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Study to Assess the Safety and Efficacy of Brincidofovir in Treatment of Early Versus Late Adenovirus Infection

Phase 3
Completed
Conditions
Adenovirus Infection
Interventions
Registration Number
NCT02087306
Lead Sponsor
Chimerix
Brief Summary

This was a Phase 3 open-label, non-randomized, multicenter study of oral brincidofovir (BCV) administered twice weekly for the treatment of adenovirus (AdV) infection detected during asymptomatic AdV viremia or during symptomatic AdV infection.

Detailed Description

This was a Phase 3 open-label, non-randomized, multicenter study of the safety, tolerability, and efficacy of oral brincidofovir (BCV) when administered twice weekly for the treatment of disseminated adenovirus (AdV) disease and for the treatment of AdV infection when treatment was initiated in subjects who were at risk of progression to disseminated disease (i.e., during the asymptomatic or localized phases of infection).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
201
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
BrincidofovirBrincidofovirSubjects who weighed \<50 kg received 2 mg/kg (not to exceed 100 mg) BCV twice weekly administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received 100 mg BCV twice weekly administered orally as one 100 mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine).
Primary Outcome Measures
NameTimeMethod
Number of Participants With All-Cause Mortality60 days

The primary efficacy endpoint was the evaluation of the effect of brincidofovir (BCV) on all-cause mortality when used for the treatment of disseminated adenovirus (AdV) disease in all hematopoietic cell transplant (HCT) recipients. The primary endpoint associated with this objective was all-cause mortality through Day 60.

Secondary Outcome Measures
NameTimeMethod
Number of Participants With Reduction in Adenovirus ViremiaAssessed 13 weeks (through 7 days post-last BCV dose); during treatment up to 12 weeks reported

A secondary endpoint was the evaluation of virologic response (plasma adenovirus \[AdV\] DNA viremia) to brincidofovir treatment. Blood (plasma) was collected at screening, before dosing on Day 1 (to establish baseline), and at each subsequent assessment during the treatment and post-treatment phases for the analysis of AdV DNA viremia. All samples collected for analysis of AdV were analyzed by the designated central virology laboratory using proprietary real-time quantitative polymerase chain reaction (qPCR) assays. AdV in plasma were analyzed using the 7500 AdV qPCR Test, where the standardized assay plasma ranged from 190 copies/mL to 1 X 10\^10 copies/mL. A "positive or detectable" result referred to the measurement of AdV DNA at concentrations ≥190 copies/mL, a result below the lower limit of detection (LLOQ) (i.e., not detected) was imputed as 1 copy/mL, and a result below the lower limit of quantitation but detected will be imputed at 1 unit less than LLOQ (e.g., 189 copies/mL).

Mean Minimum On-treatment Value log10 Copies/mL Change From BaselineBaseline to 12 weeks

A secondary endpoint was the evaluation of virologic response (plasma adenovirus \[AdV\] DNA viremia) to brincidofovir treatment. Blood (plasma) was collected at screening, before dosing on Day 1 (to establish baseline), and at each subsequent assessment during the treatment and post-treatment phases for the analysis of AdV DNA viremia. All samples collected for analysis of AdV were analyzed by the designated central virology laboratory using proprietary real-time quantitative polymerase chain reaction (qPCR) assays. AdV in plasma were analyzed using the 7500 AdV qPCR Test, where the standardized assay plasma ranged from 190 copies/mL to 1 X 10\^10 copies/mL. A "positive or detectable" result referred to the measurement of AdV DNA at concentrations ≥190 copies/mL, a result below the lower limit of detection (LLOQ) (i.e., not detected) was imputed as 1 copy/mL, and a result below the lower limit of quantitation but detected will be imputed at 1 unit less than LLOQ (e.g., 189 copies/mL).

Trial Locations

Locations (33)

Children's Hospital

🇺🇸

New Orleans, Louisiana, United States

Children's National Health System

🇺🇸

Washington, District of Columbia, United States

Montifore Medical Center

🇺🇸

Bronx, New York, United States

Stanford Children's Hospital

🇺🇸

Palo Alto, California, United States

Children's Hospital Colorado

🇺🇸

Aurora, Colorado, United States

Stanford University

🇺🇸

Stanford, California, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

Cook Children's Medical Center

🇺🇸

Fort Worth, Texas, United States

University of Utah Huntsman Cancer Institute

🇺🇸

Salt Lake City, Utah, United States

Phoenix Children's Hospital

🇺🇸

Phoenix, Arizona, United States

Children's Hospital of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

Children's Hospital Los Angeles

🇺🇸

Los Angeles, California, United States

Johns Hopkins University

🇺🇸

Baltimore, Maryland, United States

Brigham and Woman's Hospital

🇺🇸

Boston, Massachusetts, United States

Fred Hutchingson Cancer Center

🇺🇸

Seattle, Washington, United States

Ann & Robert H. Lurie Children's Hospital of Chicago

🇺🇸

Chicago, Illinois, United States

University of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

Cincinnati Children's Hospital

🇺🇸

Cincinnati, Ohio, United States

Intermountain Healthcare Research

🇺🇸

Salt Lake City, Utah, United States

University of Nebraska

🇺🇸

Omaha, Nebraska, United States

Memorial Sloan Kettering Cancer Center

🇺🇸

New York, New York, United States

Weill Cornell Medical College/ New York Presbyterian Hospital

🇺🇸

New York, New York, United States

Levine Children's Hospital

🇺🇸

Charlotte, North Carolina, United States

Baylor College of Medicine

🇺🇸

Houston, Texas, United States

Medical College of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

University of Chicago

🇺🇸

Chicago, Illinois, United States

Seattle Children's Hospital

🇺🇸

Seattle, Washington, United States

Children's Healthcare of Atlanta, Aflac Cancer and Blood Center

🇺🇸

Atlanta, Georgia, United States

Children's Hospital of Pittsburgh

🇺🇸

Pittsburgh, Pennsylvania, United States

St. Jude Children's Hospital

🇺🇸

Memphis, Tennessee, United States

Children's Mercy Hospital

🇺🇸

Kansas City, Missouri, United States

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