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: November 26, 2020
• 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]	Phase 1

Detailed Description:

The study will enroll up to 48 subjects, with up to 5 dose escalating cohorts of 6 open-label subjects enrolled for Type A-SLE and 3 dose escalating cohorts of 6 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: cohort based escalation of 6 subjects (Type A and Type B)
• Masking: None (Open Label)
• Masking Description: Type A and Type B are open-label.
• Primary Purpose: Treatment
• Official Title: A Phase 1b 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: March 2022
• Estimated Study Completion Date: August 2022

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 5 cohorts with dosing to be determined in the range of 0.4 -- 3.2 mg/kg).	Drug: Itolizumab [Bmab 600]; EQ001; Other Names: Bmab600; Itolizumab
Experimental: EQ001 for Type B cohort; EQ001 administered in an unblinded dose escalating cohort fashion by subcutaneous injection every two weeks for a total of 13 doses (up to 3 cohorts with dosing to be determined in the range of 0.8 -- 3.2 mg/kg).	Drug: Itolizumab [Bmab 600]; EQ001; Other Names: Bmab600; Itolizumab

Outcome Measures

Primary Outcome Measures :

1. Incidence of Treatment Emergent Adverse Events [ Time Frame: Type A Day 57 or Type B Day 253 ]
   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 253 ]
   Time to maximum EQ001 serum concentration, Tmax
2. Maximum EQ001 serum drug concentration, Cmax [ Time Frame: Type A Day 57 or Type B Day 253 ]
   Maximum EQ001 serum drug concentration, Cmax
3. Minimum EQ001 serum drug concentration, Cmin [ Time Frame: Type A Day 57 or Type B Day 253 ]
   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 253 ]
   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 253 ]
   Half life of EQ001, t1/2
6. Volume of distribution of EQ001, Vd [ Time Frame: Type A Day 57 or Type B Day 253 ]
   Volume of distribution of EQ001, Vd
7. Clearance, Cl [ Time Frame: Type A Day 57 or Type B Day 253 ]
   Clearance, Cl
8. Inflammatory Markers [ Time Frame: Type A Day 57 or Type B Day 253 ]
   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 253 ]
   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, California

University of California San Diego Perlman Ambulatory Clinic; Not yet recruiting

La Jolla, California, United States, 92037

United States, Florida

Clinical Research of West Florida - Clearwater; Recruiting

Clearwater, Florida, United States, 33765-2616

Centre for Rheumatology, Immunology and Arthritis; Active, not recruiting

Fort Lauderdale, Florida, United States, 33309

SouthCoast Research Center Inc; Recruiting

Miami, Florida, United States, 33136

Hope Clinical Trials; Recruiting

Miami, Florida, United States, 33165

Omega Research Maitland, LLC; Recruiting

Orlando, Florida, United States, 32810

Clinical Research of West Florida - Tampa; Recruiting

Tampa, Florida, United States, 33603

United States, Georgia

Georgia Nephrology; Not yet recruiting

Lawrenceville, Georgia, United States, 30046

United States, New York

Albert Einstein College of Medicine, Montefiore Medical Center; Active, not recruiting

Bronx, New York, United States, 10461

Northwell Health / Division of Rheumatology; Not yet recruiting

Great Neck, New York, United States, 11021

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: November 26, 2020
• Last Verified: November 2020

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