Study of CMX001 to Prevent/Control Cytomegalovirus Infection in R+ Hematopoietic Stem Cell Transplant Recipients
Condition: Cytomegalovirus Infection
MeSH terms: Infections; Communicable Diseases; Cytomegalovirus Infections
Intervention: Brincidofovir; Placebo
Intervention description: 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.
Intervention MeSH terms: Brincidofovir
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Double (Participant, Investigator)
Enrollment: 239.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Allogeneic stem cell transplant; CMV seropositive (R+); transplant

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.
    

Eligibility criteria:

        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.