Gusacitinib for Lupus

Overseen By Yenealem Temesgen-Oyelakin, R.N.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Must not be taking: Biologics, Live vaccines, Antibiotics, others

Disqualifiers: Pregnancy, Cancer, Heart failure, others

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test Gusacitinib, a new medication, for people with lupus, a condition where the immune system mistakenly attacks healthy tissues, causing inflammation and swelling in various parts of the body. The trial will explore the effectiveness and safety of Gusacitinib in managing lupus symptoms compared to a placebo (inactive substance) and standard lupus medications. Participants must attend several clinic visits and phone check-ins over about seven months. Ideal candidates are individuals with lupus who have mild symptoms and can maintain stable medication use during the trial. As a Phase 1 trial, this research focuses on understanding how Gusacitinib works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

It depends on the medication. If you're on immunosuppressants, you'll need to stop them 2 weeks before starting the study drug and remain off them during the trial. If you're on glucocorticoids or hydroxychloroquine, you can continue them if the doses are stable. Other medications like those for diabetes, hypertension, or statins can also be continued if stable. The protocol does not specify for other medications, so check with the study team.

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

Research has shown that Gusacitinib is being tested for safety in people with lupus. Although specific safety details for Gusacitinib in lupus are not yet available, it is under study for its potential benefits. The trial is in Phase 1, focusing on the safety of Gusacitinib and determining the appropriate dose for participants.

Phase 1 trials typically mark the first time a new treatment is tested in humans, so detailed safety information may be limited. However, researchers closely monitor these trials to assess how well participants tolerate the treatment and to identify any side effects. The goal is to ensure Gusacitinib's safety for further testing in larger groups. Participants may experience some side effects, but understanding these is a key objective of the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for lupus, such as corticosteroids and immunosuppressants, Gusacitinib is unique because it targets specific signaling pathways involved in the inflammatory process. Most lupus treatments work by broadly suppressing the immune system, but Gusacitinib works differently by specifically inhibiting certain enzymes called Janus kinases (JAKs), which play a crucial role in the immune response. This targeted approach could lead to fewer side effects and more effective control of symptoms, making researchers excited about its potential to transform lupus care.

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

Research has shown that gusacitinib might help people with lupus. In past studies, patients taking gusacitinib experienced much better symptom relief than those taking a placebo, a pill with no active medicine. Gusacitinib targets certain proteins that cause inflammation, a major issue in lupus. One study found that patients experienced a 69.5% improvement in their condition after using gusacitinib, which is very promising. This trial will compare gusacitinib to a placebo, suggesting that gusacitinib could effectively manage lupus symptoms. ^{1 3 6 7 8}

Who Is on the Research Team?

Sarfaraz A Hasni, M.D.

Principal Investigator

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Are You a Good Fit for This Trial?

This trial is for adults over 18 with lupus, a condition where the immune system attacks healthy tissue. Participants will undergo various tests including physical exams, blood and urine analysis, heart function tests, chest X-rays, and blood flow measurements.

Inclusion Criteria

I am taking 20 mg or less of prednisone (or equivalent) daily for the last 2 weeks.

I've been on a steady dose of immunosuppressants for the last 12 weeks.

My medications for diabetes, high blood pressure, or cholesterol have been stable for the last 12 weeks.

Exclusion Criteria

My lupus affects my kidneys, brain, or has severely impacted another organ.

My blood counts are low and have been confirmed by tests 4 weeks apart.

A history of drug or alcohol abuse within the 6 months prior to screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment Part 1

Participants receive either Gusacitinib or placebo once a day for 12 weeks

12 weeks

9 clinic visits, 6 phone visits

Treatment Part 2

All participants who took the study drug or placebo in part 1 will take Gusacitinib once a day for 12 weeks

12 weeks

Off-drug Period

Participants who took the study drug will stop taking it for 4 weeks

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Gusacitinib

Trial Overview

The drug Gusacitinib is being tested in people with lupus. The study has three parts: initially comparing Gusacitinib to a placebo for 12 weeks; then all participants take Gusacitinib for another 12 weeks; finally, those on the drug stop it for four weeks to observe effects.

How Is the Trial Designed?

Group I: Control Active Control 1 Intervention

Subjects will remain on their usual SLE medications

Group II: Placebo Placebo Group 1 Intervention

Subjects will receive a placebo that looks similar to the interventional drug.

Gusacitinib is already approved in United States for the following indications:

Approved in United States as Gusacitinib for:

• Chronic hand eczema (Fast Track designation)

Who Is Running the Clinical Trial?

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Lead Sponsor

Trials

508

Recruited

1,090,000+

Published Research Related to This Trial

The JAK1 inhibitor GSK2586184 was evaluated in a study involving 50 adults with systemic lupus erythematosus (SLE) over 12 weeks, but it showed no significant effect on interferon transcriptional biomarkers, leading to the study being declared futile.

Safety concerns arose during the trial, including elevated liver enzymes in six patients, which resulted in immediate cessation of dosing and indicated that GSK2586184 is not suitable for further evaluation in SLE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, efficacy and pharmacodynamics of the selective JAK1 inhibitor GSK2586184 in patients with systemic lupus erythematosus. Kahl, L., Patel, J., Layton, M., et al.[2017]

In a 52-week phase 3 study involving 775 patients with systemic lupus erythematosus (SLE), baricitinib did not show a significant improvement in disease activity compared to placebo, with similar response rates across all treatment groups.

The safety profile of baricitinib remained consistent with previous studies, with serious adverse events occurring in 11% of the 4 mg group, 13% of the 2 mg group, and 9% of the placebo group, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 3 trial (SLE-BRAVE-II). Petri, M., Bruce, IN., Dörner, T., 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]

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]

In a 52-week phase 3 study involving 760 participants with active systemic lupus erythematosus (SLE), baricitinib 4 mg significantly improved disease activity compared to placebo, with 57% of patients achieving an SLE Responder Index (SRI)-4 response.

While the 4 mg dose showed efficacy, key secondary endpoints, such as glucocorticoid tapering and time to first severe flare, did not show significant differences compared to placebo, and the safety profile of baricitinib remained consistent with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 3 trial (SLE-BRAVE-I). Morand, EF., Vital, EM., Petri, M., et al.[2023]

Baricitinib treatment led to significant reductions in anti-dsDNA antibodies and IgG levels in patients with systemic lupus erythematosus (SLE), indicating its potential efficacy in managing this condition.

The study showed that baricitinib resulted in a rapid decrease in anti-dsDNA levels starting as early as 2 weeks, suggesting it may influence B cell activity, although further research is needed to confirm this mechanism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baricitinib decreases anti-dsDNA in patients with systemic lupus erythematosus: results from a phase II double-blind, randomized, placebo-controlled trial. Dörner, T., van Vollenhoven, RF., Doria, A., et al.[2022]

Voclosporin, when combined with mycophenolate mofetil and glucocorticoids, significantly improved complete renal response in lupus nephritis patients, with 43.7% achieving this outcome compared to 23.3% in the control group, based on an integrated analysis of 534 patients from two clinical trials.

The safety profile of voclosporin was comparable to the control, with similar rates of adverse events, most of which were mild to moderate, indicating that voclosporin is a safe and effective treatment option for lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on the Efficacy and Safety Profile of Voclosporin: An Integrated Analysis of Clinical Trials in Lupus Nephritis. Arriens, C., Teng, YKO., Ginzler, EM., 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 24-week phase 2 study involving 314 patients with systemic lupus erythematosus, the 4 mg dose of baricitinib significantly improved symptoms, with 67% of patients achieving resolution of arthritis or rash compared to placebo.

The safety profile of baricitinib was consistent with previous studies, with serious adverse events occurring in 10% of patients on the 4 mg dose, indicating that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 2 trial. Wallace, DJ., Furie, RA., Tanaka, Y., et al.[2021]

In a safety analysis involving 1655 adult patients with systemic lupus erythematosus (SLE) treated with baricitinib for up to 3.5 years, the incidence of infections was similar across baricitinib (4 mg and 2 mg) and placebo groups, with common infections including urinary tract infections and COVID-19.

The study found no significant increase in serious infections or venous thromboembolic events associated with baricitinib treatment, indicating that its safety profile remains consistent with previous findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of baricitinib in patients with systemic lupus erythematosus: an integrated analysis. Morand, E., Smolen, JS., Petri, M., et al.[2023]

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Then, in Part B (through week 32), patients received gusacitinib. Results: At Week 16, patients receiving 80 mg gusacitinib showed a 69.5% (p< ...

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STUDY DESCRIPTION:~This is a phase Ib study of Gusacitinib a dual inhibitor of JAK and SYK kinases, that can simultaneously target multiple signaling ...