Open Label Study of IV Brincidofovir in Adult Transplant Recipients With Adenovirus Viremia

Overview

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).

Full Title of Study: “A Randomized, Controlled, Open-Label, Multiple Ascending Dose Study of Intravenous Brincidofovir in Adult Allogeneic Hematopoietic Cell Transplant Recipients With Adenovirus Viremia”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: May 10, 2019

Interventions

  • Drug: Brincidofovir
    • 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).
  • Drug: Standard 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.

Arms, Groups and Cohorts

  • Experimental: Brincidofovir (BCV)
    • 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.
  • Active Comparator: Standard of Care (SoC)
    • 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.

Clinical Trial Outcome Measures

Primary Measures

  • Plasma area under the curve (AUC) of BCV
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 22 days

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 99 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Chimerix
  • Provider of Information About this Clinical Study
    • Sponsor

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