Adenovirus
Conditions
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).
Interventions
DRUGBrincidofovir
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).
DRUGStandard of Care
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.
Sponsors
Jazz Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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) 1. 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 2. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma area under the curve (AUC) of BCV | 15 days | 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 | 15 days | 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 | 22 days | — |
Countries
Italy, Spain, United States
Outcome results
None listed