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CMX001 in Post-transplant Patients With BK Virus Viruria

This study has been completed.
Sponsor:
Information provided by:
Chimerix
ClinicalTrials.gov Identifier:
NCT00793598
First received: November 17, 2008
Last updated: March 15, 2011
Last verified: March 2011
  Purpose

Twelve renal transplant subjects and twelve hematopoietic stem cell recipients will be enrolled in Cohort 3A. Subjects enrolled in Cohort 3A will receive 40mg CMX001 or placebo once weekly for a total of 5 doses. After 12 renal subjects have been enrolled into Cohort 3A, up to three additional cohorts (4A, 4B and 4C) of 12 renal transplant subjects each may be enrolled in a sequential manner


Condition Intervention Phase
Viruria
Drug: Placebo
Drug: CMX001
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study of the Safety, Tolerability and Population Pharmacokinetics of CMX001 in Post-Transplant Subjects With BK Virus Viruria

Resource links provided by NLM:


Further study details as provided by Chimerix:

Primary Outcome Measures:
  • Safety measures (adverse events, clinical laboratory values, vital signs, renal and gastrointestinal function) [ Time Frame: Multiple time points throughout the study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • BK Viral load [ Time Frame: Multiple times, relative to dosing, throughout the study ] [ Designated as safety issue: Yes ]
  • • The clinical and laboratory endpoints to be measured and analyzed include adverse events (and Serious Adverse Events, SAEs), changes in laboratory values (hematology, clinical chemistry), ECG results, vital signs, renal and gastrointestinal function [ Time Frame: Throughout the course of the study ] [ Designated as safety issue: No ]
  • Patient drop-out rate [ Time Frame: Through out the course of the study ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: November 2008
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CMX001
Cohort 3A 40 mg of CMX001 given on Days 0, 7, 14, 21, and 28 Cohort 4A 100 mg of CMX001 given twice weekly for a total of 9 doses Cohort 4B 200 mg of CMX001 given once or twice weekly Cohort 4C 300 mg of CMX001 given once or twice weekly
Drug: CMX001
Cohort 3A 40mg CMX001 once weekly for a total of 5 doses Cohort 4A 100mg CMX001 twice weekly for a total of nine doses Cohort 4B 200mg CMX001 once or twice weekly Cohort 4C 300mg CMX001 once or twice weekly
Placebo Comparator: Placebo
Cohort 3A once weekly for a total of 5 doses Cohort 4A twice weekly for a total of 9 doses Cohort 4B once or twice weekly Cohort 4C once or twice weekly
Drug: Placebo
Placebo Cohort 3A placebo once weekly for a total of 5 doses Cohort 4A placebo twice weekly for a total of nine doses Cohort 4B placebo once or twice weekly Cohort 4C placebo once or twice weekly

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age between 18 - 75 years, inclusive. Males must be able and willing to use adequate contraceptive methods throughout the study and for 3 months after the final dose. Females must be post-menopausal, surgically sterile or willing to use adequate contraception for the duration of the study (screening through the Day 49 visit).
  • Renal (Cohorts 3A, 4A, 4B and 4C) or hematopoietic stem cell (Cohort 3A only) transplant patients who meet the following criteria.

Renal transplant patients who:

are at least 28 days post transplant are in stable condition with hemoglobin >10g/100mL (Cohort 3A) or ≥8g/100mL (Cohorts 4A, 4B and 4C)

  • have no evidence of graft rejection (i.e., serum creatinine is not increasing (+/- 30%), creatinine clearance is not decreasing)
  • have been on a stable immunosuppressant (IS) regimen for at least 14 days prior to dosing. Stable immunosuppression allows for changes that are standard of care for the management of the immunosuppression regimen (e.g., steroid tapering or dose adjustments to maintain trough levels in the therapeutic range). These also include adjustments of dosing due to known side effects of the IS (e.g., GI symptoms with MMF).
  • have either urine levels of BKV DNA ≥ 104 copies/mL without viremia or plasma levels of BKV DNA < 104 copies/mL (with or without viruria). -Plasma levels of BKV DNA between 104 - 105 copies/mL will be considered on a case by case basis in consultation with the medical monitor (Cohorts 4A, 4B and 4C).

Stem cell transplant patients (Cohort 3A only) who:

are a minimum of 3 days post documentation of successful engraftment as evidenced by an absolute neutrophil count > 500 cells/mm3 have urine levels of BKV ≥ 104 copies/mL Glomerular filtration rate > 30 mL/min. Able to swallow tablets. Willing and able to understand and provide written informed consent. Willing and able to participate in all required study activities for the duration of the study (including ingestion of oral medication).

Exclusion Criteria:

  • Currently nursing or pregnant females.
  • Current use of illicit drugs; current abuse of alcohol.
  • Subjects with hypersensitivity to cidofovir or CMX001.
  • Patients who received aminoglycosides (IV) or NSAIDS (except as given for cardioprotective treatment) within 7 days prior to enrollment; patients who received leflunomide, cidofovir or any other medication for treatment of BK virus infection or disease within 14 days prior to enrollment; patients who received any investigational drug (including maribavir) within 30 days prior to enrollment.
  • Patients who are HIV positive (results must be obtained within one year prior to dosing); patients with active HCV or HBV infection as evidenced by plasma levels of HCV RNA or HBV DNA, respectively.
  • Renal transplant patients with evidence of biopsy proven acute rejection in the 3 weeks prior to enrollment. This exclusion criteria applies only to those patients for whom a biopsy was performed within the three weeks prior to enrollment.
  • Stem cell transplant patients (Cohort 3A only) who:

    1. have cystitis ≥ Grade 3 (NCI, CTCAE v3.0)
    2. have Grade 3 or 4 Graft Versus Host Disease (GvHD)
    3. have untreated or uncontrolled Grade 2 GvHD
    4. received ganciclovir or valganciclovir within 14 days prior to enrollment
  • Patients with mucositis preventing ingestion of oral medication.
  • Patients with hypotony, uveitis, or retinitis or any intraocular pathology that would predispose the patient to any one of these conditions.
  • Patients with unstable or poorly controlled diabetes defined as having frequent hypoglycemic and/or hyperglycemic events on a daily basis (brittle diabetes), with fluctuating short acting insulin requirements daily, or requiring unpredictable insulin supplementation to oral hypoglycemic agents on a regular basis.
  • Patients with bilirubin > 2.5 x ULN.
  • Patients with cardiovascular disease which, in the opinion of the investigator, would interfere with the conduct of the study.
  • Patients with any of the following autoimmune diseases; Addison's disease, autoimmune hemolytic anemia, autoimmune hepatitis, bullous pemphigoid, celiac disease, dermatomyositis, active Goodpasture's syndrome, idiopathic thrombocytopenic purpura, active lupus erythematosus, multiple sclerosis, myasthenia gravis, pemphigus vulgaris, polymyositis, primary biliary cirrhosis, vasculitis, Wegener's granulomatosis.
  • Patients with active malignancies (with the exception of basal cell carcinoma or the condition under treatment for HSCT patients).
  • Patients with concurrent or ongoing ≥ Grade 2 GI symptoms including nausea, vomiting, diarrhea, constipation or gastroenteritis. Patients with active GI disease including inflammatory bowel disease, irritable bowel syndrome (IBS), or celiac sprue.
  • 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: NCT00793598

Locations
United States, California
California Pacific Medical Center
San Francisco, California, United States, 94115
University of California, San Francisco
San Francisco, California, United States, 94143-0780
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Rush
Chicago, Illinois, United States
United States, Louisiana
Tulane Center for Abdominal Transplant
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins Medical Institutions
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New York
Mt Sinai
New York, New York, United States
United States, North Carolina
UNC Kidney Center
Chapel Hill, North Carolina, United States, 27599
Wake Forest University Health Sciences
Winston Salem, North Carolina, United States, 27157
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States
United States, Vermont
Vermont University
Burlington, Vermont, United States
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 19024
Sponsors and Collaborators
Chimerix
  More Information

No publications provided

Responsible Party: Wendy Painter/ Chief Medical Officer, Chimerix
ClinicalTrials.gov Identifier: NCT00793598     History of Changes
Other Study ID Numbers: CMX001-104
Study First Received: November 17, 2008
Last Updated: March 15, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Chimerix:
CMX001
Kidney transplant
HSCT transplant
BK Virus
Post kidney transplant patients with BK virus viruria > 10^4
Post HSCT transplant patients with BK virus viruria > 10^4

ClinicalTrials.gov processed this record on November 25, 2014