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

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

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).

Study Overview

• Status: Withdrawn
• Conditions: Adenovirus
• Intervention / Treatment: Drug: Brincidofovir; Drug: Standard of Care

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20132
    • University Vita-Salute San Raffaele. San Faffaele Scientific Institute
• Spain
  • Barcelona, Spain, 8035
    • Hospital Universitari Vall d'Hebron
  • Salamanca, Spain, 37007
    • Hospital Clínico Universitario de Salamanca
  • Valencia, Spain, 46016
    • Hospital Universitari i Politecnic La Fe
• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chigago
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Womens Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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).; Other Names: BCV
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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	15 days
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	15 days
Incidence (number and percentage of subjects) of treatment-emergent adverse events		22 days

Collaborators and Investigators

• Sponsor: Chimerix

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2018
• Primary Completion (Actual): May 10, 2019
• Study Completion (Actual): May 10, 2019

Study Registration Dates

• First Submitted: April 26, 2018
• First Submitted That Met QC Criteria: May 18, 2018
• First Posted (Actual): May 22, 2018

Study Record Updates

• Last Update Posted (Actual): July 21, 2021
• Last Update Submitted That Met QC Criteria: July 19, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; DNA Virus Infections; Sepsis; Viremia; Adenoviridae Infections; Anti-Infective Agents; Antiviral Agents; Brincidofovir
• Other Study ID Numbers: CMX001-211

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No