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

• ClinicalTrials.gov Identifier: NCT04128579
• Recruitment Status: Recruiting
• First Posted: October 16, 2019
• Last Update Posted: October 16, 2019
• Sponsor: Equillium
• Collaborator: Biocon Limited
• Information provided by (Responsible Party): Equillium

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Lupus Erythematosus; Lupus Nephritis	Drug: Itolizumab [Bmab 600]; Drug: EQ001 Placebo	Phase 1

Detailed Description:

The study will enroll up to 56 subjects, with up to 4 dose escalating cohorts of either 6 open-label (Type A-SLE) or 8 double-blind (Type B-Lupus Nephritis) subjects (enrolled in a 3:1 ratio). Subjects will receive itolizumab (Type A) or blinded itolizumab or placebo (Type B) administered subcutaneously every two weeks for a total of either 2 or 7 doses with 4 or 12 weeks of follow-up after the last dose of investigational product.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: cohort based escalation of either 6 (Type A) or 8 (Type B) subjects
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Type A is open-label. For Type B, there will be a designated unblinded individual (e.g. pharmacist) for drug preparation. Relevant vendors including PK will be unblinded.
• Primary Purpose: Treatment
• Official Title: A Phase 1b Randomized, Double-blind, Placebo-controlled, Multiple Ascending-dose Study of EQ001 in Subjects With Systemic Lupus Erythematosus With or Without Active Proliferative Lupus Nephritis
• Actual Study Start Date: October 1, 2019
• Estimated Primary Completion Date: June 2021
• Estimated Study Completion Date: November 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: EQ001 Type A cohort; EQ001 administered in an unblinded dose escalating cohort fashion by subcutaneous injection every two weeks for a total of 2 doses (up to 4 cohorts with dosing to be determined in the range of 0.4 -- 2.4 mg/kg).	Drug: Itolizumab [Bmab 600]; EQ001; Other Names: Bmab600; Itolizumab
Experimental: EQ001 for Type B cohort; EQ001 administered in a blinded dose escalating cohort fashion by subcutaneous injection every two weeks for a total of 7 doses (up to 4 cohorts with dosing to be determined in the range of 0.4 -- 2.4 mg/kg).	Drug: Itolizumab [Bmab 600]; EQ001; Other Names: Bmab600; Itolizumab
Placebo Comparator: EQ001 Placebo for Type B cohort; Placebo administered in a blinded dose escalating cohort fashion by subcutaneous injection every two weeks for a total of 7 doses (up to 4 cohorts with dosing to be determined in the range of 0.4 -- 2.4 mg/kg).	Drug: EQ001 Placebo; EQ001 Placebo

Outcome Measures

Primary Outcome Measures :

1. Incidence of Treatment Emergent Adverse Events [ Time Frame: Type A Day 57 or Type B Day 169 ]
   Number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Secondary Outcome Measures :

1. Time to maximum EQ001 serum concentration, Tmax [ Time Frame: Type A Day 57 or Type B Day 169 ]
   Time to maximum EQ001 serum concentration, Tmax
2. Maximum EQ001 serum drug concentration, Cmax [ Time Frame: Type A Day 57 or Type B Day 169 ]
   Maximum EQ001 serum drug concentration, Cmax
3. Minimum EQ001 serum drug concentration, Cmin [ Time Frame: Type A Day 57 or Type B Day 169 ]
   Minimum EQ001 serum drug concentration, Cmin
4. Total EQ001 exposure across time, AUC (from zero to infinity) [ Time Frame: Type A Day 57 or Type B Day 169 ]
   Total EQ001 exposure across time, AUC (from zero to infinity)
5. Half life of EQ001, t1/2 [ Time Frame: Type A Day 57 or Type B Day 169 ]
   Half life of EQ001, t1/2
6. Volume of distribution of EQ001, Vd [ Time Frame: Type A Day 57 or Type B Day 169 ]
   Volume of distribution of EQ001, Vd
7. Clearance, Cl [ Time Frame: Type A Day 57 or Type B Day 169 ]
   Clearance, Cl
8. Inflammatory Markers [ Time Frame: Type A Day 57 or Type B Day 169 ]
   Including but not limited to: IL-1β, IL-2, IL-6, IL-17, IL-21, IL-22, IL-23, IFN-γ, and TGF-β, C-reactive protein
9. CD6 receptor occupancy [ Time Frame: Type A Day 57 or Type B Day 169 ]
   the % levels of free versus EQ001-bound CD6 receptor on T cells

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Type A Cohort Key Inclusion Criteria:

1. Is male or female, age ≥ 18 and ≤ 75 years
2. 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
3. Received at least 1 immunosuppressive or immunomodulatory treatment for SLE at any time in the past or currently
4. Has documented elevation of antinuclear antibodies (ANA) in the past or during Screening
5. Restricted SLE treatments are stable and/or washed out
6. During Screening, has adequate hematologic function

Type B Cohort Key Inclusion Criteria:

1. Is male or female, age ≥ 18 and ≤ 75 years
2. Meets SLICC and/or ACR criteria for SLE
3. Kidney biopsy with a histologic diagnosis of LN Classes III or IV (+/- V)
4. Has a urine protein to creatinine ratio of > 1000 mg/g

5. Meets criterion a and/or b

   1. Has previously completed induction treatment for active proliferative LN and is currently receiving one of the following: mycophenolate mofetil (MMF), mycophenolic acid (MPA), azathioprine or a calcineurin inhibitor.
   2. Has been receiving induction treatment with MMF/MPA and has a < 50% reduction in proteinuria at or after 12 weeks of induction
6. During Screening has adequate hematologic function
7. Restricted SLE treatments are stable and/or washed out
8. Most recent eGFR ≥ 40 mL/min/1.73m2
9. Has evidence of serologic activity during Screening

Key Exclusion Criteria:

1. Acute or chronic infections requiring systemic antibacterial, antifungal, or antiviral therapy
2. Positive for hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV
3. Active TB or a positive TB test

Contacts and Locations

Contacts

Contact: Catherine Kim; 858 412 5302; clinicaltrials@equilliumbio.com

Locations

United States, Florida

Clinical Research of West Florida - Clearwater; Recruiting

Clearwater, Florida, United States, 33765-2616

SouthCoast Research Center Inc; Recruiting

Miami, Florida, United States, 33136

Hope Clinical Trials; Recruiting

Miami, Florida, United States, 33165

Clinical Research of West Florida - Tampa; Recruiting

Tampa, Florida, United States, 33603

Sponsors and Collaborators

Equillium

Biocon Limited

Investigators

• Principal Investigator: Kenneth Kalunian, MD; UCSD

More Information

Additional Information:

company website 

• Responsible Party: Equillium
• ClinicalTrials.gov Identifier: NCT04128579
• Other Study ID Numbers: EQ001-19-002
• First Posted: October 16, 2019
• Last Update Posted: October 16, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Equillium:

Systemic Lupus Erythematosus; Active Proliferative Lupus Nephritis

Additional relevant MeSH terms:

Nephritis; Lupus Nephritis; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Kidney Diseases; Urologic Diseases; Glomerulonephritis