A Clinical Trial to Evaluate Safety of Gusacitinib in Patients With Systemic Lupus Erythematosus (SLE) or Lupus

NCT06238531 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: 10001700001700-AR
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Systemic lupus erythematosus (SLE), also called lupus, is a disease that causes the body s immune system to attack healthy tissue. Lupus causes swelling and inflammation in the skin, skin, joints, kidneys, brain, blood vessels, and other organs. There is no cure for lupus. Current treatments do not help everyone and may have adverse effects. Better treatments are needed. Objective: To test a study drug (Gusacitinib) in people with lupus. Eligibility: People aged 18 years and older with lupus. Design: Participants will be screened. They will have a physical exam with blood and urine tests and a test of their heart function. They will have a chest X-ray. They will have tests that use blood pressure cuffs to measure blood flow and pressure throughout the body. Participants will have 9 clinic visits and 6 phone visits over about 7 months. The study has 3 parts. Part 1: Gusacitinib is a tablet taken by mouth. Participants will be divided into 3 groups. One group will receive the study drug, and a second group will get a placebo. The placebo looks like the study drug but does not contain any medicine. Both of these groups will take their tablets once a day for 12 weeks. The third group will continue to take their usual medications for lupus throughout the study. Part 2: All participants who took the study drug or placebo in part 1 will take the study drug once a day for 12 weeks. Part 3: All participants who took the study drug will stop taking it for 4 weeks.

Conditions

Systemic Lupus Erythematosus

Keywords

SLE; Lupus; Systemic Lupus Erythematosus; Gusacitinib; Investigational Drug; Treatment; Mild

Outcome Measures

Primary Outcomes (1)

• Adverse Events severity (as defined by AEs equal or greater than grade 3 as per the National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (CTCAE) v5.0) and frequency as compared to placebo at week 12

  Adverse Events severity (as defined by AEs equal or greater than grade 3 as per the National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (CTCAE) v5.0) and frequency as compared to placebo

  Week 12

Secondary Outcomes (1)

• Change in the proportion of patients achieving SLE Responder Index-4 (SRI 4) response at week 24 compared to baseline. Another efficacy analysis will be done by comparing subjects treated with Gusacitinib vs. placebo at week 12.

  Week 12

Study Arms (2)

Control

NO INTERVENTION

Subjects will remain on their usual SLE medications

Placebo

PLACEBO COMPARATOR

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

Drug: Gusacitinib

Interventions

Gusacitinib DRUG

An orally active dual SYK/JAK kinase inhibitor

Placebo

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subject, 18 years of age or older, at the time of consent
• Meets at least 4 of 11 modified American College of Rheumatology (ACR) (1997) Revised Criteria for the Classification of Systemic Lupus Erythematosus
• Has no to mild disease activity defined as a SLEDAI 2K score between 0-6.
• If on glucocorticoids, the dose must be prednisone \<=20 mg daily (or equivalent) for 2 weeks at the time of screening. At the investigator s discretion, glucocorticoids may be tapered during the second (open label) period of the study.
• If on hydroxychloroquine, the dose must have been stable for the 12 weeks prior to screening visit. The maximum allowed dose is hydroxychloroquine up to 400 mg/day or 6.5 mg/kg/day if more than 400 mg/day; or equivalent dose of other antimalarial medications
• Stable doses of immunosuppressant for the 12 weeks prior to the screening visit. Immunosuppressant medications include azathioprine up to 2 mg/kg, methotrexate up to 20 mg/week, mycophenolate mofetil up to 3000 mg/day or mycophenolic acid \<= 2.16 g/day. The subject will be taken off these immunosuppressant medications 2 weeks prior to administration of study medication and will be kept off these medications for the duration of study. Any subject experiencing worsening of SLE disease activity will be treated by a single dose of intra-muscular corticosteroid. This will be allowed only once during each period of the study. A second flare during each period requiring treatment would lead to withdrawal of the subject. The subjects in comparator group will continue on standard of care treatment.
• Stable medications for diabetes, hypertension and/or statins for 12 weeks prior to the screening visit.
• For female subject of childbearing potential involved in any sexual intercourse that could lead to pregnancy: the subject must agree to use a highly effective contraceptive method from at least 4 weeks before Day 1 until at least 4 weeks after the last study product administration. Highly effective contraceptive methods include hormonal contraceptives (e.g. combined oral contraceptive, patch, vaginal ring, injectable, or implant, or progesterone only pill or injections), intrauterine devices or intrauterine systems, vasectomized partner(s), tubal ligation, or double barrier methods of contraception (e.g. male condom with cervical cap, male condom with diaphragm, or male condom with contraceptive sponge) in conjunction with spermicide.
• Note: Subjects must have been on a stable dose of hormonal contraceptives for at least 4 weeks before Day 1.
• Note: The above list of contraceptive methods does not apply to subjects who are abstinent for at least 4 weeks before Day 1 and will continue to be abstinent from penile-vaginal intercourse throughout the study. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant.
• Note: A female subject of nonchildbearing potential is as follows:
• Female subject who has had surgical sterilization (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy);
• Female subject who has had a cessation of menses for at least 12 months without an alternative medical cause, and a follicle-stimulating hormone (FSH) test confirming nonchildbearing potential (as per the reference range of the testing laboratory).
• Male subjects must not donate sperm from Day 1 until at least 90 days after the last study product administration.
• Female subject of childbearing potential has had a negative serum pregnancy test at screening and negative urine pregnancy test on Day 1.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Subject is a female who is breastfeeding, pregnant, or who is planning to become pregnant during the study.
• Subject has a history of cancer or lymphoproliferative disease within 5 years prior to Day 1. Note: Subjects with successfully treated nonmetastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix are not to be excluded.
• Subject has any clinically significant medical condition or physical / laboratory / ECG / vital signs abnormality that would, in the opinion of the investigator, put the subject at undue risk or interfere with interpretation of study results.
• Subject has 12-lead ECG abnormalities considered by the investigator to be clinically
• significant or a QTcF \>= 450 milliseconds, regardless of clinical significance, at screening. Abnormal ECG may be confirmed with one repeated assessment. For subjects with a QTcF \>= 450 msec on initial ECG, the mean of the two QTcF values will determine eligibility.
• Subject has congestive heart failure class III or IV as per the New York Heart Association (NYHA) classification.
• Subject has a history of untreated recurrent venous thromboembolic event (VTE) (\>= 2 episodes in the past).
• Subject has experienced any of the following within the last 6 months prior to Day 1: VTE, myocardial infarction, angioplasty, or cardiac stent placement, unstable ischemic heart disease, or stroke.
• Subject had other major surgery within 8 weeks prior to Day 1 or has a major surgery planned during the study.
• Subject has positive results for hepatitis B surface antigens (HBsAg), antibodies to hepatitis B core antigens (anti-HBc), hepatitis C virus (HCV), human immunodeficiency virus (HIV), or BK viremia at the screening visit.
• Subject has a known active tuberculosis (TB) or a positive TB infection test. Subject will be evaluated for latent TB infection with a purified protein derivative (PPD) test or a QuantiFERON-TB Gold test. Subjects who demonstrate evidence of latent TB infection (either PPD \>= 5 mm of induration or positive QuantiFERON-TB Gold test, irrespective of Bacillus Calmette-Gu(SqrRoot)(Copyright)rin vaccination status) will only be allowed to participate in the study if there is documented evidence of a completed adequate treatment course for latent TB (with negative chest x-ray findings for active TB).
• Subject has a known history of diverticulitis.
• Subject has received any marketed or investigational biologic agent (such as rituximab, belimumab, anifrolumab etc.) within 12 months or 5 half-lives (whichever is longer) prior to Day 1.
• Subject has received a live attenuated vaccine within 4 weeks prior to Day 1 or plans to receive a live attenuated vaccine during the study and up to 4 weeks or 5 half-lives (of the study product), whichever is longer, after the last study product administration.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Lymphoma, Follicular

Interventions

gusacitinib

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders

Study Officials

• Sarfaraz A Hasni, M.D.

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2024
• First Posted: February 2, 2024
• Study Start: January 22, 2025
• Primary Completion: January 22, 2025
• Study Completion: January 23, 2025
• Last Updated: March 13, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)