PRV-3279-2a Trial in Systemic Lupus

Study Overview
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Brief Summary
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The PREVAIL-2 study is designed to assess the safety and potential efficacy of PRV-3279 in flare prevention in systemic lupus erythematosus (SLE) patients with active disease after amelioration induced by corticosteroid treatment.

Detailed Description
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This is a randomized, double-blind, placebo-controlled study in adult patients with active SLE. Approximately 100 eligible patients will be randomized at a 1:1 ratio to receive treatment with either PRV-3279 or placebo. Eligible subjects include male or female adults, 18 to 70 years of age, with a diagnosis of SLE for at least 6 months. The study drug will be administered every 4 weeks for 20 weeks in a double-blind fashion, followed by an 8-week safety follow-up period.

Official Title
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Phase 2a, Randomized, Double-blind, Placebo-controlled Trial of PRV-3279 EVAluation In Lupus (PREVAIL-2)

Conditions
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Efficacy and Safety

Intervention / Treatment
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* Biological: PRV-3279
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A diagnosis of SLE for at least 6 months prior to the Screening visit Meet the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria for SLE at Screening Have moderate to severe disease activity despite stable standard-of-care medication defined as: At screening: hSLEDAI score ≥6 (≥4 points of which must come from non-serological finding), OR at least one BILAG A or one B score; At randomization: ≥4-point drop in hSLEDAI, OR one BILAG letter grade improvement in at least one A or B score present at Screening, and investigator or central adjudication committee (CAC) rating of definite improvement or major or complete improvement Able and willing to stop all lupus treatments, except antimalarials, corticosteroids (prednisone equivalent ≤ 10 mg), and NSAIDs Exclusion Criteria: Active lupus nephritis or active central nervous system manifestations of SLE Other inflammatory or autoimmune diseases that, in the opinion of the Investigator or CAC, may confound efficacy evaluations Common variable immunodeficiency syndrome or any other clinically significant immunodeficiency Known COVID-19 infection in the 4 weeks before Screening or positive SARS-CoV-2 RNA test Received a live attenuated vaccine within 2 months of Screening, received a non-live or mRNA vaccine within 2 weeks of Screening, or expecting to receive any vaccine during the study period Any recent infection requiring antibiotics within two weeks of Screening or any recent infection requiring IV antibiotics or hospitalization within 1 month of Screening Any condition for which, in the opinion of the Investigator or CAC, participation in the study would not be in the best interest of the patient (e.g., compromise their well-being) or that could prevent, limit, or confound the protocol-specified assessments Participated in any interventional clinical trial within 42 days prior to Screening or within five half-lives of the investigational product, whichever is longer Received rituximab or equivalent treatment that depletes B cells within 6 months of Screening unless return of B cells to pre-treatment value or normal range can be demonstrated. Received tumor necrosis factor inhibitors, interleukin antagonists, or other biologics, including belimumab, within 42 days or five half-lives of the agent, whichever is longer. Received IV immunoglobulin (IVIG) or IV cyclophosphamide within 2 months, prednisone ≥ 100 mg/day for more than 30 days within 2 months, or plasmapheresis within two months of the Screening visit.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRV-3279<br>Sterile solution for intravenous administration, every 4 weeks | Biological: PRV-3279<br>* Bi-specific antibody-based molecule<br>|
| Experimental: Placebo<br>Sterile solution for intravenous administration, every 4 weeks | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the ability of PRV-3279 to prevent flare, defined by LFA international consensus definition of flare, worsening on CGIC, and increase in hSLEDAI/BILAG scores | A flare is defined according to LFA international consensus definition of flare, worsening on Clinician's Global Impression of Change (CGIC), increases in hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI)/British Isles Lupus Assessment Group (BILAG) Index scores | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate whether PRV-3279 prolongs the duration of disease amelioration induced by corticosteroids | Time to treatment failure | 24 weeks | 
| To evaluate the safety of PRV-3279 | Frequency of TEAEs, SAEs, TEAEs leading to drug withdrawal, AESIs | 32 weeks |