Clinical Trial Results:
A Phase 2, Randomized, Double-Blind Study of Ipilimumab Administered at 3 mg/kg vs 10 mg/kg in Adult Subjects with Metastatic Chemotherapy-Naïve Castration Resistant Prostate Cancer Who are Asymptomatic or Minimally Symptomatic
Summary
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EudraCT number |
2014-002987-34 |
Trial protocol |
DE GB IT ES NL |
Global end of trial date |
15 Dec 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
31 Dec 2017
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First version publication date |
31 Dec 2017
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CA184-437
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Bristol-Myers Squibb
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Sponsor organisation address |
Chaussée de la Hulpe 185, Brussels, Belgium, 1170
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Public contact |
Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.com
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Scientific contact |
Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
15 Dec 2016
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
15 Dec 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the rate of severe immune-related adverse events (irAEs). To assess the safety profile of subjects with chemotherapy-naive mCRPC randomized to ipilimumab 3 mg/kg and 10 mg/kg.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
16 Dec 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Australia: 2
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Country: Number of subjects enrolled |
Chile: 8
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Country: Number of subjects enrolled |
France: 11
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Country: Number of subjects enrolled |
Germany: 21
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Country: Number of subjects enrolled |
Netherlands: 2
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Country: Number of subjects enrolled |
Spain: 12
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Country: Number of subjects enrolled |
United Kingdom: 5
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Country: Number of subjects enrolled |
United States: 21
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Worldwide total number of subjects |
82
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EEA total number of subjects |
51
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
27
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From 65 to 84 years |
51
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85 years and over |
4
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Recruitment
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Recruitment details |
- | |||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
82 subjects were enrolled; 53 were randomized; 51 were treated with study drug. 29 were not randomized due to screening failures. 2 were randomized and not treated due to administrative reason by sponsor and "other" reason | |||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | |||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Ipilimumab 3 mg/kg | |||||||||||||||||||||||||||||||||
Arm description |
Ipilimumab at 3 mg/kg was administered by intravenous (IV) infusion over a time period of 60-100 minutes, based on body weight. Induction Phase dosing consisted of a single dose every 3 weeks (Q3W) for 4 doses. This was followed by Maintenance Phase dosing of a single dose every 12 weeks (Q12W). Treatment was for a maximum treatment period of 3 years from the first induction dose of blinded study therapy, or until subject met treatment stopping criteria. | |||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Ipilimumab
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Investigational medicinal product code |
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Other name |
Yervoy, BMS-734016
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Ipilimumab, at either 3 mg/kg or 10 mg/kg, was administered by intravenous (IV) infusion over a time period of 60-100 minutes, based on subject body weight. Induction Phase dosing consisted of a single dose every 3 weeks (Q3W) for 4 doses. This was followed by Maintenance Phase dosing of a single dose every 12 weeks (Q12W). Treatment was for a maximum treatment period of 3 years from the first induction dose of blinded study therapy, or until subject met treatment stopping criteria.
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Arm title
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Ipilimumab 10 mg/kg | |||||||||||||||||||||||||||||||||
Arm description |
Ipilimumab at 10 mg/kg was administered by intravenous (IV) infusion over a time period of 60-100 minutes, based on body weight. Induction Phase dosing consisted of a single dose every 3 weeks (Q3W) for 4 doses. This was followed by Maintenance Phase dosing of a single dose every 12 weeks (Q12W). Treatment was for a maximum treatment period of 3 years from the first induction dose of blinded study therapy, or until subject met treatment stopping criteria. | |||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Ipilimumab
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Investigational medicinal product code |
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Other name |
Yervoy, BMS-734016
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Ipilimumab, at either 3 mg/kg or 10 mg/kg, was administered by intravenous (IV) infusion over a time period of 60-100 minutes, based on subject body weight. Induction Phase dosing consisted of a single dose every 3 weeks (Q3W) for 4 doses. This was followed by Maintenance Phase dosing of a single dose every 12 weeks (Q12W). Treatment was for a maximum treatment period of 3 years from the first induction dose of blinded study therapy, or until subject met treatment stopping criteria.
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 82 subjects were enrolled; 53 were randomized; 51 were treated with study drug. 29 were not randomized due to screening failures. 2 were randomized and not treated due to administrative reason by sponsor and "other" reason |
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Baseline characteristics reporting groups
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Reporting group title |
Ipilimumab 3 mg/kg
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Reporting group description |
Ipilimumab at 3 mg/kg was administered by intravenous (IV) infusion over a time period of 60-100 minutes, based on body weight. Induction Phase dosing consisted of a single dose every 3 weeks (Q3W) for 4 doses. This was followed by Maintenance Phase dosing of a single dose every 12 weeks (Q12W). Treatment was for a maximum treatment period of 3 years from the first induction dose of blinded study therapy, or until subject met treatment stopping criteria. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Ipilimumab 10 mg/kg
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Reporting group description |
Ipilimumab at 10 mg/kg was administered by intravenous (IV) infusion over a time period of 60-100 minutes, based on body weight. Induction Phase dosing consisted of a single dose every 3 weeks (Q3W) for 4 doses. This was followed by Maintenance Phase dosing of a single dose every 12 weeks (Q12W). Treatment was for a maximum treatment period of 3 years from the first induction dose of blinded study therapy, or until subject met treatment stopping criteria. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Ipilimumab 3 mg/kg
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Reporting group description |
Ipilimumab at 3 mg/kg was administered by intravenous (IV) infusion over a time period of 60-100 minutes, based on body weight. Induction Phase dosing consisted of a single dose every 3 weeks (Q3W) for 4 doses. This was followed by Maintenance Phase dosing of a single dose every 12 weeks (Q12W). Treatment was for a maximum treatment period of 3 years from the first induction dose of blinded study therapy, or until subject met treatment stopping criteria. | ||
Reporting group title |
Ipilimumab 10 mg/kg
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Reporting group description |
Ipilimumab at 10 mg/kg was administered by intravenous (IV) infusion over a time period of 60-100 minutes, based on body weight. Induction Phase dosing consisted of a single dose every 3 weeks (Q3W) for 4 doses. This was followed by Maintenance Phase dosing of a single dose every 12 weeks (Q12W). Treatment was for a maximum treatment period of 3 years from the first induction dose of blinded study therapy, or until subject met treatment stopping criteria. |
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End point title |
Radiographic progression-free survival (rPFS) [1] | ||||||||||||
End point description |
rPFS was defined as the time from the date of randomization until the date of disease progression based on radiographic evidence and/or death from any cause, whichever occurs first. Radiographic disease progression is defined as: Confirmed bone disease progression according to criteria adapted from the Prostate Cancer Clinical Trials Working Group 2 (PCWG2), OR Non-bone disease progression according to the modified Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
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End point type |
Primary
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End point timeframe |
From date of randomization until disease progression or death (assessed up to December 2016, approximately 24 months)
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only summary statistics were planned for this endpoint |
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No statistical analyses for this end point |
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End point title |
Number of subjects who experienced immune-related adverse events (irAEs) | |||||||||
End point description |
The total number of subjects with immune-related adverse events of any grade is reported for each arm.
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End point type |
Secondary
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End point timeframe |
From first dose of ipilimumab to last dose plus 90 days
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No statistical analyses for this end point |
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End point title |
Overall Survival (OS) | ||||||||||||
End point description |
OS was defined as the time from the date of randomization until the date of death. For those subjects who have not died, OS was censored at the last date the subject was known to be alive.
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End point type |
Secondary
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End point timeframe |
From randomization to death from any cause (assessed up to December 2016, approximately 24 months)
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No statistical analyses for this end point |
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End point title |
Prostate Specific Antigen Progression-free Survival (PSA PFS) | ||||||||||||
End point description |
Prostate specific antigen progression-free survival (PSA PFS) was defined as the time from randomization to the earliest date of PSA progression or death, whichever occurs earlier. Subjects who did not progress or die were censored at the last PSA assessment date.
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End point type |
Secondary
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End point timeframe |
From randomization to the earliest date of PSA progression or death, whichever comes earlier (assessed up to December 2016, approximately 24 months)
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No statistical analyses for this end point |
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End point title |
Time to Pain Progression | ||||||||||||
End point description |
Pain progression was defined as the earliest of the following: 1) Increase in BPI-SF pain Item #3 score of >= 2 point from baseline maintained over 2 consecutive time periods. 2) Initiation of opioid analgesic (excluding codeine or dextropropoxyphene) as: - Subjects with no opioid analgesic use at baseline: initiation of opioid analgesic for palliation of disease related pain - Subjects with baseline opioid analgesic use: increase in opioid analgesic use >= 3 days (consecutive or not) over a 14-day period. 3) Initiation of palliative radiotherapy for prostate cancer 4) Increase in mean analgesic score (AS): - Subjects with baseline AS > 10: an increase in AS of >= 25% from baseline - Subjects with baseline AS <= 10: an increase in AS of >= 10 points from baseline.
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End point type |
Secondary
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End point timeframe |
From randomization until pain progression (assessed up to December 2016, approximately 24 months)
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No statistical analyses for this end point |
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End point title |
Prostate specific antigen response rate | ||||||||||||
End point description |
PSA response rate was defined as the proportion of subjects with a 50% or greater decrease from baseline to the lowest post-baseline PSA result (confirmed 3 weeks later) for each randomized arm.
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End point type |
Secondary
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End point timeframe |
From baseline to PSA response (assessed up to December 2016, approximately 48 months)
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
On-study adverse events: events reported between first dose and 90 days after last dose of study therapy.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.1
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Reporting groups
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Reporting group title |
10 MG/KG IPILIMUMAB
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Reporting group description |
10 MG/KG IPILIMUMAB- was administered by intravenous (IV) infusion over a time period of 60-100 minutes, based on subject body weight. Induction Phase dosing consisted of a single dose every 3 weeks (Q3W) for 4 doses. This was followed by Maintenance Phase dosing of a single dose every 12 weeks (Q12W). Treatment was for a maximum treatment period of 3 years from the first induction dose of blinded study therapy, or until subject met treatment stopping criteria. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
3 MG/KG IPILIMUMAB
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Reporting group description |
3 MG/KG IPILIMUMAB-was administered by intravenous (IV) infusion over a time period of 60-100 minutes, based on subject body weight. Induction Phase dosing consisted of a single dose every 3 weeks (Q3W) for 4 doses. This was followed by Maintenance Phase dosing of a single dose every 12 weeks (Q12W). Treatment was for a maximum treatment period of 3 years from the first induction dose of blinded study therapy, or until subject met treatment stopping criteria. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |