Phase 2 Study to Evaluate Brincidofovir for the Prevention of Adenovirus Disease

NCT01241344 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CMX001-202
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 30

Brief Summary

This study was designed to assess the safety and efficacy of preemptive treatment with oral brincidofovir (BCV), as compared to placebo, for the prevention of adenovirus (AdV) disease in recipients of hematopoietic stem cell transplantation (HCT) with asymptomatic AdV viremia.

Conditions

Adenovirus Disease

Keywords

AdV; Hematopoeitic Stem Cell Transplant; HSCT

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Clinically Significant AdV Infection

  The primary objective of this study was to evaluate the safety and efficacy of preemptive treatment with brincidofovir (BCV) versus placebo for the prevention of adenovirus (AdV) disease in recipients of hematopoietic stem cell transplantation (HCT) with asymptomatic AdV viremia. The outcome measure for the primary endpoint was treatment failure, a composite endpoint that consisted of the following: * Progression to probable AdV disease (other positive causes/agents have been ruled out and subject has disease-targeted organ-specific signs or symptoms) or definitive AdV disease (AdV detected in disease-targeted organ/system biopsy via antigen/immunohistochemistry, culture, and/or polymerase chain reaction and has at least 1 disease-targeted organ-specific sign or symptom); or * Increasing AdV viremia (defined as an increase from baseline in AdV viremia by ≥1 log10, confirmed on a second measurement, at least 1 week apart) and requiring discontinuation from blinded therapy.

  12 weeks

Study Arms (2)

Brincidofovir

ACTIVE COMPARATOR

* Adult subjects: 200mg BCV administered as 50mg tablets taken orally either once weekly (QW; 4 tablets) or twice weekly (BIW; 2 tablets). * Pediatric subjects: 4mg/kg BCV (not to exceed a total single dose of 200mg) administered using a 10 mg/mL liquid formulation taken orally either QW (as 4 mg/kg) or BIW (as 2 mg/kg).

Drug: Brincidofovir

Placebo

PLACEBO COMPARATOR

* Adult subjects: Matching placebo tablets taken orally either once weekly (QW; 4 tablets) or twice weekly (BIW; 2 tablets). * Pediatric subjects: Matching liquid placebo taken orally either QW (as 4 mg/kg) or BIW (as 2 mg/kg).

Other: Placebo

Interventions

Brincidofovir DRUG

* Adult subjects: 200mg BCV administered as 50mg tablets taken orally either once weekly (QW; 4 tablets) or twice weekly (BIW; 2 tablets). * Pediatric subjects: 4mg/kg BCV (not to exceed a total single dose of 200mg) administered using a 10 mg/mL liquid formulation taken orally either QW (as 4 mg/kg) or BIW (as 2 mg/kg).

Also known as: BCV, CMX001

Brincidofovir

Placebo OTHER

Adult subjects: Matching placebo tablets taken orally either once weekly (QW; 4 tablets) or twice weekly (BIW; 2 tablets). • Pediatric subjects: Matching liquid placebo taken orally either QW (as 4 mg/kg) or BIW (as 2 mg/kg).

Placebo

Eligibility Criteria

• Age: 3 Months - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Were males or female aged ≥3 months to ≤75 years.
• Received an allogeneic hematopoietic stem cell transplant (HCT).
• Had positive serum adenovirus (AdV) PCR (\>100 copies/mL) as measured by the central laboratory (unless the subject developed AdV disease while participating in the prescreening activities and after concurrence from the Chimerix medical monitor or designee).
• Was on dialysis during treatment if he/she had an estimated glomerular filtration rate (eGFR) ≤30 mL/minute.
• Subject or guardian(s) were willing to comply with the protocol.
• Subject or guardian(s) were willing and able to understand the informed consent/assent.
• Female subjects of child-bearing potential must have had a negative pregnancy test and must have agreed to use 2 acceptable methods of birth control throughout the study with at least 1 being a barrier method. Sexually active males of procreation potential must have been able and willing to se a reliable and medically approved contraceptive method throughout the study. At least 1 barrier method of contraception must have been used.

You may not qualify if:

• Had possible, probable, or definitive AdV disease (unless the subject developed probable or definitive AdV disease while participating in prescreening activities and after concurrence from he Chimerix medical monitor or designee).
• Had suspected gut graft versus host disease that was not biopsy-proven (subjects with a biopsy performed were included in the study).
• Had an eGFR ≤30 mL/minute and was not currently on dialysis.
• Had an alanine aminotransferase or aspartate aminotransferase \>5 x the upper limit of normal (ULN), total bilirubin ≥2 x the ULN, or conjugated (direct) bilirubin ≥1.5 x the ULN.
• Had a condition that prevented oral dosing of study drug.
• Was HIV antibody positive, based upon available medical records.
• Had ocular hypotony, uveitis, or retinitis or any other intraocular pathology that would have predisposed the subject to 1 of these conditions.
• Had participated in another clinical study of an investigational drug/biologic or was exposed to an investigational drug/biologic within 30 days of enrollment without the prior written approval of the Chimerix medical monitor or designee. For subjects who were participating in any clinical study involving non-investigational drugs and/or biologics, the investigator must have obtained approval from the Chimerix medical monitor or designee prior to enrolling the subject.
• Was pregnant or breast-feeding or intended to conceive during the course of the study, including the follow-up period after drug discontinuation.
• Had known immunologic hypersensitivity to cidofovir (CDV) or brincidofovir (BCV) drug or any of its excipients.
• Had a history of illicit drug use or alcohol abuse within the previous 6 months.
• Had any medical condition that, in the opinion of the investigator, might have interfered with the subject's participation in the study, posed an added risk for the subject, or confounded the assessment of the subject (e.g. severe cardiovascular, central nervous system or pulmonary disease).
• Received BCV, CDV, ribavirin, or leflunomide within the previous 14 days.
• Was receiving or was anticipated to need treatment with digoxin that could not have been withheld for the duration of BCV therapy.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (30)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Pheonix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Childrens hospital of LA

Los Angeles, California, 90033, United States

Location

CHOC Children's Hospital

Orange, California, 92868, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Lucile Packard Childrens hopsital at Stanford

Stanford, California, 94304, United States

Location

The Children's Hospital-Denver

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

LSU Health Sciences Center New Orleans Childrens Hospital

New Orleans, Louisiana, 70118, United States

Location

Harvard-Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Univeristy of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

St. Louis Children's Hosptial

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan Kettering

New York, New York, 10021, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Childrens Hospital

Cincinnati, Ohio, 45229, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

St. Judes Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

UT Southwestern

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine, Texas Childrens Hospital

Houston, Texas, 77030, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Methodist Hospital

San Antonio, Texas, 78229, United States

Location

Primary Children's Medical of Utah

Salt Lake City, Utah, 84113, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Related Publications (2)

• Grimley MS, Chemaly RF, Englund JA, Kurtzberg J, Chittick G, Brundage TM, Bae A, Morrison ME, Prasad VK. Brincidofovir for Asymptomatic Adenovirus Viremia in Pediatric and Adult Allogeneic Hematopoietic Cell Transplant Recipients: A Randomized Placebo-Controlled Phase II Trial. Biol Blood Marrow Transplant. 2017 Mar;23(3):512-521. doi: 10.1016/j.bbmt.2016.12.621. Epub 2017 Jan 5.

  PMID: 28063938 RESULT

• Tippin TK, Morrison ME, Brundage TM, Mommeja-Marin H. Brincidofovir Is Not a Substrate for the Human Organic Anion Transporter 1: A Mechanistic Explanation for the Lack of Nephrotoxicity Observed in Clinical Studies. Ther Drug Monit. 2016 Dec;38(6):777-786. doi: 10.1097/FTD.0000000000000353.

  PMID: 27851688 DERIVED

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 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2010
• First Posted: November 16, 2010
• Study Start: November 1, 2010
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: July 21, 2021
• Results First Posted: July 16, 2021

Record last verified: 2021-07

Locations

US (30)