Clinical trial NCT03532035: 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
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Adenovirus
Lead sponsor: Chimerix
Sponsor class: INDUSTRY
First posted: 2018-05-22
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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)

  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.

Primary outcomes:
measure: Plasma area under the curve (AUC) of BCV
timeFrame: 15 days
measure: Plasma Cmax of BCV
timeFrame: 15 days
measure: Incidence (number and percentage of subjects) of treatment-emergent adverse events
timeFrame: 22 days
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Chicago
country: United States
facility: University of Chigago
state: Illinois
city: Boston
country: United States
facility: Brigham and Womens Hospital
state: Massachusetts
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Milan
country: Italy
facility: University Vita-Salute San Raffaele. San Faffaele Scientific Institute
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
city: Valencia
country: Spain
facility: Hospital Universitari I Politecnic la Fe
Study officials:
References: