Systemic Lupus Erythematosus
Conditions
Keywords
Lupus, SLE, Biologics, Open-label, Monoclonal, Anti-CD19
Brief summary
The main objective is to assess the safety and tolerability of budoprutug in adults with SLE. Pharmacokinetics, pharmacodynamics, and preliminary clinical efficacy will also be assessed.
Detailed description
Budoprutug is a humanized, immunoglobulin (Ig) G1 monoclonal antibody that selectively binds to CD19 and is projected to deplete targeted cells through antibody-dependent cellular cytotoxicity. This Phase 1b, open-label study will evaluate budoprutug administered as a single intravenous infusion in ascending dose cohorts of patients aged 18 years and above with active, seropositive SLE and inadequate response to standard therapy. The study will also assess the pharmacokinetics, pharmacodynamics and early indications of efficacy of budoprutug in SLE, where pharmacodynamics will be evaluated as the change in the number of B cells and immunoglobulins (antibodies) in the blood over time following a single infusion.
Interventions
DRUGBudoprutug
Single IV dose of study product on Day 1 of study
Sponsors
Climb Bio, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is an open-label study in which subjects will be enrolled into four single-dose ascending cohorts. Each subject's participation will last approximately 198 days, including a 30-day screening period, a 1-day treatment period, and follow-up through Week 24.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Aged 18 to 65 years at the time of consent. 2. Diagnosis of SLE according to the 2019 European League Against. Rheumatism and the American College of Rheumatology (ACR) classification criteria. 3. Active, seropositive disease, with SLEDAI 2K \>=8. 4. Inadequate response to at least 2 therapeutic interventions, including at least one oral immunosuppressive or biologic standard-of care therapy.
Exclusion criteria
1. Active neuropsychiatric SLE. 2. History of inflammatory or autoimmune diseases including, but not limited to, rheumatoid arthritis, scleroderma, myositis, vasculitis, inflammatory bowel disease, or other conditions that require immune suppressive therapy. Subjects with stable concurrent Sjogren's, asthma, or autoimmune thyroid disease may be considered for participation. 3. Active systemic infection or history of chronic, recurrent, latent, or recent serious infections.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events (TEAEs) | Up to Week 24 | Number of participants experiencing TEAEs, graded per NCI CTCAE v5.0. |
| Incidence of Clinical Laboratory Abnormalities | Up to Week 24 | Number of participants with clinically significant laboratory abnormalities. |
| Change from Baseline in Systolic Blood Pressure | Up to Week 24 | Mean change from baseline in systolic blood pressure (mmHg). |
| Change from Baseline in Diastolic Blood Pressure | Up to Week 24 | Mean change from baseline in diastolic blood pressure (mmHg). |
| Change from Baseline in Heart Rate | Up to Week 24 | Mean change from baseline in heart rate (bpm). |
| Change from Baseline in Respiratory Rate | Up to Week 24 | Mean change from baseline in respiratory rate. |
| Change from Baseline in Body Temperature | Up to Week 24 | Mean change from baseline in body temperature (°C). |
| Change from Baseline in PR Interval | Up to Week 24 | Mean change from baseline in PR interval (ms). |
| Change from Baseline in QRS Duration | Up to Week 24 | Mean change from baseline in QRS duration (ms). |
| Change from Baseline in QT Interval | Up to Week 24 | Mean change from baseline in QT interval (ms). |
| Change from Baseline in QTc Interval | Up to Week 24 | Mean change from baseline in corrected QT interval (QTc). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) of Budoprutug | Up to Week 24 | Measurement of the area under the drug concentration-time curve. |
| Maximum Observed Plasma Concentration (Cmax) | Up to Week 24 | Measurement of the maximum observed plasma concentration. |
| Time to Maximum Observed Concentration (Tmax) | Up to Week 24 | Measurement of the time to maximum observed concentration. |
| Terminal Half-Life (T1/2) | Up to Week 24 | Measurement of the terminal half-life in days. |
| Apparent Clearance (CL/F) of budoprutug | Up to Week 24 | Measurement of the apparent clearance in L/hour. |
| Volume of Distribution (Vd) | Up to Week 24 | Measurement of the volume of distribution in liters. |
| Change from Baseline in Circulating B Cell Count | Up to Week 24 | Change in absolute number of CD19+ B cells in peripheral blood. |
| Incidence of Anti-Drug Antibodies (ADAs) | Up to Week 24 | Number of participants with detectable ADAs. |
| ADA Titer Over Time | Up to Week 24 | Measurement of ADA titer over time. |
Countries
Bulgaria, Georgia, Greece, Puerto Rico, Romania, Spain, Ukraine, United States
Contacts
CONTACTClimb Bio Study Director
STUDY_DIRECTORStudy Director
Climb Bio, Inc.
Outcome results
None listed