Dose-escalation Study of the Safety, Tolerability and Ability of CMX001 to Prevent or Control Cytomegalovirus (CMV) Infection in R+ Hematopoietic Stem Cell Transplant Recipients

This study has been completed.
Sponsor:
Information provided by:
Chimerix
ClinicalTrials.gov Identifier:
NCT00942305
First received: July 17, 2009
Last updated: January 16, 2012
Last verified: January 2012
  Purpose

This is a multicenter, randomized, double-blind, placebo-controlled, dose-escalation study of CMX001 administered once weekly for up to 11 weeks. Dosing will be initiated immediately following engraftment (between Days 14-30 post-transplant) to prevent/control CMV infection or prevent disease in R+ allogeneic stem cell transplant recipients.


Condition Intervention Phase
Cytomegalovirus Infection
Drug: CMX001
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Chimerix:

Primary Outcome Measures:
  • Safety endpoints include clinical assessments and laboratory values, incidence adn severity of GvHD, AEs (and SAEs). Efficacy endpoint includes lack of emergence or progression of CMV infection. [ Time Frame: throghout the treatment and follow-up phases ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Emergence or increase in CMV DNA, Occurrence of CMV diseasePatient drop-out and/or discontinuation rate,Trough levels of CMX001, CDV, and other metabolites,urine and/or plasma levels of AdV, BKV, or EBV DNA [ Time Frame: throughout the treatment and follow-up phases ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 150
Study Start Date: October 2009
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
Placebo tablets once weekly for a total of up to 11 doses.
Experimental: CMX001 Drug: CMX001
CMX001 200mg twice weekly for a total of up to 18 doses.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years. Males must be able and willing to use adequate contraceptive methods throughout the treatment and follow-up phases of the study. Females must be postmenopausal,surgically sterile or, for those female subjects of reproductive potential, willing to agree to use 2 acceptable methods of birth control throughout the treatment phase of the study, with at least one being a barrier method.
  2. Allogeneic HSCT recipients who were CMV seropositive before transplantation (i.e., R+ patients).
  3. Recipients who are less than 30 days post qualifying transplant. [Note: Under extreme circumstances due to timing issues associated with logistics, patients may be enrolled, i.e.receive first dose of study drug, up to Day 32 post-transplant. Sites must first contact the Chimerix Medical Monitor to receive permission for FDD to be Days 31 or 32 post-transplant.]
  4. Recipients must have evidence of engraftment before randomization and receiving their first dose of study drug. Evidence of engraftment will be defined as one of the following:

    • Absolute neutrophil count (ANC) increasing for 3 consecutive days with a count ≥ 500 cells/mm3 by the third day OR
    • Three (3) consecutive days with an ANC ≥ 500 cells/mm3. [Notes: For sites where standard site practice is to monitor white blood count (WBC) early after transplant as opposed to ANC, then engraftment will be defined as WBC increasing for 3 consecutive days with an ANC ≥ 500 cell/mm3 on the third day. For non-myeloablative or reduced-intensity transplants (i.e., mini-transplants) where ANC does not fall below 500 cells/mm3, the site definition of engraftment should be used.] Able to ingest and absorb oral medication (in the judgment of the investigator and based on lack of significant GI events). [Note: Use of TPN (total parenteral nutrition) is not in and of itself exclusionary as long as the reason for use would not disqualify the patient based on this criterion.]

6. Willing and able to understand and provide written informed consent. 7. To the best of his or her knowledge, willing and able to participate in all required study activities for the duration of the study.

Exclusion Criteria:

  1. Females who are pregnant or currently nursing.
  2. Patients with a BMI > 35 kg/m2.
  3. Patients with hypersensitivity to cidofovir or CMX001.
  4. Recipients for whom the current, predose clinical course of CMV infection suggests 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. [Note: Patients who, with a high probability, will not be able to have their first efficacy assessment because of CMV infection should not be enrolled into the study. That is, investigators should not enroll recipients with increasing CMV viral loads predose such that, in the PI's opinion, continuation along the same clinical course would result in discontinuation (due to requirement for CMV treatment with a prohibited medication) within the first week.]
  5. Recipients who received any of the following:

    • GCV, vGCV, 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 dsDNA viruses within 14 days prior to enrollment, [Note: An investigational drug is defined as a drug that is not approved for any indication by the FDA.]
    • any other investigational drug (i.e., those without any "anti-dsDNA virus" activity; for example, anti-influenza compounds) within 14 days prior to enrollment without the prior written consent of the medical monitor.

Patients receiving high dose ACV (> 2000 mg total oral daily dose or > 5 mg/kg IV three times daily) or vACV (Valtrex; > 3000 mg total daily dose) at the time of dosing. [Note: These doses are for patients with normal renal function; patients who dose reduce on the FDD are not excluded from the study.] 7. Patients with active CMV disease diagnosed within 6 months prior to enrollment; patients with CMV DNAemia requiring intervention with antiviral therapy at the time of enrollment.

8. Patients who are HIV positive; patients with active HCV or HBV infection as evidenced by plasma levels of HCV RNA or HBV DNA, respectively. [Note: Tests for viral serology/infection performed prior to transplant and within 6 months of dosing may be used to satisfy this criteria.] 9. HSCT recipients who, other than the qualifying HSCT, received another allogeneic HSCT within the past 2 years. [Note: Patients who received one or more autologous transplants in addition to the qualifying allogeneic HSCT are not excluded from participation.] 10. Patients with renal insufficiency as evidenced by GFR < 30 mL/min. [Note: GFR will be calculated by the central laboratory using the MDRD study formula.] 11. Patients with a current diagnosis of hypotony, uveitis, or retinitis or any intraocular pathology that would predispose the patient to any one of these conditions.

12. Patients with hepatic dysfunction as evidenced by ALT or AST > 5 x ULN or direct bilirubin > 2.5 x ULN. [Note: for these laboratory values, one retest is allowed per visit (i.e.,screening or predose) at the central laboratory, local laboratory retest results may be used at the discretion of the medical monitor.] 13. Patients with 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. Patients with active solid tumor malignancies with the exception of basal cell carcinoma or the condition under treatment (for example, lymphomas).

15. Patients who have had one or more episodes of hyperglycemic coma or diabetic ketoacidosis within the past 6 months.

16. Patients with cardiovascular disease which, in the opinion of the investigator, would interfere with the conduct of the study.

17. Patients with Grade 3 or 4 GVHD of the GI tract; patients with any GI disease that would, in the judgment of the investigator, preclude the patient 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 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00942305

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Sponsors and Collaborators
Chimerix
  More Information

No publications provided by Chimerix

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Alice Robertson, PhD, Chimerix, Inc
ClinicalTrials.gov Identifier: NCT00942305     History of Changes
Other Study ID Numbers: CMX001-201
Study First Received: July 17, 2009
Last Updated: January 16, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Chimerix:
Allogeneic stem cell transplant
CMV seropositive (R+)
transplant
Allogeneic stem cell transplant recipients who were CMV seropositive (R+) at the time of transplant will be eligible for enrollment

Additional relevant MeSH terms:
Communicable Diseases
Cytomegalovirus Infections
Infection
DNA Virus Infections
Herpesviridae Infections
Virus Diseases

ClinicalTrials.gov processed this record on October 23, 2014