An Open-label, Randomized, Multi-center, Parallel Group, Two-arm Study to Assess the Safety, Overall Tolerability, and Antiviral Activity of Brincidofovir versus Standard of Care for Treatment of Adenovirus Infections in High-risk Pediatric Allogeneic Hematopoietic Cell Transplant Recipients
- Conditions
- 10047438Adenovirus Infections in High-risk Pediatric Allogeneic Hematopoietic Cell Transplant Recipients
- Registration Number
- NL-OMON46433
- Lead Sponsor
- Chimerix, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 10
1. Aged at least 2 months and less than 18-years-old on Day 1
2. Have received a T cell-depleted allogeneic (i.e., non-autologous) HCT within the previous 100 days, where *T cell-depleted* describes EITHER:
* ex vivo T cell depletion via positive selection (e.g., CD34+ cell) or negative selection (e.g., T cell receptor */* or CD3+ cell removal by column filtration), OR
* serotherapy with ATG (cumulative dose of * 3 mg/kg rabbit-derived ATG or * 50 mg/kg of equine-derived ATG) administered within 10 days prior to transplant or at any time post-transplant and prior to Day 1 OR
* serotherapy with alemtuzumab administered within 30 days prior to transplant or at any time post-transplant and prior to Day 1
3. First detectable AdV DNA viremia since the qualifying transplant occurred within 21 days prior to Day 1
4. EITHER:
* AdV DNA viremia * 1000 copies/mL and rising, defined as two consecutive results * 1000 copies/mL from the designated central virology laboratory, with the second result being greater than the first. The second sample must be drawn at least 48 hours after the first sample and no more than 7 days prior to Day 1 OR
* AdV DNA viremia * 10,000 copies/mL from the designated central virology laboratory
5. If male of reproductive potential, willing to use an acceptable contraceptive method(s) throughout the duration of his participation in the study and until 90 days following last dose of BCV when engaging in sexual intercourse with a female partner of childbearing potential
6. If female of child-bearing potential (i.e., post menarche and not surgically sterilized), willing to use two acceptable contraceptive methods, one of which must be a barrier method, throughout the duration of her participation in the study and until 90 days following last dose of BCV when engaging in sexual intercourse with a non-sterile male
7. Able to provide written informed consent or assent, with legal guardian consent, as required by applicable local or national law and institutional practice, based on the age of the subject
8. Available to participate in all required study activities for the entire duration of the study (i.e., inclusive of the Week 36 assessment)
1. Any CTCAE Grade 4 diarrhea (i.e., life-threatening consequences with urgent intervention indicated) within 7 days prior to Day 1
2. Any CTCAE Grade 2 or 3 diarrhea (i.e., increase of * 4 stools per day over baseline), unless attributed to AdV, within 7 days prior to Day 1
3. NIH Stage 4 acute GVHD of the skin (i.e., generalized erythroderma with bullous formation) within 7 days prior to Day 1
4. NIH Stage 2 or higher acute GVHD of the liver (i.e., bilirubin > 3 mg/dL [SI: > 51 *mol/L]) within 7 days prior to Day 1
5. NIH Stage 2 or higher acute GVHD of the gut (i.e., diarrhea > 556 mL/m2 /day, or severe abdominal pain with or without ileus) within 7 days prior to Day 1
6. Active malignancy (with the exception of non-melanoma skin cancer), including relapse or progression of the underlying disease for which qualifying transplant was performed
7. Use of vasopressors within 7 days prior to Day 1
8. PT-INR > 2x upper limit of normal reference range (ULN) in the absence of anticoagulation within 7 days prior to Day 1
9. Requirement for mechanical ventilation within 7 days prior to Day 1, or sustained oxygen delivery for > 24 hours within 7 days prior to Day 1, or any oxygen requirement within 48 hours prior to Day 1
10. Estimated creatinine clearance < 30 mL/min or use of renal replacement therapy (e.g., hemodialysis, continuous renal replacement therapy, peritoneal dialysis) within 7 days prior to Day 1
11. ALT > 5x ULN, AST > 5x ULN, or total bilirubin > 3 mg/dL [SI: > 51 *mol/L] within 7 days prior to Day 1
12. Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection within 6 months prior to Day 1, as demonstrated by detectable HBV DNA or HCV ribonucleic acid (RNA) in blood, plasma, or serum. [Note: A negative or undetectable HBV DNA or HCV RNA test is required at screening to confirm the absence of active infection unless testing was performed by the local laboratory within 6 months prior to screening.]
13. Human immunodeficiency virus (HIV) infection as detected through any laboratory method (e.g., enzyme-linked immunosorbent assay, Western Blot, RNA PCR).
[Note: Testing to confirm the absence of HIV infection is required at screening unless testing was performed by the local laboratory within 6 months prior to screening.]
14. Females who are pregnant or breastfeeding or planning to become pregnant within 90 days after their last anticipated dose of BCV
15. Receiving or anticipated to receive medications prohibited in this protocol (see Section 8.6.1)
16. Hypersensitivity (not including renal dysfunction or eye disorder) to CDV or to BCV or its formulation excipients
17. Receipt of IV CDV within 48 hours prior to Day 1
18. Previous receipt of BCV at any time
19. Participation in another interventional clinical trial unless prior approval has been received from the Chimerix Medical Monitor (or designee) (see Section 8.6.1.3)
20. Received any anti-AdV specific cell-based therapy within 6 weeks prior to Day 1 or previously received an anti-AdV vaccine at any time
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary objective of this study is to compare the safety, overall<br /><br>tolerability, and virologic response of BCV vs. SoC (i.e.,<br /><br>investigator-assigned therapy) for the treatment of AdV infection in high-risk<br /><br>pediatric allogeneic HCT recipients. A virologic response-driven approach to<br /><br>the duration of treatment will be evaluated, in which subjects randomized to<br /><br>BCV therapy are treated until AdV viremia is confirmed as undetectable or until<br /><br>a maximum of 16 weeks of therapy, whichever occurs first. The primary efficacy<br /><br>endpoint is the AAUC for AdV viremia (log10 copies/mL) from randomization<br /><br>through Week 16 post-randomization.</p><br>
- Secondary Outcome Measures
Name Time Method