Adult Study: ABT-414 Alone or ABT-414 Plus Temozolomide v... | NCT02343406 | Trialant
NCT02343406
Sponsor
AbbVie
Status
Completed
Last Update Posted
May 22, 2020Actual
Enrollment
266Actual
Phase
Phase 2
Conditions
Glioblastoma
Interventions
Depatuxizumab mafodotin
Temozolomide
Lomustine
Countries
United States
Australia
Austria
Belgium
Canada
Czechia
Finland
France
Germany
Hungary
Ireland
Italy
Mexico
Netherlands
Poland
Singapore
South Korea
Spain
Switzerland
Taiwan
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT02343406
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
M14-483
Secondary IDs
ID
Type
Description
Link
2014-004438-24
EudraCT Number
EORTC 1410-BTG
Other Grant/Funding Number
European Organization for Research and Treatment of Cancer
Brief Title
Adult Study: ABT-414 Alone or ABT-414 Plus Temozolomide vs. Lomustine or Temozolomide for Recurrent Glioblastoma Pediatric Study: Evaluation of ABT-414 in Children With High Grade Gliomas
Official Title
INTELLANCE-2: ABT-414 Alone or ABT-414 Plus Temozolomide Versus Lomustine or Temozolomide for Recurrent Glioblastoma: A Randomized Phase 2 Study of the EORTC Brain Tumor Group
Acronym
INTELLANCE-2
Organization
AbbVieINDUSTRY
Status Module
Record Verification Date
May 2020
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Feb 17, 2015Actual
Primary Completion Date
Jun 24, 2019Actual
Completion Date
Jun 24, 2019Actual
First Submitted Date
Dec 22, 2014
First Submission Date that Met QC Criteria
Jan 16, 2015
First Posted Date
Jan 22, 2015Estimated
Results Waived
Not provided
Results First Submitted Date
Mar 30, 2020
Results First Submitted that Met QC Criteria
May 8, 2020
Results First Posted Date
May 22, 2020Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
May 8, 2020
Last Update Posted Date
May 22, 2020Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
AbbVieINDUSTRY
Collaborators
Name
Class
European Organisation for Research and Treatment of Cancer - EORTC
NETWORK
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
No
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This study was conducted to evaluate the efficacy and safety of depatuxizumab mafodotin (ABT-414) alone or with temozolomide versus temozolomide or lomustine alone in adult participants with recurrent glioblastoma. The study also included a substudy to evaluate safety, tolerability and pharmacokinetics of ABT-414 in a pediatric population.
Detailed Description
The study objectives were to assess whether depatuxizumab mafodotin (ABT-414) alone or in combination with temozolomide (TMZ) improved overall survival (OS), progression-free survival (PFS), tumor response, quality of life, neurological deterioration-free survival (NDFS), and steroid use compared to standard treatment with lomustine single agent or TMZ re-challenge in adult subjects ≥ 18 years of age with centrally-confirmed recurrent epidermal growth factor receptor (EGFR)-amplified glioblastoma. The safety, pharmacokinetics, and efficacy of depatuxizumab mafodotin in children <18 years of age was evaluated in a pediatric substudy. The EMEA-001732-PIP02-15 pediatric investigation plan was withdrawn on 07 July 2019 due to the discontinuation of the depatuxizumab mafodotin research program.
Conditions Module
Conditions
Glioblastoma
Keywords
Glioblastoma
Epithelial Growth Factor vIII mutation
Temozolomide
Lomustine
ABT-414
European Organization for Research and Treatment of Cancer
Recurrent glioblastoma
Epithelial Growth Factor
Brain Tumor
Brain Tumor Group
Antibody Drug Conjugate
EORTC
Pediatric High Grade Gliomas
Pediatric Diffuse Intrinsic Pontine Glioma
Pediatric WHO grade III glioma
Pediatric WHO grade IV glioma
EGFR amplification
Children
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
266Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
ABT-414/temozolomide
Experimental
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult participants
Drug: Depatuxizumab mafodotin
Drug: Temozolomide
ABT-414_adult
Experimental
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to adult participants
Drug: Depatuxizumab mafodotin
Control_lomustine
Active Comparator
Adult participants relapsing during temozolomide (TMZ) treatment or within the first 16 weeks after the first day of the last TMZ cycle received lomustine on Day 1 of every 42-day treatment period until one of the treatment withdrawal criteria was met, up to a maximum of 1 year.
Drug: Lomustine
Control_ temozolomide
Active Comparator
Adult participants relapsing 16 weeks or more after the first day of the last temozolomide (TMZ) cycle received TMZ on Day 1 to Day 5 for the first 28-day cycle, with dose escalation in subsequent cycles in case of adequate tolerance and treatment continuing until one of the treatment withdrawal criteria was met.
Drug: Temozolomide
ABT-414_ pediatric
Experimental
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Depatuxizumab mafodotin
Drug
Adults: intravenous administration (1.25 mg/kg or 1.0 mg/kg body weight) over 30 to 40 minutes once every 2 weeks until one of the treatment withdrawal criteria was met. The dose was 1.25 mg/kg in the original protocol (Version 1) and Version 2, Amendment 1, and was lowered to 1.0 mg/kg in protocol Version 3, Amendment 2. Pediatric participants: Intravenous administration (1.0 mg/kg body weight for those who were 6 to 17 years old at the date of first dose, or 1.3 mg/kg for those who were 0 to 5 years old) over 30 to 40 minutes or as directed by the guidelines once every 2 weeks until one of the treatment withdrawal criteria was met, for a maximum of one year. If used in combination with temozolomide, depatuxizumab mafodotin was dosed on Day 1 and Day 15 of the TMZ cycle (assuming a standard regimen of 200 mg/m^2/day for 5 days of each 28-day cycle; for other TMZ schedules, timing of the depatuxizumab mafodotin dosing schedule were to be discussed with the medical monitor).
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Adult Study: Overall Survival (OS)
Overall Survival (OS) was defined as time from randomization to death due to any cause, regardless of whether the event occurred on or off study drug (depatuxizumab mafodotin/temozolomide/lomustine).
From the date of randomization up to the date of participant's death; participants who completed treatment were to be assessed every 12 weeks, up to 28 months.
Adult Study: Progression-Free Survival (PFS)
Progression-free survival was assessed per response assessment in neuro-oncology criteria (RANO) criteria and assessed by an independent review committee and was defined as the length of time during and after the treatment of a disease, that the participant lived with the disease but did not get worse.
Measured every 8 weeks from date of randomization until the date of first objective progression or subject's death, whichever occurred first, up to 2 years
Pediatric Study: Percentage of Participants With Adverse Events From the First Visit Until 49 Days After the Last Dose of Study Drug
The severity of each adverse event was rated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Version 4.0)
From participant's first visit until 49 days after the participant's last dose of study drug, up to 63 weeks
Pediatric Study: Maximum Observed Serum Concentration (Cmax) of ABT-414
Cmax is the peak concentration that a drug achieves in a specified compartment after the drug has been administrated and before administration of a second dose.
Samples collected Cycle 1 Days 1, 2,3,5,8,15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 5 Day 1; Day 1 of every two cycles starting with Cycle 5; and 35 days after the last dose
Pediatric Study: Maximum Observed Plasma Concentration (Cmax) of Cys-mcMMAF
Secondary Outcomes
Measure
Description
Time Frame
Adult Study: Objective Response Rate (ORR)
The objective response rate (ORR) included best overall responses - complete response (CR) and partial response (PR) - assessed by the independent review committee per response assessment in neurooncology criteria (RANO) criteria from the date of randomization until disease progression or death, whichever came first. All objective responses (CR and PR) must be have been confirmed by repeat MRI 4 weeks after the first time when CR or PR is identified. Any subject who did not meet CR or PR including those who did not have post-baseline radiological assessments was considered a nonresponder.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Adult participants (greater than or equal to 18 years old):
Histologically confirmed de novo (primary) glioblastoma with unequivocal tumor progression or recurrence.
In case of testing at the time of first progression: either at least 3 months after the end of radiotherapy or have tumor progression that is clearly outside the radiation field or have tumor progression unequivocally proven by surgery/biopsy
Absence of any psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule; such conditions should be assessed with the patient before registration in the trial.
Availability of adequate biological material (formalin-fixed paraffin embedded [FFPE] tumor) for central testing of Epithelial Growth Factor Receptor (EGFR) amplification
Presence of EGFR amplification confirmed by central assessment; participants with undetermined EGFR status are excluded
World Health Organization (WHO) Performance status 0 - 2
No more than one line of chemotherapy (concurrent and adjuvant Temozolomide based chemotherapy including in combination with another investigational agent is considered one line of chemotherapy). Chemotherapy must have been completed at least 4 weeks prior to randomization.
Post surgery MRI within 48 hours following surgery, however an MRI scan has to be done within 2 weeks prior to randomization.
Surgery completed at least 2 weeks before randomization and patients should have fully recovered as assessed by investigators.
Renal function: calculated creatinine clearance ≥ 30 mL/min by the Cockcroft-Gault formula.
Liver function: bilirubin < 1.5× upper limit of the normal range (ULN), alkaline phosphatase and transaminases (ASAT) < 2.5× ULN
Pediatric sub-study participants (less than 18 years old):
Histologically proven high grade glioma (HGG: WHO grade III glioma [e.g anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma], grade IV glioma [e.g. glioblastoma, gliosarcoma] or diffuse intrinsic pontine glioma [DIPG]).
Must either have recurrent/progressive tumor or, if newly diagnosed, have completed any planned radiation therapy at least 4 weeks prior to first dose of ABT-414.
The tumor tissue must have been determined to have EGFR amplification, (by local or other testing service).
Availability of adequate biological material for retrospective confirmatory central testing of EGFR amplification
Participant has sufficiently recovered from previous therapy. The investigator believes that benefit of treating the pediatric subject with ABT-414 outweighs the expected risks and that this treatment is in the best interests of the pediatric subject.
Renal function: calculated creatinine clearance ≥ 30 mL/min by the Cockcroft-Gault formula for pediatric patients ≥12 years of age and estimated glomerular filtration rate ≥ 30 mL/min/1.73 m^2 by modified Schwartz equation for pediatric patients < 12 years of age.
Liver function: Total bilirubin ≤ 1.5× upper limit of the normal range (ULN), Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) <= 3× ULN. Participants with Gilbert's syndrome documented in medical history may be enrolled if total bilirubin is < 3 times ULN. Not allowed are participants with known chronic liver disease and/or cirrhosis.
Exclusion Criteria:
Adult population (greater than or equal to 18 years old):
Prior treatment with nitrosoureas
Prior treatment with bevacizumab
Previous exposure to Epithelial Growth Factor Receptor (EGFR) targeted agents, including EGFRvIII targeting agents
Prior discontinuation of temozolomide chemotherapy for toxicity reasons
Prior Radiation Therapy (RT) with a dose over 65 Gy to the brain, stereotactic radiosurgery or brachytherapy unless the recurrence is histologically proven
Previous other malignancies, except for any previous malignancy which was treated with curative intent more than 5 years prior to randomization, and except for adequately controlled limited basal cell carcinoma of the skin, squamous carcinoma of the skin or carcinoma in situ of the cervix
Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to randomization.
No history of wheat allergies and Coeliac disease.
No EIAED, patients who require anti-convulsant therapy must be taking non-enzyme inducing antiepileptic drugs (non-EIAED). Patients previously on EIAED must be fully switched to non-EIAED at least 2 weeks prior to randomization.
Pediatric sub-study (less than 18 years old):
(For recurrent disease) No prior RT with a dose over 65 Gy to the brain, stereotactic radiosurgery or brachytherapy unless the recurrence is histologically proven
No current or recent (within 4 weeks or 5 half-lives [whichever is shorter] before enrollment) treatment with another investigational drug
Female participants of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to randomization.
Clement PMJ, Dirven L, Eoli M, Sepulveda-Sanchez JM, Walenkamp AME, Frenel JS, Franceschi E, Weller M, Chinot O, De Vos FYFL, Whenham N, Sanghera P, Looman J, Kundu MG, Peter de Geus J, Nuyens S, Spruyt M, Gorlia T, Coens C, Golfinopoulos V, Reijneveld JC, van den Bent MJ. Impact of depatuxizumab mafodotin on health-related quality of life and neurological functioning in the phase II EORTC 1410/INTELLANCE 2 trial for EGFR-amplified recurrent glioblastoma. Eur J Cancer. 2021 Apr;147:1-12. doi: 10.1016/j.ejca.2021.01.010. Epub 2021 Feb 15.
AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
Types
Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Analytic Code
Time Frame
Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
Access Criteria
Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
Intention-to-treat population (ITT): all randomized participants. Nine enrolled adult participants did not have a screen failure form reported and were not randomized. In the table below, "Completed" and "Not completed" refer to study drug treatment, and the reasons not completed listings refer to study drug treatment.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
ABT-414/Temozolomide
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult participants
FG001
ABT-414_adult
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to adult participants
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Jan 4, 2019
Mar 18, 2020
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement).
Drug: Depatuxizumab mafodotin
ABT-414/temozolomide
ABT-414_ pediatric
ABT-414_adult
ABT-414
Temozolomide
Drug
Capsules administered orally, 150 mg/m^2 on Days 1-5 for the first 28-day cycle, with dose escalation to 200 mg/m^2 in subsequent cycles in case of adequate tolerance until one of the treatment withdrawal criteria was met.
ABT-414/temozolomide
Control_ temozolomide
TMZ
Lomustine
Drug
Capsules administered orally, 110 mg/m^2 on Day 1 of every 42-day treatment period. Treatment continued until one of the treatment withdrawal criteria was met, for a maximum of one year.
Control_lomustine
Gleostine
Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose. Cys-mcMMAF is a toxic metabolite of depatuxizumab mafodotin.
Samples collected Cycle 1 Days 1, 2, 3, 5, 8
Pediatric Study: Half-life (t1/2) Observed for ABT-414
Half-life is the calculated time it takes for half of the drug to leave the body.
Samples collected Cycle 1 Days 1, 2,3,5,8,15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 5 Day 1; Day 1 of every two cycles starting with Cycle 5; and 35 days after the last dose
Pediatric Study: Half-life (t1/2) Observed for Cys-mcMMAF
Half-life is the calculated time it takes for half of the drug or drug metabolite to leave the body. CysmcMMAF is a toxic metabolite of depatuxizumab mafodotin.
Samples collected Cycle 1 Days 1, 2, 3, 5, 8
Pediatric Study: Area Under the Concentration-time Curve (AUC) Observed for ABT-414
AUC is a measure of how long and how much drug is present in the body after dosing. The AUC of depatuxizumab mafodotin (ABT-414) in the pediatric population was measured following treatment to confirm that this was comparable to adults, and that the dosing levels are appropriate for a pediatric population.
Samples collected Cycle 1 Days 1, 2,3,5,8,15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 5 Day 1; Day 1 of every two cycles starting with Cycle 5; and 35 days after the last dose
Pediatric Study: Area Under the Concentration-time-curve (AUC) Observed for Unconjugated Cys-mcMMAF
AUC is a measure of how long and how much drug or drug metabolite is present in the body after dosing. The AUC of Cys-mcMMAF, a toxic metabolite of depatuxizumab mafodotin, in the pediatric population was measured following treatment to confirm that this was comparable to adults, and that the dosing levels are appropriate for a pediatric population.
Samples collected Cycle 1 Days 1, 2, 3, 5, 8
Every 8 weeks at each assessment of disease, up to 28 months
Adult Study: Overall Survival in the Subgroup With Epidermal Growth Factor Receptor (EGFRvIII) Mutation
Overall Survival (OS) was defined as time from randomization to death due to any cause, regardless of whether the event occurred on or off study drug (depatuxizumab mafodotin/temozolomide/lomustine) for all randomized participants that had the Epidermal Growth Factor Receptor (EGFRvIII) mutation.
From the date of randomization up to the date of participant's death; participants who completed treatment were to be assessed every 12 weeks, up to 28 months
Pediatric Study: Objective Response Rate (ORR)
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Evaluated every 8 weeks (+/- 7 days) at each assessment of disease according to response assessment in neuro-oncology criteria (RANO), until progression or withdrawal up to approximately 52 weeks
Pediatric Study: Best Tumor Response Rate
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Evaluated every 8 weeks (+/- 7 days) at each assessment of disease according to response assessment in neuro-oncology criteria (RANO), until progression or withdrawal up to approximately 52 weeks
Pediatric Study: Duration of Response
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Evaluated every 8 weeks (+/- 7 days) at each assessment of disease according to response assessment in neuro-oncology criteria (RANO), until progression or withdrawal up to approximately 52 weeks
Pediatric Study: Overall Survival
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
From the date of enrollment to the date of death; participants who completed treatment were to be assessed every 12 weeks, up to 28 months
Pediatric Study: Time to Progression
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/ temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, pediatric time to progression data analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Evaluated every 8 weeks (+/- 7 days) from the date of enrollment until the date of first objective progression or participant's death, whichever occurs first, up to approximately 52 weeks
Pediatric Study: Progression-Free Survival
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Evaluated every 8 weeks (+/- 7 days) from the date of enrollment until the date of first objective progression or participant's death, whichever occurs first, up to approximately 52 weeks
Pediatric Study: Percentage of Participants With Changes in Neurological Status and Functioning
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Baseline, Day 1 and 15 of each cycle, every 6 months for 5 years thereafter, and then annually
Aurora
Colorado
80045
United States
Univ of Colorado Cancer Center /ID# 134882
Aurora
Colorado
80045
United States
Sarah Cannon Research Institute at HealthONE - Denver /ID# 141798
Denver
Colorado
80218
United States
Rush University Medical Center /ID# 137542
Chicago
Illinois
60612
United States
Dana-Farber Cancer Institute /ID# 154210
Boston
Massachusetts
02215
United States
Long Island Brain Tumor Center /ID# 134496
Lake Success
New York
11042
United States
Weill Cornell Medicine /ID# 152656
New York
New York
10032-3725
United States
Cleveland Clinic Main Campus /ID# 137540
Cleveland
Ohio
44195
United States
University of Pittsburgh MC /ID# 134491
Pittsburgh
Pennsylvania
15260
United States
Tennessee Oncology, PLLC /ID# 134492
Nashville
Tennessee
37203
United States
UT Southwestern Medical Center /ID# 136718
Dallas
Texas
75390-7208
United States
Swedish Medical Center /ID# 136719
Seattle
Washington
98104
United States
Port Macquarie Base Hospital /ID# 134569
Port Macquarie
New South Wales
2444
Australia
Sydney Children's Hospital /ID# 153533
Randwick
New South Wales
2031
Australia
Royal North Shore Hospital /ID# 147092
Saint Leonards
New South Wales
2065
Australia
Calvary Mater Newcastle /ID# 134570
Waratah
New South Wales
2298
Australia
Southern Medical Day Care Ctr /ID# 134495
Wollongong
New South Wales
2500
Australia
Royal Brisbane and Women's Hospital /ID# 147091
Herston
Queensland
4029
Australia
Royal Adelaide Hospital /ID# 135208
Adelaide
South Australia
5000
Australia
Royal Hobart Hospital /ID# 135209
Hobart
Tasmania
7000
Australia
Barwon Health University Hospital Geelong /ID# 134493
Ospedale Bellaria.Azienda USL IRCCS.Istituto delle Scienze Neurologiche di Bolog /ID# 138335
Bologna
40139
Italy
Ospedale Generale di Bolzano /ID# 138338
Bolzano
39100
Italy
Fondazione IRCCS Istituto Neurologico Carlo Besta /ID# 140395
Milan
20133
Italy
Istituto Oncologico Veneto /ID# 138336
Padova
35128
Italy
Azienda Ospedaliera Sant' Andrea /ID# 138337
Rome
00189
Italy
Hospital Zambrano Hellion /ID# 138076
San Pedro Garza GarcÃa
66278
Mexico
Vrije Universiteit Medisch Centrum /ID# 137221
Amsterdam
1081 HV
Netherlands
Universitair Medisch Centrum Groningen /ID# 138266
Groningen
9713 GZ
Netherlands
Erasmus Medisch Centrum /ID# 136981
Rotterdam
3015 CE
Netherlands
Haaglanden Medisch Centrum /ID# 137222
The Hague
2512 VA
Netherlands
Universitair Medisch Centrum Utrecht /ID# 137219
Utrecht
3584 CX
Netherlands
Prinses Maxima Centrum /ID# 204409
Utrecht
3584 EA
Netherlands
Uniwersyteckie Centrum Kliniczne /ID# 137919
Gdansk
Masovian Voivodeship
80-214
Poland
Wojewodzkie Wielospecjalistycz /ID# 137654
Lodz
93-509
Poland
National University Hospital /ID# 135951
Singapore
119074
Singapore
National Cancer Ctr Singapore /ID# 135952
Singapore
169610
Singapore
KK Women's & Children Hospital /ID# 153676
Singapore
229899
Singapore
Seoul National Univ Bundang ho /ID# 136841
Seongnam
Gyeonggido
13620
South Korea
Samsung Medical Center /ID# 136842
Seoul
Seoul Teugbyeolsi
06351
South Korea
Seoul National University Hospital /ID# 136840
Seoul
03080
South Korea
Instituto Catalán de OncologÃa (ICO) Badalona /ID# 140976
Badalona
Barcelona
08916
Spain
Clinica Universitar de Navarra - Pamplona /ID# 140047
Pamplona
Navarra, Comunidad
31008
Spain
Instituto Catalan de Oncologia (ICO) & Hosp. de Bellvitge /ID# 137688
Barcelona
08908
Spain
Hospital Universitario Nino /ID# 153800
Madrid
28009
Spain
Hosp Univ 12 de Octubre /ID# 137908
Madrid
28041
Spain
Centre Hospitalier Univ Vaudoi /ID# 137929
Lausanne
1011
Switzerland
University Hospital Zurich /ID# 137930
Zurich
8091
Switzerland
China Medical University Hosp /ID# 136976
Taichung
Taichung
40447
Taiwan
National Taiwan Univ Hosp /ID# 136975
Taipei City
Taipei
10002
Taiwan
Taichung Veterans General Hosp /ID# 136977
Taichung
40705
Taiwan
Taipei Veterans General Hosp /ID# 136974
Taipei
11217
Taiwan
Linkou Chang Gung Memorial Ho /ID# 136944
Taoyuan City
33305
Taiwan
Guy's and St Thomas' NHS Found /ID# 140312
London
London, City of
SE1 9RT
United Kingdom
Univ Hospitals Birmingham NHS Foundation trust /ID# 136978
Birmingham
B15 2TG
United Kingdom
Gartnavel General Hospital /ID# 136979
Glasgow
G12 0YN
United Kingdom
Hull and East Yorkshire NHS /ID# 136917
Hull
HU8 9HE
United Kingdom
University College Hospitals /ID# 136879
London
NW1 2BU
United Kingdom
Great Ormond St Hospital NHS /ID# 153421
London
WC1N 3JH
United Kingdom
Christie NHS Foundation Trust /ID# 140313
Manchester
M20 4BX
United Kingdom
Derived
Van Den Bent M, Eoli M, Sepulveda JM, Smits M, Walenkamp A, Frenel JS, Franceschi E, Clement PM, Chinot O, De Vos F, Whenham N, Sanghera P, Weller M, Dubbink HJ, French P, Looman J, Dey J, Krause S, Ansell P, Nuyens S, Spruyt M, Brilhante J, Coens C, Gorlia T, Golfinopoulos V. INTELLANCE 2/EORTC 1410 randomized phase II study of Depatux-M alone and with temozolomide vs temozolomide or lomustine in recurrent EGFR amplified glioblastoma. Neuro Oncol. 2020 May 15;22(5):684-693. doi: 10.1093/neuonc/noz222.
Lassman AB, van den Bent MJ, Gan HK, Reardon DA, Kumthekar P, Butowski N, Lwin Z, Mikkelsen T, Nabors LB, Papadopoulos KP, Penas-Prado M, Simes J, Wheeler H, Walbert T, Scott AM, Gomez E, Lee HJ, Roberts-Rapp L, Xiong H, Ansell PJ, Bain E, Holen KD, Maag D, Merrell R. Safety and efficacy of depatuxizumab mafodotin + temozolomide in patients with EGFR-amplified, recurrent glioblastoma: results from an international phase I multicenter trial. Neuro Oncol. 2019 Jan 1;21(1):106-114. doi: 10.1093/neuonc/noy091.
Gan HK, Reardon DA, Lassman AB, Merrell R, van den Bent M, Butowski N, Lwin Z, Wheeler H, Fichtel L, Scott AM, Gomez EJ, Fischer J, Mandich H, Xiong H, Lee HJ, Munasinghe WP, Roberts-Rapp LA, Ansell PJ, Holen KD, Kumthekar P. Safety, pharmacokinetics, and antitumor response of depatuxizumab mafodotin as monotherapy or in combination with temozolomide in patients with glioblastoma. Neuro Oncol. 2018 May 18;20(6):838-847. doi: 10.1093/neuonc/nox202.
Reardon DA, Lassman AB, van den Bent M, Kumthekar P, Merrell R, Scott AM, Fichtel L, Sulman EP, Gomez E, Fischer J, Lee HJ, Munasinghe W, Xiong H, Mandich H, Roberts-Rapp L, Ansell P, Holen KD, Gan HK. Efficacy and safety results of ABT-414 in combination with radiation and temozolomide in newly diagnosed glioblastoma. Neuro Oncol. 2017 Jul 1;19(7):965-975. doi: 10.1093/neuonc/now257.
FG002
Control_lomustine
Adult participants relapsing during temozolomide (TMZ) treatment or within the first 16 weeks after the first day of the last TMZ cycle received lomustine on Day 1 of every 42-day treatment period until one of the treatment withdrawal criteria was met, up to a maximum of 1 year.
FG003
Control_ Temozolomide
Adult participants relapsing 16 weeks or more after the first day of the last temozolomide (TMZ) cycle received TMZ on Day 1 to Day 5 for the first 28-day cycle, with dose escalation in subsequent cycles in case of adequate tolerance and treatment continuing until one of the treatment withdrawal criteria was met.
FG004
ABT-414_ Pediatric
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement).
FG00088 subjects
FG00186 subjects
FG00260 subjects
FG00326 subjects
FG0046 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0022 subjects
FG0030 subjects
FG0041 subjects
NOT COMPLETED
FG00088 subjects
FG00186 subjects
FG00258 subjects
FG00326 subjects
FG0045 subjects
Type
Comment
Reasons
Progressive disease
FG00072 subjects
FG00170 subjects
FG00243 subjects
FG00315 subjects
FG0045 subjects
Adverse Event
FG0006 subjects
FG0018 subjects
FG0026 subjects
FG0033 subjects
FG004
Withdrawal by Subject
FG0006 subjects
FG0014 subjects
FG0028 subjects
FG0033 subjects
FG004
Death
FG0002 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Start of a new anti-cancer treatment
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0031 subjects
FG004
Other primary malignancy
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Other, not specified
FG0002 subjects
FG0011 subjects
FG0021 subjects
FG0034 subjects
FG004
Intention-to-treat population (ITT): all randomized participants
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
ABT-414/Temozolomide
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult participants
BG001
ABT-414_adult
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to adult participants
BG002
Control_lomustine
Adult participants relapsing during temozolomide (TMZ) treatment or within the first 16 weeks after the first day of the last TMZ cycle received lomustine on Day 1 of every 42-day treatment period until one of the treatment withdrawal criteria was met, up to a maximum of 1 year.
BG003
Control_ Temozolomide
Adult participants relapsing 16 weeks or more after the first day of the last temozolomide (TMZ) cycle received TMZ on Day 1 to Day 5 for the first 28-day cycle, with dose escalation in subsequent cycles in case of adequate tolerance and treatment continuing until one of the treatment withdrawal criteria was met.
BG004
ABT-414_ Pediatric
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement).
BG005
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00088
BG00186
BG00260
BG00326
BG0046
BG005266
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00057.9± 8.15
BG00158.1± 9.18
BG00257.8± 10.62
BG003
Sex: Female, Male
Count of Participants
Participants
No
Title
Denominators
Categories
Title
Measurements
Female
BG00029
BG00136
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
No
Title
Denominators
Categories
American Indian or Alaska Native
Title
Measurements
BG0000
BG0010
BG002
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
Adult Study: Overall Survival (OS)
Overall Survival (OS) was defined as time from randomization to death due to any cause, regardless of whether the event occurred on or off study drug (depatuxizumab mafodotin/temozolomide/lomustine).
All randomized adult participants; participants in the control arms were treated based on the time of relapse and they differ in prognostic profile, therefore data were combined.
Posted
Number
95% Confidence Interval
months
From the date of randomization up to the date of participant's death; participants who completed treatment were to be assessed every 12 weeks, up to 28 months.
ID
Title
Description
OG000
ABT-414/Temozolomide
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult participants
OG001
ABT-414_adult
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to adult participants
OG002
Control (Temozolomide/Lomustine)
Adult participants relapsing during temozolomide (TMZ) treatment or within the first 16 weeks after the first day of the last TMZ cycle who received lomustine on Day 1 of every 42-day treatment period until one of the treatment withdrawal criteria was met, up to a maximum of 1 year OR adult subjects relapsing 16 weeks or more after the first day of the last temozolomide (TMZ) cycle who received TMZ on Day 1 to Day 5 for the first 28-day cycle, with dose escalation in subsequent cycles in case of adequate tolerance and treatment continuing until one of the treatment withdrawal criteria was met.
Units
Counts
Participants
OG00088
OG00186
OG00286
Title
Denominators
Categories
25th quartile
Title
Measurements
OG0005.7(4.0 to 6.8)
OG0014.6(3.5 to 5.5)
OG0024.9(4.1 to 5.4)
50th quartile
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
Stratified at randomization by regions of the world (North America, Europe and Australia, Asia/Other Regions), WHO performance status (0, > 0), timing of relapse (< 16 weeks, ≥ 16 weeks after first day of last TMZ cycle).
Log Rank
= 0.062
2-sided
Cox Proportional Hazard
0.71
2-Sided
95
0.5
1.02
Other
Primary
Adult Study: Progression-Free Survival (PFS)
Progression-free survival was assessed per response assessment in neuro-oncology criteria (RANO) criteria and assessed by an independent review committee and was defined as the length of time during and after the treatment of a disease, that the participant lived with the disease but did not get worse.
All randomized adult participants; participants in the control arms were treated based on the time of relapse and they differ in prognostic profile, therefore data were combined.
Posted
Number
95% Confidence Interval
months
Measured every 8 weeks from date of randomization until the date of first objective progression or subject's death, whichever occurred first, up to 2 years
ID
Title
Description
OG000
ABT-414/Temozolomide
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult participants
OG001
ABT-414_adult
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to adult participants
OG002
Control (Temozolomide/Lomustine)
Adult participants relapsing during temozolomide (TMZ) treatment or within the first 16 weeks after the first day of the last TMZ cycle who received lomustine on Day 1 of every 42-day treatment period until one of the treatment withdrawal criteria was met, up to a maximum of 1 year OR adult subjects relapsing 16 weeks or more after the first day of the last temozolomide (TMZ) cycle who received TMZ on Day 1 to Day 5 for the first 28-day cycle, with dose escalation in subsequent cycles in case of adequate tolerance and treatment continuing until one of the treatment withdrawal criteria was met.
Primary
Pediatric Study: Percentage of Participants With Adverse Events From the First Visit Until 49 Days After the Last Dose of Study Drug
The severity of each adverse event was rated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Version 4.0)
Pediatric participants (safety population)
Posted
Number
percentage of participants
From participant's first visit until 49 days after the participant's last dose of study drug, up to 63 weeks
ID
Title
Description
OG000
ABT-414_ Pediatric
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement).
Units
Counts
Participants
OG000
Primary
Pediatric Study: Maximum Observed Serum Concentration (Cmax) of ABT-414
Cmax is the peak concentration that a drug achieves in a specified compartment after the drug has been administrated and before administration of a second dose.
Pediatric participants with available data
Posted
Mean
Standard Deviation
µg/mL
Samples collected Cycle 1 Days 1, 2,3,5,8,15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 5 Day 1; Day 1 of every two cycles starting with Cycle 5; and 35 days after the last dose
ID
Title
Description
OG000
ABT-414_ Pediatric
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement).
Units
Counts
Participants
OG000
Primary
Pediatric Study: Maximum Observed Plasma Concentration (Cmax) of Cys-mcMMAF
Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose. Cys-mcMMAF is a toxic metabolite of depatuxizumab mafodotin.
Pediatric participants with available data
Posted
Mean
Standard Deviation
ng/mL
Samples collected Cycle 1 Days 1, 2, 3, 5, 8
ID
Title
Description
OG000
ABT-414_ Pediatric
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement).
Units
Counts
Participants
OG000
Primary
Pediatric Study: Half-life (t1/2) Observed for ABT-414
Half-life is the calculated time it takes for half of the drug to leave the body.
Pediatric participants with available data
Posted
Mean
Standard Deviation
days
Samples collected Cycle 1 Days 1, 2,3,5,8,15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 5 Day 1; Day 1 of every two cycles starting with Cycle 5; and 35 days after the last dose
ID
Title
Description
OG000
ABT-414_ Pediatric
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement).
Units
Counts
Participants
OG000
Primary
Pediatric Study: Half-life (t1/2) Observed for Cys-mcMMAF
Half-life is the calculated time it takes for half of the drug or drug metabolite to leave the body. CysmcMMAF is a toxic metabolite of depatuxizumab mafodotin.
Pediatric participants with available data
Posted
Mean
Standard Deviation
days
Samples collected Cycle 1 Days 1, 2, 3, 5, 8
ID
Title
Description
OG000
ABT-414_ Pediatric
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement).
Units
Counts
Participants
OG000
Primary
Pediatric Study: Area Under the Concentration-time Curve (AUC) Observed for ABT-414
AUC is a measure of how long and how much drug is present in the body after dosing. The AUC of depatuxizumab mafodotin (ABT-414) in the pediatric population was measured following treatment to confirm that this was comparable to adults, and that the dosing levels are appropriate for a pediatric population.
Pediatric participants with available data
Posted
Mean
Standard Deviation
µg*h/mL
Samples collected Cycle 1 Days 1, 2,3,5,8,15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 5 Day 1; Day 1 of every two cycles starting with Cycle 5; and 35 days after the last dose
ID
Title
Description
OG000
ABT-414_ Pediatric
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement).
Units
Counts
Participants
OG000
Primary
Pediatric Study: Area Under the Concentration-time-curve (AUC) Observed for Unconjugated Cys-mcMMAF
AUC is a measure of how long and how much drug or drug metabolite is present in the body after dosing. The AUC of Cys-mcMMAF, a toxic metabolite of depatuxizumab mafodotin, in the pediatric population was measured following treatment to confirm that this was comparable to adults, and that the dosing levels are appropriate for a pediatric population.
Pediatric participants with available data
Posted
Mean
Standard Deviation
ng*h/mL
Samples collected Cycle 1 Days 1, 2, 3, 5, 8
ID
Title
Description
OG000
ABT-414_ Pediatric
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement).
Units
Counts
Participants
OG000
Secondary
Adult Study: Objective Response Rate (ORR)
The objective response rate (ORR) included best overall responses - complete response (CR) and partial response (PR) - assessed by the independent review committee per response assessment in neurooncology criteria (RANO) criteria from the date of randomization until disease progression or death, whichever came first. All objective responses (CR and PR) must be have been confirmed by repeat MRI 4 weeks after the first time when CR or PR is identified. Any subject who did not meet CR or PR including those who did not have post-baseline radiological assessments was considered a nonresponder.
Participants with measurable disease at baseline; participants in the control arms were treated based on the time of relapse and they differ in prognostic profile, therefore data were combined.
Posted
Number
95% Confidence Interval
percentage of participants
Every 8 weeks at each assessment of disease, up to 28 months
ID
Title
Description
OG000
ABT-414/Temozolomide
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult participants
OG001
ABT-414_adult
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to adult participants
OG002
Control (Temozolomide/Lomustine)
Secondary
Adult Study: Overall Survival in the Subgroup With Epidermal Growth Factor Receptor (EGFRvIII) Mutation
Overall Survival (OS) was defined as time from randomization to death due to any cause, regardless of whether the event occurred on or off study drug (depatuxizumab mafodotin/temozolomide/lomustine) for all randomized participants that had the Epidermal Growth Factor Receptor (EGFRvIII) mutation.
Randomized adult participants with EGFRvIII-mutated tumors; participants in the control arms were treated based on the time of relapse and they differ in prognostic profile, therefore data were combined.
Posted
Number
95% Confidence Interval
months
From the date of randomization up to the date of participant's death; participants who completed treatment were to be assessed every 12 weeks, up to 28 months
ID
Title
Description
OG000
ABT-414/Temozolomide
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult participants
OG001
ABT-414_adult
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to adult participants
OG002
Control (Temozolomide/Lomustine)
Adult participants relapsing during temozolomide (TMZ) treatment or within the first 16 weeks after the first day of the last TMZ cycle who received lomustine on Day 1 of every 42-day treatment period until one of the treatment withdrawal criteria was met, up to a maximum of 1 year OR adult subjects relapsing 16 weeks or more after the first day of the last temozolomide (TMZ) cycle who received TMZ on Day 1 to Day 5 for the first 28-day cycle, with dose escalation in subsequent cycles in case of adequate tolerance and treatment continuing until one of the treatment withdrawal criteria was met.
Secondary
Pediatric Study: Objective Response Rate (ORR)
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Pediatric efficacy data were not collected
Posted
Evaluated every 8 weeks (+/- 7 days) at each assessment of disease according to response assessment in neuro-oncology criteria (RANO), until progression or withdrawal up to approximately 52 weeks
ID
Title
Description
OG000
ABT-414_ Pediatric
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement).
Units
Counts
Participants
Secondary
Pediatric Study: Best Tumor Response Rate
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Pediatric efficacy data were not collected
Posted
Evaluated every 8 weeks (+/- 7 days) at each assessment of disease according to response assessment in neuro-oncology criteria (RANO), until progression or withdrawal up to approximately 52 weeks
ID
Title
Description
OG000
ABT-414_ Pediatric
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement).
Units
Counts
Participants
Secondary
Pediatric Study: Duration of Response
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Pediatric efficacy data were not collected
Posted
Evaluated every 8 weeks (+/- 7 days) at each assessment of disease according to response assessment in neuro-oncology criteria (RANO), until progression or withdrawal up to approximately 52 weeks
ID
Title
Description
OG000
ABT-414_ Pediatric
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement).
Units
Counts
Participants
Secondary
Pediatric Study: Overall Survival
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Pediatric efficacy data were not collected
Posted
From the date of enrollment to the date of death; participants who completed treatment were to be assessed every 12 weeks, up to 28 months
ID
Title
Description
OG000
ABT-414_ Pediatric
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement).
Units
Counts
Participants
Secondary
Pediatric Study: Time to Progression
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/ temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, pediatric time to progression data analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Pediatric efficacy data were not collected
Posted
Evaluated every 8 weeks (+/- 7 days) from the date of enrollment until the date of first objective progression or participant's death, whichever occurs first, up to approximately 52 weeks
ID
Title
Description
OG000
ABT-414_ Pediatric
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement).
Units
Counts
Participants
Secondary
Pediatric Study: Progression-Free Survival
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Pediatric efficacy data were not collected
Posted
Evaluated every 8 weeks (+/- 7 days) from the date of enrollment until the date of first objective progression or participant's death, whichever occurs first, up to approximately 52 weeks
ID
Title
Description
OG000
ABT-414_ Pediatric
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement).
Units
Counts
Participants
Secondary
Pediatric Study: Percentage of Participants With Changes in Neurological Status and Functioning
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Pediatric efficacy data were not collected
Posted
Baseline, Day 1 and 15 of each cycle, every 6 months for 5 years thereafter, and then annually
ID
Title
Description
OG000
ABT-414_ Pediatric
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement).
Units
Counts
Participants
Time Frame
Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 35 days (adults) or 49 days (pediatric subjects) after the last dose of study drug, up to 125 weeks.
Description
Serious and non-serious adverse events occurring after the subject signed the study-specific informed consent and prior to the initial dose of study drug were to be collected only if they were considered by the Investigator to be causally related to required study procedures.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
ABT-414/Temozolomide
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult subjects
80
88
39
88
84
88
EG001
ABT-414_adult
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to adult subjects
80
84
30
84
76
84
EG002
Control_lomustine
Adult subjects relapsing during temozolomide (TMZ) treatment or within the first 16 weeks after the first day of the last TMZ cycle received lomustine on Day 1 of every 42-day treatment period until one of the treatment withdrawal criteria was met, up to a maximum of 1 year.
52
56
19
56
46
56
EG003
Control_ Temozolomide
Adult subjects relapsing 16 weeks or more after the first day of the last temozolomide (TMZ) cycle received TMZ on Day 1 to Day 5 for the first 28-day cycle, with dose escalation in subsequent cycles in case of adequate tolerance and treatment continuing until one of the treatment withdrawal criteria was met.
21
21
5
21
20
21
EG004
ABT-414_ Pediatric
Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement).
5
6
3
6
6
6
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
FEBRILE NEUTROPENIA
Blood and lymphatic system disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0021 events1 affected56 at risk
EG0030 events0 affected21 at risk
EG0040 events0 affected6 at risk
THROMBOCYTOPENIA
Blood and lymphatic system disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0021 events1 affected56 at risk
EG003
VERTIGO
Ear and labyrinth disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
CORNEAL EPITHELIAL MICROCYSTS
Eye disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
ABDOMINAL PAIN
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
CONSTIPATION
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0021 events1 affected56 at risk
EG003
DIARRHOEA
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
DIVERTICULAR PERFORATION
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
NAUSEA
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
VOMITING
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0021 events1 affected56 at risk
EG003
DISEASE PROGRESSION
General disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
FATIGUE
General disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0021 events1 affected56 at risk
EG003
GENERAL PHYSICAL HEALTH DETERIORATION
General disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
PYREXIA
General disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
HEPATIC STEATOSIS
Hepatobiliary disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
DIVERTICULITIS
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
LOWER RESPIRATORY TRACT INFECTION
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
MENINGITIS
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
PNEUMONIA
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
RESPIRATORY TRACT INFECTION
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0021 events1 affected56 at risk
EG003
RESPIRATORY TRACT INFECTION VIRAL
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
SEPSIS
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0002 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
UPPER RESPIRATORY TRACT INFECTION
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
URINARY TRACT INFECTION
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0022 events1 affected56 at risk
EG003
WOUND INFECTION
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
CLAVICLE FRACTURE
Injury, poisoning and procedural complications
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0021 events1 affected56 at risk
EG003
FALL
Injury, poisoning and procedural complications
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0011 events1 affected84 at risk
EG0023 events1 affected56 at risk
EG003
FEMORAL NECK FRACTURE
Injury, poisoning and procedural complications
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
HIP FRACTURE
Injury, poisoning and procedural complications
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
HUMERUS FRACTURE
Injury, poisoning and procedural complications
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
LUMBAR VERTEBRAL FRACTURE
Injury, poisoning and procedural complications
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0021 events1 affected56 at risk
EG003
PELVIC FRACTURE
Injury, poisoning and procedural complications
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0022 events1 affected56 at risk
EG003
ALANINE AMINOTRANSFERASE INCREASED
Investigations
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
BODY TEMPERATURE INCREASED
Investigations
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0021 events1 affected56 at risk
EG003
DECREASED APPETITE
Metabolism and nutrition disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
DEHYDRATION
Metabolism and nutrition disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0021 events1 affected56 at risk
EG003
HYPERGLYCAEMIA
Metabolism and nutrition disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
HYPONATRAEMIA
Metabolism and nutrition disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
ARTHRALGIA
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0021 events1 affected56 at risk
EG003
BACK PAIN
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0021 events1 affected56 at risk
EG003
MUSCULAR WEAKNESS
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
MALIGNANT NEOPLASM PROGRESSION
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 22.0
Systematic Assessment
EG00016 events11 affected88 at risk
EG00110 events7 affected84 at risk
EG0024 events2 affected56 at risk
EG003
METASTASES TO PERITONEUM
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0013 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
NEOPLASM PROGRESSION
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
TUMOUR HAEMORRHAGE
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 22.0
Systematic Assessment
EG0002 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
APHASIA
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
APRAXIA
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
BRAIN OEDEMA
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0002 events2 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
CEREBROVASCULAR ACCIDENT
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
EPILEPSY
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0012 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
GENERALISED TONIC-CLONIC SEIZURE
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0021 events1 affected56 at risk
EG003
HAEMORRHAGE INTRACRANIAL
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0013 events2 affected84 at risk
EG0021 events1 affected56 at risk
EG003
HEADACHE
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
HEMIPARESIS
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0021 events1 affected56 at risk
EG003
HEMIPLEGIA
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
HYDROCEPHALUS
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0021 events1 affected56 at risk
EG003
MUSCLE SPASTICITY
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0002 events2 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
NERVOUS SYSTEM DISORDER
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0012 events2 affected84 at risk
EG0020 events0 affected56 at risk
EG003
NEUROLOGICAL DECOMPENSATION
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0013 events3 affected84 at risk
EG0021 events1 affected56 at risk
EG003
PARTIAL SEIZURES
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0002 events1 affected88 at risk
EG0012 events2 affected84 at risk
EG0020 events0 affected56 at risk
EG003
SEIZURE
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0009 events9 affected88 at risk
EG0013 events3 affected84 at risk
EG0024 events4 affected56 at risk
EG003
STATUS EPILEPTICUS
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
SUBDURAL HYGROMA
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
SYNCOPE
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0021 events1 affected56 at risk
EG003
TRANSIENT ISCHAEMIC ATTACK
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
COMPLETED SUICIDE
Psychiatric disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
CONFUSIONAL STATE
Psychiatric disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0021 events1 affected56 at risk
EG003
SUICIDAL IDEATION
Psychiatric disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0021 events1 affected56 at risk
EG003
SUICIDE ATTEMPT
Psychiatric disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
NEPHROLITHIASIS
Renal and urinary disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
HYPOXIA
Respiratory, thoracic and mediastinal disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
PNEUMONIA ASPIRATION
Respiratory, thoracic and mediastinal disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
PNEUMONITIS
Respiratory, thoracic and mediastinal disorders
MedDRA 22.0
Systematic Assessment
EG0002 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
PULMONARY EMBOLISM
Respiratory, thoracic and mediastinal disorders
MedDRA 22.0
Systematic Assessment
EG0004 events3 affected88 at risk
EG0010 events0 affected84 at risk
EG0022 events2 affected56 at risk
EG003
RESPIRATORY FAILURE
Respiratory, thoracic and mediastinal disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
DEEP VEIN THROMBOSIS
Vascular disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0021 events1 affected56 at risk
EG003
SUBGALEAL HAEMATOMA
Vascular disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
ANAEMIA
Blood and lymphatic system disorders
MedDRA 22.0
Systematic Assessment
EG0007 events7 affected88 at risk
EG00113 events4 affected84 at risk
EG0027 events5 affected56 at risk
EG0030 events0 affected21 at risk
EG0041 events1 affected6 at risk
LEUKOPENIA
Blood and lymphatic system disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG00211 events5 affected56 at risk
EG003
LYMPHOPENIA
Blood and lymphatic system disorders
MedDRA 22.0
Systematic Assessment
EG00017 events9 affected88 at risk
EG00116 events8 affected84 at risk
EG00213 events9 affected56 at risk
EG003
NEUTROPENIA
Blood and lymphatic system disorders
MedDRA 22.0
Systematic Assessment
EG0002 events2 affected88 at risk
EG0013 events1 affected84 at risk
EG00212 events10 affected56 at risk
EG003
THROMBOCYTOPENIA
Blood and lymphatic system disorders
MedDRA 22.0
Systematic Assessment
EG00055 events19 affected88 at risk
EG00111 events7 affected84 at risk
EG00234 events19 affected56 at risk
EG003
BRADYCARDIA
Cardiac disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
SINUS BRADYCARDIA
Cardiac disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
EAR PAIN
Ear and labyrinth disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
CUSHINGOID
Endocrine disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
CATARACT
Eye disorders
MedDRA 22.0
Systematic Assessment
EG0004 events4 affected88 at risk
EG0015 events5 affected84 at risk
EG0020 events0 affected56 at risk
EG003
CORNEAL EPITHELIAL MICROCYSTS
Eye disorders
MedDRA 22.0
Systematic Assessment
EG00064 events25 affected88 at risk
EG00122 events12 affected84 at risk
EG0020 events0 affected56 at risk
EG003
CORNEAL OPACITY
Eye disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0013 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
DRY EYE
Eye disorders
MedDRA 22.0
Systematic Assessment
EG00036 events20 affected88 at risk
EG00133 events22 affected84 at risk
EG0021 events1 affected56 at risk
EG003
EYE IRRITATION
Eye disorders
MedDRA 22.0
Systematic Assessment
EG0008 events6 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
EYE PAIN
Eye disorders
MedDRA 22.0
Systematic Assessment
EG00010 events7 affected88 at risk
EG00120 events11 affected84 at risk
EG0020 events0 affected56 at risk
EG003
EYELID PTOSIS
Eye disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
KERATITIS
Eye disorders
MedDRA 22.0
Systematic Assessment
EG00024 events16 affected88 at risk
EG00145 events27 affected84 at risk
EG0020 events0 affected56 at risk
EG003
KERATOPATHY
Eye disorders
MedDRA 22.0
Systematic Assessment
EG00024 events15 affected88 at risk
EG0018 events7 affected84 at risk
EG0020 events0 affected56 at risk
EG003
LACRIMATION INCREASED
Eye disorders
MedDRA 22.0
Systematic Assessment
EG00010 events9 affected88 at risk
EG0015 events3 affected84 at risk
EG0020 events0 affected56 at risk
EG003
OCULAR DISCOMFORT
Eye disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
PHOTOPHOBIA
Eye disorders
MedDRA 22.0
Systematic Assessment
EG00014 events12 affected88 at risk
EG00111 events8 affected84 at risk
EG0020 events0 affected56 at risk
EG003
PUNCTATE KERATITIS
Eye disorders
MedDRA 22.0
Systematic Assessment
EG0006 events3 affected88 at risk
EG0016 events6 affected84 at risk
EG0020 events0 affected56 at risk
EG003
PUPILLARY REFLEX IMPAIRED
Eye disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0013 events2 affected84 at risk
EG0020 events0 affected56 at risk
EG003
VISION BLURRED
Eye disorders
MedDRA 22.0
Systematic Assessment
EG00052 events30 affected88 at risk
EG00127 events17 affected84 at risk
EG0021 events1 affected56 at risk
EG003
VISUAL IMPAIRMENT
Eye disorders
MedDRA 22.0
Systematic Assessment
EG0003 events3 affected88 at risk
EG0016 events5 affected84 at risk
EG0020 events0 affected56 at risk
EG003
ABDOMINAL DISTENSION
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0012 events2 affected84 at risk
EG0021 events1 affected56 at risk
EG003
ABDOMINAL PAIN
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0002 events2 affected88 at risk
EG0012 events2 affected84 at risk
EG0020 events0 affected56 at risk
EG003
ABDOMINAL PAIN UPPER
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
CONSTIPATION
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG00028 events23 affected88 at risk
EG0019 events8 affected84 at risk
EG0022 events2 affected56 at risk
EG003
DIARRHOEA
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0009 events8 affected88 at risk
EG0016 events6 affected84 at risk
EG0023 events3 affected56 at risk
EG003
NAUSEA
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG00033 events21 affected88 at risk
EG0018 events8 affected84 at risk
EG0026 events6 affected56 at risk
EG003
PROCTALGIA
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
VOMITING
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG00023 events19 affected88 at risk
EG0015 events5 affected84 at risk
EG0024 events3 affected56 at risk
EG003
ASTHENIA
General disorders
MedDRA 22.0
Systematic Assessment
EG0009 events6 affected88 at risk
EG0014 events3 affected84 at risk
EG0027 events4 affected56 at risk
EG003
FATIGUE
General disorders
MedDRA 22.0
Systematic Assessment
EG00060 events33 affected88 at risk
EG00139 events27 affected84 at risk
EG00216 events13 affected56 at risk
EG003
GAIT DISTURBANCE
General disorders
MedDRA 22.0
Systematic Assessment
EG0005 events4 affected88 at risk
EG0015 events3 affected84 at risk
EG0022 events2 affected56 at risk
EG003
INFLUENZA LIKE ILLNESS
General disorders
MedDRA 22.0
Systematic Assessment
EG0004 events4 affected88 at risk
EG0010 events0 affected84 at risk
EG0021 events1 affected56 at risk
EG003
OEDEMA PERIPHERAL
General disorders
MedDRA 22.0
Systematic Assessment
EG0009 events7 affected88 at risk
EG0012 events2 affected84 at risk
EG0025 events4 affected56 at risk
EG003
PYREXIA
General disorders
MedDRA 22.0
Systematic Assessment
EG0005 events5 affected88 at risk
EG0014 events4 affected84 at risk
EG0021 events1 affected56 at risk
EG003
CONJUNCTIVITIS
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0008 events7 affected88 at risk
EG0016 events6 affected84 at risk
EG0021 events1 affected56 at risk
EG003
EYE INFECTION
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
INFLUENZA
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
NASOPHARYNGITIS
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0006 events5 affected88 at risk
EG0011 events1 affected84 at risk
EG0023 events3 affected56 at risk
EG003
ORAL CANDIDIASIS
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0002 events2 affected88 at risk
EG0012 events2 affected84 at risk
EG0021 events1 affected56 at risk
EG003
UPPER RESPIRATORY TRACT INFECTION
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
VAGINAL INFECTION
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
VULVOVAGINAL CANDIDIASIS
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
FALL
Injury, poisoning and procedural complications
MedDRA 22.0
Systematic Assessment
EG0005 events4 affected88 at risk
EG0015 events4 affected84 at risk
EG0023 events3 affected56 at risk
EG003
ALANINE AMINOTRANSFERASE INCREASED
Investigations
MedDRA 22.0
Systematic Assessment
EG00024 events11 affected88 at risk
EG00117 events12 affected84 at risk
EG0024 events3 affected56 at risk
EG003
ASPARTATE AMINOTRANSFERASE INCREASED
Investigations
MedDRA 22.0
Systematic Assessment
EG00012 events9 affected88 at risk
EG00115 events13 affected84 at risk
EG0022 events2 affected56 at risk
EG003
BLOOD CULTURE POSITIVE
Investigations
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
GAMMA-GLUTAMYLTRANSFERASE INCREASED
Investigations
MedDRA 22.0
Systematic Assessment
EG0006 events4 affected88 at risk
EG00115 events8 affected84 at risk
EG0020 events0 affected56 at risk
EG003
LYMPHOCYTE COUNT DECREASED
Investigations
MedDRA 22.0
Systematic Assessment
EG00011 events7 affected88 at risk
EG0014 events4 affected84 at risk
EG00213 events6 affected56 at risk
EG003
NEUTROPHIL COUNT DECREASED
Investigations
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0011 events1 affected84 at risk
EG00211 events8 affected56 at risk
EG003
PLATELET COUNT DECREASED
Investigations
MedDRA 22.0
Systematic Assessment
EG00046 events21 affected88 at risk
EG00117 events9 affected84 at risk
EG00231 events15 affected56 at risk
EG003
WEIGHT DECREASED
Investigations
MedDRA 22.0
Systematic Assessment
EG0004 events4 affected88 at risk
EG0019 events7 affected84 at risk
EG0024 events3 affected56 at risk
EG003
WEIGHT INCREASED
Investigations
MedDRA 22.0
Systematic Assessment
EG0008 events6 affected88 at risk
EG0019 events6 affected84 at risk
EG0023 events3 affected56 at risk
EG003
WHITE BLOOD CELL COUNT DECREASED
Investigations
MedDRA 22.0
Systematic Assessment
EG0007 events3 affected88 at risk
EG0012 events2 affected84 at risk
EG00215 events5 affected56 at risk
EG003
DECREASED APPETITE
Metabolism and nutrition disorders
MedDRA 22.0
Systematic Assessment
EG00011 events10 affected88 at risk
EG0017 events5 affected84 at risk
EG0022 events2 affected56 at risk
EG003
HYPERGLYCAEMIA
Metabolism and nutrition disorders
MedDRA 22.0
Systematic Assessment
EG0008 events5 affected88 at risk
EG0013 events3 affected84 at risk
EG0021 events1 affected56 at risk
EG003
HYPERKALAEMIA
Metabolism and nutrition disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
HYPERMAGNESAEMIA
Metabolism and nutrition disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
HYPOKALAEMIA
Metabolism and nutrition disorders
MedDRA 22.0
Systematic Assessment
EG00012 events7 affected88 at risk
EG0012 events2 affected84 at risk
EG0021 events1 affected56 at risk
EG003
ARTHRALGIA
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0007 events6 affected88 at risk
EG0013 events3 affected84 at risk
EG0023 events3 affected56 at risk
EG003
BACK PAIN
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0008 events7 affected88 at risk
EG0017 events7 affected84 at risk
EG0024 events4 affected56 at risk
EG003
MUSCLE SPASMS
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0011 events1 affected84 at risk
EG0021 events1 affected56 at risk
EG003
MUSCULAR WEAKNESS
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0004 events4 affected88 at risk
EG0013 events3 affected84 at risk
EG0022 events2 affected56 at risk
EG003
MUSCULOSKELETAL PAIN
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0006 events5 affected88 at risk
EG0012 events2 affected84 at risk
EG0020 events0 affected56 at risk
EG003
PAIN IN EXTREMITY
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0007 events6 affected88 at risk
EG0011 events1 affected84 at risk
EG0021 events1 affected56 at risk
EG003
PAIN IN JAW
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0021 events1 affected56 at risk
EG003
APHASIA
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG00010 events9 affected88 at risk
EG00110 events9 affected84 at risk
EG0023 events3 affected56 at risk
EG003
ATAXIA
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0011 events1 affected84 at risk
EG0022 events2 affected56 at risk
EG003
BALANCE DISORDER
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0003 events2 affected88 at risk
EG0011 events1 affected84 at risk
EG0023 events3 affected56 at risk
EG003
DEPRESSED LEVEL OF CONSCIOUSNESS
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
DIZZINESS
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0009 events7 affected88 at risk
EG0012 events2 affected84 at risk
EG0021 events1 affected56 at risk
EG003
DYSARTHRIA
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0013 events3 affected84 at risk
EG0024 events3 affected56 at risk
EG003
ENCEPHALOPATHY
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
HEADACHE
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG00031 events21 affected88 at risk
EG00121 events20 affected84 at risk
EG0028 events8 affected56 at risk
EG003
HEMIPARESIS
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0002 events2 affected88 at risk
EG0017 events7 affected84 at risk
EG0029 events7 affected56 at risk
EG003
HYDROCEPHALUS
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
PERIPHERAL MOTOR NEUROPATHY
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0024 events3 affected56 at risk
EG003
SEIZURE
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG00013 events6 affected88 at risk
EG00111 events7 affected84 at risk
EG0029 events5 affected56 at risk
EG003
SOMNOLENCE
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0003 events3 affected88 at risk
EG0013 events3 affected84 at risk
EG0026 events3 affected56 at risk
EG003
ANXIETY
Psychiatric disorders
MedDRA 22.0
Systematic Assessment
EG0006 events5 affected88 at risk
EG0012 events2 affected84 at risk
EG0021 events1 affected56 at risk
EG003
DEPRESSION
Psychiatric disorders
MedDRA 22.0
Systematic Assessment
EG0004 events4 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
DISINHIBITION
Psychiatric disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
INSOMNIA
Psychiatric disorders
MedDRA 22.0
Systematic Assessment
EG00010 events8 affected88 at risk
EG0017 events6 affected84 at risk
EG0022 events2 affected56 at risk
EG003
URINARY INCONTINENCE
Renal and urinary disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0013 events3 affected84 at risk
EG0023 events3 affected56 at risk
EG003
COUGH
Respiratory, thoracic and mediastinal disorders
MedDRA 22.0
Systematic Assessment
EG0007 events5 affected88 at risk
EG0012 events2 affected84 at risk
EG0023 events3 affected56 at risk
EG003
DYSPHONIA
Respiratory, thoracic and mediastinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0021 events1 affected56 at risk
EG003
DYSPNOEA
Respiratory, thoracic and mediastinal disorders
MedDRA 22.0
Systematic Assessment
EG0008 events8 affected88 at risk
EG0011 events1 affected84 at risk
EG0021 events1 affected56 at risk
EG003
EPISTAXIS
Respiratory, thoracic and mediastinal disorders
MedDRA 22.0
Systematic Assessment
EG0003 events2 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
NASAL CONGESTION
Respiratory, thoracic and mediastinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
OROPHARYNGEAL PAIN
Respiratory, thoracic and mediastinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
PRODUCTIVE COUGH
Respiratory, thoracic and mediastinal disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
DERMATITIS DIAPER
Skin and subcutaneous tissue disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
DRY SKIN
Skin and subcutaneous tissue disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0015 events5 affected84 at risk
EG0020 events0 affected56 at risk
EG003
ERYTHEMA
Skin and subcutaneous tissue disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
HYPERKERATOSIS
Skin and subcutaneous tissue disorders
MedDRA 22.0
Systematic Assessment
EG0000 events0 affected88 at risk
EG0010 events0 affected84 at risk
EG0020 events0 affected56 at risk
EG003
PRURITUS
Skin and subcutaneous tissue disorders
MedDRA 22.0
Systematic Assessment
EG0002 events2 affected88 at risk
EG0011 events1 affected84 at risk
EG0020 events0 affected56 at risk
EG003
RASH
Skin and subcutaneous tissue disorders
MedDRA 22.0
Systematic Assessment
EG0007 events7 affected88 at risk
EG0013 events2 affected84 at risk
EG0021 events1 affected56 at risk
EG003
HYPERTENSION
Vascular disorders
MedDRA 22.0
Systematic Assessment
EG00018 events9 affected88 at risk
EG0019 events6 affected84 at risk
EG0025 events4 affected56 at risk
EG003
HYPOTENSION
Vascular disorders
MedDRA 22.0
Systematic Assessment
EG0001 events1 affected88 at risk
EG0013 events3 affected84 at risk
EG0020 events0 affected56 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
OG00016.9(14.4 to NA)Not calculable due to insufficient number of participants with events
OG00115.5(10.2 to 19.0)
OG00212.6(10.2 to 14.9)
OG001
OG002
Stratified at randomization by regions of the world (North America, Europe and Australia, Asia/Other Regions), WHO performance status (0, > 0), timing of relapse (< 16 weeks, ≥ 16 weeks after first day of last TMZ cycle).
Log Rank
= 0.835
2-sided
Cox Proportional Hazard
1.04
2-Sided
95
0.73
1.48
Other
Units
Counts
Participants
OG00088
OG00186
OG00286
Title
Denominators
Categories
25th quartile
Title
Measurements
OG0001.8(1.7 to 2.0)
OG0011.5(1.1 to 1.7)
OG0021.6(1.3 to 1.7)
50th quartile
Title
Measurements
OG0002.7(2.0 to 3.8)
OG0011.9(1.8 to 2.0)
OG0021.9(1.9 to 2.2)
75th quartile
Title
Measurements
OG0004.9(3.9 to 9.3)
OG0013.5(2.1 to 3.9)
OG0024.2(3.4 to 5.8)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
Log Rank
= 0.123
2-sided
Cox Proportional Hazard
0.77
2-Sided
95
0.55
1.07
Other
OG001
OG002
Log Rank
= 0.117
2-sided
Cox Proportional Hazard
1.31
2-Sided
95
0.93
1.84
Other
6
Title
Denominators
Categories
Title
Measurements
OG000100
5
Title
Denominators
Categories
Title
Measurements
OG00031.4± 15.0
5
Title
Denominators
Categories
Title
Measurements
OG0000.272± 0.0983
4
Title
Denominators
Categories
Title
Measurements
OG0009.0± 1.5
2
Title
Denominators
Categories
Title
Measurements
OG00011.2± 22.9
5
Title
Denominators
Categories
Title
Measurements
OG0003170± 1320
5
Title
Denominators
Categories
Title
Measurements
OG00014.1± 6.22
Adult participants relapsing during temozolomide (TMZ) treatment or within the first 16 weeks after the first day of the last TMZ cycle who received lomustine on Day 1 of every 42-day treatment period until one of the treatment withdrawal criteria was met, up to a maximum of 1 year OR adult subjects relapsing 16 weeks or more after the first day of the last temozolomide (TMZ) cycle who received TMZ on Day 1 to Day 5 for the first 28-day cycle, with dose escalation in subsequent cycles in case of adequate tolerance and treatment continuing until one of the treatment withdrawal criteria was met.
Units
Counts
Participants
OG00049
OG00139
OG00245
Title
Denominators
Categories
Title
Measurements
OG00014.3(5.9 to 27.2)
OG0017.7(1.6 to 20.9)
OG0024.4(0.5 to 15.1)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
Comparison is based on Cochran-Mantel-Haenszel method with stratification factors. Stratified at randomization by regions of the world (North America, Europe and Australia, Asia/Other Regions), WHO performance status (0, > 0), timing of relapse (< 16 weeks, ≥ 16 weeks after first day of last TMZ cycle).
Cochran-Mantel-Haenszel
= 0.06
2-sided
Odds Ratio (OR)
3.1
2-Sided
95
0.6
16.16
Other
OG001
OG002
Comparison is based on Cochran-Mantel-Haenszel method with stratification factors. Stratified at randomization by regions of the world (North America, Europe and Australia, Asia/Other Regions), WHO performance status (0, > 0), timing of relapse (< 16 weeks, ≥ 16 weeks after first day of last TMZ cycle).
Cochran-Mantel-Haenszel
= 0.767
2-sided
Odds Ratio (OR)
1.21
2-Sided
95
0.12
12.49
Other
Units
Counts
Participants
OG00039
OG00136
OG00247
Title
Denominators
Categories
25th quartile
Title
Measurements
OG0006.3(3.1 to 7.4)
OG0015.0(3.1 to 5.9)
OG0024.7(3.0 to 5.8)
50th quartile
Title
Measurements
OG0009.4(7.1 to 11.0)
OG0018.4(5.5 to 9.0)
OG0027.5(5.1 to 9.6)
75th quartile
Title
Measurements
OG00014.4(10.3 to NA)Not calculable due to insufficient number of participants with events
OG00113.9(8.7 to NA)Not calculable due to insufficient number of participants with events