Adenovirus DiseasePhase 2NCT01241344
Phase 2 Study to Evaluate Brincidofovir for the Prevention of Adenovirus Disease
A Phase 2 study testing Brincidofovir in people with Adenovirus Disease, run by Jazz Pharmaceuticals at 30 sites in United States.
Trial summary
This study was designed to assess the safety and efficacy of preemptive treatment with oral brincidofovir (BCV), as compared to placebo, for the prevention of adenovirus (AdV) disease in recipients of hematopoietic stem cell transplantation (HCT) with asymptomatic AdV viremia. Read more about this study
- Who is it for?
- Ages 3 months to 75 years
- Conditions the study is for
- Adenovirus Disease
- 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
- 52 participants
- Where
- 30 sitesUnited States
- Study dates
- Nov 2010to Jun 2013
- 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 3 months to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- For inclusion into the study, subjects were required to fulfill all of the following criteria:
- Were males or female aged ≥3 months to ≤75 years.
- Received an allogeneic hematopoietic stem cell transplant (HCT).
- Had positive serum adenovirus (AdV) PCR (>100 copies/mL) as measured by the central laboratory (unless the subject developed AdV disease while participating in the prescreening activities and after concurrence from the Chimerix medical monitor or designee).
- Was on dialysis during treatment if he/she had an estimated glomerular filtration rate (eGFR) ≤30 mL/minute.
- Subject or guardian(s) were willing to comply with the protocol.
- Subject or guardian(s) were willing and able to understand the informed consent/assent.
- Female subjects of child-bearing potential must have had a negative pregnancy test and must have agreed to use 2 acceptable methods of birth control throughout the study with at least 1 being a barrier method. Sexually active males of procreation potential must have been able and willing to se a reliable and medically approved contraceptive method throughout the study. At least 1 barrier method of contraception must have been used.
Who cannot join
- Subjects meeting any of the following exclusion criteria were excluded from participation in the study:
- Had possible, probable, or definitive AdV disease (unless the subject developed probable or definitive AdV disease while participating in prescreening activities and after concurrence from he Chimerix medical monitor or designee).
- Had suspected gut graft versus host disease that was not biopsy-proven (subjects with a biopsy performed were included in the study).
- Had an eGFR ≤30 mL/minute and was not currently on dialysis.
- Had an alanine aminotransferase or aspartate aminotransferase >5 x the upper limit of normal (ULN), total bilirubin ≥2 x the ULN, or conjugated (direct) bilirubin ≥1.5 x the ULN.
- Had a condition that prevented oral dosing of study drug.
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- Was HIV antibody positive, based upon available medical records.
- Had ocular hypotony, uveitis, or retinitis or any other intraocular pathology that would have predisposed the subject to 1 of these conditions.
- Had participated in another clinical study of an investigational drug/biologic or was exposed to an investigational drug/biologic within 30 days of enrollment without the prior written approval of the Chimerix medical monitor or designee. For subjects who were participating in any clinical study involving non-investigational drugs and/or biologics, the investigator must have obtained approval from the Chimerix medical monitor or designee prior to enrolling the subject.
- Was pregnant or breast-feeding or intended to conceive during the course of the study, including the follow-up period after drug discontinuation.
- Had known immunologic hypersensitivity to cidofovir (CDV) or brincidofovir (BCV) drug or any of its excipients.
- Had a history of illicit drug use or alcohol abuse within the previous 6 months.
- Had any medical condition that, in the opinion of the investigator, might have interfered with the subject's participation in the study, posed an added risk for the subject, or confounded the assessment of the subject (e.g. severe cardiovascular, central nervous system or pulmonary disease).
- Received BCV, CDV, ribavirin, or leflunomide within the previous 14 days.
- Was receiving or was anticipated to need treatment with digoxin that could not have been withheld for the duration of BCV therapy.
- Any exemptions to the protocol inclusion or exclusion criteria, as applicable, for subjects who developed probably or definitive AdV disease while participating in prescreening activities must have been discussed with and approved by the Chimerix medical monitor or designee before the subject was allowed to receive open-label BCV therapy.
Trial locations and contacts
30 sites in 1 country.
30 sites in 1 country
United States30 sites
The Children's Hospital-Denver
Aurora, Colorado, 80045
Children's Hospital of Alabama
Birmingham, Alabama, 35233
Harvard-Children's Hospital Boston
Boston, Massachusetts, 02115
Cincinnati Childrens Hospital
Cincinnati, Ohio, 45229
Cleveland Clinic
Cleveland, Ohio, 44195
UT Southwestern
Dallas, Texas, 75390
City of Hope National Medical Center
Duarte, California, 91010
Duke University Medical Center
Durham, North Carolina, 27710
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Baylor College of Medicine, Texas Childrens Hospital
Houston, Texas, 77030
MD Anderson Cancer Center
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202
Childrens hospital of LA
Los Angeles, California, 90033
St. Judes Children's Research Hospital
Memphis, Tennessee, 38105
Univeristy of Minnesota
Minneapolis, Minnesota, 55455
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
LSU Health Sciences Center New Orleans Childrens Hospital
New Orleans, Louisiana, 70118
Memorial Sloan Kettering
New York, New York, 10021
CHOC Children's Hospital
Orange, California, 92868
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Pheonix Children's Hospital
Phoenix, Arizona, 85016
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Primary Children's Medical of Utah
Salt Lake City, Utah, 84113
Methodist Hospital
San Antonio, Texas, 78229
University of California, San Francisco
San Francisco, California, 94143
Seattle Cancer Care Alliance
Seattle, Washington, 98109
St. Louis Children's Hosptial
St Louis, Missouri, 63110
Lucile Packard Childrens hopsital at Stanford
Stanford, California, 94304
New York Medical College
Valhalla, New York, 10595
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: A Randomized, Placebo-controlled, Multi-site Phase 2 Study Evaluating the Safety and Efficacy of Preemptive Treatment With CMX001 for the Prevention of Adenovirus Disease Following Hematopoietic Stem Cell Transplantation
This study was designed to assess the safety and efficacy of preemptive treatment with oral brincidofovir (BCV), as compared to placebo, for the prevention of adenovirus (AdV) disease in recipients of hematopoietic stem cell transplantation (HCT) with asymptomatic AdV viremia.
Read the detailed description
This was a Phase 2, randomized, multicenter, placebo-controlled study for pediatric and adult subjects who had undergone hematopoietic stem cell transplantation (HCT) and who had been identified as having asymptomatic adenovirus (AdV) viremia [i.e., had detectable AdV DNA in plasma based on polymerase chain reaction testing performed at the local laboratory with no AdV disease symptoms]. The primary objectives of the study were to assess the safety and tolerability of oral brincidofovir (BCV), and to estimate the treatment failure rate based on an efficacy endpoint with 2 different dosing regimens of oral BCV versus placebo.
- Conditions
- Adenovirus Disease
- Being tested
- Brincidofovir, Placebo
- Keywords
- AdV, Hematopoeitic Stem Cell Transplant, HSCT
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrincidofovirDrug
Also called BCV, CMX001
- Adult subjects: 200mg BCV administered as 50mg tablets taken orally either once weekly (QW; 4 tablets) or twice weekly (BIW; 2 tablets).
- Pediatric subjects: 4mg/kg BCV (not to exceed a total single dose of 200mg) administered using a 10 mg/mL liquid formulation taken orally either QW (as 4 mg/kg) or BIW (as 2 mg/kg).
PlaceboOther
Adult subjects: Matching placebo tablets taken orally either once weekly (QW; 4 tablets) or twice weekly (BIW; 2 tablets).
- Pediatric subjects: Matching liquid placebo taken orally either QW (as 4 mg/kg) or BIW (as 2 mg/kg).
| Study group | Role | What they receive |
|---|---|---|
| Brincidofovir | Active comparator | * Adult subjects: 200mg BCV administered as 50mg tablets taken orally either once weekly (QW; 4 tablets) or twice weekly (BIW; 2 tablets).
* Pediatric subjects: 4mg/kg BCV (not to exceed a total single dose of 200mg) administered using a 10 mg/mL liquid formulation taken orally either QW (as 4 mg/kg) or BIW (as 2 mg/kg). Receives: Drug: Brincidofovir |
| Placebo | Placebo comparator | * Adult subjects: Matching placebo tablets taken orally either once weekly (QW; 4 tablets) or twice weekly (BIW; 2 tablets).
* Pediatric subjects: Matching liquid placebo taken orally either QW (as 4 mg/kg) or BIW (as 2 mg/kg). Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Clinically Significant AdV Infection
The primary objective of this study was to evaluate the safety and efficacy of preemptive treatment with brincidofovir (BCV) versus placebo for the prevention of adenovirus (AdV) disease in recipients of hematopoietic stem cell transplantation (HCT) with asymptomatic AdV viremia.
The outcome measure for the primary endpoint was treatment failure, a composite endpoint that consisted of the following:
- Progression to probable AdV disease (other positive causes/agents have been ruled out and subject has disease-targeted organ-specific signs or symptoms) or definitive AdV disease (AdV detected in disease-targeted organ/system biopsy via antigen/immunohistochemistry, culture, and/or polymerase chain reaction and has at least 1 disease-targeted organ-specific sign or symptom); or
- Increasing AdV viremia (defined as an increase from baseline in AdV viremia by ≥1 log10, confirmed on a second measurement, at least 1 week apart) and requiring discontinuation from blinded therapy.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2010 (estimated)
- Study startNov 2010
- Primary completionJun 2013
- Study completionJun 2013
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 (2)Papers the sponsor has linked to this study.
- Other trials for Adenovirus 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 52 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
- NCT01241344
- Sponsor's protocol ID
- CMX001-202
- Status last verified
- Jul 2021
- First submitted
- 12 Nov 2010
- Last updated
- 21 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Grimley MS, Chemaly RF, Englund JA, Kurtzberg J, Chittick G, Brundage TM, Bae A, Morrison ME, Prasad VK. Brincidofovir for Asymptomatic Adenovirus Viremia in Pediatric and Adult Allogeneic Hematopoietic Cell Transplant Recipients: A Randomized Placebo-Controlled Phase II Trial. Biol Blood Marrow Transplant. 2017 Mar;23(3):512-521. doi: 10.1016/j.bbmt.2016.12.621. Epub 2017 Jan 5.
PubMed 28063938Tippin 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 21 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo-controlled, Multi-site Phase 2 Study Evaluating the Safety and Efficacy of Preemptive Treatment With CMX001 for the Prevention of Adenovirus Disease Following Hematopoietic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT01241344
- Acronym / sponsor ID
- CMX001-202
- Conditions
- Adenovirus Disease
- Keywords
- AdV, Hematopoeitic Stem Cell Transplant, HSCT
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Nov 2010 (actual)
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 16 Nov 2010 (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 study was designed to assess the safety and efficacy of preemptive treatment with oral brincidofovir (BCV), as compared to placebo, for the prevention of adenovirus (AdV) disease in recipients of hematopoietic stem cell transplantation (HCT) with asymptomatic AdV viremia.
Detailed description
This was a Phase 2, randomized, multicenter, placebo-controlled study for pediatric and adult subjects who had undergone hematopoietic stem cell transplantation (HCT) and who had been identified as having asymptomatic adenovirus (AdV) viremia [i.e., had detectable AdV DNA in plasma based on polymerase chain reaction testing performed at the local laboratory with no AdV disease symptoms]. The primary objectives of the study were to assess the safety and tolerability of oral brincidofovir (BCV), and to estimate the treatment failure rate based on an efficacy endpoint with 2 different dosing regimens of oral BCV versus placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Brincidofovir | Active comparator | Drug: Brincidofovir* Adult subjects: 200mg BCV administered as 50mg tablets taken orally either once weekly (QW; 4 tablets) or twice weekly (BIW; 2 tablets). * Pediatric subjects: 4mg/kg BCV (not to exceed a total single dose of 200mg) administered using a 10 mg/mL liquid formulation taken orally either QW (as 4 mg/kg) or BIW (as 2 mg/kg). |
| Placebo | Placebo comparator | Other: Placebo* Adult subjects: Matching placebo tablets taken orally either once weekly (QW; 4 tablets) or twice weekly (BIW; 2 tablets). * Pediatric subjects: Matching liquid placebo taken orally either QW (as 4 mg/kg) or BIW (as 2 mg/kg). |
Who may qualify
- Ages
- 3 months to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- For inclusion into the study, subjects were required to fulfill all of the following criteria:
- Were males or female aged ≥3 months to ≤75 years.
- Received an allogeneic hematopoietic stem cell transplant (HCT).
- Had positive serum adenovirus (AdV) PCR (>100 copies/mL) as measured by the central laboratory (unless the subject developed AdV disease while participating in the prescreening activities and after concurrence from the Chimerix medical monitor or designee).
- Was on dialysis during treatment if he/she had an estimated glomerular filtration rate (eGFR) ≤30 mL/minute.
Key exclusion criteria (16 listed)
- Subjects meeting any of the following exclusion criteria were excluded from participation in the study:
- Had possible, probable, or definitive AdV disease (unless the subject developed probable or definitive AdV disease while participating in prescreening activities and after concurrence from he Chimerix medical monitor or designee).
- Had suspected gut graft versus host disease that was not biopsy-proven (subjects with a biopsy performed were included in the study).
- Had an eGFR ≤30 mL/minute and was not currently on dialysis.
- Had an alanine aminotransferase or aspartate aminotransferase >5 x the upper limit of normal (ULN), total bilirubin ≥2 x the ULN, or conjugated (direct) bilirubin ≥1.5 x the ULN.
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* Adult subjects: 200mg BCV administered as 50mg tablets taken orally either once weekly (QW; 4 tablets) or twice weekly (BIW; 2 tablets). * Pediatric subjects: 4mg/kg BCV (not to exceed a total single dose of 200mg) administered using a 10 mg/mL liquid formulation taken orally either QW (as 4 mg/kg) or BIW (as 2 mg/kg). | Drug | Brincidofovir |
| PlaceboAdult subjects: Matching placebo tablets taken orally either once weekly (QW; 4 tablets) or twice weekly (BIW; 2 tablets). • Pediatric subjects: Matching liquid placebo taken orally either QW (as 4 mg/kg) or BIW (as 2 mg/kg). | Other | Placebo |
Primary outcome
Number of Participants With Clinically Significant AdV Infection
Time frame: 12 weeks
The primary objective of this study was to evaluate the safety and efficacy of preemptive treatment with brincidofovir (BCV) versus placebo for the prevention of adenovirus (AdV) disease in recipients of hematopoietic stem cell transplantation (HCT) with asymptomatic AdV viremia. The outcome measure for the primary endpoint was treatment failure, a composite endpoint that consisted of the following: * Progression to probable AdV disease (other positive causes/agents have been ruled out and subject has disease-targeted organ-specific signs or symptoms) or definitive AdV disease (AdV detected in disease-targeted organ/system biopsy via antigen/immunohistochemistry, culture, and/or polymerase chain reaction and has at least 1 disease-targeted organ-specific sign or symptom); or * Increasing AdV viremia (defined as an increase from baseline in AdV viremia by ≥1 log10, confirmed on a second measurement, at least 1 week apart) and requiring discontinuation from blinded therapy.
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 28063938Grimley MS, Chemaly RF, Englund JA, Kurtzberg J, Chittick G, Brundage TM, Bae A, Morrison ME, Prasad VK. Brincidofovir for Asymptomatic Adenovirus Viremia in Pediatric and Adult Allogeneic Hematopoietic Cell Transplant Recipients: A Randomized Placebo-Controlled Phase II Trial. Biol Blood Marrow Transplant. 2017 Mar;23(3):512-521. doi: 10.1016/j.bbmt.2016.12.621. Epub 2017 Jan 5.
- 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.
30 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 Adenovirus Disease, run by Jazz Pharmaceuticals at 30 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 16 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 30 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 AdV Infection (time frame: 12 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 NCT01241344, which also lists 2 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 21 Jul 2021; AzTrials last refreshed its copy on 1 Nov 2026.