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This randomized, open-label, parallel group, two-arm, multi-center assessment will compare IV BCV with IV CDV in adult and pediatric allogeneic HCT recipients with AdV viremia. A virologic response-driven approach to duration of treatment will be evaluated, in which randomized subjects are treated with either BCV or CDV until AdV viremia is confirmed as undetectable or until a maximum of 12 weeks of therapy, whichever occurs first. All subjects will be followed for a total of 24 weeks post-randomization, regardless of treatment assignment. Subjects will be assessed on a weekly basis through the end of treatment visit (EOT). Additional assessments will be performed at the test of cure (TOC) visit, which is 4 weeks after the last dose of study drug and at Weeks 12 and 24 post W1D1.
This Phase 3 multi-center, randomized, open-label study will assess efficacy of IV BCV, compared to IV CDV, in allo-HCT subjects with AdV viremia. Randomized subjects will be treated for up to a maximum of 12 weeks of therapy for both arms. Primary efficacy assessment will be performed at W5D1. Consistent with ECIL guidelines for high-risk patients, AdV viremia will be assessed weekly. Subjects randomized to receive BCV or CDV are treated until AdV DNA is confirmed to be undetectable in plasma for two consecutive tests 7 days apart, or until Week 12 post W1D1, whichever occurs first. Subjects will continue BCV or CDV as long as AdV viremia is detectable, contingent on tolerability, until viremia clears, or the subject reaches a maximum duration of 12 weeks of study drug treatment.
Subjects will receive assigned randomized therapy until time of AdV virological success plus 2 weeks, for up to a maximum of 12 weeks. All subjects will be followed through 24 weeks. All study visits and follow-up assessments must be completed regardless of the study drug treatment duration. All subjects are considered on study through the Week 24 follow-up visit.
For subjects who achieve virological success from their initial randomized study drug treatment and experience an AdV viremia recurrence, repeat treatment with their randomized study drug is allowed. There is no cross-over study drug treatment allowed in this study and subjects can only receive retreatment with their randomized study drug.
Subjects who stop study drug therapy due to confirmed undetectable AdV viremia may re-initiate study drug treatment if AdV viremia is subsequently confirmed at ≥ 1000 IU/mL by the designated central virology laboratory (recurrence). For the purposes of re-initiating study drug therapy, "confirmed viremia ≥ 1000 IU/mL" is defined as two consecutive results ≥ 1000 IU/mL from the designated central laboratory, with the second sample drawn at least 48 hours after the first sample.
Subjects who permanently discontinue study drug therapy for toxicity reasons are not eligible to re-initiate study drug dosing. Study procedures are to be followed during these Retreatment visits as applicable for BCV and CDV outlined in the schedule of assessments (SOA).
An independent Data Safety Monitoring Board (DSMB) will review accumulated safety data for this study when total combined enrollment in both arms is approximately 25% (45 subjects) and 50% (90 subjects). They will also review adverse events on an ongoing basis. They will make recommendations to the Sponsor based on review of these safety data. Further details regarding data safety monitoring guidelines will be included in the DSMB Charter. The DSMB will make determinations regarding continued enrolment and/or stopping the study for safety reasons.
An Endpoint Adjudication Committee (EAC) will be convened to evaluate baseline diagnosis and AdV disease clinical response as outlined in the EAC charter.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IV BCV | Experimental |
| |
| IV CDV | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| cidofovir | Drug | CDV does not have a labeled indication for treating Adenovirus infection. CDV will be administered according to local guidelines and institutional standard of care practice. |
| Measure | Description | Time Frame |
|---|---|---|
| To assess efficacy of intravenous (IV) brincidofovir (BCV), compared with IV cidofovir (CDV), in subjects after allo-HCT with adenovirus (AdV) viremia. | The primary efficacy endpoint is defined as AdV virological success at W5D1. -Proportion of subjects with AdV virological success | Week (W) 5 Day (D) 1. |
| Measure | Description | Time Frame |
|---|---|---|
| To assess the efficacy and safety of IV BCV, and IV CDV, in subjects after allo-HCT with AdV viremia. | The proportion of subjects with overall success, as adjuducated by the EAC | Test Of Cure (Last Dose + 30 days) |
| To assess the efficacy and safety of IV BCV, and IV CDV, in subjects after allo-HCT with AdV viremia. |
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Inclusion Criteria:
Male and female, post-allo HCT within last 180 days, aged 2 months and older at time of signing informed consent form.
Subject/Guardian willing and able to understand and provide written informed consent to participate in the study.
In the investigator's judgement, the subject's clinical condition justifies treatment with IV BCV or IV CDV for AdV infection.
Has adenoviremia, based on any of:
1. Lymphocyte count <180/mm3, OR 2. Received T cell depletion, cord blood, or haploidentical transplant, OR 3. prior alemtuzumab, OR 4. anti-thymocyte globulin (ATG)
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Rochelle Maher | Contact | +1-917-656-6951 | MedInfo@symbiopharma.com |
| Name | Affiliation | Role |
|---|---|---|
| Nkechi Azie | SymBio Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Phoenix Children's Hospital | Recruiting | Phoenix | Arizona | 85016 | United States | |
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|
| Brincidofovir | Drug | Intravenous |
|
|
Incidence and severity of treatment-emergent adverse events (TEAEs). |
| Week 1 Day 1 Through End Of Study (Week 24). |
| To assess the efficacy and safety of IV BCV, and IV CDV, in subjects after allo-HCT with AdV viremia. | All cause mortality | Week 5 Day 1, Last Dose + 4 Days, Last Dose + 30 days, Week 12, and Week 24. |
| BCV Plasma Concentrations will be collected, measured and reported | The drug level (BCV) in plasma will be measured and used to examine the variability in drug concentrations among patients within the study population (i.e., population pharmacokinetics analysis). | Plasma samples will be collected at Week 1 Day 1, and Week 5 Day 1 |
| City of Hope |
| Not yet recruiting |
| Duarte |
| California |
| 91010 |
| United States |
| University of California Davis | Not yet recruiting | Sacramento | California | 95616 | United States |
| Rady Children's Hospital | Not yet recruiting | San Diego | California | 92123 | United States |
| Children's Hospital Colorado-Center for Cancer and Blood Disorders | Not yet recruiting | Aurora | Colorado | 80045 | United States |
| Children's National Hospital | Recruiting | Washington D.C. | District of Columbia | 20010 | United States |
| Children's Healthcare of Atlanta/Emory | Not yet recruiting | Atlanta | Georgia | 30329 | United States |
| Ann and Robert H Lurie Children's Hospital | Recruiting | Chicago | Illinois | 60611 | United States |
| University of Chicago | Not yet recruiting | Chicago | Illinois | 60637 | United States |
| Dana-Farber Cancer Institute-Brighman and Women's | Not yet recruiting | Boston | Massachusetts | 02115 | United States |
| Dana-Farber/Boston Children's Cancer and Blood Disorders Center | Not yet recruiting | Boston | Massachusetts | 02139 | United States |
| Helen Devos Children's Hospital / Michigan State University | Not yet recruiting | Grand Rapids | Michigan | 49503 | United States |
| University of Minnesota | Not yet recruiting | Minneapolis | Minnesota | 55455 | United States |
| St Louis Children's Hospital - Barnes Jewish Hospital | Recruiting | St Louis | Missouri | 63110 | United States |
| University of Nebraska | Not yet recruiting | Omaha | Nebraska | 68182 | United States |
| Joseph M Sanzari Children's Hospital | Not yet recruiting | Hackensack | New Jersey | 07601 | United States |
| Cohen Children's Medical Center | Recruiting | New Hyde Park | New York | 11042 | United States |
| Weill Cornell Medicine | Not yet recruiting | New York | New York | 10065 | United States |
| Duke University Medical Center | Recruiting | Durham | North Carolina | 27710 | United States |
| Cincinnati Children's Hospital | Recruiting | Cincinnati | Ohio | 45229 | United States |
| Nationwide Children's Hospital | Not yet recruiting | Columbus | Ohio | 43205 | United States |
| Children's Hospital of Philadelphia | Not yet recruiting | Philadelphia | Pennsylvania | 19104 | United States |
| University of Pittsburgh Medical Center Children's Hospital | Not yet recruiting | Pittsburgh | Pennsylvania | 15213 | United States |
| St. Jude Children's Research Hospital | Recruiting | Memphis | Tennessee | 38105 | United States |
| Seattle Children's Hospital | Not yet recruiting | Seattle | Washington | 98105 | United States |
| Fred Hutchinson Cancer Center | Not yet recruiting | Seattle | Washington | 98109 | United States |
| St. Anna Kinderspital- Childrens Hospital | Not yet recruiting | Vienna | Austria |
| Leuven, University Hospital Gasthuisberg | Not yet recruiting | Leuven | Belgium |
| Alberta Children's Hospital University of Calgary | Not yet recruiting | Calgary | Canada |
| CHU Sainte Justine Hospital | Recruiting | Montreal | Canada |
| The Hospital for Sick Children | Not yet recruiting | Toronto | Canada |
| Hôpital Saint-Louis | Not yet recruiting | Paris | France |
| Necker Hospital | Not yet recruiting | Paris | France |
| Robert-Debré Hospital, APHP Nord Université de Paris Cité. | Not yet recruiting | Paris | France |
| Charité University Hospital | Not yet recruiting | Berlin | Germany |
| Essen University Hospital | Not yet recruiting | Essen | Germany |
| University Hospital Frankfurt, am Main | Not yet recruiting | Frankfurt | Germany |
| University Medical Center Hamburg-Eppendorf (UKE) | Not yet recruiting | Hamburg | Germany |
| Medizinische Hochschule Hannover | Not yet recruiting | Hanover | Germany |
| University Children's Hospital | Not yet recruiting | Münster | Germany |
| Kinderheilkunde I | Universitätsklinikum Tübingen | Not yet recruiting | Tübingen | Germany |
| Istituto Giannina Gaslini | Not yet recruiting | Genova | Italy |
| Fondazione IRCCS Policlinico San Matteo | Not yet recruiting | Pavia | Italy |
| Perugia Hospital | Not yet recruiting | Perugia | Italy |
| Ospedale Pediatrico Bambino Gesu' | Not yet recruiting | Rome | Italy |
| IRCCS San Raffaele Hospital | Not yet recruiting | San Raffaele | Italy |
| Leiden Unviversity Medical Center | Not yet recruiting | Leiden | Netherlands |
| Princess Maxima Center & UMC Utrecht | Not yet recruiting | Utrecht | Netherlands |
| Instituto Português de Oncologia do Porto (IPO Porto) Francisco Gentil, EPE | Not yet recruiting | Porto | Portugal |
| Vall d'Hebron University Hospital | Not yet recruiting | Barcelona | Spain |
| Hospital Universitario La Paz | Not yet recruiting | Madrid | Spain |
| Clinica Universidad de Navarra | Not yet recruiting | Pamplona | Spain |
| Karolinska University Hospital | Not yet recruiting | Stockholm | Sweden |
| Birmingham Women's and Children's Hospital | Not yet recruiting | Birmingham | United Kingdom |
| Leeds Teaching Hospitals NHS Trust | Not yet recruiting | Leeds | United Kingdom |
| Great Ormond Street Hospital for Children | Not yet recruiting | London | United Kingdom |
| University College London Hospitals NHS Foundation Trust | Recruiting | London | United Kingdom |
| Royal Manchester Children's Hospital | Not yet recruiting | Manchester | United Kingdom |
| The Newcastle upon Tyne Hospitals NHS Foundation Trust - Freeman Hospital | Not yet recruiting | Newcastle upon Tyne | United Kingdom |
| Sheffield Children's Hospital | Not yet recruiting | Sheffield | United Kingdom |
| Royal Marsden Hospital | Not yet recruiting | Sutton | United Kingdom |
| ID | Term |
|---|---|
| D000257 | Adenoviridae Infections |
| ID | Term |
|---|---|
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D000077404 | Cidofovir |
| C525733 | brincidofovir |
| ID | Term |
|---|---|
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D003596 | Cytosine |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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