Pilot Trial of Ustekinumab for Primary Sjögren's Syndrome

Overseen By Dustina Holt, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Rochester

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 4

Duration: 24 weeks

12 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing the safety of ustekinumab, a medication that reduces inflammation, in patients with Primary Sjögren's Syndrome (PSS). PSS is a condition where the immune system causes chronic inflammation. Ustekinumab helps by blocking certain proteins in the immune system to reduce this inflammation. It has been approved for the treatment of other conditions like psoriasis, psoriatic arthritis, and Crohn's disease.

Will I have to stop taking my current medications?

The trial does not specify that you must stop taking your current medications, but it does require that certain medications be stable for a period before starting the trial. For example, if you're taking prednisone, the dose must be stable for at least 4 weeks, and for hydroxychloroquine, it must be stable for 12 weeks before the trial begins.

What data supports the effectiveness of the drug Ustekinumab (Stelara)?

Ustekinumab (Stelara) has been shown to be effective in treating conditions like Crohn's Disease and psoriatic arthritis. In Crohn's Disease, about 50% of patients experienced clinical remission after one year of treatment. For psoriatic arthritis, it was significantly more effective than a placebo in improving symptoms and maintaining long-term response. ^{1 2 3 4 5}

What safety data exists for Ustekinumab (Stelara)?

Ustekinumab (Stelara) is generally well tolerated, with serious infections or major cardiovascular events occurring rarely during long-term treatment. However, there have been reports of adverse effects like eosinophilic pneumonia, which is a lung condition that can occur during treatment. ^{3 4 5 6 7}

How is the drug Ustekinumab different from other treatments for psoriasis?

Ustekinumab is unique because it targets specific proteins called interleukins-12 and -23, which are involved in the inflammatory process of psoriasis. This mechanism is different from other treatments like TNF inhibitors, making it a valuable option for patients who do not respond well to other therapies. ^{2 3 4 5 6}

Research Team

Ummara Shah, MD

Principal Investigator

Assistant Professor of Medicine

Eligibility Criteria

Inclusion Criteria

Has provided written informed consent

Body weight ≥ 40 kg

Meets the 2016 ACR EULAR criteria (score >4)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an infusion loading dose of 6 mg/kg of ustekinumab at baseline, followed by 90 mg subcutaneous injections at week 4, week 12, and week 20

24 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ustekinumab

Participant Groups

Group I: Ustekinumab Experimental Treatment 1 Intervention

All subjects will receive an intravenous loading dose of 6 mg/kg at their baseline visit. 650mg acetaminophen and 60mg allegra will be given as premedication to the infusion. All patients will receive 90mg ustekinumab by a subcutaneous injection at all subsequent dosing visits. Subcutaneous injections do not require any premedication. Drug will be administered by qualified personnel.

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 Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

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

Findings from Research

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]

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 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]

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]

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 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]

The study found that AVT04, a biosimilar to ustekinumab (Stelara®), demonstrated therapeutic equivalence in treating moderate-to-severe chronic plaque psoriasis, with similar efficacy as shown by a percent improvement in the psoriasis area and severity index (PASI) of 87.3% for AVT04 compared to 86.8% for the reference product.

Safety and tolerability profiles were comparable between AVT04 and the reference product throughout the 52-week study, with no clinically meaningful impact from the incidence of antibodies to ustekinumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, double-blind, multicenter study to evaluate efficacy, safety, tolerability, and immunogenicity between AVT04 and the reference product ustekinumab in patients with moderate-to-severe chronic plaque psoriasis. Feldman, SR., Reznichenko, N., Berti, F., et al.[2023]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

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

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

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

4. 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]

5. France pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

Randomized, double-blind, multicenter study to evaluate efficacy, safety, tolerability, and immunogenicity between AVT04 and the reference product ustekinumab in patients with moderate-to-severe chronic plaque psoriasis. [2023]