Study of EQ001 (Itolizumab) in Systemic Lupus Erythematosus With or Without Active Proliferative Nephritis

Study Overview
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Brief Summary
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This is a multi-center study to evaluate the safety, tolerability, PK, PD, and clinical activity of itolizumab (EQ001) in subjects with Systemic Lupus Erythematosus with or without Active Proliferative Lupus Nephritis

Detailed Description
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The study will enroll approximately 55 subjects, with up to 5 dose escalating cohorts of 6 open-label subjects enrolled for Type A-SLE and a single dose cohort of approximately 20 open-label subjects enrolled for Type B-Lupus Nephritis. Subjects will receive itolizumab administered subcutaneously every two weeks for a total of either 2 (Type A) or 13 (Type B) doses with 4 or 12 weeks of follow-up after the last dose of investigational product.

Official Title
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A Phase 1b Multiple Ascending-dose Study of EQ001 in Subjects With Systemic Lupus Erythematosus With or Without Active Proliferative Lupus Nephritis

Conditions
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Lupus Erythematosus, Lupus Nephritis

Intervention / Treatment
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* Drug: Itolizumab [Bmab 600]


Participation Criteria
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Eligibility Criteria
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Type A Cohort Key Inclusion Criteria: Is male or female, age ≥ 18 and ≤ 75 years Has previously been documented to have met or currently meets Systemic Lupus International Collaborating Clinics (SLICC) and/or American College of Rheumatology (ACR) criteria for SLE Received at least 1 immunosuppressive or immunomodulatory treatment for SLE at any time in the past or currently Has documented elevation of antinuclear antibodies (ANA) in the past or during Screening Restricted SLE treatments are stable and/or washed out During Screening, has adequate hematologic function Type B Cohort Key Inclusion Criteria: Is male or female, age ≥ 18 and ≤ 75 years Has a diagnosis of SLE Kidney biopsy with a histologic diagnosis of LN Classes III or IV (+/- V) Has a urine protein to creatinine ratio of > 1000 mg/g Requires induction treatment due to newly diagnosed LN or relapsing/flaring disease or has an incomplete response to current treatment Has adequate hematologic function Restricted SLE treatments are stable and/or washed out Most recent eGFR ≥ 40 mL/min/1.73m2 Has evidence of serologic activity Key Exclusion Criteria: Acute or chronic infections requiring systemic antibacterial, antifungal, or antiviral therapy Positive for hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV Active TB or a positive TB test

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: cohort based escalation of 6 subjects (Type A) single dose cohort of 20 subjects (Type B)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EQ001 Type A cohort<br>EQ001 administered in an unblinded dose escalating cohort fashion by subcutaneous injection every two weeks for a total of 2 doses (up to 5 cohorts with dosing to be determined in the range of 0.4 -- 3.2 mg/kg). | Drug: Itolizumab [Bmab 600]<br>* EQ001<br>* Other names: Itolizumab;|
| Experimental: EQ001 for Type B cohort<br>EQ001 administered in an unblinded single dose cohort by subcutaneous injection every two weeks for a total of 13 doses (1.6 mg/kg). | Drug: Itolizumab [Bmab 600]<br>* EQ001<br>* Other names: Itolizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Emergent Adverse Events | Number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. | Type A up to Day 57 or Type B up to Day 253 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To characterize the PK of itolizumab | To characterize the pharmacokinetics of itolizumab | Type A up to Day 57 or Type B up to Day 253 | 
| CD6 receptor occupancy | the % levels of free versus EQ001-bound CD6 receptor on T cells | Type A up to Day 57 or Type B up to Day 253 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic Lupus Erythematosus, Active Proliferative Lupus Nephritis