CMX001 in Post-transplant Patients With BK Virus Viruria

NCT00793598 | Completed Phase 1 Results DMC

• 1 other identifier: CMX001-104
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 15

Brief Summary

This was a randomized, double-blind, multiple-dose placebo-controlled study of oral brincidofovir (BCV) in hematopoietic stem cell transplant and renal transplant recipients with BK virus viruria.

Conditions

Viruria

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events in Post-Transplant Patients With BK Virus Viruria

  The primary objective of this study was to determine the safety and tolerability of brincidofovir (BCV) in post-transplant patients with BK virus viruria. Safety measures included adverse events, clinical laboratory values, vital signs, and renal and gastrointestinal function.

  35 days (Day 0 to Day 35)

Secondary Outcomes (2)

• Percentage of Patients Who Achieved BK Viruria Resolution

  28 days

• Number of Patients Who Achieved a Clinically Significant Decrease in BK Viruria

  28 days

Study Arms (2)

Brincidofovir

EXPERIMENTAL

Under Amendments 1 and 2, subjects received 1 of 2 dose regimens of brincidofovir, as follows: * 20 mg BCV once weekly (QW) on Days 0, 7, and 14; or * 10 mg BCV twice weekly (BIW) BIW on Days 0, 3, 7, 10, and 14. Under Amendment 3, subjects received 40 mg BCV QW for a total of 5 doses on Days 0, 7, 14, 21, and 28.

Drug: Brincidofovir

Placebo

PLACEBO COMPARATOR

Under Amendments 1 and 2, subjects received placebo twice weekly (BIW) for a total of 5 doses on Days 0, 3, 7, 10, and 14. Under Amendment 3, subjects received placebo once weekly (QW) for a total of 5 doses on Days 0, 7, 14, 21, and 28.

Drug: Placebo

Interventions

Placebo DRUG

Placebo

Brincidofovir DRUG

Also known as: BCV, CMX001

Brincidofovir

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged between 18 to 75 years, inclusive. Males must have been able and willing to use adequate contraceptive methods throughout the study and for 3 months after the final dose. Females must have been post-menopausal, surgically sterile, or willing to use adequate contraception for the duration of the study (screening through the Day 48 visit).
• Were renal or hematopoietic stem cell transplant patients who met the following criteria:
• Renal transplant patients who:
• Were at least 28 days post transplant;
• Were in stable condition with hemoglobin \>10 g/100 mL;
• Had no evidence of graft rejection (i.e., serum creatinine was not increasing \[±30%\], creatinine clearance was not decreasing);
• Were on a stable immunosuppressant regimen for at least 14 days prior to dosing.
• Had either urine levels of BK virus DNA ≥10\^4 copies/mL without viremia or plasma levels of BK virus DNA \<10\^4 copies/mL (with or without viruria).
• Stem cell transplant patients who:
• Were a minimum of 3 days post documentation of successful engraftment as evidenced by an absolute neutrophil count \>500 cells/mm3;
• Had urine levels of BKV ≥10\^4 copies/mL.
• Had GFR \>30 mL/min.
• Were able to swallow tablets.
• Were willing and able to understand and provide written informed consent.
• Were willing and able to participate in all required study activities for the duration of the study (including ingestion of oral medication).

You may not qualify if:

• Females who were currently nursing or pregnant.
• Were using illicit drugs or abusing alcohol.
• Had hypersensitivity to cidofovir or brincidofovir.
• Had received aminoglycosides (intravenously) or NSAIDS (except as given for cardioprotective treatment) within 7 days prior to enrollment; had received leflunomide, cidofovir, or any other medication for treatment of BK virus infection or disease within 14 days prior to enrollment; had received any investigational drug (including maribavir) within 30 days prior to enrollment.
• Were HIV positive (results must have been obtained within 1 year prior to dosing); had active hepatitis C virus (HCV) or hepatitis B virus (HBV) infection as evidenced by plasma levels of HCV RNA or HBV DNA, respectively.
• Were stem cell transplant patients who:
• Had cystitis ≥Grade 3 National Cancer Institute, Common Terminology Criteria for Adverse Events version 3.0.
• Had Grade 3 or 4 graft versus host disease (GVHD).
• Had untreated or uncontrolled Grade 2 GVHD.
• Had received ganciclovir or valganciclovir within 14 days prior to enrollment.
• Had mucositis that prevented ingestion of oral medication.
• Had hypotony, uveitis, or retinitis or any intraocular pathology that would have predisposed the patient to any one of these conditions.
• Had 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.
• Had bilirubin \>2.5 x the upper limit of normal.
• Had cardiovascular disease which, in the opinion of the investigator, would have interfered with the conduct of the study.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (15)

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

University of California, San Francisco

San Francisco, California, 94143-0780, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Tulane Center for Abdominal Transplant

New Orleans, Louisiana, 70112, United States

Location

Johns Hopkins Medical Institutions

Baltimore, Maryland, 21287, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Mt. Sinai Medical Center

New York, New York, 10029, United States

Location

UNC Kidney Center

Chapel Hill, North Carolina, 27599, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15260, United States

Location

University of Vermont

Burlington, Vermont, 05405, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 19024, United States

Location

MeSH Terms

Interventions

brincidofovir

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Chimerix, Inc.

dmoore@chimerix.com

919-806-1074

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: November 17, 2008
• First Posted: November 19, 2008
• Study Start: November 1, 2009
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: August 16, 2021
• Results First Posted: July 16, 2021

Record last verified: 2021-07

Locations

US (15)