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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-002980-16 | EudraCT Number |
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Priortization of other Programs
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The primary objectives of this study are to evaluate the safety and tolerability of emerfetamab in adults with relapsed/refractory acute myeloid leukemia (AML) and to estimate the maximum tolerated dose (MTD) and/or a biologically active dose (eg, recommended phase 2 dose [RP2D]).
This is a first-in-human, open-label, phase 1, sequential dose escalation study. Emerfetamab will be evaluated as a short term intravenous (IV) infusion in adults with relapsed/refractory AML The study will consist of a dose escalation phase and a dose expansion phase. The study was terminated prior to the start of the expansion phase.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose Escalation | Experimental | The dose-escalation cohorts to estimate the MTD will use 2 schedules of emerfetamab administration: Schedule A (Day 1/Day 5 dosing in 14-day cycles) and Schedule B (once daily dosing for cycle 1 followed by twice weekly dosing in following cycles). For Schedule A the starting dose for the first cohort will be 0.05 μg emerfetamab administered as short term IV infusions on day 1 and day 5. The doses administered for the following cohorts will be recommended by the Dose Level Review Team (DLRT). For Schedule B the starting dose will be 72 μg emerfetamab administered as short-term IV infusions daily (QD) during the 14-day cycle 1 after the 72 μg target dose is found to be relatively safe and tolerable by the DLRT for Schedule A. |
|
| Expansion Phase | Experimental | For each schedule, upon completion of the dose escalation cohorts, additional participants may be enrolled to receive emerfetamab at a dose at or below the MTD estimated in the dose escalation cohorts. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Emerfetamab | Drug | Administered by intravenous (IV) infusion. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events | The severity of each adverse event (AE) was graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria, where Grade 1 = mild AE, Grade 2 = moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening and Grade 5 = death due to AE. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria:
| From first dose of study drug until the end of study; median (minimum, maximum) duration was 1.22 (0.10, 5.98) months. |
| Number of Participants With Dose-limiting Toxicities (DLT) | A DLT was defined as any of the events described below occurring in a participant during the DLT window, unless clearly attributable to causes other than emerfetamab:
| Schedule A: From the start of the first infusion on day 1 until day 14. Schedule B: From the start of the first infusion on day 1 to day 28. |
| Measure | Description | Time Frame |
|---|---|---|
| Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of pharmacokinetic (PK) parameters. Concentrations below the lower limit of quantitation (LLOQ; 0.0015 ng/mL) were set to zero before data analysis. | Cycle 1 day 1 at predose and at 1, 6, 24, and 48 hours after the start of infusion, and day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion. |
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Inclusion Criteria
Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
Subjects ≥ 18 years of age at the time of signing consent.
AML as defined by the World Health Organisation (WHO) Classification persisting or recurring following 1 or more treatment courses except promyelocytic leukemia (APML).
Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35294 | United States | ||
| City of Hope National Medical Center |
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| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
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De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
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This study was conducted at 7 centers in United States, Australia, and Germany.
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| ID | Title | Description |
|---|---|---|
| FG000 | Schedule A Cohort 1: 0.05 µg Emerfetamab | Participants received 0.05 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| FG001 | Schedule A Cohort 2: 0.15 µg Emerfetamab | Participants received 0.15 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| FG002 | Schedule A Cohort 3: 0.45 µg Emerfetamab | Participants received 0.45 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| FG003 | Schedule A Cohort 4: 1.5 µg Emerfetamab | Participants received 1.5 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| FG004 | Schedule A Cohort 5: 4.5 µg Emerfetamab | Participants received 4.5 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| FG005 | Schedule A Cohort 6: 7 µg Emerfetamab | Participants received 7 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| FG006 | Schedule A Cohort 7: 9 µg Emerfetamab | Participants received 9 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| FG007 | Schedule A Cohort 8: 18 µg Emerfetamab | Participants received 18 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| FG008 | Schedule A Cohort 9: 36 µg Emerfetamab | Participants received 36 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| FG009 | Schedule A Cohort 10: 72 µg Emerfetamab | Participants received 72 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| FG010 | Schedule A Cohort 11: 110 µg Emerfetamab | Participants received 110 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| FG011 | Schedule A Cohort 12: 36/72 µg Emerfetamab | Participants received 36 µg emerfetamab intravenously on day 1 and 72 µg emerfetamab on day 5 and thereafter of each 14-day cycle for up to 12 total treatment cycles. |
| FG012 | Schedule B Cohort 1: 72 µg Emerfetamab | Participants received 72 µg emerfetamab intravenously once a day (QD) from days 1 to 14 for the first treatment cycle then on day 1, day 4, day 8, and day 11 of each subsequent 14-day cycle for up to a total of 12 cycles. |
| FG013 | Schedule B Cohort 2: 110 µg Emerfetamab | Participants received 72 µg emerfetamab intravenously on day 1 and day 2 then 110 µg emerfetamab once a day from days 3 to 14 in the first treatment cycle, then 110 µg emerfetamab on day 1, day 4, day 8, and day 11 of each subsequent 14-day cycle for up to a total of 12 cycles. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Schedule A Cohort 1: 0.05 µg Emerfetamab | Participants received 0.05 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| BG001 | Schedule A Cohort 2: 0.15 µg Emerfetamab |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Treatment-emergent Adverse Events | The severity of each adverse event (AE) was graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria, where Grade 1 = mild AE, Grade 2 = moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening and Grade 5 = death due to AE. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria:
| All enrolled participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | From first dose of study drug until the end of study; median (minimum, maximum) duration was 1.22 (0.10, 5.98) months. |
|
All-cause mortality is reported from enrollment until end of study; median (min, max) time on study was 1.31 (0.20, 5.98) months. Adverse events are reported from first dose of study drug until the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Schedule A Cohort 1: 0.05 µg Emerfetamab | Participants received 0.05 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Amgen Inc. | 866-572-6436 | medinfo@amgen.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 11, 2019 | Oct 17, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 4, 2022 | Oct 17, 2022 | SAP_001.pdf |
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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Bayesian Model
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| Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. | Cycle 1 day 1 at predose and at 1, 6, 24, and 48 hours after the start of infusion, and day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion. |
| Schedule A: Area Under the Concentration-time Curve From Time Zero to 96 Hours Post-dose (AUC0-96) on Day 1 for Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The area under the curve (AUC) from time zero to 96 hours postdose was calculated using the linear trapezoidal method. | Cycle 1 day 1 at predose and at 1, 6, 24, 48, and 96 hours after the start of infusion. |
| Schedule A: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Non-compartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The area under the concentration-time curve from time 0 relative to the start of the IV infusion to the last quantifiable concentration was estimated using the linear trapezoidal method. | Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion. |
| Schedule A: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Non-compartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The area under the concentration-time curve from time 0 relative to the start of the IV infusion to infinity was estimated using the linear trapezoidal method. | Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion. |
| Schedule A: AUC Total for Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Non-compartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The AUC total was calculated as the sum of AUC0-96hr following the Day 1 dose and AUCinf following the Day 5 dose. | Cycle 1 day 1 at predose and at 1, 6, 24, and 48 hours after the start of infusion, and day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion. |
| Schedule A: Terminal Half-life (T1/2,z) of Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Non-compartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. Terminal half-life (t1/2,z) was calculated as t1/2,z = ln(2)/λz, where λz is the first-order terminal rate constant estimated via linear regression of the terminal log-linear phase. | Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion. |
| Schedule A: Clearance (CL) of Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Non-compartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. Clearance was calculated as Dose/λz*AUCinf. | Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion. |
| Schedule B: Maximum Observed Concentration (Cmax) of Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. | Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion. |
| Schedule B: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. | Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion. |
| Schedule B: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The area under the concentration-time curve from time 0 relative to the start of the IV infusion to the last quantifiable concentration was estimated using the linear trapezoidal method. | Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion. |
| Schedule B: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The area under the concentration-time curve from time 0 relative to the start of the IV infusion to infinity was estimated using the linear trapezoidal method. | Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion. |
| Schedule B: Terminal Half-life (T1/2,z) of Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. | Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion. |
| Schedule B: Clearance of Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. | Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion. |
| Response Rate | Disease response was based upon review of cytogenetics, bone marrow (BM) aspirates/biopsies, and peripheral blood count. Response rate is defined as the percentage of participants with a best overall response of complete remission (CR), CR with incomplete recovery (CRi) or morphologic leukemia-free state (MLFS) according to Revised International Working Group (IWG) response criteria, or CR with partial hematologic recovery (CRh*). CR: BM blasts < 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) > 1.0 x 10^9/L; platelet count > 100 x 10^9/L; independence of red cell transfusions. CRi: All CR criteria except residual neutropenia or thrombocytopenia. MLFS: BM blasts < 5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required. CRh*: < 5% blasts in BM; no evidence of disease; partial recovery of peripheral blood counts: platelets > 50,000/μl, and ANC > 500/μl; no extramedullary disease. | Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months. |
| Duration of Response | Duration of response is defined as the interval from the date of the first disease assessment indicating an overall response to the first documented relapse or death due to any cause, whichever occurred first. | Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months. |
| Time to Response | Time to response is defined as the interval from the first administration of study drug to the first documentation of response. Time to response was evaluated only for participants who achieved a response. | Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months. |
| Time to Progression | Time to progression (event-free survival) is defined as the interval from first administration of study drug to the earliest of date of treatment failure, relapse for responders, or death due to any cause. For non-responders, the event date for treatment failure was assigned as the date of first administration of study drug. | Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months. |
| Duarte |
| California |
| 91010 |
| United States |
| University of Texas MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| University of Washington | Seattle | Washington | 98109 | United States |
| The Alfred Hospital | Melbourne | Victoria | 3004 | Australia |
| The Royal Melbourne Hospital | Parkville | Victoria | 3050 | Australia |
| Klinikum der Ludwig Maximilians Univeritaet | München | 81377 | Germany |
| Sponsor Decision |
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| Lost to Follow-up |
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| Death |
|
Participants received 0.15 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles.
| BG002 | Schedule A Cohort 3: 0.45 µg Emerfetamab | Participants received 0.45 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| BG003 | Schedule A Cohort 4: 1.5 µg Emerfetamab | Participants received 1.5 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| BG004 | Schedule A Cohort 5: 4.5 µg Emerfetamab | Participants received 4.5 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| BG005 | Schedule A Cohort 6: 7 µg Emerfetamab | Participants received 7 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| BG006 | Schedule A Cohort 7: 9 µg Emerfetamab | Participants received 9 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| BG007 | Schedule A Cohort 8: 18 µg Emerfetamab | Participants received 18 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| BG008 | Schedule A Cohort 9: 36 µg Emerfetamab | Participants received 36 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| BG009 | Schedule A Cohort 10: 72 µg Emerfetamab | Participants received 72 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| BG010 | Schedule A Cohort 11: 110 µg Emerfetamab | Participants received 110 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| BG011 | Schedule A Cohort 12: 36/72 µg Emerfetamab | Participants received 36 µg emerfetamab intravenously on day 1 and 72 µg emerfetamab on day 5 and thereafter of each 14-day cycle for up to 12 total treatment cycles. |
| BG012 | Schedule B Cohort 1: 72 µg Emerfetamab | Participants received 72 µg emerfetamab intravenously once a day (QD) from days 1 to 14 for the first treatment cycle then on day 1, day 4, day 8, and day 11 of each subsequent 14-day cycle for up to a total of 12 cycles. |
| BG013 | Schedule B Cohort 2: 110 µg Emerfetamab | Participants received 72 µg emerfetamab intravenously on day 1 and day 2 then 110 µg emerfetamab once a day from days 3 to 14 in the first treatment cycle, then 110 µg emerfetamab on day 1, day 4, day 8, and day 11 of each subsequent 14-day cycle for up to a total of 12 cycles. |
| BG014 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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Participants received 0.05 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| OG001 | Schedule A Cohort 2: 0.15 µg Emerfetamab | Participants received 0.15 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| OG002 | Schedule A Cohort 3: 0.45 µg Emerfetamab | Participants received 0.45 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| OG003 | Schedule A Cohort 4: 1.5 µg Emerfetamab | Participants received 1.5 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| OG004 | Schedule A Cohort 5: 4.5 µg Emerfetamab | Participants received 4.5 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| OG005 | Schedule A Cohort 6: 7 µg Emerfetamab | Participants received 7 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| OG006 | Schedule A Cohort 7: 9 µg Emerfetamab | Participants received 9 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| OG007 | Schedule A Cohort 8: 18 µg Emerfetamab | Participants received 18 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| OG008 | Schedule A Cohort 9: 36 µg Emerfetamab | Participants received 36 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| OG009 | Schedule A Cohort 10: 72 µg Emerfetamab | Participants received 72 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| OG010 | Schedule A Cohort 11: 110 µg Emerfetamab | Participants received 110 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. |
| OG011 | Schedule A Cohort 12: 36/72 µg Emerfetamab | Participants received 36 µg emerfetamab intravenously on day 1 and 72 µg emerfetamab on day 5 and thereafter of each 14-day cycle for up to 12 total treatment cycles. |
| OG012 | Schedule B Cohort 1: 72 µg Emerfetamab | Participants received 72 µg emerfetamab intravenously once a day (QD) from days 1 to 14 for the first treatment cycle then on day 1, day 4, day 8, and day 11 of each subsequent 14-day cycle for up to a total of 12 cycles. |
| OG013 | Schedule B Cohort 2: 110 µg Emerfetamab | Participants received 72 µg emerfetamab intravenously on day 1 and day 2 then 110 µg emerfetamab once a day from days 3 to 14 in the first treatment cycle, then 110 µg emerfetamab on day 1, day 4, day 8, and day 11 of each subsequent 14-day cycle for up to a total of 12 cycles. |
|
|
| Primary | Number of Participants With Dose-limiting Toxicities (DLT) | A DLT was defined as any of the events described below occurring in a participant during the DLT window, unless clearly attributable to causes other than emerfetamab:
| Enrolled participants who received at least 1 dose of study drug who received the minimum cycle 1 doses planned for the respective cohort: Schedule A: 2 doses within 14-day window; Schedule B: completed ≥ 70% of the planned target doses within 28-day window. | Posted | Count of Participants | Participants | Schedule A: From the start of the first infusion on day 1 until day 14. Schedule B: From the start of the first infusion on day 1 to day 28. |
|
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| Secondary | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of pharmacokinetic (PK) parameters. Concentrations below the lower limit of quantitation (LLOQ; 0.0015 ng/mL) were set to zero before data analysis. | Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter. | Posted | Mean | Standard Deviation | ng/mL | Cycle 1 day 1 at predose and at 1, 6, 24, and 48 hours after the start of infusion, and day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion. |
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| Secondary | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. | Participants who received at least 1 dose of study drug, had at least 1 pharmacokinetic (PK) sample collected, with enough data for calculation of the PK parameter. | Posted | Median | Full Range | hours | Cycle 1 day 1 at predose and at 1, 6, 24, and 48 hours after the start of infusion, and day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion. |
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| Secondary | Schedule A: Area Under the Concentration-time Curve From Time Zero to 96 Hours Post-dose (AUC0-96) on Day 1 for Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The area under the curve (AUC) from time zero to 96 hours postdose was calculated using the linear trapezoidal method. | Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter. | Posted | Mean | Standard Deviation | hr*ng/mL | Cycle 1 day 1 at predose and at 1, 6, 24, 48, and 96 hours after the start of infusion. |
|
|
|
| Secondary | Schedule A: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Non-compartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The area under the concentration-time curve from time 0 relative to the start of the IV infusion to the last quantifiable concentration was estimated using the linear trapezoidal method. | Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter. | Posted | Mean | Standard Deviation | hr*ng/mL | Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion. |
|
|
|
| Secondary | Schedule A: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Non-compartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The area under the concentration-time curve from time 0 relative to the start of the IV infusion to infinity was estimated using the linear trapezoidal method. | Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter. | Posted | Mean | Standard Deviation | hr*ng/mL | Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion. |
|
|
|
| Secondary | Schedule A: AUC Total for Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Non-compartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The AUC total was calculated as the sum of AUC0-96hr following the Day 1 dose and AUCinf following the Day 5 dose. | Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter. | Posted | Mean | Standard Deviation | hr*ng/mL | Cycle 1 day 1 at predose and at 1, 6, 24, and 48 hours after the start of infusion, and day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion. |
|
|
|
| Secondary | Schedule A: Terminal Half-life (T1/2,z) of Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Non-compartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. Terminal half-life (t1/2,z) was calculated as t1/2,z = ln(2)/λz, where λz is the first-order terminal rate constant estimated via linear regression of the terminal log-linear phase. | Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter. | Posted | Mean | Standard Deviation | hours | Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion. |
|
|
|
| Secondary | Schedule A: Clearance (CL) of Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Non-compartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. Clearance was calculated as Dose/λz*AUCinf. | Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter. | Posted | Mean | Standard Deviation | mL/hr | Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion. |
|
|
|
| Secondary | Schedule B: Maximum Observed Concentration (Cmax) of Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. | Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter. | Posted | Mean | Standard Deviation | ng/mL | Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion. |
|
|
|
| Secondary | Schedule B: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. | Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter. | Posted | Median | Full Range | hours | Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion. |
|
|
|
| Secondary | Schedule B: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The area under the concentration-time curve from time 0 relative to the start of the IV infusion to the last quantifiable concentration was estimated using the linear trapezoidal method. | Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter. | Posted | Mean | Standard Deviation | hr*ng/mL | Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion. |
|
|
|
| Secondary | Schedule B: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The area under the concentration-time curve from time 0 relative to the start of the IV infusion to infinity was estimated using the linear trapezoidal method. | Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter. No participants in Schedule B cohort 2 had data available for calculation of AUCinf. | Posted | Mean | Standard Deviation | hr*ng/mL | Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion. |
|
|
|
| Secondary | Schedule B: Terminal Half-life (T1/2,z) of Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. | Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter. No participants in Schedule B cohort 2 had data available for calculation of T1/2,z. | Posted | Mean | Standard Deviation | hours | Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion. |
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|
|
| Secondary | Schedule B: Clearance of Emerfetamab | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. | Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter. No participants in Schedule B cohort 2 had data available for calculation of clearance. | Posted | Mean | Standard Deviation | mL/hr | Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion. |
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| Secondary | Response Rate | Disease response was based upon review of cytogenetics, bone marrow (BM) aspirates/biopsies, and peripheral blood count. Response rate is defined as the percentage of participants with a best overall response of complete remission (CR), CR with incomplete recovery (CRi) or morphologic leukemia-free state (MLFS) according to Revised International Working Group (IWG) response criteria, or CR with partial hematologic recovery (CRh*). CR: BM blasts < 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) > 1.0 x 10^9/L; platelet count > 100 x 10^9/L; independence of red cell transfusions. CRi: All CR criteria except residual neutropenia or thrombocytopenia. MLFS: BM blasts < 5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required. CRh*: < 5% blasts in BM; no evidence of disease; partial recovery of peripheral blood counts: platelets > 50,000/μl, and ANC > 500/μl; no extramedullary disease. | All participants who received at least one dose of study drug. | Posted | Number | 80% Confidence Interval | percentage of participants | Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months. |
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| Secondary | Duration of Response | Duration of response is defined as the interval from the date of the first disease assessment indicating an overall response to the first documented relapse or death due to any cause, whichever occurred first. | All participants who received at least one dose of study drug with a best response of CR, CRi, MLFS, or CRh* | Posted | Median | Full Range | days | Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months. |
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| Secondary | Time to Response | Time to response is defined as the interval from the first administration of study drug to the first documentation of response. Time to response was evaluated only for participants who achieved a response. | All participants who received at least one dose of study drug with a best response of CR, CRi, MLFS, or CRh* | Posted | Median | Full Range | days | Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months. |
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| Secondary | Time to Progression | Time to progression (event-free survival) is defined as the interval from first administration of study drug to the earliest of date of treatment failure, relapse for responders, or death due to any cause. For non-responders, the event date for treatment failure was assigned as the date of first administration of study drug. | All participants who received at least one dose of study drug. | Posted | Median | Full Range | days | Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months. |
|
|
|
| 0 |
| 1 |
| 1 |
| 1 |
| 1 |
| 1 |
| EG001 | Schedule A Cohort 2: 0.15 µg Emerfetamab | Participants received 0.15 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. | 1 | 1 | 1 | 1 | 1 | 1 |
| EG002 | Schedule A Cohort 3: 0.45 µg Emerfetamab | Participants received 0.45 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. | 0 | 3 | 2 | 3 | 2 | 3 |
| EG003 | Schedule A Cohort 4: 1.5 µg Emerfetamab | Participants received 1.5 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. | 0 | 3 | 1 | 3 | 3 | 3 |
| EG004 | Schedule A Cohort 5: 4.5 µg Emerfetamab | Participants received 4.5 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. | 0 | 3 | 2 | 3 | 3 | 3 |
| EG005 | Schedule A Cohort 6: 7 µg Emerfetamab | Participants received 7 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. | 0 | 3 | 1 | 3 | 3 | 3 |
| EG006 | Schedule A Cohort 7: 9 µg Emerfetamab | Participants received 9 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. | 0 | 3 | 2 | 3 | 3 | 3 |
| EG007 | Schedule A Cohort 8: 18 µg Emerfetamab | Participants received 18 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. | 1 | 3 | 3 | 3 | 3 | 3 |
| EG008 | Schedule A Cohort 9: 36 µg Emerfetamab | Participants received 36 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. | 0 | 4 | 2 | 4 | 4 | 4 |
| EG009 | Schedule A Cohort 10: 72 µg Emerfetamab | Participants received 72 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. | 0 | 6 | 5 | 6 | 6 | 6 |
| EG010 | Schedule A Cohort 11: 110 µg Emerfetamab | Participants received 110 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. | 0 | 4 | 3 | 4 | 4 | 4 |
| EG011 | Schedule A Cohort 12: 36/72 µg Emerfetamab | Participants received 36 µg emerfetamab intravenously on day 1 and 72 µg emerfetamab on day 5 and thereafter of each 14-day cycle for up to 12 total treatment cycles. | 1 | 4 | 4 | 4 | 4 | 4 |
| EG012 | Schedule B Cohort 1: 72 µg Emerfetamab | Participants received 72 µg emerfetamab intravenously once a day (QD) from days 1 to 14 for the first treatment cycle then on day 1, day 4, day 8, and day 11 of each subsequent 14-day cycle for up to a total of 12 cycles. | 0 | 5 | 1 | 5 | 5 | 5 |
| EG013 | Schedule B Cohort 2: 110 µg Emerfetamab | Participants received 72 µg emerfetamab intravenously on day 1 and day 2 then 110 µg emerfetamab once a day from days 3 to 14 in the first treatment cycle, then 110 µg emerfetamab on day 1, day 4, day 8, and day 11 of each subsequent 14-day cycle for up to a total of 12 cycles. | 0 | 3 | 2 | 3 | 3 | 3 |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Splenomegaly | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Multiple organ dysfunction syndrome | General disorders | MedDRA 25.0 | Systematic Assessment |
|
| Physical deconditioning | General disorders | MedDRA 25.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 25.0 | Systematic Assessment |
|
| Cytokine release syndrome | Immune system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Bacteraemia | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Perirectal abscess | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Pneumonia fungal | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Pneumonia viral | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Septic shock | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Tonsillitis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Vascular device infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Transfusion reaction | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| White blood cell count increased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Tumour lysis syndrome | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Aplastic anaemia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Haemolysis | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hypofibrinogenaemia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Increased tendency to bruise | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
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| Intravascular haemolysis | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Lymph node pain | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Microangiopathic haemolytic anaemia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Pancytopenia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Splenic infarction | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Splenomegaly | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA 25.0 | Systematic Assessment |
|
| Pericardial effusion | Cardiac disorders | MedDRA 25.0 | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA 25.0 | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA 25.0 | Systematic Assessment |
|
| Ventricular arrhythmia | Cardiac disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hypoacusis | Ear and labyrinth disorders | MedDRA 25.0 | Systematic Assessment |
|
| Adrenal insufficiency | Endocrine disorders | MedDRA 25.0 | Systematic Assessment |
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| Conjunctival haemorrhage | Eye disorders | MedDRA 25.0 | Systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA 25.0 | Systematic Assessment |
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| Eye irritation | Eye disorders | MedDRA 25.0 | Systematic Assessment |
|
| Eye pain | Eye disorders | MedDRA 25.0 | Systematic Assessment |
|
| Iridocyclitis | Eye disorders | MedDRA 25.0 | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA 25.0 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Abdominal tenderness | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Anal fissure | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
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| Anal incontinence | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
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| Aphthous ulcer | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
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| Ascites | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
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| Colitis | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Diverticular perforation | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Gastrointestinal disorder | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Mouth haemorrhage | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Oral disorder | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Proctalgia | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Retching | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Salivary hypersecretion | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 25.0 | Systematic Assessment |
|
| Catheter site pain | General disorders | MedDRA 25.0 | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA 25.0 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 25.0 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 25.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 25.0 | Systematic Assessment |
|
| Gait disturbance | General disorders | MedDRA 25.0 | Systematic Assessment |
|
| Generalised oedema | General disorders | MedDRA 25.0 | Systematic Assessment |
|
| Localised oedema | General disorders | MedDRA 25.0 | Systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA 25.0 | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA 25.0 | Systematic Assessment |
|
| Oedema | General disorders | MedDRA 25.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 25.0 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 25.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 25.0 | Systematic Assessment |
|
| Gallbladder oedema | Hepatobiliary disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hepatic cyst | Hepatobiliary disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hepatomegaly | Hepatobiliary disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hypertransaminasaemia | Hepatobiliary disorders | MedDRA 25.0 | Systematic Assessment |
|
| Cytokine release syndrome | Immune system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Abscess limb | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Bacteriuria | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Clostridium difficile colitis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Cytomegalovirus colitis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Cytomegalovirus infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Device related infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Enterocolitis infectious | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Gastrointestinal infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Genitourinary tract infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Infusion site infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Soft tissue infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
|
| Genital contusion | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
|
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
|
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
|
| Skin wound | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
|
| Spinal column injury | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
|
| Transfusion reaction | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
|
| Activated partial thromboplastin time | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Activated partial thromboplastin time prolonged | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Activated partial thromboplastin time shortened | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Amylase increased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Blast cell count increased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Blood calcium decreased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Blood fibrinogen decreased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Blood lactate dehydrogenase increased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Blood lactic acid increased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Blood phosphorus increased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Blood potassium decreased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Blood urea increased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| C-reactive protein increased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Glomerular filtration rate decreased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Hepatic enzyme abnormal | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| International normalised ratio increased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Lipase increased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Liver function test abnormal | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Protein total decreased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Serum ferritin increased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Troponin I increased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Troponin increased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| White blood cell count increased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Abnormal loss of weight | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
|
| Acidosis | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
|
| Fluid retention | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hypermagnesaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hypernatraemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hyperphosphataemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hyperphosphatasaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hypervolaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
|
| Metabolic acidosis | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
|
| Tumour lysis syndrome | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Haemarthrosis | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Joint range of motion decreased | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Muscle twitching | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Osteoporosis | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Soft tissue mass | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Ataxia | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Haemorrhage intracranial | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Speech disorder | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA 25.0 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 25.0 | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hallucination | Psychiatric disorders | MedDRA 25.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 25.0 | Systematic Assessment |
|
| Restlessness | Psychiatric disorders | MedDRA 25.0 | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
|
| Leukocyturia | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
|
| Renal impairment | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
|
| Renal tubular necrosis | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
|
| Atelectasis | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Lung infiltration | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Pulmonary alveolar haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Pulmonary fibrosis | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Pulmonary mass | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Respiratory alkalosis | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Tachypnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Decubitus ulcer | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Erythema multiforme | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Skin disorder | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA 25.0 | Systematic Assessment |
|
| Haematoma | Vascular disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 25.0 | Systematic Assessment |
|
| Lymphoedema | Vascular disorders | MedDRA 25.0 | Systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA 25.0 | Systematic Assessment |
|
| Thrombosis | Vascular disorders | MedDRA 25.0 | Systematic Assessment |
|
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.
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| Alanine aminotransferase increased |
|
| Acute kidney injury |
|
| Aspartate aminotransferase increased |
|
| Bone pain |
|
| Cytokine release syndrome |
|
| Gamma-glutamyltransferase increased |
|
| Lipase increased |
|
|
| Day 5 |
|
|
|
| Day 5 |
|
|