Back to resultsOpen Label Study of IV Brincidofovir in Adult Transplant Recipients With Adenovirus Viremia
Primary Purpose
Adenovirus
Status
Withdrawn
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Brincidofovir
Standard of Care
Sponsored by
About this trial
This is an interventional treatment trial for Adenovirus
Eligibility Criteria
Inclusion Criteria:
- Be ≥ 18-years-old (or per local law or regulations on legal age of consent).
- Have received an allogeneic hematopoietic cell transplant (HCT) within the previous 100 days.
- Have plasma AdV DNA viremia ≥ 1,000 copies/mL (via quantitative polymerase chain reaction assay; local results must be confirmed by the designated central virology laboratory).
Exclusion Criteria:
- Diarrhea meeting the US National Institutes of Health (NIH)/National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater
Acute graft versus host disease (GVHD)
- NIH Stage 2 or higher acute GVHD of the gut (i.e., diarrhea > 1,000 mL/day, or severe abdominal pain with or without ileus) or liver (i.e., bilirubin > 3 mg/dL : > 51 μmol/L) within 7 days prior to Day 1
- Any NIH Stage 3 or Stage 4 acute GVHD within 7 days prior to Day 1
- Concurrent human immunodeficiency virus or active hepatitis B or C infection
- An estimated creatinine clearance of < 30 mL/min, and/or use of renal replacement therapy within 7 days prior to Day 1.
- Poor clinical prognosis, including active malignancy, irreversible organ failure, use of vasopressors, requirement for mechanical ventilation, resting oxygen saturation < 88%, or Pulmonary Arterial oxygen (PaO2) ≤ 55 mm Hg without supplemental oxygen at any time within 7 days prior to Day 1.
- Receiving or anticipated to start systemic cyclosporine immunosuppressant treatment during study participation.
- Received treatment with CDV within 14 days prior to Day 1.
- Previous receipt of cell-based anti-AdV therapy within 6 weeks prior to Day 1 or prior receipt of an anti-AdV vaccine at any time.
- Consumed food products containing sesame seeds, sesame oil, or dietary supplements containing sesamin within 3 days prior to Day 1.
- Received any investigational drug within 28 days prior to Day 1 or currently participating in another interventional study.
- Pregnant or breastfeeding.
Sites / Locations
- UCLA Medical Center
- University of Chigago
- Brigham and Womens Hospital
- MD Anderson Cancer Center
- University Vita-Salute San Raffaele. San Faffaele Scientific Institute
- Hospital Universitari Vall d'Hebron
- Hospital Clinico Universitario de Salamanca
- Hospital Universitari I Politecnic la Fe
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Brincidofovir (BCV)
Standard of Care (SoC)
Arm Description
Cohort 1: BCV 10 mg twice weekly via IV infusion over 2 hours Cohort 2: BCV 15 mg twice weekly via IV infusion over 2 hours Cohort 3: BCV In Cohort 3, the actual dose may be higher or lower than doses administered in previous cohorts; the maximum dose of IV BCV will be ≤ 25 mg.
Subjects randomized to the SoC in each cohort will be managed per local institutional guidelines and investigator judgement. SoC treatment options may include, but are not limited to, taking a "watch and-wait" approach, with or without decreased immunosuppression (i.e., no active treatment), or treatment with IV Cidofovir (CDV), ganciclovir, or ribavirin.
Outcomes
Primary Outcome Measures
Plasma area under the curve (AUC) of BCV
BCV AUC will be determined by analysis of BCV plasma concentrations at the following time points after the start of Dose 1 and Dose 4: 30 minutes, and 2.5, 3, 4, 8, 10, 12, 36, and 72 hours
Plasma Cmax of BCV
BCV Cmax will be determined by analysis of BCV plasma concentrations at the following time points after the start of Dose 1 and Dose 4: 30 minutes, and 2.5, 3, 4, 8, 10, 12, 36, and 72 hours
Incidence (number and percentage of subjects) of treatment-emergent adverse events
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03532035
Brief Title
Open Label Study of IV Brincidofovir in Adult Transplant Recipients With Adenovirus Viremia
Official Title
A Randomized, Controlled, Open-Label, Multiple Ascending Dose Study of Intravenous Brincidofovir in Adult Allogeneic Hematopoietic Cell Transplant Recipients With Adenovirus Viremia
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Withdrawn
Why Stopped
terminated due to low enrollment rate
Study Start Date
December 15, 2018 (Actual)
Primary Completion Date
May 10, 2019 (Actual)
Study Completion Date
May 10, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chimerix
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a randomized, controlled, open-label, multicenter study to evaluate the safety, tolerability, pharmacokinetic (PK), and adenovirus (AdV) antiviral activity of multiple ascending doses of IV brincidofovir (BCV). Approximately 30 eligible subjects will be sequentially enrolled into 1 of 3 planned cohorts. Within each cohort, subjects will be randomized in a 4:1 ratio to receive IV BCV dosed twice weekly (BIW) (on Days 1, 4, 8, and 11) or to receive investigator-assigned standard of care (SoC).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenovirus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Brincidofovir (BCV)
Arm Type
Experimental
Arm Description
Cohort 1: BCV 10 mg twice weekly via IV infusion over 2 hours
Cohort 2: BCV 15 mg twice weekly via IV infusion over 2 hours
Cohort 3: BCV In Cohort 3, the actual dose may be higher or lower than doses administered in previous cohorts; the maximum dose of IV BCV will be ≤ 25 mg.
Arm Title
Standard of Care (SoC)
Arm Type
Active Comparator
Arm Description
Subjects randomized to the SoC in each cohort will be managed per local institutional guidelines and investigator judgement. SoC treatment options may include, but are not limited to, taking a "watch and-wait" approach, with or without decreased immunosuppression (i.e., no active treatment), or treatment with IV Cidofovir (CDV), ganciclovir, or ribavirin.
Intervention Type
Drug
Intervention Name(s)
Brincidofovir
Other Intervention Name(s)
BCV
Intervention Description
Subjects will receive BCV administered as a continuous IV infusion over 2 hours twice weekly (on Days 1, 4, 8, and 11) for a period of 2 weeks (total of 4 doses).
Intervention Type
Drug
Intervention Name(s)
Standard of Care
Intervention Description
Subjects randomized to the SoC in each cohort will be managed per local institutional guidelines and investigator judgement. SoC treatment options may include, but are not limited to, taking a "watch and-wait" approach, with or without decreased immunosuppression (i.e., no active treatment), or treatment with IV CDV, ganciclovir, or ribavirin.
Primary Outcome Measure Information:
Title
Plasma area under the curve (AUC) of BCV
Description
BCV AUC will be determined by analysis of BCV plasma concentrations at the following time points after the start of Dose 1 and Dose 4: 30 minutes, and 2.5, 3, 4, 8, 10, 12, 36, and 72 hours
Time Frame
15 days
Title
Plasma Cmax of BCV
Description
BCV Cmax will be determined by analysis of BCV plasma concentrations at the following time points after the start of Dose 1 and Dose 4: 30 minutes, and 2.5, 3, 4, 8, 10, 12, 36, and 72 hours
Time Frame
15 days
Title
Incidence (number and percentage of subjects) of treatment-emergent adverse events
Time Frame
22 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Be ≥ 18-years-old (or per local law or regulations on legal age of consent).
Have received an allogeneic hematopoietic cell transplant (HCT) within the previous 100 days.
Have plasma AdV DNA viremia ≥ 1,000 copies/mL (via quantitative polymerase chain reaction assay; local results must be confirmed by the designated central virology laboratory).
Exclusion Criteria:
Diarrhea meeting the US National Institutes of Health (NIH)/National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater
Acute graft versus host disease (GVHD)
NIH Stage 2 or higher acute GVHD of the gut (i.e., diarrhea > 1,000 mL/day, or severe abdominal pain with or without ileus) or liver (i.e., bilirubin > 3 mg/dL : > 51 μmol/L) within 7 days prior to Day 1
Any NIH Stage 3 or Stage 4 acute GVHD within 7 days prior to Day 1
Concurrent human immunodeficiency virus or active hepatitis B or C infection
An estimated creatinine clearance of < 30 mL/min, and/or use of renal replacement therapy within 7 days prior to Day 1.
Poor clinical prognosis, including active malignancy, irreversible organ failure, use of vasopressors, requirement for mechanical ventilation, resting oxygen saturation < 88%, or Pulmonary Arterial oxygen (PaO2) ≤ 55 mm Hg without supplemental oxygen at any time within 7 days prior to Day 1.
Receiving or anticipated to start systemic cyclosporine immunosuppressant treatment during study participation.
Received treatment with CDV within 14 days prior to Day 1.
Previous receipt of cell-based anti-AdV therapy within 6 weeks prior to Day 1 or prior receipt of an anti-AdV vaccine at any time.
Consumed food products containing sesame seeds, sesame oil, or dietary supplements containing sesamin within 3 days prior to Day 1.
Received any investigational drug within 28 days prior to Day 1 or currently participating in another interventional study.
Pregnant or breastfeeding.
Facility Information:
Facility Name
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of Chigago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Brigham and Womens Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University Vita-Salute San Raffaele. San Faffaele Scientific Institute
City
Milan
ZIP/Postal Code
20132
Country
Italy
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
8035
Country
Spain
Facility Name
Hospital Clinico Universitario de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
Hospital Universitari I Politecnic la Fe
City
Valencia
ZIP/Postal Code
46016
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
Open Label Study of IV Brincidofovir in Adult Transplant Recipients With Adenovirus Viremia
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