Dose Ranging Study of Brentuximab Vedotin in Adults With Lupus

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of brentuximab vedotin in adults with active systemic lupus erythematosus (SLE).

Detailed Description
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Systemic lupus erythematosus (SLE) is a chronic, multisystem, disabling autoimmune condition, which predominantly affects women of childbearing years. Treatment options for SLE remain relatively limited. Regardless of the specific therapy chosen, the majority of patients continue to require long term immunomodulatory or cytotoxic therapy, resulting in long-term morbidity and mortality. Brentuximab vedotin is an antibody-drug conjugate (ADC) consisting of: 1) the chimeric immunoglobulin (Ig) G1 antibody cAC10, specific for human CD30, 2) the microtubule disrupting agent monomethyl auristatin E (MMAE), and 3) a protease-cleavable linker that covalently attaches MMAE to cAC10. Since CD30 and/or CD30-expressing immune cells may play significant key roles in the pathogenesis of SLE, brentuximab vedotin may be an efficacious therapy. This study intends to explore the potential for brentuximab vedotin as a therapy for SLE.

Official Title
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A Multi-center, Randomized, Double-blinded, Placebo-controlled, Multiple-ascending-dose Study of Brentuximab Vedotin in Adults With Active Systemic Lupus Erythematosus

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: Brentuximab vedotin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults ≥ 18 years Diagnosis of SLE for at least 6 months prior to screening Active SLE as indicated by SLE Disease Activity Index (SLEDAI) ≥ 4 at screening Must have failed a treatment for SLE after a trial of at least 3 months Exclusion Criteria: The subject has any serious health condition, which, in the opinion of the Investigator, would place the subject at undue risk from the study Subject has had recent serious or ongoing infection, or risk for serious infection Subject has a history of new or recurrent malignancy within the past 5 years The subject is pregnant and/or breastfeeding The subject fulfills diagnostic criteria for another rheumatic (overlap) disease that may confound clinical assessments in the study The subject has urgent, severe SLE disease activity, which, in the opinion of the Investigator, warrants immediate immunosuppressive therapy and would not be appropriate for the study

Ages Eligible for Study
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Minimum Age: 18 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: Brentuximab vedotin<br>4 dose groups | Drug: Brentuximab vedotin<br> <br> * Other names: ADCETRIS (brentuximab vedotin);|
| Placebo Comparator: Placebo<br>Matching placebo | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and Percentage of Subjects Having an Adverse Event (AE) | Any treatment-emergent adverse events (TEAEs), any drug-related TEAEs, any SAEs, treatment-related serious adverse events (SAE), deaths, adverse events (AEs) leading to study discontinuation, and number of patients experiencing Grade 1, 2, and 3 TEAEs. | Up to 127 days (9 weeks after final dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects Achieving an SRI Response at Day 85 | Assessment for response was made using data only for the visit of interest (Day 85), without regard for changes at prior on-treatment visits. SRI: SLE Responder Index; SLE: Systemic lupus erythematosus | 85 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lupus