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

28 juin 2021 mis à jour par: 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.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Réel)

239

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

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

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: La prévention
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation séquentielle
  • Masquage: Double

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Comparateur placebo: 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
Médicament: 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.
Expérimental: 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
Médicament: 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.
Autres noms:
  • BCV
  • CMX001

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Number of Participants With Clinically Significant CMV Infection
Délai: 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)

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Chimerix

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Liens utiles

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

1 octobre 2009

Achèvement primaire (Réel)

1 janvier 2012

Achèvement de l'étude (Réel)

1 janvier 2012

Dates d'inscription aux études

Première soumission

17 juillet 2009

Première soumission répondant aux critères de contrôle qualité

17 juillet 2009

Première publication (Estimation)

20 juillet 2009

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

16 juillet 2021

Dernière mise à jour soumise répondant aux critères de contrôle qualité

28 juin 2021

Dernière vérification

1 juin 2021

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • CMX001-201

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

Non

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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