Cytomegalovirus Infection Clinical Trial
Official title:
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
Verified date | June 2021 |
Source | Chimerix |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 239 |
Est. completion date | January 2012 |
Est. primary completion date | January 2012 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria For inclusion into the study, all prospective subjects were required to fulfill all of the following criteria (as applicable): 1. 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. 2. Were cytomegalovirus (CMV) seropositive before allogeneic hematopoietic stem cell transplantation (HCT) (i.e., R+ subjects). 3. Were less than 30 days post qualifying transplant. 4. Had evidence of engraftment before randomization and receiving their first dose of study drug. 5. Were able to ingest and absorb oral medication (in the judgment of the investigator and based on lack of significant gastrointestinal [GI] events). 6. Were willing and able to understand and provide written informed consent. 7. 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. Exclusion Criteria Subjects meeting any of the following exclusion criteria were to be excluded from participation in the study: 1. Females who were pregnant or currently nursing. 2. Had a body mass index >35 kg/m2. [Note: This criterion was removed per Protocol Amendment 2 dated 27 August 2010.] 3. Had hypersensitivity to cidofovir (CDV) or brincidofovir. 4. 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. 5. 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. 6. 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. 7. 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. 8. 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. 9. Received another allogeneic HCT within the past 2 years, other than the qualifying HCT. 10. Had renal insufficiency as evidenced by glomerular filtration rate (GFR) <30 mL/min. 11. Had a current diagnosis of hypotony, uveitis, or retinitis or any intraocular pathology that would predispose the subject to any one of these conditions. 12. Had hepatic dysfunction as evidenced by alanine aminotransferase or aspartate aminotransferase >5 x the upper limit of normal (ULN) or direct bilirubin >2.5 x the ULN. 13. Had any of the following active autoimmune disorders: myasthenia gravis, Addison's disease, Wegener's granulomatosis, primary biliary cirrhosis, bullous pemphigoid, autoimmune hemolytic anemia, autoimmune hepatitis, multiple sclerosis, Goodpasture's syndrome, idiopathic thrombocytopenic purpura, lupus erythematosus, dermatomyositis, polymyositis, or vasculitis. 14. Had active solid tumor malignancies with the exception of basal cell carcinoma or the condition under treatment (e.g., lymphomas). 15. Had 1 or more episode of hyperglycemic coma or diabetic ketoacidosis within the 6 months prior to enrollment. 16. Had cardiovascular disease which, in the opinion of the investigator, would interfere with the conduct of the study. 17. Had Grade 3 or 4 graft versus host disease of the GI tract; subjects with any GI disease that would, in the judgment of the investigator, preclude the subject from taking or absorbing oral medication (e.g. clinically active Crohn's disease, ischemic colitis, moderate or severe ulcerative colitis, or any condition expected to require abdominal surgery during the course of study participation). 18. Any other condition including abnormal laboratory values that would have, in the judgment of the investigator, put the subject at increased risk for participating in the trial, or interferes with the conduct of the trial. |
Country | Name | City | State |
---|---|---|---|
United States | University of Michigan Medical School | Ann Arbor | Michigan |
United States | Winship Cancer Institute at Emory University | Atlanta | Georgia |
United States | University of Colorado Denver | Aurora | Colorado |
United States | The University of Alabama at Birmingham | Birmingham | Alabama |
United States | Brigham and Womens Hospital, Division of Infectious Disease | Boston | Massachusetts |
United States | Montefiore Medical Center Oncology | Bronx | New York |
United States | UNC Health Care Center | Chapel Hill | North Carolina |
United States | University of Chicago Medical Center | Chicago | Illinois |
United States | The Cleveland Clinic | Cleveland | Ohio |
United States | Baylor University Medical Center | Dallas | Texas |
United States | UT Southwestern Medical Center at Dallas | Dallas | Texas |
United States | Harper University Hospital | Detroit | Michigan |
United States | Duke University Medical Center | Durham | North Carolina |
United States | Hackensack University Medical Center | Hackensack | New Jersey |
United States | University of Texas, MD Anderson Cancer Center | Houston | Texas |
United States | Moores UCSD Cancer Center | La Jolla | California |
United States | UCLA Medical Center | Los Angeles | California |
United States | University of Minnesota Medical Center | Minneapolis | Minnesota |
United States | Memorial Sloan Kettering Cancer Center | New York | New York |
United States | Mt. Sinai School of Medicine | New York | New York |
United States | Nebraska Medical Center | Omaha | Nebraska |
United States | Oregon Health and Science University | Portland | Oregon |
United States | University of Rochester Medical Center | Rochester | New York |
United States | Utah Cancer Specialists - Intermountain Healthcare | Salt Lake City | Utah |
United States | Fred Hutchinson Cancer Research Center | Seattle | Washington |
United States | Wake Forest University School of Medicine | Winston-Salem | North Carolina |
Lead Sponsor | Collaborator |
---|---|
Chimerix |
United States,
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. — View Citation
Marty FM, Winston DJ, Rowley SD, Vance E, Papanicolaou GA, Mullane KM, Brundage TM, Robertson AT, Godkin S, Momméja-Marin H, Boeckh M; CMX001-201 Clinical Study Group. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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) |
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