- - 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), 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).
- - For male subject involved in any sexual intercourse that could lead to pregnancy,
subject must agree to use one of the highly effective contraceptive methods
listed in Inclusion Criterion #6, from Day 1 until at least 90 days after the
last study product administration.
If the female partner of a male subject use
any of the hormonal contraceptive methods listed above, this contraceptive method
must be used by the female partner from at least 4 weeks before Day 1 until at
least 90 days after the last study product administration by the male subject.
- - 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.
- - Subject is willing to participate and can give informed consent.
- - Subjects must be willing to comply with all study procedures and must be
available for the duration of the study.
EXCLUSION CRITERIA. 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 a history of congestive heart failure of 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.
- - Subject has used systemic (Intravenous) antibiotics within 2 weeks prior to Day 1.
- - Treatment with cyclophosphamide within the 6 months prior to screening.
- - A history of drug or alcohol abuse within the 6 months prior to screening.
- - Blood pressure not adequately controlled on the current medications.
- - History of chronic liver disease or elevated LFTs:
ALT or AST >= 2x upper limit of normal at screening.
serum unconjugated bilirubin > 2mg/dL at screening.
- - Dialysis or serum creatinine >2 mg/dL.
- - Protein to creatinine ratio of more than 1000 mg/mg or 24 hours urine protein of more
than 1000 mg.
- - Active urinary sediment (WBC casts, RBC casts or mixed cellular casts 1+ or more/hpf).
- - Hypercholesterolemia: Values after an 8-12 hour fasting blood specimen: total
cholesterol >250 mg/dL or LDL >180 mg/dl or hypertriglyceridemia (triglyceride >300
mg/dL) at screening visit.
- - Subjects with active renal or central nervous system involvement due to SLE or a BILAG
A in any organ system.
- - WBC <2500/ L or ANC <1,000/ L, Hgb <9.0 g/dL or platelets <70,000/ L or absolute
lymphocyte count < 500/ L at screening and present on repeat testing up to 4 weeks
apart.
- - Current treatment with potent inhibitors of Cytochrome P450 3A4 (CYP3A4) (e.g.,
ketoconazole) or receiving one or more concomitant medications that result in both
moderate inhibition of CYP3A4 and potent inhibition of CYP2C19 (e.g., fluconazole)
that would increase serum availability of Gusacitinib.
Past treatment with the above
mentioned agent is allowed if it was more than a week prior to the administration of
the first dose of study medication.
- - Current treatment with strong and moderate inhibitors of CYPs 3A4, 2C8, 2D6, and
inhibitors of BCRP and MDR1.
Past treatment with the above mentioned agent is allowed
if it was more than a week prior to the administration of the first dose of study
medication.
- - Subjects with moderate and severe hepatic impairment (Child-Pugh B and C).
