Efficacy and Safety of Intravenous Brincidofovir Versus Cidofovir in Adenovirus Viremia Post-Allogeneic Hematopoietic Cell Transplantation
- Trial ID
- 2025-521903-28-00
- Protocol
- BCV-PA02
- Sponsor
- Symbio Pharmaceuticals Ltd.
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to evaluate the efficacy of intravenous brincidofovir compared to intravenous cidofovir in subjects presenting with adenovirus viremia following allogeneic hematopoietic cell transplantation. Secondary objectives include:
- Assessment of the safety profile of intravenous brincidofovir relative to cidofovir.
- Evaluation of the pharmacokinetics of intravenous brincidofovir.
Participants
This clinical trial involves a total of 108 participants. The study population consists of male and female patients, including vulnerable populations, who are aged 2 months or older. Participants are required to have undergone an allogeneic hematopoietic stem cell transplant within the previous 180 days and must be diagnosed with adenovirus viremia. Inclusion is contingent upon clinical judgment regarding the necessity of treatment with intravenous brincidofovir or intravenous cidofovir. To ensure safety, women of childbearing potential must agree to specific contraception requirements, and participants must be non-pregnant and either not breastfeeding or willing to discontinue breastfeeding prior to randomization.
Plans and Procedures
This Phase 3, multicenter, prospective, randomized, open-label study is designed to evaluate the efficacy and safety of intravenous brincidofovir compared to intravenous cidofovir for the treatment of adenovirus infection. The study focuses on subjects, including pediatric and adult populations, who have undergone allogeneic hematopoietic cell transplantation within the preceding 180 days and present with adenovirus viremia. The primary endpoint is the proportion of subjects achieving virological success, while secondary endpoints include clinical success, adenovirus-free survival, and the incidence of treatment-emergent adverse events. The research methodology involves comparing the test product against a comparator to determine clinical outcomes and safety profiles. Specific details regarding the sequence of study visits, total duration of participant involvement, and criteria for early termination are not provided.
Treatment
The experimental treatment consists of brincidofovir, an orphan drug administered as a solution for infusion. This medication is delivered via intravenous infusion to subjects with adenovirus infection following allogeneic hematopoietic cell transplantation.
The comparator treatment is cidofovir, provided in a solution for infusion. This substance is administered through intravenous infusion.
Efficacy
The efficacy of intravenous brincidofovir compared to intravenous cidofovir in subjects with adenovirus viremia following allogeneic hematopoietic cell transplantation is evaluated through several endpoints. The primary endpoint is the proportion of subjects achieving adenovirus virological success.
Secondary efficacy parameters include:
- Proportion of subjects achieving overall success and clinical success
- Correlation between virologic success and clinical response
- Adenovirus-free survival
- Time to adenovirus virological success
- Rate of adenovirus recurrence
- Length of hospitalization and length of ICU stay
- Desirability Of Outcome Ranking (DOOR) analysis for benefit-risk estimation
- All-cause mortality
- Adenovirus attributed mortality, as adjudicated by an external adjudication committee
- Primary malignancy relapse-free survival
Inclusion and Exclusion Criteria
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
- Men and women of childbearing potential (WOCBP) must be willing to use acceptable method(s) of contraception during the study and for at least 6 months after the last dose of IV BCV or at least 6 months after the last dose of IV CDV.
- Women of childbearing potential (WOCBP) must agree to use two (2) acceptable forms of contraception (one of which must be a barrier method) during heterosexual intercourse. Males capable of fathering a child must agree to use acceptable method(s) of contraception during heterosexual intercourse.
- Subject is non-pregnant, and either not breast feeding or willing to discontinue breast feeding prior to randomization.
Exclusion Criteria
- Subject received an allo-HCT with a matched sibling donor
- Subject received more than 5 mg/kg of CDV for any reason in the 21 days prior to first dose of study drug.
- Subject is allergic or hypersensitive to IV BCV or IV CDV or any of their components.
- Subject received anti-AdV-specific cell-based therapy within 3 weeks prior to W1D1 or an anti-AdV vaccine at any time.
- Subject has participated in any other investigational study within 30 days (or within 5.5 half-lives of the investigational product, whichever is longer) before signing the informed consent form (ICF), is currently participating in another interventional treatment trial with an investigational agent or is using an investigational device at the time of Screening.
- Subject has NIH Stage 3 or higher acute GVHD of the gut within 7 days prior to W1D1.
- Subject has NIH Stage 2 or higher acute GVHD of the liver within 7 days prior to W1D1 (i.e., bilirubin>3 mg/dL [International System, SI: >51 μmol/L]).
- Subject has exclusionary hepatic parameters within 7 days prior to W1D1: • Total bilirubin >3 mg/dL (SI: >51 μmol/L) except for subjects with Gilbert’s Disease, • Prothrombin time-international normalized ratio (PT INR) >2x ULN, unless attributed to AdV. • ALT or AST >5x upper limit of normal (ULN), except if it is judged by the PI to be due to the AdV infection. Note: Subjects with elevated serum transaminases >5x ULN (CTCAE Grade 3 or higher) due to AdV will be required to demonstrate improvement and must stop study drug if the elevated values have not improved by W3D1: either at least one CTCAE grade or clinical improvement based on the physician’s assessment.
- Subject has uncontrolled viral (other than AdV), bacterial, or fungal infection(s) leading to hemodynamic instability or radiologic or laboratory evidence attributable to worsening disease.
- Subject has any other disease, or laboratory abnormality, or clinical finding that, in the judgment of the investigator, would put the subject at unacceptable risk for participation or interfere with study assessments or data quality.
- Subject is expected to die from a non-adenovirus cause within 30 days from the date of ICF.
- Subject is critically ill, for example with sepsis on high dose vasopressors and mechanical ventilation.
- Subject is unable to comply with protocol visits and procedures.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Recruiting | 30 Apr 2026 | 15 |
 Germany | Recruiting | 30 Apr 2026 | 19 |
 Italy | Recruiting | 30 Apr 2026 | 19 |
 Spain | Recruiting | 30 Apr 2026 | 19 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Brincidofovir | Test | SOLUTION FOR INFUSION | INFUSION | 0 | 12 | PRD12494992 |
Cidofovir | Comparator | SOLUTION FOR INFUSION | INFUSION | 0 | 12 | PRD12494993 |