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

NCT03532035 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: CMX001-211
• Study Type: interventional
• Target: N/A
• Locations: 3 countries
• Sites: 8

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

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• Incidence (number and percentage of subjects) of treatment-emergent adverse events

  22 days

Study Arms (2)

Brincidofovir (BCV)

EXPERIMENTAL

* 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

Standard of Care (SoC)

ACTIVE COMPARATOR

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

Interventions

Brincidofovir 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).

Also known as: BCV

Brincidofovir (BCV)

Standard of Care 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.

Standard of Care (SoC)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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)
• 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
• 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.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (8)

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

University of Chigago

Chicago, Illinois, 60637, United States

Location

Brigham and Womens Hospital

Boston, Massachusetts, 02115, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University Vita-Salute San Raffaele. San Faffaele Scientific Institute

Milan, 20132, Italy

Location

Hospital Universitari Vall d'Hebron

Barcelona, 8035, Spain

Location

Hospital Clinico Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitari I Politecnic la Fe

Valencia, 46016, Spain

Location

MeSH Terms

Conditions

Adenoviridae Infections

Interventions

brincidofovir; Standard of Care

Condition Hierarchy (Ancestors)

DNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2018
• First Posted: May 22, 2018
• Study Start: December 15, 2018
• Primary Completion: May 10, 2019
• Study Completion: May 10, 2019
• Last Updated: July 21, 2021

Record last verified: 2021-07

Locations

IT (1); ES (3); US (4)