Cytomegalovirus DiseasePhase 3SUSTAINNCT02439970
A Phase 3 Study of Brincidofovir Versus Valganciclovir for the Prevention of Cytomegalovirus Disease
A Phase 3 study testing Brincidofovir and Valganciclovir in people with Cytomegalovirus Disease, run by Jazz Pharmaceuticals at 3 sites in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cytomegalovirus Disease
- What is being tested?
- Brincidofovir and Valganciclovir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 3 sitesUnited States
- Study dates
- Sep 2015to 30 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 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.
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- 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).
Who cannot join
- 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.
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- 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.
- Had severe vomiting, diarrhea, or malabsorption syndrome on or prior to the first dose of study drug.
- Had gastrointestinal (GI) disease that would have, in the judgement of the investigator, precluded the subject form taking or absorbing oral medication (e.g., gastroparesis, diabetic autonomic neuropathy affecting the GI tract, clinically active Crohn's disease, ischemic colitis, moderate or severe ulcerative colitis, small bowel resection, ileus, or any condition that was expected to require abdominal surgery during the course of study participation).
- Had serum alanine aminotransferase or aspartate aminotransferase concentrations >5 x the upper limit of normal (ULN).
- Had total serum bilirubin >2 x the ULN and direct bilirubin >1.5x the ULN.
- Had moderate (Class B) to severe (Class C) hepatic dysfunction according to the Child-Pugh Turcotte scoring system.
- Were receiving or would require digoxin or ketoconazole therapy (other than topical formulations) during the treatment phase of the study.
- Had active malignancies (with the exception of basal cell carcinoma).
- Had a serious psychiatric, medical disorder, 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 of the study.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Colorado Hospital/Health Science Center
Aurora, Colorado, 80045
St. Vincent Medical Center
Los Angeles, California, 90057
Yale New Haven Hospital
New Haven, Connecticut, 06520
About this study
Official title: SUSTAIN: A Randomized, Double-Blind, Multicenter, Phase 3 Study of the Efficacy, Safety, and Tolerability of Brincidofovir Versus Valganciclovir for the Prevention of Cytomegalovirus Disease in High-Risk Kidney Allograft Recipients
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
Read the detailed description
This was a randomized, double-blind, double-dummy, parallel-group, multicenter study of the efficacy, safety, and tolerability of oral BCV versus vGCV for the prevention of CMV disease in high-risk kidney transplant allograft recipients, defined as CMV-seronegative recipients (R-) receiving a CMV-seropositive graft (D+). The study comprised a screening evaluation period (up to 14 days posttransplant), a treatment period (up to 28 weeks posttransplant), and a posttreatment follow-up period (24 weeks, through Week 52 posttransplant).
- Conditions
- Cytomegalovirus Disease
- Being tested
- Brincidofovir, Valganciclovir
- Keywords
- kidney transplant allograft, recipients
- 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 CMX001, BCV
ValganciclovirDrug
Also called vGCV
| Study group | Role | What they receive |
|---|---|---|
| Treatment 1 | Active comparator | 100 mg brincidofovir (BCV; 1 tablet) administered orally twice weekly, plus valganciclovir (vGCV) placebo (2 tablets) administered orally once daily. Receives: 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. Receives: Drug: Valganciclovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 52 weeks (± 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2015 (estimated)
- Study startSep 2015
- Primary completion30 Jan 2016
- Study completion30 Jan 2016
Why it stopped: Study was terminated early due to results from another CMX001 study
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.
- Other trials for Cytomegalovirus DiseaseStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 5 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
- NCT02439970
- Sponsor's protocol ID
- CMX001-303
- Acronym
- SUSTAIN
- Status last verified
- Jun 2021
- First submitted
- 7 May 2015
- Last updated
- 16 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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
- SUSTAIN: A Randomized, Double-Blind, Multicenter, Phase 3 Study of the Efficacy, Safety, and Tolerability of Brincidofovir Versus Valganciclovir for the Prevention of Cytomegalovirus Disease in High-Risk Kidney Allograft Recipients
- ClinicalTrials.gov ID
- NCT02439970
- Acronym / sponsor ID
- SUSTAIN / CMX001-303
- Conditions
- Cytomegalovirus Disease
- Keywords
- kidney transplant allograft, recipients
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated early due to results from another CMX001 study
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Sep 2015 (actual)
- Primary completion
- 30 Jan 2016 (actual)
- Study completion
- 30 Jan 2016 (actual)
- First posted
- 12 May 2015 (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.
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
Detailed description
This was a randomized, double-blind, double-dummy, parallel-group, multicenter study of the efficacy, safety, and tolerability of oral BCV versus vGCV for the prevention of CMV disease in high-risk kidney transplant allograft recipients, defined as CMV-seronegative recipients (R-) receiving a CMV-seropositive graft (D+). The study comprised a screening evaluation period (up to 14 days posttransplant), a treatment period (up to 28 weeks posttransplant), and a posttreatment follow-up period (24 weeks, through Week 52 posttransplant).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment 1 | Active comparator | Drug: Brincidofovir100 mg brincidofovir (BCV; 1 tablet) administered orally twice weekly, plus valganciclovir (vGCV) placebo (2 tablets) administered orally once daily. |
| Treatment 2 | Active comparator | Drug: Valganciclovir900 mg valganciclovir (vGCV; two 450 mg tablets) administered orally once daily, plus brincidofovir (BCV) placebo (1 tablet) 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 (10 listed)
- 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.
Key exclusion criteria (23 listed)
- 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.
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: CMX001, BCV | Drug | Treatment 1 |
| ValganciclovirAlso: vGCV | Drug | Treatment 2 |
Primary outcome
The Incidence of CMV Disease
Time frame: 52 weeks (± 28 days)
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.
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.
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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.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Brincidofovir and Valganciclovir in people with Cytomegalovirus Disease, run by Jazz Pharmaceuticals at 3 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 10 inclusion and 23 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: stopped early, 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 3 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. 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 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?
The Incidence of CMV Disease (time frame: 52 weeks (± 28 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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.