Double-stranded DNA VirusPhase 3NCT01143181
Study to Assess Brincidofovir Treatment of Serious Diseases or Conditions Caused by Double-stranded DNA Viruses
A Phase 3 study testing Brincidofovir in people with Double-stranded DNA Virus, run by Jazz Pharmaceuticals at 37 sites in United States.
Trial summary
This was a multicenter, open-label study of oral brincidofovir (BCV) treatment of serious disease or conditions caused by double-stranded DNA (dsDNA) virus(es). Subjects received either a weight-based or a fixed dose of oral BCV once weekly (QW) or twice weekly (BIW) for up to 3 months until clinical disease was… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Double-stranded DNA Virus
- What is being tested?
- Brincidofovir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 210 participants
- Where
- 37 sitesUnited States
- Study dates
- Dec 2010to Dec 2012
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Subjects were required to meet all of the following inclusion criteria in order to participate in the study:
- Had an immediately life-threatening or serious disease or condition caused by infection with a double-stranded DNA virus (including subjects with recurrent viral disease). [Note: During the course of the study, the viral disease indications were narrow to focus on indications that were under study in controlled clinical trials of brincidofovir (BCV) and on viral diseases that had few, if any, options for treatment, including cytomegalovirus (CMV), adenovirus (AdV), herpes simplex virus (HSV), vaccinia virus (VAVC), variola virus (VARV) or monkeypox viruses(s).]
- Had a life expectancy of at least 2 weeks and commitment to continuation of supportive care for at least 4 weeks.
- Were able to ingest and absorb oral medication (in the judgment of the investigator and based on lack of significant gastrointestinal [GI] pathology such as small bowel resection or ileus). [Note: Use of total parenteral nutrition was not in and of itself exclusionary as long as the reason for use did not disqualify the subject based on this criterion.]
- Were willing and able to understand and provide written informed consent. [Note: For minors or those incapable of providing written informed consent (i.e., incapacitated), consent was provided by a parent or legal guardian or representative who could understand and provide written informed consent.]
- Were willing and able, to the best of his or her (or parent/guardian) knowledge, to participate in all required study activities for the duration of the study.
- If female of reproductive potential, agreed to use 2 acceptable methods of birth control throughout the study with at least 1 being a barrier method.
- In the judgment of the investigator, subjects for whom no comparable or satisfactory therapeutic alternative was available
Who cannot join
- Subjects were not to be enrolled if they met any of the following exclusion criteria:
- Were pregnant or currently nursing.
- Had hypersensitivity to cidofovir or BCV.
- Had a long-term prognosis that included a poor likelihood of survival due to irreversible organ failure including, for example, subjects with frank hepatic failure and adults with Grade 4 graft versus host disease of the GI tract.
- Were eligible for enrollment and able to participate in a clinical trial evaluating BCV. [Note: Per the FDA guidance, subjects eligible and able to participate in a controlled clinical study evaluating BCV were not eligible for participation in this study. Subjects who did not meet eligibility criteria for a controlled BCV clinical study or who were unable to participate because, for example, of logistical or other issues were eligible to participate in this study. The investigator verified that his/her subjects met this criterion on the Eligibility electronic case report form. A subject simply preferring enrollment in this study over a BCV controlled clinical trial did not qualify for enrollment in this study.]
- Had any other condition that would have, in the judgment of the investigator, put the subject at increased risk during participation in the study or interfered with the conduct of the study.
- Had a serum total bilirubin value >5 x the upper limit of normal reference range, taking into account the age and/or gender of the subject. [Note: In order to avoid any unwarranted delay to the start of BCV treatment, compliance with this exclusion criterion may have been determined based on the results of testing performed at a local safety laboratory, rather than waiting for results from the designated central safety laboratory. If relying on local safety laboratory test results, the blood sample must have been collected no more than 7 days prior to the scheduled first dose administration on Day 0, otherwise it was repeated. A subject whose elevated bilirubin was due to the underlying viral disease may still have been enrolled into the study if the participation of the subject was prospectively approved by the Chimerix Medical Monitor.]
- Subjects with acute or chronic renal impairment, pediatric and adolescent subjects, and subjects aged 65 years and older were included in this study. Subjects with hepatic impairment were included unless the investigator judged that the subject had irreversible hepatic compromise.
Trial locations and contacts
37 sites in 1 country.
37 sites in 1 country
United States37 sites
University of Michigan
Ann Arbor, Michigan, 48109
Children's Hospital of Colorado
Aurora, Colorado, 80045
NIH
Bethesda, Maryland, 20892
Tufts Medical Center
Boston, Massachusetts, 02111
Brigham and Womens Hospital
Boston, Massachusetts, 02115
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Levine Children's Hospital Carolina Medical Center
Charlotte, North Carolina, 28203
University of Chicago
Chicago, Illinois, 60637
Cincinnati Childrens Hospital
Cincinnati, Ohio, 45229
Cleveland Clinic
Cleveland, Ohio, 44195
Nationwide Children's Hospital
Columbus, Ohio, 43205
Duke University Medical Center
Durham, North Carolina, 27710
Cook Children's Medical Center
Fort Worth, Texas, 76104-2796
Hackensack University Medical Center
Hackensack, New Jersey, 07601
UT MD Anderson Cancer Center
Houston, Texas, 77030
University of Iowa
Iowa City, Iowa, 52242
Loma Linda University Hospital
Loma Linda, California, 92354
Children's Hospital of LA
Los Angeles, California, 90027
UCLA Department of Medicine
Los Angeles, California, 90095
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
University of Minnesota
Minneapolis, Minnesota, 55455
Childrens Hospital LSU
New Orleans, Louisiana, 70118
Mt. Sinai
New York, New York, 10029
Columbia University
New York, New York, 10032
Memorial Sloan Kettering Cancer Institute
New York, New York, 10065
University of Nebraska Medical Center
Omaha, Nebraska, 68198-5130
CHOC Children's
Orange, California, 92868
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
UPMC
Pittsburgh, Pennsylvania, 15213
Childrens Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
Oregon Health and Science University
Portland, Oregon, 97239
Intermountain BMT program LDS Hospital
Salt Lake City, Utah, 84143
Univeristy of San Francisco
San Francisco, California, 94143
University of Washington-Fred Hutchinson Cancer Center
Seattle, Washington, 98109
St. Louis Children's Hospital
St Louis, Missouri, 63110
Lucile Packard Children's Hospital
Stanford, California, 94304
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: A Multicenter, Open-label Study of CMX001 Treatment of Serious Diseases or Conditions Caused by Double-stranded DNA Viruses
This was a multicenter, open-label study of oral brincidofovir (BCV) treatment of serious disease or conditions caused by double-stranded DNA (dsDNA) virus(es). Subjects received either a weight-based or a fixed dose of oral BCV once weekly (QW) or twice weekly (BIW) for up to 3 months until clinical disease was resolved or stabilized and/or viral DNA by polymerase chain reaction testing was negative for 4 consecutive weeks, whichever was longer. Under the first protocol amendment, adults and adolescents (≥13 years) received 200 mg or 300 mg BCV BIW (not to exceed 4 mg/kg total weekly dose) depending on the difficulty of treating their disease (i.e., Group 1 or Group 2, respectively), and pediatric subjects (≤12 years) received 4 mg/kg BCV BIW. Under the second protocol amendment, adults and adolescents (≥13 years), regardless of viral infection/disease, had a maximum weekly dose of 200 mg, i.e., 200 mg QW or 100 mg BIW; not to exceed 4mg/kg total weekly dose. Pediatric subjects (≤12 years), regardless of viral infection/disease, had a maximum weekly dose of 4 mg/kg, i.e., 4 mg/kg QW or 2 mg/kg BIW; not to exceed 200 mg.
Read the detailed description
This was a multicenter, open-label study of oral brincidofovir (BCV) treatment of serious disease or conditions caused by double-stranded DNA (dsDNA) virus(es).
Subjects with a life-threatening or serious disease or condition caused by infection with any dsDNA virus(es), who met the protocol eligibility criteria and who were approved by the Chimerix Medical Monitor were enrolled in this open-label treatment study. During the course of the study, the viral disease indications were narrowed in Amendment 2 to cytomegalovirus, adenovirus, herpes simplex virus, vaccinia virus, variola virus, or monkeypox virus to focus on indications that were under study in controlled clinical trials of oral BCV and on viral disease with few, if any, options for treatment. However, subjects with other viral disease indications may have been enrolled with the approval of the Chimerix Medical Monitor.
Subjects received either a weight-based or a fixed dose of oral BCV once weekly (QW) or twice weekly (BIW) for up to 3 months until clinical disease was resolved or stabilized and/or viral DNA by polymerase chain reaction testing was negative for 4 consecutive weeks, whichever was longer. Subjects who met criteria for resolution of viral disease may have: 1) discontinued BCV; 2) reduced the dose or dosing frequency of BCV; or 3) continued BCV QW or BIW, depending on the investigator's assessment of the risk of relapse and following discussion with the Chimerix medical monitor.
- Conditions
- Double-stranded DNA Virus
- Being tested
- Brincidofovir
- Keywords
- Cytomegalovirus, Adenovirus, Herpes simplex virus, Vaccinia virus, Variola virus
- Medical subject headings
- Adenoviridae Infections, Herpes Simplex, Vaccinia, Smallpox
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrincidofovirDrug
Also called CMX001, BCV
Brincidofovir (BCV) was administered orally either once or twice weekly for up to 3 months. Treatment may have been extended for an additional 3 months depending a satisfactory review of safety parameters. Subjects could not receive more than a total of 6 months of treatment with BCV without prior approval.
| Study group | Role | What they receive |
|---|---|---|
| Brincidofovir | Experimental | Subjects received either a weight-based or a fixed-dose of oral brincidofovir (BCV) once weekly or twice weekly for up to 3 months until clinical disease was resolved or stabilized and/or viral DNA polymerase chain reaction testing was negative for 4 consecutive weeks, whichever was longer. Receives: Drug: Brincidofovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects Who Had a Sustained and Significant Reduction in Plasma Viral Load of Primary dsDNA Virus
Proportion of subjects who achieved a confirmed reduction in viral load for the primary dsDNA virus of ≥1 log10 copies/mL from baseline or to an undetectable level. Confirmation required the reduction in viral load (i.e., decrease of ≥ 1 log10 copies/mL from baseline or to undetectable levels) to be maintained at the next assessment for the subject to be considered a success.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2010 (estimated)
- Study startDec 2010
- Primary completionDec 2012
- Study completionDec 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 (1)Papers the sponsor has linked to this study.
- Other trials for Double-stranded DNA VirusStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 210 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
- NCT01143181
- Sponsor's protocol ID
- CMX001-350
- Status last verified
- Jul 2021
- First submitted
- 11 Jun 2010
- Last updated
- 12 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Tippin 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 12 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-label Study of CMX001 Treatment of Serious Diseases or Conditions Caused by Double-stranded DNA Viruses
- ClinicalTrials.gov ID
- NCT01143181
- Acronym / sponsor ID
- CMX001-350
- Conditions
- Double-stranded DNA Virus
- Keywords
- Cytomegalovirus, Adenovirus, Herpes simplex virus, Vaccinia virus, Variola virus
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 210 participants (actual)
- Lead sponsor
- Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Dec 2010 (actual)
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 14 Jun 2010 (estimated)
- Results
- Posted 12 Aug 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, open-label study of oral brincidofovir (BCV) treatment of serious disease or conditions caused by double-stranded DNA (dsDNA) virus(es). Subjects received either a weight-based or a fixed dose of oral BCV once weekly (QW) or twice weekly (BIW) for up to 3 months until clinical disease was resolved or stabilized and/or viral DNA by polymerase chain reaction testing was negative for 4 consecutive weeks, whichever was longer. Under the first protocol amendment, adults and adolescents (≥13 years) received 200 mg or 300 mg BCV BIW (not to exceed 4 mg/kg total weekly dose) depending on the difficulty of treating their disease (i.e., Group 1 or Group 2, respectively), and pediatric subjects (≤12 years) received 4 mg/kg BCV BIW. Under the second protocol amendment, adults and adolescents (≥13 years), regardless of viral infection/disease, had a maximum weekly dose of 200 mg, i.e., 200 mg QW or 100 mg BIW; not to exceed 4mg/kg total weekly dose. Pediatric subjects (≤12 years), regardless of viral infection/disease, had a maximum weekly dose of 4 mg/kg, i.e., 4 mg/kg QW or 2 mg/kg BIW; not to exceed 200 mg.
Detailed description
This was a multicenter, open-label study of oral brincidofovir (BCV) treatment of serious disease or conditions caused by double-stranded DNA (dsDNA) virus(es).
Subjects with a life-threatening or serious disease or condition caused by infection with any dsDNA virus(es), who met the protocol eligibility criteria and who were approved by the Chimerix Medical Monitor were enrolled in this open-label treatment study. During the course of the study, the viral disease indications were narrowed in Amendment 2 to cytomegalovirus, adenovirus, herpes simplex virus, vaccinia virus, variola virus, or monkeypox virus to focus on indications that were under study in controlled clinical trials of oral BCV and on viral disease with few, if any, options for treatment. However, subjects with other viral disease indications may have been enrolled with the approval of the Chimerix Medical Monitor.
Subjects received either a weight-based or a fixed dose of oral BCV once weekly (QW) or twice weekly (BIW) for up to 3 months until clinical disease was resolved or stabilized and/or viral DNA by polymerase chain reaction testing was negative for 4 consecutive weeks, whichever was longer. Subjects who met criteria for resolution of viral disease may have: 1) discontinued BCV; 2) reduced the dose or dosing frequency of BCV; or 3) continued BCV QW or BIW, depending on the investigator's assessment of the risk of relapse and following discussion with the Chimerix medical monitor.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Brincidofovir | Experimental | Drug: BrincidofovirSubjects received either a weight-based or a fixed-dose of oral brincidofovir (BCV) once weekly or twice weekly for up to 3 months until clinical disease was resolved or stabilized and/or viral DNA polymerase chain reaction testing was negative for 4 consecutive weeks, whichever was longer. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Subjects were required to meet all of the following inclusion criteria in order to participate in the study:
- Had an immediately life-threatening or serious disease or condition caused by infection with a double-stranded DNA virus (including subjects with recurrent viral disease). [Note: During the course of the study, the viral disease indications were narrow to focus on indications that were under study in controlled clinical trials of brincidofovir (BCV) and on viral diseases that had few, if any, options for treatment, including cytomegalovirus (CMV), adenovirus (AdV), herpes simplex virus (HSV), vaccinia virus (VAVC), variola virus (VARV) or monkeypox viruses(s).]
- Had a life expectancy of at least 2 weeks and commitment to continuation of supportive care for at least 4 weeks.
- Were able to ingest and absorb oral medication (in the judgment of the investigator and based on lack of significant gastrointestinal [GI] pathology such as small bowel resection or ileus). [Note: Use of total parenteral nutrition was not in and of itself exclusionary as long as the reason for use did not disqualify the subject based on this criterion.]
- Were willing and able to understand and provide written informed consent. [Note: For minors or those incapable of providing written informed consent (i.e., incapacitated), consent was provided by a parent or legal guardian or representative who could understand and provide written informed consent.]
Key exclusion criteria (8 listed)
- Were pregnant or currently nursing.
- Had hypersensitivity to cidofovir or BCV.
- Had a long-term prognosis that included a poor likelihood of survival due to irreversible organ failure including, for example, subjects with frank hepatic failure and adults with Grade 4 graft versus host disease of the GI tract.
- Were eligible for enrollment and able to participate in a clinical trial evaluating BCV. [Note: Per the FDA guidance, subjects eligible and able to participate in a controlled clinical study evaluating BCV were not eligible for participation in this study. Subjects who did not meet eligibility criteria for a controlled BCV clinical study or who were unable to participate because, for example, of logistical or other issues were eligible to participate in this study. The investigator verified that his/her subjects met this criterion on the Eligibility electronic case report form. A subject simply preferring enrollment in this study over a BCV controlled clinical trial did not qualify for enrollment in this study.]
- Had any other condition that would have, in the judgment of the investigator, put the subject at increased risk during participation in the study or interfered with the conduct of the study.
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, BCVBrincidofovir (BCV) was administered orally either once or twice weekly for up to 3 months. Treatment may have been extended for an additional 3 months depending a satisfactory review of safety parameters. Subjects could not receive more than a total of 6 months of treatment with BCV without prior approval. | Drug | Brincidofovir |
Primary outcome
Number of Subjects Who Had a Sustained and Significant Reduction in Plasma Viral Load of Primary dsDNA Virus
Time frame: 3 months
Proportion of subjects who achieved a confirmed reduction in viral load for the primary dsDNA virus of ≥1 log10 copies/mL from baseline or to an undetectable level. Confirmation required the reduction in viral load (i.e., decrease of ≥ 1 log10 copies/mL from baseline or to undetectable levels) to be maintained at the next assessment for the subject to be considered a success.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
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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.
37 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 in people with Double-stranded DNA Virus, run by Jazz Pharmaceuticals at 37 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 8 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 12 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 37 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 12 Aug 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 Subjects Who Had a Sustained and Significant Reduction in Plasma Viral Load of Primary dsDNA Virus (time frame: 3 months). 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 NCT01143181, 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 12 Aug 2021.