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

Sponsor

Chimerix (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT03532035

Collaborator

(none)

Enrollment

Locations

Arms

4.8

Actual Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

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

Actual Enrollment :

0 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 :

Dec 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 Names: 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.

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 Names:

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

Outcome Measures

Primary Outcome Measures

Plasma area under the curve (AUC) of BCV [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
Plasma Cmax of BCV [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
Incidence (number and percentage of subjects) of treatment-emergent adverse events [22 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Medical Center	Los Angeles	California	United States	90095
2	University of Chigago	Chicago	Illinois	United States	60637
3	Brigham and Womens Hospital	Boston	Massachusetts	United States	02115
4	MD Anderson Cancer Center	Houston	Texas	United States	77030
5	University Vita-Salute San Raffaele. San Faffaele Scientific Institute	Milan		Italy	20132
6	Hospital Universitari Vall d'Hebron	Barcelona		Spain	8035
7	Hospital Clinico Universitario de Salamanca	Salamanca		Spain	37007
8	Hospital Universitari I Politecnic la Fe	Valencia		Spain	46016

Sponsors and Collaborators

Chimerix

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Chimerix

ClinicalTrials.gov Identifier:

NCT03532035

Other Study ID Numbers:

CMX001-211

First Posted:

May 22, 2018

Last Update Posted:

Jul 21, 2021

Last Verified:

Jul 1, 2021

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Adenoviridae Infections

Viremia

Brincidofovir

Study Results

No Results Posted as of Jul 21, 2021