Systemic Lupus Erythematosus
Conditions
Keywords
Lupus
Brief summary
The purpose of this study is to evaluate the safety and tolerability of brentuximab vedotin in adults with active systemic lupus erythematosus (SLE).
Detailed description
Systemic lupus erythematosus (SLE) is a chronic, multisystem, disabling autoimmune condition, which predominantly affects women of childbearing years. Treatment options for SLE remain relatively limited. Regardless of the specific therapy chosen, the majority of patients continue to require long term immunomodulatory or cytotoxic therapy, resulting in long-term morbidity and mortality. Brentuximab vedotin is an antibody-drug conjugate (ADC) consisting of: 1) the chimeric immunoglobulin (Ig) G1 antibody cAC10, specific for human CD30, 2) the microtubule disrupting agent monomethyl auristatin E (MMAE), and 3) a protease-cleavable linker that covalently attaches MMAE to cAC10. Since CD30 and/or CD30-expressing immune cells may play significant key roles in the pathogenesis of SLE, brentuximab vedotin may be an efficacious therapy. This study intends to explore the potential for brentuximab vedotin as a therapy for SLE.
Interventions
DRUGBrentuximab vedotin
DRUGPlacebo
Sponsors
Seagen Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults ≥ 18 years * Diagnosis of SLE for at least 6 months prior to screening * Active SLE as indicated by SLE Disease Activity Index (SLEDAI) ≥ 4 at screening * Must have failed a treatment for SLE after a trial of at least 3 months
Exclusion criteria
* The subject has any serious health condition, which, in the opinion of the Investigator, would place the subject at undue risk from the study * Subject has had recent serious or ongoing infection, or risk for serious infection * Subject has a history of new or recurrent malignancy within the past 5 years * The subject is pregnant and/or breastfeeding * The subject fulfills diagnostic criteria for another rheumatic (overlap) disease that may confound clinical assessments in the study * The subject has urgent, severe SLE disease activity, which, in the opinion of the Investigator, warrants immediate immunosuppressive therapy and would not be appropriate for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number and Percentage of Subjects Having an Adverse Event (AE) | Up to 127 days (9 weeks after final dose) | Any treatment-emergent adverse events (TEAEs), any drug-related TEAEs, any SAEs, treatment-related serious adverse events (SAE), deaths, adverse events (AEs) leading to study discontinuation, and number of patients experiencing Grade 1, 2, and 3 TEAEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Achieving an SRI Response at Day 85 | 85 days | Assessment for response was made using data only for the visit of interest (Day 85), without regard for changes at prior on-treatment visits. SRI: SLE Responder Index; SLE: Systemic lupus erythematosus |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Intravenous (IV) placebo every 3 weeks for a total of 4 doses | 4 |
| Brentuximab Vedotin 0.3 mg/kg Intravenous (IV) Brentuximab vedotin (0.3 mg/kg) every 3 weeks for a total of 4 doses | 8 |
| Brentuximab Vedotin 0.6 mg/kg Intravenous (IV) Brentuximab vedotin (0.6 mg/kg) every 3 weeks for a total of 4 doses | 8 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Brentuximab Vedotin 0.3 mg/kg | Brentuximab Vedotin 0.6 mg/kg | Total |
|---|---|---|---|---|
| Age, Continuous | 45.5 years STANDARD_DEVIATION 8.66 | 50.8 years STANDARD_DEVIATION 14.06 | 45.0 years STANDARD_DEVIATION 11.2 | 47.4 years STANDARD_DEVIATION 11.78 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 8 Participants | 5 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 5 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 6 Participants | 3 Participants | 12 Participants |
| Region of Enrollment United States | 4 Participants | 8 Participants | 8 Participants | 20 Participants |
| Sex: Female, Male Female | 4 Participants | 8 Participants | 8 Participants | 20 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 3 / 4 | 6 / 8 | 8 / 8 |
| serious Total, serious adverse events | 0 / 4 | 1 / 8 | 1 / 8 |
Outcome results
Primary
Number and Percentage of Subjects Having an Adverse Event (AE)
Any treatment-emergent adverse events (TEAEs), any drug-related TEAEs, any SAEs, treatment-related serious adverse events (SAE), deaths, adverse events (AEs) leading to study discontinuation, and number of patients experiencing Grade 1, 2, and 3 TEAEs.
Time frame: Up to 127 days (9 weeks after final dose)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number and Percentage of Subjects Having an Adverse Event (AE) | Treatment-Related Serious Adverse Events | 0 Participants |
| Placebo | Number and Percentage of Subjects Having an Adverse Event (AE) | Any Grade 3 Adverse Event | 0 Participants |
| Placebo | Number and Percentage of Subjects Having an Adverse Event (AE) | Adverse Events Leading to Study Discontinuation | 0 Participants |
| Placebo | Number and Percentage of Subjects Having an Adverse Event (AE) | Deaths | 0 Participants |
| Placebo | Number and Percentage of Subjects Having an Adverse Event (AE) | Treatment-Emergent Adverse Event | 3 Participants |
| Placebo | Number and Percentage of Subjects Having an Adverse Event (AE) | Any Grade 2 Adverse Event | 2 Participants |
| Placebo | Number and Percentage of Subjects Having an Adverse Event (AE) | Serious Adverse Event | 0 Participants |
| Placebo | Number and Percentage of Subjects Having an Adverse Event (AE) | Treatment-Related Adverse Event | 0 Participants |
| Placebo | Number and Percentage of Subjects Having an Adverse Event (AE) | Any Grade 1 Adverse Event | 2 Participants |
| Brentuximab Vedotin 0.3 mg/kg | Number and Percentage of Subjects Having an Adverse Event (AE) | Deaths | 0 Participants |
| Brentuximab Vedotin 0.3 mg/kg | Number and Percentage of Subjects Having an Adverse Event (AE) | Treatment-Emergent Adverse Event | 6 Participants |
| Brentuximab Vedotin 0.3 mg/kg | Number and Percentage of Subjects Having an Adverse Event (AE) | Treatment-Related Adverse Event | 3 Participants |
| Brentuximab Vedotin 0.3 mg/kg | Number and Percentage of Subjects Having an Adverse Event (AE) | Serious Adverse Event | 1 Participants |
| Brentuximab Vedotin 0.3 mg/kg | Number and Percentage of Subjects Having an Adverse Event (AE) | Treatment-Related Serious Adverse Events | 1 Participants |
| Brentuximab Vedotin 0.3 mg/kg | Number and Percentage of Subjects Having an Adverse Event (AE) | Adverse Events Leading to Study Discontinuation | 1 Participants |
| Brentuximab Vedotin 0.3 mg/kg | Number and Percentage of Subjects Having an Adverse Event (AE) | Any Grade 1 Adverse Event | 6 Participants |
| Brentuximab Vedotin 0.3 mg/kg | Number and Percentage of Subjects Having an Adverse Event (AE) | Any Grade 2 Adverse Event | 4 Participants |
| Brentuximab Vedotin 0.3 mg/kg | Number and Percentage of Subjects Having an Adverse Event (AE) | Any Grade 3 Adverse Event | 1 Participants |
| Brentuximab Vedotin 0.6 mg/kg | Number and Percentage of Subjects Having an Adverse Event (AE) | Serious Adverse Event | 1 Participants |
| Brentuximab Vedotin 0.6 mg/kg | Number and Percentage of Subjects Having an Adverse Event (AE) | Treatment-Emergent Adverse Event | 8 Participants |
| Brentuximab Vedotin 0.6 mg/kg | Number and Percentage of Subjects Having an Adverse Event (AE) | Any Grade 1 Adverse Event | 2 Participants |
| Brentuximab Vedotin 0.6 mg/kg | Number and Percentage of Subjects Having an Adverse Event (AE) | Treatment-Related Adverse Event | 1 Participants |
| Brentuximab Vedotin 0.6 mg/kg | Number and Percentage of Subjects Having an Adverse Event (AE) | Any Grade 3 Adverse Event | 2 Participants |
| Brentuximab Vedotin 0.6 mg/kg | Number and Percentage of Subjects Having an Adverse Event (AE) | Deaths | 0 Participants |
| Brentuximab Vedotin 0.6 mg/kg | Number and Percentage of Subjects Having an Adverse Event (AE) | Treatment-Related Serious Adverse Events | 0 Participants |
| Brentuximab Vedotin 0.6 mg/kg | Number and Percentage of Subjects Having an Adverse Event (AE) | Any Grade 2 Adverse Event | 7 Participants |
| Brentuximab Vedotin 0.6 mg/kg | Number and Percentage of Subjects Having an Adverse Event (AE) | Adverse Events Leading to Study Discontinuation | 1 Participants |
Secondary
Proportion of Subjects Achieving an SRI Response at Day 85
Assessment for response was made using data only for the visit of interest (Day 85), without regard for changes at prior on-treatment visits. SRI: SLE Responder Index; SLE: Systemic lupus erythematosus
Time frame: 85 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Proportion of Subjects Achieving an SRI Response at Day 85 | 0 Participants |
| Brentuximab Vedotin 0.3 mg/kg | Proportion of Subjects Achieving an SRI Response at Day 85 | 1 Participants |
| Brentuximab Vedotin 0.6 mg/kg | Proportion of Subjects Achieving an SRI Response at Day 85 | 2 Participants |