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

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2017-001735-39-FR
• Date of registration: 08/03/2018
• Prospective Registration: No
• Primary sponsor: Chimerix, Inc
• Public title: A clinical study to compare brincidofovir with current care for adenovirus infection in children after a bone marrow transplant
• Scientific title: 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 - AdAPT: Adenovirus after Allogeneic Pediatric Transplantation
• Date of first enrolment: 02/02/2018
• Target sample size: 141
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001735-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: Standard of Care; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Ireland, Italy, Netherlands, Poland, Spain, United Kingdom, United States

Contacts

• Name: Chief Medical Officer
• Affiliation: Chimerix Inc.

• Name: Chief Medical Officer
• Affiliation: Chimerix Inc.

Key inclusion & exclusion criteria

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Virus Diseases [C02]

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

Intervention(s)

Product Name: Brincidofovir
Product Code: CMX001
Pharmaceutical Form: Oral suspension
INN or Proposed INN: Brincidofovir (USAN)
CAS Number: 444805-28-1
Current Sponsor code: CMX001
Other descriptive name: CMX001 / BRINCIDOFOVIR
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-

Primary Outcome(s)

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.

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
• To assess the correlation between virologic response and clinical outcome
• To describe the incidence of and time to virologic relapse in subjects who have previously achieved undetectable AdV viremia

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.

Timepoint(s) of evaluation of this end point: Week 16 post-randomization.

Secondary Outcome(s)

Secondary end point(s): • Time to all-cause mortality.
• Incidence of and time to all-cause mortality.
• Incidence of and time to non-relapse mortality.
• Incidence of and time to AdV-associated mortality.
• Proportion of subjects with = 2-log10 decline from baseline or undetectable AdV viremia at Weeks 2, 4, 6, 12 and 16.

Timepoint(s) of evaluation of this end point: Efficacy Endpoints: until Week 16
Safety Endpoints: until Week 36

Secondary ID(s)

CMX001-999

NCT03339401

2017-001735-39-IE

Source(s) of Monetary Support

Chimerix Inc.

Ethics review

Status: Approved
Approval date:
Contact: