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Daratumumab (HuMax®-CD38) Safety Study in Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT00574288
Recruitment Status : Completed
First Posted : December 17, 2007
Results First Posted : March 9, 2017
Last Update Posted : April 27, 2018
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Myeloma
Interventions Drug: Part 1: Daratumumab
Drug: Part 2: Daratumumab
Other: Methylprednisolone
Other: Dexamethasone
Enrollment 104
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Part 1 - <4 mg/kg Part 1 - 4 mg/kg Part 1 - 8 mg/kg Part 1 - 16 mg/kg Part 1 - 24 mg/kg Part 2 - 8 mg/kg Part 2 - 16 mg/kg
Hide Arm/Group Description Participants were administered with 7 full intravenous (IV) infusion of 0.005, 0.05, 0.1, 0.5, 1 and 2 milligram per kilogram body weight (mg/kg) daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. Participants were administered with 7 full IV infusion of 4 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. Participants were administered with 7 full IV infusion of 8 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. Participants were administered with 7 full IV infusion of 16 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. Participants were administered with 7 full IV infusion of 24 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. Participants were administered with 8 full IV infusions of 8 mg/kg daratumumab once weekly for 8 weeks, then every 2 weeks (q2w) for 16 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20–25 mg methylprednisolone orally for 2 days after all full infusions. Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 weeks (q2w) for 14 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20–25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Period Title: Overall Study
Started 20 3 3 3 3 30 42
Completed 0 0 0 1 1 4 14
Not Completed 20 3 3 2 2 26 28
Reason Not Completed
Adverse Event             2             0             0             0             1             0             0
Death             0             0             0             0             0             25             21
Lost to Follow-up             0             0             0             0             0             1             2
Study Terminated By Sponsor             0             0             0             0             0             0             5
Progressive Disease             17             2             3             2             1             0             0
Other             1             1             0             0             0             0             0
Arm/Group Title Part 1 - <4 mg/kg Part 1 - 4 mg/kg Part 1 - 8 mg/kg Part 1 - 16 mg/kg Part 1 - 24 mg/kg Part 2 - 8 mg/kg Part 2 - 16 mg/kg Total
Hide Arm/Group Description Participants were administered with 7 full intravenous (IV) infusion of 0.005, 0.05, 0.1, 0.5, 1 and 2 milligram per kilogram body weight (mg/kg) daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. Participants were administered with 7 full IV infusion of 4 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. Participants were administered with 7 full IV infusion of 8 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. Participants were administered with 7 full IV infusion of 16 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. Participants were administered with 7 full IV infusion of 24 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. Participants were administered with 8 full IV infusions of 8 mg/kg daratumumab once weekly for 8 weeks, then every 2 weeks (q2w) for 16 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20–25 mg methylprednisolone orally for 2 days after all full infusions. Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 weeks (q2w) for 14 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20–25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. Total of all reporting groups
Overall Number of Baseline Participants 20 3 3 3 3 30 42 104
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 3 participants 3 participants 3 participants 3 participants 30 participants 42 participants 104 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
11
  55.0%
2
  66.7%
2
  66.7%
3
 100.0%
2
  66.7%
21
  70.0%
22
  52.4%
63
  60.6%
>=65 years
9
  45.0%
1
  33.3%
1
  33.3%
0
   0.0%
1
  33.3%
9
  30.0%
20
  47.6%
41
  39.4%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 20 participants 3 participants 3 participants 3 participants 3 participants 30 participants 42 participants 104 participants
61.8  (9.24) 64  (2) 61.3  (6.11) 53  (1.73) 59  (9.54) 58.6  (10.05) 63.8  (8.27) 61.4  (9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 3 participants 3 participants 3 participants 3 participants 30 participants 42 participants 104 participants
Female
7
  35.0%
2
  66.7%
0
   0.0%
0
   0.0%
0
   0.0%
9
  30.0%
15
  35.7%
33
  31.7%
Male
13
  65.0%
1
  33.3%
3
 100.0%
3
 100.0%
3
 100.0%
21
  70.0%
27
  64.3%
71
  68.3%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 3 participants 3 participants 3 participants 3 participants 30 participants 42 participants 104 participants
Denmark
11
  55.0%
1
  33.3%
2
  66.7%
2
  66.7%
0
   0.0%
5
  16.7%
9
  21.4%
30
  28.8%
Netherlands
4
  20.0%
2
  66.7%
1
  33.3%
1
  33.3%
2
  66.7%
14
  46.7%
8
  19.0%
32
  30.8%
Sweden
5
  25.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
5
  16.7%
11
  26.2%
22
  21.2%
United States
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
6
  20.0%
14
  33.3%
20
  19.2%
No. of Prior Lines of Therapy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 3 participants 3 participants 3 participants 3 participants 30 participants 42 participants 104 participants
<= 3 Lines
2
  10.0%
2
  66.7%
0
   0.0%
0
   0.0%
0
   0.0%
6
  20.0%
16
  38.1%
26
  25.0%
> 3 Lines
18
  90.0%
1
  33.3%
3
 100.0%
3
 100.0%
3
 100.0%
24
  80.0%
26
  61.9%
78
  75.0%
Refractory to proteasome inhibitor (PI)/immunomodulatory agent (IMiD)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 3 participants 3 participants 3 participants 3 participants 30 participants 42 participants 104 participants
Both a PI and IMiD
0
   0.0%
2
  66.7%
3
 100.0%
1
  33.3%
2
  66.7%
19
  63.3%
27
  64.3%
54
  51.9%
PI only
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
2
   6.7%
3
   7.1%
6
   5.8%
IMiD only
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
1
  33.3%
6
  20.0%
4
   9.5%
12
  11.5%
None
20
 100.0%
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
3
  10.0%
8
  19.0%
32
  30.8%
1.Primary Outcome
Title Number of Participants With Adverse Events
Hide Description An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time Frame Up to Week 28 (for Part 1) and up to approximately 2.5 years (for Part 2)
Hide Outcome Measure Data
Hide Analysis Population Description
All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug.
Arm/Group Title Part 1: Daratumumab Less Than (<) 4 mg/kg Part 1: Daratumumab 4 mg/kg Part 1:Daratumumab 8 mg/kg Part 1: Daratumumab 16 mg/kg Part 1:Daratumumab 24 mg/kg Part 2: Daratumumab 8 mg/kg Part 2: Daratumumab 16 mg/kg
Hide Arm/Group Description:
Participants were administered with 7 full intravenous (IV) infusion of 0.005, 0.05, 0.1, 0.5, 1 and 2 milligram per kilogram body weight (mg/kg) daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Participants were administered with 7 full IV infusion of 4 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Participants were administered with 7 full IV infusion of 8 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w), along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Participants were administered with 7 full IV infusion of 24 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Participants were administered with 8 full IV infusions of 8 mg/kg daratumumab once weekly for 8 weeks, then every 2 weeks (q2w) for 16 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20–25 mg methylprednisolone orally for 2 days after all full infusions.
Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 weeks (q2w) for 14 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20–25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Overall Number of Participants Analyzed 20 3 3 3 3 30 42
Measure Type: Number
Unit of Measure: participants
19 3 3 3 3 30 41
2.Secondary Outcome
Title Overall Response Rate
Hide Description Overall response defined as percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). Per IMWG criteria, sCR: is defined as normal free light chain (FLC) ratio, and absence of clonal plasma cells (PCs) by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5 % plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or >= 90% reduction in serum M-protein plus urine M-protein level < 100mg/24 hours; PR: >= 50 % reduction of serum M-protein and reduction in 24 hour urinary M-protein by >= 90% or to <200 mg/24 hours; if the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria.
Time Frame Up to Week 28 (for Part 1) and Week 27 (for Part 2)
Hide Outcome Measure Data
Hide Analysis Population Description
All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug. For Part 1, only participants treated with >= 4 mg/kg daratumumab were used for efficacy analyses and less than (<) 4 mg/kg doses were considered under the therapeutic levels.
Arm/Group Title Part 1: Daratumumab 4 mg/kg Part 1:Daratumumab 8 mg/kg Part 1: Daratumumab 16 mg/kg Part 1:Daratumumab 24 mg/kg Part 2: Daratumumab 8 mg/kg Part 2: Daratumumab 16 mg/kg
Hide Arm/Group Description:
Participants were administered with 7 full IV infusion of 4 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Participants were administered with 7 full IV infusion of 8 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w), along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Participants were administered with 7 full IV infusion of 24 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Participants were administered with 8 full IV infusions of 8 mg/kg daratumumab once weekly for 8 weeks, then every 2 weeks (q2w) for 16 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20–25 mg methylprednisolone orally for 2 days after all full infusions.
Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 weeks (q2w) for 14 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20–25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Overall Number of Participants Analyzed 3 3 3 3 30 42
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
33.3
(0.8 to 90.6)
0
(0 to 0)
33.3
(0.8 to 90.6)
66.7
(9.4 to 99.2)
10.0
(2.1 to 26.5)
35.7
(21.6 to 52.0)
3.Secondary Outcome
Title Part 1: Time to Response
Hide Description Time to first response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better). Time to best response was defined as the time between the date of first dose of daratumumab and the date of the initial evaluation of the best response (PR or better) to treatment. Kaplan-Meier method was used to estimate the distribution of time to response and time to best response.
Time Frame Up to Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug. For Part 1, only participants treated with >= 4 mg/kg daratumumab were used for efficacy analyses and less than (<) 4 mg/kg doses were considered under the therapeutic levels.
Arm/Group Title Part 1: Daratumumab 4 mg/kg Daratumumab 8 mg/kg Daratumumab 16 mg/kg Part 1:Daratumumab 24 mg/kg
Hide Arm/Group Description:
Participants were administered with 7 full IV infusion of 4 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Participants were administered with 8 mg/kg daratumumab weekly once for 8 weeks, then every 2 week (q2w) for 16 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with participants received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions.
Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with participants received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Participants were administered with 7 full IV infusion of 24 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Overall Number of Participants Analyzed 3 3 3 3
Median (95% Confidence Interval)
Unit of Measure: months
Time to first response
NA [1] 
(1.2 to NA)
NA [2] 
(NA to NA)
8.4 [3] 
(NA to NA)
1.9
(0.5 to 1.9)
Time to best response
NA [4] 
(1.2 to NA)
NA [2] 
(NA to NA)
8.4 [3] 
(NA to NA)
1.9
(0.5 to 1.9)
[1]
Median and upper limit of confidence interval (CI) was not estimable due to insufficient number of participants with events.
[2]
Median and CI was not estimable due to insufficient number of participants with events.
[3]
Among the 3 participants on 16 mg/kg, only one participant had event, the median was set to this single uncensored value of “time to event” (defaults in PROC LIFETEST), no lower or upper bound of 95% CI calculated.
[4]
Median and upper limit of CI was not estimable due to insufficient number of participants with events.
4.Secondary Outcome
Title Part 2: Time to Progression (TTP)
Hide Description TTP was defined as the number of days from the date of first infusion (Day 1) to the date of first record of disease progression. Disease progression (IMWG criteria): increase of 25 percent (%) from lowest response level in Serum M-component and/or (the absolute increase must be >=0.5 g/dL); urine M-component and/or (the absolute increase must be >=200 mg/24 hour; only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels (absolute increase must be >10 mg/dL); Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder. Median TTP was estimated by using the Kaplan-Meier method.
Time Frame Up to Week 27
Hide Outcome Measure Data
Hide Analysis Population Description
All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug.
Arm/Group Title Daratumumab 8 mg/kg Daratumumab 16 mg/kg
Hide Arm/Group Description:
Participants were administered with 8 mg/kg daratumumab weekly once for 8 weeks, then every 2 week (q2w) for 16 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20–25 mg methylprednisolone orally for 2 days after all full infusions.
Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20–25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Overall Number of Participants Analyzed 30 42
Median (95% Confidence Interval)
Unit of Measure: months
2.4
(1.4 to 3.5)
5.6 [1] 
(4.7 to NA)
[1]
Upper limit of CI was not estimable due to insufficient number of participants with events.
5.Secondary Outcome
Title Part 2: Duration of Response as Assessed Using the Method of Kaplan-Meier
Hide Description Duration of response was calculated from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the International Myeloma Working Group (IMWG) criteria.
Time Frame Up to Week 27
Hide Outcome Measure Data
Hide Analysis Population Description
Subset of All-Treated Analysis Set included those who had overall response in Part 2.
Arm/Group Title Daratumumab 8 mg/kg Daratumumab 16 mg/kg
Hide Arm/Group Description:
Participants were administered with 8 mg/kg daratumumab weekly once for 8 weeks, then every 2 week (q2w) for 16 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20–25 mg methylprednisolone orally for 2 days after all full infusions.
Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20–25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Overall Number of Participants Analyzed 3 15
Median (Full Range)
Unit of Measure: months
6.9
(6.2 to 10.6)
NA [1] 
(5.6 to NA)
[1]
Median and upper limit of confidence interval (CI) was not estimable due to insufficient number of participants with events.
6.Secondary Outcome
Title Part 2: Progression-Free Survival
Hide Description Progression free survival (PFS) was defined as the time between the date of first dose of daratumumab and either disease progression or death, whichever occurs first.
Time Frame Up to Week 27
Hide Outcome Measure Data
Hide Analysis Population Description
All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug.
Arm/Group Title Daratumumab 8 mg/kg Daratumumab 16 mg/kg
Hide Arm/Group Description:
Participants were administered with 8 mg/kg daratumumab weekly once for 8 weeks, then every 2 week (q2w) for 16 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20–25 mg methylprednisolone orally for 2 days after all full infusions.
Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20–25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Overall Number of Participants Analyzed 30 42
Median (95% Confidence Interval)
Unit of Measure: months
2.4
(1.4 to 3.5)
5.6
(4.2 to 8.1)
7.Secondary Outcome
Title Part 2: Time to Response
Hide Description Time to first response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better). Time to best response was defined as the time between the date of first dose of daratumumab and the date of the initial evaluation of the best response (PR or better) to treatment. Time to VGPR (very good partial response) was defined as the time from the date of first dose of daratumumab to the date of initial documentation of VGPR response. The Kaplan-Meier method was used to estimate time to response.
Time Frame Up to Week 27
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Hide Analysis Population Description
All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug. Here 'n' (Number of Participants Analyzed) signifies number of participants analyzed at specific time point.
Arm/Group Title Daratumumab 8 mg/kg Daratumumab 16 mg/kg
Hide Arm/Group Description:
Participants were administered with 8 mg/kg daratumumab weekly once for 8 weeks, then every 2 week (q2w) for 16 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20–25 mg methylprednisolone orally for 2 days after all full infusions.
Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20–25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Overall Number of Participants Analyzed 30 42
Mean (Standard Deviation)
Unit of Measure: months
Time to first response Number Analyzed 3 participants 15 participants
1.36  (0.774) 1.33  (0.955)
Time to best response Number Analyzed 3 participants 15 participants
1.36  (0.774) 2.46  (2.800)
Time to VGPR or better response Number Analyzed 0 participants 4 participants
0.49  (0.000)
8.Secondary Outcome
Title Part 2: Overall Survival
Hide Description Overall Survival (OS) was defined as the number of days from administration of the first infusion (Day 1) to date of death. Median Overall Survival was estimated by using the Kaplan-Meier method.
Time Frame Approximately 3 years
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Hide Analysis Population Description
All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug.
Arm/Group Title Daratumumab 8 mg/kg Daratumumab 16 mg/kg
Hide Arm/Group Description:
Participants were administered with 8 mg/kg daratumumab weekly once for 8 weeks, then every 2 week (q2w) for 16 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20–25 mg methylprednisolone orally for 2 days after all full infusions.
Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20–25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Overall Number of Participants Analyzed 30 42
Median (95% Confidence Interval)
Unit of Measure: months
18.2
(7.5 to 22.6)
34.3 [1] 
(19.9 to NA)
[1]
Upper limit of CI was not estimable due to insufficient number of participants with events.
Time Frame Up to Week 28 (for Part 1) and approximately 2.5 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Part 1 - <4 mg/kg Part 1 - 4 mg/kg Part 1 - 8 mg/kg Part 1 - 16 mg/kg Part 1 - 24 mg/kg Part 2 - 8 mg/kg Part 2 - 16 mg/kg
Hide Arm/Group Description Participants were administered with 7 full intravenous (IV) infusion of 0.005, 0.05, 0.1, 0.5, 1 and 2 milligram per kilogram body weight (mg/kg) daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. Participants were administered with 7 full IV infusion of 4 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. Participants were administered with 7 full IV infusion of 8 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. Participants were administered with 7 full IV infusion of 16 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. Participants were administered with 7 full IV infusion of 24 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. Participants were administered with 8 full IV infusions of 8 mg/kg daratumumab once weekly for 8 weeks, then every 2 weeks (q2w) for 16 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20–25 mg methylprednisolone orally for 2 days after all full infusions. Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 weeks (q2w) for 14 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20–25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
All-Cause Mortality
Part 1 - <4 mg/kg Part 1 - 4 mg/kg Part 1 - 8 mg/kg Part 1 - 16 mg/kg Part 1 - 24 mg/kg Part 2 - 8 mg/kg Part 2 - 16 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Part 1 - <4 mg/kg Part 1 - 4 mg/kg Part 1 - 8 mg/kg Part 1 - 16 mg/kg Part 1 - 24 mg/kg Part 2 - 8 mg/kg Part 2 - 16 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/20 (35.00%)   0/3 (0.00%)   1/3 (33.33%)   2/3 (66.67%)   2/3 (66.67%)   12/30 (40.00%)   16/42 (38.10%) 
Blood and lymphatic system disorders               
Anaemia * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  0/42 (0.00%) 
Neutropenia * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  1/42 (2.38%) 
Thrombocytopenia * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  0/42 (0.00%) 
Cardiac disorders               
Atrial Fibrillation * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Atrial Flutter * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  1/42 (2.38%) 
Gastrointestinal disorders               
Abdominal Pain * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Nausea * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  1/42 (2.38%) 
General disorders               
Chest Pain * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  0/42 (0.00%) 
Oedema Peripheral * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  1/42 (2.38%) 
Pyrexia * 1  1/20 (5.00%)  0/3 (0.00%)  1/3 (33.33%)  1/3 (33.33%)  0/3 (0.00%)  1/30 (3.33%)  2/42 (4.76%) 
Hepatobiliary disorders               
Hepatic Function Abnormal * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Immune system disorders               
Cytokine Release Syndrome * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Infections and infestations               
Bacteraemia * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  0/42 (0.00%) 
Bacterial Sepsis * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  1/42 (2.38%) 
Herpes Zoster * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  2/42 (4.76%) 
Influenza * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  0/42 (0.00%) 
Metapneumovirus Infection * 1  0/20 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Pneumonia * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  3/30 (10.00%)  3/42 (7.14%) 
Respiratory Syncytial Virus Infection * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  0/42 (0.00%) 
Urinary Tract Infection * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/30 (0.00%)  0/42 (0.00%) 
Varicella * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  1/42 (2.38%) 
Injury, poisoning and procedural complications               
Limb Traumatic Amputation * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  0/42 (0.00%) 
Spinal Compression Fracture * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  1/42 (2.38%) 
Investigations               
Blood Creatinine Increased * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  0/42 (0.00%) 
Crossmatch Incompatible * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  3/42 (7.14%) 
Free Haemoglobin Present * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
International Normalised Ratio Increased * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  0/42 (0.00%) 
Metabolism and nutrition disorders               
Hypokalaemia * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  1/42 (2.38%) 
Hypomagnesaemia * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  1/42 (2.38%) 
Musculoskeletal and connective tissue disorders               
Back Pain * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  1/42 (2.38%) 
Bone Pain * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  1/42 (2.38%) 
Osteoporotic Fracture * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  0/42 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Plasmacytoma * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  1/42 (2.38%) 
Nervous system disorders               
Amnesia * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  1/42 (2.38%) 
Transient Ischaemic Attack * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  1/42 (2.38%) 
Vith Nerve Paralysis * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  0/42 (0.00%) 
Psychiatric disorders               
Confusional State * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Bronchospasm * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/30 (0.00%)  0/42 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part 1 - <4 mg/kg Part 1 - 4 mg/kg Part 1 - 8 mg/kg Part 1 - 16 mg/kg Part 1 - 24 mg/kg Part 2 - 8 mg/kg Part 2 - 16 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   19/20 (95.00%)   3/3 (100.00%)   3/3 (100.00%)   3/3 (100.00%)   3/3 (100.00%)   30/30 (100.00%)   41/42 (97.62%) 
Blood and lymphatic system disorders               
Anaemia * 1  4/20 (20.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  3/42 (7.14%) 
Haemolysis * 1  3/20 (15.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Leukopenia * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  4/42 (9.52%) 
Lymphopenia * 1  2/20 (10.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  0/42 (0.00%) 
Monocytopenia * 1  2/20 (10.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Neutropenia * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  4/42 (9.52%) 
Thrombocytopenia * 1  3/20 (15.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/30 (6.67%)  3/42 (7.14%) 
Cardiac disorders               
Palpitations * 1  0/20 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  1/42 (2.38%) 
Supraventricular Extrasystoles * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Tachycardia * 1  2/20 (10.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Eye disorders               
Ocular Hyperaemia * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Vision Blurred * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/30 (6.67%)  5/42 (11.90%) 
Gastrointestinal disorders               
Abdominal Pain * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  1/42 (2.38%) 
Aphthous Stomatitis * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/30 (6.67%)  0/42 (0.00%) 
Constipation * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  4/30 (13.33%)  4/42 (9.52%) 
Diarrhoea * 1  1/20 (5.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  9/30 (30.00%)  6/42 (14.29%) 
Dry Mouth * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  0/42 (0.00%) 
Dyspepsia * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  3/30 (10.00%)  1/42 (2.38%) 
Lip Oedema * 1  0/20 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Mouth Ulceration * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Nausea * 1  2/20 (10.00%)  1/3 (33.33%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  4/30 (13.33%)  10/42 (23.81%) 
Oesophagitis * 1  0/20 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Stomatitis * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  3/30 (10.00%)  1/42 (2.38%) 
Vomiting * 1  0/20 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  5/30 (16.67%)  2/42 (4.76%) 
General disorders               
Chest Discomfort * 1  0/20 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  1/42 (2.38%) 
Chest Pain * 1  2/20 (10.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  5/42 (11.90%) 
Chills * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  3/30 (10.00%)  5/42 (11.90%) 
Fatigue * 1  2/20 (10.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  13/30 (43.33%)  19/42 (45.24%) 
Influenza Like Illness * 1  3/20 (15.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  1/30 (3.33%)  1/42 (2.38%) 
Oedema Peripheral * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  3/30 (10.00%)  1/42 (2.38%) 
Pyrexia * 1  7/20 (35.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  12/30 (40.00%)  9/42 (21.43%) 
Hepatobiliary disorders               
Hepatic Function Abnormal * 1  0/20 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Immune system disorders               
Cytokine Release Syndrome * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Hypersensitivity * 1  1/20 (5.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  0/42 (0.00%) 
Infections and infestations               
Gastroenteritis * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  0/42 (0.00%) 
Herpes Zoster * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  4/30 (13.33%)  2/42 (4.76%) 
Nasopharyngitis * 1  2/20 (10.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  7/30 (23.33%)  16/42 (38.10%) 
Oral Candidiasis * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  3/30 (10.00%)  1/42 (2.38%) 
Pneumonia * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  1/42 (2.38%) 
Sinusitis * 1  0/20 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  4/42 (9.52%) 
Upper Respiratory Tract Infection * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  8/30 (26.67%)  11/42 (26.19%) 
Urinary Tract Infection * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/30 (6.67%)  2/42 (4.76%) 
Viral Infection * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Vulvovaginal Candidiasis * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Investigations               
Blood Creatine Phosphokinase Increased * 1  0/20 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  2/42 (4.76%) 
Electrocardiogram QT Prolonged * 1  5/20 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  1/42 (2.38%) 
Free Haemoglobin Present * 1  4/20 (20.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Haptoglobin Decreased * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Lymphocyte Count Decreased * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Metabolism and nutrition disorders               
Decreased Appetite * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  4/42 (9.52%) 
Enzyme Abnormality * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Hypercalcaemia * 1  0/20 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  0/42 (0.00%) 
Hyperglycaemia * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  5/42 (11.90%) 
Hyponatraemia * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  1/42 (2.38%) 
Musculoskeletal and connective tissue disorders               
Arthralgia * 1  2/20 (10.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  4/30 (13.33%)  8/42 (19.05%) 
Back Pain * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  3/30 (10.00%)  14/42 (33.33%) 
Bone Pain * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  6/30 (20.00%)  4/42 (9.52%) 
Kyphosis * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Musculoskeletal Chest Pain * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  3/30 (10.00%)  4/42 (9.52%) 
Musculoskeletal Pain * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/30 (6.67%)  4/42 (9.52%) 
Myalgia * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  6/30 (20.00%)  1/42 (2.38%) 
Pain in Extremity * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  6/42 (14.29%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Basal Cell Carcinoma * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  3/42 (7.14%) 
Benign Neoplasm of Skin * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Nervous system disorders               
Dizziness * 1  3/20 (15.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  5/30 (16.67%)  4/42 (9.52%) 
Dysgeusia * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/30 (6.67%)  0/42 (0.00%) 
Headache * 1  1/20 (5.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  3/30 (10.00%)  4/42 (9.52%) 
Hypoaesthesia * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  2/42 (4.76%) 
Paraesthesia * 1  0/20 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  1/42 (2.38%) 
Peripheral Sensory Neuropathy * 1  0/20 (0.00%)  1/3 (33.33%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  5/30 (16.67%)  1/42 (2.38%) 
Psychiatric disorders               
Confusional State * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Insomnia * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  4/30 (13.33%)  5/42 (11.90%) 
Renal and urinary disorders               
Pollakiuria * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  1/42 (2.38%) 
Proteinuria * 1  9/20 (45.00%)  1/3 (33.33%)  3/3 (100.00%)  1/3 (33.33%)  1/3 (33.33%)  0/30 (0.00%)  0/42 (0.00%) 
Renal Impairment * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Reproductive system and breast disorders               
Prostatitis * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/30 (0.00%)  0/42 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Bronchospasm * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/30 (3.33%)  0/42 (0.00%) 
Cough * 1  4/20 (20.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  6/30 (20.00%)  11/42 (26.19%) 
Dysphonia * 1  0/20 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Dyspnoea * 1  0/20 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  8/30 (26.67%)  7/42 (16.67%) 
Epistaxis * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/30 (6.67%)  0/42 (0.00%) 
Laryngitis Allergic * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  3/30 (10.00%)  1/42 (2.38%) 
Nasal Congestion * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  4/30 (13.33%)  7/42 (16.67%) 
Oropharyngeal Pain * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/30 (6.67%)  5/42 (11.90%) 
Productive Cough * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  3/30 (10.00%)  0/42 (0.00%) 
Rhinitis Allergic * 1  1/20 (5.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  12/30 (40.00%)  10/42 (23.81%) 
Throat Irritation * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  3/42 (7.14%) 
Throat Tightness * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  3/42 (7.14%) 
Skin and subcutaneous tissue disorders               
Eczema Asteatotic * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
Erythema * 1  0/20 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  1/42 (2.38%) 
Hyperhidrosis * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  3/30 (10.00%)  2/42 (4.76%) 
Pruritus * 1  0/20 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  2/30 (6.67%)  1/42 (2.38%) 
Rash * 1  1/20 (5.00%)  1/3 (33.33%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  4/30 (13.33%)  2/42 (4.76%) 
Vascular disorders               
Flushing * 1  2/20 (10.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/30 (3.33%)  1/42 (2.38%) 
Hot Flush * 1  0/20 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/30 (6.67%)  1/42 (2.38%) 
Hypertension * 1  2/20 (10.00%)  0/3 (0.00%)  2/3 (66.67%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  3/42 (7.14%) 
Hypotension * 1  2/20 (10.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/30 (0.00%)  0/42 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 18.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Director
Organization: Janssen Research & Development, LLC
EMail: ClinicalTrialDisclosure@its.jnj.com
Layout table for additonal information
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT00574288     History of Changes
Other Study ID Numbers: CR101876
GEN501 ( Other Identifier: Janssen Research & Development, LLC )
DARA-GEN501 ( Other Identifier: Janssen Research & Development, LLC )
2007-003783-22 ( EudraCT Number )
First Submitted: December 14, 2007
First Posted: December 17, 2007
Results First Submitted: October 21, 2016
Results First Posted: March 9, 2017
Last Update Posted: April 27, 2018