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

• ClinicalTrials.gov Identifier: NCT03532035
• Recruitment Status: Terminated
• First Posted: May 22, 2018
• Last Update Posted: May 17, 2019
• Sponsor: Chimerix
• Information provided by (Responsible Party): Chimerix

Study Description

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

Study Design

• 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

Arms and Interventions

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.

Outcome Measures

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 ]

Eligibility Criteria

• 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.

Contacts and Locations

Locations

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

More Information

• Responsible Party: Chimerix
• ClinicalTrials.gov Identifier: NCT03532035 History of Changes
• Other Study ID Numbers: CMX001-211
• First Posted: May 22, 2018
• Last Update Posted: May 17, 2019
• Last Verified: May 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Adenoviridae Infections; Viremia; DNA Virus Infections; Virus Diseases; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Ganciclovir; Antiviral Agents; Anti-Infective Agents