Treatment of adenovirus infections in adult allogeneic hematopoietic cell transplant recipients MedDRA version: 21.1 Level: PT Classification code 10060931 Term: Adenovirus infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: Brincidofovir
Product Code: CMX001
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Brincidofovir (USAN)
CAS Number: 444805-28-1
Current Sponsor code: CMX001
Concentratio
Sponsors
CHIMERIX, INC.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For inclusion in this study, subjects must: 1. Be = 18-years-old (or per local law or regulations on legal age of consent). 2. Have received an allogeneic HCT within the previous 100 days. 3. 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). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Diarrhea meeting the US National Institutes of Health (NIH)/National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater (i.e., increase of = 4 stools per day over usual pretransplant stool output) within 7 days prior to Day 1. 2. Acute graft versus host disease (GVHD) meeting the following criteria: - 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 [SI: > 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. 3. Concurrent human immunodeficiency virus or active hepatitis B or C infection. 4. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 5x the upper limit of the normal reference range (ULN), total bilirubin > 3 mg/dL (SI: > 51 µmol/L), or prothrombin time – international normalized ratio (PT-INR) > 2x ULN within 7 days prior to Day 1.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and pharmacokinetics (PK) of selected doses of brincidofovir (BCV) administered intravenously (IV) in allogeneic hematopoietic cell transplant (HCT) recipients with adenovirus (AdV) viremia.;Secondary Objective: ¿ To assess the clinical safety of IV BCV with respect to adverse events (AEs) and changes in laboratory parameters. ¿ To assess PK of BCV and cidofovir (CDV) in plasma and CDV diphosphate (CDV-PP) in peripheral blood mononuclear cells (PBMCs) and red blood cells (RBCs) following multiple IV doses of BCV. ¿ To evaluate the virologic response, based on change from baseline in AdV deoxyribonucleic acid (DNA) in plasma, stool and/or urine and incidence of undetectable AdV viremia, of the selected IV BCV doses in HCT recipients.;Primary end point(s): To evaluate the safety and pharmacokinetics (PK) of selected doses of brincidofovir (BCV) administered intravenously (IV) in allogeneic hematopoietic cell transplant (HCT) recipients with adenovirus (AdV) viremia;Timepoint(s) of evaluation of this end point: To evaluate the safety and pharmacokinetics (PK) of selected doses of brincidofovir (BCV) administered intravenously (IV) in allogeneic hematopoietic cell transplant (HCT) recipients with adenovirus (AdV) viremia | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ¿ Incidence of TEAEs, particularly those of = CTCAE Grade 3 severity and serious adverse events (SAEs). ¿ Absolute and changes over time in safety laboratory parameters (i.e., hematology and clinical chemistry). ¿ Plasma BCV Cmax, tmax, AUCt, AUClast, AUCinf, %AUCextrap, Clast, tlast, t¿, CL, Vz, and Vss following Dose 1 and Dose 4, as data permit. ¿ Change in AdV viremia from baseline. ¿ Relationship between plasma BCV exposure and virologic endpoints of interest and influence of various covariates of interest on the exposure-response relationships and endpoints.;Timepoint(s) of evaluation of this end point: Safety: through AEs Pharmacokinetics: Day 1 and Day 11 Pharmacodynamics: Day 8 and Day 15 | — |
Countries
Italy, Spain, United States
Contacts
Public ContactChief Medical Officer
Chimerix Inc.
Outcome results
None listed