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

Adenovirus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03532035
• Other study ID #: CMX001-211
• Status: Withdrawn
• Phase: Phase 2
• Start date: December 15, 2018
• Est. completion date: May 10, 2019

Study information

• Verified date: July 2021
• Source: Chimerix
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: May 10, 2019
• Est. primary completion date: May 10, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Adenoviridae Infections
• Adenovirus
• Viremia

Intervention

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).
• 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.

Locations

Country	Name	City	State
Italy	University Vita-Salute San Raffaele. San Faffaele Scientific Institute	Milan
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Clinico Universitario de Salamanca	Salamanca
Spain	Hospital Universitari I Politecnic la Fe	Valencia
United States	Brigham and Womens Hospital	Boston	Massachusetts
United States	University of Chigago	Chicago	Illinois
United States	MD Anderson Cancer Center	Houston	Texas
United States	UCLA Medical Center	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Chimerix

Countries where clinical trial is conducted

United States,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Incidence (number and percentage of subjects) of treatment-emergent adverse events		22 days