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A Study of the Safety and Efficacy of CMX001 for the Prevention of CMV Infection in CMV-seropositive HCT Recipients

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ClinicalTrials.gov Identifier: NCT01769170
Recruitment Status : Completed
First Posted : January 16, 2013
Results First Posted : January 5, 2021
Last Update Posted : July 21, 2021
Sponsor:
Information provided by (Responsible Party):
Chimerix

Brief Summary:
This randomized, double-blind, placebo-controlled, parallel group, multicenter study compared the effectiveness of oral brincidofovir (BCV) to placebo for the prevention of cytomegalovirus (CMV) infection in stem cell transplant patients who were CMV seropositive but negative for CMV viremia before starting treatment with BCV.

Condition or disease Intervention/treatment Phase
CMV Drug: Brincidofovir Other: Placebo Phase 3

Detailed Description:
This was a randomized, double-blind, placebo-controlled, parallel group multicenter study of oral brincidofovir (BCV) in approximately 450 cytomegalovirus (CMV)-seropositive subjects who had undergone allogeneic hematopoietic stem cell transplantation (HCT). The study consisted of a screening evaluation and a treatment phase of 10 to 14 weeks. Dosing with the study drug (BCV or placebo) was initiated as soon as individual subjects could ingest tablets after transplant but no later than Day 28 post-transplant, and was continued through Week 14. All randomized subjects remained on study and followed the same scheduled study treatment. Study assessments were performed weekly from randomization through completion of the first post-treatment follow-up assessment at Week 15, and every 3 weeks thereafter through Week 24.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 452 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3 Study of the Safety, Tolerability, and Efficacy of CMX001 for the Prevention of Cytomegalovirus (CMV) Infection in CMV-seropositive (R+) Hematopoietic Stem Cell Transplant Recipients
Actual Study Start Date : August 2013
Actual Primary Completion Date : December 2015
Actual Study Completion Date : January 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
Matching placebo administered orally twice weekly
Other: Placebo
Active Comparator: Brincidofovir
100 mg brincidofovir administered orally twice weekly
Drug: Brincidofovir
Other Names:
  • BCV
  • CMX001
  • Hexadecyloxypropyl cidofovir
  • HDP-CDV




Primary Outcome Measures :
  1. Number of Participants With Clinically Significant CMV Infection Through Week 24 Post-Transplant [ Time Frame: 24 weeks ]

    Clinically significant cytomegalovirus (CMV) infection was defined by either of the following outcomes:

    1. Onset of CMV end-organ disease; or
    2. Initiation of anti-CMV-specific preemptive therapy based on documented CMV viremia (as measured by the central virology laboratory) and the clinical condition of the subject.

    CMV viremia (i.e., the measurement of CMV DNA in plasma) was determined by the designated central virology laboratory at all scheduled visits via quantitative polymerase chain reaction (qPCR) testing using the Roche COBAS® AmpliPrep/COBAS® TaqMan® CMV Test.



Secondary Outcome Measures :
  1. Incidence of Clinically Significant CMV Infection Through Week 14 [ Time Frame: 14 weeks ]

    The incidence of clinically significant cytomegalovirus (CMV) infection through Week 14.

    Blood and urine for virologic evaluations were collected at screening, pre-dose on the first day of study drug administration, and at pre-specified intervals throughout the treatment phases of the study and sent to a designated central virology laboratory for analysis. Blood samples were used for real-time assay of CMV viremia in plasma using a qPCR assay. Urine samples were stored for possible future retrospective analyses of CMV.




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Subjects were required to meet all of the following criteria, as applicable, to be eligible to participate in this study:

  1. Were allogeneic hematopoietic stem cell transplant (HCT) recipients who had prior evidence of cytomegalovirus (CMV) exposure (CMV-seropositive) before transplantation and were CMV viremia negative at screening and at any other assessments performed prior to the first dose of study drug.
  2. Were aged ≥18 years.
  3. If male, were willing to use an acceptable contraceptive method(s) throughout the duration of his participation in the study, i.e., through Week 24, when engaging in sexual intercourse with a female subject of childbearing potential.
  4. If female of childbearing potential, i.e., not postmenopausal or surgically sterile, were willing to use 2 acceptable contraceptive methods, 1 of which must have been a barrier method, throughout the duration of her participation in the study, i.e., through Week 24, when engaging in sexual intercourse with a nonsterile male partner.
  5. Were able to begin study drug dosing within 28 days following the qualifying HCT.
  6. Were able to comfortably ingest and absorb oral medication (in the judgment of the investigator and base don lack of significant gastrointestinal events/medical history).
  7. Were willing and able to understand and provide written informed consent.
  8. Were willing and able to participate in all required study activities for the entire duration of the study (i.e., through Week 24).

Exclusion Criteria

Subjects who met any of the following criteria, as applicable, were not eligible to participate in this study:

  1. Was pregnant or planned to become pregnant during the anticipated duration of her participation in the study (i.e., through Week 24), or was nursing a child.
  2. Had a positive CMV viremia test (at the designated central virology laboratory or a local virology laboratory) at any time between transplant and the first dose of study drug.
  3. Weighed ≥120 kg (~265 lbs).
  4. Had hypersensitivity (not renal dysfunction or eye disorder) to cidofovir (CDV), brincidofovir (BCV), or its excipients.
  5. Had received (or were anticipated to need treatment with) any of the following:

    • Ganciclovir, valganciclovir, foscarnet, intravenous CDV, or any other anti-CMV therapy (including CMV immune globulin, cell-based therapies, and investigational anti-CMV drugs, e.g., leflunomide, letermovir, or maribavir) at any time post-transplant;
    • Any anti-CMV vaccine at any time;
    • Any other investigation drug within 14 days prior to the first dose of study drug (unless prior approval had been received from the Chimerix medical monitor or designee); or
    • Prior treatment with BCV at any time.
  6. Were receiving of the following drugs on the first dose of study drug or were anticipated to receive any of these drugs at the doses described after the first dose of study drug:

    • Acyclovir orally at >2000 mg total daily dose (TDD) or intravenously at >15 mg/kg TDD;
    • Valaciclovir at >3000 mg TDD; or
    • Leflunomide at any dose.
  7. Were receiving digoxin or ketoconazole (other than topical formulations) at the first dose of study drug or were anticipated to need treatment with either digoxin or ketoconazole during the treatment phase (through Week 14).
  8. Had possible, probably, or definitive CMV disease diagnosed within 6 months prior to first dose of study drug.
  9. Were infected with HIV (based on serology), or had an active hepatitis C virus (HCV) or hepatitis B virus (HBV) infection, as evidence by detectable plasma HCV RNA or HBV DNA, respectively.
  10. Had received another allogeneic HCT (i.e., other than the qualifying HCT) within 2 years prior to the first dose of study drug.
  11. Had renal insufficiency, as evidence by an estimated glomerular filtration rate (eGFR) <15 mL/min or required renal dialysis.
  12. Had hepatic abnormalities as evidence by a screening of alanine aminotransferase or aspartate aminotransferase >5 x the upper limit of normal (ULN), as reported by the central safety laboratory.
  13. Had a screening total bilirubin >2 x the ULN and direct bilirubin >1.5 x the ULN, as reported by the central safety laboratory.
  14. Had active solid tumor malignancies with the exception of basal cell carcinoma or the underlying condition necessitating HCT (e.g., lymphomas).
  15. Had Stage 2 or higher graft versus host disease of the gut or any other GI disease that would have, in the judgment of the investigator, precluded the subject from taking or absorbing oral medication (e.g., clinically active Crohn's disease, ischemic colitis, moderate or severe ulcerative colitis, small bowel resection, ileus, or any condition expected to require abdominal surgery during the course of study participation).
  16. Had any other condition, including abnormal laboratory values, that would have, in the judgement of the investigator, put the subject at increased risk by participating in the study or would have interfered with the conduct or planned analyses of the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01769170


Locations
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Sponsors and Collaborators
Chimerix
Publications of Results:
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Responsible Party: Chimerix
ClinicalTrials.gov Identifier: NCT01769170    
Other Study ID Numbers: CMX001-301
First Posted: January 16, 2013    Key Record Dates
Results First Posted: January 5, 2021
Last Update Posted: July 21, 2021
Last Verified: July 2021
Keywords provided by Chimerix:
CMV
Hematopoietic Stem Cell Transplant Recipients
Prevention
Additional relevant MeSH terms:
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Infection
Cidofovir
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action