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A Phase 1 Study of AMG 330 in Subjects With Myeloid Malignancies

A Phase 1 First-in-human Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of AMG 330 Administered as Continuous Intravenous Infusion in Subjects With Myeloid Malignancies

Status
Terminated
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02520427
Enrollment
95
Registered
2015-08-11
Start date
2015-08-31
Completion date
2022-01-09
Last updated
2024-07-31

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Minimal Residual Disease Positive AML, Myelodysplastic Syndrome, Relapsed/Refractory AML

Keywords

Amgen, Phase 1, Clinical Trial, Oncology/Hematology, Relapsed/Refractory AML, Immunotherapy

Brief summary

The purpose of this First-in-Human Phase 1 study is to determine if AMG 330 given as a continuous IV infusion is safe and tolerable in adult subjects that have myeloid malignancies, and to determine the maximum tolerated dose and/or a biologically active dose. The study will be conducted in multiple sites and test increasing doses of AMG 330. The safety of subjects will be monitored by intensive assessment of vital signs, electrocardiograms, physical examinations, and laboratory tests.

Interventions

DRUGAMG 330

0.5 µg/day - 1.6 mg/day cIV infusion administered in cycles from 14 to 28 days.

Sponsors

Amgen
Lead SponsorINDUSTRY

Study design

Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* Informed consent provided * 18 years or older * Relapsed/refractory AML: AML as defined by the WHO Classification persisting or recurring following one or more treatment courses except promyelocytic leukemia (APML)

Exclusion criteria

* Active extramedullary AML in testes or central nervous system (CNS) * Known hypersensitivity to immunoglobulins or to any other component of the IP formulation (eg, sucrose, captisol, potassium, polysorbate 80, citrate, lysine) * Prior malignancy (other than in situ cancer) unless treated with curative intent and without evidence of disease for \> 1 years before screening

Design outcomes

Primary

MeasureTime frameDescription
Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)Day 1 to Day 14A participant was not DLT-evaluable if they dropped out before completion of the DLT window (14 days) for reasons other than an adverse event related to study drug or the participant had not received investigational product (IP) treatment for at least 14 days at the target dose for a 3- or 4-week cycle or at least 7 days at a target dose for a 2- week cycle. Furthermore, following drug interruptions, if a participant was unable to complete 2 repeat cycles for reasons other than DLT, the participant was not DLT evaluable.
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Day 1 until 30 days after last dose. Median duration of treatment was: Group 1 - 29.0 days; Group 2 - 29.0 days; Group 3 - 49.50 days; Group 4 - 23.50 daysThe severity of TEAEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria. The general guideline for assessment ranged from Grade 1 to 5, with higher grades indicating a worse outcome, and included: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, and Grade 5 = death.

Secondary

MeasureTime frameDescription
Response Rate in Participants With MRD-positive AMLFrom first dose of IP (Day 1) until the end of study, up to approximately 6 monthsResponse for participants with MRD-positive AML was defined as the percentage of participants with a conversion from MRD+ status with 0.1% threshold to CRMDR- or CRiMD-.
Response Rate in Participants With MDSFrom first dose of IP (Day 1) until the end of study, up to approximately 6 monthsResponse for participants with MDS was defined as the percentage of participants with CR or marrow complete remission per IWG.
Duration of ResponseFrom first dose of IP (Day 1) until the end of study, up to approximately 6 monthsDuration of response was defined as the interval from the date of the first disease assessment indicating an overall response to the first documented relapse, disease progression, or death due to any cause, whichever occurs first.
Time to ResponseFrom first dose of IP (Day 1) until the end of study, up to approximately 6 monthsTime to response was defined as the interval from the first administration of AMG 330 to the first documentation of response.
Event-free SurvivalFrom first dose of IP (Day 1) until the end of study, up to approximately 6 monthsEvent-free survival was defined as the interval from first administration of AMG 330 to the earliest of date of treatment failure, relapse for responders, or death due to any cause.
Overall SurvivalBaseline until the end of study, up to approximately 6 monthsOverall survival was defined as the time from enrollment until death due to any cause.
14 Day Infusion Duration: Terminal Half Life (t1/2 z) of AMG 33014 day infusion duration: Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days)—
Number of Participants Who Experienced an Incident of Anti-AMG 330 Antibody FormationBaseline until the end of study, up to approximately 6 monthsNumber of participants with a binding anti-body positive result at any timepoint post-baseline who had a negative or no result at baseline.
14 Day Infusion Duration: Steady State Serum Concentration After End of Infusion (Css) of AMG 330Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days)—
28 Day Infusion Duration: Css After End of Infusion of AMG 330Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 days)—
14 Day Infusion Duration: Volume of Distribution at Steady State (Vz) of AMG 330Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days)—
28 Day Infusion Duration: Vz of AMG 330Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 day)—
14 Day Infusion Duration: Clearance at Steady State (CL) for AMG 330Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days)—
28 Day Infusion Duration: CL of AMG 330Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 days)—
28 Day Infusion Duration: t1/2 z of AMG 330Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 days)—
Response Rate in Participants With R/R AMLFrom first dose of IP (Day 1) until the end of study, up to approximately 6 monthsResponse for participants with R/R AML was defined as the percentage of participants with complete response (CR)/complete remission with incomplete count recovery (CRi)/morphologic leukemia-free state (MLFS) \[per modified international working group (IWG) criteria\] or complete remission with partial hematologic recovery (CRh).

Countries

Canada, Germany, Netherlands, United States

Participant flow

Recruitment details

Participants were enrolled at 9 research centers in the United States, Germany and the Netherlands and participated in the trial from August 2015 to December 2021.

Pre-assignment details

95 participants were enrolled and received treatment.

Participants by arm

ArmCount
Group 1 - Cohort 1 AMG 330 0.5 µg/Day
Participants with R/R AML (Group 1) received AMG 330 0.5 µg/day as a 14 day continuous infusion (cIV).
1
Group 1 - Cohort 2 AMG 330 1.5 µg/Day
Participants with R/R AML (Group 1) received AMG 330 1.5 µg/day as a 14 day cIV.
1
Group 1 - Cohort 3 AMG 330 4 µg/Day
Participants with R/R AML (Group 1) received AMG 330 4 µg/day as a 14 day cIV.
3
Group 1 - Cohort 4 AMG 330 10 µg/Day
Participants with R/R AML (Group 1) received AMG 330 10 µg/day as a 14 day cIV.
3
Group 1 - Cohort 5 AMG 330 30 µg/Day
Participants with R/R AML (Group 1) received AMG 330 30 µg/day as a 14 day cIV.
3
Group 1 - Cohort 6 AMG 330 10/30 µg/Day
Participants with R/R AML (Group 1) received AMG 330 at an initial step dose of 10 µg/day and then the target dose of 30 µg/day as a 14 day cIV.
3
Group 1 - Cohort 7 AMG 330 10/60 µg/Day
Participants with R/R AML (Group 1) received AMG 330 at an initial step dose of 10 µg/day and then the target dose of 60 µg/day as a 14 day cIV.
4
Group 1 - Cohort 8 AMG 330 10/120 µg/Day
Participants with R/R AML (Group 1) received AMG 330 at an initial step dose of 10 µg/day and then the target dose of 120 µg/day as a 14 day cIV.
4
Group 1 - Cohort 9 AMG 330 10/240 µg/Day
Participants with R/R AML (Group 1) received AMG 330 at an initial step dose of 10 µg/day and then the target dose of 240 µg/day as a 14 day cIV.
4
Group 1 - Cohort 10 AMG 330 10/480 µg/Day
Participants with R/R AML (Group 1) received AMG 330 at an initial step dose of 10 µg/day and then the target dose of 480 µg/day as a 14 day cIV.
3
Group 1 - Cohort 11 AMG 330 10/60/240 µg/Day
Participants with R/R AML (Group 1) received AMG 330 at an initial daily step dose of 10 µg/day and a second step dose of 60 µg/day, and then the target dose of 240 µg/day as a 28 day cIV.
4
Group 1 - Cohort 12 AMG 330 10/60/240 ug/Day
Participants with R/R AML (Group 1) received AMG 330 at an initial daily step dose of 10 µg/day and a second step dose of 60 µg/day, then the target dose of 240 µg/day as a 28 day cIV.
7
Group 1 - Cohort 13 AMG 330 10/60/360 µg/Day
Participants with R/R AML (Group 1) received AMG 330 at an initial daily step dose of 10 µg/day and a second step dose of 60 µg/day, and then the target dose of 360 µg/day as a 28 day cIV.
3
Group 1 - Cohort 14 AMG 330 10/60/480 µg/Day
Participants with R/R AML (Group 1) received AMG 330 at an initial daily step dose of 10 µg/day and a second step dose of 60 µg/day, and then the target dose of 480 µg/day as a 28 day cIV.
3
Group 1 - Cohort 15 AMG 330 10/240/600 µg/Day
Participants with R/R AML (Group 1) received AMG 330 at an initial daily step dose of 10 µg/day and a second step dose of 240 µg/day, and then the target dose of 600 µg/day as a 28 day cIV.
6
Group 1 - Cohort 16 AMG 330 10/240/600/720 µg/Day
Participants with R/R AML (Group 1) received AMG 330 at initial daily step doses of 10, 240 and 600 µg/day and then the target dose of 720 µg/day as a 28 day cIV.
3
Group 1 - Cohort 17 AMG 330 10/240/600/840 µg/Day
Participants with R/R AML (Group 1) received AMG 330 at initial daily step doses of 10, 240 and 600 µg/day and then the target dose of 840 µg/day as a 28 day cIV.
5
Group 1 - Cohort 18 AMG 330 10/240/600/960 µg/Day
Participants with R/R AML (Group 1) received AMG 330 at initial daily step doses of 10, 240 and 600 µg/day and then the target dose of 960 µg/day as a 28 day cIV.
4
Group 1 - Cohort 19 AMG 330 10/240/600/960/1300 µg/Day
Participants with R/R AML (Group 1) received AMG 330 at initial daily step doses of 10, 240, 600, and 960 µg/day and then the target dose of 1300 µg/day as a 28 day cIV.
5
Group 1 - Cohort 20 AMG 330 10/60/240/600/960/1600 µg/Day
Participants with R/R AML (Group 1) received AMG 330 at initial daily step doses of 10, 60, 240, 600, and 960 µg/day and then the target dose of 1600 µg/day as a 28 day cIV.
8
Group 2 - Cohort 1 AMG 300 30/240/600 µg/Day
Participants with MRD+ AML (Group 2) received AMG 330 at initial daily step doses of 30 µg/day for up to 2 days, 240 µg/day for up to 5 days and then the target dose of 600 µg/day as a 28 day cIV.
4
Group 2 - Cohort 2 AMG 330 30/240/840 µg/Day
Participants with MRD+ AML (Group 2) received AMG 330 at initial step daily doses of 30 µg/day for up to 2 days, 240 µg/day for up to 5 days and then the target dose of 840 µg/day as a 28 day cIV.
2
Group 3 - Cohort 1 AMG 330 30/240/600 µg/Day
Participants with MDS (Group 3) received AMG 330 at initial daily step doses of 30 µg/day for up to 2 days and 240 µg/day for up to 5 days and then the target dose of 600 µg/day for a total of a 28 day cIV.
4
Group 4 - Etanercept and AMG 330
Participants with R/R AML received etanercept 50 mg as a subcutaneous (SC) injection in combination with AMG 330. Participants received AMG 330 at initial daily step doses of 10 µg/day for 2 days, 60 µg/day for 3 days and 240 µg/day for 9 days for a total of a 14 day cIV. Participants received etanercept 1 day before first AMG 330 administration and on Day 4 of each cycle.
3
Group 4 - Etanercept, Dexamethasone and AMG 330
Participants with R/R AML received etanercept 50 mg as a SC injection and dexamethsone 8 mg IV infusion in combination with AMG 330. Participants received AMG 330 at initial daily step doses of 10 µg/day for 2 days, 60 µg/day for 3 days and 240 µg/day for 9 days for a total of a 14 day cIV. Participants received etanercept 1 day before first AMG 330 administration and on Day 4 of each cycle. Participants received dexamethasone 1 hour before AMG 330 dose.
4
Group 4: Tocilizumab, Dexamethasone and AMG 330
Participants with R/R AML received tocilizumab 8 mg/kg IV infusion and dexamethsone 8 mg IV infusion in combination with AMG 330. Participants received AMG 330 at initial daily step doses of 10 µg/day for 2 days, 60 µg/day for 3 days and 240 µg/day for 9 days for a total of a 14 day cIV. Participants received tocilizumab on Day 1, 1 hour before the 1st dose of AMG 330 of each cycle. Participants received dexamethasone 1 hour before AMG 330 dose.
1
Total95

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003FG004FG005FG006FG007FG008FG009FG010FG011FG012FG013FG014FG015FG016FG017FG018FG019FG020FG021FG022FG023FG024FG025
Overall StudyDeath10000000000000002132001010
Overall StudyDecision by sponsor00000000110000000000000000
Overall StudyWithdrawal by Subject00100000000011101003200000

Baseline characteristics

CharacteristicGroup 1 - Cohort 2 AMG 330 1.5 µg/DayGroup 1 - Cohort 3 AMG 330 4 µg/DayGroup 1 - Cohort 4 AMG 330 10 µg/DayGroup 1 - Cohort 5 AMG 330 30 µg/DayGroup 1 - Cohort 6 AMG 330 10/30 µg/DayGroup 1 - Cohort 7 AMG 330 10/60 µg/DayGroup 1 - Cohort 8 AMG 330 10/120 µg/DayGroup 1 - Cohort 9 AMG 330 10/240 µg/DayGroup 1 - Cohort 10 AMG 330 10/480 µg/DayGroup 1 - Cohort 11 AMG 330 10/60/240 µg/DayGroup 1 - Cohort 12 AMG 330 10/60/240 ug/DayGroup 1 - Cohort 13 AMG 330 10/60/360 µg/DayGroup 1 - Cohort 14 AMG 330 10/60/480 µg/DayGroup 1 - Cohort 1 AMG 330 0.5 µg/DayGroup 1 - Cohort 15 AMG 330 10/240/600 µg/DayGroup 1 - Cohort 16 AMG 330 10/240/600/720 µg/DayGroup 1 - Cohort 17 AMG 330 10/240/600/840 µg/DayGroup 1 - Cohort 18 AMG 330 10/240/600/960 µg/DayGroup 1 - Cohort 19 AMG 330 10/240/600/960/1300 µg/DayGroup 1 - Cohort 20 AMG 330 10/60/240/600/960/1600 µg/DayGroup 2 - Cohort 1 AMG 300 30/240/600 µg/DayGroup 2 - Cohort 2 AMG 330 30/240/840 µg/DayGroup 3 - Cohort 1 AMG 330 30/240/600 µg/DayGroup 4 - Etanercept and AMG 330Group 4 - Etanercept, Dexamethasone and AMG 330Group 4: Tocilizumab, Dexamethasone and AMG 330Total
Age, Customized
18-64 years
1 Participants2 Participants2 Participants1 Participants2 Participants3 Participants1 Participants2 Participants2 Participants2 Participants5 Participants3 Participants2 Participants0 Participants4 Participants2 Participants3 Participants3 Participants3 Participants4 Participants2 Participants2 Participants2 Participants2 Participants3 Participants0 Participants58 Participants
Age, Customized
65-74 years
0 Participants1 Participants1 Participants2 Participants1 Participants0 Participants2 Participants1 Participants1 Participants2 Participants2 Participants0 Participants1 Participants1 Participants2 Participants1 Participants2 Participants1 Participants1 Participants3 Participants2 Participants0 Participants2 Participants1 Participants1 Participants0 Participants31 Participants
Age, Customized
75-84 years
0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants1 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants6 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants0 Participants0 Participants0 Participants2 Participants1 Participants0 Participants0 Participants1 Participants2 Participants1 Participants0 Participants0 Participants0 Participants1 Participants0 Participants1 Participants1 Participants1 Participants0 Participants0 Participants1 Participants1 Participants1 Participants2 Participants0 Participants16 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
1 Participants3 Participants3 Participants3 Participants1 Participants3 Participants4 Participants4 Participants2 Participants2 Participants6 Participants3 Participants3 Participants1 Participants5 Participants3 Participants4 Participants3 Participants4 Participants8 Participants4 Participants1 Participants3 Participants2 Participants2 Participants1 Participants79 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race/Ethnicity, Customized
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants3 Participants
Race/Ethnicity, Customized
Asian
0 Participants0 Participants1 Participants1 Participants0 Participants0 Participants0 Participants1 Participants0 Participants1 Participants0 Participants1 Participants1 Participants1 Participants1 Participants1 Participants1 Participants1 Participants1 Participants0 Participants1 Participants1 Participants1 Participants1 Participants0 Participants0 Participants16 Participants
Race/Ethnicity, Customized
Black (or African American)
0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants4 Participants
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants
Race/Ethnicity, Customized
Other
0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants2 Participants
Race/Ethnicity, Customized
White
1 Participants3 Participants1 Participants2 Participants1 Participants4 Participants4 Participants3 Participants3 Participants3 Participants7 Participants2 Participants1 Participants0 Participants5 Participants2 Participants4 Participants2 Participants4 Participants6 Participants2 Participants1 Participants3 Participants2 Participants2 Participants1 Participants69 Participants
Sex: Female, Male
Female
1 Participants1 Participants2 Participants2 Participants0 Participants1 Participants0 Participants3 Participants2 Participants2 Participants3 Participants2 Participants1 Participants1 Participants2 Participants1 Participants3 Participants2 Participants2 Participants3 Participants1 Participants1 Participants1 Participants2 Participants3 Participants0 Participants42 Participants
Sex: Female, Male
Male
0 Participants2 Participants1 Participants1 Participants3 Participants3 Participants4 Participants1 Participants1 Participants2 Participants4 Participants1 Participants2 Participants0 Participants4 Participants2 Participants2 Participants2 Participants3 Participants5 Participants3 Participants1 Participants3 Participants1 Participants1 Participants1 Participants53 Participants

Adverse events

Event typeEG000
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
EG008
affected / at risk
EG009
affected / at risk
EG010
affected / at risk
EG011
affected / at risk
EG012
affected / at risk
EG013
affected / at risk
EG014
affected / at risk
EG015
affected / at risk
EG016
affected / at risk
EG017
affected / at risk
EG018
affected / at risk
EG019
affected / at risk
EG020
affected / at risk
EG021
affected / at risk
EG022
affected / at risk
EG023
affected / at risk
EG024
affected / at risk
EG025
affected / at risk
deaths
Total, all-cause mortality
1 / 10 / 10 / 30 / 30 / 30 / 30 / 40 / 40 / 40 / 30 / 40 / 70 / 30 / 30 / 60 / 32 / 51 / 43 / 52 / 80 / 40 / 21 / 40 / 31 / 40 / 1
other
Total, other adverse events
1 / 11 / 12 / 33 / 33 / 33 / 34 / 44 / 44 / 43 / 34 / 47 / 73 / 33 / 36 / 63 / 35 / 54 / 45 / 58 / 84 / 42 / 24 / 43 / 34 / 41 / 1
serious
Total, serious adverse events
1 / 11 / 11 / 33 / 33 / 31 / 33 / 42 / 42 / 43 / 33 / 46 / 71 / 32 / 36 / 60 / 33 / 51 / 44 / 54 / 81 / 40 / 21 / 42 / 32 / 40 / 1

Outcome results

Primary

Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)

A participant was not DLT-evaluable if they dropped out before completion of the DLT window (14 days) for reasons other than an adverse event related to study drug or the participant had not received investigational product (IP) treatment for at least 14 days at the target dose for a 3- or 4-week cycle or at least 7 days at a target dose for a 2- week cycle. Furthermore, following drug interruptions, if a participant was unable to complete 2 repeat cycles for reasons other than DLT, the participant was not DLT evaluable.

Time frame: Day 1 to Day 14

Population: DLT-evaluable Analysis Set: All DLT-evaluable participants.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Group 1 - Cohort 1 AMG 330 0.5 µg/DayNumber of Participants Who Experienced a Dose-limiting Toxicity (DLT)0 Participants
Group 1 - Cohort 2 AMG 330 1.5 µg/DayNumber of Participants Who Experienced a Dose-limiting Toxicity (DLT)0 Participants
Group 1 - Cohort 3 AMG 330 4 µg/DayNumber of Participants Who Experienced a Dose-limiting Toxicity (DLT)0 Participants
Group 1 - Cohort 4 AMG 330 10 µg/DayNumber of Participants Who Experienced a Dose-limiting Toxicity (DLT)0 Participants
Group 1 - Cohort 5 AMG 330 30 µg/DayNumber of Participants Who Experienced a Dose-limiting Toxicity (DLT)1 Participants
Group 1 - Cohort 6 AMG 330 10/30 µg/DayNumber of Participants Who Experienced a Dose-limiting Toxicity (DLT)0 Participants
Group 1 - Cohort 7 AMG 330 10/60 µg/DayNumber of Participants Who Experienced a Dose-limiting Toxicity (DLT)0 Participants
Group 1 - Cohort 8 AMG 330 10/120 µg/DayNumber of Participants Who Experienced a Dose-limiting Toxicity (DLT)0 Participants
Group 1 - Cohort 9 AMG 330 10/240 µg/DayNumber of Participants Who Experienced a Dose-limiting Toxicity (DLT)0 Participants
Group 1 - Cohort 10 AMG 330 10/480 µg/DayNumber of Participants Who Experienced a Dose-limiting Toxicity (DLT)0 Participants
Group 1 - Cohort 11 AMG 330 10/60/240 µg/DayNumber of Participants Who Experienced a Dose-limiting Toxicity (DLT)0 Participants
Group 1 - Cohort 12 AMG 330 10/60/240 ug/DayNumber of Participants Who Experienced a Dose-limiting Toxicity (DLT)0 Participants
Group 1 - Cohort 13 AMG 330 10/60/360 µg/DayNumber of Participants Who Experienced a Dose-limiting Toxicity (DLT)0 Participants
Group 1 - Cohort 14 AMG 330 10/60/480 µg/DayNumber of Participants Who Experienced a Dose-limiting Toxicity (DLT)0 Participants
Group 1 - Cohort 15 AMG 330 10/240/600 µg/DayNumber of Participants Who Experienced a Dose-limiting Toxicity (DLT)0 Participants
Group 1 - Cohort 16 AMG 330 10/240/600/720 µg/DayNumber of Participants Who Experienced a Dose-limiting Toxicity (DLT)0 Participants
Group 1 - Cohort 17 AMG 330 10/240/600/840 µg/DayNumber of Participants Who Experienced a Dose-limiting Toxicity (DLT)0 Participants
Group 1 - Cohort 18 AMG 330 10/240/600/960 µg/DayNumber of Participants Who Experienced a Dose-limiting Toxicity (DLT)0 Participants
Group 1 - Cohort 19 AMG 330 10/240/600/960/1300 µg/DayNumber of Participants Who Experienced a Dose-limiting Toxicity (DLT)0 Participants
Group 1 - Cohort 20 AMG 330 10/60/240/600/960/1600 µg/DayNumber of Participants Who Experienced a Dose-limiting Toxicity (DLT)0 Participants
Group 2 - Cohort 1 AMG 300 30/240/600 µg/DayNumber of Participants Who Experienced a Dose-limiting Toxicity (DLT)0 Participants
Group 2 - Cohort 2 AMG 330 30/240/840 µg/DayNumber of Participants Who Experienced a Dose-limiting Toxicity (DLT)1 Participants
Group 3 - Cohort 1 AMG 330 30/240/600 µg/DayNumber of Participants Who Experienced a Dose-limiting Toxicity (DLT)0 Participants
Group 4 - Etanercept and AMG 330Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)0 Participants
Group 4 - Etanercept, Dexamethasone and AMG 330Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)0 Participants
Primary

Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)

The severity of TEAEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria. The general guideline for assessment ranged from Grade 1 to 5, with higher grades indicating a worse outcome, and included: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, and Grade 5 = death.

Time frame: Day 1 until 30 days after last dose. Median duration of treatment was: Group 1 - 29.0 days; Group 2 - 29.0 days; Group 3 - 49.50 days; Group 4 - 23.50 days

Population: Safety Analysis Set: All participants that were enrolled and received at least 1 dose of AMG 330.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Group 1 - Cohort 1 AMG 330 0.5 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs1 Participants
Group 1 - Cohort 1 AMG 330 0.5 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 40 Participants
Group 1 - Cohort 1 AMG 330 0.5 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 21 Participants
Group 1 - Cohort 1 AMG 330 0.5 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 51 Participants
Group 1 - Cohort 1 AMG 330 0.5 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 11 Participants
Group 1 - Cohort 1 AMG 330 0.5 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 31 Participants
Group 1 - Cohort 2 AMG 330 1.5 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 50 Participants
Group 1 - Cohort 2 AMG 330 1.5 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 11 Participants
Group 1 - Cohort 2 AMG 330 1.5 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 31 Participants
Group 1 - Cohort 2 AMG 330 1.5 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 21 Participants
Group 1 - Cohort 2 AMG 330 1.5 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs1 Participants
Group 1 - Cohort 2 AMG 330 1.5 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 41 Participants
Group 1 - Cohort 3 AMG 330 4 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 41 Participants
Group 1 - Cohort 3 AMG 330 4 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 12 Participants
Group 1 - Cohort 3 AMG 330 4 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 32 Participants
Group 1 - Cohort 3 AMG 330 4 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs3 Participants
Group 1 - Cohort 3 AMG 330 4 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 22 Participants
Group 1 - Cohort 3 AMG 330 4 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 50 Participants
Group 1 - Cohort 4 AMG 330 10 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 23 Participants
Group 1 - Cohort 4 AMG 330 10 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs3 Participants
Group 1 - Cohort 4 AMG 330 10 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 41 Participants
Group 1 - Cohort 4 AMG 330 10 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 13 Participants
Group 1 - Cohort 4 AMG 330 10 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 33 Participants
Group 1 - Cohort 4 AMG 330 10 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 50 Participants
Group 1 - Cohort 5 AMG 330 30 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 42 Participants
Group 1 - Cohort 5 AMG 330 30 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs3 Participants
Group 1 - Cohort 5 AMG 330 30 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 50 Participants
Group 1 - Cohort 5 AMG 330 30 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 12 Participants
Group 1 - Cohort 5 AMG 330 30 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 23 Participants
Group 1 - Cohort 5 AMG 330 30 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 33 Participants
Group 1 - Cohort 6 AMG 330 10/30 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 33 Participants
Group 1 - Cohort 6 AMG 330 10/30 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 50 Participants
Group 1 - Cohort 6 AMG 330 10/30 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs3 Participants
Group 1 - Cohort 6 AMG 330 10/30 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 40 Participants
Group 1 - Cohort 6 AMG 330 10/30 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 13 Participants
Group 1 - Cohort 6 AMG 330 10/30 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 23 Participants
Group 1 - Cohort 7 AMG 330 10/60 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs4 Participants
Group 1 - Cohort 7 AMG 330 10/60 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 41 Participants
Group 1 - Cohort 7 AMG 330 10/60 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 24 Participants
Group 1 - Cohort 7 AMG 330 10/60 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 50 Participants
Group 1 - Cohort 7 AMG 330 10/60 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 34 Participants
Group 1 - Cohort 7 AMG 330 10/60 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 14 Participants
Group 1 - Cohort 8 AMG 330 10/120 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 14 Participants
Group 1 - Cohort 8 AMG 330 10/120 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs4 Participants
Group 1 - Cohort 8 AMG 330 10/120 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 50 Participants
Group 1 - Cohort 8 AMG 330 10/120 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 41 Participants
Group 1 - Cohort 8 AMG 330 10/120 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 34 Participants
Group 1 - Cohort 8 AMG 330 10/120 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 24 Participants
Group 1 - Cohort 9 AMG 330 10/240 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 32 Participants
Group 1 - Cohort 9 AMG 330 10/240 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 41 Participants
Group 1 - Cohort 9 AMG 330 10/240 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 24 Participants
Group 1 - Cohort 9 AMG 330 10/240 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs4 Participants
Group 1 - Cohort 9 AMG 330 10/240 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 50 Participants
Group 1 - Cohort 9 AMG 330 10/240 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 14 Participants
Group 1 - Cohort 10 AMG 330 10/480 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 50 Participants
Group 1 - Cohort 10 AMG 330 10/480 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 13 Participants
Group 1 - Cohort 10 AMG 330 10/480 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 42 Participants
Group 1 - Cohort 10 AMG 330 10/480 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs3 Participants
Group 1 - Cohort 10 AMG 330 10/480 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 23 Participants
Group 1 - Cohort 10 AMG 330 10/480 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 33 Participants
Group 1 - Cohort 11 AMG 330 10/60/240 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 24 Participants
Group 1 - Cohort 11 AMG 330 10/60/240 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 50 Participants
Group 1 - Cohort 11 AMG 330 10/60/240 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 42 Participants
Group 1 - Cohort 11 AMG 330 10/60/240 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 14 Participants
Group 1 - Cohort 11 AMG 330 10/60/240 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs4 Participants
Group 1 - Cohort 11 AMG 330 10/60/240 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 34 Participants
Group 1 - Cohort 12 AMG 330 10/60/240 ug/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 50 Participants
Group 1 - Cohort 12 AMG 330 10/60/240 ug/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 17 Participants
Group 1 - Cohort 12 AMG 330 10/60/240 ug/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 26 Participants
Group 1 - Cohort 12 AMG 330 10/60/240 ug/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs7 Participants
Group 1 - Cohort 12 AMG 330 10/60/240 ug/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 36 Participants
Group 1 - Cohort 12 AMG 330 10/60/240 ug/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 44 Participants
Group 1 - Cohort 13 AMG 330 10/60/360 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 13 Participants
Group 1 - Cohort 13 AMG 330 10/60/360 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs3 Participants
Group 1 - Cohort 13 AMG 330 10/60/360 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 23 Participants
Group 1 - Cohort 13 AMG 330 10/60/360 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 33 Participants
Group 1 - Cohort 13 AMG 330 10/60/360 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 41 Participants
Group 1 - Cohort 13 AMG 330 10/60/360 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 50 Participants
Group 1 - Cohort 14 AMG 330 10/60/480 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 32 Participants
Group 1 - Cohort 14 AMG 330 10/60/480 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 13 Participants
Group 1 - Cohort 14 AMG 330 10/60/480 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 40 Participants
Group 1 - Cohort 14 AMG 330 10/60/480 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 23 Participants
Group 1 - Cohort 14 AMG 330 10/60/480 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 50 Participants
Group 1 - Cohort 14 AMG 330 10/60/480 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs3 Participants
Group 1 - Cohort 15 AMG 330 10/240/600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs6 Participants
Group 1 - Cohort 15 AMG 330 10/240/600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 35 Participants
Group 1 - Cohort 15 AMG 330 10/240/600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 50 Participants
Group 1 - Cohort 15 AMG 330 10/240/600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 43 Participants
Group 1 - Cohort 15 AMG 330 10/240/600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 16 Participants
Group 1 - Cohort 15 AMG 330 10/240/600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 26 Participants
Group 1 - Cohort 16 AMG 330 10/240/600/720 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 13 Participants
Group 1 - Cohort 16 AMG 330 10/240/600/720 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 50 Participants
Group 1 - Cohort 16 AMG 330 10/240/600/720 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 23 Participants
Group 1 - Cohort 16 AMG 330 10/240/600/720 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 33 Participants
Group 1 - Cohort 16 AMG 330 10/240/600/720 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs3 Participants
Group 1 - Cohort 16 AMG 330 10/240/600/720 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 42 Participants
Group 1 - Cohort 17 AMG 330 10/240/600/840 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 15 Participants
Group 1 - Cohort 17 AMG 330 10/240/600/840 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 25 Participants
Group 1 - Cohort 17 AMG 330 10/240/600/840 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs5 Participants
Group 1 - Cohort 17 AMG 330 10/240/600/840 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 52 Participants
Group 1 - Cohort 17 AMG 330 10/240/600/840 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 34 Participants
Group 1 - Cohort 17 AMG 330 10/240/600/840 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 44 Participants
Group 1 - Cohort 18 AMG 330 10/240/600/960 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 33 Participants
Group 1 - Cohort 18 AMG 330 10/240/600/960 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 14 Participants
Group 1 - Cohort 18 AMG 330 10/240/600/960 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs4 Participants
Group 1 - Cohort 18 AMG 330 10/240/600/960 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 44 Participants
Group 1 - Cohort 18 AMG 330 10/240/600/960 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 24 Participants
Group 1 - Cohort 18 AMG 330 10/240/600/960 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 51 Participants
Group 1 - Cohort 19 AMG 330 10/240/600/960/1300 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 35 Participants
Group 1 - Cohort 19 AMG 330 10/240/600/960/1300 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 25 Participants
Group 1 - Cohort 19 AMG 330 10/240/600/960/1300 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 15 Participants
Group 1 - Cohort 19 AMG 330 10/240/600/960/1300 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 43 Participants
Group 1 - Cohort 19 AMG 330 10/240/600/960/1300 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs5 Participants
Group 1 - Cohort 19 AMG 330 10/240/600/960/1300 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 53 Participants
Group 1 - Cohort 20 AMG 330 10/60/240/600/960/1600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 17 Participants
Group 1 - Cohort 20 AMG 330 10/60/240/600/960/1600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs8 Participants
Group 1 - Cohort 20 AMG 330 10/60/240/600/960/1600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 51 Participants
Group 1 - Cohort 20 AMG 330 10/60/240/600/960/1600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 45 Participants
Group 1 - Cohort 20 AMG 330 10/60/240/600/960/1600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 28 Participants
Group 1 - Cohort 20 AMG 330 10/60/240/600/960/1600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 38 Participants
Group 2 - Cohort 1 AMG 300 30/240/600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 50 Participants
Group 2 - Cohort 1 AMG 300 30/240/600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 41 Participants
Group 2 - Cohort 1 AMG 300 30/240/600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 14 Participants
Group 2 - Cohort 1 AMG 300 30/240/600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs4 Participants
Group 2 - Cohort 1 AMG 300 30/240/600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 24 Participants
Group 2 - Cohort 1 AMG 300 30/240/600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 33 Participants
Group 2 - Cohort 2 AMG 330 30/240/840 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 50 Participants
Group 2 - Cohort 2 AMG 330 30/240/840 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 12 Participants
Group 2 - Cohort 2 AMG 330 30/240/840 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 22 Participants
Group 2 - Cohort 2 AMG 330 30/240/840 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 32 Participants
Group 2 - Cohort 2 AMG 330 30/240/840 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs2 Participants
Group 2 - Cohort 2 AMG 330 30/240/840 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 42 Participants
Group 3 - Cohort 1 AMG 330 30/240/600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 24 Participants
Group 3 - Cohort 1 AMG 330 30/240/600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 34 Participants
Group 3 - Cohort 1 AMG 330 30/240/600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 44 Participants
Group 3 - Cohort 1 AMG 330 30/240/600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs4 Participants
Group 3 - Cohort 1 AMG 330 30/240/600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 14 Participants
Group 3 - Cohort 1 AMG 330 30/240/600 µg/DayNumber of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 51 Participants
Group 4 - Etanercept and AMG 330Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs3 Participants
Group 4 - Etanercept and AMG 330Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 42 Participants
Group 4 - Etanercept and AMG 330Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 23 Participants
Group 4 - Etanercept and AMG 330Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 33 Participants
Group 4 - Etanercept and AMG 330Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 13 Participants
Group 4 - Etanercept and AMG 330Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 50 Participants
Group 4 - Etanercept, Dexamethasone and AMG 330Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs4 Participants
Group 4 - Etanercept, Dexamethasone and AMG 330Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 50 Participants
Group 4 - Etanercept, Dexamethasone and AMG 330Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 14 Participants
Group 4 - Etanercept, Dexamethasone and AMG 330Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 41 Participants
Group 4 - Etanercept, Dexamethasone and AMG 330Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 33 Participants
Group 4 - Etanercept, Dexamethasone and AMG 330Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 24 Participants
Group 4: Tocilizumab, Dexamethasone and AMG 330Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 31 Participants
Group 4: Tocilizumab, Dexamethasone and AMG 330Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)All TEAEs1 Participants
Group 4: Tocilizumab, Dexamethasone and AMG 330Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 11 Participants
Group 4: Tocilizumab, Dexamethasone and AMG 330Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 50 Participants
Group 4: Tocilizumab, Dexamethasone and AMG 330Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 21 Participants
Group 4: Tocilizumab, Dexamethasone and AMG 330Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)Grade 41 Participants
Secondary

14 Day Infusion Duration: Clearance at Steady State (CL) for AMG 330

Time frame: Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days)

Population: Includes all participants who had analyzable samples.

ArmMeasureValue (MEDIAN)Dispersion
Group 1 - Cohort 2 AMG 330 1.5 µg/Day14 Day Infusion Duration: Clearance at Steady State (CL) for AMG 3302.71 L/hrFull Range 2.71
Group 1 - Cohort 3 AMG 330 4 µg/Day14 Day Infusion Duration: Clearance at Steady State (CL) for AMG 3303.08 L/hrFull Range 2.74
Group 1 - Cohort 4 AMG 330 10 µg/Day14 Day Infusion Duration: Clearance at Steady State (CL) for AMG 3302.64 L/hrFull Range 1.44
Group 1 - Cohort 5 AMG 330 30 µg/Day14 Day Infusion Duration: Clearance at Steady State (CL) for AMG 3305.67 L/hrFull Range 5.66
Group 1 - Cohort 6 AMG 330 10/30 µg/Day14 Day Infusion Duration: Clearance at Steady State (CL) for AMG 3308.06 L/hrFull Range 5.34
Group 1 - Cohort 7 AMG 330 10/60 µg/Day14 Day Infusion Duration: Clearance at Steady State (CL) for AMG 3308.26 L/hrFull Range 6.1
Group 1 - Cohort 8 AMG 330 10/120 µg/Day14 Day Infusion Duration: Clearance at Steady State (CL) for AMG 3309.42 L/hrFull Range 6.02
Group 1 - Cohort 9 AMG 330 10/240 µg/Day14 Day Infusion Duration: Clearance at Steady State (CL) for AMG 3304.37 L/hrFull Range 3.97
Group 1 - Cohort 10 AMG 330 10/480 µg/Day14 Day Infusion Duration: Clearance at Steady State (CL) for AMG 3305.38 L/hrFull Range 4.03
Group 1 - Cohort 12 AMG 330 10/60/240 ug/Day14 Day Infusion Duration: Clearance at Steady State (CL) for AMG 33010.5 L/hrFull Range 10.5
Secondary

14 Day Infusion Duration: Steady State Serum Concentration After End of Infusion (Css) of AMG 330

Time frame: Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days)

Population: Includes all participants who had analyzable samples.

ArmMeasureValue (MEDIAN)Dispersion
Group 1 - Cohort 1 AMG 330 0.5 µg/Day14 Day Infusion Duration: Steady State Serum Concentration After End of Infusion (Css) of AMG 3300.00 ng/mLFull Range 0
Group 1 - Cohort 2 AMG 330 1.5 µg/Day14 Day Infusion Duration: Steady State Serum Concentration After End of Infusion (Css) of AMG 3300.0231 ng/mLFull Range 0.0231
Group 1 - Cohort 3 AMG 330 4 µg/Day14 Day Infusion Duration: Steady State Serum Concentration After End of Infusion (Css) of AMG 3300.0541 ng/mLFull Range 0.0378
Group 1 - Cohort 4 AMG 330 10 µg/Day14 Day Infusion Duration: Steady State Serum Concentration After End of Infusion (Css) of AMG 3300.158 ng/mLFull Range 0.0856
Group 1 - Cohort 5 AMG 330 30 µg/Day14 Day Infusion Duration: Steady State Serum Concentration After End of Infusion (Css) of AMG 3300.221 ng/mLFull Range 0.22
Group 1 - Cohort 6 AMG 330 10/30 µg/Day14 Day Infusion Duration: Steady State Serum Concentration After End of Infusion (Css) of AMG 3300.155 ng/mLFull Range 0.134
Group 1 - Cohort 7 AMG 330 10/60 µg/Day14 Day Infusion Duration: Steady State Serum Concentration After End of Infusion (Css) of AMG 3300.325 ng/mLFull Range 0.24
Group 1 - Cohort 8 AMG 330 10/120 µg/Day14 Day Infusion Duration: Steady State Serum Concentration After End of Infusion (Css) of AMG 3300.610 ng/mLFull Range 0.39
Group 1 - Cohort 9 AMG 330 10/240 µg/Day14 Day Infusion Duration: Steady State Serum Concentration After End of Infusion (Css) of AMG 3302.29 ng/mLFull Range 1.16
Group 1 - Cohort 10 AMG 330 10/480 µg/Day14 Day Infusion Duration: Steady State Serum Concentration After End of Infusion (Css) of AMG 3303.97 ng/mLFull Range 2.97
Group 1 - Cohort 12 AMG 330 10/60/240 ug/Day14 Day Infusion Duration: Steady State Serum Concentration After End of Infusion (Css) of AMG 3300.952 ng/mLFull Range 0.952
Secondary

14 Day Infusion Duration: Terminal Half Life (t1/2 z) of AMG 330

Time frame: 14 day infusion duration: Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days)

Population: Includes all participants who had analyzable samples.

ArmMeasureValue (MEDIAN)Dispersion
Group 1 - Cohort 3 AMG 330 4 µg/Day14 Day Infusion Duration: Terminal Half Life (t1/2 z) of AMG 3302.68 hoursFull Range 2.68
Group 1 - Cohort 4 AMG 330 10 µg/Day14 Day Infusion Duration: Terminal Half Life (t1/2 z) of AMG 3303.28 hoursFull Range 2.9
Group 1 - Cohort 6 AMG 330 10/30 µg/Day14 Day Infusion Duration: Terminal Half Life (t1/2 z) of AMG 3304.03 hoursFull Range 2.59
Group 1 - Cohort 7 AMG 330 10/60 µg/Day14 Day Infusion Duration: Terminal Half Life (t1/2 z) of AMG 3305.34 hoursFull Range 5.05
Group 1 - Cohort 8 AMG 330 10/120 µg/Day14 Day Infusion Duration: Terminal Half Life (t1/2 z) of AMG 3308.07 hoursFull Range 8.07
Group 1 - Cohort 9 AMG 330 10/240 µg/Day14 Day Infusion Duration: Terminal Half Life (t1/2 z) of AMG 3307.34 hoursFull Range 7.2
Secondary

14 Day Infusion Duration: Volume of Distribution at Steady State (Vz) of AMG 330

Time frame: Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days)

Population: Includes all participants who had analyzable samples.

ArmMeasureValue (MEDIAN)Dispersion
Group 1 - Cohort 3 AMG 330 4 µg/Day14 Day Infusion Duration: Volume of Distribution at Steady State (Vz) of AMG 33011.9 LitersFull Range 11.9
Group 1 - Cohort 4 AMG 330 10 µg/Day14 Day Infusion Duration: Volume of Distribution at Steady State (Vz) of AMG 33017.0 LitersFull Range 6.02
Group 1 - Cohort 6 AMG 330 10/30 µg/Day14 Day Infusion Duration: Volume of Distribution at Steady State (Vz) of AMG 33031.0 LitersFull Range 30.1
Group 1 - Cohort 7 AMG 330 10/60 µg/Day14 Day Infusion Duration: Volume of Distribution at Steady State (Vz) of AMG 33062.7 LitersFull Range 49.5
Group 1 - Cohort 8 AMG 330 10/120 µg/Day14 Day Infusion Duration: Volume of Distribution at Steady State (Vz) of AMG 330149 LitersFull Range 149
Group 1 - Cohort 9 AMG 330 10/240 µg/Day14 Day Infusion Duration: Volume of Distribution at Steady State (Vz) of AMG 33044.1 LitersFull Range 42.9
Secondary

28 Day Infusion Duration: CL of AMG 330

Time frame: Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 days)

ArmMeasureValue (MEDIAN)Dispersion
Group 1 - Cohort 1 AMG 330 0.5 µg/Day28 Day Infusion Duration: CL of AMG 33022.8 L/hrFull Range 1.95
Group 1 - Cohort 2 AMG 330 1.5 µg/Day28 Day Infusion Duration: CL of AMG 3308.20 L/hrFull Range 7.43
Group 1 - Cohort 3 AMG 330 4 µg/Day28 Day Infusion Duration: CL of AMG 33012.8 L/hrFull Range 12.8
Group 1 - Cohort 4 AMG 330 10 µg/Day28 Day Infusion Duration: CL of AMG 3304.98 L/hrFull Range 3.04
Group 1 - Cohort 5 AMG 330 30 µg/Day28 Day Infusion Duration: CL of AMG 3305.04 L/hrFull Range 1.54
Group 1 - Cohort 6 AMG 330 10/30 µg/Day28 Day Infusion Duration: CL of AMG 3309.76 L/hrFull Range 2.77
Group 1 - Cohort 7 AMG 330 10/60 µg/Day28 Day Infusion Duration: CL of AMG 33013.7 L/hrFull Range 9.62
Group 1 - Cohort 8 AMG 330 10/120 µg/Day28 Day Infusion Duration: CL of AMG 3302.23 L/hrFull Range 0.86
Group 1 - Cohort 9 AMG 330 10/240 µg/Day28 Day Infusion Duration: CL of AMG 3308.87 L/hrFull Range 4.9
Group 1 - Cohort 10 AMG 330 10/480 µg/Day28 Day Infusion Duration: CL of AMG 33014.8 L/hrFull Range 11.3
Group 1 - Cohort 11 AMG 330 10/60/240 µg/Day28 Day Infusion Duration: CL of AMG 3304.17 L/hrFull Range 4.17
Group 1 - Cohort 12 AMG 330 10/60/240 ug/Day28 Day Infusion Duration: CL of AMG 33021.9 L/hrFull Range 21.9
Group 1 - Cohort 13 AMG 330 10/60/360 µg/Day28 Day Infusion Duration: CL of AMG 3305.68 L/hrFull Range 5
Secondary

28 Day Infusion Duration: Css After End of Infusion of AMG 330

Time frame: Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 days)

Population: Includes all participants who had analyzable samples.

ArmMeasureValue (MEDIAN)Dispersion
Group 1 - Cohort 1 AMG 330 0.5 µg/Day28 Day Infusion Duration: Css After End of Infusion of AMG 3300.440 ng/mLFull Range 0.2
Group 1 - Cohort 2 AMG 330 1.5 µg/Day28 Day Infusion Duration: Css After End of Infusion of AMG 3301.83 ng/mLFull Range 1.07
Group 1 - Cohort 3 AMG 330 4 µg/Day28 Day Infusion Duration: Css After End of Infusion of AMG 3301.56 ng/mLFull Range 1.56
Group 1 - Cohort 4 AMG 330 10 µg/Day28 Day Infusion Duration: Css After End of Infusion of AMG 3305.92 ng/mLFull Range 3.61
Group 1 - Cohort 5 AMG 330 30 µg/Day28 Day Infusion Duration: Css After End of Infusion of AMG 3305.95 ng/mLFull Range 4.62
Group 1 - Cohort 6 AMG 330 10/30 µg/Day28 Day Infusion Duration: Css After End of Infusion of AMG 3307.36 ng/mLFull Range 2.09
Group 1 - Cohort 7 AMG 330 10/60 µg/Day28 Day Infusion Duration: Css After End of Infusion of AMG 3303.20 ng/mLFull Range 2.24
Group 1 - Cohort 8 AMG 330 10/120 µg/Day28 Day Infusion Duration: Css After End of Infusion of AMG 33024.2 ng/mLFull Range 5.46
Group 1 - Cohort 9 AMG 330 10/240 µg/Day28 Day Infusion Duration: Css After End of Infusion of AMG 3307.52 ng/mLFull Range 5.82
Group 1 - Cohort 10 AMG 330 10/480 µg/Day28 Day Infusion Duration: Css After End of Infusion of AMG 3301.79 ng/mLFull Range 1.37
Group 1 - Cohort 11 AMG 330 10/60/240 µg/Day28 Day Infusion Duration: Css After End of Infusion of AMG 3308.40 ng/mLFull Range 8.4
Group 1 - Cohort 12 AMG 330 10/60/240 ug/Day28 Day Infusion Duration: Css After End of Infusion of AMG 3301.14 ng/mLFull Range 1.14
Group 1 - Cohort 14 AMG 330 10/60/480 µg/Day28 Day Infusion Duration: Css After End of Infusion of AMG 3300.952 ng/mLFull Range 0.952
Group 1 - Cohort 16 AMG 330 10/240/600/720 µg/Day28 Day Infusion Duration: Css After End of Infusion of AMG 3301.76 ng/mLFull Range 0.92
Secondary

28 Day Infusion Duration: t1/2 z of AMG 330

Time frame: Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 days)

Population: Includes all participants who had analyzable samples.

ArmMeasureValue (MEDIAN)Dispersion
Group 1 - Cohort 1 AMG 330 0.5 µg/Day28 Day Infusion Duration: t1/2 z of AMG 3308.34 HoursFull Range 8.34
Group 1 - Cohort 2 AMG 330 1.5 µg/Day28 Day Infusion Duration: t1/2 z of AMG 3306.49 HoursFull Range 6.49
Group 1 - Cohort 4 AMG 330 10 µg/Day28 Day Infusion Duration: t1/2 z of AMG 3304.57 HoursFull Range 4.47
Group 1 - Cohort 5 AMG 330 30 µg/Day28 Day Infusion Duration: t1/2 z of AMG 3305.03 HoursFull Range 4.37
Group 1 - Cohort 6 AMG 330 10/30 µg/Day28 Day Infusion Duration: t1/2 z of AMG 3304.96 HoursFull Range 4.96
Group 1 - Cohort 7 AMG 330 10/60 µg/Day28 Day Infusion Duration: t1/2 z of AMG 3308.67 HoursFull Range 7.71
Group 1 - Cohort 8 AMG 330 10/120 µg/Day28 Day Infusion Duration: t1/2 z of AMG 3303.71 HoursFull Range 3.21
Group 1 - Cohort 9 AMG 330 10/240 µg/Day28 Day Infusion Duration: t1/2 z of AMG 3304.99 HoursFull Range 2.58
Group 1 - Cohort 10 AMG 330 10/480 µg/Day28 Day Infusion Duration: t1/2 z of AMG 3303.80 HoursFull Range 2.9
Group 1 - Cohort 11 AMG 330 10/60/240 µg/Day28 Day Infusion Duration: t1/2 z of AMG 3309.14 HoursFull Range 9.14
Group 1 - Cohort 12 AMG 330 10/60/240 ug/Day28 Day Infusion Duration: t1/2 z of AMG 3304.22 HoursFull Range 3.32
Group 1 - Cohort 13 AMG 330 10/60/360 µg/Day28 Day Infusion Duration: t1/2 z of AMG 3306.43 HoursFull Range 6.3
Secondary

28 Day Infusion Duration: Vz of AMG 330

Time frame: Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 day)

Population: Includes all participants who had analyzable samples.

ArmMeasureValue (MEDIAN)Dispersion
Group 1 - Cohort 1 AMG 330 0.5 µg/Day28 Day Infusion Duration: Vz of AMG 330293 LitersFull Range 293
Group 1 - Cohort 2 AMG 330 1.5 µg/Day28 Day Infusion Duration: Vz of AMG 33069.6 LitersFull Range 69.6
Group 1 - Cohort 4 AMG 330 10 µg/Day28 Day Infusion Duration: Vz of AMG 33033.1 LitersFull Range 19.6
Group 1 - Cohort 5 AMG 330 30 µg/Day28 Day Infusion Duration: Vz of AMG 33047.1 LitersFull Range 9.69
Group 1 - Cohort 6 AMG 330 10/30 µg/Day28 Day Infusion Duration: Vz of AMG 33019.8 LitersFull Range 19.8
Group 1 - Cohort 7 AMG 330 10/60 µg/Day28 Day Infusion Duration: Vz of AMG 330165 LitersFull Range 107
Group 1 - Cohort 8 AMG 330 10/120 µg/Day28 Day Infusion Duration: Vz of AMG 3308.79 LitersFull Range 3.98
Group 1 - Cohort 9 AMG 330 10/240 µg/Day28 Day Infusion Duration: Vz of AMG 33063.8 LitersFull Range 18.2
Group 1 - Cohort 10 AMG 330 10/480 µg/Day28 Day Infusion Duration: Vz of AMG 33076.6 LitersFull Range 76.3
Group 1 - Cohort 11 AMG 330 10/60/240 µg/Day28 Day Infusion Duration: Vz of AMG 33054.9 LitersFull Range 54.9
Group 1 - Cohort 12 AMG 330 10/60/240 ug/Day28 Day Infusion Duration: Vz of AMG 330105 LitersFull Range 105
Group 1 - Cohort 13 AMG 330 10/60/360 µg/Day28 Day Infusion Duration: Vz of AMG 33060.2 LitersFull Range 46.4
Secondary

Duration of Response

Duration of response was defined as the interval from the date of the first disease assessment indicating an overall response to the first documented relapse, disease progression, or death due to any cause, whichever occurs first.

Time frame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months

Population: Per the Statistical Analysis Plan, duration of response was only planned to be measured in the expansion cohorts. Therefore, this endpoint was not summarized due to early termination of the trial prior to dose expansion.

Secondary

Event-free Survival

Event-free survival was defined as the interval from first administration of AMG 330 to the earliest of date of treatment failure, relapse for responders, or death due to any cause.

Time frame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months

Population: Per the Statistical Analysis Plan, event-free survival was only planned to be measured in the expansion cohorts. Therefore, this endpoint was not summarized due to early termination of the trial prior to dose expansion.

Secondary

Number of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation

Number of participants with a binding anti-body positive result at any timepoint post-baseline who had a negative or no result at baseline.

Time frame: Baseline until the end of study, up to approximately 6 months

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Group 1 - Cohort 1 AMG 330 0.5 µg/DayNumber of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation0 Participants
Group 1 - Cohort 2 AMG 330 1.5 µg/DayNumber of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation0 Participants
Group 1 - Cohort 3 AMG 330 4 µg/DayNumber of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation1 Participants
Group 1 - Cohort 4 AMG 330 10 µg/DayNumber of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation0 Participants
Group 1 - Cohort 5 AMG 330 30 µg/DayNumber of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation0 Participants
Group 1 - Cohort 6 AMG 330 10/30 µg/DayNumber of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation0 Participants
Group 1 - Cohort 7 AMG 330 10/60 µg/DayNumber of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation1 Participants
Group 1 - Cohort 8 AMG 330 10/120 µg/DayNumber of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation0 Participants
Group 1 - Cohort 9 AMG 330 10/240 µg/DayNumber of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation0 Participants
Group 1 - Cohort 10 AMG 330 10/480 µg/DayNumber of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation0 Participants
Group 1 - Cohort 11 AMG 330 10/60/240 µg/DayNumber of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation0 Participants
Group 1 - Cohort 12 AMG 330 10/60/240 ug/DayNumber of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation1 Participants
Group 1 - Cohort 13 AMG 330 10/60/360 µg/DayNumber of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation0 Participants
Group 1 - Cohort 14 AMG 330 10/60/480 µg/DayNumber of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation0 Participants
Group 1 - Cohort 15 AMG 330 10/240/600 µg/DayNumber of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation0 Participants
Group 1 - Cohort 16 AMG 330 10/240/600/720 µg/DayNumber of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation0 Participants
Group 1 - Cohort 17 AMG 330 10/240/600/840 µg/DayNumber of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation0 Participants
Group 1 - Cohort 18 AMG 330 10/240/600/960 µg/DayNumber of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation0 Participants
Group 1 - Cohort 19 AMG 330 10/240/600/960/1300 µg/DayNumber of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation0 Participants
Group 1 - Cohort 20 AMG 330 10/60/240/600/960/1600 µg/DayNumber of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation0 Participants
Group 2 - Cohort 1 AMG 300 30/240/600 µg/DayNumber of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation0 Participants
Group 2 - Cohort 2 AMG 330 30/240/840 µg/DayNumber of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation1 Participants
Group 3 - Cohort 1 AMG 330 30/240/600 µg/DayNumber of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation2 Participants
Group 4 - Etanercept and AMG 330Number of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation1 Participants
Group 4 - Etanercept, Dexamethasone and AMG 330Number of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation1 Participants
Group 4: Tocilizumab, Dexamethasone and AMG 330Number of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation0 Participants
Secondary

Overall Survival

Overall survival was defined as the time from enrollment until death due to any cause.

Time frame: Baseline until the end of study, up to approximately 6 months

Population: Per the Statistical Analysis Plan, overall survival was only planned to be measured in the expansion cohorts. Therefore, this endpoint was not summarized due to early termination of the trial prior to dose expansion.

Secondary

Response Rate in Participants With MDS

Response for participants with MDS was defined as the percentage of participants with CR or marrow complete remission per IWG.

Time frame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months

ArmMeasureValue (NUMBER)Dispersion
Group 1 - Cohort 1 AMG 330 0.5 µg/DayResponse Rate in Participants With MDS25.0 Percentage of participants95% Confidence Interval 0.6
Secondary

Response Rate in Participants With MRD-positive AML

Response for participants with MRD-positive AML was defined as the percentage of participants with a conversion from MRD+ status with 0.1% threshold to CRMDR- or CRiMD-.

Time frame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months

ArmMeasureValue (NUMBER)Dispersion
Group 1 - Cohort 1 AMG 330 0.5 µg/DayResponse Rate in Participants With MRD-positive AML25.0 Percentage of participants95% Confidence Interval 0.6
Group 1 - Cohort 2 AMG 330 1.5 µg/DayResponse Rate in Participants With MRD-positive AML0.0 Percentage of participants95% Confidence Interval 0
Secondary

Response Rate in Participants With R/R AML

Response for participants with R/R AML was defined as the percentage of participants with complete response (CR)/complete remission with incomplete count recovery (CRi)/morphologic leukemia-free state (MLFS) \[per modified international working group (IWG) criteria\] or complete remission with partial hematologic recovery (CRh).

Time frame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months

ArmMeasureValue (NUMBER)Dispersion
Group 1 - Cohort 1 AMG 330 0.5 µg/DayResponse Rate in Participants With R/R AML0.0 Percentage of participants95% Confidence Interval 0
Group 1 - Cohort 2 AMG 330 1.5 µg/DayResponse Rate in Participants With R/R AML100.0 Percentage of participants95% Confidence Interval 2.5
Group 1 - Cohort 3 AMG 330 4 µg/DayResponse Rate in Participants With R/R AML0.0 Percentage of participants95% Confidence Interval 0
Group 1 - Cohort 4 AMG 330 10 µg/DayResponse Rate in Participants With R/R AML0.0 Percentage of participants95% Confidence Interval 0
Group 1 - Cohort 5 AMG 330 30 µg/DayResponse Rate in Participants With R/R AML0.0 Percentage of participants95% Confidence Interval 0
Group 1 - Cohort 6 AMG 330 10/30 µg/DayResponse Rate in Participants With R/R AML0.0 Percentage of participants95% Confidence Interval 0
Group 1 - Cohort 7 AMG 330 10/60 µg/DayResponse Rate in Participants With R/R AML0.0 Percentage of participants95% Confidence Interval 0
Group 1 - Cohort 8 AMG 330 10/120 µg/DayResponse Rate in Participants With R/R AML25.0 Percentage of participants95% Confidence Interval 0.6
Group 1 - Cohort 9 AMG 330 10/240 µg/DayResponse Rate in Participants With R/R AML25.0 Percentage of participants95% Confidence Interval 0.6
Group 1 - Cohort 10 AMG 330 10/480 µg/DayResponse Rate in Participants With R/R AML0.0 Percentage of participants95% Confidence Interval 0
Group 1 - Cohort 11 AMG 330 10/60/240 µg/DayResponse Rate in Participants With R/R AML25.0 Percentage of participants95% Confidence Interval 0.6
Group 1 - Cohort 12 AMG 330 10/60/240 ug/DayResponse Rate in Participants With R/R AML14.3 Percentage of participants95% Confidence Interval 0.4
Group 1 - Cohort 13 AMG 330 10/60/360 µg/DayResponse Rate in Participants With R/R AML0.0 Percentage of participants95% Confidence Interval 0
Group 1 - Cohort 14 AMG 330 10/60/480 µg/DayResponse Rate in Participants With R/R AML0.0 Percentage of participants95% Confidence Interval 0
Group 1 - Cohort 15 AMG 330 10/240/600 µg/DayResponse Rate in Participants With R/R AML33.3 Percentage of participants95% Confidence Interval 4.3
Group 1 - Cohort 16 AMG 330 10/240/600/720 µg/DayResponse Rate in Participants With R/R AML33.3 Percentage of participants95% Confidence Interval 0.8
Group 1 - Cohort 17 AMG 330 10/240/600/840 µg/DayResponse Rate in Participants With R/R AML0.0 Percentage of participants95% Confidence Interval 0
Group 1 - Cohort 18 AMG 330 10/240/600/960 µg/DayResponse Rate in Participants With R/R AML0.0 Percentage of participants95% Confidence Interval 0
Group 1 - Cohort 19 AMG 330 10/240/600/960/1300 µg/DayResponse Rate in Participants With R/R AML0.0 Percentage of participants95% Confidence Interval 0
Group 1 - Cohort 20 AMG 330 10/60/240/600/960/1600 µg/DayResponse Rate in Participants With R/R AML0.0 Percentage of participants95% Confidence Interval 0
Group 2 - Cohort 1 AMG 300 30/240/600 µg/DayResponse Rate in Participants With R/R AML0.0 Percentage of participants95% Confidence Interval 0
Group 2 - Cohort 2 AMG 330 30/240/840 µg/DayResponse Rate in Participants With R/R AML0.0 Percentage of participants95% Confidence Interval 0
Group 3 - Cohort 1 AMG 330 30/240/600 µg/DayResponse Rate in Participants With R/R AML0.0 Percentage of participants95% Confidence Interval 0
Secondary

Time to Response

Time to response was defined as the interval from the first administration of AMG 330 to the first documentation of response.

Time frame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months

Population: Per the Statistical Analysis Plan, time to response was only planned to be measured in the expansion cohorts. Therefore, this endpoint was not summarized due to early termination of the trial prior to dose expansion.

Source: ClinicalTrials.gov · Data processed: Feb 28, 2026