Cidofovir in Renal Transplant Recipients With BKVN

NCT00138424 | Terminated Phase 1 Results

• 2 other identifiers: 04-047CASG 209
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 12

Brief Summary

This study will look at the safety, tolerability and effectiveness of cidofovir in kidney transplant patients who have been diagnosed with BK virus nephropathy (BKVN), a viral condition that can cause patients to reject transplanted kidneys. Up to 48 adult (age 18 years and older) kidney or pancreas transplant recipients with newly diagnosed BKVN will receive 1 of 3 cidofovir dose levels or placebo (non medicated substance) to identify the maximum tolerated dose. Dosing will be administered intravenously (by a tube running into a blood vessel). In addition to the screening visit, volunteers will actively participate for approximately 8-10 weeks with a single follow up phone call at 4 months. Blood samples, urine samples, eye exams and physical exams are included in study procedures.

Conditions

BK Virus (Nephropathy)

Keywords

Vistide®, Cidofovir, renal transplant, BK Virus Nephropathy

Outcome Measures

Primary Outcomes (8)

• Safety and Tolerability of Cidofovir Assessed by Enumeration of Adverse Events Per Subject

  The measure is the number of adverse events (ie: events that are change from baseline)experienced by subjects. The median or average number of events and the range of events across all subjects is reported.

  Baseline through day 49

• Number of Adverse Events by Grade of Event

  Adverse events are reported as grades: Toxicity Grade I: a mild event (an event that requires minimal or no treatment and does not interfere with the subject's daily activities. Toxicity Grade II: a moderate event (an event that results in a low level of inconvenience or concern with the therapeutic measures and may cause some interference with functioning. Toxicity Grade III: a severe event (an event that interrupts a subject's usual daily activity and may require systemic drug therapy or other treatment and may be incapacitating. Toxicity Grade IV: Life threatening (any adverse drug experience that places the patient or subject at immediate risk of death from the reaction as it occurred)

  Baseline through day 49.

• Number of Related Adverse Events

  The investigator's assessment of an AE's relationship to study drug is part of the documentation process. All adverse events had their relationship to study product assessed using the following terms: associated (related)or not associated (not related). To help assess, the following guidelines were used. * Associated - There was a known temporal relationship and/or, if re-challenge was done, the event abates with de-challenge and reappears with re-challenge and/or the event was known to occur in association study product or with a product in a similar class of study products * Not Associated -the AE was completely independent of study product administration; and/or evidence existed that the event was definitely related to another etiology.

  Baseline through day 49.

• Changes Observed in the Physical Examination : Respiratory Rate (Per Minute)

  Respiratory rate is the number of breaths per minute.

  Baseline through day 49.

• Changes Observed in the Physical Examination: Blood Pressure (mm/hg)

  Blood pressure (BP) is the pressure exerted by circulating blood upon the walls of blood vessels. "Blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, blood pressure varies between a maximum (systolic) and a minimum (diastolic) pressure. The measure is the difference between the baseline systolic and baseline diastolic value with the day 49 systolic and day 49 diastolic value.

  Baseline through day 49.

• Changes Observed in the Physical Examination: Body Temperature (Fahrenheit)

  The temperature is a measure of body temperature in fahrenheit (F). The measure is a change between baseline temperature and day 49 temperature.

  Baseline through day 49.

• Changes Observed in the Physical Examination: Heart Rate (Per Minute)

  The heart rate is the number of heart beats per minute. The outcome measure is the change from baseline heart rate to day 49 heart rate.

  Baseline through day 49.

• Number of Subjects Experiencing at Least One Laboratory Abnormality

  The following lab values assessed during the 49 days of subject involvement were the following: hemoglobin, hematocrit, platelets, sodium, potassium, chloride, bicarbonate, blood urea nitrogen (BUN), serum creatinine, calcium, phosphorous, serum albumin, glucose, uric acid, magnesium, total protein, total bilirubin, alanine aminotransferase (ALT), asparate aminotransferase (AST) and alkaline phosphate. The outcome measure is the number of subjects experiencing at least 1 grade 1 (mild) or higher event.

  Baseline through day 49

Secondary Outcomes (8)

• The Effect of Cidofovir on BK Virus Determined by Percentage of Subjects Achieving an Undetectable BK Virus in Urine and Plasma PCR

  Day 35.

• Percentage Change of Viral Load in Urine and Plasma BK Virus by Quantitative PCR Between Baseline and Each Visit

  Baseline, and each visit: day 7, 21, 35 and 49.

• Subjects Achieving 50% Reduction Viral Load in Plasma and Urine

  Baseline through day 49.

• Number of Days to at Least 50% Reduction of Viral Load in Plasma and Urine

  Baseline through day 49.

• Allograft Function at the Completion of the Study

  Day 49.

Study Arms (2)

Cidofovir

EXPERIMENTAL

32 subjects will be randomized to 1 of 3 possible cohorts. Cohort I will receive dose 0.25 mg/kg; Cohort II will receive 0.5 mg/kg, Cohort III will receive 1.0 mg/kg. Maximum tolerated dose is to be determined.

Drug: Cidofovir

Placebo

PLACEBO COMPARATOR

16 subjects to receive placebo.

Drug: Placebo

Interventions

Cidofovir DRUG

Cidofovir is a marketed product for treatment of Cytomegalovirus disease (retinitis) in human immunodeficiency virus (HIV) infected patients. It is packaged as a sterile, hypertonic aqueous solution for intravenous infusion only. Dosages: 0.25 mg/kg, 0.5 mg/kg, and 1.0 mg/kg.

Cidofovir

Placebo DRUG

The control for this study is sterile, 0.9% normal saline for intravenous use.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged greater than or equal to 18 years.
• Kidney or kidney/pancreas transplant recipient.
• New onset BK Virus Nephropathy (BKVN) diagnosed by a positive plasma polymerase chain reaction (PCR) assay for BK virus deoxyribonucleic acid (DNA) or by a renal biopsy demonstrating BK virus (by immunohistochemistry, electron microscopy and/or in situ hybridization) obtained as part of standard medical care within 60 days prior to receipt of first dose of study drug.
• BK virus load in plasma greater than 10,000 copies/mL within prior 21 days.
• Glomerular filtration rate greater than 30 mL/min using Levey calculations.
• Absolute neutrophil count greater than 1000/microliter \[with granulocyte colony stimulating factor (GCSF) support as necessary\].
• Women must be post-menopausal, surgically sterile or willing to use adequate contraception (barrier method with spermicide, intrauterine device, oral contraceptives, implant or other licensed hormone method) from time of study enrollment through 1 month after the last dose of study treatment. Men must be surgically sterile or willing to use contraception (barrier method with spermicide) from time of study enrollment through 3 months after the last dose of study treatment.

You may not qualify if:

• Unable to provide valid informed consent.
• History of intolerance to cidofovir or related compounds (i.e. other nucleotide derivatives \[adefovir or tenofovir\]).
• Pregnant or breast feeding women.
• Prior treatment with cidofovir within the last 2 weeks.
• Receipt of another investigational drug with proven nephrotoxic drug interaction with cidofovir or known antipolyoma virus activity one month prior to study entry.
• Contraindication to renal biopsy (e.g., anticoagulant medication, unwilling to undergo biopsy).
• Currently receiving or anticipated to receive any of the following within 2 weeks of randomization:
• Amphotericin preparation (intravenous)
• Aminoglycosides (intravenous)
• Platinum - based chemotherapeutic agents
• NSAIDs - non steroidal anti-inflammatory drugs (aspirin given for cardioprotective treatment is acceptable up to 650 mg per oral daily)
• Foscarnet
• Pentamidine (intravenous)
• Probenecid
• Leflunomide

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (12)

University of Alabama Hospital - Nephrology

Birmingham, Alabama, 35249-0001, United States

Location

California Pacific Medical Center - Sutter Pacific Medical Foundation - Transplant Nephrology

San Francisco, California, 94115-1932, United States

Location

University of California San Francisco Medical Center at Parnassus - Organ Transplant

San Francisco, California, 94143-2204, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045-2541, United States

Location

Northwestern University - Comprehensive Transplant Center

Chicago, Illinois, 60611-2927, United States

Location

The University of Chicago Medical Center - Kindney Trasnplant - Nephrology

Chicago, Illinois, 60637-1447, United States

Location

University of Minnesota Medical Center, Fairview - Infectious Diseases and International Medicine

Minneapolis, Minnesota, 55455-0356, United States

Location

Mayo Clinic, Rochester - Infectious Diseases

Rochester, Minnesota, 55905-0001, United States

Location

Dartmouth-Hitchcock Medical Center - Infectious Disease

Lebanon, New Hampshire, 03756-1000, United States

Location

Dallas Nephrology Associates - Dallas Transplant Institute

Dallas, Texas, 75204-6168, United States

Location

University of Washington - Medicine

Seattle, Washington, 98195-7110, United States

Location

University of Wisconsin Hospital and Clinics - Clinical Science Center - Nephrology

Madison, Wisconsin, 53792-0001, United States

Location

Related Publications (1)

• Razonable RR. Management of viral infections in solid organ transplant recipients. Expert Rev Anti Infect Ther. 2011 Jun;9(6):685-700. doi: 10.1586/eri.11.43.

  PMID: 21692673 DERIVED

MeSH Terms

Conditions

Kidney Diseases

Interventions

Cidofovir

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Cytosine; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

The study closed early due to failure to enroll in a timely manner.

Results Point of Contact

• Title: Penelope Jester, BSN,MPH,CCRC
• Organization: Collaborative Antiviral Study Group

PJester@peds.uab.edu

(205) 877-975-7280

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2005
• First Posted: August 30, 2005
• Study Start: May 1, 2006
• Primary Completion: June 1, 2010
• Study Completion: April 1, 2011
• Last Updated: March 8, 2013
• Results First Posted: January 7, 2013

Record last verified: 2011-04

Locations

US (12)