Lupus Erythematosus, Systemic
Conditions
Keywords
Systemic lupus erythematosus, SLE, MEDI-570
Brief summary
The purpose of this study is to evaluate the safety and tolerability of MEDI-570 in adult subjects with moderately to severely active systemic lupus erythematosus (SLE).
Detailed description
This is a Phase 1, double-blind, randomized, placebo-controlled study to evaluate the safety and tolerability of escalating single subcutaneous doses of MEDI-570 in adult subjects with moderately to severely active SLE.
Interventions
OTHERPlacebo
A single double-blind dose of placebo matched to MEDI-570 subcutaneous injection on Day 1.
BIOLOGICALMEDI-570 0.03 MG
A single open-label dose of MEDI-570, 0.03 milligram (mg) subcutaneous injection on Day 1.
BIOLOGICALMEDI-570 0.1 MG
A single open-label dose of MEDI-570, 0.1 mg subcutaneous injection on Day 1.
BIOLOGICALMEDI-570 0.3 MG
A single double-blind dose of MEDI-570, 0.3 mg subcutaneous injection on Day 1.
BIOLOGICALMEDI-570 1 MG
A single double-blind dose of MEDI-570, 1 mg subcutaneous injection on Day 1.
Sponsors
AstraZeneca
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Meet or have met at least 4 of the 11 revised American College of Rheumatology (ACR) classification criteria for systemic lupus erythematosus (SLE) * Score greater than or equal to (\>=) 6 points on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) at Screening * Ability to complete the study period, including follow-up period through Day 169 * Willingness to forego other forms of experimental treatment during the study.
Exclusion criteria
* History of cancer except basal cell carcinoma treated with apparent success with curative therapy \>=1 year before randomization into the study * Evidence of active or latent tuberculosis (TB) * History of primary immunodeficiency * Evidence of infection at any time with hepatitis B or C virus or human immunodeficiency virus (HIV)-1 or HIV-2, or active infection with hepatitis A, as determined by results of testing at Screening * History of sepsis or serious, recurrent, chronic infection, current signs and symptoms of clinically significant chronic infection, or recent (within 6 months before Baseline visit) serious infection * Any history or evidence of opportunistic infection within 6 months of Screening including severe cytomegalovirus (CMV) or herpetic infections (such as disseminated herpes, herpes encephalitis, ophthalmic herpes) * Receipt of cyclophosphamide (intravenous or oral) within 6 months of Screening * Have any absolute contraindications to skin punch biopsies, for example, a history of coagulation disorders.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Day 1 to Day 169 | An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between administration of study drug and Day 169 that were absent before treatment or that worsened relative to pretreatment state. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameters for MEDI-570 | Predose and postdose on Day 1; Day 3, 5, 8, 15, 29, 57, 85, 113, 141, and 169 | Following pharmacokinetic parameters were to be evaluated by using non-compartmental analysis: t1/2 = terminal phase elimination half-life which is the time measured for the serum concentration to decrease by one half; tmax = time to maximum observed serum concentration; Cmax = maximum observed serum concentration; AUC (0-t) = area under the serum concentration-time curve from time 0 to last measurable concentration; AUC (0-infinity) = area under the serum concentration-time curve from time 0 to extrapolated infinite time obtained from AUC (0-t) plus AUC (t-infinity); Vz/F = apparent volume of distribution, which is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug; CL/F = apparent clearance which is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. |
| Number of Participants With Anti-Drug Antibodies to MEDI-570 at Any Visit | Predose on Day 1; Day 85, 113, and 169 | — |
Countries
Canada, Mexico, Peru, South Africa, United States
Participant flow
Pre-assignment details
Due to premature termination of the study, planned treatment cohorts, MEDI-570, 3 milligram (mg) and MEDI-570, 10 mg, were not administered. A total of 17 participants were randomized in the study. An additional 27 participants were screened but not randomized in the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo A single double-blind dose of placebo matched to MEDI-570 subcutaneous injection on Day 1. | 3 |
| MEDI-570 0.03 MG A single open-label dose of MEDI-570, 0.03 milligram (mg) subcutaneous injection on Day 1. | 1 |
| MEDI-570 0.1 MG A single open-label dose of MEDI-570, 0.1 mg subcutaneous injection on Day 1. | 1 |
| MEDI-570 0.3 MG A single double-blind dose of MEDI-570, 0.3 mg subcutaneous injection on Day 1. | 7 |
| MEDI-570 1 MG A single double-blind dose of MEDI-570, 1 mg subcutaneous injection on Day 1. | 5 |
| Total | 17 |
Baseline characteristics
| Characteristic | Placebo | MEDI-570 0.03 MG | MEDI-570 0.1 MG | MEDI-570 0.3 MG | MEDI-570 1 MG | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 38.3 years STANDARD_DEVIATION 10.6 | 49.0 years | 41.0 years | 35.6 years STANDARD_DEVIATION 22.2 | 39.6 years STANDARD_DEVIATION 13.8 | 38.4 years STANDARD_DEVIATION 16.1 |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 1 Participants | 6 Participants | 5 Participants | 16 Participants |
| Sex: Female, Male Male | 0 Participants | 0 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 1 / 1 | 1 / 1 | 7 / 7 | 5 / 5 |
| serious Total, serious adverse events | 0 / 3 | 0 / 1 | 1 / 1 | 2 / 7 | 0 / 5 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between administration of study drug and Day 169 that were absent before treatment or that worsened relative to pretreatment state.
Time frame: Day 1 to Day 169
Population: Safety population included all participants who were randomized into the study and received at least 1 dose of investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 3 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 participants |
| MEDI-570 0.03 MG | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 1 participants |
| MEDI-570 0.03 MG | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 participants |
| MEDI-570 0.1 MG | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 1 participants |
| MEDI-570 0.1 MG | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 1 participants |
| MEDI-570 0.3 MG | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 2 participants |
| MEDI-570 0.3 MG | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 7 participants |
| MEDI-570 1 MG | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 4 participants |
| MEDI-570 1 MG | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 participants |
Secondary
Number of Participants With Anti-Drug Antibodies to MEDI-570 at Any Visit
Time frame: Predose on Day 1; Day 85, 113, and 169
Population: Safety population included all participants who were randomized into the study and received at least 1 dose of investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Anti-Drug Antibodies to MEDI-570 at Any Visit | 0 participants |
| MEDI-570 0.03 MG | Number of Participants With Anti-Drug Antibodies to MEDI-570 at Any Visit | 0 participants |
| MEDI-570 0.1 MG | Number of Participants With Anti-Drug Antibodies to MEDI-570 at Any Visit | 0 participants |
| MEDI-570 0.3 MG | Number of Participants With Anti-Drug Antibodies to MEDI-570 at Any Visit | 1 participants |
| MEDI-570 1 MG | Number of Participants With Anti-Drug Antibodies to MEDI-570 at Any Visit | 1 participants |
Secondary
Pharmacokinetic Parameters for MEDI-570
Following pharmacokinetic parameters were to be evaluated by using non-compartmental analysis: t1/2 = terminal phase elimination half-life which is the time measured for the serum concentration to decrease by one half; tmax = time to maximum observed serum concentration; Cmax = maximum observed serum concentration; AUC (0-t) = area under the serum concentration-time curve from time 0 to last measurable concentration; AUC (0-infinity) = area under the serum concentration-time curve from time 0 to extrapolated infinite time obtained from AUC (0-t) plus AUC (t-infinity); Vz/F = apparent volume of distribution, which is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug; CL/F = apparent clearance which is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Time frame: Predose and postdose on Day 1; Day 3, 5, 8, 15, 29, 57, 85, 113, 141, and 169
Population: Due to early termination of the study, the results were reported as individual participant's listings but not statistically summarized.