Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03532035
Recruitment Status : Terminated (terminated due to low enrollment rate)
First Posted : May 22, 2018
Last Update Posted : May 17, 2019
Sponsor:
Information provided by (Responsible Party):
Chimerix

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).

Condition or disease Intervention/treatment Phase
Adenovirus Drug: Brincidofovir Drug: Standard of Care Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Controlled, Open-Label, Multiple Ascending Dose Study of Intravenous Brincidofovir in Adult Allogeneic Hematopoietic Cell Transplant Recipients With Adenovirus Viremia
Actual Study Start Date : December 15, 2018
Actual Primary Completion Date : May 10, 2019
Actual Study Completion Date : May 10, 2019

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 Name: 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.




Primary Outcome Measures :
  1. 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

  2. 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

  3. Incidence (number and percentage of subjects) of treatment-emergent adverse events [ Time Frame: 22 days ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03532035


Locations
Layout table for location information
United States, California
UCLA Medical Center
Los Angeles, California, United States, 90095
United States, Illinois
University of Chigago
Chicago, Illinois, United States, 60637
United States, Massachusetts
Brigham and Womens Hospital
Boston, Massachusetts, United States, 02115
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Italy
University Vita-Salute San Raffaele. San Faffaele Scientific Institute
Milan, Italy, 20132
Spain
Hospital Universitari Vall d'Hebron
Barcelona, Spain, 8035
Hospital Clinico Universitario de Salamanca
Salamanca, Spain, 37007
Hospital Universitari I Politecnic la Fe
Valencia, Spain, 46016
Sponsors and Collaborators
Chimerix

Layout table for additonal information
Responsible Party: Chimerix
ClinicalTrials.gov Identifier: NCT03532035     History of Changes
Other Study ID Numbers: CMX001-211
First Posted: May 22, 2018    Key Record Dates
Last Update Posted: May 17, 2019
Last Verified: May 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Adenoviridae Infections
Viremia
DNA Virus Infections
Virus Diseases
Sepsis
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Ganciclovir
Antiviral Agents
Anti-Infective Agents