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Study of CMX001 to Prevent/Control Cytomegalovirus Infection in R+ Hematopoietic Stem Cell Transplant Recipients

28. juni 2021 opdateret af: Chimerix

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

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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

This was to be a 2-part study. Part 1 was a randomized, double-blind, placebo-controlled, dose-escalation study of multiple doses of oral brincidofovir (BCV) in R+ hematopoietic stem cell transplant (HCT) recipients. In Part 2, one of the dose levels administered in Part 1 was to be tested against placebo to evaluate the statistical significance of BCV as a therapy for preventing progression of cytomegalovirus (CMV) infection or preventing CMV disease. The first 3 dose-escalating cohorts in Part 1 were to include 32 subjects within each cohort (24 randomized to receive oral BCV and 8 randomized to receive placebo in a 3:1 ratio) for a total of 96 planned subjects. Following completion of the first 3 cohorts and subsequent safety review of the data, up to an additional 3 cohorts of 32 subjects each could have been enrolled. Two additional cohorts (labeled Cohort 4 and Cohort 4A) beyond the initial 3 cohorts were actually enrolled in Part 1 of the study. Following the safety and antiviral activity analyses of the 5 cohorts in Part 1 and the number of subjects enrolled in each of those cohorts, Part 2 of the study was not conducted.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

239

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Forenede Stater
    • Alabama
      • Birmingham, Alabama, Forenede Stater, 35294
        • The University of Alabama at Birmingham
    • California
      • La Jolla, California, Forenede Stater, 92093
        • Moores UCSD Cancer Center
      • Los Angeles, California, Forenede Stater, 90095
        • UCLA Medical Center
    • Colorado
      • Aurora, Colorado, Forenede Stater, 80045
        • University of Colorado Denver
    • Georgia
      • Atlanta, Georgia, Forenede Stater, 30322
        • Winship Cancer Institute at Emory University
    • Illinois
      • Chicago, Illinois, Forenede Stater, 60637
        • University of Chicago Medical Center
    • Massachusetts
      • Boston, Massachusetts, Forenede Stater, 02115
        • Brigham and Womens Hospital, Division of Infectious Disease
    • Michigan
      • Ann Arbor, Michigan, Forenede Stater, 48109
        • University of Michigan Medical School
      • Detroit, Michigan, Forenede Stater, 48201
        • Harper University Hospital
    • Minnesota
      • Minneapolis, Minnesota, Forenede Stater, 55455
        • University of Minnesota Medical Center
    • Nebraska
      • Omaha, Nebraska, Forenede Stater, 68198-5130
        • Nebraska Medical Center
    • New Jersey
      • Hackensack, New Jersey, Forenede Stater, 07601
        • Hackensack University Medical Center
    • New York
      • Bronx, New York, Forenede Stater, 10467
        • Montefiore Medical Center Oncology
      • New York, New York, Forenede Stater, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, Forenede Stater, 10029
        • Mt. Sinai School of Medicine
      • Rochester, New York, Forenede Stater, 14642
        • University of Rochester Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, Forenede Stater, 27599
        • UNC Health Care Center
      • Durham, North Carolina, Forenede Stater, 27710
        • Duke University Medical Center
      • Winston-Salem, North Carolina, Forenede Stater, 27517
        • Wake Forest University School of Medicine
    • Ohio
      • Cleveland, Ohio, Forenede Stater, 44195
        • The Cleveland Clinic
    • Oregon
      • Portland, Oregon, Forenede Stater, 97239
        • Oregon Health and Science University
    • Texas
      • Dallas, Texas, Forenede Stater, 75246
        • Baylor University Medical Center
      • Dallas, Texas, Forenede Stater, 75390-8565
        • UT Southwestern Medical Center at Dallas
      • Houston, Texas, Forenede Stater, 77030
        • University of Texas, MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, Forenede Stater, 84088
        • Utah Cancer Specialists - Intermountain Healthcare
    • Washington
      • Seattle, Washington, Forenede Stater, 98109
        • Fred Hutchinson Cancer Research Center

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Forebyggelse
  • Tildeling: Randomiseret
  • Interventionel model: Sekventiel tildeling
  • Maskning: Dobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Placebo komparator: Placebo
  • 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
Medicin: Placebo

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.
Eksperimentel: Brincidofovir
  • 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
Medicin: Brincidofovir
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.
Andre navne:
  • BCV
  • CMX001

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of Participants With Clinically Significant CMV Infection
Tidsramme: Randomization to Week 8 post-treatment (~19 weeks)
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)

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Chimerix

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Hjælpsomme links

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

1. oktober 2009

Primær færdiggørelse (Faktiske)

1. januar 2012

Studieafslutning (Faktiske)

1. januar 2012

Datoer for studieregistrering

Først indsendt

17. juli 2009

Først indsendt, der opfyldte QC-kriterier

17. juli 2009

Først opslået (Skøn)

20. juli 2009

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

16. juli 2021

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

28. juni 2021

Sidst verificeret

1. juni 2021

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • CMX001-201

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

Ingen

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Cytomegalovirus infektion

Kliniske forsøg med Placebo

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