Deucravacitinib for Lupus

(POETYK SLE-1 Trial)

Recruiting at 434 trial locations

Overseen By BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Must be taking: Immunosuppressants, Antimalarials

Must not be taking: Cytotoxic agents

Disqualifiers: Drug-induced SLE, Other autoimmune diseases, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

490 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates how well the new drug deucravacitinib (also known as Sotyktu or BMS-986165) works compared to a placebo in people with moderate to severe Systemic Lupus Erythematosus (SLE). SLE causes the immune system to attack its own tissues, leading to joint pain, rashes, and more. Participants must have been diagnosed with SLE for at least six months and have ongoing symptoms like joint pain or skin rashes. The study aims to determine if deucravacitinib can safely manage these symptoms. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you stay on at least one SLE background therapy (like an immunosuppressant or antimalarial) at a stable dose for the duration of the study. If you're taking oral corticosteroids, the dose must also be stable. So, you won't have to stop your current medications if they meet these criteria.

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

Research has shown that deucravacitinib is consistently safe for people with Systemic Lupus Erythematosus (SLE). In earlier studies, most patients tolerated deucravacitinib well. The reported side effects aligned with known effects of the treatment, with no new issues. This suggests that continuing to study this treatment in people with lupus is safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for lupus, which often include immunosuppressants and corticosteroids, Deucravacitinib acts on a different biological pathway. It uniquely targets the TYK2 enzyme, a part of the JAK family involved in immune response, which offers a new mechanism of action. Researchers are excited about Deucravacitinib because it has the potential to provide a more targeted approach to managing lupus, potentially resulting in fewer side effects compared to broad-spectrum immunosuppressants. This specificity could mean better disease control and improved quality of life for patients.

What evidence suggests that deucravacitinib might be an effective treatment for lupus?

Research has shown that deucravacitinib, which participants in this trial may receive, may help treat systemic lupus erythematosus (SLE). In studies, patients taking deucravacitinib experienced noticeable improvements in their symptoms compared to those taking a placebo. By Week 16, more patients on deucravacitinib achieved at least a 20% improvement in their disease symptoms. Additionally, by Week 48, these patients reported less pain, reduced fatigue, and a better quality of life than those on a placebo. These results suggest that deucravacitinib could be an effective treatment option for people with SLE. ^{1 2 3 4 6}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for adults with active moderate to severe Systemic Lupus Erythematosus (SLE) who have a certain level of disease activity. Participants must have been diagnosed at least 24 weeks prior and be on stable SLE medication. Those with lupus overlap syndromes, recent serious infections, multiple immunosuppressants, or unstable neuropsychiatric manifestations cannot join.

Inclusion Criteria

I was diagnosed with Lupus more than 24 weeks ago.

I have been on a stable dose of my lupus medication for at least 8 weeks.

Meet the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for SLE

Exclusion Criteria

My lupus was caused by medication, not naturally occurring.

I have a history of immune system problems.

I have severe lupus affecting my kidneys that might need strong medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either deucravacitinib or placebo to evaluate effectiveness and safety in active SLE

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Deucravacitinib
• Placebo

Trial Overview The study tests the effectiveness and safety of Deucravacitinib versus a placebo in treating SLE. It aims to see if Deucravacitinib can help manage symptoms better than an inactive substance without any therapeutic effect.

How Is the Trial Designed?

Group I: Arm 1: Deucravacitinib Experimental Treatment 1 Intervention

Group II: Arm 2: Placebo Placebo Group 1 Intervention

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

Approved in United States as Sotyktu for:

• Moderate to severe plaque psoriasis

Approved in European Union as Sotyktu for:

• Moderate to severe plaque psoriasis

Approved in Canada as Sotyktu for:

• Moderate to severe plaque psoriasis

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

In two phase III clinical trials involving 1684 patients with systemic lupus erythematosus (SLE), the EQ-5D-3L index score demonstrated strong discriminant validity, effectively distinguishing between the effects of belimumab and placebo, with a significant odds ratio of 1.47.

Higher EQ-5D index scores were also able to differentiate between responders and non-responders to treatment, suggesting that even scores below full health can provide meaningful insights into health-related quality of life for SLE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sensitivity analysis of EQ-5D-3L index scores in terms of discriminative and known-groups validity in SLE: introducing Adequate Health State. Hua, N., Gomez, A., Lindblom, J., et al.[2023]

Dapirolizumab pegol (DZP) showed improvements in clinical and immunological outcomes for patients with moderately to severely active systemic lupus erythematosus (SLE) after 24 weeks, although the primary dose-response relationship was not statistically significant.

DZP was well tolerated with low incidences of serious adverse events, suggesting it is a safe option for SLE treatment, warranting further investigation into its clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2, randomized, placebo-controlled trial of dapirolizumab pegol in patients with moderate-to-severe active systemic lupus erythematosus. Furie, RA., Bruce, IN., Dörner, T., et al.[2022]

In a study of 188 patients with active systemic lupus erythematosus (SLE) treated with belimumab over an average of 17.5 months, 77% and 68.7% achieved significant improvement in disease activity at 12 and 24 months, respectively, indicating its efficacy.

Belimumab demonstrated a low rate of severe adverse events and maintained a high drug survival rate of 86.9% at 6 months, suggesting it is a safe treatment option for SLE in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical predictors of response and discontinuation of belimumab in patients with systemic lupus erythematosus in real life setting. Results of a large, multicentric, nationwide study. Iaccarino, L., Andreoli, L., Bocci, EB., et al.[2022]

In a phase II trial involving 363 adults with active systemic lupus erythematosus (SLE), deucravacitinib significantly improved response rates compared to placebo, with 58% of patients on the 3 mg twice daily dose achieving the SLE Responder Index 4 (SRI-4) response at week 32.

The safety profile of deucravacitinib was generally acceptable, with similar rates of serious adverse events compared to placebo, although there were higher incidences of infections and skin-related issues like rash and acne in the treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deucravacitinib, a Tyrosine Kinase 2 Inhibitor, in Systemic Lupus Erythematosus: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial. Morand, E., Pike, M., Merrill, JT., et al.[2023]

In a phase 3 study involving 516 patients with active systemic lupus erythematosus (SLE), ustekinumab did not show superior efficacy compared to placebo, with similar response rates at week 52 (44% for ustekinumab vs. 56% for placebo).

The study was discontinued due to lack of efficacy, but there were no safety concerns, and the adverse events reported were consistent with ustekinumab's known safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3, multicentre, randomised, placebo-controlled study evaluating the efficacy and safety of ustekinumab in patients with systemic lupus erythematosus. van Vollenhoven, RF., Kalunian, KC., Dörner, T., et al.[2022]

Deucravacitinib, a selective tyrosine kinase 2 inhibitor, was found to be safe and well tolerated in a study involving 40 healthy Chinese subjects, with no serious adverse events reported.

The drug showed rapid absorption and a dose-dependent increase in systemic exposure, indicating that it effectively reaches the bloodstream and maintains consistent pharmacokinetics across different doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Safety of the Tyrosine Kinase 2 Inhibitor Deucravacitinib in Healthy Chinese Subjects. Jing, S., Lin, Y., Dockens, R., et al.[2023]

In a study involving 100 healthy volunteers, deucravacitinib was found to be rapidly absorbed with a half-life of 8-15 hours, showing a favorable pharmacokinetic profile and no serious adverse events, indicating good safety.

Deucravacitinib effectively inhibited key immune pathways (IL-12/IL-23 and type I IFN) in a dose-dependent manner, suggesting its potential as a therapeutic option for various immune-mediated diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human study of deucravacitinib: A selective, potent, allosteric small-molecule inhibitor of tyrosine kinase 2. Catlett, IM., Aras, U., Hansen, L., et al.[2023]

In a phase 3 trial involving 66 Japanese patients with moderate to severe plaque psoriasis, deucravacitinib showed significantly higher efficacy compared to placebo and apremilast, with 78.1% of patients achieving a ≥75% reduction in PASI score at Week 16.

The safety profile of deucravacitinib was comparable to that of placebo and apremilast, with similar incidence rates of adverse events, and the most common side effect being nasopharyngitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the selective TYK2 inhibitor, deucravacitinib, in Japanese patients with moderate to severe plaque psoriasis: Subgroup analysis of a randomized, double-blind, placebo-controlled, global phase 3 trial. Imafuku, S., Tada, Y., Hippeli, L., et al.[2023]

Deucravacitinib is a first-in-class oral TYK2 inhibitor that works by stabilizing an inhibitory interaction within the TYK2 enzyme, which is important for treating various immune-mediated diseases.

It received its first approval in the USA on September 9, 2022, for adults with moderate-to-severe plaque psoriasis, and has since been approved in Japan for multiple forms of psoriasis, indicating its efficacy and safety in managing these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deucravacitinib: First Approval. Hoy, SM.[2022]

In a study involving 364 patients with systemic lupus erythematosus (SLE), long-term treatment with belimumab combined with standard therapy demonstrated a stable or declining incidence of adverse events over 4 years, indicating a favorable safety profile.

The most common side effects were mild, such as arthralgia and upper respiratory infections, and serious infusion reactions were rare, suggesting that belimumab can be safely administered for extended periods in SLE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety profile of belimumab plus standard therapy in patients with systemic lupus erythematosus. Merrill, JT., Ginzler, EM., Wallace, DJ., et al.[2013]

In a study of 49 patients with active systemic lupus erythematosus (SLE), sirolimus treatment significantly reduced disease activity (SLEDAI-2K score decreased from 6.2 to 4.0) and allowed for a successful tapering of prednisone dosage.

Sirolimus showed promising efficacy in improving serological markers and achieving remission in various SLE manifestations, with 100% remission in arthritis and 88.8% in skin rash, although further research is needed to clarify its role in lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of sirolimus in systemic lupus erythematosus: a real-world study and meta-analysis. Peng, L., Wu, C., Hong, R., et al.[2022]

Citations

1. news.bms.com news.bms.com/news/details/2025/Bristol-Myers-Squibb-Presents-Two-Late-Breaking-Presentations-Demonstrating-Sotyktu-deucravacitinib-Efficacy-in-Psoriatic-Arthritis-and-Systemic-Lupus-Erythematosus/default.aspx

Corporate news details New data showed ACR20 responses (at least a 20 percent improvement in signs and symptoms of disease) achieved at Week 16 (Sotyktu, 54.2%; ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40920289/

Design of Two Randomized, Placebo-Controlled, Phase 3 ... Conclusions: The POETYK SLE-1 and SLE-2 trials in progress are important to the continued evaluation of deucravacitinib as a potential well- ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05620407

NCT05620407 | A Study to Evaluate Effectiveness and ... The purpose of this study is to evaluate the effectiveness and safety of deucravacitinib compared with placebo in an active moderate to severe Systemic Lupus ...

4. lupus.bmj.com lupus.bmj.com/content/12/1/e001517

Deucravacitinib, an oral, selective, allosteric, tyrosine ... Deucravacitinib treatment resulted in greater improvements in pain, fatigue and HRQoL at week 48 in patients with SLE than did treatment with placebo.

5. acrabstracts.org acrabstracts.org/abstract/four-year-safety-and-efficacy-of-deucravacitinib-in-systemic-lupus-erythematosus-results-from-a-phase-2-program/

Four-Year Safety and Efficacy of Deucravacitinib in ... Patients who switched from PBO during the LTE study achieved outcomes comparable to those treated from baseline. These data represent the ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0003496725021934

POS0781 EFFICACY AND SAFETY OF ORAL ... Deucravacitinib was well tolerated, and AEs were consistent with the known safety profile. These data support further evaluation of deucravacitinib for the ...