E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of adenovirus infections in high-risk (i.e., T cell depleted) pediatric allogeneic hematopoietic cell transplant recipients |
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E.1.1.1 | Medical condition in easily understood language |
Treatment of adenovirus infection in children after a bone marrow transplant |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060931 |
E.1.2 | Term | Adenovirus infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to compare the safety, overall tolerability, and virologic response of BCV vs. SoC (i.e. investigator-assigned therapy) for the treatment of AdV infection in high-risk pediatric allogeneic HCT recipients. |
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E.2.2 | Secondary objectives of the trial |
• 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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
• Have had a first detectable AdV DNA plasma viremia since the qualifying transplant occurred within 21 days prior to Day 1 and either
• a confirmed AdV viremia of ≥ 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 from the designated central virology laboratory from a sample no more than 7 days prior to Day 1. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
16 weeks or until AdV deoxyribonucleic acid (DNA) is confirmed to be undetectable in plasma whichever occurs first |
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E.5.2 | 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. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy Endpoints: until Week 16
Safety Endpoints: until Week 36
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Standard of Care as per physician's discretion |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Germany |
Ireland |
Italy |
Netherlands |
Poland |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |