AIH autoimmune disease(s) autoimmune hepatitis
Conditions
Interventions
Intervention Groups and Duration: In Part A, participants in each cohort will
receive a single SC dose of VIS171 or placebo on Day 1. The starting dose in
Part A is 1 jig/kg. The proposed doses for
Sponsors
Parexel Nederland
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Summary of Key Inclusion and Exclusion Criteria: Inclusion Criteria Male or female participant between 18 and 55 years of age, inclusive, at the screening visit (Part A and Part B [participants with AIH, FSGS, and AA]) or between 18 and 75 years of age, inclusive, at the screening visit (Part B [participants with SLE]). Body mass index between 17 and 35 kg/m2, inclusive, at the screening visit. Additional inclusion criteria: * Part A: Healthy, as determined by prestudy medical evaluation (medical history, physical examination, vital signs, 12-lead electrocardiogram, and clinical laboratory evaluations), as judged by the principal investigator. * Part B (participants with SLE only): Diagnosis of adult SLE according to the 2019 American College of Rheumatology classification criteria for at least 6 months prior to signing the informed consent form (ICF) and an estimated glomerular filtration rate (eGFR) >= 30 mL/min/1.73 m2 (calculated using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula [2021]). * Part B (participants with AIH only): Adult meeting criteria for autoimmune hepatitis (simplified diagnostic criteria) and must have completed induction therapy with standard of care (eg, steroids) and be on maintenance therapy (eg, azathioprine and/or low dose steroids).
Exclusion criteria
Exclusion criteria: Key Exclusion Criteria Receipt of high dose corticosteroid therapy within 4 weeks prior to screening as either (a) intravenous (IV) pulse corticosteroid therapy or (b) daily oral corticosteroid therapy of >= 1 mg/kg or 80 mg/day prednisone (or equivalent), receipt of belimumab within 6 months prior to screening, history of treatment with rituximab or ocrelizumab (or other B cell-depleting agent) within 12 months prior to screening, history of cytotoxic medications (eg, cyclophosphamide) within the preceding 12 months, and receipt of blood products within 6 months prior to screening. Participants with uncontrolled hypertension (systolic blood pressure [SBP] > 140 mmHg, diastolic blood pressure [DBP] > 90 mmHg in any position) or symptomatic hypotension, any chronic infectious disease, or participants with a positive urine drug or alcohol breath screen test result at screening or Day *1. Current symptoms of infection, diagnosis of Coronavirus Disease 2019 (COVID-19) (reverse transcription polymerase chain reaction [RT-PCR], antigen testing, or clinical diagnosis) in 21 days prior to screening, or ongoing diagnosis of *Long-COVID* symptoms due to a prior COVID-19 infection. Received a vaccination, other than COVID-19 vaccination, during the 30 days prior to administration of the first dose of study intervention. A COVID-19 vaccination cannot be received within 7 days prior to the first dose of study intervention and until 14 days after the last dose. Additional exclusion criteria: * Part B (participants with SLE only): Presence of life- or organ-threatening manifestations of lupus requiring intense immunosuppressive therapy, organ support systems, or plasmapheresis. Lupus cerebritis, or active severe or unstable neuropsychiatric SLE. * Part B (participants with AIH only): Advanced cirrhosis/liver disease. Protocol VIS171-101 11 Confidential - Proprietary Information Approval: 19 Nov 2021 * Part B (participants with FSGS only): Steroid resistant nephrotic syndrome defined as absence of complete or partial remission following at least 12 weeks of full dose corticosteroid therapy. Known secondary causes of FSGS (eg, genetic/familial, viral, reflux uropathy, toxic causes [eg, bisphosphonates]). * Part B (participants with AA only): Participant has concomitant hair loss of another form, including but not limited to traction alopecia, central centrifugal cicatricial alopecia, lichen planopilaris, frontal fibrosing alopecia, or androgenetic alopecia. Presence of other severe autoimmune diseases - requiring additional immunosuppressive treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objectives and Endpoints - Part A (Single Ascending Dose) Objectives Endpoints Primary: · To evaluate the safety and tolerability of VIS171. Primary endpoint: · Incidence and severity of TEAEs. Objectives and Endpoints - Part B (Multiple Ascending Dose) Objectives Endpoints Primary: · To Endpoint evaluate the safety and tolerability of VIS171. Primary: · Incidence and severity of TEAEs. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary part A: · To determine the PD effect of VIS171. · To assess the PK of VIS171. Secondary Endpoint: · Mean fold change from baseline in immune cell types, including the following: · Absolute number (cells/µL) and frequency (%) of Treg. · Absolute number (cells/µL) and frequency (%) of helper T cells, cytotoxic T cells, and natural killer cells. · Pharmacokinetic parameters: · Cmax, tmax, AUClast, and AUC*. Secondary part B: · To determine the PD effect of VIS171. · To assess the PK of VIS171. · To evaluate the immunogenicity of VIS171. Secondary Endpoint: · Mean fold change from baseline in immune cell types, including the following: · Absolute number (cells/µL) and frequency (%) of Treg. · Absolute number (cells/µL) and frequency (%) of helper T cells, cytotoxic T cells, and natural killer cells. · Pharmacokinetic parameters: · Cmax, tmax, and AUCtau. · Characterization of ADA to VIS171 over time. | — |
Countries
Netherlands
Outcome results
None listed