A clinical study to compare brincidofovir with current care for adenovirus infection in children after a bone marrow transplant
- Conditions
- Treatment of adenovirus infections in high-risk pediatric allogeneic allogenic hematopoietic cell transplant recipientsMedDRA version: 20.1Level: PTClassification code 10060931Term: Adenovirus infectionSystem Organ Class: 10021881 - Infections and infestationsTherapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2017-001735-39-GB
- Lead Sponsor
- Chimerix, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 29
· Aged at least 2 months and less than 18-years-old on Day 1.
· Have received a high risk allogeneic HCT within the previous 100 days
· If previously treated with IV CDV, have a cumulative exposure to IV CDV of no more than 10 mg/Kg within 21 days prior to Day 1.
Have either
· A confirmed AdV 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.
OR
Single AdV viremia measurement of = 10,000 copies/mL reported by the designated central virology laboratory from a sample no more than 7 days prior to Day 1.
Are the trial subjects under 18? yes
Number of subjects for this age range: 141
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
· Any CTCAE Grade 4 diarrhea (i.e., life-threatening consequences with urgent intervention indicated) within 7 days prior to Day 1.
· Any CTCAE Grade 2 or 3 diarrhea (i.e., increase of = 4 stools per day over baseline) [pre-transplant] diarrheal output), unless attributed to AdV, within 7 days prior to Day 1.
· NIH Stage 4 acute GVHD of the skin (i.e., generalized erythroderma with bullous formation) within 7 days prior to Day 1.
· NIH Stage 2 or higher acute GVHD of the liver (i.e., bilirubin > 3 mg/dL [SI: > 51 µmol/L]) within 7 days prior to Day 1.
· 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.
· Active malignancy (with the exception of non-melanoma skin cancer), including relapse or progression of the underlying disease for which qualifying transplant was performed.
· Use of vasopressors other than low-dose (e.g., = 5 µg/kg/min) dopamine for renal perfusion within 7 days prior to Day 1.
· PT-INR > 2x upper limit of normal reference range (ULN) in the absence of anticoagulation within 7 days prior to Day 1 [Note: Where the results of screening PT INR testing performed at the central safety laboratory are not available in time to allow a subject to be qualified for the study, to avoid delaying randomization and the start of treatment, with the approval of the Chimerix Medical Monitor (or designee), subjects may be qualified for the study based on the results of PT-INR testing performed at a local laboratory.]
· Requirement for mechanical ventilation within 7 days prior to Day 1, or requirement for sustained oxygen delivery for > 24 hours within 7 days prior to Day 1, or any oxygen requirement within 48 hours prior to Day 1.
· 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.
· ALT > 5x ULN, AST > 5x ULN, or total bilirubin > 3 mg/dL [SI: > 51 µmol/L] within 7 days prior to Day 1.
· 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.].
· Females who are pregnant or breastfeeding or planning to become pregnant within 90 days after their last anticipated dose of BCV.
· Receiving or anticipated to receive medications prohibited in this protocol (e.g., letermovir, systemic ketoconazole, sesamin-containing products, anti-AdV vaccines).
· Hypersensitivity (not including renal dysfunction or eye disorder) to CDV or to BCV or its formulation excipients.
· 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).
· Received any cell-based anti-AdV therapy within 6 weeks prior to Day 1 or previously received an anti-AdV vaccine at any time.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of the study is to compare the safety, overall tolerability, and virologic response of BCV vs. SoC for the treatment of AdV infection in high-risk pediatric allogeneic HCT recipients.;Secondary Objective: • To assess the incidence of and time to all-cause, non-relapse, and AdV-associated mortality in pediatric subjects treated with BCV vs. SoC<br>• To assess the correlation between virologic response and clinical outcome<br>• To describe the incidence of and time to virologic relapse in subjects who have previously achieved undetectable AdV viremia;Primary end point(s): The primary efficacy endpoint is the time-averaged area under the concentration-time curve (AAUC) for AdV viremia (log10 copies/mL) through Week 16 post-randomization. ;Timepoint(s) of evaluation of this end point: Week 16 post randomization
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Time to all-cause mortality <br>• Incidence of and time to all-cause mortality <br>• Incidence of and time to non-relapse mortality <br>• Incidence of and time to AdV-associated mortality <br>• Proportion of subjects with = 2-log10 decline from baseline or undetectable AdV viremia at Weeks 2, 4, 6, 12, and 16<br>;Timepoint(s) of evaluation of this end point: Efficacy Endpoints: until Week 16 <br>Safety Endpoints: until Week 36 <br><br>