Systemic Lupus Erythematosus
Conditions
Keywords
Japan, Phase2, Safety, Tolerability, Systemic Lupus Erythematosus, SLE, MEDI-546
Brief summary
The purpose of this study is to assess safety, tolerability, pharmacokinetics and pharmacodynamics of MEDI-546 in Japanese SLE patients.
Detailed description
A phase 2, multicenter, open-label, dose-escalation study to evaluate the safety and tolerability of intravenous dose of MEDI-546, a human monoclonal antibody directed against type I interferon receptor (IFNAR), in Japanese subjects with active systemic lupus erythematosus (SLE)
Interventions
DRUGMEDI-546
Stage I: 100 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks
Sponsors
MedImmune LLC
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Fulfils at least 4 of the 11 American College of Rheumatology (ACR) classification criteria for SLE. * Weight greater than or equal to 40.0 kg. * Diagnosis of pediatric or adult SLE with chronic disease activity requiring ongoing treatment or observation for ≥ 24 weeks prior to screening. * Currently receiving stable dose of oral prednisone and/or antimalarials/immunosuppressives. * Active moderate to severe SLE disease based on SLE disease activity score.
Exclusion criteria
* Active severe or unstable neuropsychiatric SLE. * Active severe SLE-driven renal disease or unstable renal disease. * Clinically significant active infection including ongoing and chronic infections. * Known history of a primary immunodeficiency or an underlying condition such as human immunodeficiency virus infection or splenectomy that predisposes the subject to infection. * Confirmed positive tests for hepatitis B or positive test for hepatitis C.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Summary of Adverse Events | Stage I (up to 48 weeks) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameters of MEDI-546 After Single Dose: Cmax | Pre-dose and within 30 minutes after end of infusion on Day 1, Days 2, 8, 15, and 22, and pre-dose on Day 29 | — |
| Pharmacokinetic Parameters of MEDI-546 After Single Dose: AUClast | Pre-dose and within 30 minutes after end of infusion on Day 1, Days 2, 8, 15, and 22, and pre-dose on Day 29 | — |
| Anti-drug Antibody (ADA) | Stage I (up to Week 48) | MEDI-546 antibody detection measured by electrochemiluminescence (ECL). |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MEDI-546 100 mg IV Stage I: 100 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks | 6 |
| MEDI-546 300 mg IV Stage I: 300 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks | 5 |
| MEDI-546 1000 mg IV Stage I: 1000 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 1000 mg IV, multiple doses once every 4 wks for 156 wks, the dose at Stage II was changed to 300 mg IV | 6 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Stage I | Withdrawal by Subject | 2 | 2 | 3 |
| Stage II | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | MEDI-546 100 mg IV | MEDI-546 300 mg IV | MEDI-546 1000 mg IV | Total |
|---|---|---|---|---|
| Age, Continuous | 43 years STANDARD_DEVIATION 12 | 34 years STANDARD_DEVIATION 11 | 37 years STANDARD_DEVIATION 10 | 38 years STANDARD_DEVIATION 11 |
| Sex/Gender, Customized Female | 6 male/female | 4 male/female | 6 male/female | 1 male/female |
| Sex/Gender, Customized Male | 0 male/female | 1 male/female | 0 male/female | 16 male/female |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 5 | 0 / 6 |
| other Total, other adverse events | 6 / 6 | 5 / 5 | 6 / 6 |
| serious Total, serious adverse events | 2 / 6 | 2 / 5 | 3 / 6 |
Outcome results
Primary
Overall Summary of Adverse Events
Time frame: Stage I (up to 48 weeks)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI-546 100 mg IV | Overall Summary of Adverse Events | Any AE of grade 3 or higher | 1 Participants |
| MEDI-546 100 mg IV | Overall Summary of Adverse Events | Any AE leading to discontinuation of IP | 2 Participants |
| MEDI-546 100 mg IV | Overall Summary of Adverse Events | Any SAE | 2 Participants |
| MEDI-546 100 mg IV | Overall Summary of Adverse Events | Any AE | 6 Participants |
| MEDI-546 100 mg IV | Overall Summary of Adverse Events | Any causally related AE | 5 Participants |
| MEDI-546 100 mg IV | Overall Summary of Adverse Events | Any other significant AE | 0 Participants |
| MEDI-546 100 mg IV | Overall Summary of Adverse Events | Any AE with outcome=death | 0 Participants |
| MEDI-546 300 mg IV | Overall Summary of Adverse Events | Any SAE | 2 Participants |
| MEDI-546 300 mg IV | Overall Summary of Adverse Events | Any AE | 5 Participants |
| MEDI-546 300 mg IV | Overall Summary of Adverse Events | Any AE of grade 3 or higher | 1 Participants |
| MEDI-546 300 mg IV | Overall Summary of Adverse Events | Any AE with outcome=death | 0 Participants |
| MEDI-546 300 mg IV | Overall Summary of Adverse Events | Any AE leading to discontinuation of IP | 1 Participants |
| MEDI-546 300 mg IV | Overall Summary of Adverse Events | Any other significant AE | 0 Participants |
| MEDI-546 300 mg IV | Overall Summary of Adverse Events | Any causally related AE | 4 Participants |
| MEDI-546 1000 mg IV | Overall Summary of Adverse Events | Any AE of grade 3 or higher | 1 Participants |
| MEDI-546 1000 mg IV | Overall Summary of Adverse Events | Any causally related AE | 4 Participants |
| MEDI-546 1000 mg IV | Overall Summary of Adverse Events | Any other significant AE | 0 Participants |
| MEDI-546 1000 mg IV | Overall Summary of Adverse Events | Any AE leading to discontinuation of IP | 1 Participants |
| MEDI-546 1000 mg IV | Overall Summary of Adverse Events | Any SAE | 3 Participants |
| MEDI-546 1000 mg IV | Overall Summary of Adverse Events | Any AE with outcome=death | 0 Participants |
| MEDI-546 1000 mg IV | Overall Summary of Adverse Events | Any AE | 6 Participants |
Secondary
Anti-drug Antibody (ADA)
MEDI-546 antibody detection measured by electrochemiluminescence (ECL).
Time frame: Stage I (up to Week 48)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI-546 100 mg IV | Anti-drug Antibody (ADA) | Positive | 1 Participants |
| MEDI-546 100 mg IV | Anti-drug Antibody (ADA) | Negative | 5 Participants |
| MEDI-546 300 mg IV | Anti-drug Antibody (ADA) | Positive | 1 Participants |
| MEDI-546 300 mg IV | Anti-drug Antibody (ADA) | Negative | 4 Participants |
| MEDI-546 1000 mg IV | Anti-drug Antibody (ADA) | Positive | 1 Participants |
| MEDI-546 1000 mg IV | Anti-drug Antibody (ADA) | Negative | 5 Participants |
Secondary
Pharmacokinetic Parameters of MEDI-546 After Single Dose: AUClast
Time frame: Pre-dose and within 30 minutes after end of infusion on Day 1, Days 2, 8, 15, and 22, and pre-dose on Day 29
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MEDI-546 100 mg IV | Pharmacokinetic Parameters of MEDI-546 After Single Dose: AUClast | 221.5 ug.day/mL | Geometric Coefficient of Variation 18.8 |
| MEDI-546 300 mg IV | Pharmacokinetic Parameters of MEDI-546 After Single Dose: AUClast | 666.5 ug.day/mL | Geometric Coefficient of Variation 36.8 |
| MEDI-546 1000 mg IV | Pharmacokinetic Parameters of MEDI-546 After Single Dose: AUClast | 3151.9 ug.day/mL | Geometric Coefficient of Variation 14.6 |
Secondary
Pharmacokinetic Parameters of MEDI-546 After Single Dose: Cmax
Time frame: Pre-dose and within 30 minutes after end of infusion on Day 1, Days 2, 8, 15, and 22, and pre-dose on Day 29
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MEDI-546 100 mg IV | Pharmacokinetic Parameters of MEDI-546 After Single Dose: Cmax | 41.1 ug/mL | Geometric Coefficient of Variation 27.6 |
| MEDI-546 300 mg IV | Pharmacokinetic Parameters of MEDI-546 After Single Dose: Cmax | 75.1 ug/mL | Geometric Coefficient of Variation 12.5 |
| MEDI-546 1000 mg IV | Pharmacokinetic Parameters of MEDI-546 After Single Dose: Cmax | 254.8 ug/mL | Geometric Coefficient of Variation 20.7 |