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A Study to Evaluate the Safety and Efficacy of Inactivated Varicella-zoster Vaccine (VZV) as a Preventative Treatment for Herpes Zoster (HZ) and HZ-related Complications in Participants Undergoing Hematopoietic Cell Transplants (HCTs) (V212-001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01229267
Recruitment Status : Completed
First Posted : October 27, 2010
Results First Posted : July 2, 2018
Last Update Posted : September 30, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Condition Herpes Zoster
Interventions Biological: V212
Biological: Matching placebo
Enrollment 1257
Recruitment Details Adult participants scheduled to undergo Autologous Hematopoietic Cell Transplant (auto-HCT) within 60 days were enrolled at 150 sties
Pre-assignment Details A total of 1323 participants were screened and 1257 were randomized. Twenty-seven randomized participants were removed from all analyses due to the identification of major Good Clinical Practice compliance issues at a single site.
Arm/Group Title V212 Consistency Lot 1 V212 Consistency Lot 2 V212 Consistency Lot 3 V212 High Antigen Lot Placebo
Hide Arm/Group Description Participants randomized to receive V212 consistency Lot 1 given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT. Participants randomized to receive V212 Consistency Lot 2 given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT. Participants randomized to receive V212 Consistency Lot 3 given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT. Participants randomized to receive V212 High Antigen Lot given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT. Participants randomized to receive matching placebo given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT.
Period Title: Overall Study
Started 189 184 187 106 564
Received Vaccination 1 188 180 186 104 556
Received Vaccination 2 171 163 168 94 511
Received Vaccination 3 163 155 160 89 491
Received Vaccination 4 155 149 149 87 477
Completed 108 102 101 71 344
Not Completed 81 82 86 35 220
Reason Not Completed
Adverse Event             4             6             3             2             10
Death             40             37             35             13             103
Withdrawal by Subject             23             22             32             14             59
Protocol Violation             0             1             0             0             0
Progressive disease             0             0             0             0             1
Physician Decision             8             11             8             3             25
Lost to Follow-up             6             5             8             3             22
Arm/Group Title V212 Consistency Lot 1 V212 Consistency Lot 2 V212 Consistency Lot 3 V212 High Antigen Lot Placebo Total
Hide Arm/Group Description Participants randomized to receive V212 consistency Lot 1 given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT. Participants randomized to receive V212 Consistency Lot 2 given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT. Participants randomized to receive V212 Consistency Lot 3 given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT. Participants randomized to receive V212 High Antigen Lot given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT. Participants randomized to receive matching placebo given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT. Total of all reporting groups
Overall Number of Baseline Participants 189 184 187 106 564 1230
Hide Baseline Analysis Population Description
A total of 1257 participants were enrolled. Twenty-seven participants were excluded from the analysis due to Good Clinical Practice non-compliance at a single site.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 189 participants 184 participants 187 participants 106 participants 564 participants 1230 participants
54.6  (12.8) 54.2  (12.6) 53.4  (12.4) 54.3  (12.2) 54.1  (12.2) 54.1  (12.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 189 participants 184 participants 187 participants 106 participants 564 participants 1230 participants
Female
69
  36.5%
73
  39.7%
61
  32.6%
48
  45.3%
204
  36.2%
455
  37.0%
Male
120
  63.5%
111
  60.3%
126
  67.4%
58
  54.7%
360
  63.8%
775
  63.0%
Age categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 189 participants 184 participants 187 participants 106 participants 564 participants 1230 participants
From 18-49 years
53
  28.0%
51
  27.7%
54
  28.9%
29
  27.4%
159
  28.2%
346
  28.1%
From 50-59 years
56
  29.6%
60
  32.6%
64
  34.2%
40
  37.7%
187
  33.2%
407
  33.1%
From 60-69 years
63
  33.3%
61
  33.2%
65
  34.8%
31
  29.2%
188
  33.3%
408
  33.2%
From 70-79 years
17
   9.0%
12
   6.5%
4
   2.1%
6
   5.7%
30
   5.3%
69
   5.6%
Intended duration of antiviral prophylaxis  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 189 participants 184 participants 187 participants 106 participants 564 participants 1230 participants
≤3 months post auto-HCT
80
  42.3%
80
  43.5%
79
  42.2%
43
  40.6%
255
  45.2%
537
  43.7%
>3 to ≤6 months post auto-HCT
109
  57.7%
103
  56.0%
108
  57.8%
63
  59.4%
308
  54.6%
691
  56.2%
Not reported
0
   0.0%
1
   0.5%
0
   0.0%
0
   0.0%
1
   0.2%
2
   0.2%
1.Primary Outcome
Title Incidence of Confirmed Herpes-Zoster
Hide Description Clinical criteria for suspected Herpes-Zoster (HZ) cases were the development of a papular or vesicular rash with a dermatomal or generalized distribution, or in the absence of a rash, clinical suspicion of VZV infection with or without the detection of VZV in diagnostic specimens from blood, cerebrospinal fluid, lung, liver, or other organ. All suspected cases of HZ were subjected to adjudication by the Clinical Adjudication Committee (CAC). Case confirmation was based on skin lesion polymerase chain reaction, if available, or by adjudication of the clinical case description by the CAC, conducted according to the CAC Standard Operations Procedure.
Time Frame Up to approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The population included participants who received ≥1 dose and had auto-HCT. To comply with regulatory requests, results for the V212 consistency lots were combined for the efficacy analyses, and the V212 High Antigen Lot was not included in the efficacy analyses for concerns that its inclusion would inflate efficacy estimates.
Arm/Group Title V212 Consistency Lots Placebo
Hide Arm/Group Description:
Participants randomized to receive V212 consistency Lot 1, 2, or 3 given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT.
Participants randomized to receive matching placebo given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT.
Overall Number of Participants Analyzed 538 535
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Number of cases per 1000 person years
32.889
(23.703 to 44.456)
91.883
(75.725 to 110.469)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection V212 Consistency Lots, Placebo
Comments Vaccine efficacy was calculated as 1 minus the hazard ratio of HZ in the V212 consistency lot group versus the placebo group. The success criterion for vaccine efficacy required that the lower bound of the 95% confidence interval (CI) is >0.25.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine Efficacy
Estimated Value 0.638
Confidence Interval (2-Sided) 95%
0.484 to 0.746
Estimation Comments Point estimate and 95% CI of vaccine efficacy were obtained from a Cox proportional hazards regression model, adjusting for age (<50 versus ≥50 years of age), and intended duration of antiviral prophylaxis (≤3 versus 3 to 6 months after auto-HCT).
2.Primary Outcome
Title Percentage of Participants With One or More Serious Adverse Events
Hide Description An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. A serious adverse event (SAE) is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, is a cancer, is an overdose, or is another important medical event.
Time Frame Up to 28 days after vaccination 4 (up to 118 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The population included all participants who received ≥1 dose and had safety follow-up. To comply with regulatory requests, results for all lots of V212 were combined in the primary and secondary safety analyses. One participant randomized to placebo was cross-treated; this participant was excluded from the safety analyses.
Arm/Group Title All V212 (Including High Antigen Lot) Placebo
Hide Arm/Group Description:
V212 (all lots, including High Antigen Lot) administered by subcutaneous injection 30 days before and 30, 60, and 90 days after auto-HCT.
Participants randomized to receive matching placebo given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT.
Overall Number of Participants Analyzed 657 554
Measure Type: Number
Unit of Measure: Percentage of participants
32.9 32.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All V212 (Including High Antigen Lot), Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.942
Comments [Not Specified]
Method Normal approximation
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-5.1 to 5.5
Estimation Comments Miettinen & Nurminen
3.Secondary Outcome
Title Incidence of Moderate to Severe Herpes-Zoster-Associated Pain
Hide Description Moderate to severe HZ-associated pain was defined as 2 or more occurrences of a score 3 or greater (0-to-10 scale, where 0 is no pain and 10 is pain as bad as you can imagine) on the Zoster Brief Pain Inventory (ZBPI) at any time from HZ onset through the end of the 6 month HZ-follow-up period.
Time Frame Up to 6 months after onset of HZ (up to approximately 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The population included participants who received ≥1 dose and had auto-HCT. To comply with regulatory requests, results for the V212 consistency lots were combined for the efficacy analyses, and the V212 High Antigen Lot was not included in the efficacy analyses for concerns that its inclusion would inflate efficacy estimates.
Arm/Group Title V212 Consistency Lots Placebo
Hide Arm/Group Description:
Participants randomized to receive V212 consistency Lot 1, 2, or 3 given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT.
Participants randomized to receive matching placebo given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT.
Overall Number of Participants Analyzed 538 535
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Number of cases per 1000 person years
14.878
(8.958 to 23.234)
49.601
(37.941 to 63.714)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection V212 Consistency Lots, Placebo
Comments Vaccine efficacy was calculated as 1 minus the hazard ratio of HZ in the V212 consistency lot group versus the placebo group. The success criterion for vaccine efficacy required that the lower bound of the 95% CI is >0.25.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine Efficacy
Estimated Value 0.695
Confidence Interval (2-Sided) 95%
0.490 to 0.818
Estimation Comments Point estimate and 95% CI of vaccine efficacy were obtained from a Cox proportional hazards regression model, adjusting for age (<50 versus ≥50 years of age), and intended duration of antiviral prophylaxis (≤3 versus 3 to 6 months after auto-HCT).
4.Secondary Outcome
Title Incidence of Herpes-Zoster Complications
Hide Description The composite efficacy endpoint of the incidence of HZ complications was defined as the occurrence of any of the following during the study: hospitalization or prolongation of hospitalization due to HZ, disseminated HZ (including disseminated HZ rash or VZV viremia), visceral HZ, ophthalmic HZ, neurological impairment due to HZ, or administration of intravenous acyclovir therapy for treatment of HZ.
Time Frame Up to 6 months after onset of HZ (up to approximately 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The population included participants who received ≥1 dose and had auto-HCT. To comply with regulatory requests, results for the V212 consistency lots were combined for the efficacy analyses, and the V212 High Antigen Lot was not included in the efficacy analyses for concerns that its inclusion would inflate efficacy estimates.
Arm/Group Title V212 Consistency Lots Placebo
Hide Arm/Group Description:
Participants randomized to receive V212 consistency Lot 1, 2, or 3 given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT.
Participants randomized to receive matching placebo given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT.
Overall Number of Participants Analyzed 538 535
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Number of cases per 1000 person years
9.397
(4.855 to 16.414)
35.777
(25.996 to 48.030)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection V212 Consistency Lots, Placebo
Comments Vaccine efficacy was calculated as 1 minus the hazard ratio of HZ in the V212 consistency lot group versus the placebo group. The success criterion for vaccine efficacy required that the lower bound of the 95% CI is >0.25.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine Efficacy
Estimated Value 0.735
Confidence Interval (2-Sided) 95%
0.498 to 0.860
Estimation Comments Point estimate and 95% CI of vaccine efficacy were obtained from a Cox proportional hazards regression model, adjusting for age (<50 versus ≥50 years of age), and intended duration of antiviral prophylaxis (≤3 versus 3 to 6 months after auto-HCT).
5.Secondary Outcome
Title Incidence of Postherpetic Neuralgia
Hide Description Postherpetic Neuralgia (PHN) was defined as pain in the area of the HZ rash with pain in the last 24 hours scored as 3 or greater (on a 0 to 10 scale, where 0 is no pain and 10 is pain as bad as you can imagine) on the ZBPI that persists or appears greater than or equal to 90 days after HZ rash onset.
Time Frame Up to 6 months after the onset of HZ rash (up to approximately 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The population included participants who received ≥1 dose and had auto-HCT. To comply with regulatory requests, results for the V212 consistency lots were combined for the efficacy analyses, and the V212 High Antigen Lot was not included in the efficacy analyses for concerns that its inclusion would inflate efficacy estimates.
Arm/Group Title V212 Consistency Lots Placebo
Hide Arm/Group Description:
Participants randomized to receive V212 consistency Lot 1, 2, or 3 given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT.
Participants randomized to receive matching placebo given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT.
Overall Number of Participants Analyzed 538 535
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Number of cases per 1000 person years
2.349
(0.484 to 6.865)
14.636
(8.674 to 23.132)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection V212 Consistency Lots, Placebo
Comments Vaccine efficacy was calculated as 1 minus the hazard ratio of HZ in the V212 consistency lot group versus the placebo group. The success criterion for vaccine efficacy required that the lower bound of the 95% CI is >0.25.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine Efficacy
Estimated Value 0.837
Confidence Interval (2-Sided) 95%
0.446 to 0.952
Estimation Comments Point estimate and 95% CI of vaccine efficacy were obtained from a Cox proportional hazards regression model, adjusting for age (<50 versus ≥50 years of age), and intended duration of antiviral prophylaxis (≤3 versus 3 to 6 months after auto-HCT).
6.Other Pre-specified Outcome
Title Percentage of Participants With Study Medication Withdrawn Due to an Adverse Event
Hide Description An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. A serious adverse event (SAE) is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, is a cancer, is an overdose, or is another important medical event.
Time Frame Up to 28 days after vaccination 4 (up to 118 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The population included all participants who received ≥1 dose and had safety follow-up. To comply with regulatory requests, results for all lots of V212 were combined in the primary and secondary safety analyses. One participant randomized to placebo was cross-treated; this participant was excluded from the safety analyses.
Arm/Group Title All V212 (Including High Antigen Lot) Placebo
Hide Arm/Group Description:
V212 (all lots, including High Antigen Lot) administered by subcutaneous injection 30 days before and 30, 60, and 90 days after auto-HCT.
Participants randomized to receive matching placebo given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT.
Overall Number of Participants Analyzed 657 554
Measure Type: Number
Unit of Measure: Percentage of participants
3.0 3.1
Time Frame Adverse events were collected up to approximately 5 years after vaccination 1.
Adverse Event Reporting Description The population included all participants who received ≥1 dose and had safety follow-up. To comply with regulatory requests, results for all lots of V212 were combined in the primary and secondary safety analyses. One participant randomized to placebo was cross-treated; this participant was excluded from the safety analyses.
 
Arm/Group Title V212 [Including High Antigen Lot] Placebo
Hide Arm/Group Description Participants received V212 Consistency Lot 1, 2, 3 or High Antigen Lot 0.5 mL administered by subcutaneous injection 30 days before and 30, 60, and 90 days after auto-HCT. Participants randomized to receive matching placebo given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT.
All-Cause Mortality
V212 [Including High Antigen Lot] Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   136/657 (20.70%)      107/554 (19.31%)    
Hide Serious Adverse Events
V212 [Including High Antigen Lot] Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   420/657 (63.93%)      374/554 (67.51%)    
Blood and lymphatic system disorders     
Abdominal lymphadenopathy  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Acquired haemophilia  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Agranulocytosis  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Anaemia  1  3/657 (0.46%)  3 3/554 (0.54%)  3
Anaemia megaloblastic  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Bone marrow failure  1  0/657 (0.00%)  0 1/554 (0.18%)  2
Febrile neutropenia  1  42/657 (6.39%)  44 38/554 (6.86%)  47
Heparin-induced thrombocytopenia  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Immune thrombocytopenic purpura  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Leukocytosis  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Lymphadenopathy  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Methaemoglobinaemia  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Neutropenia  1  2/657 (0.30%)  2 2/554 (0.36%)  3
Pancytopenia  1  4/657 (0.61%)  4 2/554 (0.36%)  2
Sickle cell anaemia with crisis  1  0/657 (0.00%)  0 1/554 (0.18%)  2
Splenic infarction  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Thrombocytopenia  1  8/657 (1.22%)  8 7/554 (1.26%)  7
Cardiac disorders     
Acute myocardial infarction  1  5/657 (0.76%)  5 3/554 (0.54%)  3
Arrhythmia  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Atrial fibrillation  1  4/657 (0.61%)  6 5/554 (0.90%)  6
Atrial flutter  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Bradycardia  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Cardiac amyloidosis  1  0/657 (0.00%)  0 3/554 (0.54%)  3
Cardiac failure  1  3/657 (0.46%)  3 4/554 (0.72%)  4
Cardiac failure acute  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Cardiac failure chronic  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Cardiac failure congestive  1  5/657 (0.76%)  5 5/554 (0.90%)  6
Cardiac ventricular thrombosis  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Cardiogenic shock  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Coronary artery disease  1  2/657 (0.30%)  2 1/554 (0.18%)  1
Coronary artery occlusion  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Myocardial infarction  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Pericarditis  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Supraventricular tachycardia  1  1/657 (0.15%)  1 2/554 (0.36%)  2
Tachycardia  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Ear and labyrinth disorders     
Acute vestibular syndrome  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Endocrine disorders     
Hyperthyroidism  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Eye disorders     
Diabetic retinopathy  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Intraocular haematoma  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Retinal haemorrhage  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Vitreous haemorrhage  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Gastrointestinal disorders     
Abdominal discomfort  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Abdominal pain  1  1/657 (0.15%)  1 2/554 (0.36%)  2
Anal fissure  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Anal incontinence  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Aphthous ulcer  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Ascites  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Colitis  1  1/657 (0.15%)  1 2/554 (0.36%)  2
Crohn's disease  1  2/657 (0.30%)  2 0/554 (0.00%)  0
Diarrhoea  1  7/657 (1.07%)  7 15/554 (2.71%)  16
Diverticulum intestinal  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Dyskinesia oesophageal  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Dysphagia  1  2/657 (0.30%)  2 0/554 (0.00%)  0
Faecaloma  1  2/657 (0.30%)  2 0/554 (0.00%)  0
Gastric ulcer  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Gastric ulcer haemorrhage  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Gastritis  1  1/657 (0.15%)  1 2/554 (0.36%)  2
Gastrointestinal disorder  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Gastrointestinal haemorrhage  1  1/657 (0.15%)  1 5/554 (0.90%)  7
Gastrointestinal obstruction  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Haematemesis  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Haematochezia  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Haemorrhoids  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Ileus  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Impaired gastric emptying  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Inguinal hernia  1  3/657 (0.46%)  3 2/554 (0.36%)  2
Intestinal infarction  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Intestinal ischaemia  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Intestinal obstruction  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Intra-abdominal haematoma  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Large intestine perforation  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Large intestine polyp  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Lower gastrointestinal haemorrhage  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Mesenteritis  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Nausea  1  3/657 (0.46%)  3 3/554 (0.54%)  3
Neutropenic colitis  1  2/657 (0.30%)  2 0/554 (0.00%)  0
Pancreatic insufficiency  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Pancreatitis  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Pancreatitis acute  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Rectal haemorrhage  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Small intestinal obstruction  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Stomatitis  1  2/657 (0.30%)  2 0/554 (0.00%)  0
Upper gastrointestinal haemorrhage  1  2/657 (0.30%)  2 2/554 (0.36%)  2
Vomiting  1  4/657 (0.61%)  4 5/554 (0.90%)  5
General disorders     
Adverse drug reaction  1  2/657 (0.30%)  2 0/554 (0.00%)  0
Asthenia  1  4/657 (0.61%)  4 3/554 (0.54%)  3
Death  1  5/657 (0.76%)  5 4/554 (0.72%)  4
Drug withdrawal syndrome  1  1/657 (0.15%)  1 0/554 (0.00%)  0
General physical health deterioration  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Influenza like illness  1  0/657 (0.00%)  0 2/554 (0.36%)  2
Malaise  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Mucosal inflammation  1  8/657 (1.22%)  8 6/554 (1.08%)  6
Multiple organ dysfunction syndrome  1  3/657 (0.46%)  3 3/554 (0.54%)  3
Pneumatosis  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Pyrexia  1  33/657 (5.02%)  37 26/554 (4.69%)  26
Systemic inflammatory response syndrome  1  2/657 (0.30%)  2 1/554 (0.18%)  2
Ulcer haemorrhage  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Hepatobiliary disorders     
Bile duct stenosis  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Bile duct stone  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Cholangitis  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Cholangitis acute  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Cholecystitis  1  2/657 (0.30%)  2 0/554 (0.00%)  0
Cholecystitis acute  1  2/657 (0.30%)  2 1/554 (0.18%)  1
Cholelithiasis obstructive  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Granulomatous liver disease  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Hepatic cirrhosis  1  1/657 (0.15%)  2 0/554 (0.00%)  0
Hepatic failure  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Hydrocholecystis  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Jaundice  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Jaundice cholestatic  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Portal hypertension  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Immune system disorders     
Acute graft versus host disease in skin  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Amyloidosis  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Anaphylactic reaction  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Anaphylactic shock  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Drug hypersensitivity  1  1/657 (0.15%)  1 2/554 (0.36%)  2
Engraftment syndrome  1  0/657 (0.00%)  0 2/554 (0.36%)  2
Graft versus host disease  1  0/657 (0.00%)  0 2/554 (0.36%)  2
Graft versus host disease in gastrointestinal tract  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Graft versus host disease in liver  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Graft versus host disease in lung  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Graft versus host disease in skin  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Hypersensitivity  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Primary amyloidosis  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Infections and infestations     
Abdominal abscess  1  2/657 (0.30%)  2 0/554 (0.00%)  0
Actinomycotic pulmonary infection  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Acute sinusitis  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Adenovirus infection  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Anal abscess  1  0/657 (0.00%)  0 2/554 (0.36%)  2
Appendicitis  1  2/657 (0.30%)  2 2/554 (0.36%)  2
Appendicitis perforated  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Arthritis bacterial  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Aspergilloma  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Aspergillus infection  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Atypical pneumonia  1  6/657 (0.91%)  6 0/554 (0.00%)  0
BK virus infection  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Bacteraemia  1  4/657 (0.61%)  4 7/554 (1.26%)  8
Bacterial sepsis  1  0/657 (0.00%)  0 2/554 (0.36%)  2
Bronchiolitis  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Bronchitis  1  4/657 (0.61%)  4 4/554 (0.72%)  5
Bronchitis bacterial  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Bronchitis viral  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Bronchopulmonary aspergillosis  1  6/657 (0.91%)  6 4/554 (0.72%)  4
Candida sepsis  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Cellulitis  1  4/657 (0.61%)  6 3/554 (0.54%)  3
Cholangitis infective  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Chronic hepatitis B  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Clostridial infection  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Clostridium colitis  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Clostridium difficile colitis  1  5/657 (0.76%)  5 5/554 (0.90%)  5
Clostridium difficile infection  1  3/657 (0.46%)  3 0/554 (0.00%)  0
Coxsackie viral infection  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Cystitis  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Cytomegalovirus colitis  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Cytomegalovirus infection  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Cytomegalovirus oesophagitis  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Dengue fever  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Device related infection  1  5/657 (0.76%)  6 2/554 (0.36%)  2
Device related sepsis  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Diverticulitis  1  3/657 (0.46%)  3 0/554 (0.00%)  0
Empyema  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Enterococcal bacteraemia  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Enterococcal infection  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Enterocolitis bacterial  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Enterovirus infection  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Epididymitis  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Erysipelas  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Escherichia bacteraemia  1  2/657 (0.30%)  2 1/554 (0.18%)  1
Escherichia sepsis  1  1/657 (0.15%)  1 2/554 (0.36%)  2
Escherichia urinary tract infection  1  3/657 (0.46%)  3 0/554 (0.00%)  0
Febrile infection  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Fungal oesophagitis  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Gastroenteritis  1  5/657 (0.76%)  5 4/554 (0.72%)  4
Gastroenteritis rotavirus  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Gastroenteritis viral  1  1/657 (0.15%)  1 2/554 (0.36%)  2
Gastrointestinal candidiasis  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Gastrointestinal infection  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Groin abscess  1  1/657 (0.15%)  1 0/554 (0.00%)  0
H1N1 influenza  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Haemophilus infection  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Herpes zoster  1  3/657 (0.46%)  3 12/554 (2.17%)  12
Herpes zoster disseminated  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Infected lymphocele  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Infection  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Infection in an immunocompromised host  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Infective exacerbation of chronic obstructive airways disease  1  1/657 (0.15%)  2 0/554 (0.00%)  0
Influenza  1  8/657 (1.22%)  8 7/554 (1.26%)  7
Klebsiella bacteraemia  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Klebsiella infection  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Lower respiratory tract infection  1  1/657 (0.15%)  3 0/554 (0.00%)  0
Lower respiratory tract infection viral  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Lung abscess  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Lung infection  1  3/657 (0.46%)  3 0/554 (0.00%)  0
Lung infection pseudomonal  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Meningitis  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Meningitis pneumococcal  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Meningoencephalitis herpetic  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Nasopharyngitis  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Neutropenic sepsis  1  3/657 (0.46%)  3 3/554 (0.54%)  3
Oral candidiasis  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Parainfluenzae virus infection  1  0/657 (0.00%)  0 2/554 (0.36%)  2
Pharyngitis  1  2/657 (0.30%)  2 0/554 (0.00%)  0
Pneumococcal bacteraemia  1  0/657 (0.00%)  0 2/554 (0.36%)  2
Pneumococcal sepsis  1  1/657 (0.15%)  1 3/554 (0.54%)  3
Pneumocystis jirovecii infection  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Pneumocystis jirovecii pneumonia  1  1/657 (0.15%)  1 2/554 (0.36%)  2
Pneumonia  1  61/657 (9.28%)  74 56/554 (10.11%)  67
Pneumonia bacterial  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Pneumonia cytomegaloviral  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Pneumonia fungal  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Pneumonia parainfluenzae viral  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Pneumonia respiratory syncytial viral  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Pneumonia viral  1  2/657 (0.30%)  2 2/554 (0.36%)  2
Postoperative abscess  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Postoperative wound infection  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Pseudomembranous colitis  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Pseudomonal bacteraemia  1  2/657 (0.30%)  2 1/554 (0.18%)  1
Pseudomonal sepsis  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Pseudomonas infection  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Pulmonary mycosis  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Pulmonary sepsis  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Pulmonary tuberculosis  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Respiratory syncytial virus infection  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Respiratory tract infection  1  2/657 (0.30%)  2 0/554 (0.00%)  0
Respiratory tract infection viral  1  2/657 (0.30%)  2 0/554 (0.00%)  0
Retinitis  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Rhinovirus infection  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Scrotal abscess  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Sepsis  1  19/657 (2.89%)  19 12/554 (2.17%)  14
Sepsis syndrome  1  1/657 (0.15%)  1 2/554 (0.36%)  2
Septic shock  1  7/657 (1.07%)  7 4/554 (0.72%)  4
Sialoadenitis  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Sinusitis  1  1/657 (0.15%)  1 3/554 (0.54%)  4
Staphylococcal bacteraemia  1  4/657 (0.61%)  4 3/554 (0.54%)  3
Staphylococcal infection  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Staphylococcal sepsis  1  2/657 (0.30%)  2 4/554 (0.72%)  4
Streptococcal bacteraemia  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Streptococcal sepsis  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Systemic candida  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Thrombophlebitis septic  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Tooth abscess  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Tuberculosis  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Upper respiratory tract infection  1  5/657 (0.76%)  5 5/554 (0.90%)  5
Urinary tract infection  1  8/657 (1.22%)  10 5/554 (0.90%)  5
Urosepsis  1  0/657 (0.00%)  0 2/554 (0.36%)  2
Varicella  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Varicella zoster virus infection  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Viral infection  1  2/657 (0.30%)  2 5/554 (0.90%)  6
Viral sepsis  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Viral upper respiratory tract infection  1  2/657 (0.30%)  2 2/554 (0.36%)  2
Wound infection bacterial  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Injury, poisoning and procedural complications     
Allergic transfusion reaction  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Brain contusion  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Comminuted fracture  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Compression fracture  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Delayed engraftment  1  0/657 (0.00%)  0 2/554 (0.36%)  2
Femur fracture  1  1/657 (0.15%)  1 2/554 (0.36%)  2
Foot fracture  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Forearm fracture  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Hip fracture  1  1/657 (0.15%)  1 3/554 (0.54%)  3
Infusion related reaction  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Multiple fractures  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Peroneal nerve injury  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Post lumbar puncture syndrome  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Procedural hypotension  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Seroma  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Spinal compression fracture  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Spinal fracture  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Subdural haematoma  1  1/657 (0.15%)  1 2/554 (0.36%)  2
Subdural haemorrhage  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Tendon rupture  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Toxicity to various agents  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Transfusion reaction  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Transplant dysfunction  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Traumatic haemothorax  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Upper limb fracture  1  2/657 (0.30%)  2 0/554 (0.00%)  0
Wound dehiscence  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Investigations     
Transaminases increased  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Metabolism and nutrition disorders     
Decreased appetite  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Dehydration  1  2/657 (0.30%)  3 2/554 (0.36%)  2
Diabetes mellitus  1  2/657 (0.30%)  2 0/554 (0.00%)  0
Failure to thrive  1  3/657 (0.46%)  3 0/554 (0.00%)  0
Food intolerance  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Hypercalcaemia  1  2/657 (0.30%)  2 2/554 (0.36%)  2
Hyperglycaemia  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Hypocalcaemia  1  0/657 (0.00%)  0 2/554 (0.36%)  2
Hypoglycaemia  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Hypokalaemia  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Lactose intolerance  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Tetany  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Tumour lysis syndrome  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Back pain  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Bone pain  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Cervical spinal stenosis  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Intervertebral disc degeneration  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Intervertebral disc protrusion  1  2/657 (0.30%)  2 0/554 (0.00%)  0
Neck pain  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Osteoarthritis  1  0/657 (0.00%)  0 2/554 (0.36%)  2
Osteolysis  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Osteonecrosis  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Pathological fracture  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Pseudarthrosis  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Spinal column stenosis  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute leukaemia  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Acute myeloid leukaemia  1  2/657 (0.30%)  2 2/554 (0.36%)  2
Acute myeloid leukaemia recurrent  1  0/657 (0.00%)  0 3/554 (0.54%)  4
Acute promyelocytic leukaemia  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Adenocarcinoma gastric  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Anaplastic large cell lymphoma T- and null-cell types  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Anaplastic large cell lymphoma T- and null-cell types recurrent  1  0/657 (0.00%)  0 2/554 (0.36%)  2
Anaplastic large-cell lymphoma  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Angiocentric lymphoma  1  0/657 (0.00%)  0 3/554 (0.54%)  3
Angioimmunoblastic T-cell lymphoma recurrent  1  1/657 (0.15%)  1 2/554 (0.36%)  2
B-cell lymphoma  1  0/657 (0.00%)  0 2/554 (0.36%)  2
B-cell lymphoma recurrent  1  3/657 (0.46%)  3 5/554 (0.90%)  5
B-cell lymphoma stage IV  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Basal cell carcinoma  1  1/657 (0.15%)  2 3/554 (0.54%)  3
Basosquamous carcinoma  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Bladder cancer  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Bladder cancer recurrent  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Breast cancer  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Breast cancer recurrent  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Central nervous system lymphoma  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Cholangiocarcinoma  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Chronic lymphocytic leukaemia recurrent  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Chronic myeloid leukaemia  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Colon adenoma  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Colon cancer metastatic  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Colorectal cancer  1  2/657 (0.30%)  2 0/554 (0.00%)  0
Diffuse large B-cell lymphoma  1  10/657 (1.52%)  11 10/554 (1.81%)  11
Diffuse large B-cell lymphoma recurrent  1  14/657 (2.13%)  14 10/554 (1.81%)  10
Diffuse large B-cell lymphoma refractory  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Extranodal marginal zone B-cell lymphoma (MALT type) recurrent  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Follicle centre lymphoma, follicular grade I, II, III recurrent  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Hodgkin's disease  1  8/657 (1.22%)  8 5/554 (0.90%)  7
Hodgkin's disease nodular sclerosis  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Hodgkin's disease recurrent  1  7/657 (1.07%)  8 6/554 (1.08%)  6
Langerhans' cell histiocytosis  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Laryngeal squamous cell carcinoma  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Leukaemia recurrent  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Lung neoplasm malignant  1  1/657 (0.15%)  1 2/554 (0.36%)  2
Lymphoma  1  9/657 (1.37%)  9 6/554 (1.08%)  7
Lymphoplasmacytoid lymphoma/immunocytoma  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Malignant lymphoid neoplasm  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Malignant melanoma  1  1/657 (0.15%)  1 4/554 (0.72%)  4
Mantle cell lymphoma  1  1/657 (0.15%)  1 4/554 (0.72%)  4
Mantle cell lymphoma recurrent  1  10/657 (1.52%)  10 9/554 (1.62%)  9
Metastases to meninges  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Myelodysplastic syndrome  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Neuroendocrine carcinoma  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Non-Hodgkin's lymphoma  1  6/657 (0.91%)  6 3/554 (0.54%)  3
Non-Hodgkin's lymphoma recurrent  1  10/657 (1.52%)  11 13/554 (2.35%)  13
Non-Hodgkin's lymphoma refractory  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Nonkeratinising carcinoma of nasopharynx  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Pancreatic carcinoma  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Papillary thyroid cancer  1  1/657 (0.15%)  1 3/554 (0.54%)  3
Paraneoplastic syndrome  1  2/657 (0.30%)  2 0/554 (0.00%)  0
Pericardial effusion malignant  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Peripheral T-cell lymphoma unspecified  1  3/657 (0.46%)  3 2/554 (0.36%)  2
Peripheral T-cell lymphoma unspecified recurrent  1  4/657 (0.61%)  4 2/554 (0.36%)  2
Plasma cell myeloma  1  67/657 (10.20%)  75 51/554 (9.21%)  57
Plasma cell myeloma recurrent  1  50/657 (7.61%)  51 53/554 (9.57%)  56
Plasmablastic lymphoma  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Plasmacytoma  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Precursor T-lymphoblastic lymphoma/leukaemia  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Precursor T-lymphoblastic lymphoma/leukaemia recurrent  1  1/657 (0.15%)  2 0/554 (0.00%)  0
Primary mediastinal large B-cell lymphoma  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Prostate cancer  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Rectal cancer  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Rectal cancer recurrent  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Renal cell carcinoma  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Small cell carcinoma  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Squamous cell carcinoma  1  2/657 (0.30%)  2 0/554 (0.00%)  0
Squamous cell carcinoma of skin  1  2/657 (0.30%)  2 1/554 (0.18%)  2
T-cell lymphoma  1  1/657 (0.15%)  1 2/554 (0.36%)  2
T-cell lymphoma recurrent  1  8/657 (1.22%)  8 2/554 (0.36%)  3
Tumour flare  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Nervous system disorders     
Autonomic nervous system imbalance  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Carotid artery aneurysm  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Carotid artery disease  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Cerebellar infarction  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Cerebral haemorrhage  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Cerebrovascular accident  1  4/657 (0.61%)  4 1/554 (0.18%)  1
Dizziness  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Facial paralysis  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Headache  1  2/657 (0.30%)  2 1/554 (0.18%)  1
Hepatic encephalopathy  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Hypoglycaemic coma  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Intracranial venous sinus thrombosis  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Metabolic encephalopathy  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Migraine  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Paraesthesia  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Presyncope  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Sciatica  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Syncope  1  6/657 (0.91%)  7 5/554 (0.90%)  5
Transient ischaemic attack  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Pregnancy, puerperium and perinatal conditions     
Threatened labour  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Psychiatric disorders     
Anxiety  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Confusional state  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Delirium  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Depression  1  2/657 (0.30%)  2 0/554 (0.00%)  0
Disorientation  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Hypomania  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Mania  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Mental status changes  1  2/657 (0.30%)  2 0/554 (0.00%)  0
Schizoaffective disorder  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Suicide attempt  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury  1  8/657 (1.22%)  10 10/554 (1.81%)  11
Acute prerenal failure  1  0/657 (0.00%)  0 2/554 (0.36%)  2
Cystitis haemorrhagic  1  0/657 (0.00%)  0 1/554 (0.18%)  1
End stage renal disease  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Haematuria  1  2/657 (0.30%)  2 2/554 (0.36%)  2
Nephrolithiasis  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Renal failure  1  4/657 (0.61%)  5 5/554 (0.90%)  5
Renal injury  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Renal tubular necrosis  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Tubulointerstitial nephritis  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Ureterolithiasis  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Urinary retention  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Reproductive system and breast disorders     
Acquired phimosis  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Benign prostatic hyperplasia  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Acute respiratory failure  1  1/657 (0.15%)  1 2/554 (0.36%)  2
Asthma  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Chronic obstructive pulmonary disease  1  3/657 (0.46%)  3 2/554 (0.36%)  2
Dyspnoea  1  2/657 (0.30%)  2 0/554 (0.00%)  0
Emphysema  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Hypoxia  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Idiopathic pneumonia syndrome  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Interstitial lung disease  1  2/657 (0.30%)  2 1/554 (0.18%)  1
Lung consolidation  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Lung infiltration  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Obstructive airways disorder  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Organising pneumonia  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Oropharyngeal pain  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Pleural effusion  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Pneumomediastinum  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Pneumonia aspiration  1  1/657 (0.15%)  1 2/554 (0.36%)  2
Pneumonitis  1  1/657 (0.15%)  1 2/554 (0.36%)  2
Pneumothorax  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Pulmonary embolism  1  6/657 (0.91%)  6 5/554 (0.90%)  5
Pulmonary hypertension  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Pulmonary mass  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Pulmonary oedema  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Respiratory distress  1  3/657 (0.46%)  4 2/554 (0.36%)  2
Respiratory failure  1  3/657 (0.46%)  4 1/554 (0.18%)  1
Restrictive pulmonary disease  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Sleep apnoea syndrome  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Skin and subcutaneous tissue disorders     
Blister  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Dermal cyst  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Dermatitis exfoliative  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Eczema  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Rash  1  1/657 (0.15%)  1 1/554 (0.18%)  1
Rash maculo-papular  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Rash vesicular  1  3/657 (0.46%)  3 3/554 (0.54%)  3
Vascular disorders     
Aortic aneurysm  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Aortic stenosis  1  2/657 (0.30%)  2 0/554 (0.00%)  0
Deep vein thrombosis  1  7/657 (1.07%)  7 2/554 (0.36%)  2
Embolism  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Hypertension  1  0/657 (0.00%)  0 1/554 (0.18%)  1
Hypertensive crisis  1  0/657 (0.00%)  0 3/554 (0.54%)  3
Hypotension  1  5/657 (0.76%)  5 3/554 (0.54%)  3
Orthostatic hypotension  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Peripheral arterial occlusive disease  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Peripheral artery thrombosis  1  1/657 (0.15%)  1 0/554 (0.00%)  0
Venoocclusive disease  1  2/657 (0.30%)  2 0/554 (0.00%)  0
Venous thrombosis limb  1  0/657 (0.00%)  0 1/554 (0.18%)  1
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
V212 [Including High Antigen Lot] Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   625/657 (95.13%)      512/554 (92.42%)    
Blood and lymphatic system disorders     
Anaemia  1  175/657 (26.64%)  201 134/554 (24.19%)  168
Febrile neutropenia  1  184/657 (28.01%)  191 135/554 (24.37%)  138
Leukopenia  1  33/657 (5.02%)  34 32/554 (5.78%)  41
Neutropenia  1  163/657 (24.81%)  187 129/554 (23.29%)  157
Pancytopenia  1  63/657 (9.59%)  64 53/554 (9.57%)  54
Thrombocytopenia  1  238/657 (36.23%)  289 212/554 (38.27%)  264
Cardiac disorders     
Tachycardia  1  45/657 (6.85%)  47 34/554 (6.14%)  35
Gastrointestinal disorders     
Abdominal pain  1  87/657 (13.24%)  103 78/554 (14.08%)  81
Abdominal pain upper  1  51/657 (7.76%)  51 34/554 (6.14%)  35
Constipation  1  107/657 (16.29%)  120 102/554 (18.41%)  113
Diarrhoea  1  394/657 (59.97%)  492 341/554 (61.55%)  396
Dyspepsia  1  61/657 (9.28%)  65 47/554 (8.48%)  52
Nausea  1  370/657 (56.32%)  452 319/554 (57.58%)  391
Stomatitis  1  83/657 (12.63%)  94 51/554 (9.21%)  56
Vomiting  1  211/657 (32.12%)  265 200/554 (36.10%)  260
General disorders     
Asthenia  1  72/657 (10.96%)  77 60/554 (10.83%)  68
Chills  1  39/657 (5.94%)  44 35/554 (6.32%)  42
Fatigue  1  144/657 (21.92%)  159 121/554 (21.84%)  131
Injection site erythema  1  153/657 (23.29%)  323 14/554 (2.53%)  19
Injection site pain  1  133/657 (20.24%)  283 21/554 (3.79%)  24
Injection site pruritus  1  35/657 (5.33%)  52 4/554 (0.72%)  5
Injection site swelling  1  124/657 (18.87%)  257 9/554 (1.62%)  9
Mucosal inflammation  1  254/657 (38.66%)  271 226/554 (40.79%)  244
Oedema peripheral  1  77/657 (11.72%)  89 65/554 (11.73%)  72
Pyrexia  1  317/657 (48.25%)  526 248/554 (44.77%)  374
Metabolism and nutrition disorders     
Decreased appetite  1  152/657 (23.14%)  161 132/554 (23.83%)  150
Hyperglycaemia  1  33/657 (5.02%)  40 16/554 (2.89%)  16
Hypocalcaemia  1  55/657 (8.37%)  65 40/554 (7.22%)  45
Hypokalaemia  1  141/657 (21.46%)  165 111/554 (20.04%)  135
Hypomagnesaemia  1  76/657 (11.57%)  88 62/554 (11.19%)  75
Hypophosphataemia  1  41/657 (6.24%)  48 40/554 (7.22%)  42
Musculoskeletal and connective tissue disorders     
Back pain  1  56/657 (8.52%)  63 46/554 (8.30%)  51
Pain in extremity  1  33/657 (5.02%)  35 24/554 (4.33%)  26
Nervous system disorders     
Dizziness  1  44/657 (6.70%)  46 46/554 (8.30%)  51
Dysgeusia  1  29/657 (4.41%)  29 28/554 (5.05%)  28
Headache  1  131/657 (19.94%)  149 114/554 (20.58%)  141
Psychiatric disorders     
Anxiety  1  35/657 (5.33%)  38 31/554 (5.60%)  32
Insomnia  1  84/657 (12.79%)  91 68/554 (12.27%)  71
Respiratory, thoracic and mediastinal disorders     
Cough  1  76/657 (11.57%)  84 80/554 (14.44%)  93
Dyspnoea  1  55/657 (8.37%)  60 36/554 (6.50%)  36
Epistaxis  1  41/657 (6.24%)  48 24/554 (4.33%)  26
Oropharyngeal pain  1  68/657 (10.35%)  78 43/554 (7.76%)  48
Skin and subcutaneous tissue disorders     
Erythema  1  33/657 (5.02%)  37 22/554 (3.97%)  31
Pruritus  1  66/657 (10.05%)  72 38/554 (6.86%)  45
Rash  1  89/657 (13.55%)  110 74/554 (13.36%)  84
Vascular disorders     
Hypertension  1  33/657 (5.02%)  38 33/554 (5.96%)  36
Hypotension  1  57/657 (8.68%)  64 48/554 (8.66%)  52
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
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.
The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/ presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission. SPONSOR review can be expedited to meet publication timelines.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01229267    
Other Study ID Numbers: V212-001
2010-020150-34 ( EudraCT Number )
V212-001 ( Other Identifier: Merck Protocol Number )
First Submitted: October 25, 2010
First Posted: October 27, 2010
Results First Submitted: April 16, 2018
Results First Posted: July 2, 2018
Last Update Posted: September 30, 2019