Study to Assess the Safety and Efficacy of Brincidofovir in Treatment of Early Versus Late Adenovirus Infection
Study Details
Study Description
Brief Summary
This was a Phase 3 open-label, non-randomized, multicenter study of oral brincidofovir (BCV) administered twice weekly for the treatment of adenovirus (AdV) infection detected during asymptomatic AdV viremia or during symptomatic AdV infection.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
This was a Phase 3 open-label, non-randomized, multicenter study of the safety, tolerability, and efficacy of oral brincidofovir (BCV) when administered twice weekly for the treatment of disseminated adenovirus (AdV) disease and for the treatment of AdV infection when treatment was initiated in subjects who were at risk of progression to disseminated disease (i.e., during the asymptomatic or localized phases of infection).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Brincidofovir Subjects who weighed <50 kg received 2 mg/kg (not to exceed 100 mg) BCV twice weekly administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received 100 mg BCV twice weekly administered orally as one 100 mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine). |
Drug: Brincidofovir
BCV administered twice weekly, dose depending on weight.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With All-Cause Mortality [60 days]
The primary efficacy endpoint was the evaluation of the effect of brincidofovir (BCV) on all-cause mortality when used for the treatment of disseminated adenovirus (AdV) disease in all hematopoietic cell transplant (HCT) recipients. The primary endpoint associated with this objective was all-cause mortality through Day 60.
Secondary Outcome Measures
- Number of Participants With Reduction in Adenovirus Viremia [Assessed 13 weeks (through 7 days post-last BCV dose); during treatment up to 12 weeks reported]
A secondary endpoint was the evaluation of virologic response (plasma adenovirus [AdV] DNA viremia) to brincidofovir treatment. Blood (plasma) was collected at screening, before dosing on Day 1 (to establish baseline), and at each subsequent assessment during the treatment and post-treatment phases for the analysis of AdV DNA viremia. All samples collected for analysis of AdV were analyzed by the designated central virology laboratory using proprietary real-time quantitative polymerase chain reaction (qPCR) assays. AdV in plasma were analyzed using the 7500 AdV qPCR Test, where the standardized assay plasma ranged from 190 copies/mL to 1 X 10^10 copies/mL. A "positive or detectable" result referred to the measurement of AdV DNA at concentrations ≥190 copies/mL, a result below the lower limit of detection (LLOQ) (i.e., not detected) was imputed as 1 copy/mL, and a result below the lower limit of quantitation but detected will be imputed at 1 unit less than LLOQ (e.g., 189 copies/mL).
- Mean Minimum On-treatment Value log10 Copies/mL Change From Baseline [Baseline to 12 weeks]
A secondary endpoint was the evaluation of virologic response (plasma adenovirus [AdV] DNA viremia) to brincidofovir treatment. Blood (plasma) was collected at screening, before dosing on Day 1 (to establish baseline), and at each subsequent assessment during the treatment and post-treatment phases for the analysis of AdV DNA viremia. All samples collected for analysis of AdV were analyzed by the designated central virology laboratory using proprietary real-time quantitative polymerase chain reaction (qPCR) assays. AdV in plasma were analyzed using the 7500 AdV qPCR Test, where the standardized assay plasma ranged from 190 copies/mL to 1 X 10^10 copies/mL. A "positive or detectable" result referred to the measurement of AdV DNA at concentrations ≥190 copies/mL, a result below the lower limit of detection (LLOQ) (i.e., not detected) was imputed as 1 copy/mL, and a result below the lower limit of quantitation but detected will be imputed at 1 unit less than LLOQ (e.g., 189 copies/mL).
Eligibility Criteria
Criteria
Inclusion Criteria Subjects were required to meet all of the following criteria, as applicable, to be eligible to participate in this study.
-
Were male or female, aged 2 months or older.
-
Had either of the following:
-
Disseminated adenovirus (AdV) disease; or
-
An underlying immunocompromised state and were at risk of progression to disseminated AdV disease.
[Note: Subjects with symptomatic AdV infection (i.e., localized or disseminated AdV disease) could have been screening immediately, with brincidofovir (BCV) therapy initiated after receipt of the screening virology results from the designated central virology laboratory confirming study eligibility. Subjects with asymptomatic AdV infection (i.e., had no symptoms of AdV disease) could have been consented and screened only if they had at least 1 positive or detectable AdV DNA (quantitative [q]) polymerase chain reaction (PCR) test (in any blood fluid or compartment) from the local virology laboratory, with treatment initiated only after confirmation of AdV positivity by 2 separate measurements at the designated central virology laboratory. Where the results from 2 AdV DNA (q)PCR measurements in plasma or non-plasma body fluid or compartment were needed to show that a subject was at risk of progression to disseminated AdV disease, the second measurement had to be resulted prior to the initiation of BCV therapy.]
-
Were able to ingest and absorb oral medication (in the judgement of the investigator and based on lack of significant gastrointestinal [GI] events/medical history).
-
If male of reproductive potential, were willing to use an acceptable contraceptive method(s) during sexual intercourse with a female partner of reproductive potential throughout the duration of this participation in the study and for at least 6 months after his last dose of BCV.
-
If female of reproductive potential, i.e., not premenarche, postmenopausal, surgically sterile, or had documented ovarian failure, were willing to use 2 acceptable contraceptive methods, 1 of which must have been a barrier method, during sexual intercourse with a nonsterile male partner, throughout the duration of her participation in the study and for at least 6 months after her last dose of BCV.
-
Were willing and able to understand and provide written informed consent to participate in the study. [Note: If the subject was under 18 years of age or was otherwise unable to legally give his or her informed consent to participate in the study, then written informed consent to participate had to be obtained from the parent(s) or legal guardian(s) of the subject or other legal personal representative(s), as applicable. In addition, in the case of minor subjects, the written assent of the subject to participate in the study was obtained where required by applicable institutional policy on the consenting of minor study participants.]
-
The subject and his or her caregivers (as applicable) were willing and able to participate in all required study activities for the entire duration of the study (i.e., through completion of Week 36).
Exclusion Criteria
Subjects who met any of the following criteria (as applicable) were not eligible to participate in this study:
-
If a female of reproductive potential, the subject was pregnant, planning to become pregnant during the study or within 6 months after their anticipated last BCV dose, or was nursing a child.
-
Had hypersensitivity (not including renal dysfunction or eye disorder) to cidofovir (CDV) or to BCV or its formulation excipients.
-
Had received treatment with another investigational drug within 14 days prior to Day 1 unless prior approval was received from the Chimerix medical monitor (or designee).
-
Were participating in another interventional clinical trial unless prior approval was received from the Chimerix medical monitor (or designee).
-
Had previously received an anti-AdV vaccine or a cell-based anti-AdV therapy.
-
Were receiving intravenous (IV) CDV, leflunomide, vidarabine, systemic ribavirin, or another investigational anti-AdV drug at Day 1. [Note: Subjects who were receiving treatment with IV CDV prior to enrollment had to discontinue IV CDV and wait until a minimum of 48 hours had elapsed from last IV CDV administration before initiating BCV therapy. All other drugs had to be discontinued prior to Day 1.]
-
Were receiving digoxin or ketoconazole (other than topical formulations) at Day 1 or were anticipated to need treatment with either drug during the treatment phase of the study.
-
Were infected with HIV, hepatitis B virus (HBV), and/or hepatitis C virus (HCV), had evidence of active viral replication within 6 months prior to screening, as demonstrated by detectable HIV or HCV RNA, or had detectable HBV DNA in blood, plasma or serum.
-
Had end-stage renal disease, i.e., an estimated glomerular filtration rate <15 mL/min, unless receiving renal replacement therapy.
-
Had a serum alanine aminotransferase or aspartate aminotransferase concentration >5 x the upper limit of normal (ULN), or a serum total bilirubin concentration >2 x the ULN and a serum direct (conjugated) bilirubin concentration >1.5 x the ULN, as reported by the central safety laboratory, unless, in the judgment of the investigator, the abnormality(ies) was/were related to the subject's AdV infection/disease.
-
Had ongoing Grade 3 or higher diarrhea, unless, in the judgment of the investigator, the diarrhea was related to the subject's underlying AdV infection/disease.
-
Had Stage 3 or higher graft versus host disease (GVHD) of the intestine (GI-GVHD or any other GI disease that would have, in the judgment of the investigator, precluded the subject from taking or absorbing oral medication (e.g., clinically active Crohn's disease, ischemic colitis, moderate or severe ulcerative colitis, small bowel resection, ileus, or any condition expected to require abdominal surgery during the course of study participation).
-
Had any other condition, including abnormal laboratory values, that would have, in the judgment of the investigator, put the subject at increased risk by participating in the study, or would have interfered with the conduct or planned analyses of the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Phoenix Children's Hospital | Phoenix | Arizona | United States | 85016 |
| 2 | Children's Hospital Los Angeles | Los Angeles | California | United States | 90027 |
| 3 | Stanford Children's Hospital | Palo Alto | California | United States | 94305 |
| 4 | Stanford University | Stanford | California | United States | 94305 |
| 5 | Children's Hospital Colorado | Aurora | Colorado | United States | 80045 |
| 6 | Children's National Health System | Washington | District of Columbia | United States | 20010 |
| 7 | Children's Healthcare of Atlanta, Aflac Cancer and Blood Center | Atlanta | Georgia | United States | 30322 |
| 8 | Ann & Robert H. Lurie Children's Hospital of Chicago | Chicago | Illinois | United States | 60611 |
| 9 | University of Chicago | Chicago | Illinois | United States | 60637 |
| 10 | Children's Hospital | New Orleans | Louisiana | United States | 70118 |
| 11 | Johns Hopkins University | Baltimore | Maryland | United States | 21231 |
| 12 | Brigham and Woman's Hospital | Boston | Massachusetts | United States | 02115 |
| 13 | University of Minnesota | Minneapolis | Minnesota | United States | 55455 |
| 14 | Children's Mercy Hospital | Kansas City | Missouri | United States | 64108 |
| 15 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 16 | University of Nebraska | Omaha | Nebraska | United States | 68198 |
| 17 | Montifore Medical Center | Bronx | New York | United States | 10467 |
| 18 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 19 | Weill Cornell Medical College/ New York Presbyterian Hospital | New York | New York | United States | 10065 |
| 20 | Levine Children's Hospital | Charlotte | North Carolina | United States | 28203 |
| 21 | Duke University Medical Center | Durham | North Carolina | United States | 27712 |
| 22 | Cincinnati Children's Hospital | Cincinnati | Ohio | United States | 45229 |
| 23 | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | 19104 |
| 24 | Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania | United States | 15224 |
| 25 | St. Jude Children's Hospital | Memphis | Tennessee | United States | 38105 |
| 26 | Cook Children's Medical Center | Fort Worth | Texas | United States | 76104 |
| 27 | Baylor College of Medicine | Houston | Texas | United States | 77030 |
| 28 | MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 29 | Intermountain Healthcare Research | Salt Lake City | Utah | United States | 84103 |
| 30 | University of Utah Huntsman Cancer Institute | Salt Lake City | Utah | United States | 84112 |
| 31 | Fred Hutchingson Cancer Center | Seattle | Washington | United States | 19024 |
| 32 | Seattle Children's Hospital | Seattle | Washington | United States | 98105 |
| 33 | 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.- CMX001-304
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Cohort A | Cohort B | Cohort C |
|---|---|---|---|
| Arm/Group Description | Allogeneic hematopoietic cell transplant recipients at risk of progression to disseminated adenovirus (AdV) disease (i.e., subjects with either asymptomatic AdV infection or localized adenovirus disease) and who weighed ≤120 kg. Subjects who weighed <50 kg received 2 mg/kg (not-to-exceed 100 mg) brincidofovir (BCV) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received BCV 100 mg twice weekly, administered orally as one 100-mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine). | Allogeneic hematopoietic cell transplant recipients with disseminated adenovirus disease who weigh ≤120 kg. Subjects who weighed <50 kg received 2 mg/kg brincidofovir (BCV; not to exceed 100 mg) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received 100 mg BCV twice weekly, administered orally as one 100 mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine). | Allogeneic hematopoietic cell transplant recipients who weighed >120 kg and all other immunocompromised subjects with disseminated adenovirus (AdV) disease or subjects who were at risk of progression to disseminated AdV disease, as well as non-immunocompromised subjects with disseminated AdV disease. Subjects who weighed <50 kg received 2 mg/kg (not to exceed 100 mg) brincidofovir (BCV) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received 100 mg BCV twice weekly, administered orally as one 100-mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine). |
| Period Title: Overall Study | |||
| STARTED | 65 | 93 | 43 |
| COMPLETED | 29 | 29 | 16 |
| NOT COMPLETED | 36 | 64 | 27 |
Baseline Characteristics
| Arm/Group Title | Cohort A | Cohort B | Cohort C | Total |
|---|---|---|---|---|
| Arm/Group Description | Allogeneic hematopoietic cell transplant recipients at risk of progression to disseminated adenovirus (AdV) disease (i.e., subjects with either asymptomatic AdV infection or localized adenovirus disease) and who weighed ≤120 kg. Subjects who weighed <50 kg received 2 mg/kg (not-to-exceed 100 mg) brincidofovir (BCV) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received BCV 100 mg twice weekly, administered orally as one 100-mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine). | Allogeneic hematopoietic cell transplant recipients with disseminated adenovirus disease who weigh ≤120 kg. Subjects who weighed <50 kg received 2 mg/kg brincidofovir (BCV; not to exceed 100 mg) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received 100 mg BCV twice weekly, administered orally as one 100 mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine). | Allogeneic hematopoietic cell transplant recipients who weighed >120 kg and all other immunocompromised subjects with disseminated adenovirus (AdV) disease or subjects who were at risk of progression to disseminated AdV disease, as well as non-immunocompromised subjects with disseminated AdV disease. Subjects who weighed <50 kg received 2 mg/kg (not to exceed 100 mg) brincidofovir (BCV) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received 100 mg BCV twice weekly, administered orally as one 100-mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine). | Total of all reporting groups |
| Overall Participants | 65 | 93 | 43 | 201 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
19
(17.4)
|
20
(23.1)
|
17
(21.9)
|
19
(21.1)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
26
40%
|
30
32.3%
|
16
37.2%
|
72
35.8%
|
| Male |
39
60%
|
63
67.7%
|
27
62.8%
|
129
64.2%
|
Outcome Measures
| Title | Number of Participants With All-Cause Mortality |
|---|---|
| Description | The primary efficacy endpoint was the evaluation of the effect of brincidofovir (BCV) on all-cause mortality when used for the treatment of disseminated adenovirus (AdV) disease in all hematopoietic cell transplant (HCT) recipients. The primary endpoint associated with this objective was all-cause mortality through Day 60. |
| Time Frame | 60 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Cohort A | Cohort B | Cohort C |
|---|---|---|---|
| Arm/Group Description | Allogeneic hematopoietic cell transplant recipients at risk of progression to disseminated adenovirus (AdV) disease (i.e., subjects with either asymptomatic AdV infection or localized adenovirus disease) and who weighed ≤120 kg. Subjects who weighed <50 kg received 2 mg/kg (not-to-exceed 100 mg) brincidofovir (BCV) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received BCV 100 mg twice weekly, administered orally as one 100-mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine). | Allogeneic hematopoietic cell transplant recipients with disseminated adenovirus disease who weigh ≤120 kg. Subjects who weighed <50 kg received 2 mg/kg brincidofovir (BCV; not to exceed 100 mg) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received 100 mg BCV twice weekly, administered orally as one 100 mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine). | Allogeneic hematopoietic cell transplant recipients who weighed >120 kg and all other immunocompromised subjects with disseminated adenovirus (AdV) disease or subjects who were at risk of progression to disseminated AdV disease, as well as non-immunocompromised subjects with disseminated AdV disease. Subjects who weighed <50 kg received 2 mg/kg (not to exceed 100 mg) brincidofovir (BCV) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received 100 mg BCV twice weekly, administered orally as one 100-mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine). |
| Measure Participants | 65 | 93 | 43 |
| Count of Participants [Participants] |
9
13.8%
|
27
29%
|
8
18.6%
|
| Title | Number of Participants With Reduction in Adenovirus Viremia |
|---|---|
| Description | A secondary endpoint was the evaluation of virologic response (plasma adenovirus [AdV] DNA viremia) to brincidofovir treatment. Blood (plasma) was collected at screening, before dosing on Day 1 (to establish baseline), and at each subsequent assessment during the treatment and post-treatment phases for the analysis of AdV DNA viremia. All samples collected for analysis of AdV were analyzed by the designated central virology laboratory using proprietary real-time quantitative polymerase chain reaction (qPCR) assays. AdV in plasma were analyzed using the 7500 AdV qPCR Test, where the standardized assay plasma ranged from 190 copies/mL to 1 X 10^10 copies/mL. A "positive or detectable" result referred to the measurement of AdV DNA at concentrations ≥190 copies/mL, a result below the lower limit of detection (LLOQ) (i.e., not detected) was imputed as 1 copy/mL, and a result below the lower limit of quantitation but detected will be imputed at 1 unit less than LLOQ (e.g., 189 copies/mL). |
| Time Frame | Assessed 13 weeks (through 7 days post-last BCV dose); during treatment up to 12 weeks reported |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects with AdV viremia at baseline in the Intention-to-Treat Analysis Set. The Intention-to-Treat Analysis Set included all subjects who received at least 1 dose of BCV. |
| Arm/Group Title | Cohort A | Cohort B | Cohort C |
|---|---|---|---|
| Arm/Group Description | Allogeneic hematopoietic cell transplant recipients at risk of progression to disseminated adenovirus (AdV) disease (i.e., subjects with either asymptomatic AdV infection or localized adenovirus disease) and who weighed ≤120 kg. Subjects who weighed <50 kg received 2 mg/kg (not-to-exceed 100 mg) brincidofovir (BCV) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received BCV 100 mg twice weekly, administered orally as one 100-mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine). | Allogeneic hematopoietic cell transplant recipients with disseminated adenovirus disease who weigh ≤120 kg. Subjects who weighed <50 kg received 2 mg/kg brincidofovir (BCV; not to exceed 100 mg) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received 100 mg BCV twice weekly, administered orally as one 100 mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine). | Allogeneic hematopoietic cell transplant recipients who weighed >120 kg and all other immunocompromised subjects with disseminated adenovirus (AdV) disease or subjects who were at risk of progression to disseminated AdV disease, as well as non-immunocompromised subjects with disseminated AdV disease. Subjects who weighed <50 kg received 2 mg/kg (not to exceed 100 mg) brincidofovir (BCV) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received 100 mg BCV twice weekly, administered orally as one 100-mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine). |
| Measure Participants | 41 | 86 | 30 |
| Undetectable AdV viremia at any time on-treatment |
30
46.2%
|
52
55.9%
|
17
39.5%
|
| Undetectable AdV viremia at last on-treatment value |
25
38.5%
|
41
44.1%
|
16
37.2%
|
| Title | Mean Minimum On-treatment Value log10 Copies/mL Change From Baseline |
|---|---|
| Description | A secondary endpoint was the evaluation of virologic response (plasma adenovirus [AdV] DNA viremia) to brincidofovir treatment. Blood (plasma) was collected at screening, before dosing on Day 1 (to establish baseline), and at each subsequent assessment during the treatment and post-treatment phases for the analysis of AdV DNA viremia. All samples collected for analysis of AdV were analyzed by the designated central virology laboratory using proprietary real-time quantitative polymerase chain reaction (qPCR) assays. AdV in plasma were analyzed using the 7500 AdV qPCR Test, where the standardized assay plasma ranged from 190 copies/mL to 1 X 10^10 copies/mL. A "positive or detectable" result referred to the measurement of AdV DNA at concentrations ≥190 copies/mL, a result below the lower limit of detection (LLOQ) (i.e., not detected) was imputed as 1 copy/mL, and a result below the lower limit of quantitation but detected will be imputed at 1 unit less than LLOQ (e.g., 189 copies/mL). |
| Time Frame | Baseline to 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who had adenovirus viremia at baseline. |
| Arm/Group Title | Cohort A | Cohort B | Cohort C |
|---|---|---|---|
| Arm/Group Description | Allogeneic hematopoietic cell transplant recipients at risk of progression to disseminated adenovirus (AdV) disease (i.e., subjects with either asymptomatic AdV infection or localized adenovirus disease) and who weighed ≤120 kg. Subjects who weighed <50 kg received 2 mg/kg (not-to-exceed 100 mg) brincidofovir (BCV) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received BCV 100 mg twice weekly, administered orally as one 100-mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine). | Allogeneic hematopoietic cell transplant recipients with disseminated adenovirus disease who weigh ≤120 kg. Subjects who weighed <50 kg received 2 mg/kg brincidofovir (BCV; not to exceed 100 mg) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received 100 mg BCV twice weekly, administered orally as one 100 mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine). | Allogeneic hematopoietic cell transplant recipients who weighed >120 kg and all other immunocompromised subjects with disseminated adenovirus (AdV) disease or subjects who were at risk of progression to disseminated AdV disease, as well as non-immunocompromised subjects with disseminated AdV disease. Subjects who weighed <50 kg received 2 mg/kg (not to exceed 100 mg) brincidofovir (BCV) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received 100 mg BCV twice weekly, administered orally as one 100-mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine). |
| Measure Participants | 41 | 86 | 29 |
| Minimum on-treatment value log10 copies/mL change from baseline |
-2.67
(1.559)
|
-3.27
(2.163)
|
-3.11
(2.127)
|
| Last on-treatment value log10 copies/mL change from baseline |
-2.06
(1.898)
|
-2.61
(2.338)
|
-2.87
(2.291)
|
Adverse Events
| Time Frame | Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting. | |||
| Arm/Group Title | Pediatric | Adult | ||
| Arm/Group Description | Subjects aged 2 months to <18 years. | Subjects aged ≥18 years | ||
All Cause Mortality |
||||
| Pediatric | Adult | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Pediatric | Adult | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 93/130 (71.5%) | 58/71 (81.7%) | ||
| Blood and lymphatic system disorders | ||||
| Febrile neutropenia | 3/130 (2.3%) | 1/71 (1.4%) | ||
| Neutropenia | 1/130 (0.8%) | 2/71 (2.8%) | ||
| Pancytopenia | 1/130 (0.8%) | 1/71 (1.4%) | ||
| Thrombotic microangiopathy | 1/130 (0.8%) | 1/71 (1.4%) | ||
| Coagulopathy | 1/130 (0.8%) | 0/71 (0%) | ||
| Histiocytosis haematophagic | 1/130 (0.8%) | 0/71 (0%) | ||
| Lymphopenia | 0/130 (0%) | 1/71 (1.4%) | ||
| Thrombocytopenia | 0/130 (0%) | 1/71 (1.4%) | ||
| Cardiac disorders | ||||
| Arrhythmia | 0/130 (0%) | 1/71 (1.4%) | ||
| Atrial flutter | 0/130 (0%) | 1/71 (1.4%) | ||
| Atrioventricular block complete | 1/130 (0.8%) | 0/71 (0%) | ||
| Cardiac arrest | 0/130 (0%) | 1/71 (1.4%) | ||
| Cardiac failure | 0/130 (0%) | 1/71 (1.4%) | ||
| Cardio-respiratory arrest | 1/130 (0.8%) | 0/71 (0%) | ||
| Left ventricular dysfunction | 1/130 (0.8%) | 0/71 (0%) | ||
| Pericardial effusion | 1/130 (0.8%) | 0/71 (0%) | ||
| Pericarditis | 0/130 (0%) | 1/71 (1.4%) | ||
| Supraventricular tachycardia | 0/130 (0%) | 1/71 (1.4%) | ||
| Tachyarrhythmia | 0/130 (0%) | 1/71 (1.4%) | ||
| Tachycardia | 1/130 (0.8%) | 0/71 (0%) | ||
| Congenital, familial and genetic disorders | ||||
| Metachromatic leukodystrophy | 0/130 (0%) | 1/71 (1.4%) | ||
| Eye disorders | ||||
| Cataract | 1/130 (0.8%) | 0/71 (0%) | ||
| Uveitis | 0/130 (0%) | 1/71 (1.4%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 12/130 (9.2%) | 9/71 (12.7%) | ||
| Vomiting | 4/130 (3.1%) | 6/71 (8.5%) | ||
| Abdominal pain | 5/130 (3.8%) | 1/71 (1.4%) | ||
| Nausea | 0/130 (0%) | 5/71 (7%) | ||
| Gastrointestinal haemorrhage | 4/130 (3.1%) | 0/71 (0%) | ||
| Ileus | 1/130 (0.8%) | 1/71 (1.4%) | ||
| Lower gastrointestinal haemorrhage | 1/130 (0.8%) | 1/71 (1.4%) | ||
| Pneumatosis intestinalis | 2/130 (1.5%) | 0/71 (0%) | ||
| Upper gastrointestinal haemorrhage | 2/130 (1.5%) | 0/71 (0%) | ||
| Abdominal distension | 1/130 (0.8%) | 0/71 (0%) | ||
| Colitis | 1/130 (0.8%) | 0/71 (0%) | ||
| Duodenal ulcer perforation | 0/130 (0%) | 1/71 (1.4%) | ||
| Faecal volume increased | 0/130 (0%) | 1/71 (1.4%) | ||
| Ileal ulcer | 1/130 (0.8%) | 0/71 (0%) | ||
| Ileus paralytic | 0/130 (0%) | 1/71 (1.4%) | ||
| Pancreatitis acute | 1/130 (0.8%) | 0/71 (0%) | ||
| Rectal haemorrhage | 1/130 (0.8%) | 0/71 (0%) | ||
| Small intestinal obstruction | 1/130 (0.8%) | 0/71 (0%) | ||
| General disorders | ||||
| Pyrexia | 15/130 (11.5%) | 4/71 (5.6%) | ||
| Multi-organ failure | 12/130 (9.2%) | 5/71 (7%) | ||
| Asthenia | 0/130 (0%) | 1/71 (1.4%) | ||
| Chest pain | 0/130 (0%) | 1/71 (1.4%) | ||
| Medical device complication | 1/130 (0.8%) | 0/71 (0%) | ||
| Systemic inflammatory response syndrome | 1/130 (0.8%) | 0/71 (0%) | ||
| Hepatobiliary disorders | ||||
| Acute hepatic failure | 2/130 (1.5%) | 0/71 (0%) | ||
| Venoocclusive liver disease | 1/130 (0.8%) | 1/71 (1.4%) | ||
| Autoimmune hepatitis | 1/130 (0.8%) | 0/71 (0%) | ||
| Cholelithiasis | 1/130 (0.8%) | 0/71 (0%) | ||
| Hepatic function abnormal | 0/130 (0%) | 1/71 (1.4%) | ||
| Hyperbilirubinaemia | 1/130 (0.8%) | 0/71 (0%) | ||
| Immune system disorders | ||||
| Acute graft versus host disease | 25/130 (19.2%) | 14/71 (19.7%) | ||
| Chronic graft versus host disease | 0/130 (0%) | 4/71 (5.6%) | ||
| Engraftment syndrome | 1/130 (0.8%) | 0/71 (0%) | ||
| Infections and infestations | ||||
| Septic shock | 8/130 (6.2%) | 23/71 (32.4%) | ||
| Adenovirus infection | 3/130 (2.3%) | 5/71 (7%) | ||
| Staphylococcal bacteraemia | 6/130 (4.6%) | 0/71 (0%) | ||
| BK virus infection | 2/130 (1.5%) | 3/71 (4.2%) | ||
| Device-related infection | 4/130 (3.1%) | 1/71 (1.4%) | ||
| Pneumonia | 2/130 (1.5%) | 2/71 (2.8%) | ||
| Sepsis | 1/130 (0.8%) | 3/71 (4.2%) | ||
| Clostridium difficile colitis | 2/130 (1.5%) | 1/71 (1.4%) | ||
| Escherichia baceraemia | 1/130 (0.8%) | 2/71 (2.8%) | ||
| Klebsiella sepsis | 3/130 (2.3%) | 0/71 (0%) | ||
| Rhinovirus infection | 3/130 (2.3%) | 0/71 (0%) | ||
| Staphylococcal infection | 3/130 (2.3%) | 0/71 (0%) | ||
| Candida infection | 1/130 (0.8%) | 1/71 (1.4%) | ||
| Cystitis viral | 1/130 (0.8%) | 1/71 (1.4%) | ||
| Cytomegalovirus viraemia | 0/130 (0%) | 2/71 (2.8%) | ||
| Enterococcal bacteraemia | 2/130 (1.5%) | 0/71 (0%) | ||
| Enterovirus infection | 2/130 (1.5%) | 0/71 (0%) | ||
| Fungal infection | 2/130 (1.5%) | 0/71 (0%) | ||
| Klebsiella bacteraemia | 2/130 (1.5%) | 0/71 (0%) | ||
| Klebsiella infection | 2/130 (1.5%) | 0/71 (0%) | ||
| Otitis media acute | 1/130 (0.8%) | 1/71 (1.4%) | ||
| Pneumonia adenoviral | 0/130 (0%) | 2/71 (2.8%) | ||
| Pseudomonas infection | 1/130 (0.8%) | 1/71 (1.4%) | ||
| Viral haemorrhagic cystitis | 0/130 (0%) | 2/71 (2.8%) | ||
| Zygomycosis | 2/130 (1.5%) | 0/71 (0%) | ||
| Acinetobacter infection | 1/130 (0.8%) | 0/71 (0%) | ||
| Acute sinusitis | 1/130 (0.8%) | 0/71 (0%) | ||
| Adenoviral hepatitis | 1/130 (0.8%) | 0/71 (0%) | ||
| Bacillus bacteraemia | 1/130 (0.8%) | 0/71 (0%) | ||
| Bacterial infection | 1/130 (0.8%) | 0/71 (0%) | ||
| Bronchopulmonary aspergillosis | 1/130 (0.8%) | 0/71 (0%) | ||
| Candida pneumonia | 1/130 (0.8%) | 0/71 (0%) | ||
| Candida sepsis | 1/130 (0.8%) | 0/71 (0%) | ||
| Cerebral toxoplasmosis | 0/130 (0%) | 1/71 (1.4%) | ||
| Clostridium bacteraemia | 1/130 (0.8%) | 0/71 (0%) | ||
| Clostridium difficile infection | 0/130 (0%) | 1/71 (1.4%) | ||
| Cronobacter infection | 1/130 (0.8%) | 0/71 (0%) | ||
| Cystitis klebsiella | 0/130 (0%) | 1/71 (1.4%) | ||
| Cytomegalovirus infection | 0/130 (0%) | 1/71 (1.4%) | ||
| Enteroabacter bacteraemia | 1/130 (0.8%) | 0/71 (0%) | ||
| Enterobacter sepsis | 1/130 (0.8%) | 0/71 (0%) | ||
| Epstein-Barr viraemia | 1/130 (0.8%) | 0/71 (0%) | ||
| Escherichia urinary tract infection | 0/130 (0%) | 1/71 (1.4%) | ||
| Eye infection bacterial | 1/130 (0.8%) | 0/71 (0%) | ||
| Fusarium infection | 1/130 (0.8%) | 0/71 (0%) | ||
| Gastroenteritis rotavirus | 1/130 (0.8%) | 0/71 (0%) | ||
| Listeriosis | 1/130 (0.8%) | 0/71 (0%) | ||
| Mastoiditis | 0/130 (0%) | 1/71 (1.4%) | ||
| Mycobacterium avium complex infection | 0/130 (0%) | 1/71 (1.4%) | ||
| Oral infection | 1/130 (0.8%) | 0/71 (0%) | ||
| Pancreatitis bacterial | 1/130 (0.8%) | 0/71 (0%) | ||
| Peritonitis | 1/130 (0.8%) | 0/71 (0%) | ||
| Pneumonia staphylococcal | 1/130 (0.8%) | 0/71 (0%) | ||
| Pneumonia streptococcal | 0/130 (0%) | 1/71 (1.4%) | ||
| Pseudomonal bacteraemia | 1/130 (0.8%) | 0/71 (0%) | ||
| Respiratory syncytial virus infection | 1/130 (0.8%) | 0/71 (0%) | ||
| Rotavirus infection | 1/130 (0.8%) | 0/71 (0%) | ||
| Soft tissue infection | 1/130 (0.8%) | 0/71 (0%) | ||
| Staphylococcal sepsis | 1/130 (0.8%) | 0/71 (0%) | ||
| Upper respiratory tract infection | 1/130 (0.8%) | 0/71 (0%) | ||
| Urinary tract infection | 1/130 (0.8%) | 0/71 (0%) | ||
| Urinary tract infection enterococcal | 1/130 (0.8%) | 0/71 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Transplant failure | 3/130 (2.3%) | 1/71 (1.4%) | ||
| Feeding tube complication | 1/130 (0.8%) | 0/71 (0%) | ||
| Post procedural haemorrhage | 0/130 (0%) | 1/71 (1.4%) | ||
| Stoma complication | 1/130 (0.8%) | 0/71 (0%) | ||
| Investigations | ||||
| Blood bilirubin increased | 6/130 (4.6%) | 0/71 (0%) | ||
| Alanine aminotransferase increased | 2/130 (1.5%) | 0/71 (0%) | ||
| Transaminases increased | 1/130 (0.8%) | 1/71 (1.4%) | ||
| Blood potassium decreased | 1/130 (0.8%) | 0/71 (0%) | ||
| Respiratory syncytial virus test positive | 0/130 (0%) | 1/71 (1.4%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 3/130 (2.3%) | 2/71 (2.8%) | ||
| Lactic acidosis | 1/130 (0.8%) | 1/71 (1.4%) | ||
| Metabolic acidosis | 2/130 (1.5%) | 0/71 (0%) | ||
| Acidosis | 1/130 (0.8%) | 0/71 (0%) | ||
| Diabetes mellitus | 1/130 (0.8%) | 0/71 (0%) | ||
| Fluid overload | 1/130 (0.8%) | 0/71 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 1/130 (0.8%) | 0/71 (0%) | ||
| Myositis | 1/130 (0.8%) | 0/71 (0%) | ||
| Synovitis | 1/130 (0.8%) | 0/71 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Acute myeloid leukaemia recurrent | 3/130 (2.3%) | 2/71 (2.8%) | ||
| Leukaemia recurrent | 1/130 (0.8%) | 0/71 (0%) | ||
| Post transplant lymphoproliferative disorder | 1/130 (0.8%) | 0/71 (0%) | ||
| Nervous system disorders | ||||
| Posterior reversible encephalopathy syndrome | 2/130 (1.5%) | 2/71 (2.8%) | ||
| Brain mass | 0/130 (0%) | 1/71 (1.4%) | ||
| Central nervous system lesion | 1/130 (0.8%) | 0/71 (0%) | ||
| Cerebral ventricle dilatation | 1/130 (0.8%) | 0/71 (0%) | ||
| Haemorrhagic stroke | 1/130 (0.8%) | 0/71 (0%) | ||
| Metabolic encephalopathy | 0/130 (0%) | 1/71 (1.4%) | ||
| Seizure | 1/130 (0.8%) | 0/71 (0%) | ||
| Serotonin syndrome | 0/130 (0%) | 1/71 (1.4%) | ||
| Syncope | 0/130 (0%) | 1/71 (1.4%) | ||
| Wernicke's encephalopathy | 1/130 (0.8%) | 0/71 (0%) | ||
| Psychiatric disorders | ||||
| Mental status changes | 1/130 (0.8%) | 2/71 (2.8%) | ||
| Renal and urinary disorders | ||||
| Acute kidney injury | 12/130 (9.2%) | 4/71 (5.6%) | ||
| Renal failure | 3/130 (2.3%) | 2/71 (2.8%) | ||
| Renal impairment | 0/130 (0%) | 2/71 (2.8%) | ||
| Chronic kidney disease | 1/130 (0.8%) | 0/71 (0%) | ||
| Oliguria | 1/130 (0.8%) | 0/71 (0%) | ||
| Renal tubular acidosis | 0/130 (0%) | 1/71 (1.4%) | ||
| Renal tubular necrosis | 0/130 (0%) | 1/71 (1.4%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Respiratory failure | 14/130 (10.8%) | 5/71 (7%) | ||
| Pulmonary haemorrhage | 6/130 (4.6%) | 0/71 (0%) | ||
| Acute respiratory failure | 3/130 (2.3%) | 2/71 (2.8%) | ||
| Hypoxia | 3/130 (2.3%) | 2/71 (2.8%) | ||
| Pneumomediastinum | 2/130 (1.5%) | 1/71 (1.4%) | ||
| Acute respiratory distress syndrome | 1/130 (0.8%) | 0/71 (0%) | ||
| Aspiration | 1/130 (0.8%) | 0/71 (0%) | ||
| Diffuse alveolar damage | 0/130 (0%) | 1/71 (1.4%) | ||
| Dyspnoea | 1/130 (0.8%) | 0/71 (0%) | ||
| Epistaxis | 1/130 (0.8%) | 0/71 (0%) | ||
| Interstitial lung disease | 0/130 (0%) | 1/71 (1.4%) | ||
| Lung disorder | 1/130 (0.8%) | 0/71 (0%) | ||
| Organising pneumonia | 1/130 (0.8%) | 0/71 (0%) | ||
| Pleural effusion | 1/130 (0.8%) | 0/71 (0%) | ||
| Pleuritic pain | 0/130 (0%) | 1/71 (1.4%) | ||
| Pneumonia aspiration | 0/130 (0%) | 1/71 (1.4%) | ||
| Pulmonary oedema | 1/130 (0.8%) | 0/71 (0%) | ||
| Respiratory acidosis | 1/130 (0.8%) | 0/71 (0%) | ||
| Respiratory distress | 2/130 (1.5%) | 1/71 (1.4%) | ||
| Pneumothorax | 1/130 (0.8%) | 1/71 (1.4%) | ||
| Respiratory depression | 0/130 (0%) | 1/71 (1.4%) | ||
| Respiratory disorder | 1/130 (0.8%) | 0/71 (0%) | ||
| Vascular disorders | ||||
| Hypotension | 4/130 (3.1%) | 3/71 (4.2%) | ||
| Hypertension | 1/130 (0.8%) | 3/71 (4.2%) | ||
| Deep vein thrombosis | 1/130 (0.8%) | 1/71 (1.4%) | ||
| Microangiopathy | 1/130 (0.8%) | 0/71 (0%) | ||
| Orthostatic hypotension | 0/130 (0%) | 1/71 (1.4%) | ||
| Shock haemorrhagic | 1/130 (0.8%) | 0/71 (0%) | ||
| Visceral arterial ischaemia | 0/130 (0%) | 1/71 (1.4%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Pediatric | Adult | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 127/130 (97.7%) | 71/71 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Neutropenia | 16/130 (12.3%) | 7/71 (9.9%) | ||
| Anaemia | 7/130 (5.4%) | 2/71 (2.8%) | ||
| Thrombocytopenia | 4/130 (3.1%) | 4/71 (5.6%) | ||
| Pancytopenia | 1/130 (0.8%) | 4/71 (5.6%) | ||
| Cardiac disorders | ||||
| Tachycardia | 16/130 (12.3%) | 4/71 (5.6%) | ||
| Eye disorders | ||||
| Vision blurred | 1/130 (0.8%) | 4/71 (5.6%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 58/130 (44.6%) | 26/71 (36.6%) | ||
| Vomiting | 27/130 (20.8%) | 20/71 (28.2%) | ||
| Abdominal pain | 20/130 (15.4%) | 23/71 (32.4%) | ||
| Nausea | 10/130 (7.7%) | 18/71 (25.4%) | ||
| Abdominal distension | 8/130 (6.2%) | 11/71 (15.5%) | ||
| Constipation | 13/130 (10%) | 5/71 (7%) | ||
| Gastrointestinal haemorrhage | 9/130 (6.9%) | 3/71 (4.2%) | ||
| Abdominal pain upper | 3/130 (2.3%) | 4/71 (5.6%) | ||
| Colitis | 7/130 (5.4%) | 0/71 (0%) | ||
| Dyspepsia | 3/130 (2.3%) | 4/71 (5.6%) | ||
| General disorders | ||||
| Pyrexia | 48/130 (36.9%) | 16/71 (22.5%) | ||
| Fatigue | 5/130 (3.8%) | 14/71 (19.7%) | ||
| Multi-organ failure | 12/130 (9.2%) | 5/71 (7%) | ||
| Oedema peripheral | 5/130 (3.8%) | 8/71 (11.3%) | ||
| Asthenia | 1/130 (0.8%) | 4/71 (5.6%) | ||
| Immune system disorders | ||||
| Acute graft versus host disease | 43/130 (33.1%) | 23/71 (32.4%) | ||
| Chronic graft versus host disease | 4/130 (3.1%) | 5/71 (7%) | ||
| Infections and infestations | ||||
| Candida infection | 8/130 (6.2%) | 7/71 (9.9%) | ||
| BK virus infection | 8/130 (6.2%) | 6/71 (8.5%) | ||
| Clostridium difficile colitis | 9/130 (6.9%) | 3/71 (4.2%) | ||
| Staphylococcal bacteraemia | 11/130 (8.5%) | 1/71 (1.4%) | ||
| Pneumonia | 5/130 (3.8%) | 6/71 (8.5%) | ||
| Rhinovirus infection | 10/130 (7.7%) | 1/71 (1.4%) | ||
| Septic shock | 8/130 (6.2%) | 3/71 (4.2%) | ||
| Adenovirus infection | 3/130 (2.3%) | 5/71 (7%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 25/130 (19.2%) | 8/71 (11.3%) | ||
| Aspartate aminotransferase increased | 23/130 (17.7%) | 8/71 (11.3%) | ||
| Blood bilirubin increased | 23/130 (17.7%) | 5/71 (7%) | ||
| Blood potassium decreased | 20/130 (15.4%) | 6/71 (8.5%) | ||
| Blood glucose increased | 14/130 (10.8%) | 8/71 (11.3%) | ||
| Blood magnesium decreased | 19/130 (14.6%) | 2/71 (2.8%) | ||
| Transaminases increased | 8/130 (6.2%) | 6/71 (8.5%) | ||
| Blood albumin decreased | 11/130 (8.5%) | 1/71 (1.4%) | ||
| Blood sodium increased | 9/130 (6.9%) | 3/71 (4.2%) | ||
| Blood sodium decreased | 9/130 (6.9%) | 2/71 (2.8%) | ||
| Blood calcium decreased | 10/130 (7.7%) | 0/71 (0%) | ||
| Blood potassium increased | 7/130 (5.4%) | 3/71 (4.2%) | ||
| Gamma-glutamyltranferase increased | 7/130 (5.4%) | 2/71 (2.8%) | ||
| Weight decreased | 5/130 (3.8%) | 4/71 (5.6%) | ||
| Blood alkaline phosphatase increased | 2/130 (1.5%) | 5/71 (7%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 10/130 (7.7%) | 11/71 (15.5%) | ||
| Dehydration | 13/130 (10%) | 5/71 (7%) | ||
| Fluid overload | 10/130 (7.7%) | 3/71 (4.2%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 9/130 (6.9%) | 3/71 (4.2%) | ||
| Nervous system disorders | ||||
| Headache | 4/130 (3.1%) | 4/71 (5.6%) | ||
| Dizziness | 1/130 (0.8%) | 5/71 (7%) | ||
| Psychiatric disorders | ||||
| Depression | 7/130 (5.4%) | 4/71 (5.6%) | ||
| Insomnia | 9/130 (6.9%) | 2/71 (2.8%) | ||
| Mental status changes | 3/130 (2.3%) | 6/71 (8.5%) | ||
| Agitation | 4/130 (3.1%) | 4/71 (5.6%) | ||
| Renal and urinary disorders | ||||
| Acute kidney injury | 22/130 (16.9%) | 7/71 (9.9%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Respiratory failure | 17/130 (13.1%) | 5/71 (7%) | ||
| Cough | 9/130 (6.9%) | 8/71 (11.3%) | ||
| Epistaxis | 8/130 (6.2%) | 7/71 (9.9%) | ||
| Dyspnoea | 5/130 (3.8%) | 9/71 (12.7%) | ||
| Hypoxia | 6/130 (4.6%) | 7/71 (9.9%) | ||
| Pleural effusion | 7/130 (5.4%) | 4/71 (5.6%) | ||
| Nasal congestion | 7/130 (5.4%) | 3/71 (4.2%) | ||
| Atelectasis | 7/130 (5.4%) | 1/71 (1.4%) | ||
| Pulmonary haemorrhage | 8/130 (6.2%) | 0/71 (0%) | ||
| Pulmonary oedema | 7/130 (5.4%) | 1/71 (1.4%) | ||
| Oropharyngeal pain | 1/130 (0.8%) | 4/71 (5.6%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 11/130 (8.5%) | 0/71 (0%) | ||
| Rash | 7/130 (5.4%) | 4/71 (5.6%) | ||
| Dry skin | 5/130 (3.8%) | 4/71 (5.6%) | ||
| Vascular disorders | ||||
| Hypotension | 17/130 (13.1%) | 14/71 (19.7%) | ||
| Hypertension | 12/130 (9.2%) | 7/71 (9.9%) | ||
| Deep vein thrombosis | 2/130 (1.5%) | 5/71 (7%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Within 12 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 |
- CMX001-304