Systemic Lupus Erythematosus Systemic Lupus Erythematosus
Conditions
Interventions
The IRF5 inhibitor, may be used 
in vitro. The following investigational medicinal product (IMP) is planned to be used in  
in 4 ascending concentrations, up to a concentration were full IRF inhibition in vitro is expected.HOT-DNo comparative (reference) drug will be used in this study.TL8-506, a TLR8/9 agonist, will be us
in vitro challenge agent.
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Eligible healthy volunteers must meet all the following inclusion criteria at screening: Signed informed consent prior to any study-mandated procedure. Male or female participants, > 18 to 75 years of age at the time of signing informed consent; in general, stable good health as per judgement of the investigator based upon the results of a medical history, physical examination, vital signs, ECG, and laboratory assessments performed at screening. Repeated laboratory testing may be performed at the discretion of the clinical investigator. Body mass index (BMI) > 18.0 and < 35.0 kg/m2. No clinically significant auto-immune or auto-inflammatory disease as judged by the investigator. Participant has the ability to communicate well with the investigator in the Dutch language and is willing to comply with the study requirements. Eligible SLE patients must meet all the following inclusion criteria at screening: Signed informed consent prior to any study-mandated procedure. Male or female SLE patients, 18 to 75 years of age at the time of signing informed consent (inclusive). Body mass index (BMI) > 18.0 and < 35.0 kg/m2. Patient has the ability to communicate well with the investigator in the Dutch language and is willing to comply with the study requirements. Participants must have a diagnosis of SLE that fulfils the following: - SLE diagnosed according to the 2019 ACR/EULAR criteria (Aringer et al 2019) - The presence of SLE autoantibodies measured at any time prior to screening: ANA (greater than or equal to 1:80); OR anti dsDNA above the upper limit of normal (ULN); OR anti-Sm above the ULN For patients with renal involvement: (history of) renal involvement in SLE as diagnosed by the treating rheumatologist or nephrologist
Exclusion criteria
Exclusion criteria: Eligible healthy volunteers must meet none of the following exclusion criteria at screening: (History of) immunological abnormality (e.g., immune suppression) that may interfere with study objectives, in the opinion of the investigator. Antibiotic use, operation, or intervention by surgeon/dentist within one month before visit 1 and one month before visit 2. Participation in an investigational drug study within 5 times the expected half live of the investigated drug. Loss or donation of blood over 500mL within three months prior to screening. The use of any medication within 7 days prior to visit 1 or within 5 half-lives (whichever is longer), if the investigator judges it may interfere with the study objectives. Intention to receive any vaccination(s) within 4 weeks before day 1 until the day 2 visit. Person of childbearing potential who is pregnant (as confirmed by urine pregnancy test), breast-feeding, or planning to become pregnant during the study. (A history of) any clinically significant medical condition, factor or abnormality that might interfere with study conduct or interpretation, as judged by the investigatorChronic or past infection with HIV, hepatitis B (HBV) or hepatitis C (HCV). A positive HBV surface antigen (HBsAg) at screening excludes a participant.Eligible SLE patients must meet none of the abovementioned and following exclusion criteria at screening: Any active or chronic and/or uncontrolled condition that, in the opinion of the investigator, may influence study conduct or interpretation. For clarity, active disease or disease sequalae related to the patient’s diagnosis with SLE are allowed. History of pathological scar formation (keloid, hypertrophic scar) in case skin biopsies are planned.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| IRF5-driven biomarkers in peripheral blood by transcriptomicsIRF5-driven biomarkers in peripheral blood with and without TL8-506 stimulant and IMPs: Gene expression via transcriptomics Cytokines / signalling proteins | — |
Secondary
| Measure | Time frame |
|---|---|
| Other disease-specific biomarkers in peripheral blood with and without TL8-506 stimulant Gene expression via transcriptomics Cytokines / signalling proteins General immune status and disease-associated serological markers in peripheral blood: CBC including leukocyte differentiation SLE autoantibody panel Complement (C3, C4) Immunoglobulins (IgG, IgA, IgM) CRP, ferritin, kreatinin, eGFR (MDRD) General disease-associated markers in urine Urine sediment IRF5-driven and other disease-specific biomarkers in peripheral blood: Gene expression via transcriptomics Cytokines / signalling proteins General immune status and disease-associated serological markers in peripheral blood and urine IRF5-driven and other disease-specific biomarkers in peripheral blood with and without TL8-506 stimulant and IMP Gene expression via transcriptomics Cytokines / signalling proteins IRF5-driven and other disease-specific biomarkers in peripheral blood with and without TL8-506 stimulant and IMP | — |
Countries
Netherlands
Contacts
Public ContactN.B. Klarenbeek
Centre for Human Drug Research
Outcome results
None listed