Inclusion criteria are listed as follows:
1. Male or female of 18 years of age or older at the time of signing the informed consent
form (ICF).
2. Body mass index (BMI) between 18 and 40 kg/m2.
3. Able and willing to adhere to the visit schedule and other protocol requirements.
4. Diagnosed with SLE according to the 2019 EULAR/ACR criteria for SLE (See Appendix 1).
5. Meeting SLE activity requirements as described below:
- - For the Phase 1b part of the study, patients with or without active SLE may be
enrolled if, in the opinion of the Investigator, the disease activity is stable
and there will be no need for change or increase in SLE therapy anticipated for
the study duration.
If patients are on stable standard care of SLE treatment,
this should comply with inclusion criteria No. 11.
- - For the Phase 2a part of the study, patients must have a Systemic Lupus
Erythematosus Disease Activity Index (SLEDAI-2K) score of ≥ 6 points at Screening
visit with a SLEDAI-2K clinical score ≥ 4 points at Baseline visit.
The
"clinical" score is the SLEDAI-2K assessment score without the inclusion of
points attributable to any urine or blood laboratory results including
immunologic measures. Neurologic descriptors of the SLEDAI-2K are not counted
towards the SLEDAI study entry criteria. In addition, the patient must be on
stable standard care of SLE treatment with at least one of the followings: oral
corticosteroids (OCS), anti-malarial, or immunosuppressant (see inclusion
criteria No. 11 for allowed medications and doses).
6. Documented history or presence at Screening of positive autoantibodies associated with
SLE, which must include at least 1 of the following:
- - Positive antinuclear antibody (ANA) test with a titer of 1:80 or greater.
- - Anti-dsDNA antibodies elevated to above normal.
- - Anti-Smith antibody elevated to above normal.
7. Women of childbearing potential (WOCBP) must:
- - Have 2 negative serum pregnancy tests as verified by the Investigator prior to
starting study therapy, 1 at Screening and again within 3 days before taking the
first dose of KPG-818, then have a negative urine pregnancy test at Baseline
before dosing.
WOCBP must agree to ongoing pregnancy testing during the course of
the study and after end of study treatment. This applies even if the patient
practices true abstinence from heterosexual contact.
- - Either commit to true abstinence from heterosexual contact (which must be
reviewed on a monthly basis and source documented) or agree to use 2 forms of
reliable contraception simultaneously.
One must be a highly effective method and
1 additional effective (barrier) method (see Appendix 5 for more details), and
both must be practiced without interruption, at least 28 days before starting
investigational medicinal product (IMP), during the study therapy (including dose
interruptions), and for 28 days after discontinuation of study therapy.
8. Male patients must: Practice true abstinence or agree to use a barrier contraception
(male latex condom or non-latex condom NOT made out of natural [animal] membrane [for
example, polyurethane]) during sexual contact with WOCBP while participating in the
study, and for at least 90 days following IMP discontinuation, even if he has
undergone a successful vasectomy. Male patients must agree not to donate semen or
sperm during the treatment period and for at least 90 days following the
discontinuation of KPG-818.
9. Female patients who are postmenopausal must demonstrate a follicle stimulating hormone
(FSH) blood levels of ≥ than 40 mIU/mL at the Screening visit. Women aged > 60 years
old whose FSH values are not equal to or greater than 40 mIU/mL may be included at the
discretion of the Investigator and in consultation with the Sponsor (see Appendix 5
for more details).
10. All patients must:
- - Understand that KPG-818 could have potential teratogenic risk.
- - Agree not to share KPG-818 with another person.
- - Be counseled about pregnancy precautions and risks of fetal exposure as described
in the Pregnancy Prevention Plan.
11. In Phase 2a part of the study, the patient must be on stable standard care of SLE
treatment with at least one of the followings: oral corticosteroid, anti-malarial, or
immunosuppressant:
1. If taking OCS, must be on-treatment for ≥ 4 weeks before the Screening visit, and
maintained on a stable dose of ≤ 20 mg/day of prednisone or equivalent for at
least 4 weeks before the Baseline visit.
2. If taking an anti-malarial agent (hydroxychloroquine, chloroquine, or
quinacrine), must be on-treatment for ≥ 8 weeks before the Screening visit and be
on a stable dose for ≥ 4 weeks before the Screening visit. Anti-malarials at the
following doses are allowed:
- - Hydroxychloroquine (≤ 400 mg/day)
- Chloroquine (≤ 500 mg/day)
- Quinacrine (≤ 200 mg/day)
3.
If taking allowed immunosuppressants, must be on-treatment for ≥ 8 weeks prior to
the Screening visit and be on a stable dose for ≥ 4 weeks before the Screening
visit. Only 1 of the immunosuppressants below is allowed at the indicated doses:
- - Micophenolate mofetil (≤ 2 g/day) or mycophenolic acid (≤ 1.44 g/day)
- Azathioprine (≤ 200 mg/day)
- Methotrexate (≤ 20 mg/week)
- Leflunomide (≤ 20 mg/day)
4.
If taking NSAIDs or other regularly administered analgesics, these will be
allowed if treatment started ≥ 4 weeks before the Baseline visit and dosing has
not been changed within the last 2 weeks before the Baseline visit.
5. If immunosuppressants, anti-malarial, or OCS is discontinued, the last dose must
be more than 4 weeks prior to Screening visit.
12. Patients must agree not to donate blood (or any component of blood) from 3 months
before Screening until 3 months after the last dose of KPG-818.
13. Patients must be willing to comply with precautions to reduce the risk of COVID-19
infection in accordance with recommendations from the applicable medical associations
and the Investigator for the duration of the study, and to undergo COVID-19 polymerase
chain reaction (PCR) test as required based on the Investigator judgment and/or local
requirements.
Exclusion criteria are listed as follows:
1. Use of any prohibited medications within the pre-specified time (see Appendix 6 for
details on the required washout period for each drug class).
2. Any of the following noted at Screening (within 6 weeks before Week 1 [Day 1] in Phase
1b, within 4 weeks before Week 1 [Day 1] in Phase 2a):
- - Aspartate aminotransferase (AST) > 2.0 × ULN.
- - Alanine aminotransferase (ALT) > 2.0 × ULN.
- - Total bilirubin > 1.5 × ULN (unless due to Gilbert's syndrome)
- Serum creatinine > 2.5 mg/dL (or > 221 μmol/L)
- Neutrophil count < 1500/µL (or < 1.5 × 109/L) (< 1000/µL [or < 1.0 × 109/L] if
the neutropenia is related to SLE)
- Platelet count < 50 000/µL (or < 50 × 109/L) (< 25 000/µL [or < 25 × 109/L] if
the thrombocytopenia is related to SLE)
- Hemoglobin < 8 g/dL (or < 80 g/L) (< 7 g/dL [or <70 g/L] if related to SLE)
3.
Have an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2 (CKD-EPI
formula) at Screening.
4. Have a spot urine protein to creatinine ratio (sUPCR) > 2000 mg/g (226 mg/mmol, as an
estimate of approximate proteinuria > 2 g/day) at Screening.
5. Active and/or unstable neuropsychiatric SLE (e.g., neuropsychiatric SLE including
seizures, psychosis, acute confusional state, cerebrovascular accident, aseptic
meningitis, or polyneuropathy).
6. Positive serology test for hepatitis B virus (HBV), hepatitis C virus (HCV), or human
immunodeficiency virus (HIV-1 and HIV-2) at Screening. In cases of a positive
screening test, patient may be enrolled if a confirmatory test is negative (see
Appendix 3 for details). Exception: patient who test positive for HCV antibodies may
be enrolled if confirmed with cured HCV infection and documented completion of
treatment more than 3 months before screening and HCV must not be detectable at
screening.
7. Active or history of severe systemic bacterial, viral, fungal, mycobacterial, or
parasitic infections (requires hospitalizations or IV antibiotics) within 6 months
prior to Screening.
8. Any current or recent (within 4 weeks of Screening) signs or symptoms of infection,
except for fungal infections of the nail beds, oral or vaginal candidiasis that has
resolved, or minor infections (e.g., common cold, viral gastroenteritis, urinary tract
infection) that have in the Investigator's judgment, completely resolved prior to the
Baseline visit.
9. Any severe, recurrent, disseminated viral infections, particularly herpes viruses such
as HSV-1, HSV-2, VZV, CMV (e.g., herpes encephalitis, ophthalmic herpes, disseminated
zoster, CMV colitis) per Investigator's judgment. Recurrent is defined as 2 or more
episodes in the past 2 years and/or with an episode within 3 months of Screening.
10. Known history of congenital or acquired immunodeficiency, splenectomy, or any
underlying condition that predisposes the patient to infection.
11. Active tuberculosis (TB) or a history of incompletely treated TB, or a positive,
QuantiFERON®-TB Gold test. If a patient's initial TB test result is indeterminate, the
test can be repeated once. If the test result is again indeterminate (or positive),
the patient will be excluded from the study. An exception for positive or
indeterminate results may be made for patients who have documentation of having
completed appropriate standard treatment for latent TB before screening and do not
have other risk factors, radiologic findings, or physical evidence supporting latent
or active TB.
12. History of malignancy within 5 years of Screening with the exception of basal cell or
squamous cell in situ skin carcinomas or carcinoma in situ of the cervix that has been
treated with no evidence of recurrence.
13. History of antiphospholipid syndrome with thromboembolic event within 12 months of
screening or not on an adequate anticoagulation regimen. However, presence of
antiphospholipid antibodies alone (without a history of thromboembolic event) is not
exclusionary.
14. Other non-SLE driven inflammatory joint or skin disease, mixed connective tissue
disease, scleroderma, and/or overlap syndromes. An exception may be allowed for
rheumatoid arthritis overlapping with SLE (i.e., RUPUS) with no erosive joint disease
after a discussion with the medical monitor. Patients with SLE and secondary Sjogren
syndrome are not exclusionary.
15. Clinically significant or unstable or uncontrolled acute or chronic disease not
related to SLE that in the Investigator's opinion would preclude patient
participation.
16. Concomitant condition (such as asthma) that required systemic corticosteroid use
within 1 year before Screening. Use of inhaled corticosteroid is not exclusionary.
17. History of alcohol or drug abuse within 1 year before screening based on the
Investigator's judgement.
18. Have a positive urine drug test at screening (see Appendix 3) except if the patient
has a valid prescription for an allowed concomitant medication or substance
abuse/dependence has been ruled out in the Investigator's judgment.
19. History of major surgery within 12 weeks prior to Screening or any planned major
surgery during the study.
20. Clinically significant ECG abnormalities or have a corrected QT (QTc) interval value >
480 ms at Screening, in the Investigator's opinion would preclude patient
participation.
21. Pregnant or breastfeeding female.
22. Signs or symptoms that in the opinion of the Investigator, may be suggestive of
COVID-19 infection. The patient may be allowed to enter the study if a COVID-19 PCR
test performed during the Screening results in a negative outcome.
23. Known allergic reaction to any of the ingredients for study drug or placebo.
