Lupus Erythematosus, Lupus Nephritis
Conditions
Keywords
Systemic Lupus Erythematosus, Active Proliferative Lupus Nephritis
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
Detailed description
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.
Interventions
DRUGItolizumab [Bmab 600]
EQ001
Sponsors
Biocon Limited
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Type A and Type B are open-label.
Intervention model description
cohort based escalation of 6 subjects (Type A) single dose cohort of 20 subjects (Type B)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion 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. Has a diagnosis of 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. Requires induction treatment due to newly diagnosed LN or relapsing/flaring disease or has an incomplete response to current treatment 6. 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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment Emergent Adverse Events | Type A up to Day 57 or Type B up to Day 253 | Number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Characterize the PK of Itolizumab | Type A up to Day 57 or Type B up to Day 253 | To characterize the pharmacokinetics of itolizumab |
| CD6 Receptor Occupancy | Type A up to Day 57 or Type B up to Day 253 | the % levels of free versus EQ001-bound CD6 receptor on T cells |
Countries
India, Poland, United States
Contacts
PRINCIPAL_INVESTIGATORKenneth Kalunian, MD
UCSD
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| EQ001 Type A Cohort (0.4mg/kg) EQ001 administered in an unblinded dose escalating cohort fashion by subcutaneous injection every two weeks for a total of 2 doses - 0.4mg/kg.
Itolizumab \[Bmab 600\]: EQ001 | 6 |
| EQ001 for Type B Cohort EQ001 administered in an unblinded single dose cohort by subcutaneous injection every two weeks for a total of 13 doses (1.6 mg/kg).
Itolizumab \[Bmab 600\]: EQ001 | 17 |
| EQ001 Type A Cohort (0.8mg/kg) EQ001 administered in an unblinded dose escalating cohort fashion by subcutaneous injection every two weeks for a total of 2 doses - 0.8mg/kg.
Itolizumab \[Bmab 600\]: EQ001 | 7 |
| EQ001 Type A Cohort (1.6mg/kg) EQ001 administered in an unblinded dose escalating cohort fashion by subcutaneous injection every two weeks for a total of 2 doses - 1.6mg/kg.
Itolizumab \[Bmab 600\]: EQ001 | 7 |
| EQ001 Type A Cohort (2.4mg/kg) EQ001 administered in an unblinded dose escalating cohort fashion by subcutaneous injection every two weeks for a total of 2 doses - 2.4mg/kg.
Itolizumab \[Bmab 600\]: EQ001 | 6 |
| EQ001 Type A Cohort (3.2mg/kg) EQ001 administered in an unblinded dose escalating cohort fashion by subcutaneous injection every two weeks for a total of 2 doses - 3.2mg/kg.
Itolizumab \[Bmab 600\]: EQ001 | 9 |
| Total | 52 |
Baseline characteristics
| Characteristic | EQ001 Type A Cohort (0.4mg/kg) | Total | EQ001 Type A Cohort (3.2mg/kg) | EQ001 Type A Cohort (2.4mg/kg) | EQ001 Type A Cohort (1.6mg/kg) | EQ001 Type A Cohort (0.8mg/kg) | EQ001 for Type B Cohort |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 59.5 years STANDARD_DEVIATION 12.94 | 45.3 years STANDARD_DEVIATION 14.52 | 55.0 years STANDARD_DEVIATION 11.09 | 48.2 years STANDARD_DEVIATION 11.63 | 47.1 years STANDARD_DEVIATION 6.82 | 44.6 years STANDARD_DEVIATION 16.2 | 33.8 years STANDARD_DEVIATION 11.18 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 17 Participants | 0 Participants | 4 Participants | 3 Participants | 5 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 35 Participants | 9 Participants | 2 Participants | 4 Participants | 2 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 14 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 14 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 9 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 29 Participants | 7 Participants | 5 Participants | 6 Participants | 5 Participants | 3 Participants |
| Region of Enrollment India | 0 participants | 12 participants | 0 participants | 0 participants | 0 participants | 0 participants | 12 participants |
| Region of Enrollment United States | 6 participants | 40 participants | 9 participants | 6 participants | 7 participants | 7 participants | 5 participants |
| Sex: Female, Male Female | 6 Participants | 49 Participants | 8 Participants | 6 Participants | 6 Participants | 7 Participants | 16 Participants |
| Sex: Female, Male Male | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 17 | 0 / 7 | 0 / 7 | 0 / 6 | 0 / 9 |
| other Total, other adverse events | 0 / 6 | 17 / 17 | 2 / 7 | 4 / 7 | 3 / 6 | 8 / 9 |
| serious Total, serious adverse events | 0 / 6 | 2 / 17 | 0 / 7 | 0 / 7 | 0 / 6 | 1 / 9 |
Outcome results
Primary
Number 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.
Time frame: Type A up to Day 57 or Type B up to Day 253
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EQ001 Type A Cohort (0.4mg/kg) | Number of Treatment Emergent Adverse Events | 0 Participants |
| EQ001 for Type B Cohort | Number of Treatment Emergent Adverse Events | 17 Participants |
| EQ001 Type A Cohort (0.8mg/kg) | Number of Treatment Emergent Adverse Events | 2 Participants |
| EQ001 Type A Cohort (1.6mg/kg) | Number of Treatment Emergent Adverse Events | 4 Participants |
| EQ001 Type A Cohort (2.4mg/kg) | Number of Treatment Emergent Adverse Events | 3 Participants |
| EQ001 Type A Cohort (3.2mg/kg) | Number of Treatment Emergent Adverse Events | 8 Participants |
Secondary
CD6 Receptor Occupancy
the % levels of free versus EQ001-bound CD6 receptor on T cells
Time frame: Type A up to Day 57 or Type B up to Day 253
Secondary
To Characterize the PK of Itolizumab
To characterize the pharmacokinetics of itolizumab
Time frame: Type A up to Day 57 or Type B up to Day 253