| ≥ 18 to ≤ 75 years of age at the time of signing the informed consent.
Are up to date according to local guidelines/recommendations. Recombinant zoster vaccination is encouraged but not mandatory.
Cutaneous manifestation criteria:
• Diagnosis of DLE and/or SCLE documented in medical history, with or without SLE.
• Active ACLE as sole cutaneous manifestations is allowed in the presence of SLE (meeting criterion 4) and should be present for at least 6 weeks prior to the Screening visit.
• Other skin manifestations will be allowed (e.g. lupus tumidus, lupus profundus, Chilblain lupus, etc.) on a case-by-case basis if the main diagnosis is active DLE, SCLE, and/or ACLE, as described above.
Confirmation of diagnosis must include 1 of the following options:
a. Pathology report from punch or shave biopsy within 10 years prior to Screening visit and confirmation of current diagnosis by mandatory skin photography at Screening visit.
OR
b. Fresh punch skin biopsy and confirmation of current diagnosis by mandatory skin photography, both performed at/during Screening.
OR
c. On a case-by-case basis (e.g. the target lesion is unsuitable for biopsy), mandatory skin photography may be used for diagnosis in lieu of a skin biopsy, if feasible, after discussion with the medical monitor.
The Sponsor/SET may provide expert opinion for disease diagnosis based on the required photographs submitted at Screening.
For participants with SLE:
a. Diagnosis of SLE and fulfill EULAR/ACR 2019 classification criteria (Aringer 2019).
b. Positive ANA (IFA titer ≥ 1:80) and/or dsDNA and/or a-Sm autoantibody at Screening.
Note: All participants, regardless of initial diagnosis, will be reviewed at Screening for meeting SLE classification criteria. BILAG will be performed in all SLE participants at Screening to confirm level of disease activity.
Disease duration (both cutaneous disease and SLE, where applicable) of ≥ 6 months from time of diagnosis to Screening.
CLASI-A ≥ 8 at Screening and Day 1 Visits |
Primary diagnosis of autoimmune rheumatic disease (e.g. systemic sclerosis, rheumatoid arthritis) other than CLE and SLE.
Note: Secondary Sjögren’s syndrome is not exclusionary.
Any condition including dermatological diseases other than cutaneous manifestations of lupus (e.g. psoriasis), any uncontrolled disease (e.g. asthma, chronic obstructive pulmonary disease, interstitial lung disease, bronchiectasis, pulmonary arterial hypertension), or life-threatening manifestations of lupus (e.g. active systemic vasculitis) that in Investigator’s or Sponsor/designee’s opinion constitutes inappropriate risk or contraindication for participation.
Drug-induced lupus (SLE or CLE).
Active lupus nephritis on induction therapy, or induction therapy completed within 3 months of Screening visit (stable maintenance therapy with either mycophenolate, azathioprine or an oral calcineurin inhibitor is allowed).
UPCR > 339 mg/mmol, and/or eGFR < 40 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation by the central laboratory:
eGFR = 175 × (serum creatinine in mg/dL)–1.154 × (age in years) – 0.203 × 0.742 (if female) × 1.212 (if race is black)
Any active signs, symptoms or diagnoses considered related to CNS lupus within the past 3 months or any history of uncontrolled seizures.
Any other history of epilepsy or other neurological disorder with seizure propensity which requires ongoing pharmacological treatment, or neuropsychiatric conditions that may interfere with study evaluations.
Significant thrombotic (e.g. catastrophic antiphospholipid syndrome, pulmonary embolism) or cardiovascular events (e.g. acute myocardial infarction, unstable angina, or peripheral vascular disease symptoms, hospitalization for congestive heart failure, uncontrolled, or New York Heart Association Class 3 or 4 congestive heart failure, cardiac surgery, ischemic or hemorrhagic stroke, or transient ischemic attack), ≤ 6 months before Screening Visit.
Any clinically significant ECG abnormality (e.g. acute myocardial infarction, WPW, etc.) that in the Investigator’s or Sponsor/designee’s opinion constitutes inappropriate risk or contraindication for study participation.
Suicide risk in the last 6 months (including suicidal ideation and/or suicidal behavior on the C-SSRS during Screening or Day 1).
History of or planned solid organ transplant.
Ongoing or active clinically significant viral (including SARS CoV 2), parasitic, bacterial (including active or untreated latent TB, see Exclusion Criterion 14) or fungal infection:
• Requiring hospitalization or,
• Treatment with parenteral anti-infectives ≤ 4 weeks prior to or during Screening Period, or
• Completion of oral anti-infectives ≤ 2 weeks prior to Day 1 Visit.
• Investigators should follow their local guidelines for SARS CoV 2 testing during the Screening period (e.g. testing regardless of symptoms, or potential exposure may be required before entering a research study, symptomatic, or exposure-based testing at Screening only, etc.).
• Vaginal candidiasis, onychomycosis, and genital, or oral herpes simplex virus considered to be sufficiently controlled will not be exclusionary.
Any of the following:
a. A positive HIV test.
b. Positive HCV Ab and detectable HCV RNA NAAT performed reflexively at Screening, or history of treated HCV with detectable HCV RNA NAAT performed reflexively at Screening.
c. Positive HBV surface antigen, or positive HBV core Ab with negative HBV surface Ab and reflexive detectable HBV DNA NAAT at Screening, or no history of HBV vaccination with positive HBV surface and/or core Abs and reflexive detectable HBV DNA NAAT at Screening.
See Appendix 10 for country-specific requirements.
Any of the following:
a. Active TB.
Note: Participants with a history of active or latent TB who have documented evidence of appropriate treatment, no history of re-exposure and no current evidence on imaging of active TB since their treatment was completed would not be required to undergo the protocol-specific TB testing for purified protein derivative, QuantiFERON test, or T SPOT test. Recent chest imaging (chest X-ray, CT, MRI) within 3 months from Screening visit is acceptable as long as there are no clinical changes that could be attributed to active TB since completion of this test.
b. Untreated LTBI.
c. Undergoing current treatment for LTBI.
d. Participants with current household contacts with active TB.
In the absence of an active TB diagnosis, or clinical features consistent with an active TB diagnosis, LTBI is determined by any of the following:
• Prior TB skin test with purified protein derivative with induration ≥ 5 mm (unless vaccinated with Bacille Calmette-Guérin).
• Prior positive T-SPOT.TB (Elispot) result.
• Positive QuantiFERON test, either at Screening, or with documented past results.
Note: All participants, except those who have previously completed appropriate and documented LTBI treatment, must undergo QuantiFERON testing during Screening. Participants with indeterminate or positive QuantiFERON results that may represent a false-positive result by the Investigator with no clinical features consistent with active TB will be evaluated with either a repeat QuantiFERON test (local or central laboratory test) or a T SPOT. TB (local laboratory test) at the request of the Investigator.
• If the subsequent QuantiFERON or T SPOT.TB result is negative, the participant may be enrolled after approval by the SET.
• If the repeat result is indeterminate and a subsequent chest X-ray is negative, the participant may be allowed into the study on a case-by-case basis after consultation with Sponsor.
History of malignancy (e.g. hematologic, skin, solid tumor) ≤ 10 years prior to Screening Visit, except adequately treated basal cell or squamous cell carcinomas of the skin (≤ 3 lesions requiring treatment in lifetime) or adequately treated carcinoma in situ/cervical intraepithelial neoplasia of the uterine cervix.
Any major surgery such as abdominal, thoracic, or joint replacement surgeries ≤ 6 weeks prior to Screening Visit or planned major surgery during the study (including Follow up) or planned within the next 12 months.
History of alcohol or drug abuse ≤ 1 year prior to Screening Visit as per Investigator opinion.
History of splenectomy or functional asplenia.
Any condition that could interfere with study objectives, conduct, or evaluation in the opinion of the Investigator or Sponsor/designee.
Known hypersensitivity to any study intervention, component, or placebo.
The use, initiation, or dose change in the following therapies ≤ 2 weeks prior to or during Screening:
a. Use of CS exceeding 30 mg daily prednisone equivalent for SLE and CLE, including but not limited to oral, topical CSs Class I, and augmented betamethasone dipropionate 0.05% gel or ointment, intramuscular, or other injectable CS.
b. Use of topical calcineurin inhibitors more than 1 time per day.
c. Initiation or dose change of angiotensin-converting enzyme inhibitors or angiotensin receptor blocker, or NSAIDs, or use of NSAIDs above maximum prescribed dose per local label.
d. Initiation or dose change of NSAIDs or use of NSAIDs above maximum prescribed dose per local label.
The initiation, use, or change in the following therapies ≤ 4 weeks prior to or during Screening:
a. Use of thalidomide or lenalidomide.
b. Use of intralesional therapies.
c. Use of tripterygium and total glucosides of paeony.
The initiation, use of a dose exceeding the maximum specified dose or change in the following therapies < 8 weeks prior to Screening: antimalarials, methotrexate, azathioprine, 6 mercaptopurine, sulfasalazine, MMF or mycophenolic acid, leflunomide, oral tacrolimus, cyclosporin A, voclosporin, oral dapsone, or oral retinoids.
Vaccination as specified below:
a. Vaccination with live or live attenuated virus vaccine: ≤ 4 weeks prior to Screening.
b. Vaccination with a subunit, recombinant or inactivated vaccine (e.g. influenza virus, S. pneumoniae): ≤ 2 weeks prior to Screening and Baseline.
The use of the following therapies within the time frame specified below:
a. Belimumab ≤ 14 weeks prior to Screening
b. Anifrolumab: ≤ 16 weeks prior to Screening
c. Cyclophosphamide: ≤ 12 weeks prior to Screening.
Treatment with investigational agents or off-label drugs for SLE or CLE within the last 12 weeks or 5 half-lives, whichever is longer, or as specified below, prior to Screening Visit:
a. Use of alkylating agents other than cyclophosphamide (e.g. chlorambucil): ≤ 24 weeks prior to Screening.
b. B cell depleting/ modulating therapy such as anti-CD20 agents (e.g. Rituximab), dual or other anti-B Lymphocyte Stimulator/proliferation inducing ligand neutralizing therapies: ≤ 24 weeks prior to Screening.
c. mAb binding blood DC antigen 2 (BDCA2, e.g. litifilimab): ≤ 24 weeks prior to Screening.
d. IL-12/IL-23 pathway inhibitors (e.g. ustekinumab): ≤ 24 weeks prior to Screening.
e. Anti-IL-6 receptor (tocilizumab, sarilumab) or anti IL 6 (siltuximab): ≤ 12 weeks prior to Screening.
f. Anti-CD40 ligands (e.g. dapirolizumab pegol) ≤ 24 weeks prior to Screening.
g. Intravenous immunoglobulin: ≤ 12 weeks prior to Screening.
h. JAK/STAT or TYK2 pathway inhibitors (e.g. tofacitinib, upadacitinib, baricitinib, deucravacitinib, respectively): ≤ 4 weeks prior to Screening.
i. Participants who have enrolled in any previous TLR7/8 inhibitor studies (e.g. enpatoran) may not enter the study regardless of timing.
History of treatment with cell-based (e.g. CAR-T cells) or T-cell engager therapies.
Clinically significant or predefined abnormalities in laboratory tests at Screening Visit:
• AST or ALT > 3.0 × ULN
• Alkaline phosphatase > 2.0 × ULN
• Total bilirubin > 1.5 × ULN
• Hemoglobin < 5.0 mmol/L (9 g/dL), white blood cells < 2.5 × 109/L, absolute neutrophil count < 1,500/mm3, or platelets < 75 × 109/L, unless any of these are attributable to active SLE
• Or TSH < 0.01 mIU/L or ≥ 7.1 mIU/L per central laboratory results
Legal incapacity or limited legal capacity.
|
Adult: 18 Year(s)-44 Year(s) |
18 Year(s) |
75 Year(s) |
Both |