A Phase 3 Study of Brincidofovir Versus Valganciclovir for the Prevention of Cytomegalovirus Disease

NCT02439970 | Terminated Phase 3 Results DMC

• 1 other identifier: CMX001-303
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 3

Brief Summary

To compare the efficacy of oral brincidofovir (BCV) to valganciclovir (vGCV) for the prevention of cytomegalovirus (CMV) disease in kidney transplant allograft recipients who are CMV seronegative pretransplant and received a kidney from a CMV seropositive donor

Conditions

Cytomegalovirus Disease

Keywords

kidney transplant allograft; recipients

Outcome Measures

Primary Outcomes (1)

• The Incidence of CMV Disease

  The incidence of CMV disease included CMV tissue-invasive disease and CMV syndrome, occurring anytime between randomization and Week 52 (± 28 days). The proportion of subjects that met this failure endpoint were to be compared between brincidofovir (BCV) and valganciclovir (vGCV) using an unadjusted 95% confidence interval (CI) of the absolute difference between groups (BCV minus vGCV). If the upper bound of the 95% CI fell below 10%, BCV would have demonstrated non-inferiority to vGCV. In the event that the upper bound of the 95% CI fell below 0%, BCV would have additionally demonstrated superiority over vGCV.

  52 weeks (± 28 days)

Study Arms (2)

Treatment 1

ACTIVE COMPARATOR

100 mg brincidofovir (BCV; 1 tablet) administered orally twice weekly, plus valganciclovir (vGCV) placebo (2 tablets) administered orally once daily.

Drug: Brincidofovir

Treatment 2

ACTIVE COMPARATOR

900 mg valganciclovir (vGCV; two 450 mg tablets) administered orally once daily, plus brincidofovir (BCV) placebo (1 tablet) administered orally twice weekly.

Drug: Valganciclovir

Interventions

Brincidofovir DRUG

Also known as: CMX001, BCV

Treatment 1

Valganciclovir DRUG

Also known as: vGCV

Treatment 2

Eligibility Criteria

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

You may qualify if:

• Subjects must have met all of the following criteria, as applicable, to be eligible to participate in this study:
• Were male or female kidney transplant recipients who were ≥18 years of age (subject to local law/practice for clinical trial participation) and ≤14 days following their first or second renal allograft.
• Were at high risk of cytomegalovirus (CMV) infection defined as CMV-seronegative recipients who have received an allograft from a CMV-seropositive donor.
• Had an estimated glomerular filtration rate of \>10 mL/min (Cockcraft-Gault equation) at screening based on local laboratory results.
• Were CMV viremia negative (i.e., "not detected") as measured by the desginated central virology laboratory using the Roche COBAS® AmpliPrep/COBAS® TaqMan® CMV Test no more than 5 days prior to subject randomization, and at all prior assessments performed since transplant under local standard of care.
• Were able to ingest, absorb, and tolerate tablets.
• If male, was willing to use an acceptable contraceptive method(s) throughout the duration of his participation in the study, i.e., through Week 52.
• If female of childbearing potential, i.e., not post menopausal or surgically sterile, was willing to use 2 acceptable contraceptive methods, 1 of which must have been a barrier method, throughout the duration of her participation in the study, i.e., through Week 52.
• Were willing and able to provide informed consent.
• Were willing and able to participate in all required study activities for the entire duration of the study (i.e., through Week 52).

You may not qualify if:

• Subjects who met any of the following criteria were not eligible to participate in this study:
• Weighed ≤50 kg (110 lbs) or ≥120 kg (265 lbs).
• Were pregnant or breastfeeding or intended to conceive during the study period (i.e., through Week 52).
• Received a stem cell transplant or a solid organ transplant other than a kidney transplant.
• Had suspected CMV disease (either syndrome or tissue-invasive disease) or detectable CMV viremia by the central virology laboratory prior to the first dose of study drug.
• Had a history of CMV disease (either syndrome or tissue-invasive disease) within 6 months prior to the first dose of study drug.
• Had an absolute neutrophil count of \<500 cells/μL, platelet count of \<25,000/μL, or hemoglobin of \<8 g/dL at screening.
• Had hypersensitivity (not including renal dysfunction or an eye disorder) to valganciclovir (vGCV), ganciclovir (GCV), cidofovir (CDV) or to brincidofovir (BCV) or their excipients.
• Received (or were anticipated to need treatment with) any of the following:
• GCV, vGCV, foscarnet, intravenous CDV, or any other anti-CMV therapy (including CMV immune globulin, cell-based therapies, and investigational anti-CMV drugs, e.g., leflunomide, letermovir \[previously AIC246\], or maribavir) at any time posttransplant;
• Any anti-CMV vaccine at any time;
• Any other investigational drug within 14 days prior to the first dose of study drug (unless prior approval had been received from the Chimerix Medical Monitor or designee); or
• Prior treatment with BCV at any time. \[Note: An "investigational drug" was defined as any drug that is not approved for any indication by the FDA (or appropriate regulatory authority).\]
• Received acyclovir orally at \>2000 mg total daily dose (TDD) or intravenously at \>15 mg/kg TDD, valacyclovir at \>3000 mg TDD on the first dose of study drug or were anticipated to receive any of these drugs at the doses described after the the first dose of study drug.
• Were infected with HIV, hepatitis B virus (HBV), and/or hepatitis C virus (HCV), had evidence of active viral replication within 6 months prior to screening, as demonstrated by detectable HIV or HCV RNA, or detectable HBV DNA in blood, plasma or serum.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (3)

St. Vincent Medical Center

Los Angeles, California, 90057, United States

Location

University of Colorado Hospital/Health Science Center

Aurora, Colorado, 80045, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06520, United States

Location

MeSH Terms

Conditions

Cytomegalovirus Infections

Interventions

brincidofovir; Valganciclovir

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Ganciclovir; Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

No conclusions regarding safety or efficacy can be made from the limited data obtained in this study. Enrollment was suspended and all blinded study treatment was discontinued early January 2016.

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 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2015
• First Posted: May 12, 2015
• Study Start: September 1, 2015
• Primary Completion: January 30, 2016
• Study Completion: January 30, 2016
• Last Updated: July 16, 2021
• Results First Posted: July 16, 2021

Record last verified: 2021-06

Locations

US (3)