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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


Phase 1/Phase 2
18 Years
75 Years
Not Enrolling
Both
Viruria

Thank you

Trial Information

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


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.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

Safety measures (adverse events, clinical laboratory values, vital signs, renal and gastrointestinal function)

Outcome Time Frame:

Multiple time points throughout the study

Safety Issue:

Yes

Authority:

United States: Food and Drug Administration

Study ID:

CMX001-104

NCT ID:

NCT00793598

Start Date:

November 2008

Completion Date:

October 2010

Related Keywords:

  • Viruria
  • 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

Name

Location

University of MichiganAnn Arbor, Michigan  48109-0624
Fred Hutchinson Cancer Research CenterSeattle, Washington  98109
Washington University School of MedicineSaint Louis, Missouri  63110
Beth Israel Deaconess Medical CenterBoston, Massachusetts  02215
University of PittsburghPittsburgh, Pennsylvania  15261
University of California, San FranciscoSan Francisco, California  94143
Northwestern UniversityChicago, Illinois  60611
California Pacific Medical CenterSan Francisco, California  94115
Wake Forest University Health SciencesWinston-Salem, North Carolina  27157
Johns Hopkins Medical InstitutionsBaltimore, Maryland  21205
RushChicago, Illinois  
Tulane Center for Abdominal TransplantNew Orleans, Louisiana  70112
Mt SinaiNew York, New York  
UNC Kidney CenterChapel Hill, North Carolina  27599
Vermont UniversityBurlington, Vermont