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

Adenovirus Disease Clinical Trial

Official title:

A Randomized, Placebo-controlled, Multi-site Phase 2 Study Evaluating the Safety and Efficacy of Preemptive Treatment With CMX001 for the Prevention of Adenovirus Disease Following Hematopoietic Stem Cell Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01241344
• Other study ID #: CMX001-202
• Status: Completed
• Phase: Phase 2
• Start date: November 2010
• Est. completion date: June 2013

Study information

• Verified date: July 2021
• Source: Chimerix
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 75 Years

Eligibility

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

Subjects meeting any of the following exclusion criteria were excluded from participation in the study:

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.

Any exemptions to the protocol inclusion or exclusion criteria, as applicable, for subjects who developed probably or definitive AdV disease while participating in prescreening activities must have been discussed with and approved by the Chimerix medical monitor or designee before the subject was allowed to receive open-label BCV therapy.

Related Conditions & MeSH terms

• Adenoviridae Infections
• Adenovirus Disease

Intervention

Drug:
• 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).

Other:
• 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).

Locations

Country	Name	City	State
United States	The Children's Hospital-Denver	Aurora	Colorado
United States	Children's Hospital of Alabama	Birmingham	Alabama
United States	Harvard-Children's Hospital Boston	Boston	Massachusetts
United States	Cincinnati Childrens Hospital	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	UT Southwestern	Dallas	Texas
United States	City of Hope National Medical Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Baylor College of Medicine, Texas Childrens Hospital	Houston	Texas
United States	MD Anderson Cancer Center	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Childrens hospital of LA	Los Angeles	California
United States	St. Judes Children's Research Hospital	Memphis	Tennessee
United States	Univeristy of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	LSU Health Sciences Center New Orleans Childrens Hospital	New Orleans	Louisiana
United States	Memorial Sloan Kettering	New York	New York
United States	CHOC Children's Hospital	Orange	California
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Pheonix Children's Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	St. Louis Children's Hosptial	Saint Louis	Missouri
United States	Primary Children's Medical of Utah	Salt Lake City	Utah
United States	Methodist Hospital	San Antonio	Texas
United States	University of California, San Francisco	San Francisco	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Lucile Packard Childrens hopsital at Stanford	Stanford	California
United States	New York Medical College	Valhalla	New York
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Chimerix

Country where clinical trial is conducted

United States, 

References & Publications (1)

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-Con — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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