A Study of Single and Multiple Ascending Doses of VIB1116 in Rheumatic Diseases

Study Overview
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Brief Summary
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A first-in-human study to evaluate the safety and tolerability of escalating, single and multiple ascending doses of VIB1116 in adult participants with rheumatic diseases.

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Single and Multiple Ascending Doses of VIB1116 in Conventional Dendritic Cell (cDC) and Plasmacytoid Dendritic Cell (pDC)-Mediated Rheumatic Diseases

Conditions
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Dendritic Cell -Mediated Rheumatic Diseases

Intervention / Treatment
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* Drug: VIB1116
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 18 years of age and ≤ 60 years of age and a body mass index (BMI) < 30 kg/m² or, in patients who have completed dosing with a vaccine against COVID-19 and are at least 1 month post the last dose, ≤ 65 years of age and BMI < 35 kg/m^2 A diagnosis of one of a specified list of rheumatologic diseases at least 6 months prior to screening. Stable dosing (or no use) of glucocorticoid or disease-modifying antirheumatic drugs (DMARDs) used for treatment of rheumatologic disease for ≥ 28 days prior to randomization. Willing to practice study-required contraception. Exclusion Criteria: Planning to change treatment for rheumatologic disorder within 4 months after randomization Known immunodeficiency disorder or history of splenectomy, organ or cell-based transplantation, total lymphoid irradiation or T-cell vaccination or transfusion in prior 6 months Treatment with prednisone or equivalent at a dose > 10 mg/day or intraarticular, intravenous or intramuscular steroids within 28 days prior to screening Treatment with any of the following medications within 28 days prior to screening (unless otherwise specified below) above the given doses: Mycophenolate mofetil > 2 g/day Methotrexate > 20 mg/week Leflunomide > 20 mg/day within 6 months prior to screening or receipt of leflunomide in combination with any dose of methotrexate Azathioprine > 2 mg/kg/day Cyclosporine (except eye drops); tacrolimus (except topical), sirolimus, thalidomide, lenalidomide, 6-mercaptopurine, or voclosporin Hydroxychloroquine > 400 mg/day Chloroquine > 250 mg/day Quinacrine > 100 mg/day Sulfasalazine > 3 g/day, except that no more than 1 g/day is permitted if used in combination with methotrexate Dapsone > 100 mg/day Danazol > 800 mg/day Any other nonbiologic immunosuppressive/immunomodulatory agent not already specified (eg, mizoribine, retinoids, adrenocorticotropic hormone analogs, dehydroepiandrosterone [DHEA]) within 2 weeks prior to screening. Receipt of any biologic B cell-depleting therapy within 12 months or non-depleting B cell-directed therapy within 6 months Receipt of abatacept, etanercept, or other biologic immunomodulatory agent or immunoglobulins within 3 months Receipt of any other biologic disease modifying antirheumatic drug (bDMARD) not already specified, such as any targeted therapy (other than Janus kinase [JAK] inhibitor), or receipt of cyclophosphamide or chlorambucil within 6 months Receipt of JAK inhibitors within 3 months Receipt of anticoagulants other than anti-platelet drugs in prior 28 days Active malignancy, history of malignancy within prior 10 years (limited exceptions) or known first degree relative with a hereditary cancer syndrome unless the patient is known to be free of the predisposing genetic mutation Receipt of live vaccine or live therapeutic infectious agent within the 28 days prior to screening. Pregnancy, lactation, or planning to become pregnant or donate/retrieve eggs before the end of study follow-up. Hepatitis B or C infection, HIV infection, evidence of active TB or being at high risk for TB History of any severe herpes virus infection (including any history of severe Epstein-Barr virus, cytomegalovirus disease, end-organ disease, disseminated herpes simplex, disseminated zoster, or ophthalmic zoster) or > 1 episode of herpes zoster in the 2 years prior to screening and/or any opportunistic infection in the prior 2 years Infection requiring parenteral antimicrobial therapy within 60 days of screening or any clinically significant active or suspected infection ( within 28 days prior to screening History of anaphylaxis to any human immunoglobulin therapy or monoclonal antibody. Blood tests at screening (performed in the central laboratory) that meet study requirements including but not limited to normal coagulation testing and glomerular filtration rate < 50 mL/min/1.73 High risk for COVID-19 or for severe COVID-19

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VIB1116<br>Single dose of VIB1116, SC or IV administration. Multiple doses of VIB1116, SC administration. | Drug: VIB1116<br>* VIB1116<br>|
| Placebo Comparator: Placebo<br>Single dose of Placebo, SC or IV administration. Multiple doses of Placebo, SC administration. | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-emergent adverse events, treatment-emergent serious adverse events, and adverse events of special interest |  | Up to Day 141 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum concentration of VIB1116 and noncompartmental PK parameters |  | Up to Day 141 | 
| Change from baseline in the blood levels of plasmacytoid dendritic cells |  | Up to Day 141 | 
| Percentage of Participants who are ADA (antidrug antibody) positive |  | Up to Day 141 | 
| Titer in ADA positive participants |  | Up to Day 141 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autoimmune disease, Rheumatic disease, Phase 1