Ustekinumab for Sjögren's Syndrome

Overseen By Dustina Holt, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Rochester

Must not be taking: Anticholinergics, Rituximab, Cyclophosphamide, others

Disqualifiers: Infections, Immunodeficiency, RA, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effects of a medication called ustekinumab (also known as Stelara) for individuals with Primary Sjögren's Syndrome, an autoimmune condition that causes dry mouth and eyes. Researchers aim to determine if the treatment can reduce inflammation in the body. Participants will initially receive the medication through an IV, followed by injections. Those with a confirmed diagnosis of Primary Sjögren's Syndrome and symptoms like dry eyes or mouth may be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

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.

Is there any evidence suggesting that ustekinumab is likely to be safe for humans?

Research has shown that ustekinumab has been studied in many patients with various health conditions. In studies involving individuals with ulcerative colitis, researchers tested the safety of ustekinumab in over 960 adults. These studies found that the treatment was generally well-tolerated, although some participants reported serious infections while taking the medication.

Additional safety data comes from studies with over 3,000 adults with psoriasis, many of whom used the treatment for at least six months. These studies also found that ustekinumab was generally safe, but some patients experienced serious infections.

Since ustekinumab is already approved for other conditions, extensive information exists about its safety. However, in this trial for primary Sjögren's syndrome, researchers are specifically evaluating its safety for this group of patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Sjogren's Syndrome?

Most treatments for primary Sjögren's syndrome focus on managing symptoms like dry eyes and mouth, using methods such as artificial tears and saliva stimulants. However, Ustekinumab is unique because it directly targets the immune system, which is at the root of the condition. It works by inhibiting specific proteins, IL-12 and IL-23, that play a key role in the inflammatory process. Researchers are excited about Ustekinumab because it offers a novel approach that could potentially modify the disease itself, rather than just alleviating symptoms. This could lead to more effective long-term management of primary Sjögren's syndrome.

What evidence suggests that ustekinumab might be an effective treatment for Primary Sjogren's Syndrome?

Research has shown that ustekinumab effectively treats various inflammatory conditions. For example, in individuals with ulcerative colitis, more than half experienced significant symptom improvement, known as clinical remission. Ustekinumab reduces inflammation by targeting specific proteins responsible for it. This trial will investigate ustekinumab as a potential treatment for Primary Sjögren's Syndrome (PSS), which also involves inflammation. Although direct data for PSS is not yet available, success in treating similar conditions suggests it might alleviate PSS symptoms as well. ^{4 6 7 8 9}

Who Is on the Research Team?

Ummara Shah, MD

Principal Investigator

Assistant Professor of Medicine

Are You a Good Fit for This Trial?

Inclusion Criteria

Has provided written informed consent

Body weight ≥ 40 kg

Meets the 2016 ACR EULAR criteria (score >4)

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Ustekinumab

How Is the Trial Designed?

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, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen, LP

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9629456/

Long-Term Real-World Effectiveness and Safety of ... A recent study reported similar results to our study, with two-thirds of patients regaining response following intensification of ustekinumab to 90 mg every 4 ...

2. gi.org gi.org/journals-publications/ebgi/dalal_jul2024/

Long-Term Efficacy and Safety of Ustekinumab for ... Of 171 patients who completed endoscopic evaluations at week 200, approximately 70% in both groups had clinical remission and approximately 80% ...

3. stelarahcp.com stelarahcp.com/ulcerative-colitis/efficacy

Ulcerative Colitis (UC): Efficacy - Stelara 45% of the overall population receiving STELARA ® were in clinical remission after 1 year of treatment · Circle 1 Year icon CLINICAL REMISSION · View lasting ...

4. jnj.com jnj.com/media-center/press-releases/new-stelara-ustekinumab-long-term-data-support-its-established-safety-profile-in-inflammatory-bowel-disease-and-durable-efficacy-in-ulcerative-colitis

New STELARA® (ustekinumab) Long-Term Data Support ... More than half of STELARA-treated patients with ulcerative colitis achieved clinical remission, clinical response, and/or demonstrated endoscopic improvement ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10636694/

Clinical Outcomes of Ustekinumab in Inflammatory Bowel ... Some data shows a reduction in anti-inflammatory markers in a patient after the use of ustekinumab. Without taking into consideration ...

6. stelarahcp.com stelarahcp.com/ulcerative-colitis/safety

Ulcerative Colitis (UC): Safety Profile - Stelara The safety of STELARA® was evaluated in 2 randomized, double-blind, placebo-controlled clinical studies in 960 adult patients with moderately to severely ...

7. stelarainfo.com stelarainfo.com/safety

Important Safety Information | STELARA® (ustekinumab) STELARA® may lower your ability to fight infections and may increase your risk of infections. Some people have serious infections during treatment with STELARA® ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/761044s010lbl.pdf

STELARA® (ustekinumab) - accessdata.fda.gov The safety data reflect exposure to STELARA® in 3117 adult psoriasis subjects, including 2414 exposed for at least 6 months, 1855 exposed for at least one ...

9. imgcdn.mckesson.com imgcdn.mckesson.com/CumulusWeb/Click_and_learn/SDS_9JOM_STELARA_SYR_90MG_1ML_1MG_ML.pdf

STELARA This SDS is written to provide environmental, health and safety information for personnel that will be handling this fin- ished pharmaceutical ...