CMVPhase 3NCT01769170
A Study of the Safety and Efficacy of CMX001 for the Prevention of CMV Infection in CMV-seropositive HCT Recipients
A Phase 3 study testing Brincidofovir in people with CMV, run by Jazz Pharmaceuticals at 43 sites in 3 countries.
Trial summary
This randomized, double-blind, placebo-controlled, parallel group, multicenter study compared the effectiveness of oral brincidofovir (BCV) to placebo for the prevention of cytomegalovirus (CMV) infection in stem cell transplant patients who were CMV seropositive but negative for CMV viremia before starting treatment… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CMV
- What is being tested?
- Brincidofovir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 452 participants
- Where
- 43 sitesin 3 countries
- Study dates
- Aug 2013to Jan 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects were required to meet all of the following criteria, as applicable, to be eligible to participate in this study:
- Were allogeneic hematopoietic stem cell transplant (HCT) recipients who had prior evidence of cytomegalovirus (CMV) exposure (CMV-seropositive) before transplantation and were CMV viremia negative at screening and at any other assessments performed prior to the first dose of study drug.
- Were aged ≥18 years.
- If male, were willing to use an acceptable contraceptive method(s) throughout the duration of his participation in the study, i.e., through Week 24, when engaging in sexual intercourse with a female subject of childbearing potential.
- If female of childbearing potential, i.e., not postmenopausal or surgically sterile, were 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 24, when engaging in sexual intercourse with a nonsterile male partner.
- Were able to begin study drug dosing within 28 days following the qualifying HCT.
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- Were able to comfortably ingest and absorb oral medication (in the judgment of the investigator and base don lack of significant gastrointestinal events/medical history).
- Were willing and able to understand and provide written informed consent.
- Were willing and able to participate in all required study activities for the entire duration of the study (i.e., through Week 24).
Who cannot join
- Subjects who met any of the following criteria, as applicable, were not eligible to participate in this study:
- Was pregnant or planned to become pregnant during the anticipated duration of her participation in the study (i.e., through Week 24), or was nursing a child.
- Had a positive CMV viremia test (at the designated central virology laboratory or a local virology laboratory) at any time between transplant and the first dose of study drug.
- Weighed ≥120 kg (~265 lbs).
- Had hypersensitivity (not renal dysfunction or eye disorder) to cidofovir (CDV), brincidofovir (BCV), or its excipients.
- Had received (or were anticipated to need treatment with) any of the following:
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- Ganciclovir, valganciclovir, 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, or maribavir) at any time post-transplant;
- Any anti-CMV vaccine at any time;
- Any other investigation 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.
- Were receiving of the following drugs on the first dose of study drug or were anticipated to receive any of these drugs at the doses described after the first dose of study drug:
- Acyclovir orally at >2000 mg total daily dose (TDD) or intravenously at >15 mg/kg TDD;
- Valaciclovir at >3000 mg TDD; or
- Leflunomide at any dose.
- Were receiving digoxin or ketoconazole (other than topical formulations) at the first dose of study drug or were anticipated to need treatment with either digoxin or ketoconazole during the treatment phase (through Week 14).
- Had possible, probably, or definitive CMV disease diagnosed within 6 months prior to first dose of study drug.
- Were infected with HIV (based on serology), or had an active hepatitis C virus (HCV) or hepatitis B virus (HBV) infection, as evidence by detectable plasma HCV RNA or HBV DNA, respectively.
- Had received another allogeneic HCT (i.e., other than the qualifying HCT) within 2 years prior to the first dose of study drug.
- Had renal insufficiency, as evidence by an estimated glomerular filtration rate (eGFR) <15 mL/min or required renal dialysis.
- Had hepatic abnormalities as evidence by a screening of alanine aminotransferase or aspartate aminotransferase >5 x the upper limit of normal (ULN), as reported by the central safety laboratory.
- Had a screening total bilirubin >2 x the ULN and direct bilirubin >1.5 x the ULN, as reported by the central safety laboratory.
- Had active solid tumor malignancies with the exception of basal cell carcinoma or the underlying condition necessitating HCT (e.g., lymphomas).
- Had Stage 2 or higher graft versus host disease of the gut or any other GI disease that would have, in the judgment of the investigator, precluded the subject from taking or absorbing oral medication (e.g., clinically active Crohn's disease, ischemic colitis, moderate or severe ulcerative colitis, small bowel resection, ileus, or any condition expected to require abdominal surgery during the course of study participation).
- Had any other condition, including abnormal laboratory values, that would have, in the judgement of the investigator, put the subject at increased risk by participating in the study or would have interfered with the conduct or planned analyses of the study.
Trial locations and contacts
43 sites in 3 countries.
43 sites in 3 countries
United States39 sites
University of Michigan
Ann Arbor, Michigan, 48109
Winship Cancer Institute-Emory
Atlanta, Georgia, 30322
Northside Hospital
Atlanta, Georgia, 30342
Johns Hopkins University
Baltimore, Maryland, 21205
Beth Isreal Decaconess Medical Center
Boston, Massachusetts, 02115
Brigham and Womens Hospital
Boston, Massachusetts, 02115
Hollings Cancer Center
Charleston, South Carolina, 29425
Levine Cancer Institute/Carolinas Health
Charlotte, North Carolina, 28204
Northwestern Memorial Hospital
Chicago, Illinois, 60611
University of Chicago
Chicago, Illinois, 60637
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229
The Jewish Hospital
Cincinnati, Ohio, 45236
Baylor University Medical Center
Dallas, Texas, 75246
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75390
University of Colorado
Denver, Colorado, 80045
Colorado Blood Cancer Institute
Denver, Colorado, 80218
Harper University Hospital
Detroit, Michigan, 48201
Henry Ford Hospital
Detroit, Michigan, 48202
Duke Cancer Institute
Durham, North Carolina, 27710
Hackensack University
Hackensack, New Jersey, 07601
MD Anderson Cancer Center
Houston, Texas, 77030
The Universit of Iowa
Iowa City, Iowa, 45229
University of California, San Diego-Moores Cancer Center
La Jolla, California, 92093
UCLA Medical Center
Los Angeles, California, 90095
University of Miami Hospital
Miami, Florida, 33136
University of Minnesota
Minneapolis, Minnesota, 55455
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Mt. Sinai Medical Center
New York, New York, 10029
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Weill Cornell Medical College/NY Presbyterial Hospital
New York, New York, 10065
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Allegheny-Singer Research Institute
Pittsburgh, Pennsylvania, 15224
Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, 15224
University of Utah, Huntsman Cancer Institute
Salt Lake City, Utah, 84112
Intermountain Healthcare
Salt Lake City, Utah, 84143
Methodist Healthcare of San Antonio
San Antonio, Texas, 78229
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
Montefiore Medical Center
The Bronx, New York, 10467
Wake Forest
Winston-Salem, North Carolina, 27517
Belgium2 sites
Centre Hospitalier Universitaire Sart Tilman Liege
Brussels, Liege, 4000
Cliniques Universitaires Saint Luc
Brussels, 1200
Canada2 sites
Centre Hospitalier Universitaire de Montreal, Hopital Maisonneuve-Rosemont
Montreal, Quebec, H1T 2M4
University of Toronto
Toronto, Ontario, M5G2C4
About this study
Official title: A Phase 3 Study of the Safety, Tolerability, and Efficacy of CMX001 for the Prevention of Cytomegalovirus (CMV) Infection in CMV-seropositive (R+) Hematopoietic Stem Cell Transplant Recipients
This randomized, double-blind, placebo-controlled, parallel group, multicenter study compared the effectiveness of oral brincidofovir (BCV) to placebo for the prevention of cytomegalovirus (CMV) infection in stem cell transplant patients who were CMV seropositive but negative for CMV viremia before starting treatment with BCV.
Read the detailed description
This was a randomized, double-blind, placebo-controlled, parallel group multicenter study of oral brincidofovir (BCV) in approximately 450 cytomegalovirus (CMV)-seropositive subjects who had undergone allogeneic hematopoietic stem cell transplantation (HCT). The study consisted of a screening evaluation and a treatment phase of 10 to 14 weeks. Dosing with the study drug (BCV or placebo) was initiated as soon as individual subjects could ingest tablets after transplant but no later than Day 28 post-transplant, and was continued through Week 14. All randomized subjects remained on study and followed the same scheduled study treatment. Study assessments were performed weekly from randomization through completion of the first post-treatment follow-up assessment at Week 15, and every 3 weeks thereafter through Week 24.
- Conditions
- CMV
- Being tested
- Brincidofovir, Placebo
- Keywords
- CMV, Hematopoietic Stem Cell Transplant Recipients, Prevention
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrincidofovirDrug
Also called BCV, CMX001, Hexadecyloxypropyl cidofovir, HDP-CDV
PlaceboOther
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Matching placebo administered orally twice weekly Receives: Other: Placebo |
| Brincidofovir | Active comparator | 100 mg brincidofovir administered orally twice weekly Receives: Drug: Brincidofovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Clinically Significant CMV Infection Through Week 24 Post-Transplant
Clinically significant cytomegalovirus (CMV) infection was defined by either of the following outcomes:
- Onset of CMV end-organ disease; or
- Initiation of anti-CMV-specific preemptive therapy based on documented CMV viremia (as measured by the central virology laboratory) and the clinical condition of the subject.
CMV viremia (i.e., the measurement of CMV DNA in plasma) was determined by the designated central virology laboratory at all scheduled visits via quantitative polymerase chain reaction (qPCR) testing using the Roche COBAS® AmpliPrep/COBAS® TaqMan® CMV Test.
Measured: 24 weeks
Secondary outcomes (1)
Incidence of Clinically Significant CMV Infection Through Week 14
The incidence of clinically significant cytomegalovirus (CMV) infection through Week 14.
Blood and urine for virologic evaluations were collected at screening, pre-dose on the first day of study drug administration, and at pre-specified intervals throughout the treatment phases of the study and sent to a designated central virology laboratory for analysis. Blood samples were used for real-time assay of CMV viremia in plasma using a qPCR assay. Urine samples were stored for possible future retrospective analyses of CMV.
Measured: 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2013 (estimated)
- Study startAug 2013
- Primary completionDec 2015
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CMVStudies of the same condition, open and under way.
- More trials run by Jazz PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 452 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jazz Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01769170
- Sponsor's protocol ID
- CMX001-301
- Status last verified
- Jul 2021
- First submitted
- 14 Jan 2013
- Last updated
- 21 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Marty FM, Winston DJ, Chemaly RF, Mullane KM, Shore TB, Papanicolaou GA, Chittick G, Brundage TM, Wilson C, Morrison ME, Foster SA, Nichols WG, Boeckh MJ; SUPPRESS Trial Clinical Study Group. A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial of Oral Brincidofovir for Cytomegalovirus Prophylaxis in Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2019 Feb;25(2):369-381. doi: 10.1016/j.bbmt.2018.09.038. Epub 2018 Oct 4.
PubMed 30292744
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Study of the Safety, Tolerability, and Efficacy of CMX001 for the Prevention of Cytomegalovirus (CMV) Infection in CMV-seropositive (R+) Hematopoietic Stem Cell Transplant Recipients
- ClinicalTrials.gov ID
- NCT01769170
- Acronym / sponsor ID
- CMX001-301
- Conditions
- CMV
- Keywords
- CMV, Hematopoietic Stem Cell Transplant Recipients, Prevention
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 452 participants (actual)
- Lead sponsor
- Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Aug 2013 (actual)
- Primary completion
- Dec 2015 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 16 Jan 2013 (estimated)
- Results
- Posted 5 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized, double-blind, placebo-controlled, parallel group, multicenter study compared the effectiveness of oral brincidofovir (BCV) to placebo for the prevention of cytomegalovirus (CMV) infection in stem cell transplant patients who were CMV seropositive but negative for CMV viremia before starting treatment with BCV.
Detailed description
This was a randomized, double-blind, placebo-controlled, parallel group multicenter study of oral brincidofovir (BCV) in approximately 450 cytomegalovirus (CMV)-seropositive subjects who had undergone allogeneic hematopoietic stem cell transplantation (HCT). The study consisted of a screening evaluation and a treatment phase of 10 to 14 weeks. Dosing with the study drug (BCV or placebo) was initiated as soon as individual subjects could ingest tablets after transplant but no later than Day 28 post-transplant, and was continued through Week 14. All randomized subjects remained on study and followed the same scheduled study treatment. Study assessments were performed weekly from randomization through completion of the first post-treatment follow-up assessment at Week 15, and every 3 weeks thereafter through Week 24.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: PlaceboMatching placebo administered orally twice weekly |
| Brincidofovir | Active comparator | Drug: Brincidofovir100 mg brincidofovir administered orally twice weekly |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Subjects were required to meet all of the following criteria, as applicable, to be eligible to participate in this study:
- Were allogeneic hematopoietic stem cell transplant (HCT) recipients who had prior evidence of cytomegalovirus (CMV) exposure (CMV-seropositive) before transplantation and were CMV viremia negative at screening and at any other assessments performed prior to the first dose of study drug.
- Were aged ≥18 years.
- If male, were willing to use an acceptable contraceptive method(s) throughout the duration of his participation in the study, i.e., through Week 24, when engaging in sexual intercourse with a female subject of childbearing potential.
- If female of childbearing potential, i.e., not postmenopausal or surgically sterile, were 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 24, when engaging in sexual intercourse with a nonsterile male partner.
Key exclusion criteria (24 listed)
- Subjects who met any of the following criteria, as applicable, were not eligible to participate in this study:
- Was pregnant or planned to become pregnant during the anticipated duration of her participation in the study (i.e., through Week 24), or was nursing a child.
- Had a positive CMV viremia test (at the designated central virology laboratory or a local virology laboratory) at any time between transplant and the first dose of study drug.
- Weighed ≥120 kg (~265 lbs).
- Had hypersensitivity (not renal dysfunction or eye disorder) to cidofovir (CDV), brincidofovir (BCV), or its excipients.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BrincidofovirAlso: BCV, CMX001, Hexadecyloxypropyl cidofovir, HDP-CDV | Drug | Brincidofovir |
| Placebo | Other | Placebo |
Primary outcome
Number of Participants With Clinically Significant CMV Infection Through Week 24 Post-Transplant
Time frame: 24 weeks
Clinically significant cytomegalovirus (CMV) infection was defined by either of the following outcomes: 1. Onset of CMV end-organ disease; or 2. Initiation of anti-CMV-specific preemptive therapy based on documented CMV viremia (as measured by the central virology laboratory) and the clinical condition of the subject. CMV viremia (i.e., the measurement of CMV DNA in plasma) was determined by the designated central virology laboratory at all scheduled visits via quantitative polymerase chain reaction (qPCR) testing using the Roche COBAS® AmpliPrep/COBAS® TaqMan® CMV Test.
1 secondary outcome
Incidence of Clinically Significant CMV Infection Through Week 14
Time frame: 14 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 30292744Marty FM, Winston DJ, Chemaly RF, Mullane KM, Shore TB, Papanicolaou GA, Chittick G, Brundage TM, Wilson C, Morrison ME, Foster SA, Nichols WG, Boeckh MJ; SUPPRESS Trial Clinical Study Group. A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial of Oral Brincidofovir for Cytomegalovirus Prophylaxis in Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2019 Feb;25(2):369-381. doi: 10.1016/j.bbmt.2018.09.038. Epub 2018 Oct 4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
43 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Brincidofovir in people with CMV, run by Jazz Pharmaceuticals at 43 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 43 sites in United States, Belgium, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Clinically Significant CMV Infection Through Week 24 Post-Transplant (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01769170, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2021.