ViruriaPhase 1/2NCT00793598

CMX001 in Post-transplant Patients With BK Virus Viruria

A Phase 1/2 study testing Brincidofovir in people with Viruria, run by Jazz Pharmaceuticals at 15 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This was a randomized, double-blind, multiple-dose placebo-controlled study of oral brincidofovir (BCV) in hematopoietic stem cell transplant and renal transplant recipients with BK virus viruria. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Viruria
What is being tested?: Brincidofovir
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 29 participants
Where: 15 sitesUnited States
Study dates: Nov 2009to Oct 2010
Phase: Phase 1/2
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 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

For inclusion into the trial, subjects were required to fulfill all of the following criteria:
Aged between 18 to 75 years, inclusive. Males must have been able and willing to use adequate contraceptive methods throughout the study and for 3 months after the final dose. Females must have been post-menopausal, surgically sterile, or willing to use adequate contraception for the duration of the study (screening through the Day 48 visit).
Were renal or hematopoietic stem cell transplant patients who met the following criteria:
Renal transplant patients who:
Were at least 28 days post transplant;
Were in stable condition with hemoglobin >10 g/100 mL;

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Had no evidence of graft rejection (i.e., serum creatinine was not increasing [±30%], creatinine clearance was not decreasing);
Were on a stable immunosuppressant regimen for at least 14 days prior to dosing.
Had either urine levels of BK virus DNA ≥10^4 copies/mL without viremia or plasma levels of BK virus DNA <10^4 copies/mL (with or without viruria).
Stem cell transplant patients who:
Were a minimum of 3 days post documentation of successful engraftment as evidenced by an absolute neutrophil count >500 cells/mm3;
Had urine levels of BKV ≥10^4 copies/mL.
Had GFR >30 mL/min.
Were able to swallow tablets.
Were willing and able to understand and provide written informed consent.
Were willing and able to participate in all required study activities for the duration of the study (including ingestion of oral medication).

Who cannot join

Any of the following was regarded as a criterion for exclusion from the trial:
Females who were currently nursing or pregnant.
Were using illicit drugs or abusing alcohol.
Had hypersensitivity to cidofovir or brincidofovir.
Had received aminoglycosides (intravenously) or NSAIDS (except as given for cardioprotective treatment) within 7 days prior to enrollment; had received leflunomide, cidofovir, or any other medication for treatment of BK virus infection or disease within 14 days prior to enrollment; had received any investigational drug (including maribavir) within 30 days prior to enrollment.
Were HIV positive (results must have been obtained within 1 year prior to dosing); had active hepatitis C virus (HCV) or hepatitis B virus (HBV) infection as evidenced by plasma levels of HCV RNA or HBV DNA, respectively.

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Were renal transplant patients with evidence of biopsy proven acute rejection in the 3 weeks prior to enrollment. This exclusion criterion applied only to those patients for whom a biopsy was performed within the 3 weeks prior to enrollment.
Were stem cell transplant patients who:
Had cystitis ≥Grade 3 National Cancer Institute, Common Terminology Criteria for Adverse Events version 3.0.
Had Grade 3 or 4 graft versus host disease (GVHD).
Had untreated or uncontrolled Grade 2 GVHD.
Had received ganciclovir or valganciclovir within 14 days prior to enrollment.
Had mucositis that prevented ingestion of oral medication.
Had hypotony, uveitis, or retinitis or any intraocular pathology that would have predisposed the patient to any one of these conditions.
Had unstable or poorly controlled diabetes, defined as having frequent hypoglycemic and/or hyperglycemic events on a daily basis (brittle diabetes), with fluctuating short acting insulin requirements daily, or requiring unpredictable insulin supplementation to oral hypoglycemic agents on a regular basis.
Had bilirubin >2.5 x the upper limit of normal.
Had cardiovascular disease which, in the opinion of the investigator, would have interfered with the conduct of the study.
Had any of the following autoimmune diseases: Addison's disease, autoimmune hemolytic anemia, autoimmune hepatitis, bullous pemphigoid, celiac disease, dermatomyositis, active Goodpasture's syndrome, idiopathic thrombocytopenic purpura, active lupus erythematosus, multiple sclerosis, myasthenia gravis, pemphigus vulgaris, polymyositis, primary biliary cirrhosis, vasculitis, Wegener's granulomatosis.
Had active malignancies (with the exception of basal cell carcinoma or the condition under treatment for hematopoietic stem cell transplant patients).
Had concurrent or ongoing ≥Grade 2 gastrointestinal symptoms including nausea, vomiting, diarrhea, constipation, or gastroenteritis. Patients with active gastrointestinal disease including inflammatory bowel disease, irritable bowel syndrome, or celiac sprue.
Had any other condition including abnormal laboratory values that would have, in the judgement of the investigator, put the subject at increased risk for participating in the trial, or interfered with the conduct of the trial.

Trial locations and contacts

15 sites in 1 country.

City, postcode or hospital

15 sites in 1 country

United States15 sites

University of Michigan
Ann Arbor, Michigan, 48109
Johns Hopkins Medical Institutions
Baltimore, Maryland, 21287
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
University of Vermont
Burlington, Vermont, 05405
UNC Kidney Center
Chapel Hill, North Carolina, 27599
Northwestern University
Chicago, Illinois, 60611
Rush University Medical Center
Chicago, Illinois, 60612
Tulane Center for Abdominal Transplant
New Orleans, Louisiana, 70112
Mt. Sinai Medical Center
New York, New York, 10029
University of Pittsburgh
Pittsburgh, Pennsylvania, 15260
California Pacific Medical Center
San Francisco, California, 94115
University of California, San Francisco
San Francisco, California, 94143-0780
Fred Hutchinson Cancer Research Center
Seattle, Washington, 19024
Washington University School of Medicine
St Louis, Missouri, 63110
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study of the Safety, Tolerability and Population Pharmacokinetics of CMX001 in Post-Transplant Subjects With BK Virus Viruria

This was a randomized, double-blind, multiple-dose placebo-controlled study of oral brincidofovir (BCV) in hematopoietic stem cell transplant and renal transplant recipients with BK virus viruria.

Read the detailed description

This was a randomized, double-blind, multiple-dose placebo-controlled study of oral brincidofovir (BCV) in hematopoietic stem cell transplant and renal transplant recipients with BK virus infection.

Subjects received blinded study medication for a total of 5 doses in 1 of the following regimens:

10 mg BCV administered twice weekly (BIW) on Days 0, 3, 7, 10, 14.
20 mg BCV administered once weekly (QW) on Days 0, 7, and 14 and placebo administered on Days 3 or 10.
Placebo administered BIW on Days 0, 3, 7, 10 ,14.
40 mg BCV administered QW on Days 0, 7, 14, 21, and 28.
Placebo administered QW on Days 0, 7, 14, 21, and 28.

Conditions: Viruria
Being tested: Placebo, Brincidofovir
Keywords: CMX001, Kidney transplant, HSCT transplant, BK Virus, Post kidney transplant patients with BK virus viruria > 10^4, Post HSCT transplant patients with BK virus viruria > 10^4

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PlaceboDrug
BrincidofovirDrug
Also called BCV, CMX001

Study groups in NCT00793598
Study group	Role	What they receive
Brincidofovir	Experimental	Under Amendments 1 and 2, subjects received 1 of 2 dose regimens of brincidofovir, as follows: * 20 mg BCV once weekly (QW) on Days 0, 7, and 14; or * 10 mg BCV twice weekly (BIW) BIW on Days 0, 3, 7, 10, and 14. Under Amendment 3, subjects received 40 mg BCV QW for a total of 5 doses on Days 0, 7, 14, 21, and 28. Receives: Drug: Brincidofovir
Placebo	Placebo comparator	Under Amendments 1 and 2, subjects received placebo twice weekly (BIW) for a total of 5 doses on Days 0, 3, 7, 10, and 14. Under Amendment 3, subjects received placebo once weekly (QW) for a total of 5 doses on Days 0, 7, 14, 21, and 28. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Adverse Events in Post-Transplant Patients With BK Virus Viruria
The primary objective of this study was to determine the safety and tolerability of brincidofovir (BCV) in post-transplant patients with BK virus viruria. Safety measures included adverse events, clinical laboratory values, vital signs, and renal and gastrointestinal function.
Measured: 35 days (Day 0 to Day 35)

Secondary outcomes (2)

Percentage of Patients Who Achieved BK Viruria Resolution
The percentage of subjects who cleared the virus was calculated. Concentrations below the lower limit of quantification were indicated as below the limit of quantitation and were considered "cleared".
Measured: 28 days
Number of Patients Who Achieved a Clinically Significant Decrease in BK Viruria
A 2-log drop in viruria or viremia or clearance of virus was considered significant. Percentages of subjects with a 2-log drop in viral load were calculated.
Measured: 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2009Oct 2010

First posted19 Nov 2008 (estimated)
Study startNov 2009
Primary completionOct 2010
Study completionOct 2010

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 ViruriaStudies 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 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 29 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00793598
Sponsor's protocol ID: CMX001-104
Status last verified: Jul 2021
First submitted: 17 Nov 2008
Last updated: 16 Aug 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 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study of the Safety, Tolerability and Population Pharmacokinetics of CMX001 in Post-Transplant Subjects With BK Virus Viruria
ClinicalTrials.gov ID: NCT00793598
Acronym / sponsor ID: CMX001-104
Conditions: Viruria
Keywords: CMX001, Kidney transplant, HSCT transplant, BK Virus, Post kidney transplant patients with BK virus viruria > 10^4, Post HSCT transplant patients with BK virus viruria > 10^4
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 29 participants (actual)
Lead sponsor: Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Nov 2009 (actual)
Primary completion: Oct 2010 (actual)
Study completion: Oct 2010 (actual)
First posted: 19 Nov 2008 (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 randomized, double-blind, multiple-dose placebo-controlled study of oral brincidofovir (BCV) in hematopoietic stem cell transplant and renal transplant recipients with BK virus viruria.

Detailed description

This was a randomized, double-blind, multiple-dose placebo-controlled study of oral brincidofovir (BCV) in hematopoietic stem cell transplant and renal transplant recipients with BK virus infection.

Subjects received blinded study medication for a total of 5 doses in 1 of the following regimens:

10 mg BCV administered twice weekly (BIW) on Days 0, 3, 7, 10, 14.
20 mg BCV administered once weekly (QW) on Days 0, 7, and 14 and placebo administered on Days 3 or 10.
Placebo administered BIW on Days 0, 3, 7, 10 ,14.
40 mg BCV administered QW on Days 0, 7, 14, 21, and 28.
Placebo administered QW on Days 0, 7, 14, 21, and 28.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Brincidofovir	Experimental	Drug: BrincidofovirUnder Amendments 1 and 2, subjects received 1 of 2 dose regimens of brincidofovir, as follows: * 20 mg BCV once weekly (QW) on Days 0, 7, and 14; or * 10 mg BCV twice weekly (BIW) BIW on Days 0, 3, 7, 10, and 14. Under Amendment 3, subjects received 40 mg BCV QW for a total of 5 doses on Days 0, 7, 14, 21, and 28.
Placebo	Placebo comparator	Drug: PlaceboUnder Amendments 1 and 2, subjects received placebo twice weekly (BIW) for a total of 5 doses on Days 0, 3, 7, 10, and 14. Under Amendment 3, subjects received placebo once weekly (QW) for a total of 5 doses on Days 0, 7, 14, 21, and 28.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (16 listed)

For inclusion into the trial, subjects were required to fulfill all of the following criteria:
Aged between 18 to 75 years, inclusive. Males must have been able and willing to use adequate contraceptive methods throughout the study and for 3 months after the final dose. Females must have been post-menopausal, surgically sterile, or willing to use adequate contraception for the duration of the study (screening through the Day 48 visit).
Were renal or hematopoietic stem cell transplant patients who met the following criteria:
Had GFR >30 mL/min.
Were able to swallow tablets.

Key exclusion criteria (21 listed)

Females who were currently nursing or pregnant.
Were using illicit drugs or abusing alcohol.
Had hypersensitivity to cidofovir or brincidofovir.
Had received aminoglycosides (intravenously) or NSAIDS (except as given for cardioprotective treatment) within 7 days prior to enrollment; had received leflunomide, cidofovir, or any other medication for treatment of BK virus infection or disease within 14 days prior to enrollment; had received any investigational drug (including maribavir) within 30 days prior to enrollment.
Were HIV positive (results must have been obtained within 1 year prior to dosing); had active hepatitis C virus (HCV) or hepatitis B virus (HBV) infection as evidenced by plasma levels of HCV RNA or HBV DNA, respectively.

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
Placebo	Drug	Placebo
BrincidofovirAlso: BCV, CMX001	Drug	Brincidofovir

Primary outcome

Number of Adverse Events in Post-Transplant Patients With BK Virus Viruria
Time frame: 35 days (Day 0 to Day 35)
The primary objective of this study was to determine the safety and tolerability of brincidofovir (BCV) in post-transplant patients with BK virus viruria. Safety measures included adverse events, clinical laboratory values, vital signs, and renal and gastrointestinal function.

2 secondary outcomes

Percentage of Patients Who Achieved BK Viruria Resolution
Time frame: 28 days
Number of Patients Who Achieved a Clinically Significant Decrease in BK Viruria
Time frame: 28 days

Results and safety

Results posted to the registry on 16 Jul 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
10 mg BCV BIW RT	1	1
10 mg BCV BIW HCT	1	0
20 mg BCV QW HCT	1	1
Placebo BIW HCT	2	2
40 mg BCV QW RT	8	8
40 mg BCV QW HCT	8	7
Placebo QW RT	4	4
Placebo QW HCT	4	3

Primary outcome: Number of Adverse Events in Post-Transplant Patients With BK Virus Viruria

Time frame: 35 days (Day 0 to Day 35). Count of participants. Unit: Participants

Measure	10 mg BCV BIW RT n = 1	10 mg BCV BIW HCT n = 1	20 mg BCV BIW HCT n = 1	Placebo BIW HCT n = 2	40 mg BCV QW RT n = 8	40 mg BCV QW HCT n = 7	Placebo QW RT n = 4	Placebo QW HCT n = 4
Subjects who experienced at least 1 an adverse event	1	1	1	2	8	7	3	4
Subjects who did not experience an adverse event	0	0	0	0	0	0	1	0

Population analysed: 1 subject in the 40 mg BCV QW HCT treatment arm was not dosed with BCV and, therefore, was not included in this analysis.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Day 0 to Day 35. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
10 mg BCV BIW RT	1 of 1 (100%)	1 of 1 (100%)	Not reported
10 mg BCV BIW HCT	0 of 1 (0%)	1 of 1 (100%)	Not reported
20 mg BCV QW HCT	0 of 1 (0%)	1 of 1 (100%)	Not reported
Placebo BIW HCT	0 of 2 (0%)	2 of 2 (100%)	Not reported
40 mg BCV QW RT	0 of 8 (0%)	8 of 8 (100%)	Not reported
40 mg BCV QW HCT	2 of 7 (28.6%)	7 of 7 (100%)	Not reported
Placebo QW RT	0 of 4 (0%)	3 of 4 (75%)	Not reported
Placebo QW HCT	1 of 4 (25%)	4 of 4 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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.

15 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Brincidofovir in people with Viruria, run by Jazz Pharmaceuticals at 15 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 16 inclusion and 21 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 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 15 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 Adverse Events in Post-Transplant Patients With BK Virus Viruria (time frame: 35 days (Day 0 to Day 35)). 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 NCT00793598.

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 Aug 2021.