Deucravacitinib for Lupus

(POETYK SLE-2 Trial)

Recruiting at 403 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: Immunosuppressant, Antimalarial

Must not be taking: Multiple immunosuppressants

Disqualifiers: Drug-induced SLE, Other autoimmune diseases, Active lupus nephritis, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

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 examines the effectiveness and safety of deucravacitinib, a potential new drug for treating moderate to severe Systemic Lupus Erythematosus (SLE), a condition where the immune system attacks the body's tissues. Participants will receive either the new treatment or a placebo (a non-active substance) to assess its impact on their symptoms. Suitable candidates have been diagnosed with SLE for at least six months, have specific positive blood tests, and are on stable lupus medication. As a Phase 3 trial, this study is the final step before potential FDA approval, offering participants the opportunity to contribute to the development of a promising new treatment.

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. The protocol does not specify stopping other medications, but you should discuss your current medications with the trial team.

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

Research has shown that deucravacitinib was well-tolerated in past studies. People with systemic lupus erythematosus (SLE) have used this treatment for up to four years, and its safety profile has remained consistent. The side effects are known and have not changed significantly. Previous studies also found that the side effects align with expectations for this type of medication.

In simpler terms, deucravacitinib has been tested before, and the side effects are predictable and manageable. This suggests that the treatment is generally safe, though, like any medication, some side effects are possible. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lupus?

Deucravacitinib is unique because it works by targeting the TYK2 enzyme, a part of the immune system that plays a key role in inflammation. Most treatments for lupus, like corticosteroids and immunosuppressants, broadly suppress the immune system, which can lead to significant side effects. Deucravacitinib's targeted approach may offer a more precise treatment option, potentially reducing side effects and improving patient outcomes. Researchers are excited because this novel mechanism of action could provide a more effective and safer alternative for managing lupus.

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 one study, patients who took deucravacitinib reported less pain and fatigue and noticed an overall improvement in their quality of life compared to those who took a placebo (a pill with no active medicine). Specifically, the data revealed that 54.2% of participants experienced at least a 20% improvement in their symptoms by week 16. This suggests that deucravacitinib could effectively reduce the signs and symptoms of lupus. ^{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 meet specific criteria, including a certain score on the SLEDAI-2K disease activity index and evidence of joint or skin involvement. Participants may be taking stable doses of steroids, antimalarials, or immunosuppressants but cannot have severe lupus nephritis, other autoimmune diseases except some exceptions, recent major infections, or more than one immunosuppressant.

Inclusion Criteria

My lupus is active, with a score showing moderate to severe symptoms including joint or skin issues.

I have lupus with specific symptoms not counting towards my screening score.

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

Exclusion Criteria

History of congenital or acquired immunodeficiency

My lupus was caused by medication, not naturally occurring.

I am taking more than one immunosuppressant.

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 Systemic Lupus Erythematosus

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

Trial Overview The study tests Deucravacitinib's effectiveness and safety against a placebo in treating SLE. Participants will randomly receive either the investigational drug or an inactive substance to compare outcomes between the two groups over time.

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

The approval of belimumab by the US FDA marks a significant advancement in the treatment options for systemic lupus erythematosus (SLE), highlighting the potential for biologic therapies in managing this autoimmune disease.

Recent clinical trials for SLE have successfully utilized well-defined outcome measures and evidence-based strategies, which have contributed to their success and may lead to improved trial designs and therapeutic options in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring outcomes in systemic lupus erythematosus clinical trials. Strand, V., Chu, AD.[2022]

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 24-week study involving 274 patients with systemic lupus erythematosus (SLE), the JAK1 and JAK2 inhibitor baricitinib significantly reduced the expression of genes associated with the JAK/STAT pathway, which is crucial in SLE pathogenesis.

Baricitinib treatment also led to a significant decrease in serum levels of key cytokines IL-12p40 and IL-6, which are elevated in SLE, indicating its potential efficacy in managing the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baricitinib-associated changes in global gene expression during a 24-week phase II clinical systemic lupus erythematosus trial implicates a mechanism of action through multiple immune-related pathways. Dörner, T., Tanaka, Y., Petri, MA., et al.[2021]

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]

Deucravacitinib (SOTYKTUTM) is an effective oral treatment for moderate to severe plaque psoriasis, with up to 58.4% of patients showing symptom improvement by week 16 in phase 3 trials involving 840 participants.

The drug has a favorable safety profile, with common side effects like upper respiratory infections and herpes simplex infections occurring at manageable rates, and its selectivity may enhance long-term safety compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SOTYKTUTM (Deucravacitinib 6-mg Tablets)- A New Agent for the Management of Adult Plaque Psoriasis. Gupta, AK., Wang, T., Vincent, K., 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]

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 II trial involving 239 adults with systemic lupus erythematosus (SLE), baricitinib at a dose of 4 mg significantly reduced several inflammatory cytokines compared to placebo after 12 weeks, indicating its potential efficacy in managing SLE-related inflammation.

The study suggests that baricitinib may work through a multitargeted mechanism by downregulating key cytokines associated with SLE, which could lead to improved disease activity, although further research is needed to fully understand its clinical relevance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanism of action of baricitinib and identification of biomarkers and key immune pathways in patients with active systemic lupus erythematosus. Dörner, T., Tanaka, Y., Dow, ER., et al.[2022]

A selective small molecule inhibitor of NF-κB-inducing kinase (NIK) effectively treats experimental lupus in NZB/W F1 mice, showing similar benefits to BAFF blockade, which is known to be clinically effective in systemic lupus erythematosus (SLE).

NIK inhibition leads to improved survival rates, reduced kidney damage, and lower protein levels in urine, indicating its potential as a promising therapeutic strategy for managing SLE by modulating T cell activity and inflammatory responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NF-κB inducing kinase is a therapeutic target for systemic lupus erythematosus. Brightbill, HD., Suto, E., Blaquiere, N., et al.[2023]

In patients with systemic lupus erythematosus (SLE), decreased expression of the TGF-β type I receptor (TGFβRI) in naïve CD4+ T cells correlates with higher disease activity, suggesting its importance in T cell regulation.

The JAK inhibitor tofacitinib was found to enhance TGFβRI expression and inhibit T cell activation, leading to improved clinical outcomes in SLE mouse models, including reduced disease markers and kidney damage, indicating its potential as an effective treatment for SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib Ameliorates Lupus Through Suppression of T Cell Activation Mediated by TGF-Beta Type I Receptor. Yan, Q., Chen, W., Song, H., et al.[2021]

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 study using lupus-prone ABIN1[D485N] knock-in mice, pacritinib effectively prevented various symptoms of lupus, such as splenomegaly and elevated autoantibody levels, over a 10-week treatment period.

The results suggest that pacritinib could be a promising treatment option for managing multiorgan inflammation in lupus patients, as it reduced immune cell expansion and inflammation in multiple organs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pacritinib abrogates the lupus phenotype in ABIN1[D485N] mice. Petrova, T., Figueras-Vadillo, C., Nanda, SK., et al.[2023]

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 ...