Deucravacitinib for Lupus

(POETYK SLE-2 Trial)

Recruiting at 337 trial locations

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

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

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)

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing a new medication called deucravacitinib to see if it is safe and effective for people with moderate to severe lupus, a disease where the immune system attacks the body. The medication aims to reduce inflammation by targeting specific enzymes in the immune system.

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.

What data supports the effectiveness of the drug Deucravacitinib for treating lupus?

A study showed that Deucravacitinib, which works by blocking a specific protein involved in the immune response, was tested in patients with lupus and showed promise in a phase II trial. This suggests it might help manage lupus symptoms by targeting the immune system. ^{1 2 3 4 5}

Is Deucravacitinib safe for humans?

Deucravacitinib has been studied for safety in a phase II trial for systemic lupus erythematosus (SLE), which is an autoimmune disease. While the study focused on SLE, it provides some information about the safety of the drug in humans. ^{3 4 6 7 8}

How is the drug deucravacitinib unique for treating lupus?

Deucravacitinib is unique because it is an oral medication that selectively inhibits tyrosine kinase 2 (TYK2), a protein involved in immune system signaling, which may help reduce inflammation in lupus. This mechanism is different from other treatments that may not target TYK2 specifically. ^{4 9 10 11 12}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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 do not have autoimmune diseases like MS or psoriasis, but I may have type 1 diabetes, thyroid issues, Celiac, or Sjögren's.

Trial Timeline

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

Treatment Details

Interventions

• Deucravacitinib (Janus Kinase (JAK) Inhibitor)

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.

Participant Groups

Group I: Arm 1: Deucravacitinib Experimental Treatment 1 Intervention

Group II: Arm 2: Placebo Placebo Group 1 Intervention

Deucravacitinib is already approved in Canada for the following indications:

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

Findings from Research

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]

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 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]

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 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]

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 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 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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Measuring outcomes in systemic lupus erythematosus clinical trials. [2022]

2. England 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. [2022]

3. England 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. [2022]

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

Deucravacitinib, a Tyrosine Kinase 2 Inhibitor, in Systemic Lupus Erythematosus: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial. [2023]

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

Pacritinib abrogates the lupus phenotype in ABIN1[D485N] mice. [2023]

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

NF-κB inducing kinase is a therapeutic target for systemic lupus erythematosus. [2023]

7. England 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. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Tofacitinib Ameliorates Lupus Through Suppression of T Cell Activation Mediated by TGF-Beta Type I Receptor. [2021]

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

First-in-human study of deucravacitinib: A selective, potent, allosteric small-molecule inhibitor of tyrosine kinase 2. [2023]

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

SOTYKTUTM (Deucravacitinib 6-mg Tablets)- A New Agent for the Management of Adult Plaque Psoriasis. [2023]

11. England 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. [2023]

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

Deucravacitinib: First Approval. [2022]