Systemic Lupus Erythematosus
Conditions
Keywords
Lupus, Healthy Volunteer, Safety Study, Placebo Control, Phase 1
Brief summary
The purpose of this study is to obtain initial information on the safety and tolerability (effects good or bad), pharmacokinetics (what the body does to the drug), and pharmacodynamics (what the drug does to the body) of a single dose of AMG 570.
Interventions
BIOLOGICALAMG 570
7 dose levels of AMG 570 administered as single dose subcutaneous in healthy volunteers.
BIOLOGICALAMG 570 Matching Placebo
Placebo administered as single dose subcutaneous in healthy volunteers.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy as determined by the investigator * Normal or clinically acceptable electrocardiogram (ECG) * Female subjects must be of documented non-reproductive potential * Subjects must be current for all vaccinations * Other inclusion criteria may apply
Exclusion criteria
* Current or chronic history of liver disease * History of active infections * History of significant respiratory disorder * Evidence of renal disease * Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Day 1 to Day 105 | TEAEs were adverse events with an onset after the administration of study treatment. TEAEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limited age appropriate instrumental activities of daily life (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolonged hospitalization indicated; disabling; limited self care ADL. Grade 4 Life-threatening consequences; urgent interventions indicated. Serious adverse events (SAEs) were defined as meeting at least 1 of the following criteria: * Results in death (fatal) * Immediately life-threatening * Requires in-patient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability/incapacity * Is a congenital anomaly/birth defect * Other medically important serious event |
| Number of Participants Who Experienced a Clinically Significant Change in Physical Examinations | Baseline to Day 105 | Physical examinations were performed by the investigator, designated physician, or nurse practitioner. A complete physical examination included, at a minimum, assessment of cardiovascular, respiratory, gastrointestinal and neurological systems. A brief physical examination included assessment of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). |
| Number of Participants Who Experienced a Clinically Significant Change in Vital Signs | Baseline to Day 105 | Any changes in blood pressure, body temperature, heart rate, and pulse rate that were deemed as clinically significant by the Investigator were reported. |
| Number of Participants Who Experienced a Clinically Significant Change in Clinical Laboratory Safety Tests | Baseline to Day 105 | Laboratory safety tests included chemistry, hematology, and urinalysis parameters. Clinically significant laboratory safety tests were any events assessed as CTCAE Grade ≥3 at any post-baseline visit. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolonged hospitalization indicated; disabling; limited self care ADL. Grade 4 Life-threatening consequences; urgent interventions indicated. |
| Number of Participants Who Experienced a Clinically Significant Change in Electrocardiograms (ECGs) | Baseline to Day 105 | Any changes in ECG parameters that were deemed clinically significant by the Investigator were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 8; Day 29; Day 57; and Day 105 | Peripheral B7RP1 (also known as inducible costimulator ligand \[ICOSL\]) receptor occupancy was calculated from the free ICOSL and total ICOSL measurement from B cells in whole blood. |
| Maximum Observed Concentration (Cmax) of AMG 570 | Pre-dose and 12 hours post-dose on Day 1 and days 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 57, 71 and 105 | AMG 570 pharmacokinetic (PK) parameters were estimated using non-compartmental analysis. |
| Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Baseline to Day 8; Day 29; Day 57 and Day 105 | — |
| Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Baseline to Day 8; Day 29; Day 57 and Day 105 | — |
| Time to Reach Maximum Observed Concentration (Tmax) of AMG 570 | Pre-dose and 12 hours post-dose on Day 1 and days 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 57, 71 and 105 | AMG 570 PK parameters were estimated using non-compartmental analysis. |
| Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUClast) of AMG 570 | Pre-dose and 12 hours post-dose on Day 1 and days 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 57, 71 and 105 | AMG 570 PK parameters were estimated using non-compartmental analysis. |
| Area Under the Concentration-time Curve Observed From Time Zero to Infinity (AUCinf) of AMG 570 | Pre-dose and 12 hours post-dose on Day 1 and days 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 57, 71 and 105 | — |
| Number of Participants With an Anti-AMG 570 Binding Antibody Positive Postbaseline Result | Baseline to Day 105 | The presence of anti-AMG 570 binding antibodies was assessed using a validated assay. The number and percentage of participants who developed binding anti-AMG 570 antibodies at any postbaseline visit are presented. |
Countries
United States
Participant flow
Recruitment details
A total of 56 healthy participants were enrolled at 3 research centers in the United States from 28 March 2016 to 06 September 2018.
Participants by arm
| Arm | Count |
|---|---|
| AMG 570 - 7 mg Participants received a single dose 7 mg dose of AMG 570 administered subcutaneously. | 6 |
| AMG 570 - 21 mg Participants received a single 21 mg dose of AMG 570 administered subcutaneously. | 6 |
| AMG 570 - 70 mg Participants received a single 70 mg dose of AMG 570 administered subcutaneously. | 6 |
| AMG 570 - 140 mg Participants received a single 140 mg dose of AMG 570 administered subcutaneously. | 6 |
| AMG 570 - 210 mg Participants received a single 210 mg dose of AMG 570 administered subcutaneously. | 6 |
| AMG 570 - 420 mg Participants received a single 420 mg dose of AMG 570 administered subcutaneously. | 6 |
| AMG 570 - 700 mg Participants received a single 700 mg dose of AMG 570 administered subcutaneously. | 6 |
| Placebo Participants received a single dose of the matching AMG 570 placebo administered subcutaneously. | 14 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | AMG 570 - 7 mg | AMG 570 - 21 mg | AMG 570 - 70 mg | AMG 570 - 140 mg | AMG 570 - 210 mg | AMG 570 - 420 mg | AMG 570 - 700 mg | Placebo | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 47.7 Years STANDARD_DEVIATION 11.4 | 45.8 Years STANDARD_DEVIATION 14.3 | 43.2 Years STANDARD_DEVIATION 16.7 | 42.0 Years STANDARD_DEVIATION 9.8 | 39.8 Years STANDARD_DEVIATION 17.6 | 39.8 Years STANDARD_DEVIATION 11.4 | 40.0 Years STANDARD_DEVIATION 17.1 | 44.4 Years STANDARD_DEVIATION 12.1 | 43.1 Years STANDARD_DEVIATION 13.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 5 Participants | 6 Participants | 6 Participants | 12 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 2 Participants | 3 Participants | 0 Participants | 5 Participants | 1 Participants | 3 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 6 Participants | 3 Participants | 3 Participants | 6 Participants | 1 Participants | 5 Participants | 11 Participants | 40 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 5 Participants | 6 Participants | 5 Participants | 6 Participants | 6 Participants | 12 Participants | 47 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 | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 14 |
| other Total, other adverse events | 6 / 6 | 5 / 6 | 4 / 6 | 4 / 6 | 2 / 6 | 3 / 6 | 4 / 6 | 9 / 14 |
| serious Total, serious adverse events | 1 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 14 |
Outcome results
Primary
Number of Participants Who Experienced a Clinically Significant Change in Clinical Laboratory Safety Tests
Laboratory safety tests included chemistry, hematology, and urinalysis parameters. Clinically significant laboratory safety tests were any events assessed as CTCAE Grade ≥3 at any post-baseline visit. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolonged hospitalization indicated; disabling; limited self care ADL. Grade 4 Life-threatening consequences; urgent interventions indicated.
Time frame: Baseline to Day 105
Population: Safety analysis set: all participants who received AMG 570 or placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AMG 570 - 7 mg | Number of Participants Who Experienced a Clinically Significant Change in Clinical Laboratory Safety Tests | 0 Participants |
| AMG 570 - 21 mg | Number of Participants Who Experienced a Clinically Significant Change in Clinical Laboratory Safety Tests | 0 Participants |
| AMG 570 - 70 mg | Number of Participants Who Experienced a Clinically Significant Change in Clinical Laboratory Safety Tests | 0 Participants |
| AMG 570 - 140 mg | Number of Participants Who Experienced a Clinically Significant Change in Clinical Laboratory Safety Tests | 0 Participants |
| AMG 570 - 210 mg | Number of Participants Who Experienced a Clinically Significant Change in Clinical Laboratory Safety Tests | 0 Participants |
| AMG 570 - 420 mg | Number of Participants Who Experienced a Clinically Significant Change in Clinical Laboratory Safety Tests | 0 Participants |
| AMG 570 - 700 mg | Number of Participants Who Experienced a Clinically Significant Change in Clinical Laboratory Safety Tests | 0 Participants |
| Placebo | Number of Participants Who Experienced a Clinically Significant Change in Clinical Laboratory Safety Tests | 3 Participants |
Primary
Number of Participants Who Experienced a Clinically Significant Change in Electrocardiograms (ECGs)
Any changes in ECG parameters that were deemed clinically significant by the Investigator were reported.
Time frame: Baseline to Day 105
Population: Safety analysis set: all participants who received AMG 570 or placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AMG 570 - 7 mg | Number of Participants Who Experienced a Clinically Significant Change in Electrocardiograms (ECGs) | 0 Participants |
| AMG 570 - 21 mg | Number of Participants Who Experienced a Clinically Significant Change in Electrocardiograms (ECGs) | 0 Participants |
| AMG 570 - 70 mg | Number of Participants Who Experienced a Clinically Significant Change in Electrocardiograms (ECGs) | 0 Participants |
| AMG 570 - 140 mg | Number of Participants Who Experienced a Clinically Significant Change in Electrocardiograms (ECGs) | 0 Participants |
| AMG 570 - 210 mg | Number of Participants Who Experienced a Clinically Significant Change in Electrocardiograms (ECGs) | 0 Participants |
| AMG 570 - 420 mg | Number of Participants Who Experienced a Clinically Significant Change in Electrocardiograms (ECGs) | 0 Participants |
| AMG 570 - 700 mg | Number of Participants Who Experienced a Clinically Significant Change in Electrocardiograms (ECGs) | 0 Participants |
| Placebo | Number of Participants Who Experienced a Clinically Significant Change in Electrocardiograms (ECGs) | 0 Participants |
Primary
Number of Participants Who Experienced a Clinically Significant Change in Physical Examinations
Physical examinations were performed by the investigator, designated physician, or nurse practitioner. A complete physical examination included, at a minimum, assessment of cardiovascular, respiratory, gastrointestinal and neurological systems. A brief physical examination included assessment of the skin, lungs, cardiovascular system, and abdomen (liver and spleen).
Time frame: Baseline to Day 105
Population: Safety analysis set: all participants who received AMG 570 or placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AMG 570 - 7 mg | Number of Participants Who Experienced a Clinically Significant Change in Physical Examinations | 0 Participants |
| AMG 570 - 21 mg | Number of Participants Who Experienced a Clinically Significant Change in Physical Examinations | 0 Participants |
| AMG 570 - 70 mg | Number of Participants Who Experienced a Clinically Significant Change in Physical Examinations | 0 Participants |
| AMG 570 - 140 mg | Number of Participants Who Experienced a Clinically Significant Change in Physical Examinations | 0 Participants |
| AMG 570 - 210 mg | Number of Participants Who Experienced a Clinically Significant Change in Physical Examinations | 0 Participants |
| AMG 570 - 420 mg | Number of Participants Who Experienced a Clinically Significant Change in Physical Examinations | 0 Participants |
| AMG 570 - 700 mg | Number of Participants Who Experienced a Clinically Significant Change in Physical Examinations | 0 Participants |
| Placebo | Number of Participants Who Experienced a Clinically Significant Change in Physical Examinations | 0 Participants |
Primary
Number of Participants Who Experienced a Clinically Significant Change in Vital Signs
Any changes in blood pressure, body temperature, heart rate, and pulse rate that were deemed as clinically significant by the Investigator were reported.
Time frame: Baseline to Day 105
Population: Safety analysis set: all participants who received AMG 570 or placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AMG 570 - 7 mg | Number of Participants Who Experienced a Clinically Significant Change in Vital Signs | 0 Participants |
| AMG 570 - 21 mg | Number of Participants Who Experienced a Clinically Significant Change in Vital Signs | 0 Participants |
| AMG 570 - 70 mg | Number of Participants Who Experienced a Clinically Significant Change in Vital Signs | 0 Participants |
| AMG 570 - 140 mg | Number of Participants Who Experienced a Clinically Significant Change in Vital Signs | 0 Participants |
| AMG 570 - 210 mg | Number of Participants Who Experienced a Clinically Significant Change in Vital Signs | 0 Participants |
| AMG 570 - 420 mg | Number of Participants Who Experienced a Clinically Significant Change in Vital Signs | 0 Participants |
| AMG 570 - 700 mg | Number of Participants Who Experienced a Clinically Significant Change in Vital Signs | 0 Participants |
| Placebo | Number of Participants Who Experienced a Clinically Significant Change in Vital Signs | 0 Participants |
Primary
Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs)
TEAEs were adverse events with an onset after the administration of study treatment. TEAEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limited age appropriate instrumental activities of daily life (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolonged hospitalization indicated; disabling; limited self care ADL. Grade 4 Life-threatening consequences; urgent interventions indicated. Serious adverse events (SAEs) were defined as meeting at least 1 of the following criteria: * Results in death (fatal) * Immediately life-threatening * Requires in-patient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability/incapacity * Is a congenital anomaly/birth defect * Other medically important serious event
Time frame: Day 1 to Day 105
Population: Safety analysis set: all participants who received AMG 570 or placebo.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AMG 570 - 7 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | SAEs | 1 Participants |
| AMG 570 - 7 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Life-threatening TEAEs | 0 Participants |
| AMG 570 - 7 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 3 TEAEs | 0 Participants |
| AMG 570 - 7 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | TEAEs | 6 Participants |
| AMG 570 - 7 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 2 TEAEs | 4 Participants |
| AMG 570 - 7 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 4 TEAEs | 0 Participants |
| AMG 570 - 7 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Fatal TEAEs | 0 Participants |
| AMG 570 - 21 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Fatal TEAEs | 0 Participants |
| AMG 570 - 21 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | SAEs | 0 Participants |
| AMG 570 - 21 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 2 TEAEs | 0 Participants |
| AMG 570 - 21 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 3 TEAEs | 0 Participants |
| AMG 570 - 21 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 4 TEAEs | 0 Participants |
| AMG 570 - 21 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | TEAEs | 5 Participants |
| AMG 570 - 21 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Life-threatening TEAEs | 0 Participants |
| AMG 570 - 70 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | SAEs | 0 Participants |
| AMG 570 - 70 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Fatal TEAEs | 0 Participants |
| AMG 570 - 70 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 4 TEAEs | 0 Participants |
| AMG 570 - 70 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 2 TEAEs | 1 Participants |
| AMG 570 - 70 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | TEAEs | 4 Participants |
| AMG 570 - 70 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Life-threatening TEAEs | 0 Participants |
| AMG 570 - 70 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 3 TEAEs | 0 Participants |
| AMG 570 - 140 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 4 TEAEs | 0 Participants |
| AMG 570 - 140 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Fatal TEAEs | 0 Participants |
| AMG 570 - 140 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 2 TEAEs | 1 Participants |
| AMG 570 - 140 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Life-threatening TEAEs | 0 Participants |
| AMG 570 - 140 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 3 TEAEs | 0 Participants |
| AMG 570 - 140 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | TEAEs | 4 Participants |
| AMG 570 - 140 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | SAEs | 0 Participants |
| AMG 570 - 210 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 4 TEAEs | 0 Participants |
| AMG 570 - 210 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | TEAEs | 2 Participants |
| AMG 570 - 210 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 2 TEAEs | 0 Participants |
| AMG 570 - 210 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 3 TEAEs | 0 Participants |
| AMG 570 - 210 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | SAEs | 0 Participants |
| AMG 570 - 210 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Life-threatening TEAEs | 0 Participants |
| AMG 570 - 210 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Fatal TEAEs | 0 Participants |
| AMG 570 - 420 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 4 TEAEs | 0 Participants |
| AMG 570 - 420 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Fatal TEAEs | 0 Participants |
| AMG 570 - 420 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | SAEs | 0 Participants |
| AMG 570 - 420 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 3 TEAEs | 0 Participants |
| AMG 570 - 420 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Life-threatening TEAEs | 0 Participants |
| AMG 570 - 420 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 2 TEAEs | 0 Participants |
| AMG 570 - 420 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | TEAEs | 3 Participants |
| AMG 570 - 700 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 2 TEAEs | 1 Participants |
| AMG 570 - 700 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | TEAEs | 4 Participants |
| AMG 570 - 700 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Life-threatening TEAEs | 0 Participants |
| AMG 570 - 700 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | SAEs | 0 Participants |
| AMG 570 - 700 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Fatal TEAEs | 0 Participants |
| AMG 570 - 700 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 3 TEAEs | 1 Participants |
| AMG 570 - 700 mg | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 4 TEAEs | 0 Participants |
| Placebo | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Fatal TEAEs | 0 Participants |
| Placebo | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 4 TEAEs | 0 Participants |
| Placebo | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Life-threatening TEAEs | 0 Participants |
| Placebo | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | TEAEs | 9 Participants |
| Placebo | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 3 TEAEs | 0 Participants |
| Placebo | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | SAEs | 0 Participants |
| Placebo | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Grade ≥ 2 TEAEs | 3 Participants |
Secondary
Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUClast) of AMG 570
AMG 570 PK parameters were estimated using non-compartmental analysis.
Time frame: Pre-dose and 12 hours post-dose on Day 1 and days 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 57, 71 and 105
Population: The PK concentration analysis set: all participants who received AMG 570 and had at least one quantifiable PK sample collected.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AMG 570 - 7 mg | Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUClast) of AMG 570 | 0.591 day*µg/mL | Standard Deviation 0.321 |
| AMG 570 - 21 mg | Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUClast) of AMG 570 | 5.12 day*µg/mL | Standard Deviation 2.62 |
| AMG 570 - 70 mg | Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUClast) of AMG 570 | 43.8 day*µg/mL | Standard Deviation 26.1 |
| AMG 570 - 140 mg | Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUClast) of AMG 570 | 88.3 day*µg/mL | Standard Deviation 50.1 |
| AMG 570 - 210 mg | Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUClast) of AMG 570 | 271 day*µg/mL | Standard Deviation 61.3 |
| AMG 570 - 420 mg | Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUClast) of AMG 570 | 561 day*µg/mL | Standard Deviation 221 |
| AMG 570 - 700 mg | Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUClast) of AMG 570 | 1660 day*µg/mL | Standard Deviation 759 |
Secondary
Area Under the Concentration-time Curve Observed From Time Zero to Infinity (AUCinf) of AMG 570
Time frame: Pre-dose and 12 hours post-dose on Day 1 and days 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 57, 71 and 105
Population: The PK concentration analysis set: all participants who received AMG 570 and had at least one quantifiable PK sample collected.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AMG 570 - 7 mg | Area Under the Concentration-time Curve Observed From Time Zero to Infinity (AUCinf) of AMG 570 | 0.928 day*µg/mL | Standard Deviation 0.248 |
| AMG 570 - 21 mg | Area Under the Concentration-time Curve Observed From Time Zero to Infinity (AUCinf) of AMG 570 | 6.24 day*µg/mL | Standard Deviation 2.76 |
| AMG 570 - 70 mg | Area Under the Concentration-time Curve Observed From Time Zero to Infinity (AUCinf) of AMG 570 | 51.1 day*µg/mL | Standard Deviation 21.9 |
| AMG 570 - 140 mg | Area Under the Concentration-time Curve Observed From Time Zero to Infinity (AUCinf) of AMG 570 | 88.6 day*µg/mL | Standard Deviation 50.1 |
| AMG 570 - 210 mg | Area Under the Concentration-time Curve Observed From Time Zero to Infinity (AUCinf) of AMG 570 | 284 day*µg/mL | Standard Deviation 59.2 |
| AMG 570 - 420 mg | Area Under the Concentration-time Curve Observed From Time Zero to Infinity (AUCinf) of AMG 570 | 624 day*µg/mL | Standard Deviation 176 |
| AMG 570 - 700 mg | Area Under the Concentration-time Curve Observed From Time Zero to Infinity (AUCinf) of AMG 570 | 1660 day*µg/mL | Standard Deviation 757 |
Secondary
Maximum Observed Concentration (Cmax) of AMG 570
AMG 570 pharmacokinetic (PK) parameters were estimated using non-compartmental analysis.
Time frame: Pre-dose and 12 hours post-dose on Day 1 and days 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 57, 71 and 105
Population: The PK concentration analysis set: all participants who received AMG 570 and had at least one quantifiable PK sample collected.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AMG 570 - 7 mg | Maximum Observed Concentration (Cmax) of AMG 570 | 0.08664 µg/mL | Standard Deviation 0.0539 |
| AMG 570 - 21 mg | Maximum Observed Concentration (Cmax) of AMG 570 | 0.624 µg/mL | Standard Deviation 0.327 |
| AMG 570 - 70 mg | Maximum Observed Concentration (Cmax) of AMG 570 | 4.33 µg/mL | Standard Deviation 3.53 |
| AMG 570 - 140 mg | Maximum Observed Concentration (Cmax) of AMG 570 | 6.05 µg/mL | Standard Deviation 3.26 |
| AMG 570 - 210 mg | Maximum Observed Concentration (Cmax) of AMG 570 | 17.2 µg/mL | Standard Deviation 3.78 |
| AMG 570 - 420 mg | Maximum Observed Concentration (Cmax) of AMG 570 | 33.5 µg/mL | Standard Deviation 15.9 |
| AMG 570 - 700 mg | Maximum Observed Concentration (Cmax) of AMG 570 | 58.5 µg/mL | Standard Deviation 19.9 |
Secondary
Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells
Peripheral B7RP1 (also known as inducible costimulator ligand \[ICOSL\]) receptor occupancy was calculated from the free ICOSL and total ICOSL measurement from B cells in whole blood.
Time frame: Day 8; Day 29; Day 57; and Day 105
Population: The pharmacodynamic (PD) analysis set: all participants who had received AMG 570 or placebo and for whom at least one PD parameter had quantifiable baseline sample and a quantifiable PD sample collected at each specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AMG 570 - 7 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 8 | 13.73 Percentage B7RP-1 receptor occupancy | Standard Deviation 8.81 |
| AMG 570 - 7 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 29 | 0.36 Percentage B7RP-1 receptor occupancy | Standard Deviation 19.12 |
| AMG 570 - 7 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 57 | 3.30 Percentage B7RP-1 receptor occupancy | Standard Deviation 14.27 |
| AMG 570 - 7 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 105 | -8.94 Percentage B7RP-1 receptor occupancy | Standard Deviation 26.16 |
| AMG 570 - 21 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 105 | 4.53 Percentage B7RP-1 receptor occupancy | Standard Deviation 10.31 |
| AMG 570 - 21 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 29 | 20.98 Percentage B7RP-1 receptor occupancy | Standard Deviation 16.6 |
| AMG 570 - 21 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 8 | 43.76 Percentage B7RP-1 receptor occupancy | Standard Deviation 16.9 |
| AMG 570 - 21 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 57 | 11.28 Percentage B7RP-1 receptor occupancy | Standard Deviation 9.2 |
| AMG 570 - 70 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 8 | 64.37 Percentage B7RP-1 receptor occupancy | Standard Deviation 14.8 |
| AMG 570 - 70 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 105 | -4.54 Percentage B7RP-1 receptor occupancy | Standard Deviation 8.76 |
| AMG 570 - 70 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 29 | 19.96 Percentage B7RP-1 receptor occupancy | Standard Deviation 10.94 |
| AMG 570 - 70 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 57 | 10.14 Percentage B7RP-1 receptor occupancy | Standard Deviation 8.5 |
| AMG 570 - 140 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 8 | 80.82 Percentage B7RP-1 receptor occupancy | Standard Deviation 6.6 |
| AMG 570 - 140 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 29 | 38.30 Percentage B7RP-1 receptor occupancy | Standard Deviation 9.95 |
| AMG 570 - 140 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 57 | 6.74 Percentage B7RP-1 receptor occupancy | Standard Deviation 5.47 |
| AMG 570 - 140 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 105 | 1.37 Percentage B7RP-1 receptor occupancy | Standard Deviation 4.45 |
| AMG 570 - 210 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 105 | -2.25 Percentage B7RP-1 receptor occupancy | Standard Deviation 8.94 |
| AMG 570 - 210 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 57 | 4.55 Percentage B7RP-1 receptor occupancy | Standard Deviation 15.36 |
| AMG 570 - 210 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 29 | 72.96 Percentage B7RP-1 receptor occupancy | Standard Deviation 9.21 |
| AMG 570 - 210 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 8 | 88.87 Percentage B7RP-1 receptor occupancy | Standard Deviation 1.83 |
| AMG 570 - 420 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 105 | -0.08 Percentage B7RP-1 receptor occupancy | Standard Deviation 7.93 |
| AMG 570 - 420 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 57 | 33.20 Percentage B7RP-1 receptor occupancy | Standard Deviation 20.56 |
| AMG 570 - 420 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 29 | 86.64 Percentage B7RP-1 receptor occupancy | Standard Deviation 4.12 |
| AMG 570 - 420 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 8 | 92.52 Percentage B7RP-1 receptor occupancy | Standard Deviation 1.52 |
| AMG 570 - 700 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 105 | 13.33 Percentage B7RP-1 receptor occupancy | Standard Deviation 17.05 |
| AMG 570 - 700 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 8 | 95.97 Percentage B7RP-1 receptor occupancy | Standard Deviation 1.85 |
| AMG 570 - 700 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 57 | 65.88 Percentage B7RP-1 receptor occupancy | Standard Deviation 31.67 |
| AMG 570 - 700 mg | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 29 | 89.60 Percentage B7RP-1 receptor occupancy | Standard Deviation 9 |
| Placebo | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 29 | 0.27 Percentage B7RP-1 receptor occupancy | Standard Deviation 14.86 |
| Placebo | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 57 | 0.85 Percentage B7RP-1 receptor occupancy | Standard Deviation 14.42 |
| Placebo | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 105 | -2.90 Percentage B7RP-1 receptor occupancy | Standard Deviation 15.86 |
| Placebo | Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Day 8 | -0.98 Percentage B7RP-1 receptor occupancy | Standard Deviation 13.52 |
Secondary
Number of Participants With an Anti-AMG 570 Binding Antibody Positive Postbaseline Result
The presence of anti-AMG 570 binding antibodies was assessed using a validated assay. The number and percentage of participants who developed binding anti-AMG 570 antibodies at any postbaseline visit are presented.
Time frame: Baseline to Day 105
Population: All participants who received AMG 570 and had a negative or no result for binding antibodies at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AMG 570 - 7 mg | Number of Participants With an Anti-AMG 570 Binding Antibody Positive Postbaseline Result | 3 Participants |
| AMG 570 - 21 mg | Number of Participants With an Anti-AMG 570 Binding Antibody Positive Postbaseline Result | 2 Participants |
| AMG 570 - 70 mg | Number of Participants With an Anti-AMG 570 Binding Antibody Positive Postbaseline Result | 1 Participants |
| AMG 570 - 140 mg | Number of Participants With an Anti-AMG 570 Binding Antibody Positive Postbaseline Result | 3 Participants |
| AMG 570 - 210 mg | Number of Participants With an Anti-AMG 570 Binding Antibody Positive Postbaseline Result | 3 Participants |
| AMG 570 - 420 mg | Number of Participants With an Anti-AMG 570 Binding Antibody Positive Postbaseline Result | 6 Participants |
| AMG 570 - 700 mg | Number of Participants With an Anti-AMG 570 Binding Antibody Positive Postbaseline Result | 4 Participants |
Secondary
Percentage Change From Baseline for CD19+ Total B Cells Percentages (%)
Time frame: Baseline to Day 8; Day 29; Day 57 and Day 105
Population: The PD analysis set: all participants who had received AMG 570 or placebo and for whom at least one PD parameters had quantifiable baseline sample and at quantifiable PD sample collected at each specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AMG 570 - 7 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 8 | 56.111 Percentage of change | Standard Deviation 88.264 |
| AMG 570 - 7 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 29 | -13.714 Percentage of change | Standard Deviation 17.368 |
| AMG 570 - 7 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 57 | 29.484 Percentage of change | Standard Deviation 84.641 |
| AMG 570 - 7 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 105 | -7.738 Percentage of change | Standard Deviation 8.988 |
| AMG 570 - 21 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 105 | -1.524 Percentage of change | Standard Deviation 17.352 |
| AMG 570 - 21 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 29 | -13.258 Percentage of change | Standard Deviation 17.292 |
| AMG 570 - 21 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 8 | 24.057 Percentage of change | Standard Deviation 10.041 |
| AMG 570 - 21 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 57 | -21.751 Percentage of change | Standard Deviation 11.893 |
| AMG 570 - 70 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 8 | 28.291 Percentage of change | Standard Deviation 16.95 |
| AMG 570 - 70 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 105 | -23.333 Percentage of change | Standard Deviation 14.53 |
| AMG 570 - 70 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 29 | -22.000 Percentage of change | Standard Deviation 9.603 |
| AMG 570 - 70 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 57 | -26.000 Percentage of change | Standard Deviation 20.346 |
| AMG 570 - 140 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 8 | 20.942 Percentage of change | Standard Deviation 7.799 |
| AMG 570 - 140 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 29 | -5.778 Percentage of change | Standard Deviation 12.947 |
| AMG 570 - 140 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 57 | -36.293 Percentage of change | Standard Deviation 18.635 |
| AMG 570 - 140 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 105 | -9.947 Percentage of change | Standard Deviation 17.88 |
| AMG 570 - 210 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 105 | -15.152 Percentage of change | Standard Deviation 13.165 |
| AMG 570 - 210 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 57 | -16.667 Percentage of change | Standard Deviation 35.355 |
| AMG 570 - 210 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 29 | 2.765 Percentage of change | Standard Deviation 28.96 |
| AMG 570 - 210 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 8 | 26.538 Percentage of change | Standard Deviation 28.906 |
| AMG 570 - 420 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 105 | -23.966 Percentage of change | Standard Deviation 13.136 |
| AMG 570 - 420 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 57 | -10.467 Percentage of change | Standard Deviation 4.058 |
| AMG 570 - 420 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 29 | 7.836 Percentage of change | Standard Deviation 20.25 |
| AMG 570 - 420 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 8 | 45.886 Percentage of change | Standard Deviation 25.595 |
| AMG 570 - 700 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 105 | -35.474 Percentage of change | Standard Deviation 10.308 |
| AMG 570 - 700 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 8 | 23.693 Percentage of change | Standard Deviation 21.414 |
| AMG 570 - 700 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 57 | -7.500 Percentage of change | Standard Deviation 19.632 |
| AMG 570 - 700 mg | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 29 | 4.063 Percentage of change | Standard Deviation 15.629 |
| Placebo | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 29 | -0.582 Percentage of change | Standard Deviation 17.259 |
| Placebo | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 57 | 0.167 Percentage of change | Standard Deviation 16.092 |
| Placebo | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 105 | 3.895 Percentage of change | Standard Deviation 16.653 |
| Placebo | Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) | Percentage change from Baseline at Day 8 | -1.241 Percentage of change | Standard Deviation 12.309 |
Secondary
Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts
Time frame: Baseline to Day 8; Day 29; Day 57 and Day 105
Population: The pharmacodynamic (PD) analysis set: all participants who had received AMG 570 or placebo and for whom at least one PD parameter had quantifiable baseline sample and a quantifiable PD sample collected at each specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AMG 570 - 7 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 8 | 41.333 Percentage of change | Standard Deviation 73.517 |
| AMG 570 - 7 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 29 | -20.284 Percentage of change | Standard Deviation 22.31 |
| AMG 570 - 7 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 57 | -2.548 Percentage of change | Standard Deviation 41.873 |
| AMG 570 - 7 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 105 | -15.143 Percentage of change | Standard Deviation 22.117 |
| AMG 570 - 21 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 105 | 17.010 Percentage of change | Standard Deviation 33.957 |
| AMG 570 - 21 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 29 | -8.084 Percentage of change | Standard Deviation 10.212 |
| AMG 570 - 21 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 8 | 53.770 Percentage of change | Standard Deviation 43.216 |
| AMG 570 - 21 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 57 | -14.215 Percentage of change | Standard Deviation 14.903 |
| AMG 570 - 70 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 8 | 66.531 Percentage of change | Standard Deviation 28.057 |
| AMG 570 - 70 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 105 | -16.872 Percentage of change | Standard Deviation 19.064 |
| AMG 570 - 70 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 29 | -17.994 Percentage of change | Standard Deviation 15.582 |
| AMG 570 - 70 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 57 | -27.494 Percentage of change | Standard Deviation 20.918 |
| AMG 570 - 140 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 8 | 32.861 Percentage of change | Standard Deviation 21.296 |
| AMG 570 - 140 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 29 | -10.047 Percentage of change | Standard Deviation 19.791 |
| AMG 570 - 140 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 57 | -37.481 Percentage of change | Standard Deviation 17.44 |
| AMG 570 - 140 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 105 | 0.841 Percentage of change | Standard Deviation 48.458 |
| AMG 570 - 210 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 105 | -8.111 Percentage of change | Standard Deviation 32.077 |
| AMG 570 - 210 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 57 | 0.386 Percentage of change | Standard Deviation 50.044 |
| AMG 570 - 210 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 29 | 22.735 Percentage of change | Standard Deviation 51.384 |
| AMG 570 - 210 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 8 | 57.123 Percentage of change | Standard Deviation 75.399 |
| AMG 570 - 420 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 105 | -24.059 Percentage of change | Standard Deviation 25.753 |
| AMG 570 - 420 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 57 | -8.882 Percentage of change | Standard Deviation 21.936 |
| AMG 570 - 420 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 29 | 26.305 Percentage of change | Standard Deviation 28.795 |
| AMG 570 - 420 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 8 | 57.478 Percentage of change | Standard Deviation 28.365 |
| AMG 570 - 700 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 105 | -30.413 Percentage of change | Standard Deviation 26.863 |
| AMG 570 - 700 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 8 | 74.509 Percentage of change | Standard Deviation 70.354 |
| AMG 570 - 700 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 57 | 1.212 Percentage of change | Standard Deviation 42.87 |
| AMG 570 - 700 mg | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 29 | 9.637 Percentage of change | Standard Deviation 28.555 |
| Placebo | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 29 | 3.031 Percentage of change | Standard Deviation 23.358 |
| Placebo | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 57 | 5.726 Percentage of change | Standard Deviation 28.059 |
| Placebo | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 105 | 1.023 Percentage of change | Standard Deviation 13.612 |
| Placebo | Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts | Percentage change from Baseline at Day 8 | 2.671 Percentage of change | Standard Deviation 20.898 |
Secondary
Time to Reach Maximum Observed Concentration (Tmax) of AMG 570
AMG 570 PK parameters were estimated using non-compartmental analysis.
Time frame: Pre-dose and 12 hours post-dose on Day 1 and days 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 57, 71 and 105
Population: The PK concentration analysis set: all participants who received AMG 570 and had at least one quantifiable PK sample collected.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AMG 570 - 7 mg | Time to Reach Maximum Observed Concentration (Tmax) of AMG 570 | 5.0 days |
| AMG 570 - 21 mg | Time to Reach Maximum Observed Concentration (Tmax) of AMG 570 | 3.0 days |
| AMG 570 - 70 mg | Time to Reach Maximum Observed Concentration (Tmax) of AMG 570 | 3.0 days |
| AMG 570 - 140 mg | Time to Reach Maximum Observed Concentration (Tmax) of AMG 570 | 5.0 days |
| AMG 570 - 210 mg | Time to Reach Maximum Observed Concentration (Tmax) of AMG 570 | 5.0 days |
| AMG 570 - 420 mg | Time to Reach Maximum Observed Concentration (Tmax) of AMG 570 | 5.0 days |
| AMG 570 - 700 mg | Time to Reach Maximum Observed Concentration (Tmax) of AMG 570 | 5.0 days |