Study to Assess Brincidofovir Treatment of Serious Diseases or Conditions Caused by Double-stranded DNA Viruses
Sponsor
Chimerix (Industry)
Overall Status
Completed
CT.gov ID
NCT01143181
Collaborator
(none)
210
37
1
24
5.7
0.2
Study Details
Study Description
Brief Summary
This was a multicenter, open-label study of oral brincidofovir (BCV) treatment of serious disease or conditions caused by double-stranded DNA (dsDNA) virus(es). Subjects received either a weight-based or a fixed dose of oral BCV once weekly (QW) or twice weekly (BIW) for up to 3 months until clinical disease was resolved or stabilized and/or viral DNA by polymerase chain reaction testing was negative for 4 consecutive weeks, whichever was longer. Under the first protocol amendment, adults and adolescents (≥13 years) received 200 mg or 300 mg BCV BIW (not to exceed 4 mg/kg total weekly dose) depending on the difficulty of treating their disease (i.e., Group 1 or Group 2, respectively), and pediatric subjects (≤12 years) received 4 mg/kg BCV BIW. Under the second protocol amendment, adults and adolescents (≥13 years), regardless of viral infection/disease, had a maximum weekly dose of 200 mg, i.e., 200 mg QW or 100 mg BIW; not to exceed 4mg/kg total weekly dose. Pediatric subjects (≤12 years), regardless of viral infection/disease, had a maximum weekly dose of 4 mg/kg, i.e., 4 mg/kg QW or 2 mg/kg BIW; not to exceed 200 mg.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
This was a multicenter, open-label study of oral brincidofovir (BCV) treatment of serious disease or conditions caused by double-stranded DNA (dsDNA) virus(es).
Subjects with a life-threatening or serious disease or condition caused by infection with any dsDNA virus(es), who met the protocol eligibility criteria and who were approved by the Chimerix Medical Monitor were enrolled in this open-label treatment study. During the course of the study, the viral disease indications were narrowed in Amendment 2 to cytomegalovirus, adenovirus, herpes simplex virus, vaccinia virus, variola virus, or monkeypox virus to focus on indications that were under study in controlled clinical trials of oral BCV and on viral disease with few, if any, options for treatment. However, subjects with other viral disease indications may have been enrolled with the approval of the Chimerix Medical Monitor.
Subjects received either a weight-based or a fixed dose of oral BCV once weekly (QW) or twice weekly (BIW) for up to 3 months until clinical disease was resolved or stabilized and/or viral DNA by polymerase chain reaction testing was negative for 4 consecutive weeks, whichever was longer. Subjects who met criteria for resolution of viral disease may have: 1) discontinued BCV; 2) reduced the dose or dosing frequency of BCV; or 3) continued BCV QW or BIW, depending on the investigator's assessment of the risk of relapse and following discussion with the Chimerix medical monitor.
Study Design
Study Type:
Interventional
Actual Enrollment
:
210 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Open-label Study of CMX001 Treatment of Serious Diseases or Conditions Caused by Double-stranded DNA Viruses
Actual Study Start Date
:
Dec 1, 2010
Actual Primary Completion Date
:
Dec 1, 2012
Actual Study Completion Date
:
Dec 1, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Brincidofovir Subjects received either a weight-based or a fixed-dose of oral brincidofovir (BCV) once weekly or twice weekly for up to 3 months until clinical disease was resolved or stabilized and/or viral DNA polymerase chain reaction testing was negative for 4 consecutive weeks, whichever was longer. |
Drug: Brincidofovir
Brincidofovir (BCV) was administered orally either once or twice weekly for up to 3 months. Treatment may have been extended for an additional 3 months depending a satisfactory review of safety parameters. Subjects could not receive more than a total of 6 months of treatment with BCV without prior approval.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Subjects Who Had a Sustained and Significant Reduction in Plasma Viral Load of Primary dsDNA Virus [3 months]
Proportion of subjects who achieved a confirmed reduction in viral load for the primary dsDNA virus of ≥1 log10 copies/mL from baseline or to an undetectable level. Confirmation required the reduction in viral load (i.e., decrease of ≥ 1 log10 copies/mL from baseline or to undetectable levels) to be maintained at the next assessment for the subject to be considered a success.
Eligibility Criteria
Criteria
Ages Eligible for Study:
N/A
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria
Subjects were required to meet all of the following inclusion criteria in order to participate in the study:
-
Had an immediately life-threatening or serious disease or condition caused by infection with a double-stranded DNA virus (including subjects with recurrent viral disease). [Note: During the course of the study, the viral disease indications were narrow to focus on indications that were under study in controlled clinical trials of brincidofovir (BCV) and on viral diseases that had few, if any, options for treatment, including cytomegalovirus (CMV), adenovirus (AdV), herpes simplex virus (HSV), vaccinia virus (VAVC), variola virus (VARV) or monkeypox viruses(s).]
-
Had a life expectancy of at least 2 weeks and commitment to continuation of supportive care for at least 4 weeks.
-
Were able to ingest and absorb oral medication (in the judgment of the investigator and based on lack of significant gastrointestinal [GI] pathology such as small bowel resection or ileus). [Note: Use of total parenteral nutrition was not in and of itself exclusionary as long as the reason for use did not disqualify the subject based on this criterion.]
-
Were willing and able to understand and provide written informed consent. [Note: For minors or those incapable of providing written informed consent (i.e., incapacitated), consent was provided by a parent or legal guardian or representative who could understand and provide written informed consent.]
-
Were willing and able, to the best of his or her (or parent/guardian) knowledge, to participate in all required study activities for the duration of the study.
-
If female of reproductive potential, agreed to use 2 acceptable methods of birth control throughout the study with at least 1 being a barrier method.
-
In the judgment of the investigator, subjects for whom no comparable or satisfactory therapeutic alternative was available
Exclusion Criteria
Subjects were not to be enrolled if they met any of the following exclusion criteria:
-
Were pregnant or currently nursing.
-
Had hypersensitivity to cidofovir or BCV.
-
Had a long-term prognosis that included a poor likelihood of survival due to irreversible organ failure including, for example, subjects with frank hepatic failure and adults with Grade 4 graft versus host disease of the GI tract.
-
Were eligible for enrollment and able to participate in a clinical trial evaluating BCV. [Note: Per the FDA guidance, subjects eligible and able to participate in a controlled clinical study evaluating BCV were not eligible for participation in this study. Subjects who did not meet eligibility criteria for a controlled BCV clinical study or who were unable to participate because, for example, of logistical or other issues were eligible to participate in this study. The investigator verified that his/her subjects met this criterion on the Eligibility electronic case report form. A subject simply preferring enrollment in this study over a BCV controlled clinical trial did not qualify for enrollment in this study.]
-
Had any other condition that would have, in the judgment of the investigator, put the subject at increased risk during participation in the study or interfered with the conduct of the study.
-
Had a serum total bilirubin value >5 x the upper limit of normal reference range, taking into account the age and/or gender of the subject. [Note: In order to avoid any unwarranted delay to the start of BCV treatment, compliance with this exclusion criterion may have been determined based on the results of testing performed at a local safety laboratory, rather than waiting for results from the designated central safety laboratory. If relying on local safety laboratory test results, the blood sample must have been collected no more than 7 days prior to the scheduled first dose administration on Day 0, otherwise it was repeated. A subject whose elevated bilirubin was due to the underlying viral disease may still have been enrolled into the study if the participation of the subject was prospectively approved by the Chimerix Medical Monitor.]
Subjects with acute or chronic renal impairment, pediatric and adolescent subjects, and subjects aged 65 years and older were included in this study. Subjects with hepatic impairment were included unless the investigator judged that the subject had irreversible hepatic compromise.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Loma Linda University Hospital | Loma Linda | California | United States | 92354 |
| 2 | Children's Hospital of LA | Los Angeles | California | United States | 90027 |
| 3 | UCLA Department of Medicine | Los Angeles | California | United States | 90095 |
| 4 | CHOC Children's | Orange | California | United States | 92868 |
| 5 | Univeristy of San Francisco | San Francisco | California | United States | 94143 |
| 6 | Lucile Packard Children's Hospital | Stanford | California | United States | 94304 |
| 7 | Children's Hospital of Colorado | Aurora | Colorado | United States | 80045 |
| 8 | Children's National Medical Center | Washington | District of Columbia | United States | 20010 |
| 9 | University of Chicago | Chicago | Illinois | United States | 60637 |
| 10 | University of Iowa | Iowa City | Iowa | United States | 52242 |
| 11 | Childrens Hospital LSU | New Orleans | Louisiana | United States | 70118 |
| 12 | NIH | Bethesda | Maryland | United States | 20892 |
| 13 | Tufts Medical Center | Boston | Massachusetts | United States | 02111 |
| 14 | Brigham and Womens Hospital | Boston | Massachusetts | United States | 02115 |
| 15 | University of Michigan | Ann Arbor | Michigan | United States | 48109 |
| 16 | University of Minnesota | Minneapolis | Minnesota | United States | 55455 |
| 17 | St. Louis Children's Hospital | Saint Louis | Missouri | United States | 63110 |
| 18 | University of Nebraska Medical Center | Omaha | Nebraska | United States | 68198-5130 |
| 19 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
| 20 | Mt. Sinai | New York | New York | United States | 10029 |
| 21 | Columbia University | New York | New York | United States | 10032 |
| 22 | Memorial Sloan Kettering Cancer Institute | New York | New York | United States | 10065 |
| 23 | University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | United States | 27599 |
| 24 | Levine Children's Hospital Carolina Medical Center | Charlotte | North Carolina | United States | 28203 |
| 25 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
| 26 | Cincinnati Childrens Hospital | Cincinnati | Ohio | United States | 45229 |
| 27 | Cleveland Clinic | Cleveland | Ohio | United States | 44195 |
| 28 | Nationwide Children's Hospital | Columbus | Ohio | United States | 43205 |
| 29 | Oregon Health and Science University | Portland | Oregon | United States | 97239 |
| 30 | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | 19104 |
| 31 | UPMC | Pittsburgh | Pennsylvania | United States | 15213 |
| 32 | Childrens Hospital of Pittsburgh | Pittsburgh | Pennsylvania | United States | 15224 |
| 33 | Cook Children's Medical Center | Fort Worth | Texas | United States | 76104-2796 |
| 34 | UT MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 35 | Intermountain BMT program LDS Hospital | Salt Lake City | Utah | United States | 84143 |
| 36 | University of Washington-Fred Hutchinson Cancer Center | Seattle | Washington | United States | 98109 |
| 37 | Medical College of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
Sponsors and Collaborators
- Chimerix
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Chimerix
ClinicalTrials.gov Identifier:
NCT01143181
Other Study ID Numbers:
- CMX001-350
First Posted:
Jun 14, 2010
Last Update Posted:
Aug 12, 2021
Last Verified:
Jul 1, 2021
Keywords provided by Chimerix
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | This was an expanded access study with the primary objective of providing brincidofovir (BCV) to subjects with serious or life-threatening conditions caused by double-stranded DNA viral infections. All subjects enrolled received BCV for up to 3 months until their clinical disease was resolved or stabilized and/or viral DNA testing was negative for 4 consecutive weeks, whichever was longer. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | BCV (≤4 mg/kg/Week) | BCV (>4 mg/kg/Week) | BCV (≤200 mg/Week) | BCV (>200 mg/Week) |
|---|---|---|---|---|
| Arm/Group Description | Pediatric subjects (≤12 years) who received BCV once or twice weekly. | Pediatric subjects (≤12 years) who received BCV once or twice weekly. | Adult/adolescent subjects (≥13 years) who received BCV once or twice weekly. | Adult/adolescent subjects (≥13 years) who received BCV once or twice weekly. |
| Period Title: Overall Study | ||||
| STARTED | 30 | 38 | 102 | 40 |
| COMPLETED | 14 | 22 | 58 | 17 |
| NOT COMPLETED | 16 | 16 | 44 | 23 |
Baseline Characteristics
| Arm/Group Title | BCV (≤4 mg/kg/Week) | BCV (>4 mg/kg/Week) | BCV (≤200 mg/Week) | BCV (>200 mg/Week) | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Pediatric subjects (≤12 years) who received BCV once or twice weekly. | Pediatric subjects (≤12 years) who received BCV once or twice weekly. | Adult/adolescent subjects (≥13 years) who received BCV once or twice weekly. | Adult/adolescent subjects (≥13 years) who received BCV once or twice weekly. | Total of all reporting groups |
| Overall Participants | 30 | 38 | 102 | 40 | 210 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
5.2
(2.68)
|
5.9
(3.70)
|
45.3
(17.21)
|
45.7
(17.57)
|
32.5
(23.51)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
14
46.7%
|
14
36.8%
|
41
40.2%
|
18
45%
|
87
41.4%
|
| Male |
16
53.3%
|
24
63.2%
|
61
59.8%
|
22
55%
|
123
58.6%
|
Outcome Measures
| Title | Number of Subjects Who Had a Sustained and Significant Reduction in Plasma Viral Load of Primary dsDNA Virus |
|---|---|
| Description | Proportion of subjects who achieved a confirmed reduction in viral load for the primary dsDNA virus of ≥1 log10 copies/mL from baseline or to an undetectable level. Confirmation required the reduction in viral load (i.e., decrease of ≥ 1 log10 copies/mL from baseline or to undetectable levels) to be maintained at the next assessment for the subject to be considered a success. |
| Time Frame | 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Only subjects who achieved a confirmed reduction in viral load for the primary dsDNA virus of ≥1 log10 copies/mL from baseline or to an undetectable level were included in this analysis. |
| Arm/Group Title | BCV (≤4 mg/kg/Week) | BCV (>4 mg/kg/Week) | BCV (≤200 mg/Week) | BCV (>200 mg/Week) |
|---|---|---|---|---|
| Arm/Group Description | Pediatric subjects (≤12 years) who received BCV once or twice weekly. | Pediatric subjects (≤12 years) who received BCV once or twice weekly. | Adult/adolescent subjects (≥13 years) who received BCV once or twice weekly. | Adult/adolescent subjects (≥13 years) who received BCV once or twice weekly. |
| Measure Participants | 25 | 28 | 79 | 28 |
| Count of Participants [Participants] |
15
50%
|
18
47.4%
|
39
38.2%
|
13
32.5%
|
Adverse Events
| Time Frame | ||||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | BCV (≤4 mg/kg/Week) | BCV (>4 mg/kg/Week) | BCV (≤200 mg/Week) | BCV (>200 mg/Week) | ||||
| Arm/Group Description | Pediatric subjects (≤12 years) who received BCV once or twice weekly. | Pediatric subjects (≤12 years) who received BCV once or twice weekly. | Adult/adolescent subjects (≥13 years) who received BCV once or twice weekly. | Adult/adolescent subjects (≥13 years) who received BCV once or twice weekly. | ||||
All Cause Mortality |
||||||||
| BCV (≤4 mg/kg/Week) | BCV (>4 mg/kg/Week) | BCV (≤200 mg/Week) | BCV (>200 mg/Week) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| BCV (≤4 mg/kg/Week) | BCV (>4 mg/kg/Week) | BCV (≤200 mg/Week) | BCV (>200 mg/Week) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 27/30 (90%) | 32/38 (84.2%) | 80/102 (78.4%) | 35/40 (87.5%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Febrile neutropenia | 2/30 (6.7%) | 2/38 (5.3%) | 4/102 (3.9%) | 0/40 (0%) | ||||
| Leukocytosis | 1/30 (3.3%) | 0/38 (0%) | 0/102 (0%) | 0/40 (0%) | ||||
| Leukopenia | 0/30 (0%) | 0/38 (0%) | 3/102 (2.9%) | 0/40 (0%) | ||||
| Lymphopenia | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Neutropenia | 0/30 (0%) | 0/38 (0%) | 9/102 (8.8%) | 0/40 (0%) | ||||
| Thrombocytopenia | 0/30 (0%) | 0/38 (0%) | 5/102 (4.9%) | 0/40 (0%) | ||||
| Thrombotic microangiopathy | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Thrombotic thrombocytopenic purpura | 0/30 (0%) | 1/38 (2.6%) | 1/102 (1%) | 0/40 (0%) | ||||
| Cardiac disorders | ||||||||
| Acute myocardial infarction | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Bradycardia | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Cardiac arrest | 0/30 (0%) | 0/38 (0%) | 3/102 (2.9%) | 0/40 (0%) | ||||
| Cardiac failure acute | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Cardiogenic shock | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Cardiopulmonary failure | 1/30 (3.3%) | 0/38 (0%) | 0/102 (0%) | 0/40 (0%) | ||||
| Pericardial effusion | 1/30 (3.3%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Tachycardia | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Ventricular fibrillation | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Endocrine disorders | ||||||||
| Adrenal insufficiency | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 3/30 (10%) | 1/38 (2.6%) | 4/102 (3.9%) | 1/40 (2.5%) | ||||
| Anal fistula | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Ascites | 0/30 (0%) | 1/38 (2.6%) | 1/102 (1%) | 1/40 (2.5%) | ||||
| Colitis | 0/30 (0%) | 0/38 (0%) | 2/102 (2%) | 0/40 (0%) | ||||
| Dental discomfort | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Diarrhoea haemorrhagic | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Diarrhoea | 2/30 (6.7%) | 3/38 (7.9%) | 17/102 (16.7%) | 6/40 (15%) | ||||
| Dysphagia | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Gastrointestinal haemorrhage | 0/30 (0%) | 2/38 (5.3%) | 1/102 (1%) | 2/40 (5%) | ||||
| Gastrointestinal necrosis | 1/30 (3.3%) | 0/38 (0%) | 0/102 (0%) | 0/40 (0%) | ||||
| Ileus | 0/30 (0%) | 1/38 (2.6%) | 1/102 (1%) | 0/40 (0%) | ||||
| Impaired gastric emptying | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Intestinal ischaemia | 1/30 (3.3%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Intestinal obstruction | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Lower gastrointestinal haemorrhage | 3/30 (10%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Malabsorption | 1/30 (3.3%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Nausea | 0/30 (0%) | 1/38 (2.6%) | 9/102 (8.8%) | 4/40 (10%) | ||||
| Pancreatitis acute | 1/30 (3.3%) | 0/38 (0%) | 0/102 (0%) | 0/40 (0%) | ||||
| Pancreatitis | 1/30 (3.3%) | 2/38 (5.3%) | 0/102 (0%) | 0/40 (0%) | ||||
| Peritoneal haemorrhage | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Pneumatosis intestinalis | 1/30 (3.3%) | 2/38 (5.3%) | 0/102 (0%) | 0/40 (0%) | ||||
| Small intestinal obstruction | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Stomatitis | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Upper gastrointestinal haemorrhage | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Vomiting | 2/30 (6.7%) | 2/38 (5.3%) | 7/102 (6.9%) | 4/40 (10%) | ||||
| General disorders | ||||||||
| Chest discomfort | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Chills | 1/30 (3.3%) | 0/38 (0%) | 0/102 (0%) | 0/40 (0%) | ||||
| Fatigue | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Generalised oedema | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Multi-organ failure | 3/30 (10%) | 1/38 (2.6%) | 7/102 (6.9%) | 6/40 (15%) | ||||
| Oedema peripheral | 0/30 (0%) | 0/38 (0%) | 2/102 (2%) | 0/40 (0%) | ||||
| Pyrexia | 5/30 (16.7%) | 6/38 (15.8%) | 11/102 (10.8%) | 0/40 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Cholestasis | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Cholestatic liver injury | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Hepatic failure | 1/30 (3.3%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Hepatocellular injury | 1/30 (3.3%) | 0/38 (0%) | 0/102 (0%) | 0/40 (0%) | ||||
| Hyperbilirubinaemia | 0/30 (0%) | 0/38 (0%) | 3/102 (2.9%) | 0/40 (0%) | ||||
| Venooclusive liver disease | 1/30 (3.3%) | 0/38 (0%) | 0/102 (0%) | 0/40 (0%) | ||||
| Immune system disorders | ||||||||
| Acute graft versus host disease | 0/30 (0%) | 2/38 (5.3%) | 13/102 (12.7%) | 7/40 (17.5%) | ||||
| Chronic graft versus host disease | 3/30 (10%) | 1/38 (2.6%) | 4/102 (3.9%) | 2/40 (5%) | ||||
| Graft versus host disease | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Immune reconstitution syndrome | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Lung transplant rejection | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Infections and infestations | ||||||||
| Adenoviral hepatitis | 1/30 (3.3%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Adenovirus infection | 1/30 (3.3%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Aspergillosis | 1/30 (3.3%) | 0/38 (0%) | 0/102 (0%) | 0/40 (0%) | ||||
| BK virus infection | 0/30 (0%) | 1/38 (2.6%) | 1/102 (1%) | 0/40 (0%) | ||||
| Bacterial infection | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Bacterial sepsis | 0/30 (0%) | 1/38 (2.6%) | 3/102 (2.9%) | 1/40 (2.5%) | ||||
| Bronchiectasis | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Bronchopulmonary aspergillosis | 1/30 (3.3%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Candidiasis | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Cellulitis | 0/30 (0%) | 1/38 (2.6%) | 1/102 (1%) | 0/40 (0%) | ||||
| Central nervous system infection | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Citrobacter infection | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Clostridium difficile colitis | 0/30 (0%) | 0/38 (0%) | 2/102 (2%) | 3/40 (7.5%) | ||||
| Corona virus infection | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Cytomegalovirus gastrointestinal infection | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Cytomegalovirus infection | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Cytomegalovirus viraemia | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Disseminated cytomegaloviral infection | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Encephalitis herpes | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Enterobacter infection | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Enterobacter pneumonia | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Enterobacter sepsis | 1/30 (3.3%) | 0/38 (0%) | 0/102 (0%) | 0/40 (0%) | ||||
| Enterobacter bacteraemia | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Enterococcal infection | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Enterococcal sepsis | 0/30 (0%) | 1/38 (2.6%) | 1/102 (1%) | 0/40 (0%) | ||||
| Enterococcal bacteraemia | 0/30 (0%) | 0/38 (0%) | 2/102 (2%) | 0/40 (0%) | ||||
| Escherichia infection | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Escherichia bacteraemia | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Fungal sepsis | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Gastroenteritis viral | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Human herpesvirus 6 infection | 1/30 (3.3%) | 0/38 (0%) | 0/102 (0%) | 0/40 (0%) | ||||
| Influenza | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| JC virus infection | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Klebsiella bacteraemia | 1/30 (3.3%) | 0/38 (0%) | 2/102 (2%) | 0/40 (0%) | ||||
| Klebsiella infection | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Klebsiella sepsis | 0/30 (0%) | 0/38 (0%) | 2/102 (2%) | 0/40 (0%) | ||||
| Legionella infection | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Lung infection | 1/30 (3.3%) | 0/38 (0%) | 0/102 (0%) | 0/40 (0%) | ||||
| Lung infection pseudomonal | 0/30 (0%) | 1/38 (2.6%) | 2/102 (2%) | 0/40 (0%) | ||||
| Meningoencephalitis adenoviral | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Osteomyelitis | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Parainfluenzae virus infection | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Pneumococcal sepsis | 0/30 (0%) | 0/38 (0%) | 2/102 (2%) | 0/40 (0%) | ||||
| Pneumocystis jiroveci pneumonia | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Pneumonia adenoviral | 1/30 (3.3%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Pneumonia bacterial | 0/30 (0%) | 0/38 (0%) | 3/102 (2.9%) | 0/40 (0%) | ||||
| Pneumonia fungal | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Pneumonia herpes viral | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Pneumonia necrotising | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Pneumonia pneumococcal | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Pneumonia primary atypical | 1/30 (3.3%) | 0/38 (0%) | 0/102 (0%) | 0/40 (0%) | ||||
| Pneumonia respiratory syncytial viral | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Pneumonia | 1/30 (3.3%) | 1/38 (2.6%) | 1/102 (1%) | 0/40 (0%) | ||||
| Pneumonia cytomegaloviral | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 1/40 (2.5%) | ||||
| Pneumonia staphylococcal | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 1/40 (2.5%) | ||||
| Pneumonia streptococcal | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Progressive multifocal leukoencephalopathy | 0/30 (0%) | 0/38 (0%) | 2/102 (2%) | 1/40 (2.5%) | ||||
| Pseudomonal sepsis | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Pseudomonal bacteraemia | 1/30 (3.3%) | 0/38 (0%) | 3/102 (2.9%) | 0/40 (0%) | ||||
| Rectal abscess | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Respiratory syncytial virus bronchiolitis | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Respiratory syncytial virus infection | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Sepsis | 0/30 (0%) | 1/38 (2.6%) | 2/102 (2%) | 1/40 (2.5%) | ||||
| Septic shock | 0/30 (0%) | 1/38 (2.6%) | 2/102 (2%) | 1/40 (2.5%) | ||||
| Serratia infection | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Sinusitis fungal | 1/30 (3.3%) | 0/38 (0%) | 0/102 (0%) | 0/40 (0%) | ||||
| Sinusitis | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Staphylococcal sepsis | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Staphylococcal bacteraemia | 2/30 (6.7%) | 1/38 (2.6%) | 3/102 (2.9%) | 1/40 (2.5%) | ||||
| Staphylococcal infection | 0/30 (0%) | 0/38 (0%) | 2/102 (2%) | 0/40 (0%) | ||||
| Stenotrophomonas infection | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Stenotrophomonas sepsis | 1/30 (3.3%) | 1/38 (2.6%) | 2/102 (2%) | 0/40 (0%) | ||||
| Toxoplasmosis | 1/30 (3.3%) | 0/38 (0%) | 0/102 (0%) | 0/40 (0%) | ||||
| Upper respiratory tract infection | 1/30 (3.3%) | 0/38 (0%) | 0/102 (0%) | 0/40 (0%) | ||||
| Zygomycosis | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Arteriovenous fistula thrombosis | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Blood stem cell transplant failure | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Transplant failure | 1/30 (3.3%) | 1/38 (2.6%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 0/30 (0%) | 0/38 (0%) | 3/102 (2.9%) | 0/40 (0%) | ||||
| Aspartate aminotransferase increased | 0/30 (0%) | 0/38 (0%) | 3/102 (2.9%) | 0/40 (0%) | ||||
| Blood bilirubin increased | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Blood creatinine increased | 0/30 (0%) | 0/38 (0%) | 3/102 (2.9%) | 0/40 (0%) | ||||
| Neutrophil count decreased | 1/30 (3.3%) | 0/38 (0%) | 0/102 (0%) | 0/40 (0%) | ||||
| Pancreatic enzymes increased | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| White blood cell count decreased | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 1/30 (3.3%) | 2/38 (5.3%) | 2/102 (2%) | 2/40 (5%) | ||||
| Dehydration | 1/30 (3.3%) | 2/38 (5.3%) | 6/102 (5.9%) | 2/40 (5%) | ||||
| Electrolyte imbalance | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Failure to thrive | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Fluid overload | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Fluid retention | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Hyperkalaemia | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Hypokalaemia | 0/30 (0%) | 1/38 (2.6%) | 1/102 (1%) | 0/40 (0%) | ||||
| Lactic acidosis | 0/30 (0%) | 1/38 (2.6%) | 1/102 (1%) | 0/40 (0%) | ||||
| Metabolic acidosis | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Back pain | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Myopathy | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Acute lymphocytic leukaemia recurrent | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Acute myeloid leukaemia | 1/30 (3.3%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Adult T-cell lymphoma/leukaemia refractory | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Diffuse large B-cell lymphoma | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Epstein-Barr virus associated lymphoproliferative disorder | 2/30 (6.7%) | 1/38 (2.6%) | 1/102 (1%) | 2/40 (5%) | ||||
| Nervous system disorders | ||||||||
| Cerebral haemorrhage | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Cerebrovascular accident | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Convulsion | 1/30 (3.3%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Embolic cerebral infarction | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Encephalopathy | 0/30 (0%) | 1/38 (2.6%) | 2/102 (2%) | 1/40 (2.5%) | ||||
| Guillain-Barre syndrome | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 2/40 (5%) | ||||
| Haemorrhage intracranial | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Hemiparesis | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Status epilepticus | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Syncope | 0/30 (0%) | 0/38 (0%) | 2/102 (2%) | 0/40 (0%) | ||||
| Psychiatric disorders | ||||||||
| Confusional state | 0/30 (0%) | 0/38 (0%) | 3/102 (2.9%) | 0/40 (0%) | ||||
| Delirium | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Mental status changes | 1/30 (3.3%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Azotaemia | 0/30 (0%) | 0/38 (0%) | 2/102 (2%) | 0/40 (0%) | ||||
| Bladder spasm | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Dysuria | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Renal failure acute | 0/30 (0%) | 2/38 (5.3%) | 4/102 (3.9%) | 4/40 (10%) | ||||
| Renal failure chronic | 0/30 (0%) | 0/38 (0%) | 2/102 (2%) | 0/40 (0%) | ||||
| Renal failure | 2/30 (6.7%) | 0/38 (0%) | 2/102 (2%) | 1/40 (2.5%) | ||||
| Renal impairment | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Reproductive system and breast disorders | ||||||||
| Oedema genital | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Acute respiratory distress syndrome | 3/30 (10%) | 1/38 (2.6%) | 1/102 (1%) | 1/40 (2.5%) | ||||
| Aspiration | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Dyspnoea | 0/30 (0%) | 2/38 (5.3%) | 4/102 (3.9%) | 0/40 (0%) | ||||
| Epistaxis | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Haemothorax | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Hypoxia | 2/30 (6.7%) | 1/38 (2.6%) | 5/102 (4.9%) | 1/40 (2.5%) | ||||
| Idiopathic pneumonia syndrome | 0/30 (0%) | 0/38 (0%) | 2/102 (2%) | 0/40 (0%) | ||||
| Lung infiltration | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Organising pneumonia | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Pleural effusion | 0/30 (0%) | 0/38 (0%) | 2/102 (2%) | 0/40 (0%) | ||||
| Pleural haemorrhage | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Pneumomediastinum | 1/30 (3.3%) | 0/38 (0%) | 0/102 (0%) | 0/40 (0%) | ||||
| Pneumonia aspiration | 1/30 (3.3%) | 0/38 (0%) | 2/102 (2%) | 0/40 (0%) | ||||
| Pneumonitis | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Pneumothorax | 1/30 (3.3%) | 0/38 (0%) | 0/102 (0%) | 0/40 (0%) | ||||
| Pulmonary alveolar haemorrhage | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Pulmonary congestion | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Pulmonary haemorrhage | 0/30 (0%) | 1/38 (2.6%) | 1/102 (1%) | 0/40 (0%) | ||||
| Pulmonary hypertension | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Pulmonary oedema | 0/30 (0%) | 1/38 (2.6%) | 1/102 (1%) | 0/40 (0%) | ||||
| Respiratory acidosis | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Respiratory arrest | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Respiratory distress | 1/30 (3.3%) | 3/38 (7.9%) | 2/102 (2%) | 3/40 (7.5%) | ||||
| Respiratory failure | 6/30 (20%) | 5/38 (13.2%) | 9/102 (8.8%) | 4/40 (10%) | ||||
| Upper-airway cough syndrome | 1/30 (3.3%) | 0/38 (0%) | 0/102 (0%) | 0/40 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Decubitus ulcer | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Skin haemorrhage | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Vascular disorders | ||||||||
| Aortic thrombosis | 1/30 (3.3%) | 0/38 (0%) | 0/102 (0%) | 0/40 (0%) | ||||
| Capillary leak syndrome | 1/30 (3.3%) | 0/38 (0%) | 0/102 (0%) | 0/40 (0%) | ||||
| Deep vein thrombosis | 0/30 (0%) | 0/38 (0%) | 2/102 (2%) | 0/40 (0%) | ||||
| Haematoma | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Hypertension | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 1/40 (2.5%) | ||||
| Hypotension | 1/30 (3.3%) | 4/38 (10.5%) | 7/102 (6.9%) | 0/40 (0%) | ||||
| Hypovolaemic shock | 0/30 (0%) | 2/38 (5.3%) | 0/102 (0%) | 0/40 (0%) | ||||
| Orthostatic hypotension | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
| Shock | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Venous stenosis | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 0/40 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| BCV (≤4 mg/kg/Week) | BCV (>4 mg/kg/Week) | BCV (≤200 mg/Week) | BCV (>200 mg/Week) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 30/30 (100%) | 37/38 (97.4%) | 101/102 (99%) | 40/40 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 2/30 (6.7%) | 3/38 (7.9%) | 5/102 (4.9%) | 3/40 (7.5%) | ||||
| Febrile neutropenia | 2/30 (6.7%) | 2/38 (5.3%) | 5/102 (4.9%) | 0/40 (0%) | ||||
| Neutropenia | 3/30 (10%) | 2/38 (5.3%) | 16/102 (15.7%) | 8/40 (20%) | ||||
| Thrombocytopenia | 0/30 (0%) | 1/38 (2.6%) | 10/102 (9.8%) | 3/40 (7.5%) | ||||
| Cardiac disorders | ||||||||
| Bradycardia | 2/30 (6.7%) | 3/38 (7.9%) | 2/102 (2%) | 1/40 (2.5%) | ||||
| Pericardial effusion | 2/30 (6.7%) | 2/38 (5.3%) | 2/102 (2%) | 1/40 (2.5%) | ||||
| Tachycardia | 2/30 (6.7%) | 1/38 (2.6%) | 9/102 (8.8%) | 1/40 (2.5%) | ||||
| Endocrine disorders | ||||||||
| Adrenal insufficiency | 1/30 (3.3%) | 2/38 (5.3%) | 2/102 (2%) | 2/40 (5%) | ||||
| Eye disorders | ||||||||
| Dry eye | 1/30 (3.3%) | 0/38 (0%) | 4/102 (3.9%) | 2/40 (5%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 6/30 (20%) | 7/38 (18.4%) | 26/102 (25.5%) | 4/40 (10%) | ||||
| Ascites | 1/30 (3.3%) | 3/38 (7.9%) | 5/102 (4.9%) | 3/40 (7.5%) | ||||
| Colitis | 0/30 (0%) | 3/38 (7.9%) | 5/102 (4.9%) | 1/40 (2.5%) | ||||
| Constipation | 2/30 (6.7%) | 1/38 (2.6%) | 8/102 (7.8%) | 2/40 (5%) | ||||
| Diarrhoea | 12/30 (40%) | 22/38 (57.9%) | 61/102 (59.8%) | 19/40 (47.5%) | ||||
| Dysphagia | 0/30 (0%) | 2/38 (5.3%) | 3/102 (2.9%) | 0/40 (0%) | ||||
| Flatulence | 0/30 (0%) | 0/38 (0%) | 6/102 (5.9%) | 0/40 (0%) | ||||
| Gastrointestinal haemorrhage | 0/30 (0%) | 4/38 (10.5%) | 1/102 (1%) | 3/40 (7.5%) | ||||
| Haematochezia | 1/30 (3.3%) | 2/38 (5.3%) | 2/102 (2%) | 1/40 (2.5%) | ||||
| Ileus | 2/30 (6.7%) | 1/38 (2.6%) | 1/102 (1%) | 2/40 (5%) | ||||
| Lower gastrointestinal haemorrhage | 3/30 (10%) | 1/38 (2.6%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Nausea | 3/30 (10%) | 6/38 (15.8%) | 42/102 (41.2%) | 9/40 (22.5%) | ||||
| Pancreatitis | 1/30 (3.3%) | 2/38 (5.3%) | 1/102 (1%) | 1/40 (2.5%) | ||||
| Pneumatosis | 1/30 (3.3%) | 2/38 (5.3%) | 1/102 (1%) | 1/40 (2.5%) | ||||
| Small intestinal obstruction | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 3/40 (7.5%) | ||||
| Vomiting | 8/30 (26.7%) | 13/38 (34.2%) | 30/102 (29.4%) | 7/40 (17.5%) | ||||
| General disorders | ||||||||
| Asthenia | 0/30 (0%) | 0/38 (0%) | 3/102 (2.9%) | 3/40 (7.5%) | ||||
| Chest pain | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 3/40 (7.5%) | ||||
| Chills | 1/30 (3.3%) | 1/38 (2.6%) | 7/102 (6.9%) | 2/40 (5%) | ||||
| Fatigue | 1/30 (3.3%) | 1/38 (2.6%) | 13/102 (12.7%) | 1/40 (2.5%) | ||||
| Generalized oedema | 2/30 (6.7%) | 1/38 (2.6%) | 6/102 (5.9%) | 0/40 (0%) | ||||
| Muscosal inflammation | 2/30 (6.7%) | 1/38 (2.6%) | 0/102 (0%) | 0/40 (0%) | ||||
| Multi-organ failure | 3/30 (10%) | 1/38 (2.6%) | 7/102 (6.9%) | 6/40 (15%) | ||||
| Oedema peripheral | 0/30 (0%) | 1/38 (2.6%) | 17/102 (16.7%) | 2/40 (5%) | ||||
| Pain | 1/30 (3.3%) | 2/38 (5.3%) | 3/102 (2.9%) | 0/40 (0%) | ||||
| Pyrexia | 13/30 (43.3%) | 9/38 (23.7%) | 25/102 (24.5%) | 4/40 (10%) | ||||
| Hepatobiliary disorders | ||||||||
| Cholelithiasis | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 2/40 (5%) | ||||
| Cholestasis | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 2/40 (5%) | ||||
| Hepatic failure | 1/30 (3.3%) | 2/38 (5.3%) | 0/102 (0%) | 0/40 (0%) | ||||
| Hyperbilirubinaemia | 1/30 (3.3%) | 1/38 (2.6%) | 7/102 (6.9%) | 3/40 (7.5%) | ||||
| Immune system disorders | ||||||||
| Acute graft versus host disease | 8/30 (26.7%) | 11/38 (28.9%) | 30/102 (29.4%) | 11/40 (27.5%) | ||||
| Chronic graft versus host disease | 3/30 (10%) | 2/38 (5.3%) | 8/102 (7.8%) | 3/40 (7.5%) | ||||
| Infections and infestations | ||||||||
| Adenovirus infection | 2/30 (6.7%) | 1/38 (2.6%) | 2/102 (2%) | 0/40 (0%) | ||||
| BK virus infection | 1/30 (3.3%) | 2/38 (5.3%) | 4/102 (3.9%) | 2/40 (5%) | ||||
| Bacteraemia | 2/30 (6.7%) | 2/38 (5.3%) | 2/102 (2%) | 1/40 (2.5%) | ||||
| Candidiasis | 0/30 (0%) | 4/38 (10.5%) | 1/102 (1%) | 0/40 (0%) | ||||
| Clostridial infection | 0/30 (0%) | 3/38 (7.9%) | 1/102 (1%) | 1/40 (2.5%) | ||||
| Clostridium difficile colitis | 0/30 (0%) | 3/38 (7.9%) | 6/102 (5.9%) | 5/40 (12.5%) | ||||
| Cytomegalovirus colitis | 2/30 (6.7%) | 0/38 (0%) | 1/102 (1%) | 1/40 (2.5%) | ||||
| Cytomegalovirus viraemia | 1/30 (3.3%) | 0/38 (0%) | 3/102 (2.9%) | 2/40 (5%) | ||||
| Enterococcal sepsis | 0/30 (0%) | 1/38 (2.6%) | 1/102 (1%) | 2/40 (5%) | ||||
| Epstein-Barr viraemia | 0/30 (0%) | 0/38 (0%) | 6/102 (5.9%) | 1/40 (2.5%) | ||||
| Gastroenteritis norovirus | 1/30 (3.3%) | 2/38 (5.3%) | 0/102 (0%) | 0/40 (0%) | ||||
| Human herpesvirus 6 infection | 2/30 (6.7%) | 0/38 (0%) | 0/102 (0%) | 0/40 (0%) | ||||
| Lung infection | 0/30 (0%) | 1/38 (2.6%) | 2/102 (2%) | 2/40 (5%) | ||||
| Oral candidiasis | 1/30 (3.3%) | 2/38 (5.3%) | 6/102 (5.9%) | 0/40 (0%) | ||||
| Pneumonia | 3/30 (10%) | 3/38 (7.9%) | 4/102 (3.9%) | 0/40 (0%) | ||||
| Pneumonia cytomegaloviral | 3/30 (10%) | 0/38 (0%) | 2/102 (2%) | 2/40 (5%) | ||||
| Pseudomonal bacteraemia | 1/30 (3.3%) | 0/38 (0%) | 4/102 (3.9%) | 2/40 (5%) | ||||
| Sinusitis | 1/30 (3.3%) | 2/38 (5.3%) | 2/102 (2%) | 2/40 (5%) | ||||
| Staphylococcal bacteraemia | 2/30 (6.7%) | 1/38 (2.6%) | 6/102 (5.9%) | 2/40 (5%) | ||||
| Systemic candida | 0/30 (0%) | 1/38 (2.6%) | 0/102 (0%) | 2/40 (5%) | ||||
| Upper respiratory tract infection | 1/30 (3.3%) | 2/38 (5.3%) | 3/102 (2.9%) | 0/40 (0%) | ||||
| Urinary tract infection enterococcal | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 3/40 (7.5%) | ||||
| Urinary tract infection | 0/30 (0%) | 2/38 (5.3%) | 2/102 (2%) | 0/40 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Transplant failure | 1/30 (3.3%) | 2/38 (5.3%) | 0/102 (0%) | 1/40 (2.5%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 6/30 (20%) | 4/38 (10.5%) | 17/102 (16.7%) | 6/40 (15%) | ||||
| Aspartate aminotransferase increased | 5/30 (16.7%) | 3/38 (7.9%) | 17/102 (16.7%) | 4/40 (10%) | ||||
| Blood alkaline phosphatase increased | 1/30 (3.3%) | 0/38 (0%) | 8/102 (7.8%) | 0/40 (0%) | ||||
| Blood bilirubin increased | 2/30 (6.7%) | 4/38 (10.5%) | 4/102 (3.9%) | 1/40 (2.5%) | ||||
| Blood creatinine increased | 0/30 (0%) | 1/38 (2.6%) | 8/102 (7.8%) | 1/40 (2.5%) | ||||
| Clostridium test positive | 1/30 (3.3%) | 0/38 (0%) | 2/102 (2%) | 2/40 (5%) | ||||
| Neutrophil count decreased | 4/30 (13.3%) | 2/38 (5.3%) | 4/102 (3.9%) | 0/40 (0%) | ||||
| Weight decreased | 1/30 (3.3%) | 1/38 (2.6%) | 6/102 (5.9%) | 2/40 (5%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 1/30 (3.3%) | 7/38 (18.4%) | 17/102 (16.7%) | 2/40 (5%) | ||||
| Dehydration | 2/30 (6.7%) | 3/38 (7.9%) | 8/102 (7.8%) | 3/40 (7.5%) | ||||
| Fluid overload | 1/30 (3.3%) | 0/38 (0%) | 3/102 (2.9%) | 3/40 (7.5%) | ||||
| Fluid retention | 2/30 (6.7%) | 2/38 (5.3%) | 1/102 (1%) | 0/40 (0%) | ||||
| Hyperglycaemia | 4/30 (13.3%) | 3/38 (7.9%) | 9/102 (8.8%) | 2/40 (5%) | ||||
| Hyperkalaemia | 1/30 (3.3%) | 0/38 (0%) | 3/102 (2.9%) | 3/40 (7.5%) | ||||
| Hypokalaemia | 7/30 (23.3%) | 4/38 (10.5%) | 9/102 (8.8%) | 2/40 (5%) | ||||
| Hypomagnesaemia | 4/30 (13.3%) | 1/38 (2.6%) | 2/102 (2%) | 0/40 (0%) | ||||
| Malnutrition | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 2/40 (5%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/30 (0%) | 1/38 (2.6%) | 8/102 (7.8%) | 1/40 (2.5%) | ||||
| Back pain | 2/30 (6.7%) | 3/38 (7.9%) | 8/102 (7.8%) | 1/40 (2.5%) | ||||
| Muscular weakness | 0/30 (0%) | 0/38 (0%) | 8/102 (7.8%) | 0/40 (0%) | ||||
| Pain in extremity | 1/30 (3.3%) | 3/38 (7.9%) | 6/102 (5.9%) | 0/40 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Epstein-Barr virus associated lymphoproliferative | 2/30 (6.7%) | 1/38 (2.6%) | 3/102 (2.9%) | 3/40 (7.5%) | ||||
| Nervous system disorders | ||||||||
| Convulsion | 1/30 (3.3%) | 0/38 (0%) | 1/102 (1%) | 2/40 (5%) | ||||
| Dizziness | 0/30 (0%) | 1/38 (2.6%) | 6/102 (5.9%) | 3/40 (7.5%) | ||||
| Encephalopathy | 0/30 (0%) | 1/38 (2.6%) | 3/102 (2.9%) | 3/40 (7.5%) | ||||
| Guillain-Barre syndrome | 0/30 (0%) | 0/38 (0%) | 0/102 (0%) | 2/40 (5%) | ||||
| Headache | 1/30 (3.3%) | 3/38 (7.9%) | 12/102 (11.8%) | 3/40 (7.5%) | ||||
| Tremor | 0/30 (0%) | 1/38 (2.6%) | 7/102 (6.9%) | 2/40 (5%) | ||||
| Neuropathy peripheral | 0/30 (0%) | 0/38 (0%) | 6/102 (5.9%) | 0/40 (0%) | ||||
| Psychiatric disorders | ||||||||
| Agitation | 1/30 (3.3%) | 0/38 (0%) | 6/102 (5.9%) | 4/40 (10%) | ||||
| Anxiety | 2/30 (6.7%) | 2/38 (5.3%) | 6/102 (5.9%) | 3/40 (7.5%) | ||||
| Confusional state | 0/30 (0%) | 0/38 (0%) | 8/102 (7.8%) | 1/40 (2.5%) | ||||
| Depression | 2/30 (6.7%) | 0/38 (0%) | 6/102 (5.9%) | 0/40 (0%) | ||||
| Insomnia | 1/30 (3.3%) | 3/38 (7.9%) | 5/102 (4.9%) | 3/40 (7.5%) | ||||
| Mental status changes | 2/30 (6.7%) | 0/38 (0%) | 8/102 (7.8%) | 2/40 (5%) | ||||
| Renal and urinary disorders | ||||||||
| Haematuria | 0/30 (0%) | 2/38 (5.3%) | 4/102 (3.9%) | 1/40 (2.5%) | ||||
| Renal failure acute | 0/30 (0%) | 6/38 (15.8%) | 6/102 (5.9%) | 4/40 (10%) | ||||
| Renal failure | 4/30 (13.3%) | 3/38 (7.9%) | 4/102 (3.9%) | 4/40 (10%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Acute respiratory distress syndrome | 3/30 (10%) | 1/38 (2.6%) | 1/102 (1%) | 1/40 (2.5%) | ||||
| Atelectasis | 0/30 (0%) | 3/38 (7.9%) | 2/102 (2%) | 0/40 (0%) | ||||
| Cough | 1/30 (3.3%) | 3/38 (7.9%) | 16/102 (15.7%) | 2/40 (5%) | ||||
| Dyspnoea | 1/30 (3.3%) | 3/38 (7.9%) | 14/102 (13.7%) | 1/40 (2.5%) | ||||
| Epistaxis | 3/30 (10%) | 2/38 (5.3%) | 7/102 (6.9%) | 1/40 (2.5%) | ||||
| Hypoxia | 3/30 (10%) | 2/38 (5.3%) | 8/102 (7.8%) | 1/40 (2.5%) | ||||
| Lung infiltration | 0/30 (0%) | 0/38 (0%) | 5/102 (4.9%) | 2/40 (5%) | ||||
| Nasal congestion | 1/30 (3.3%) | 0/38 (0%) | 8/102 (7.8%) | 0/40 (0%) | ||||
| Oropharyngeal pain | 0/30 (0%) | 3/38 (7.9%) | 3/102 (2.9%) | 0/40 (0%) | ||||
| Pleural effusion | 2/30 (6.7%) | 0/38 (0%) | 10/102 (9.8%) | 2/40 (5%) | ||||
| Pneumomediastinum | 2/30 (6.7%) | 0/38 (0%) | 0/102 (0%) | 0/40 (0%) | ||||
| Pneumothorax | 3/30 (10%) | 1/38 (2.6%) | 2/102 (2%) | 2/40 (5%) | ||||
| Respiratory distress | 4/30 (13.3%) | 6/38 (15.8%) | 3/102 (2.9%) | 3/40 (7.5%) | ||||
| Respiratory failure | 7/30 (23.3%) | 5/38 (13.2%) | 10/102 (9.8%) | 6/40 (15%) | ||||
| Tachypnoea | 2/30 (6.7%) | 1/38 (2.6%) | 2/102 (2%) | 1/40 (2.5%) | ||||
| Sleep apnoea syndrome | 0/30 (0%) | 2/38 (5.3%) | 0/102 (0%) | 0/40 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Alopecia | 1/30 (3.3%) | 2/38 (5.3%) | 2/102 (2%) | 1/40 (2.5%) | ||||
| Dry skin | 0/30 (0%) | 1/38 (2.6%) | 4/102 (3.9%) | 3/40 (7.5%) | ||||
| Erythema | 0/30 (0%) | 0/38 (0%) | 1/102 (1%) | 2/40 (5%) | ||||
| Pruritus | 4/30 (13.3%) | 1/38 (2.6%) | 6/102 (5.9%) | 1/40 (2.5%) | ||||
| Rash | 4/30 (13.3%) | 3/38 (7.9%) | 10/102 (9.8%) | 4/40 (10%) | ||||
| Skin lesion | 1/30 (3.3%) | 0/38 (0%) | 1/102 (1%) | 2/40 (5%) | ||||
| Vascular disorders | ||||||||
| Hypertension | 8/30 (26.7%) | 3/38 (7.9%) | 7/102 (6.9%) | 4/40 (10%) | ||||
| Hypotension | 6/30 (20%) | 7/38 (18.4%) | 16/102 (15.7%) | 5/40 (12.5%) | ||||
| Hypovolaemic shock | 0/30 (0%) | 2/38 (5.3%) | 0/102 (0%) | 0/40 (0%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Within 18 months after the end of the Study at all sites, if no publication of the overall multi-center results has been made, institutions are entitled to publish their locally obtained results, provided the Sponsor is given opportunity to review and comment. Institution publications may be delayed up to an additional 60 days to allow Sponsor to seek patent protection.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Chimerix, Inc. |
| Phone | 919-806-1074 ext 101 |
| dmoore@chimerix.com |
Responsible Party:
Chimerix
ClinicalTrials.gov Identifier:
NCT01143181
Other Study ID Numbers:
- CMX001-350
First Posted:
Jun 14, 2010
Last Update Posted:
Aug 12, 2021
Last Verified:
Jul 1, 2021