Cytomegalovirus InfectionPhase 2NCT00942305
Study of CMX001 to Prevent/Control Cytomegalovirus Infection in R+ Hematopoietic Stem Cell Transplant Recipients
A Phase 2 study testing Brincidofovir in people with Cytomegalovirus Infection, run by Jazz Pharmaceuticals at 26 sites in United States.
Trial summary
This was a multicenter, randomized, double-blind, placebo-controlled, dose-escalation study of brincidofovir (BCV) administered orally once or twice weekly for up to 11 weeks. Dosing was initiated immediately following engraftment (between Days 14-30 post-transplant) to prevent/control cytomegalovirus (CMV) infection… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cytomegalovirus Infection
- What is being tested?
- Brincidofovir
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 239 participants
- Where
- 26 sitesUnited States
- Study dates
- Oct 2009to Jan 2012
- Phase
- Phase 2
- 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
- For inclusion into the study, all prospective subjects were required to fulfill all of the following criteria (as applicable):
- Were aged ≥18 years. Males must have been able and willing to use adequate contraceptive methods throughout the treatment and follow-up phases of the study.
- Were cytomegalovirus (CMV) seropositive before allogeneic hematopoietic stem cell transplantation (HCT) (i.e., R+ subjects).
- Were less than 30 days post qualifying transplant.
- Had evidence of engraftment before randomization and receiving their first dose of study drug.
- Were able to ingest and absorb oral medication (in the judgment of the investigator and based on lack of significant gastrointestinal [GI] events).
- Were willing and able to understand and provide written informed consent.
- To the best of his or her knowledge, were willing and able to participate in all required study activities for the duration of the study.
Who cannot join
- Subjects meeting any of the following exclusion criteria were to be excluded from participation in the study:
- Females who were pregnant or currently nursing.
- Had a body mass index >35 kg/m2. [Note: This criterion was removed per Protocol Amendment 2 dated 27 August 2010.]
- Had hypersensitivity to cidofovir (CDV) or brincidofovir.
- Recipients for whom the current, predose clinical course of CMV infection suggested that the investigator would not be able to withhold treatment for CMV for a minimum of 5, but preferably 7 days following the subject's first dose of study drug.
- Received any of the following:
Show all 24Show fewer
- Ganciclovir, valganciclovir, foscarnet or CDV within 14 days prior to enrollment;
- Any anti-CMV therapy following transplantation (including Cytogam®1);
- Any CMV vaccine;
- Any investigational drug with antiviral activity against double-stranded DNA (dsDNA) viruses within 14 days prior to enrollment. [Note: An investigational drug was defined as a drug that was not approved for any indication by the Food and Drug Administration.]; or
- Any other investigational drug (i.e., those without any "anti-dsDNA virus" activity; e.g., anti-influenza compounds) within 14 days prior to enrollment without the prior written consent of the medical monitor. The use of investigational drugs in certain circumstances was added per Protocol Amendment 1 dated 15 January 2010.
- Received high dose acyclovir (>2000 mg total oral daily dose or >5 mg/kg intravenously 3 times daily) or valacyclovir (Valtrex; >3000 mg total daily dose) at the time of dosing.
- Were diagnosed with active CMV disease within 6 months prior to enrollment; patients with CMV DNAemia requiring intervention with antiviral therapy at the time of enrollment.
- Were HIV positive; patients with active hepatitis C virus (HCV) or hepatitis B virus (HBV) infection as evidenced by plasma levels of HCV RNA or HBV DNA, respectively.
- Received another allogeneic HCT within the past 2 years, other than the qualifying HCT.
- Had renal insufficiency as evidenced by glomerular filtration rate (GFR) <30 mL/min.
- Had a current diagnosis of hypotony, uveitis, or retinitis or any intraocular pathology that would predispose the subject to any one of these conditions.
- Had hepatic dysfunction as evidenced by alanine aminotransferase or aspartate aminotransferase >5 x the upper limit of normal (ULN) or direct bilirubin >2.5 x the ULN.
- Had any of the following active autoimmune disorders: myasthenia gravis, Addison's disease, Wegener's granulomatosis, primary biliary cirrhosis, bullous pemphigoid, autoimmune hemolytic anemia, autoimmune hepatitis, multiple sclerosis, Goodpasture's syndrome, idiopathic thrombocytopenic purpura, lupus erythematosus, dermatomyositis, polymyositis, or vasculitis.
- Had active solid tumor malignancies with the exception of basal cell carcinoma or the condition under treatment (e.g., lymphomas).
- Had 1 or more episode of hyperglycemic coma or diabetic ketoacidosis within the 6 months prior to enrollment.
- Had cardiovascular disease which, in the opinion of the investigator, would interfere with the conduct of the study.
- Had Grade 3 or 4 graft versus host disease of the GI tract; subjects with any GI disease that would, in the judgment of the investigator, preclude the subject from taking or absorbing oral medication (e.g. clinically active Crohn's disease, ischemic colitis, moderate or severe ulcerative colitis, or any condition expected to require abdominal surgery during the course of study participation).
- Any other condition including abnormal laboratory values that would have, in the judgment of the investigator, put the subject at increased risk for participating in the trial, or interferes with the conduct of the trial.
Trial locations and contacts
26 sites in 1 country.
26 sites in 1 country
United States26 sites
University of Michigan Medical School
Ann Arbor, Michigan, 48109
Winship Cancer Institute at Emory University
Atlanta, Georgia, 30322
University of Colorado Denver
Aurora, Colorado, 80045
The University of Alabama at Birmingham
Birmingham, Alabama, 35294
Brigham and Womens Hospital, Division of Infectious Disease
Boston, Massachusetts, 02115
UNC Health Care Center
Chapel Hill, North Carolina, 27599
University of Chicago Medical Center
Chicago, Illinois, 60637
The Cleveland Clinic
Cleveland, Ohio, 44195
Baylor University Medical Center
Dallas, Texas, 75246
UT Southwestern Medical Center at Dallas
Dallas, Texas, 75390-8565
Harper University Hospital
Detroit, Michigan, 48201
Duke University Medical Center
Durham, North Carolina, 27710
Hackensack University Medical Center
Hackensack, New Jersey, 07601
University of Texas, MD Anderson Cancer Center
Houston, Texas, 77030
Moores UCSD Cancer Center
La Jolla, California, 92093
UCLA Medical Center
Los Angeles, California, 90095
University of Minnesota Medical Center
Minneapolis, Minnesota, 55455
Mt. Sinai School of Medicine
New York, New York, 10029
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Nebraska Medical Center
Omaha, Nebraska, 68198-5130
Oregon Health and Science University
Portland, Oregon, 97239
University of Rochester Medical Center
Rochester, New York, 14642
Utah Cancer Specialists - Intermountain Healthcare
Salt Lake City, Utah, 84088
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
Montefiore Medical Center Oncology
The Bronx, New York, 10467
Wake Forest University School of Medicine
Winston-Salem, North Carolina, 27517
About this study
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-escalation Study of the Safety, Tolerability and Ability of CMX001 to Prevent or Control CMV Infection in R+ Hematopoietic Stem Cell Transplant Recipients
This was a multicenter, randomized, double-blind, placebo-controlled, dose-escalation study of brincidofovir (BCV) administered orally once or twice weekly for up to 11 weeks. Dosing was initiated immediately following engraftment (between Days 14-30 post-transplant) to prevent/control cytomegalovirus (CMV) infection or prevent disease in R+ hematopoietic stem cell transplant (HCT) recipients.
Read the detailed description
This was to be a 2-part study. Part 1 was a randomized, double-blind, placebo-controlled, dose-escalation study of multiple doses of oral brincidofovir (BCV) in R+ hematopoietic stem cell transplant (HCT) recipients. In Part 2, one of the dose levels administered in Part 1 was to be tested against placebo to evaluate the statistical significance of BCV as a therapy for preventing progression of cytomegalovirus (CMV) infection or preventing CMV disease. The first 3 dose-escalating cohorts in Part 1 were to include 32 subjects within each cohort (24 randomized to receive oral BCV and 8 randomized to receive placebo in a 3:1 ratio) for a total of 96 planned subjects. Following completion of the first 3 cohorts and subsequent safety review of the data, up to an additional 3 cohorts of 32 subjects each could have been enrolled. Two additional cohorts (labeled Cohort 4 and Cohort 4A) beyond the initial 3 cohorts were actually enrolled in Part 1 of the study. Following the safety and antiviral activity analyses of the 5 cohorts in Part 1 and the number of subjects enrolled in each of those cohorts, Part 2 of the study was not conducted.
- Conditions
- Cytomegalovirus Infection
- Being tested
- Brincidofovir, Placebo
- Keywords
- Allogeneic stem cell transplant, CMV seropositive (R+), transplant
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrincidofovirDrug
Also called BCV, CMX001
Subjects received their first dose of study drug of brincidofovir (BCV) within 30 (+5) days post-transplant and were treated through Week 13 post-transplant.
PlaceboDrug
Subjects received their first dose of study drug within 30 (+5) days post-transplant and were treated through Week 13 post-transplant.
Matching placebo administered for each cohort.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | * Cohort 1 = 40 mg of matching placebo administered once weekly (QW)
* Cohort 2 = 100 mg of matching placebo administered QW
* Cohort 3 = 200 mg of matching placebo administered QW
* Cohort 4 = 200 mg of matching placebo administered twice weekly (BIW)
* Cohort 4A = 100 mg of matching placebo administered BIW Receives: Drug: Placebo |
| Brincidofovir | Experimental | * Cohort 1 = 40 mg brincidofovir (BCV) administered once weekly (QW)
* Cohort 2 = 100 mg BCV administered QW
* Cohort 3 = 200 mg BCV administered QW
* Cohort 4 = 200 mg BCV administered twice weekly (BIW)
* Cohort 4A = 100 mg BCV administered BIW 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
The primary efficacy endpoint was a binomial outcome of failure to prevent cytomegalovirus (CMV) infection defined as CMV DNAemia >200 copies/mL obtained at the time of the last treatment with study drug or diagnosis of CMV disease at some point during the treatment phase.
Measured: Randomization to Week 8 post-treatment (~19 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2009 (estimated)
- Study startOct 2009
- Primary completionJan 2012
- Study completionJan 2012
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 (3)Papers the sponsor has linked to this study.
- Other trials for Cytomegalovirus InfectionStudies 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 239 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
- NCT00942305
- Sponsor's protocol ID
- CMX001-201
- Status last verified
- Jun 2021
- First submitted
- 17 Jul 2009
- Last updated
- 16 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lanier ER, Foster S, Brundage T, Chou S, Prichard MN, Kleiboeker S, Wilson C, Colville D, Mommeja-Marin H. Analysis of Mutations in the Gene Encoding Cytomegalovirus DNA Polymerase in a Phase 2 Clinical Trial of Brincidofovir Prophylaxis. J Infect Dis. 2016 Jul 1;214(1):32-5. doi: 10.1093/infdis/jiw073. Epub 2016 Mar 3.
PubMed 26941282Marty FM, Winston DJ, Rowley SD, Vance E, Papanicolaou GA, Mullane KM, Brundage TM, Robertson AT, Godkin S, Mommeja-Marin H, Boeckh M; CMX001-201 Clinical Study Group. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med. 2013 Sep 26;369(13):1227-36. doi: 10.1056/NEJMoa1303688.
PubMed 24066743Tippin 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.
PubMed 27851688
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-escalation Study of the Safety, Tolerability and Ability of CMX001 to Prevent or Control CMV Infection in R+ Hematopoietic Stem Cell Transplant Recipients
- ClinicalTrials.gov ID
- NCT00942305
- Acronym / sponsor ID
- CMX001-201
- Conditions
- Cytomegalovirus Infection
- Keywords
- Allogeneic stem cell transplant, CMV seropositive (R+), transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 239 participants (actual)
- Lead sponsor
- Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Oct 2009 (actual)
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 20 Jul 2009 (estimated)
- Results
- Posted 16 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a multicenter, randomized, double-blind, placebo-controlled, dose-escalation study of brincidofovir (BCV) administered orally once or twice weekly for up to 11 weeks. Dosing was initiated immediately following engraftment (between Days 14-30 post-transplant) to prevent/control cytomegalovirus (CMV) infection or prevent disease in R+ hematopoietic stem cell transplant (HCT) recipients.
Detailed description
This was to be a 2-part study. Part 1 was a randomized, double-blind, placebo-controlled, dose-escalation study of multiple doses of oral brincidofovir (BCV) in R+ hematopoietic stem cell transplant (HCT) recipients. In Part 2, one of the dose levels administered in Part 1 was to be tested against placebo to evaluate the statistical significance of BCV as a therapy for preventing progression of cytomegalovirus (CMV) infection or preventing CMV disease. The first 3 dose-escalating cohorts in Part 1 were to include 32 subjects within each cohort (24 randomized to receive oral BCV and 8 randomized to receive placebo in a 3:1 ratio) for a total of 96 planned subjects. Following completion of the first 3 cohorts and subsequent safety review of the data, up to an additional 3 cohorts of 32 subjects each could have been enrolled. Two additional cohorts (labeled Cohort 4 and Cohort 4A) beyond the initial 3 cohorts were actually enrolled in Part 1 of the study. Following the safety and antiviral activity analyses of the 5 cohorts in Part 1 and the number of subjects enrolled in each of those cohorts, Part 2 of the study was not conducted.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo* Cohort 1 = 40 mg of matching placebo administered once weekly (QW) * Cohort 2 = 100 mg of matching placebo administered QW * Cohort 3 = 200 mg of matching placebo administered QW * Cohort 4 = 200 mg of matching placebo administered twice weekly (BIW) * Cohort 4A = 100 mg of matching placebo administered BIW |
| Brincidofovir | Experimental | Drug: Brincidofovir* Cohort 1 = 40 mg brincidofovir (BCV) administered once weekly (QW) * Cohort 2 = 100 mg BCV administered QW * Cohort 3 = 200 mg BCV administered QW * Cohort 4 = 200 mg BCV administered twice weekly (BIW) * Cohort 4A = 100 mg BCV administered BIW |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- For inclusion into the study, all prospective subjects were required to fulfill all of the following criteria (as applicable):
- Were aged ≥18 years. Males must have been able and willing to use adequate contraceptive methods throughout the treatment and follow-up phases of the study.
- Were cytomegalovirus (CMV) seropositive before allogeneic hematopoietic stem cell transplantation (HCT) (i.e., R+ subjects).
- Were less than 30 days post qualifying transplant.
- Had evidence of engraftment before randomization and receiving their first dose of study drug.
Key exclusion criteria (24 listed)
- Subjects meeting any of the following exclusion criteria were to be excluded from participation in the study:
- Females who were pregnant or currently nursing.
- Had a body mass index >35 kg/m2. [Note: This criterion was removed per Protocol Amendment 2 dated 27 August 2010.]
- Had hypersensitivity to cidofovir (CDV) or brincidofovir.
- Recipients for whom the current, predose clinical course of CMV infection suggested that the investigator would not be able to withhold treatment for CMV for a minimum of 5, but preferably 7 days following the subject's first dose of study drug.
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, CMX001Subjects received their first dose of study drug of brincidofovir (BCV) within 30 (+5) days post-transplant and were treated through Week 13 post-transplant. | Drug | Brincidofovir |
| PlaceboSubjects received their first dose of study drug within 30 (+5) days post-transplant and were treated through Week 13 post-transplant. Matching placebo administered for each cohort. | Drug | Placebo |
Primary outcome
Number of Participants With Clinically Significant CMV Infection
Time frame: Randomization to Week 8 post-treatment (~19 weeks)
The primary efficacy endpoint was a binomial outcome of failure to prevent cytomegalovirus (CMV) infection defined as CMV DNAemia >200 copies/mL obtained at the time of the last treatment with study drug or diagnosis of CMV disease at some point during the treatment phase.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26941282Lanier ER, Foster S, Brundage T, Chou S, Prichard MN, Kleiboeker S, Wilson C, Colville D, Mommeja-Marin H. Analysis of Mutations in the Gene Encoding Cytomegalovirus DNA Polymerase in a Phase 2 Clinical Trial of Brincidofovir Prophylaxis. J Infect Dis. 2016 Jul 1;214(1):32-5. doi: 10.1093/infdis/jiw073. Epub 2016 Mar 3.
- Results publication: PubMed 24066743Marty FM, Winston DJ, Rowley SD, Vance E, Papanicolaou GA, Mullane KM, Brundage TM, Robertson AT, Godkin S, Mommeja-Marin H, Boeckh M; CMX001-201 Clinical Study Group. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med. 2013 Sep 26;369(13):1227-36. doi: 10.1056/NEJMoa1303688.
- Derived from this study: PubMed 27851688Tippin 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.
- Analysis of Mutations in Gene Encoding Cytomegalovirus DNA Polymerase in a Phase 2 Clinical Trial of Brincidofovir ProphylaxisLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Cytomegalovirus Infection
RecruitingObservational study
A Study of LIVTENCITY (Maribavir) in Adults With Cytomegalovirus (CMV) Infection After Transplantation in South Korea
Cytomegalovirus (CMV)
RecruitingObservational study
The Natural History of Severe Viral Infections and Characterization of Immune Defects in Patients Without Known Immunocompromise
EBV, HSV
RecruitingPhase 1
TETRAVI Multivirus CTL for Treatment of EBV, CMV, Adenovirus, and BK Infections Post Allogeneic SCT.
Viral Infection
RecruitingPhase 2
CMV CTLs in Neonates With CMV Infection
Congenital Cytomegaloviral (CMV) Disease
RecruitingPhase 2
CMV-MVA Triplex Vaccination in HLA-Matched Related Stem Cell Donors for the Prevention of CMV Infection in Patients Undergoing Hematopoietic Stem Cell Transplant
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
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.
26 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Brincidofovir in people with Cytomegalovirus Infection, run by Jazz Pharmaceuticals at 26 sites in United States.
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 8 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 16 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 26 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 16 Jul 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 (time frame: Randomization to Week 8 post-treatment (~19 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 NCT00942305, which also lists 3 linked publications.
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 16 Jul 2021.