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

NCT ID: NCT01241344

Last Updated: 2021-07-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2013-06-30

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.

Detailed Description

This was a Phase 2, randomized, multicenter, placebo-controlled study for pediatric and adult subjects who had undergone hematopoietic stem cell transplantation (HCT) and who had been identified as having asymptomatic adenovirus (AdV) viremia [i.e., had detectable AdV DNA in plasma based on polymerase chain reaction testing performed at the local laboratory with no AdV disease symptoms]. The primary objectives of the study were to assess the safety and tolerability of oral brincidofovir (BCV), and to estimate the treatment failure rate based on an efficacy endpoint with 2 different dosing regimens of oral BCV versus placebo.

Conditions

Adenovirus Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Brincidofovir

• 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).

Group Type: ACTIVE_COMPARATOR

Brincidofovir

Intervention Type: 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).

Placebo

• 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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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).

Interventions

Brincidofovir

• 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).

Intervention Type: DRUG

Placebo

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).

Intervention Type: OTHER

Other Intervention Names

BCV; CMX001

Eligibility Criteria

Inclusion Criteria

For inclusion into the study, subjects were required to fulfill all of the following criteria:

1. Were males or female aged ≥3 months to ≤75 years.

2. Received an allogeneic hematopoietic stem cell transplant (HCT).

3. 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).

4. Was on dialysis during treatment if he/she had an estimated glomerular filtration rate (eGFR) ≤30 mL/minute.

5. Subject or guardian(s) were willing to comply with the protocol.

6. Subject or guardian(s) were willing and able to understand the informed consent/assent.

7. 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.

Exclusion Criteria

1. 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).

2. Had suspected gut graft versus host disease that was not biopsy-proven (subjects with a biopsy performed were included in the study).

3. Had an eGFR ≤30 mL/minute and was not currently on dialysis.

4. 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.

5. Had a condition that prevented oral dosing of study drug.

6. Was HIV antibody positive, based upon available medical records.

7. Had ocular hypotony, uveitis, or retinitis or any other intraocular pathology that would have predisposed the subject to 1 of these conditions.

8. 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.

9. Was pregnant or breast-feeding or intended to conceive during the course of the study, including the follow-up period after drug discontinuation.

10. Had known immunologic hypersensitivity to cidofovir (CDV) or brincidofovir (BCV) drug or any of its excipients.

11. Had a history of illicit drug use or alcohol abuse within the previous 6 months.

12. 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).

13. Received BCV, CDV, ribavirin, or leflunomide within the previous 14 days.

14. Was receiving or was anticipated to need treatment with digoxin that could not have been withheld for the duration of BCV therapy.

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jazz Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Children's Hospital of Alabama

Birmingham, Alabama, United States

Pheonix Children's Hospital

Phoenix, Arizona, United States

City of Hope National Medical Center

Duarte, California, United States

Childrens hospital of LA

Los Angeles, California, United States

CHOC Children's Hospital

Orange, California, United States

University of California, San Francisco

San Francisco, California, United States

Lucile Packard Childrens hopsital at Stanford

Stanford, California, United States

The Children's Hospital-Denver

Aurora, Colorado, United States

Children's National Medical Center

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

Indiana University

Indianapolis, Indiana, United States

LSU Health Sciences Center New Orleans Childrens Hospital

New Orleans, Louisiana, United States

Harvard-Children's Hospital Boston

Boston, Massachusetts, United States

Univeristy of Minnesota

Minneapolis, Minnesota, United States

St. Louis Children's Hosptial

St Louis, Missouri, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Memorial Sloan Kettering

New York, New York, United States

New York Medical College

Valhalla, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Cincinnati Childrens Hospital

Cincinnati, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

St. Judes Children's Research Hospital

Memphis, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

UT Southwestern

Dallas, Texas, United States

Baylor College of Medicine, Texas Childrens Hospital

Houston, Texas, United States

MD Anderson Cancer Center

Houston, Texas, United States

Methodist Hospital

San Antonio, Texas, United States

Primary Children's Medical of Utah

Salt Lake City, Utah, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 28063938 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27851688 (View on PubMed)

Other Identifiers

CMX001-202

Identifier Type: -

Identifier Source: org_study_id