A clinical study to compare brincidofovir with current care for adenovirus infection in children after a bone marrow transplant

Phase 1

• Conditions: Treatment of adenovirus infections in high-risk (i.e., T cell depleted) pediatric allogeneic hematopoietic cell transplant recipients; MedDRA version: 20.1 Level: PT Classification code 10060931 Term: Adenovirus infection System Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2017-001735-39-FR
• Lead Sponsor: Chimerix, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-03-08
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 141

Inclusion Criteria

• Aged at least 2 months and less than 18-years-old on Day 1.
• Have received a T cell-depleted allogeneic HCT within the previous 100 days.
• First detectable AdV DNA plasma viremia since the qualifying transplant occurred within 21 days prior to Day 1.
• AdV DNA plasma 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.
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

Exclusion Criteria

• 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), 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 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.
• 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.
• 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 (see Section 8.6.1).
• 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.;<br> 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<br> ;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
<br> Timepoint(s) of evaluation of this end point: Efficacy Endpoints: until Week 16<br> Safety Endpoints: until Week 36<br> <br> ;<br> 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>