Study of CMX001 to Prevent/Control Cytomegalovirus Infection in R+ Hematopoietic Stem Cell Transplant Recipients
A Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-escalation Study of the Safety, Tolerability and Ability of CMX001 to Prevent or Control CMV Infection in R+ Hematopoietic Stem Cell Transplant Recipients
1 other identifier
interventional
239
1 country
26
Brief Summary
This was a multicenter, randomized, double-blind, placebo-controlled, dose-escalation study of brincidofovir (BCV) administered orally once or twice weekly for up to 11 weeks. Dosing was initiated immediately following engraftment (between Days 14-30 post-transplant) to prevent/control cytomegalovirus (CMV) infection or prevent disease in R+ hematopoietic stem cell transplant (HCT) recipients.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Oct 2009
26 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 17, 2009
CompletedFirst Posted
Study publicly available on registry
July 20, 2009
CompletedStudy Start
First participant enrolled
October 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2012
CompletedResults Posted
Study results publicly available
July 16, 2021
CompletedJuly 16, 2021
June 1, 2021
2.3 years
July 17, 2009
December 9, 2020
June 28, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants With Clinically Significant CMV Infection
The primary efficacy endpoint was a binomial outcome of failure to prevent cytomegalovirus (CMV) infection defined as CMV DNAemia \>200 copies/mL obtained at the time of the last treatment with study drug or diagnosis of CMV disease at some point during the treatment phase.
Randomization to Week 8 post-treatment (~19 weeks)
Study Arms (2)
Placebo
PLACEBO COMPARATOR* Cohort 1 = 40 mg of matching placebo administered once weekly (QW) * Cohort 2 = 100 mg of matching placebo administered QW * Cohort 3 = 200 mg of matching placebo administered QW * Cohort 4 = 200 mg of matching placebo administered twice weekly (BIW) * Cohort 4A = 100 mg of matching placebo administered BIW
Brincidofovir
EXPERIMENTAL* Cohort 1 = 40 mg brincidofovir (BCV) administered once weekly (QW) * Cohort 2 = 100 mg BCV administered QW * Cohort 3 = 200 mg BCV administered QW * Cohort 4 = 200 mg BCV administered twice weekly (BIW) * Cohort 4A = 100 mg BCV administered BIW
Interventions
Subjects received their first dose of study drug of brincidofovir (BCV) within 30 (+5) days post-transplant and were treated through Week 13 post-transplant.
Subjects received their first dose of study drug within 30 (+5) days post-transplant and were treated through Week 13 post-transplant. Matching placebo administered for each cohort.
Eligibility Criteria
You may qualify if:
- Were aged ≥18 years. Males must have been able and willing to use adequate contraceptive methods throughout the treatment and follow-up phases of the study.
- Were cytomegalovirus (CMV) seropositive before allogeneic hematopoietic stem cell transplantation (HCT) (i.e., R+ subjects).
- Were less than 30 days post qualifying transplant.
- Had evidence of engraftment before randomization and receiving their first dose of study drug.
- Were able to ingest and absorb oral medication (in the judgment of the investigator and based on lack of significant gastrointestinal \[GI\] events).
- Were willing and able to understand and provide written informed consent.
- To the best of his or her knowledge, were willing and able to participate in all required study activities for the duration of the study.
You may not qualify if:
- Females who were pregnant or currently nursing.
- Had a body mass index \>35 kg/m2. \[Note: This criterion was removed per Protocol Amendment 2 dated 27 August 2010.\]
- Had hypersensitivity to cidofovir (CDV) or brincidofovir.
- Recipients for whom the current, predose clinical course of CMV infection suggested that the investigator would not be able to withhold treatment for CMV for a minimum of 5, but preferably 7 days following the subject's first dose of study drug.
- Received any of the following:
- Ganciclovir, valganciclovir, foscarnet or CDV within 14 days prior to enrollment;
- Any anti-CMV therapy following transplantation (including Cytogam®1);
- Any CMV vaccine;
- Any investigational drug with antiviral activity against double-stranded DNA (dsDNA) viruses within 14 days prior to enrollment. \[Note: An investigational drug was defined as a drug that was not approved for any indication by the Food and Drug Administration.\]; or
- Any other investigational drug (i.e., those without any "anti-dsDNA virus" activity; e.g., anti-influenza compounds) within 14 days prior to enrollment without the prior written consent of the medical monitor. The use of investigational drugs in certain circumstances was added per Protocol Amendment 1 dated 15 January 2010.
- Received high dose acyclovir (\>2000 mg total oral daily dose or \>5 mg/kg intravenously 3 times daily) or valacyclovir (Valtrex; \>3000 mg total daily dose) at the time of dosing.
- Were diagnosed with active CMV disease within 6 months prior to enrollment; patients with CMV DNAemia requiring intervention with antiviral therapy at the time of enrollment.
- Were HIV positive; patients with active hepatitis C virus (HCV) or hepatitis B virus (HBV) infection as evidenced by plasma levels of HCV RNA or HBV DNA, respectively.
- Received another allogeneic HCT within the past 2 years, other than the qualifying HCT.
- Had renal insufficiency as evidenced by glomerular filtration rate (GFR) \<30 mL/min.
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (26)
The University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
Moores UCSD Cancer Center
La Jolla, California, 92093, United States
UCLA Medical Center
Los Angeles, California, 90095, United States
University of Colorado Denver
Aurora, Colorado, 80045, United States
Winship Cancer Institute at Emory University
Atlanta, Georgia, 30322, United States
University of Chicago Medical Center
Chicago, Illinois, 60637, United States
Brigham and Womens Hospital, Division of Infectious Disease
Boston, Massachusetts, 02115, United States
University of Michigan Medical School
Ann Arbor, Michigan, 48109, United States
Harper University Hospital
Detroit, Michigan, 48201, United States
University of Minnesota Medical Center
Minneapolis, Minnesota, 55455, United States
Nebraska Medical Center
Omaha, Nebraska, 68198-5130, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Mt. Sinai School of Medicine
New York, New York, 10029, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
University of Rochester Medical Center
Rochester, New York, 14642, United States
Montefiore Medical Center Oncology
The Bronx, New York, 10467, United States
UNC Health Care Center
Chapel Hill, North Carolina, 27599, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Wake Forest University School of Medicine
Winston-Salem, North Carolina, 27517, United States
The Cleveland Clinic
Cleveland, Ohio, 44195, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Baylor University Medical Center
Dallas, Texas, 75246, United States
UT Southwestern Medical Center at Dallas
Dallas, Texas, 75390-8565, United States
University of Texas, MD Anderson Cancer Center
Houston, Texas, 77030, United States
Utah Cancer Specialists - Intermountain Healthcare
Salt Lake City, Utah, 84088, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
Related Publications (3)
Lanier ER, Foster S, Brundage T, Chou S, Prichard MN, Kleiboeker S, Wilson C, Colville D, Mommeja-Marin H. Analysis of Mutations in the Gene Encoding Cytomegalovirus DNA Polymerase in a Phase 2 Clinical Trial of Brincidofovir Prophylaxis. J Infect Dis. 2016 Jul 1;214(1):32-5. doi: 10.1093/infdis/jiw073. Epub 2016 Mar 3.
PMID: 26941282BACKGROUNDMarty FM, Winston DJ, Rowley SD, Vance E, Papanicolaou GA, Mullane KM, Brundage TM, Robertson AT, Godkin S, Mommeja-Marin H, Boeckh M; CMX001-201 Clinical Study Group. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med. 2013 Sep 26;369(13):1227-36. doi: 10.1056/NEJMoa1303688.
PMID: 24066743RESULTTippin TK, Morrison ME, Brundage TM, Mommeja-Marin H. Brincidofovir Is Not a Substrate for the Human Organic Anion Transporter 1: A Mechanistic Explanation for the Lack of Nephrotoxicity Observed in Clinical Studies. Ther Drug Monit. 2016 Dec;38(6):777-786. doi: 10.1097/FTD.0000000000000353.
PMID: 27851688DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Chief Medical Officer
- Organization
- Chimerix, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- PREVENTION
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 17, 2009
First Posted
July 20, 2009
Study Start
October 1, 2009
Primary Completion
January 1, 2012
Study Completion
January 1, 2012
Last Updated
July 16, 2021
Results First Posted
July 16, 2021
Record last verified: 2021-06
Data Sharing
- IPD Sharing
- Will not share