A Phase 1 Study in Subjects With Relapsed or Refractory Multiple Myeloma

Sponsor
Amgen (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02561962
Collaborator
(none)
42
Enrollment
5
Locations
9
Arms
93.4
Anticipated Duration (Months)
8.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a first in human phase 1 multicenter open label study in subjects with relapsed or refractory multiple myeloma.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: AMG 224
Phase 1

Detailed Description

This is a first in human phase 1 multicenter open label study to evaluate the safety and tolerability of AMG 224 in subjects with relapsed or refractory multiple myeloma. The study will be conducted in 2 parts. Part 1 is the dose-exploration and part 2 is the dose-expansion. Study medication will be administered once every 3 weeks by intravenous (IV) infusion.

Study Design

Study Type:
Interventional
Actual Enrollment :
42 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1 First in Human Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 224 in Subjects With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date :
Nov 20, 2015
Actual Primary Completion Date :
Nov 30, 2018
Anticipated Study Completion Date :
Sep 1, 2023

Arms and Interventions

ArmIntervention/Treatment
Experimental: Dose Exploration: AMG 224 Dose A

Participants were administered AMG 224 Dose A as an intravenous (IV) infusion once every 3 weeks (Q3W) on Day 1 of each cycle, where each cycle is 3 weeks.

Drug: AMG 224
Administered as an IV infusion.

Experimental: Dose Exploration: AMG 224 Dose B

Participants were administered AMG 224 Dose B as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.

Drug: AMG 224
Administered as an IV infusion.

Experimental: Dose Exploration: AMG 224 Dose C

Participants were administered AMG 224 Dose C as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.

Drug: AMG 224
Administered as an IV infusion.

Experimental: Dose Exploration: AMG 224 Dose D

Participants were administered AMG 224 Dose D as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.

Drug: AMG 224
Administered as an IV infusion.

Experimental: Dose Exploration: AMG 224 Dose E

Participants were administered AMG 224 Dose E as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.

Drug: AMG 224
Administered as an IV infusion.

Experimental: Dose Exploration: AMG 224 Dose F

Participants were administered AMG 224 Dose F as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.

Drug: AMG 224
Administered as an IV infusion.

Experimental: Dose Exploration: AMG 224 Dose G

Participants were administered AMG 224 Dose G as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.

Drug: AMG 224
Administered as an IV infusion.

Experimental: Dose Expansion: AMG 224 Dose H + prior CD38 targeting antibody treatment

Participants who had prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the maximum tolerated dose [MTD] based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.

Drug: AMG 224
Administered as an IV infusion.

Experimental: Dose Expansion: AMG 224 Dose H + no prior CD38 targeting antibody treatment

Participants who had no prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the MTD based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.

Drug: AMG 224
Administered as an IV infusion.

Outcome Measures

Primary Outcome Measures

  1. Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) [Day 1 to Day 28]

    Adverse events, including DLTs, were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. A DLT was considered as any of the below, if judged by the investigator to be possibly related to AMG 224: Hematological: Grade 4 neutropenia lasting > 7 days Grade 3 or 4 neutropenia with fever > 38.5°C Grade 3 thrombocytopenia with ≥ Grade 2 hemorrhage Grade 4 thrombocytopenia lasting > 7 days Grade 3 anemia with symptoms or required intervention Grade 4 anemia Lymphopenia is not considered a DLT Non-hematological: ≥ Grade 3 nausea, vomiting or diarrhea persisting > 3 days despite optimal medical support Grade 3 fatigue persisting > 7 days ≥ Grade 3 acute kidney injury lasting > 3 days Elevation of aspartate aminotransferase or alanine aminotransferase >3x to >8x upper limit of normal (ULT) dependent on criteria Total bilirubin > 3x ULN Participants meeting the criteria for Hy's Law case were considered to have a DLT.

  2. Number of Participants With a Treatment-emergent Adverse Event (TEAE) [Day 1 of Cycle 1 to up to the end of Cycle 4, where each cycle is 3 weeks; up to 12 weeks.]

    An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. TEAEs were any AE that occurred after receiving at least 1 dose of treatment. Treatment-related TEAEs were those considered related to study treatment by the investigator. Any clinically significant changes in ECGs, vital signs, physical examination with a neurologic assessment and clinical laboratory tests were recorded as TEAEs.

Secondary Outcome Measures

  1. Maximum Observed Concentration (Cmax) of AMG 224 [AMG 224: Cycles 1-4 (each cycle = 3 weeks): pre-dose and 0 to 336 hours post-dose; Cycles 5 onwards: pre-dose to 37 days post last dose. DM1: Cycles 1-2 only: pre-dose and 0 to 96 hours post-dose.]

    Cmax of AMG 224 conjugated antibody, total anti-B-cell maturation antigen (anti-BCMA) antibody and DM1 was measured. DM1 is a semi-synthetic derivative of the ansamycin antibiotic, maytansine conjugated to the non-cleavable linker 4-[N-maleimidomethyl] cyclohexane-1-carboxylate conjugated to lysine residues in the antibody (MCC).

  2. Minimum Observed Concentration (Cmin) of AMG 224 [AMG 224: Cycles 1-4 (each cycle = 3 weeks): pre-dose and 0 to 336 hours post-dose; Cycles 5 onwards: pre-dose to 37 days post last dose. DM1: Cycles 1-2 only: pre-dose and 0 to 96 hours post-dose.]

    Cmin of AMG 224 conjugated antibody, total anti-BCMA antibody and DM1 was measured.

  3. Area Under the Concentration-time Curve (AUC) of AMG 224 [AMG 224: Cycles 1-4 (each cycle = 3 weeks): pre-dose and 0 to 336 hours post-dose; Cycles 5 onwards: pre-dose to 37 days post last dose. DM1: Cycles 1-2 only: pre-dose and 0 to 96 hours post-dose.]

    AUC of AMG 224 conjugated antibody, total anti-B-cell maturation antigen (anti-BCMA) antibody and DM1 was measured.

  4. Clearance (CL) of AMG 224 [AMG 224: Cycles 1-4 (each cycle = 3 weeks): pre-dose and 0 to 336 hours post-dose; Cycles 5 onwards: pre-dose to 37 days post last dose. DM1: Cycles 1-2 only: pre-dose and 0 to 96 hours post-dose.]

    CL of AMG 224 conjugated antibody, total anti-B-cell maturation antigen (anti-BCMA) antibody and DM1 was measured.

  5. Half-life (t1/2) of AMG 224 [AMG 224: Cycles 1-4 (each cycle = 3 weeks): pre-dose and 0 to 336 hours post-dose; Cycles 5 onwards: pre-dose to 37 days post last dose. DM1: Cycles 1-2 only: pre-dose and 0 to 96 hours post-dose.]

    t1/2 of AMG 224 conjugated antibody, total anti-B-cell maturation antigen (anti-BCMA) antibody and DM1 was measured.

  6. Best Overall Response (BOR) According to International Myeloma Working Group Uniform Response Criteria (IMWG-URC) [Day 1 of Cycle 1 to up to the end of study (up to 37 days after the last dose), where each cycle is 3 weeks]

    BOR was the best observed post baseline disease response per IMWG-URC: Stringent Complete Response (sCR): Negative immunofixation on the serum and urine, soft tissue plasmacytomas disappearance, < 5% plasma cells in bone marrow (BM). Normal serum free light chain ratio and absence of clonal cells in BM Very Good Partial Response (PR[VGPR]): Serum and urine M-protein detectable by immunofixation or ≥ 90% reduction in serum M-protein (urine M-protein level < 100 mg/24-h) PR: ≥ 50% reduction of serum M-protein and 24-hour (h) urinary M-protein by ≥ 90% or to < 200 mg/ 24-h Minor Response (MR): 25%-49% reduction of serum M-protein and 50%-89% in 24-h urinary M-protein, exceeding 200 mg/ 24-h Stable Disease (SD): Not meeting criteria above Progressive Disease (PD): ≥ 25% increase from lowest response value in serum. Development of new or increased size of existing bone lesions or soft tissue plasmacytomas. Hypercalcemia attributed to the plasma cell proliferative disorder

  7. Time To Progression (TTP) According to International Myeloma Working Group Uniform Response Criteria (IMWG-URC) [Day 1 of Cycle 1 to up to the end of study (up to 37 days after the last dose), where each cycle is 3 weeks]

    TTP was the time from the first administration of AMG 224 to the first objective assessment of disease progression as per IMWG-URC or deaths or if applicable date of censoring.

  8. Duration of Response (DOR) According to International Myeloma Working Group Uniform Response Criteria (IMWG-URC) [Day 1 of Cycle 1 to up to the end of study (up to 37 days after the last dose), where each cycle is 3 weeks]

    DOR was defined as the time between the date of the first observation indicating an objective response as PR (or better) through to the subsequent date of disease progression as classified by per the IMWG-URC for Multiple Myeloma or death or where applicable date of censoring.

  9. Percentage of Participants With Conversion to Minimal Residual Disease (MRD)-Negativity [Day 1 of Cycle 1 to up to the end of study (up to 37 days after the last dose), where each cycle is 3 weeks]

    MRD negative was defined as a tumor load of less than 1 clonal cell in 105 normal cells (as determined by flow cytometry). The percentage of participants who converted to be MRD negative was calculated.

  10. Number of Participants With an Anti-AMG 224 Antibody Formation [Day 1 of Cycle 1 to up to the end of study (up to 37 days after the last dose), where each cycle is 3 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Pathologically documented,multiple myeloma relapsed or refractory progressive disease after at least 3 lines of therapy for multiple myeloma.

Prior therapeutic treatment or regimens must include proteasome inhibitors (e.g. bortezomib) and immunomodulatory drugs (e.g. lenalidomide).

  • Willing and able to undergo bone marrow aspirate per protocol (with or without bone marrow biopsy per institutional guidelines).

  • Measurable disease per the International Myeloma Working Group (IMWG) response criteria

  • Hematological function, as follows, without transfusion support:

  • Absolute neutrophil count ≥ 1.0 X 10^9/L,

  • Platelet count ≥ 75 X 109/L (in patients with < 50% of bone marrow nucleated cells were plasma cells) or ≥ 50 X 109/L (in patients with ≥ 50% of bone marrow nucleated cells were plasma cells) without transfusion or growth factor support

  • Hemoglobin > 8 g/dL (> 80 g/L)

  • Adequate renal and hepatic function

  • Left ventricular ejection fraction (LVEF) > 50%

Exclusion Criteria:
  • Currently receiving treatment in another investigational device or drug study, or less than 28 days since ending treatment on another investigational device or drug study

  • Autologous stem cell transplant less than 90 days prior to study day 1

  • Multiple myeloma with IgM subtype

  • POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) syndrome, Plasma cell leukemia, Waldenstrom's macroglobulinemia or Amyloidosis

  • Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 7 days prior to study day

  • Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure (New York Heart Association > class II)

  • A baseline ECG QTcF > 470 msec

  • Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, or investigational agent) within 28 days prior to study day 1

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Research SiteWest HollywoodCaliforniaUnited States90069
2Research SiteBostonMassachusettsUnited States02114
3Research SiteNew YorkNew YorkUnited States10065
4Research SiteHoustonTexasUnited States77030
5Research SitePrahranVictoriaAustralia3181

Sponsors and Collaborators

  • Amgen

Investigators

  • Study Director: MD, Amgen

Study Documents (Full-Text)

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT02561962
Other Study ID Numbers:
  • 20130314
First Posted:
Sep 28, 2015
Last Update Posted:
Oct 7, 2021
Last Verified:
Sep 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Amgen
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment DetailsA total of 42 participants were enrolled in the study at 4 research centers in Australia and the United States.
Pre-assignment DetailThe results reported are based on a data snapshot date of 14 March 2019. Participants are still ongoing in the study. Doses of AMG 224 in dose exploration part range from lowest in Dose A (30mg) up to highest in Dose G (250mg). Specific doses are blinded due to the protection of propriety information.
Arm/Group TitleDose Exploration: AMG 224 Dose ADose Exploration: AMG 224 Dose BDose Exploration: AMG 224 Dose CDose Exploration: AMG 224 Dose DDose Exploration: AMG 224 Dose EDose Exploration: AMG 224 Dose FDose Exploration: AMG 224 Dose GDose Expansion: AMG 224 Dose H + Prior CD38 Targeting Antibody TreatmentDose Expansion: AMG 224 Dose H + no Prior CD38 Targeting Antibody Treatment
Arm/Group DescriptionParticipants were administered AMG 224 Dose A as an intravenous (IV) infusion once every 3 weeks (Q3W) on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose B as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose C as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose D as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose E as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose F as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose G as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants who had prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the maximum tolerated dose [MTD] identified based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants who had no prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the MTD identified based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.
Period Title: Overall Study
STARTED3333665112
Received Treatment333366592
COMPLETED133242331
NOT COMPLETED200124281

Baseline Characteristics

Arm/Group TitleDose Exploration: AMG 224 Dose ADose Exploration: AMG 224 Dose BDose Exploration: AMG 224 Dose CDose Exploration: AMG 224 Dose DDose Exploration: AMG 224 Dose EDose Exploration: AMG 224 Dose FDose Exploration: AMG 224 Dose GDose Expansion: AMG 224 Dose H + Prior CD38 Targeting Antibody TreatmentDose Expansion: AMG 224 Dose H + no Prior CD38 Targeting Antibody TreatmentTotal
Arm/Group DescriptionParticipants were administered AMG 224 Dose A as an intravenous (IV) infusion once every 3 weeks (Q3W) on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose B as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose C as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose D as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose E as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose F as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose G as an intravenous (IV) infusion once every 3 weeks (Q3W) on Day 1 of each cycle, where each cycle is 3 weeks.Participants who had prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the maximum tolerated dose [MTD] identified based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants who had no prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the MTD identified based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Total of all reporting groups
Overall Participants33336659240
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
63.3
(7.0)
63.7
(3.8)
64.3
(11.2)
70.7
(4.0)
60.5
(7.1)
65.0
(5.7)
58.2
(6.0)
71.3
(8.7)
53.0
(9.9)
64.5
(8.4)
Sex: Female, Male (Count of Participants)
Female
1
33.3%
2
66.7%
1
33.3%
1
33.3%
3
50%
4
66.7%
4
80%
4
44.4%
1
50%
21
52.5%
Male
2
66.7%
1
33.3%
2
66.7%
2
66.7%
3
50%
2
33.3%
1
20%
5
55.6%
1
50%
19
47.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
0
0%
0
0%
0
0%
0
0%
2
33.3%
2
33.3%
2
40%
1
11.1%
1
50%
8
20%
Not Hispanic or Latino
3
100%
3
100%
3
100%
3
100%
4
66.7%
4
66.7%
3
60%
8
88.9%
1
50%
32
80%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Race/Ethnicity, Customized (Count of Participants)
Asian
0
0%
0
0%
1
33.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
2.5%
Black (or African American)
0
0%
0
0%
0
0%
0
0%
1
16.7%
2
33.3%
1
20%
2
22.2%
0
0%
6
15%
White
0
0%
1
33.3%
2
66.7%
3
100%
4
66.7%
3
50%
3
60%
7
77.8%
2
100%
25
62.5%
Other
3
100%
2
66.7%
0
0%
0
0%
1
16.7%
1
16.7%
1
20%
0
0%
0
0%
8
20%

Outcome Measures

1. Primary Outcome
TitleNumber of Participants Who Experienced a Dose-Limiting Toxicity (DLT)
DescriptionAdverse events, including DLTs, were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. A DLT was considered as any of the below, if judged by the investigator to be possibly related to AMG 224: Hematological: Grade 4 neutropenia lasting > 7 days Grade 3 or 4 neutropenia with fever > 38.5°C Grade 3 thrombocytopenia with ≥ Grade 2 hemorrhage Grade 4 thrombocytopenia lasting > 7 days Grade 3 anemia with symptoms or required intervention Grade 4 anemia Lymphopenia is not considered a DLT Non-hematological: ≥ Grade 3 nausea, vomiting or diarrhea persisting > 3 days despite optimal medical support Grade 3 fatigue persisting > 7 days ≥ Grade 3 acute kidney injury lasting > 3 days Elevation of aspartate aminotransferase or alanine aminotransferase >3x to >8x upper limit of normal (ULT) dependent on criteria Total bilirubin > 3x ULN Participants meeting the criteria for Hy's Law case were considered to have a DLT.
Time FrameDay 1 to Day 28

Outcome Measure Data

Analysis Population Description
DLT analysis set: all participants who are DLT evaluable. A participant was not DLT-evaluable if the participant discontinued treatment for any reason other than a DLT prior to completing the first 28 days of AMG 224 treatment or did not receive 2 doses of AMG 224 during the 28-day DLT window.
Arm/Group TitleDose Exploration: AMG 224 Dose ADose Exploration: AMG 224 Dose BDose Exploration: AMG 224 Dose CDose Exploration: AMG 224 Dose DDose Exploration: AMG 224 Dose EDose Exploration: AMG 224 Dose FDose Exploration: AMG 224 Dose GDose Expansion: AMG 224 Dose H + Prior CD38 Targeting Antibody TreatmentDose Expansion: AMG 224 Dose H + no Prior CD38 Targeting Antibody Treatment
Arm/Group DescriptionParticipants were administered AMG 224 Dose A as an intravenous (IV) infusion once every 3 weeks (Q3W) on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose B as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose C as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose D as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose E as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose F as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose G as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants who had prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the maximum tolerated dose [MTD] identified based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants who had no prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the MTD identified based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.
Measure Participants333336481
Count of Participants [Participants]
0
0%
0
0%
0
0%
0
0%
0
0%
1
16.7%
3
60%
0
0%
0
0%
2. Primary Outcome
TitleNumber of Participants With a Treatment-emergent Adverse Event (TEAE)
DescriptionAn adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. TEAEs were any AE that occurred after receiving at least 1 dose of treatment. Treatment-related TEAEs were those considered related to study treatment by the investigator. Any clinically significant changes in ECGs, vital signs, physical examination with a neurologic assessment and clinical laboratory tests were recorded as TEAEs.
Time FrameDay 1 of Cycle 1 to up to the end of Cycle 4, where each cycle is 3 weeks; up to 12 weeks.

Outcome Measure Data

Analysis Population Description
Safety analysis set: all participants that are enrolled and received at least 1 dose of AMG 224.
Arm/Group TitleDose Exploration: AMG 224 Dose ADose Exploration: AMG 224 Dose BDose Exploration: AMG 224 Dose CDose Exploration: AMG 224 Dose DDose Exploration: AMG 224 Dose EDose Exploration: AMG 224 Dose FDose Exploration: AMG 224 Dose GDose Expansion: AMG 224 Dose H + Prior CD38 Targeting Antibody TreatmentDose Expansion: AMG 224 Dose H + no Prior CD38 Targeting Antibody Treatment
Arm/Group DescriptionParticipants were administered AMG 224 Dose A as an intravenous (IV) infusion once every 3 weeks (Q3W) on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose B as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose C as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose D as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose E as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose F as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose G as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants who had prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the maximum tolerated dose [MTD] identified based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants who had no prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the MTD identified based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.
Measure Participants333366592
TEAE
3
100%
3
100%
3
100%
3
100%
6
100%
6
100%
5
100%
9
100%
2
100%
Treatment-related TEAE
3
100%
3
100%
3
100%
3
100%
5
83.3%
5
83.3%
5
100%
7
77.8%
1
50%
3. Secondary Outcome
TitleMaximum Observed Concentration (Cmax) of AMG 224
DescriptionCmax of AMG 224 conjugated antibody, total anti-B-cell maturation antigen (anti-BCMA) antibody and DM1 was measured. DM1 is a semi-synthetic derivative of the ansamycin antibiotic, maytansine conjugated to the non-cleavable linker 4-[N-maleimidomethyl] cyclohexane-1-carboxylate conjugated to lysine residues in the antibody (MCC).
Time FrameAMG 224: Cycles 1-4 (each cycle = 3 weeks): pre-dose and 0 to 336 hours post-dose; Cycles 5 onwards: pre-dose to 37 days post last dose. DM1: Cycles 1-2 only: pre-dose and 0 to 96 hours post-dose.

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description
4. Secondary Outcome
TitleMinimum Observed Concentration (Cmin) of AMG 224
DescriptionCmin of AMG 224 conjugated antibody, total anti-BCMA antibody and DM1 was measured.
Time FrameAMG 224: Cycles 1-4 (each cycle = 3 weeks): pre-dose and 0 to 336 hours post-dose; Cycles 5 onwards: pre-dose to 37 days post last dose. DM1: Cycles 1-2 only: pre-dose and 0 to 96 hours post-dose.

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description
5. Secondary Outcome
TitleArea Under the Concentration-time Curve (AUC) of AMG 224
DescriptionAUC of AMG 224 conjugated antibody, total anti-B-cell maturation antigen (anti-BCMA) antibody and DM1 was measured.
Time FrameAMG 224: Cycles 1-4 (each cycle = 3 weeks): pre-dose and 0 to 336 hours post-dose; Cycles 5 onwards: pre-dose to 37 days post last dose. DM1: Cycles 1-2 only: pre-dose and 0 to 96 hours post-dose.

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description
6. Secondary Outcome
TitleClearance (CL) of AMG 224
DescriptionCL of AMG 224 conjugated antibody, total anti-B-cell maturation antigen (anti-BCMA) antibody and DM1 was measured.
Time FrameAMG 224: Cycles 1-4 (each cycle = 3 weeks): pre-dose and 0 to 336 hours post-dose; Cycles 5 onwards: pre-dose to 37 days post last dose. DM1: Cycles 1-2 only: pre-dose and 0 to 96 hours post-dose.

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description
7. Secondary Outcome
TitleHalf-life (t1/2) of AMG 224
Descriptiont1/2 of AMG 224 conjugated antibody, total anti-B-cell maturation antigen (anti-BCMA) antibody and DM1 was measured.
Time FrameAMG 224: Cycles 1-4 (each cycle = 3 weeks): pre-dose and 0 to 336 hours post-dose; Cycles 5 onwards: pre-dose to 37 days post last dose. DM1: Cycles 1-2 only: pre-dose and 0 to 96 hours post-dose.

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description
8. Secondary Outcome
TitleBest Overall Response (BOR) According to International Myeloma Working Group Uniform Response Criteria (IMWG-URC)
DescriptionBOR was the best observed post baseline disease response per IMWG-URC: Stringent Complete Response (sCR): Negative immunofixation on the serum and urine, soft tissue plasmacytomas disappearance, < 5% plasma cells in bone marrow (BM). Normal serum free light chain ratio and absence of clonal cells in BM Very Good Partial Response (PR[VGPR]): Serum and urine M-protein detectable by immunofixation or ≥ 90% reduction in serum M-protein (urine M-protein level < 100 mg/24-h) PR: ≥ 50% reduction of serum M-protein and 24-hour (h) urinary M-protein by ≥ 90% or to < 200 mg/ 24-h Minor Response (MR): 25%-49% reduction of serum M-protein and 50%-89% in 24-h urinary M-protein, exceeding 200 mg/ 24-h Stable Disease (SD): Not meeting criteria above Progressive Disease (PD): ≥ 25% increase from lowest response value in serum. Development of new or increased size of existing bone lesions or soft tissue plasmacytomas. Hypercalcemia attributed to the plasma cell proliferative disorder
Time FrameDay 1 of Cycle 1 to up to the end of study (up to 37 days after the last dose), where each cycle is 3 weeks

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description
9. Secondary Outcome
TitleTime To Progression (TTP) According to International Myeloma Working Group Uniform Response Criteria (IMWG-URC)
DescriptionTTP was the time from the first administration of AMG 224 to the first objective assessment of disease progression as per IMWG-URC or deaths or if applicable date of censoring.
Time FrameDay 1 of Cycle 1 to up to the end of study (up to 37 days after the last dose), where each cycle is 3 weeks

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description
10. Secondary Outcome
TitleDuration of Response (DOR) According to International Myeloma Working Group Uniform Response Criteria (IMWG-URC)
DescriptionDOR was defined as the time between the date of the first observation indicating an objective response as PR (or better) through to the subsequent date of disease progression as classified by per the IMWG-URC for Multiple Myeloma or death or where applicable date of censoring.
Time FrameDay 1 of Cycle 1 to up to the end of study (up to 37 days after the last dose), where each cycle is 3 weeks

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description
11. Secondary Outcome
TitlePercentage of Participants With Conversion to Minimal Residual Disease (MRD)-Negativity
DescriptionMRD negative was defined as a tumor load of less than 1 clonal cell in 105 normal cells (as determined by flow cytometry). The percentage of participants who converted to be MRD negative was calculated.
Time FrameDay 1 of Cycle 1 to up to the end of study (up to 37 days after the last dose), where each cycle is 3 weeks

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description
12. Secondary Outcome
TitleNumber of Participants With an Anti-AMG 224 Antibody Formation
Description
Time FrameDay 1 of Cycle 1 to up to the end of study (up to 37 days after the last dose), where each cycle is 3 weeks

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description

Adverse Events

Time FrameDay 1 of Cycle 1 to end of Cycle 4 (where each cycle is 3 weeks); a maximum of 12 weeks.
Adverse Event Reporting Description All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold of 5%.
Arm/Group TitleDose Exploration: AMG 224 Dose ADose Exploration: AMG 224 Dose BDose Exploration: AMG 224 Dose CDose Exploration: AMG 224 Dose DDose Exploration: AMG 224 Dose EDose Exploration: AMG 224 Dose FDose Exploration: AMG 224 Dose GDose Expansion: AMG 224 Dose H + Prior CD38 Targeting Antibody TreatmentDose Expansion: AMG 224 Dose H + no Prior CD38 Targeting Antibody Treatment
Arm/Group DescriptionParticipants were administered AMG 224 Dose A as an intravenous (IV) infusion once every 3 weeks (Q3W) on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose B as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose C as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose D as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose E as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose F as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants were administered AMG 224 Dose G as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants who had prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the maximum tolerated dose [MTD] identified based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.Participants who had no prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the MTD identified based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks.
All Cause Mortality
Dose Exploration: AMG 224 Dose ADose Exploration: AMG 224 Dose BDose Exploration: AMG 224 Dose CDose Exploration: AMG 224 Dose DDose Exploration: AMG 224 Dose EDose Exploration: AMG 224 Dose FDose Exploration: AMG 224 Dose GDose Expansion: AMG 224 Dose H + Prior CD38 Targeting Antibody TreatmentDose Expansion: AMG 224 Dose H + no Prior CD38 Targeting Antibody Treatment
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/11 (0%) 0/2 (0%)
Serious Adverse Events
Dose Exploration: AMG 224 Dose ADose Exploration: AMG 224 Dose BDose Exploration: AMG 224 Dose CDose Exploration: AMG 224 Dose DDose Exploration: AMG 224 Dose EDose Exploration: AMG 224 Dose FDose Exploration: AMG 224 Dose GDose Expansion: AMG 224 Dose H + Prior CD38 Targeting Antibody TreatmentDose Expansion: AMG 224 Dose H + no Prior CD38 Targeting Antibody Treatment
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total0/3 (0%) 1/3 (33.3%) 0/3 (0%) 2/3 (66.7%) 2/6 (33.3%) 2/6 (33.3%) 2/5 (40%) 6/9 (66.7%) 0/2 (0%)
Blood and lymphatic system disorders
Anaemia0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Febrile neutropenia0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Neutropenia0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Plasma cell disorder0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Thrombocytopenia0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Cardiac disorders
Atrial flutter0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Gastrointestinal disorders
Nausea0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
General disorders
Pyrexia0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Hepatobiliary disorders
Cholecystitis acute0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Infections and infestations
Acute sinusitis0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Influenza0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Lower respiratory tract infection0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Parainfluenzae virus infection0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Pneumonia0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Pneumonia pneumococcal0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Injury, poisoning and procedural complications
Clavicle fracture0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Fall0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Femur fracture0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Infusion related reaction0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Spinal fracture0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Investigations
Platelet count decreased0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Metabolism and nutrition disorders
Dehydration0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Failure to thrive0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Fluid overload0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Back pain0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Osteitis0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Pathological fracture0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Plasmacytoma0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Nervous system disorders
Facial paralysis0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Other (Not Including Serious) Adverse Events
Dose Exploration: AMG 224 Dose ADose Exploration: AMG 224 Dose BDose Exploration: AMG 224 Dose CDose Exploration: AMG 224 Dose DDose Exploration: AMG 224 Dose EDose Exploration: AMG 224 Dose FDose Exploration: AMG 224 Dose GDose Expansion: AMG 224 Dose H + Prior CD38 Targeting Antibody TreatmentDose Expansion: AMG 224 Dose H + no Prior CD38 Targeting Antibody Treatment
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total3/3 (100%) 3/3 (100%) 3/3 (100%) 3/3 (100%) 5/6 (83.3%) 6/6 (100%) 5/5 (100%) 7/9 (77.8%) 2/2 (100%)
Blood and lymphatic system disorders
Anaemia0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 3/6 (50%) 5/6 (83.3%) 3/5 (60%) 1/9 (11.1%) 0/2 (0%)
Leukopenia0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 1/5 (20%) 1/9 (11.1%) 0/2 (0%)
Neutropenia0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 1/5 (20%) 2/9 (22.2%) 1/2 (50%)
Splenic lesion0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Splenomegaly0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Thrombocytopenia2/3 (66.7%) 3/3 (100%) 2/3 (66.7%) 2/3 (66.7%) 1/6 (16.7%) 5/6 (83.3%) 3/5 (60%) 6/9 (66.7%) 1/2 (50%)
Thrombocytosis0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Cardiac disorders
Palpitations1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Tachycardia0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Ear and labyrinth disorders
Tinnitus0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Vertigo positional1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Eye disorders
Conjunctival haemorrhage0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Diplopia0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Dry eye0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 1/9 (11.1%) 1/2 (50%)
Eye irritation1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Eye pruritus1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Lacrimation increased0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 1/2 (50%)
Ocular hyperaemia0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Vision blurred0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Visual acuity reduced0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Visual impairment0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Vitreous haemorrhage1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Gastrointestinal disorders
Abdominal discomfort0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Abdominal distension0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Abdominal pain0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Abdominal pain upper0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Constipation1/3 (33.3%) 0/3 (0%) 0/3 (0%) 2/3 (66.7%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Diarrhoea1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 3/6 (50%) 1/6 (16.7%) 0/5 (0%) 4/9 (44.4%) 0/2 (0%)
Dry mouth1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Dysphagia0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Flatulence0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Gingival bleeding0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Nausea2/3 (66.7%) 2/3 (66.7%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 4/6 (66.7%) 2/5 (40%) 2/9 (22.2%) 1/2 (50%)
Oral disorder0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Oral pain0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Stomatitis0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 2/9 (22.2%) 1/2 (50%)
Toothache0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Vomiting0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 2/6 (33.3%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
General disorders
Asthenia0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 2/6 (33.3%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Chest pain0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Chills0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Fatigue2/3 (66.7%) 1/3 (33.3%) 0/3 (0%) 3/3 (100%) 3/6 (50%) 4/6 (66.7%) 0/5 (0%) 6/9 (66.7%) 0/2 (0%)
Infusion site bruising0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Malaise1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Mucosal inflammation0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Oedema0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Oedema peripheral0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Pain0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/6 (0%) 1/6 (16.7%) 1/5 (20%) 1/9 (11.1%) 1/2 (50%)
Pyrexia0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 2/6 (33.3%) 2/6 (33.3%) 1/5 (20%) 1/9 (11.1%) 0/2 (0%)
Hepatobiliary disorders
Cholecystitis acute0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Infections and infestations
Beta haemolytic streptococcal infection0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Cellulitis0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Ear infection0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Folliculitis1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Gastroenteritis0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Gastrointestinal candidiasis0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Herpes ophthalmic0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Hordeolum0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Influenza1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Lower respiratory tract infection1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Nasopharyngitis0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Oral candidiasis0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 1/2 (50%)
Otitis externa1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Picornavirus infection0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Respiratory tract infection1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Respiratory tract infection viral1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Rhinitis0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Upper respiratory tract infection2/3 (66.7%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/6 (16.7%) 1/5 (20%) 1/9 (11.1%) 0/2 (0%)
Urinary tract infection0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 1/6 (16.7%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Urinary tract infection staphylococcal0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Viral upper respiratory tract infection2/3 (66.7%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Injury, poisoning and procedural complications
Contusion1/3 (33.3%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Foot fracture0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Skin abrasion0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Skin laceration0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Skin wound0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Stress fracture1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Wound0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Investigations
Activated partial thromboplastin time prolonged0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Alanine aminotransferase increased1/3 (33.3%) 2/3 (66.7%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 3/6 (50%) 2/5 (40%) 3/9 (33.3%) 1/2 (50%)
Aspartate aminotransferase increased1/3 (33.3%) 2/3 (66.7%) 1/3 (33.3%) 1/3 (33.3%) 1/6 (16.7%) 4/6 (66.7%) 2/5 (40%) 4/9 (44.4%) 1/2 (50%)
Blood alkaline phosphatase increased0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 1/6 (16.7%) 3/5 (60%) 2/9 (22.2%) 0/2 (0%)
Blood creatine increased0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Blood creatinine decreased0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Blood creatinine increased0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/6 (33.3%) 1/6 (16.7%) 1/5 (20%) 1/9 (11.1%) 0/2 (0%)
Blood lactate dehydrogenase increased0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Blood potassium decreased0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Blood urea increased0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 2/9 (22.2%) 0/2 (0%)
Calcium ionised increased0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Coagulation time prolonged0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Gamma-glutamyltransferase increased0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Haemoglobin decreased0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Lymphocyte count decreased0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Platelet count decreased0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 1/5 (20%) 1/9 (11.1%) 0/2 (0%)
Weight decreased0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
White blood cell count decreased0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 2/6 (33.3%) 1/5 (20%) 1/9 (11.1%) 0/2 (0%)
Metabolism and nutrition disorders
Decreased appetite0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 3/9 (33.3%) 0/2 (0%)
Hyperalbuminaemia0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Hypercalcaemia0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/6 (16.7%) 1/5 (20%) 4/9 (44.4%) 0/2 (0%)
Hyperglycaemia0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 3/6 (50%) 1/5 (20%) 3/9 (33.3%) 1/2 (50%)
Hypermagnesaemia0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Hypernatraemia0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Hyperuricaemia0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/6 (16.7%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Hypoalbuminaemia0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 1/5 (20%) 1/9 (11.1%) 0/2 (0%)
Hypoglycaemia0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Hypomagnesaemia0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 2/6 (33.3%) 2/5 (40%) 2/9 (22.2%) 0/2 (0%)
Hyponatraemia0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Iron deficiency1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/6 (33.3%) 1/6 (16.7%) 0/5 (0%) 3/9 (33.3%) 1/2 (50%)
Arthritis0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Back pain2/3 (66.7%) 1/3 (33.3%) 1/3 (33.3%) 1/3 (33.3%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 2/9 (22.2%) 1/2 (50%)
Bone pain0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 1/2 (50%)
Groin pain1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Joint swelling0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Muscle spasms1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Muscular weakness0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 1/9 (11.1%) 1/2 (50%)
Musculoskeletal chest pain0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 1/2 (50%)
Musculoskeletal discomfort0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Musculoskeletal pain0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 4/9 (44.4%) 1/2 (50%)
Musculoskeletal stiffness0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Myalgia0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/6 (16.7%) 0/5 (0%) 4/9 (44.4%) 1/2 (50%)
Pain in extremity0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Tendonitis0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 1/2 (50%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Plasmacytoma0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Nervous system disorders
Dizziness0/3 (0%) 1/3 (33.3%) 0/3 (0%) 2/3 (66.7%) 0/6 (0%) 2/6 (33.3%) 1/5 (20%) 1/9 (11.1%) 0/2 (0%)
Dysgeusia1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Headache1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 1/6 (16.7%) 0/6 (0%) 1/5 (20%) 1/9 (11.1%) 2/2 (100%)
Hypoaesthesia0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/6 (16.7%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Memory impairment1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 1/2 (50%)
Neuropathy peripheral1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Paraesthesia1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Peripheral sensory neuropathy0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Tremor0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Psychiatric disorders
Agitation0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Depression0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Insomnia1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 1/9 (11.1%) 1/2 (50%)
Restlessness0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 1/2 (50%)
Sleep disorder0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Stress0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Renal and urinary disorders
Chromaturia0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Haematuria0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Urinary incontinence0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Urinary retention0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Respiratory, thoracic and mediastinal disorders
Cough1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/6 (16.7%) 0/5 (0%) 2/9 (22.2%) 1/2 (50%)
Dyspnoea1/3 (33.3%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 3/9 (33.3%) 1/2 (50%)
Epistaxis0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Hiccups1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Nasal congestion0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Nasal dryness0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Oropharyngeal pain0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Paranasal sinus discomfort0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 1/2 (50%)
Productive cough0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Rhinorrhoea1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 2/6 (33.3%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Skin and subcutaneous tissue disorders
Alopecia1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Erythema1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Hyperhidrosis0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Night sweats0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Pruritus0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Rash2/3 (66.7%) 1/3 (33.3%) 1/3 (33.3%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Rash generalised1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Rash maculo-papular0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Rosacea1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Skin hyperpigmentation0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Skin induration0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Skin lesion0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 1/2 (50%)
Surgical and medical procedures
Cholecystectomy0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/9 (11.1%) 0/2 (0%)
Skin neoplasm excision1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Vascular disorders
Flushing1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Hot flush1/3 (33.3%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/9 (0%) 0/2 (0%)
Hypertension2/3 (66.7%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 1/5 (20%) 0/9 (0%) 0/2 (0%)
Hypotension0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 1/5 (20%) 0/9 (0%) 0/2 (0%)

Limitations/Caveats

Results reported are as of the data snapshot date of March 2019. The study is ongoing.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.

Results Point of Contact

Name/TitleStudy Director
OrganizationAmgen Inc.
Phone866-572-6436
Emailmedinfo@amgen.com
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT02561962
Other Study ID Numbers:
  • 20130314
First Posted:
Sep 28, 2015
Last Update Posted:
Oct 7, 2021
Last Verified:
Sep 1, 2021