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

NCT ID: NCT03532035

Last Updated: 2021-07-21

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-15
• Study Completion Date: 2019-05-10

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).

Conditions

Adenovirus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Brincidofovir

Intervention Type: DRUG

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 (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.

Group Type: ACTIVE_COMPARATOR

Standard of Care

Intervention Type: DRUG

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.

Interventions

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).

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

BCV

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jazz Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UCLA Medical Center

Los Angeles, California, United States

University of Chigago

Chicago, Illinois, United States

Brigham and Womens Hospital

Boston, Massachusetts, United States

MD Anderson Cancer Center

Houston, Texas, United States

University Vita-Salute San Raffaele. San Faffaele Scientific Institute

Milan, , Italy

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Clinico Universitario de Salamanca

Salamanca, , Spain

Hospital Universitari I Politecnic la Fe

Valencia, , Spain

Countries

United States; Italy; Spain

Other Identifiers

CMX001-211

Identifier Type: -

Identifier Source: org_study_id