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)
Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT01229267
Collaborator
(none)
1,257
5
60.7
Study Details
Study Description
Brief Summary
This is a randomized, double-blind, placebo-controlled study to assess the safety and efficacy of inactivated VZV vaccine for the prevention of HZ and HZ-related complications in adult recipients of autologous hematopoietic cell transplants (HCTs). The primary hypothesis is that vaccination with V212 vaccine will reduce the incidence of herpes zoster (HZ) compared to placebo when administered to recipients of HCT. The statistical criterion for success requires that the lower bound of the 95% confidence interval for the estimated vaccine efficacy in the V212 recipients (excluding the high-antigen lot) compared with that in the placebo recipients is >25%.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Study participants were randomized to receive one of 3 consistency lots of V212, a high antigen lot of V212, or placebo. To comply with regulatory requests, results for all lots of V212 were combined for the primary and secondary efficacy and safety evaluations (Protocol Amendment 2); all planned comparisons between the V212 lots were exploratory and are not included in this disclosure. Further, by regulatory request, the V212 High Antigen Lot was not included in the efficacy analyses for concerns that its inclusion would inflate the efficacy estimates (Protocol Amendment 4).
Study Design
Study Type:
Interventional
Actual Enrollment
:
1257 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Prevention
Official Title:
A Phase III, Double-Blind, Randomized, Placebo-Controlled, Multicenter Clinical Trial to Study the Safety, Tolerability, Efficacy, and Immunogenicity of V212 in Recipients of Autologous Hematopoietic Cell Transplants (HCTs)
Actual Study Start Date
:
Nov 30, 2010
Actual Primary Completion Date
:
Dec 23, 2015
Actual Study Completion Date
:
Dec 23, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: V212 Consistency Lot 1 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. |
Biological: V212
V212 viral antigen for HZ. Participants will receive consistency Lot 1, 2, or 3 or the High Antigen Lot.
Other Names:
|
| Experimental: V212 Consistency Lot 2 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. |
Biological: V212
V212 viral antigen for HZ. Participants will receive consistency Lot 1, 2, or 3 or the High Antigen Lot.
Other Names:
|
| Experimental: V212 Consistency Lot 3 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. |
Biological: V212
V212 viral antigen for HZ. Participants will receive consistency Lot 1, 2, or 3 or the High Antigen Lot.
Other Names:
|
| Experimental: V212 High Antigen Lot 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. |
Biological: V212
V212 viral antigen for HZ. Participants will receive consistency Lot 1, 2, or 3 or the High Antigen Lot.
Other Names:
|
| Placebo Comparator: Placebo 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. |
Biological: Matching placebo
Vaccine stabilizer for V212 with no virus antigen
|
Outcome Measures
Primary Outcome Measures
- Incidence of Confirmed Herpes-Zoster [Up to approximately 5 years]
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.
- Percentage of Participants With One or More Serious Adverse Events [Up to 28 days after vaccination 4 (up to 118 days)]
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.
Secondary Outcome Measures
- Incidence of Moderate to Severe Herpes-Zoster-Associated Pain [Up to 6 months after onset of HZ (up to approximately 5 years)]
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.
- Incidence of Herpes-Zoster Complications [Up to 6 months after onset of HZ (up to approximately 5 years)]
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.
- Incidence of Postherpetic Neuralgia [Up to 6 months after the onset of HZ rash (up to approximately 5 years)]
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.
Other Outcome Measures
- Percentage of Participants With Study Medication Withdrawn Due to an Adverse Event [Up to 28 days after vaccination 4 (up to 118 days)]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Has prior history of varicella, antibodies to VZV (documented prior to receipt of blood products), or residence in a country with endemic VZV infection for ≥30 years or if participant is <30 years old, attended primary or secondary school in a country with endemic VZV infection.
-
Scheduled to undergo an autologous hematopoietic cell transplant within 60 days of enrollment
-
Is highly unlikely to conceive during the time period starting 2 weeks prior to enrollment through 6 months from last vaccination dose
-
Female participants of childbearing potential must have a negative serum or urine
pregnancy test.
Exclusion Criteria:
-
History of hypersensitivity reaction to any vaccine component
-
Prior history of herpes zoster within 1 year of enrollment
-
Prior receipt of any varicella or zoster vaccine
-
More than 2 relapses of the underlying cancer (participants with Hodgkin's lymphoma may have had more than 2 relapses)
-
Expectation of tandem transplant procedure
-
Is expected to receive >6 months (>180 days) of prophylactic antiviral therapy post-HCT.
-
Is pregnant or breastfeeding or expecting to conceive within the period of 2 weeks prior to enrollment through 6 months from last vaccination dose.
-
Has received a live virus vaccine or is scheduled to receive a live virus vaccine in the period from 4 weeks prior to Dose 1 through 28 days Postdose 4.
-
Has received an inactivated vaccine or is scheduled to receive an inactivated vaccine in the period between 7 days prior to and 28 days following Doses 1 through 4.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT01229267
Other Study ID Numbers:
- V212-001
- 2010-020150-34
- V212-001
First Posted:
Oct 27, 2010
Last Update Posted:
Sep 30, 2019
Last Verified:
Sep 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Merck Sharp & Dohme LLC
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Adult participants scheduled to undergo Autologous Hematopoietic Cell Transplant (auto-HCT) within 60 days were enrolled at 150 sties |
|---|---|
| Pre-assignment Detail | 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 |
|---|---|---|---|---|---|
| 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 |
Baseline Characteristics
| Arm/Group Title | V212 Consistency Lot 1 | V212 Consistency Lot 2 | V212 Consistency Lot 3 | V212 High Antigen Lot | Placebo | Total |
|---|---|---|---|---|---|---|
| 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 Participants | 189 | 184 | 187 | 106 | 564 | 1230 |
| Age (Years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [Years] |
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 (Count of Participants) | ||||||
| Female |
69
36.5%
|
73
39.7%
|
61
32.6%
|
48
45.3%
|
204
36.2%
|
455
37%
|
| Male |
120
63.5%
|
111
60.3%
|
126
67.4%
|
58
54.7%
|
360
63.8%
|
775
63%
|
| Age (Count of Participants) | ||||||
| From 18-49 years |
53
28%
|
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%
|
12
6.5%
|
4
2.1%
|
6
5.7%
|
30
5.3%
|
69
5.6%
|
| Intended duration of antiviral prophylaxis (Count of 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%
|
108
57.8%
|
63
59.4%
|
308
54.6%
|
691
56.2%
|
| Not reported |
0
0%
|
1
0.5%
|
0
0%
|
0
0%
|
1
0.2%
|
2
0.2%
|
Outcome Measures
| Title | Incidence of Confirmed Herpes-Zoster |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 538 | 535 |
| Number (95% Confidence Interval) [Number of cases per 1000 person years] |
32.889
|
91.883
|
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 0.638 | |
| Confidence Interval |
(2-Sided) 95% 0.484 to 0.746 |
|
| Parameter Dispersion |
Type: Value: |
|
| 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). | |
| Title | Incidence of Moderate to Severe Herpes-Zoster-Associated Pain |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 538 | 535 |
| Number (95% Confidence Interval) [Number of cases per 1000 person years] |
14.878
|
49.601
|
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 0.695 | |
| Confidence Interval |
(2-Sided) 95% 0.490 to 0.818 |
|
| Parameter Dispersion |
Type: Value: |
|
| 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). | |
| Title | Incidence of Herpes-Zoster Complications |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 538 | 535 |
| Number (95% Confidence Interval) [Number of cases per 1000 person years] |
9.397
|
35.777
|
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 0.735 | |
| Confidence Interval |
(2-Sided) 95% 0.498 to 0.860 |
|
| Parameter Dispersion |
Type: Value: |
|
| 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). | |
| Title | Incidence of Postherpetic Neuralgia |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 538 | 535 |
| Number (95% Confidence Interval) [Number of cases per 1000 person years] |
2.349
|
14.636
|
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 0.837 | |
| Confidence Interval |
(2-Sided) 95% 0.446 to 0.952 |
|
| Parameter Dispersion |
Type: Value: |
|
| 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). | |
| Title | Percentage of Participants With One or More Serious Adverse Events |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 657 | 554 |
| Number [Percentage of participants] |
32.9
17.4%
|
32.7
17.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | V212 Consistency Lots, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.942 |
| Comments | ||
| Method | Normal approximation | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference (RD) |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -5.1 to 5.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Miettinen & Nurminen | |
| Title | Percentage of Participants With Study Medication Withdrawn Due to an Adverse Event |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 657 | 554 |
| Number [Percentage of participants] |
3.0
1.6%
|
3.1
1.7%
|
Adverse Events
| 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 | ||
| 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 (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 136/657 (20.7%) | 107/554 (19.3%) | ||
Serious Adverse Events |
||||
| V212 [Including High Antigen Lot] | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 420/657 (63.9%) | 374/554 (67.5%) | ||
| Blood and lymphatic system disorders | ||||
| Abdominal lymphadenopathy | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Acquired haemophilia | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Agranulocytosis | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Anaemia | 3/657 (0.5%) | 3 | 3/554 (0.5%) | 3 |
| Anaemia megaloblastic | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Bone marrow failure | 0/657 (0%) | 0 | 1/554 (0.2%) | 2 |
| Febrile neutropenia | 42/657 (6.4%) | 44 | 38/554 (6.9%) | 47 |
| Heparin-induced thrombocytopenia | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Immune thrombocytopenic purpura | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Leukocytosis | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Lymphadenopathy | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Methaemoglobinaemia | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Neutropenia | 2/657 (0.3%) | 2 | 2/554 (0.4%) | 3 |
| Pancytopenia | 4/657 (0.6%) | 4 | 2/554 (0.4%) | 2 |
| Sickle cell anaemia with crisis | 0/657 (0%) | 0 | 1/554 (0.2%) | 2 |
| Splenic infarction | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Thrombocytopenia | 8/657 (1.2%) | 8 | 7/554 (1.3%) | 7 |
| Cardiac disorders | ||||
| Acute myocardial infarction | 5/657 (0.8%) | 5 | 3/554 (0.5%) | 3 |
| Arrhythmia | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Atrial fibrillation | 4/657 (0.6%) | 6 | 5/554 (0.9%) | 6 |
| Atrial flutter | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Bradycardia | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Cardiac amyloidosis | 0/657 (0%) | 0 | 3/554 (0.5%) | 3 |
| Cardiac failure | 3/657 (0.5%) | 3 | 4/554 (0.7%) | 4 |
| Cardiac failure acute | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Cardiac failure chronic | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Cardiac failure congestive | 5/657 (0.8%) | 5 | 5/554 (0.9%) | 6 |
| Cardiac ventricular thrombosis | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Cardiogenic shock | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Coronary artery disease | 2/657 (0.3%) | 2 | 1/554 (0.2%) | 1 |
| Coronary artery occlusion | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Myocardial infarction | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Pericarditis | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Supraventricular tachycardia | 1/657 (0.2%) | 1 | 2/554 (0.4%) | 2 |
| Tachycardia | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Ear and labyrinth disorders | ||||
| Acute vestibular syndrome | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Endocrine disorders | ||||
| Hyperthyroidism | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Eye disorders | ||||
| Diabetic retinopathy | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Intraocular haematoma | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Retinal haemorrhage | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Vitreous haemorrhage | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Gastrointestinal disorders | ||||
| Abdominal discomfort | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Abdominal pain | 1/657 (0.2%) | 1 | 2/554 (0.4%) | 2 |
| Anal fissure | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Anal incontinence | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Aphthous ulcer | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Ascites | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Colitis | 1/657 (0.2%) | 1 | 2/554 (0.4%) | 2 |
| Crohn's disease | 2/657 (0.3%) | 2 | 0/554 (0%) | 0 |
| Diarrhoea | 7/657 (1.1%) | 7 | 15/554 (2.7%) | 16 |
| Diverticulum intestinal | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Dyskinesia oesophageal | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Dysphagia | 2/657 (0.3%) | 2 | 0/554 (0%) | 0 |
| Faecaloma | 2/657 (0.3%) | 2 | 0/554 (0%) | 0 |
| Gastric ulcer | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Gastric ulcer haemorrhage | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Gastritis | 1/657 (0.2%) | 1 | 2/554 (0.4%) | 2 |
| Gastrointestinal disorder | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Gastrointestinal haemorrhage | 1/657 (0.2%) | 1 | 5/554 (0.9%) | 7 |
| Gastrointestinal obstruction | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Haematemesis | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Haematochezia | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Haemorrhoids | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Ileus | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Impaired gastric emptying | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Inguinal hernia | 3/657 (0.5%) | 3 | 2/554 (0.4%) | 2 |
| Intestinal infarction | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Intestinal ischaemia | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Intestinal obstruction | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Intra-abdominal haematoma | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Large intestine perforation | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Large intestine polyp | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Lower gastrointestinal haemorrhage | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Mesenteritis | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Nausea | 3/657 (0.5%) | 3 | 3/554 (0.5%) | 3 |
| Neutropenic colitis | 2/657 (0.3%) | 2 | 0/554 (0%) | 0 |
| Pancreatic insufficiency | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Pancreatitis | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Pancreatitis acute | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Rectal haemorrhage | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Small intestinal obstruction | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Stomatitis | 2/657 (0.3%) | 2 | 0/554 (0%) | 0 |
| Upper gastrointestinal haemorrhage | 2/657 (0.3%) | 2 | 2/554 (0.4%) | 2 |
| Vomiting | 4/657 (0.6%) | 4 | 5/554 (0.9%) | 5 |
| General disorders | ||||
| Adverse drug reaction | 2/657 (0.3%) | 2 | 0/554 (0%) | 0 |
| Asthenia | 4/657 (0.6%) | 4 | 3/554 (0.5%) | 3 |
| Death | 5/657 (0.8%) | 5 | 4/554 (0.7%) | 4 |
| Drug withdrawal syndrome | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| General physical health deterioration | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Influenza like illness | 0/657 (0%) | 0 | 2/554 (0.4%) | 2 |
| Malaise | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Mucosal inflammation | 8/657 (1.2%) | 8 | 6/554 (1.1%) | 6 |
| Multiple organ dysfunction syndrome | 3/657 (0.5%) | 3 | 3/554 (0.5%) | 3 |
| Pneumatosis | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Pyrexia | 33/657 (5%) | 37 | 26/554 (4.7%) | 26 |
| Systemic inflammatory response syndrome | 2/657 (0.3%) | 2 | 1/554 (0.2%) | 2 |
| Ulcer haemorrhage | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Hepatobiliary disorders | ||||
| Bile duct stenosis | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Bile duct stone | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Cholangitis | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Cholangitis acute | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Cholecystitis | 2/657 (0.3%) | 2 | 0/554 (0%) | 0 |
| Cholecystitis acute | 2/657 (0.3%) | 2 | 1/554 (0.2%) | 1 |
| Cholelithiasis obstructive | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Granulomatous liver disease | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Hepatic cirrhosis | 1/657 (0.2%) | 2 | 0/554 (0%) | 0 |
| Hepatic failure | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Hydrocholecystis | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Jaundice | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Jaundice cholestatic | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Portal hypertension | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Immune system disorders | ||||
| Acute graft versus host disease in skin | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Amyloidosis | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Anaphylactic reaction | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Anaphylactic shock | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Drug hypersensitivity | 1/657 (0.2%) | 1 | 2/554 (0.4%) | 2 |
| Engraftment syndrome | 0/657 (0%) | 0 | 2/554 (0.4%) | 2 |
| Graft versus host disease | 0/657 (0%) | 0 | 2/554 (0.4%) | 2 |
| Graft versus host disease in gastrointestinal tract | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Graft versus host disease in liver | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Graft versus host disease in lung | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Graft versus host disease in skin | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Hypersensitivity | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Primary amyloidosis | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Infections and infestations | ||||
| Abdominal abscess | 2/657 (0.3%) | 2 | 0/554 (0%) | 0 |
| Actinomycotic pulmonary infection | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Acute sinusitis | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Adenovirus infection | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Anal abscess | 0/657 (0%) | 0 | 2/554 (0.4%) | 2 |
| Appendicitis | 2/657 (0.3%) | 2 | 2/554 (0.4%) | 2 |
| Appendicitis perforated | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Arthritis bacterial | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Aspergilloma | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Aspergillus infection | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Atypical pneumonia | 6/657 (0.9%) | 6 | 0/554 (0%) | 0 |
| BK virus infection | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Bacteraemia | 4/657 (0.6%) | 4 | 7/554 (1.3%) | 8 |
| Bacterial sepsis | 0/657 (0%) | 0 | 2/554 (0.4%) | 2 |
| Bronchiolitis | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Bronchitis | 4/657 (0.6%) | 4 | 4/554 (0.7%) | 5 |
| Bronchitis bacterial | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Bronchitis viral | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Bronchopulmonary aspergillosis | 6/657 (0.9%) | 6 | 4/554 (0.7%) | 4 |
| Candida sepsis | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Cellulitis | 4/657 (0.6%) | 6 | 3/554 (0.5%) | 3 |
| Cholangitis infective | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Chronic hepatitis B | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Clostridial infection | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Clostridium colitis | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Clostridium difficile colitis | 5/657 (0.8%) | 5 | 5/554 (0.9%) | 5 |
| Clostridium difficile infection | 3/657 (0.5%) | 3 | 0/554 (0%) | 0 |
| Coxsackie viral infection | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Cystitis | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Cytomegalovirus colitis | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Cytomegalovirus infection | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Cytomegalovirus oesophagitis | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Dengue fever | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Device related infection | 5/657 (0.8%) | 6 | 2/554 (0.4%) | 2 |
| Device related sepsis | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Diverticulitis | 3/657 (0.5%) | 3 | 0/554 (0%) | 0 |
| Empyema | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Enterococcal bacteraemia | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Enterococcal infection | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Enterocolitis bacterial | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Enterovirus infection | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Epididymitis | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Erysipelas | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Escherichia bacteraemia | 2/657 (0.3%) | 2 | 1/554 (0.2%) | 1 |
| Escherichia sepsis | 1/657 (0.2%) | 1 | 2/554 (0.4%) | 2 |
| Escherichia urinary tract infection | 3/657 (0.5%) | 3 | 0/554 (0%) | 0 |
| Febrile infection | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Fungal oesophagitis | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Gastroenteritis | 5/657 (0.8%) | 5 | 4/554 (0.7%) | 4 |
| Gastroenteritis rotavirus | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Gastroenteritis viral | 1/657 (0.2%) | 1 | 2/554 (0.4%) | 2 |
| Gastrointestinal candidiasis | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Gastrointestinal infection | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Groin abscess | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| H1N1 influenza | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Haemophilus infection | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Herpes zoster | 3/657 (0.5%) | 3 | 12/554 (2.2%) | 12 |
| Herpes zoster disseminated | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Infected lymphocele | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Infection | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Infection in an immunocompromised host | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Infective exacerbation of chronic obstructive airways disease | 1/657 (0.2%) | 2 | 0/554 (0%) | 0 |
| Influenza | 8/657 (1.2%) | 8 | 7/554 (1.3%) | 7 |
| Klebsiella bacteraemia | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Klebsiella infection | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Lower respiratory tract infection | 1/657 (0.2%) | 3 | 0/554 (0%) | 0 |
| Lower respiratory tract infection viral | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Lung abscess | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Lung infection | 3/657 (0.5%) | 3 | 0/554 (0%) | 0 |
| Lung infection pseudomonal | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Meningitis | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Meningitis pneumococcal | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Meningoencephalitis herpetic | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Nasopharyngitis | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Neutropenic sepsis | 3/657 (0.5%) | 3 | 3/554 (0.5%) | 3 |
| Oral candidiasis | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Parainfluenzae virus infection | 0/657 (0%) | 0 | 2/554 (0.4%) | 2 |
| Pharyngitis | 2/657 (0.3%) | 2 | 0/554 (0%) | 0 |
| Pneumococcal bacteraemia | 0/657 (0%) | 0 | 2/554 (0.4%) | 2 |
| Pneumococcal sepsis | 1/657 (0.2%) | 1 | 3/554 (0.5%) | 3 |
| Pneumocystis jirovecii infection | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Pneumocystis jirovecii pneumonia | 1/657 (0.2%) | 1 | 2/554 (0.4%) | 2 |
| Pneumonia | 61/657 (9.3%) | 74 | 56/554 (10.1%) | 67 |
| Pneumonia bacterial | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Pneumonia cytomegaloviral | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Pneumonia fungal | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Pneumonia parainfluenzae viral | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Pneumonia respiratory syncytial viral | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Pneumonia viral | 2/657 (0.3%) | 2 | 2/554 (0.4%) | 2 |
| Postoperative abscess | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Postoperative wound infection | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Pseudomembranous colitis | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Pseudomonal bacteraemia | 2/657 (0.3%) | 2 | 1/554 (0.2%) | 1 |
| Pseudomonal sepsis | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Pseudomonas infection | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Pulmonary mycosis | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Pulmonary sepsis | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Pulmonary tuberculosis | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Respiratory syncytial virus infection | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Respiratory tract infection | 2/657 (0.3%) | 2 | 0/554 (0%) | 0 |
| Respiratory tract infection viral | 2/657 (0.3%) | 2 | 0/554 (0%) | 0 |
| Retinitis | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Rhinovirus infection | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Scrotal abscess | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Sepsis | 19/657 (2.9%) | 19 | 12/554 (2.2%) | 14 |
| Sepsis syndrome | 1/657 (0.2%) | 1 | 2/554 (0.4%) | 2 |
| Septic shock | 7/657 (1.1%) | 7 | 4/554 (0.7%) | 4 |
| Sialoadenitis | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Sinusitis | 1/657 (0.2%) | 1 | 3/554 (0.5%) | 4 |
| Staphylococcal bacteraemia | 4/657 (0.6%) | 4 | 3/554 (0.5%) | 3 |
| Staphylococcal infection | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Staphylococcal sepsis | 2/657 (0.3%) | 2 | 4/554 (0.7%) | 4 |
| Streptococcal bacteraemia | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Streptococcal sepsis | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Systemic candida | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Thrombophlebitis septic | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Tooth abscess | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Tuberculosis | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Upper respiratory tract infection | 5/657 (0.8%) | 5 | 5/554 (0.9%) | 5 |
| Urinary tract infection | 8/657 (1.2%) | 10 | 5/554 (0.9%) | 5 |
| Urosepsis | 0/657 (0%) | 0 | 2/554 (0.4%) | 2 |
| Varicella | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Varicella zoster virus infection | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Viral infection | 2/657 (0.3%) | 2 | 5/554 (0.9%) | 6 |
| Viral sepsis | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Viral upper respiratory tract infection | 2/657 (0.3%) | 2 | 2/554 (0.4%) | 2 |
| Wound infection bacterial | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Allergic transfusion reaction | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Brain contusion | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Comminuted fracture | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Compression fracture | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Delayed engraftment | 0/657 (0%) | 0 | 2/554 (0.4%) | 2 |
| Femur fracture | 1/657 (0.2%) | 1 | 2/554 (0.4%) | 2 |
| Foot fracture | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Forearm fracture | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Hip fracture | 1/657 (0.2%) | 1 | 3/554 (0.5%) | 3 |
| Infusion related reaction | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Multiple fractures | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Peroneal nerve injury | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Post lumbar puncture syndrome | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Procedural hypotension | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Seroma | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Spinal compression fracture | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Spinal fracture | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Subdural haematoma | 1/657 (0.2%) | 1 | 2/554 (0.4%) | 2 |
| Subdural haemorrhage | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Tendon rupture | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Toxicity to various agents | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Transfusion reaction | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Transplant dysfunction | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Traumatic haemothorax | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Upper limb fracture | 2/657 (0.3%) | 2 | 0/554 (0%) | 0 |
| Wound dehiscence | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Investigations | ||||
| Transaminases increased | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Dehydration | 2/657 (0.3%) | 3 | 2/554 (0.4%) | 2 |
| Diabetes mellitus | 2/657 (0.3%) | 2 | 0/554 (0%) | 0 |
| Failure to thrive | 3/657 (0.5%) | 3 | 0/554 (0%) | 0 |
| Food intolerance | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Hypercalcaemia | 2/657 (0.3%) | 2 | 2/554 (0.4%) | 2 |
| Hyperglycaemia | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Hypocalcaemia | 0/657 (0%) | 0 | 2/554 (0.4%) | 2 |
| Hypoglycaemia | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Hypokalaemia | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Lactose intolerance | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Tetany | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Tumour lysis syndrome | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Back pain | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Bone pain | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Cervical spinal stenosis | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Intervertebral disc degeneration | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Intervertebral disc protrusion | 2/657 (0.3%) | 2 | 0/554 (0%) | 0 |
| Neck pain | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Osteoarthritis | 0/657 (0%) | 0 | 2/554 (0.4%) | 2 |
| Osteolysis | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Osteonecrosis | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Pathological fracture | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Pseudarthrosis | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Spinal column stenosis | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Acute leukaemia | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Acute myeloid leukaemia | 2/657 (0.3%) | 2 | 2/554 (0.4%) | 2 |
| Acute myeloid leukaemia recurrent | 0/657 (0%) | 0 | 3/554 (0.5%) | 4 |
| Acute promyelocytic leukaemia | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Adenocarcinoma gastric | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Anaplastic large cell lymphoma T- and null-cell types | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Anaplastic large cell lymphoma T- and null-cell types recurrent | 0/657 (0%) | 0 | 2/554 (0.4%) | 2 |
| Anaplastic large-cell lymphoma | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Angiocentric lymphoma | 0/657 (0%) | 0 | 3/554 (0.5%) | 3 |
| Angioimmunoblastic T-cell lymphoma recurrent | 1/657 (0.2%) | 1 | 2/554 (0.4%) | 2 |
| B-cell lymphoma | 0/657 (0%) | 0 | 2/554 (0.4%) | 2 |
| B-cell lymphoma recurrent | 3/657 (0.5%) | 3 | 5/554 (0.9%) | 5 |
| B-cell lymphoma stage IV | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Basal cell carcinoma | 1/657 (0.2%) | 2 | 3/554 (0.5%) | 3 |
| Basosquamous carcinoma | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Bladder cancer | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Bladder cancer recurrent | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Breast cancer | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Breast cancer recurrent | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Central nervous system lymphoma | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Cholangiocarcinoma | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Chronic lymphocytic leukaemia recurrent | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Chronic myeloid leukaemia | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Colon adenoma | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Colon cancer metastatic | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Colorectal cancer | 2/657 (0.3%) | 2 | 0/554 (0%) | 0 |
| Diffuse large B-cell lymphoma | 10/657 (1.5%) | 11 | 10/554 (1.8%) | 11 |
| Diffuse large B-cell lymphoma recurrent | 14/657 (2.1%) | 14 | 10/554 (1.8%) | 10 |
| Diffuse large B-cell lymphoma refractory | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Extranodal marginal zone B-cell lymphoma (MALT type) recurrent | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Follicle centre lymphoma, follicular grade I, II, III recurrent | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Hodgkin's disease | 8/657 (1.2%) | 8 | 5/554 (0.9%) | 7 |
| Hodgkin's disease nodular sclerosis | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Hodgkin's disease recurrent | 7/657 (1.1%) | 8 | 6/554 (1.1%) | 6 |
| Langerhans' cell histiocytosis | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Laryngeal squamous cell carcinoma | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Leukaemia recurrent | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Lung neoplasm malignant | 1/657 (0.2%) | 1 | 2/554 (0.4%) | 2 |
| Lymphoma | 9/657 (1.4%) | 9 | 6/554 (1.1%) | 7 |
| Lymphoplasmacytoid lymphoma/immunocytoma | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Malignant lymphoid neoplasm | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Malignant melanoma | 1/657 (0.2%) | 1 | 4/554 (0.7%) | 4 |
| Mantle cell lymphoma | 1/657 (0.2%) | 1 | 4/554 (0.7%) | 4 |
| Mantle cell lymphoma recurrent | 10/657 (1.5%) | 10 | 9/554 (1.6%) | 9 |
| Metastases to meninges | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Myelodysplastic syndrome | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Neuroendocrine carcinoma | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Non-Hodgkin's lymphoma | 6/657 (0.9%) | 6 | 3/554 (0.5%) | 3 |
| Non-Hodgkin's lymphoma recurrent | 10/657 (1.5%) | 11 | 13/554 (2.3%) | 13 |
| Non-Hodgkin's lymphoma refractory | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Nonkeratinising carcinoma of nasopharynx | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Pancreatic carcinoma | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Papillary thyroid cancer | 1/657 (0.2%) | 1 | 3/554 (0.5%) | 3 |
| Paraneoplastic syndrome | 2/657 (0.3%) | 2 | 0/554 (0%) | 0 |
| Pericardial effusion malignant | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Peripheral T-cell lymphoma unspecified | 3/657 (0.5%) | 3 | 2/554 (0.4%) | 2 |
| Peripheral T-cell lymphoma unspecified recurrent | 4/657 (0.6%) | 4 | 2/554 (0.4%) | 2 |
| Plasma cell myeloma | 67/657 (10.2%) | 75 | 51/554 (9.2%) | 57 |
| Plasma cell myeloma recurrent | 50/657 (7.6%) | 51 | 53/554 (9.6%) | 56 |
| Plasmablastic lymphoma | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Plasmacytoma | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Precursor T-lymphoblastic lymphoma/leukaemia | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Precursor T-lymphoblastic lymphoma/leukaemia recurrent | 1/657 (0.2%) | 2 | 0/554 (0%) | 0 |
| Primary mediastinal large B-cell lymphoma | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Prostate cancer | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Rectal cancer | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Rectal cancer recurrent | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Renal cell carcinoma | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Small cell carcinoma | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Squamous cell carcinoma | 2/657 (0.3%) | 2 | 0/554 (0%) | 0 |
| Squamous cell carcinoma of skin | 2/657 (0.3%) | 2 | 1/554 (0.2%) | 2 |
| T-cell lymphoma | 1/657 (0.2%) | 1 | 2/554 (0.4%) | 2 |
| T-cell lymphoma recurrent | 8/657 (1.2%) | 8 | 2/554 (0.4%) | 3 |
| Tumour flare | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Nervous system disorders | ||||
| Autonomic nervous system imbalance | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Carotid artery aneurysm | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Carotid artery disease | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Cerebellar infarction | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Cerebral haemorrhage | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Cerebrovascular accident | 4/657 (0.6%) | 4 | 1/554 (0.2%) | 1 |
| Dizziness | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Facial paralysis | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Headache | 2/657 (0.3%) | 2 | 1/554 (0.2%) | 1 |
| Hepatic encephalopathy | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Hypoglycaemic coma | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Intracranial venous sinus thrombosis | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Metabolic encephalopathy | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Migraine | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Paraesthesia | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Presyncope | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Sciatica | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Syncope | 6/657 (0.9%) | 7 | 5/554 (0.9%) | 5 |
| Transient ischaemic attack | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Pregnancy, puerperium and perinatal conditions | ||||
| Threatened labour | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Psychiatric disorders | ||||
| Anxiety | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Confusional state | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Delirium | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Depression | 2/657 (0.3%) | 2 | 0/554 (0%) | 0 |
| Disorientation | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Hypomania | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Mania | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Mental status changes | 2/657 (0.3%) | 2 | 0/554 (0%) | 0 |
| Schizoaffective disorder | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Suicide attempt | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 8/657 (1.2%) | 10 | 10/554 (1.8%) | 11 |
| Acute prerenal failure | 0/657 (0%) | 0 | 2/554 (0.4%) | 2 |
| Cystitis haemorrhagic | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| End stage renal disease | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Haematuria | 2/657 (0.3%) | 2 | 2/554 (0.4%) | 2 |
| Nephrolithiasis | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Renal failure | 4/657 (0.6%) | 5 | 5/554 (0.9%) | 5 |
| Renal injury | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Renal tubular necrosis | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Tubulointerstitial nephritis | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Ureterolithiasis | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Urinary retention | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Reproductive system and breast disorders | ||||
| Acquired phimosis | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Benign prostatic hyperplasia | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute pulmonary oedema | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Acute respiratory failure | 1/657 (0.2%) | 1 | 2/554 (0.4%) | 2 |
| Asthma | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Chronic obstructive pulmonary disease | 3/657 (0.5%) | 3 | 2/554 (0.4%) | 2 |
| Dyspnoea | 2/657 (0.3%) | 2 | 0/554 (0%) | 0 |
| Emphysema | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Hypoxia | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Idiopathic pneumonia syndrome | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Interstitial lung disease | 2/657 (0.3%) | 2 | 1/554 (0.2%) | 1 |
| Lung consolidation | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Lung infiltration | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Obstructive airways disorder | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Organising pneumonia | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Oropharyngeal pain | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Pleural effusion | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Pneumomediastinum | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Pneumonia aspiration | 1/657 (0.2%) | 1 | 2/554 (0.4%) | 2 |
| Pneumonitis | 1/657 (0.2%) | 1 | 2/554 (0.4%) | 2 |
| Pneumothorax | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Pulmonary embolism | 6/657 (0.9%) | 6 | 5/554 (0.9%) | 5 |
| Pulmonary hypertension | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Pulmonary mass | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Pulmonary oedema | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Respiratory distress | 3/657 (0.5%) | 4 | 2/554 (0.4%) | 2 |
| Respiratory failure | 3/657 (0.5%) | 4 | 1/554 (0.2%) | 1 |
| Restrictive pulmonary disease | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Sleep apnoea syndrome | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Blister | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Dermal cyst | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Dermatitis exfoliative | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Eczema | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Rash | 1/657 (0.2%) | 1 | 1/554 (0.2%) | 1 |
| Rash maculo-papular | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Rash vesicular | 3/657 (0.5%) | 3 | 3/554 (0.5%) | 3 |
| Vascular disorders | ||||
| Aortic aneurysm | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Aortic stenosis | 2/657 (0.3%) | 2 | 0/554 (0%) | 0 |
| Deep vein thrombosis | 7/657 (1.1%) | 7 | 2/554 (0.4%) | 2 |
| Embolism | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Hypertension | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
| Hypertensive crisis | 0/657 (0%) | 0 | 3/554 (0.5%) | 3 |
| Hypotension | 5/657 (0.8%) | 5 | 3/554 (0.5%) | 3 |
| Orthostatic hypotension | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Peripheral arterial occlusive disease | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Peripheral artery thrombosis | 1/657 (0.2%) | 1 | 0/554 (0%) | 0 |
| Venoocclusive disease | 2/657 (0.3%) | 2 | 0/554 (0%) | 0 |
| Venous thrombosis limb | 0/657 (0%) | 0 | 1/554 (0.2%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| V212 [Including High Antigen Lot] | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 625/657 (95.1%) | 512/554 (92.4%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 175/657 (26.6%) | 201 | 134/554 (24.2%) | 168 |
| Febrile neutropenia | 184/657 (28%) | 191 | 135/554 (24.4%) | 138 |
| Leukopenia | 33/657 (5%) | 34 | 32/554 (5.8%) | 41 |
| Neutropenia | 163/657 (24.8%) | 187 | 129/554 (23.3%) | 157 |
| Pancytopenia | 63/657 (9.6%) | 64 | 53/554 (9.6%) | 54 |
| Thrombocytopenia | 238/657 (36.2%) | 289 | 212/554 (38.3%) | 264 |
| Cardiac disorders | ||||
| Tachycardia | 45/657 (6.8%) | 47 | 34/554 (6.1%) | 35 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 87/657 (13.2%) | 103 | 78/554 (14.1%) | 81 |
| Abdominal pain upper | 51/657 (7.8%) | 51 | 34/554 (6.1%) | 35 |
| Constipation | 107/657 (16.3%) | 120 | 102/554 (18.4%) | 113 |
| Diarrhoea | 394/657 (60%) | 492 | 341/554 (61.6%) | 396 |
| Dyspepsia | 61/657 (9.3%) | 65 | 47/554 (8.5%) | 52 |
| Nausea | 370/657 (56.3%) | 452 | 319/554 (57.6%) | 391 |
| Stomatitis | 83/657 (12.6%) | 94 | 51/554 (9.2%) | 56 |
| Vomiting | 211/657 (32.1%) | 265 | 200/554 (36.1%) | 260 |
| General disorders | ||||
| Asthenia | 72/657 (11%) | 77 | 60/554 (10.8%) | 68 |
| Chills | 39/657 (5.9%) | 44 | 35/554 (6.3%) | 42 |
| Fatigue | 144/657 (21.9%) | 159 | 121/554 (21.8%) | 131 |
| Injection site erythema | 153/657 (23.3%) | 323 | 14/554 (2.5%) | 19 |
| Injection site pain | 133/657 (20.2%) | 283 | 21/554 (3.8%) | 24 |
| Injection site pruritus | 35/657 (5.3%) | 52 | 4/554 (0.7%) | 5 |
| Injection site swelling | 124/657 (18.9%) | 257 | 9/554 (1.6%) | 9 |
| Mucosal inflammation | 254/657 (38.7%) | 271 | 226/554 (40.8%) | 244 |
| Oedema peripheral | 77/657 (11.7%) | 89 | 65/554 (11.7%) | 72 |
| Pyrexia | 317/657 (48.2%) | 526 | 248/554 (44.8%) | 374 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 152/657 (23.1%) | 161 | 132/554 (23.8%) | 150 |
| Hyperglycaemia | 33/657 (5%) | 40 | 16/554 (2.9%) | 16 |
| Hypocalcaemia | 55/657 (8.4%) | 65 | 40/554 (7.2%) | 45 |
| Hypokalaemia | 141/657 (21.5%) | 165 | 111/554 (20%) | 135 |
| Hypomagnesaemia | 76/657 (11.6%) | 88 | 62/554 (11.2%) | 75 |
| Hypophosphataemia | 41/657 (6.2%) | 48 | 40/554 (7.2%) | 42 |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 56/657 (8.5%) | 63 | 46/554 (8.3%) | 51 |
| Pain in extremity | 33/657 (5%) | 35 | 24/554 (4.3%) | 26 |
| Nervous system disorders | ||||
| Dizziness | 44/657 (6.7%) | 46 | 46/554 (8.3%) | 51 |
| Dysgeusia | 29/657 (4.4%) | 29 | 28/554 (5.1%) | 28 |
| Headache | 131/657 (19.9%) | 149 | 114/554 (20.6%) | 141 |
| Psychiatric disorders | ||||
| Anxiety | 35/657 (5.3%) | 38 | 31/554 (5.6%) | 32 |
| Insomnia | 84/657 (12.8%) | 91 | 68/554 (12.3%) | 71 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 76/657 (11.6%) | 84 | 80/554 (14.4%) | 93 |
| Dyspnoea | 55/657 (8.4%) | 60 | 36/554 (6.5%) | 36 |
| Epistaxis | 41/657 (6.2%) | 48 | 24/554 (4.3%) | 26 |
| Oropharyngeal pain | 68/657 (10.4%) | 78 | 43/554 (7.8%) | 48 |
| Skin and subcutaneous tissue disorders | ||||
| Erythema | 33/657 (5%) | 37 | 22/554 (4%) | 31 |
| Pruritus | 66/657 (10%) | 72 | 38/554 (6.9%) | 45 |
| Rash | 89/657 (13.5%) | 110 | 74/554 (13.4%) | 84 |
| Vascular disorders | ||||
| Hypertension | 33/657 (5%) | 38 | 33/554 (6%) | 36 |
| Hypotension | 57/657 (8.7%) | 64 | 48/554 (8.7%) | 52 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme Corp. |
| Phone | 1-800-672-6372 |
| ClinicalTrialsDisclosure@merck.com |
Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT01229267
Other Study ID Numbers:
- V212-001
- 2010-020150-34
- V212-001
First Posted:
Oct 27, 2010
Last Update Posted:
Sep 30, 2019
Last Verified:
Sep 1, 2019