posterior segments of the eye after 6 months of treatment, indicating its efficacy.

The treatment also led to a significant decrease in the need for corticosteroids, suggesting that adalimumab may help manage symptoms while reducing reliance on more potent immunosuppressive therapies, with no major side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Usefulness of adalimumab in the treatment of refractory uveitis associated with juvenile idiopathic arthritis. García-De-Vicuña, C., Díaz-Llopis, M., Salom, D., et al.[2022]

In a study of 7 patients with refractory juvenile idiopathic arthritis (JIA)-associated uveitis, golimumab (GLM) significantly reduced inflammation in the eye, as shown by a decrease in anterior chamber cells and improved visual acuity after 6 months of treatment.

GLM led to complete remission of uveitis in 4 out of 7 patients over an average follow-up of about 17 months, although 2 patients had to switch to another treatment due to lack of effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Golimumab in refractory uveitis associated to juvenile idiopathic arthritis: multicentre study of 7 cases and literature review. Palmou-Fontana, N., Calvo-Río, V., Martín-Varillas, JL., et al.[2018]

In a study of 76 systemic juvenile idiopathic arthritis (JIA) patients, about 51% achieved minimal disease activity and 39% reached clinically inactive disease after one year of treatment with either tocilizumab or anakinra, indicating both medications are effective in managing the condition.

Tocilizumab showed better treatment persistence, with 89% of patients continuing the therapy after one year compared to only 59% for anakinra, suggesting it may be a more favorable option for long-term management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term outcomes in patients with systemic juvenile idiopathic arthritis treated with either tocilizumab or anakinra. Kearsley-Fleet, L., Beresford, MW., Davies, R., et al.[2021]

In a study of 99 patients with early rheumatoid arthritis, adding infliximab to a combination of DMARDs and prednisolone did not significantly improve long-term remission rates or radiographic outcomes after 5 years.

Both treatment groups achieved similar rates of strict remission and minimal radiographic progression, indicating that the initial combination therapy alone is effective in managing early RA without the need for infliximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted treatment with a combination of traditional DMARDs produces excellent clinical and radiographic long-term outcomes in early rheumatoid arthritis regardless of initial infliximab. The 5-year follow-up results of a randomised clinical trial, the NEO-RACo trial. Rantalaiho, V., Kautiainen, H., Korpela, M., et al.[2022]

A 71-year-old male patient developed eosinophilic pneumonia after being treated with ustekinumab for severe psoriasis, highlighting a potential adverse effect of this medication.

After discontinuing ustekinumab and starting corticosteroid treatment, the patient's symptoms resolved, indicating that eosinophilic pneumonia can improve with treatment withdrawal and corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ustekinumab-induced eosinophilic pneumonia during the course of ustekinumab therapy for plaque psoriasis]. Amy de la Bretèque, M., Appere-De Vecchi, C., Zeboulon, C., et al.[2015]

Ustekinumab (STELARA) is effective for treating moderate-to-severe plaque psoriasis in pediatric patients aged 6 to 12, as shown by a phase III study that developed a pharmacokinetic model to predict its behavior in this age group.

The study successfully used data from adult patients to create a model that predicts clinical responses in children, indicating that ustekinumab's efficacy and safety profile can be extrapolated from adults to younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extrapolating Pharmacodynamic Effects From Adults to Pediatrics: A Case Study of Ustekinumab in Pediatric Patients With Moderate to Severe Plaque Psoriasis. Zhou, W., Hu, C., Zhu, Y., et al.[2021]

Ustekinumab (STELARA) is a safe and effective treatment for skin conditions related to inflammatory bowel diseases (IBD), including metastatic Crohn's disease and pyoderma gangrenosum, based on a review of 22 articles.

It also effectively addresses paradoxical skin reactions caused by TNF-α inhibitors, such as psoriasis, particularly when these reactions do not improve with standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab for the treatment of paradoxical skin reactions and cutaneous manifestations of inflammatory bowel diseases. Wu, J., Smogorzewski, J.[2021]

A study involving 117 Crohn's disease patients, including 39 elderly (≥65 years) and 78 nonelderly (<65 years), found that ustekinumab (UST) is safe and effective for treating elderly patients, with nearly 90% experiencing a clinical response.

Elderly patients were less likely to achieve complete clinical remission compared to nonelderly patients (28.2% vs. 52.6%), but there were no significant differences in adverse events or complications between the two age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Effectiveness and Safety of Ustekinumab in Elderly Crohn's Disease Patients. Garg, R., Aggarwal, M., Butler, R., et al.[2023]

In a study of 36 adults with Crohn's disease, 61% responded to ustekinumab treatment after one year, but no distinct gene expression signature was found to predict response, indicating that more research is needed to identify reliable biomarkers.

Among nonresponders, an increased inflammatory response was observed, with 68 genes linked to cytokine activity and chemokine receptor binding, suggesting that these pathways may play a role in treatment resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline peripheral blood mononuclear cell (PBMC) transcriptomics before ustekinumab treatment is linked with Crohn Disease clinical response at 1 year. Granot, M., Braun, T., Efroni, G., et al.[2023]

Ustekinumab is an effective treatment for adults with active psoriatic arthritis, showing significant improvement compared to placebo in phase 3 trials, with benefits maintained up to 100 weeks.

The drug has a favorable safety profile, with rare occurrences of serious infections or major cardiovascular events, making it a valuable option for patients who do not respond to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab: a review of its use in psoriatic arthritis. McKeage, K.[2021]

This case report highlights a rare instance of severe Staphylococcus aureus infection in a 64-year-old woman who had recently received ustekinumab for psoriatic arthritis, suggesting that while ustekinumab is generally safe, clinicians should remain vigilant for potential severe infections in patients on biological therapies.

The report emphasizes the importance of ongoing monitoring for rare but serious infections in patients treated with biologicals like ustekinumab, as symptoms may be nonspecific and fever may not always be present, necessitating thorough investigation when inflammatory markers are elevated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Staphylococcus aureus bacteremia with iliac artery endarteritis in a patient receiving ustekinumab. Joost, I., Steinfurt, J., Meyer, PT., et al.[2018]

Ustekinumab, an interleukin-12 and -23 antagonist, is primarily used for moderate to severe plaque psoriasis and other inflammatory conditions, but emerging literature suggests it may also be effective for various off-label uses, including other types of psoriasis and hidradenitis suppurativa.

Despite promising findings for these off-label conditions, the review highlights the need for more clinical trials to thoroughly evaluate the safety and efficacy of ustekinumab beyond its approved indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-label uses of ustekinumab. Ye, L., Wu, Z., Li, C., et al.[2023]

Ustekinumab is a highly effective treatment for moderate-to-severe psoriasis, showing better efficacy rates compared to traditional therapies, based on a review of literature up to April 2013.

The biologic has a favorable safety profile and dosing schedule, making it a suitable option for patients with difficult-to-treat psoriasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety of ustekinumab for psoriasis. Kumar, N., Narang, K., Cressey, BD., et al.[2015]

References

1. Turkey pubmed.ncbi.nlm.nih.gov

Outcome of Juvenile Idiopathic Arthritis Associated Uveitis in Two Disease Subtypes. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Usefulness of adalimumab in the treatment of refractory uveitis associated with juvenile idiopathic arthritis. [2022]

3. Italy pubmed.ncbi.nlm.nih.gov

Golimumab in refractory uveitis associated to juvenile idiopathic arthritis: multicentre study of 7 cases and literature review. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Short-term outcomes in patients with systemic juvenile idiopathic arthritis treated with either tocilizumab or anakinra. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Targeted treatment with a combination of traditional DMARDs produces excellent clinical and radiographic long-term outcomes in early rheumatoid arthritis regardless of initial infliximab. The 5-year follow-up results of a randomised clinical trial, the NEO-RACo trial. [2022]

6. France pubmed.ncbi.nlm.nih.gov

[Ustekinumab-induced eosinophilic pneumonia during the course of ustekinumab therapy for plaque psoriasis]. [2015]

7. United States pubmed.ncbi.nlm.nih.gov

Extrapolating Pharmacodynamic Effects From Adults to Pediatrics: A Case Study of Ustekinumab in Pediatric Patients With Moderate to Severe Plaque Psoriasis. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Ustekinumab for the treatment of paradoxical skin reactions and cutaneous manifestations of inflammatory bowel diseases. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Real-World Effectiveness and Safety of Ustekinumab in Elderly Crohn's Disease Patients. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Baseline peripheral blood mononuclear cell (PBMC) transcriptomics before ustekinumab treatment is linked with Crohn Disease clinical response at 1 year. [2023]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Ustekinumab: a review of its use in psoriatic arthritis. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Staphylococcus aureus bacteremia with iliac artery endarteritis in a patient receiving ustekinumab. [2018]

13. United States pubmed.ncbi.nlm.nih.gov

Off-label uses of ustekinumab. [2023]

14. England pubmed.ncbi.nlm.nih.gov

Long-term safety of ustekinumab for psoriasis. [2015]