A Phase 3, Multicenter, Prospective, Randomized, Open-Label Efficacy and Safety Study of Intravenous Brincidofovir Versus Intravenous Cidofovir for Treatment of Adenovirus Infection in Pediatric and Adult Subjects After Allogeneic Hematopoietic Cell Transplantation (Allo-Hct)

Investigating Treatments for Adenovirus Infection in Transplant Patients

Primary Investigator
J
Jodi Skiles

Primary Investigator

Enrolling By Invitation
2 months - 17 years
All
Phase 3
1 participants needed
1 Location

Brief description of study

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 STUDY IS ENROLLING BY INVITATION ONLY - Consistent with most oncology trials, patients are not actively “recruited,” but are screened by their physician for appropriate clinical trial(s) at the time of their routine clinic visit. Occasionally, a patient may be a self-referral or physician referral, but are still screened for appropriate clinical trials at the time of their routine clinic visit. PI and staff may send copies of relevant consent forms to these patients to look over prior to actually consenting or enrolling them. This may take place at the patient's visit at which the consent is presented or the patient's next visit to the outpatient hematology/oncology clinic. 
 
Interested in participating? For more information about this research study or other cancer-related clinical trials at Indiana University Simon Comprehensive Cancer Center (IUSCCC), please contact the
IU Clinical Trials Office at 
Phone: (317) 278-5632

Detailed description of study

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.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Adenovirus Infections, Riley
  • Age: 2 months - 17 years
  • Gender: All

Inclusion Criteria:

  1. Male and female, post-allo HCT within last 180 days, aged 2 months and older at time of signing informed consent form.
  2. Subject/Guardian willing and able to understand and provide written informed consent to participate in the study.
  3. In the investigator's judgement, the subject's clinical condition justifies treatment with IV BCV or IV CDV for AdV infection.
  4. Has adenoviremia, based on any of:
    • AdV viremia DNA ≥10,000 IU/mL, OR
    • Two consecutive and rising AdV viremia DNA results of ≥1,000 IU/mL at screening, OR
    • AdV viremia DNA of ≥1,000 IU/mL, AND

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:

  1. Subject received an allo-HCT with a matched sibling donor
  2. Subject received more than 5 mg/kg of CDV for any reason in the 21 days prior to first dose of study drug.
  3. Subject is allergic or hypersensitive to IV BCV or IV CDV or any of their components.
  4. Subject received anti-AdV-specific cell-based therapy within 3 weeks prior to W1D1 or an anti-AdV vaccine at any time.
  5. 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.

This study investigates treatments for adenovirus infection in patients who have received a type of transplant called allogeneic hematopoietic cell transplantation (allo-HCT). Adenovirus is a virus that can cause illness, especially in people with weakened immune systems, like those who have had a transplant. The study will compare two treatments given through a vein: an investigational medication and another treatment. Participants will be treated until the virus is no longer detectable or for up to 12 weeks.

Participants in the study will receive weekly assessments to monitor the virus levels in their blood. If the virus is undetectable, treatment may stop, but follow-up visits will continue for 24 weeks. If the virus returns, participants may restart their treatment. The study will not allow switching between the two treatments being tested. Safety data will be reviewed regularly to ensure participant well-being.

  • Who can participate: Participants must be aged 2 months and older, have had a transplant within the last 180 days, and have adenovirus in their blood. They must not have had certain treatments recently, and should not be allergic to the study medications.
  • Study details: Participants will receive one of two treatments through a vein, either the investigational medication or another treatment, until the virus is undetectable or for up to 12 weeks. They will be monitored for safety and virus levels throughout the study.
  • Study timelines: The study will last 24 weeks.
Updated on 14 Aug 2026. Study ID: 30923
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Interested in the study?

This study is accepting only persons who receive care at a certain clinic or doctor or who are part of an invited group. Questions about this study can be directed to the study team listed in the description or contact your doctor to see if you are eligible.

Accepting Referrals by Invitation Only