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Trial record 1 of 1 for:    NCT03339401
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The AdAPT Trial; Adenovirus After Allogeneic Pediatric Transplantation (AdAPT)

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ClinicalTrials.gov Identifier: NCT03339401
Recruitment Status : Terminated (terminated due to low enrollment rate)
First Posted : November 13, 2017
Results First Posted : January 25, 2021
Last Update Posted : January 25, 2021
Sponsor:
Information provided by (Responsible Party):
Chimerix

Brief Summary:
This study was designed to assess the safety, overall tolerability, and antiviral activity of "short course" brincidofovir (BCV) therapy, as compared with current standard of care (SoC), for the treatment of adenovirus (AdV) infections in high-risk (i.e., T cell depleted) pediatric allogeneic hematopoietic cell transplant (HCT) recipients. A virologic response-driven approach to the duration of treatment was to be evaluated, in which subjects randomized to BCV therapy were to be treated until AdV viremia was confirmed as undetectable or until a maximum of 16 weeks of therapy, whichever occurred first. The formulation of BCV used in this study was oral tablet/suspension.

Condition or disease Intervention/treatment Phase
Adenovirus Other: Standard of Care Drug: Brincidofovir Phase 2

Detailed Description:
This was a randomized, open-label, multi-center study of the safety, overall tolerability, and antiviral activity of BCV, as compared with SoC, in pediatric (and young adults in the United States) recipients of high-risk (i.e., T cell-depleted and/or unrelated cord blood graft, or a T cell-replete graft from ahaploidentical donor with post-transplant cyclophosphamide administration) allogeneic HCT. Subjects with AdV detected in plasma after their qualifying transplant could be screened for participation in the study. Subjects who met all applicable entry criteria were randomized in a 2:1 ratio to receive either BCV or SoC (i.e., investigator-assigned therapy). The formulation of BCV used in this study was oral tablet/suspension. Subjects were randomized within 100 days post-transplant; for study purposes, the day of randomization was defined as Day 1. During randomization, subjects were stratified based on the following variables: last AdV viremia (≥10,000 copies/mL versus <10,000 copies/mL) measurement available from the designated central virology laboratory prior to randomization, time from transplant to randomization (≥28 days versus <28 days), and T cell-depletion methodology (receipt of alemtuzumab or ex vivo depletion versus receipt of anti-thymocyte globulin [ATG] or no T cell depletion).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Study to Assess the Safety, Overall Tolerability, and Antiviral Activity of Brincidofovir Versus Standard of Care for Treatment of Adenovirus in High-risk Pediatric Allogeneic Hematopoietic Transplant Recipients
Actual Study Start Date : December 22, 2017
Actual Primary Completion Date : May 10, 2019
Actual Study Completion Date : May 10, 2019

Arm Intervention/treatment
Experimental: Brincidofovir

Brincidofovir (BCV) for the treatment of adenovirs (AdV) infection in high-risk pediatric allogeneic hematopoietic cell transplant (HCT) recipients.

Brincidofovir (BCV) treatment began no later than 100 days post-transplant and was to continue for a maximum of 16 weeks. Brincidofovir (BCV) was discontinued once AdV viremia was confirmed undetectable.

Subjects who did NOT receive concurrent cyclosporine on Day 1:

  • If ≥48kg body weight, one 100mg oral tablet BIW (or 10mL of 10mg/mL oral suspension if unable to take tablets).
  • If <48kg body weight, 2mg/kg oral volume of 10mg/mL oral suspension BIW.

Subjects who received cyclosporine on Day 1 (or initiated cyclosporine at any time):

  • 1.4mg/kg (maximum of 70mg) oral volume of 10mg/mL oral suspension BIW.
  • 2mg/kg (maximum of 100mg) oral volume of 10mg/mL oral suspension BIW if discontinued cyclosporine.
Drug: Brincidofovir
Brincidofovir (BCV) for the treatment of adenovirus infection in high-risk pediatric allogeneic hematopoietic cell transplant (HCT) recipients.
Other Name: BCV

Standard of Care

Local institutional standard of care (SoC) (i.e., investigator-assigned therapy) for the treatment of adenovirus infection in high-risk pediatric allogeneic hematopoietic cell transplant (HCT) recipients.

Management of these subjects was prescribed by the investigator as being in the best interests of the subject and may have included a "watch-and-wait" approach, with or without decreased immunosuppression (ergo, no treatment), or treatment administration with other available antivirals, most commonly cidofovir intravenously.

Decisions regarding SoC, including administration of therapy, dose and regimen of therapy, modification of immunosuppression, and monitoring was the responsibility of the clinical team caring for the subject, according to institutional guidelines, local practices, and applicable guidelines for the management of AdV infection.

Other: Standard of Care
Local institutional standard of care (SoC) (i.e., investigator-assigned therapy) for the treatment of adenovirus infection in high-risk pediatric allogeneic hematopoietic cell transplant (HCT) recipients.
Other Name: SoC




Primary Outcome Measures :
  1. Time-averaged Area Under the Concentration-time Curve for Plasma Adenovirus Viremia (Log10 Copies/mL). [ Time Frame: From randomization to 16 weeks post-randomization ]
    The primary efficacy endpoint for this study was the time-averaged area under the concentration-time curve for plasma adenovirus (AdV) viremia (log10 copies/mL) from randomization through Week 16 post-randomization. Due to the small number of subjects enrolled in the study, formal efficacy analyses were not performed. Individual subject AdV viremia profiles show the differential anti-adenoviral effect of brincidofovir (BCV) in comparison to standard of care (SoC) therapy.



Information from the National Library of Medicine

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Ages Eligible for Study:   2 Months to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects were high-risk allogeneic hematopoietic cell transplant (HCT) recipients aged 2 months to <18 years (<26 years in the United States) who met adenovirus (AdV) viremia criteria within 7 days of randomization (Day 1), and all other eligibility criteria. High-risk was defined as having received 1 of the following:

  • A T cell-depleted graft:

    • Ex vivo T cell depletion via positive selective (e.g., CD34+ cell) or negative selection (e.g., T cell receptor α/β or CD3+ cell removal by column filtration); or
    • Serotherapy with ATG (cumulative dose of ≥3 mg/kg rabbit-derived ATG or ≥30 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; or
  • A cord blood graft from an unrelated donor with or without T cell depletion, or
  • A T cell-replete graft from a haploidentical donor with high-dose cyclophosphamide (e.g., cumulative dose of ≥100 mg/kg) administered at any time post-transplant and prior to Day 1.

Subjects must have had qualifying AdV viremia within 100 days of transplant, which was defined as having either:

  1. Confirmed AdV viremia of ≥1000 copies/mL on 2 consecutive AdV DNA polymerase chain reaction (PCR) test results drawn ≥48 hours apart from the designated central virology laboratory, with the second result being greater than the first; or
  2. A single AdV viremia result of ≥10,000 copies/mL from the designated central virology laboratory Subjects who were previously treated with intravenous (IV) cidofovir (CDV) could have a cumulative exposure to IV CDV of no more than 10 mg/kg within 21 days prior to Day 1.

Written informed consent (and assent, where applicable) to participate in the study was obtained from each subject and his/her legal guardian(s) in accordance with national or local law and institutional practice.

Exclusion Criteria:

  1. Any United States National Institutes of Health (NIH)/National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (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/day over baseline [pre-transplant] diarrheal output), unless attributed to AdV, within 7 days prior to Day 1.
  3. NIH Stage 4 acute graft versus host disease (GVHD) of the skin (i.e., generalized erythroderma with bullous formation) within 7 days prior to Day 1.
  4. NIH Stage ≥2 acute GVHD of the liver (i.e., bilirubin >3 mg/dL [SI: >51 µmol/L]) within 7 days prior to Day 1.
  5. NIH Stage ≥2 acute GVHD of the gut (i.e., diarrhea >556 mL/m2/day for pediatric patients [or >1000 mL/day for young adults at centers in the United States only], or severe abdominal pain with or without ileus) within 7 days prior to Day 1.
  6. Poor clinical prognosis (including active malignancy or use of vasopressors other than low dose (e.g., ≤5 µg/kg/min) dopamine for renal perfusion within 7 days prior to Day 1.
  7. 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.
  8. Concurrent HIV, active hepatitis B virus, or hepatitis C virus infection.
  9. Specified out of range laboratory results (including alanine aminotransferase >5x the upper limit of normal [ULN], aspartate aminotransferase >5x ULN, total bilirubin >3 mg/dL [SI: >51 µmol/L], or prothrombin time-international normalized ratio >2x ULN) within 7 days prior to Day 1.
  10. Estimated creatinine clearance <30 mL/min or use of renal replacement therapy within 7 days prior to Day 1.
  11. Previous receipt of BCV at any time or receipt of CDV (IV or intravesicular) or letermovir within 48 hours prior to Day 1.
  12. 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.

When applicable, female subjects of childbearing potential (i.e., not pre-menarche) were not pregnant or breastfeeding, and if sexually active, agreed to use 2 acceptable forms of contraception, 1 of which must have been a barrier method and the other a highly-effective method of contraception. Male subjects, if sexually active and capable of fathering a child, agreed to use a barrier method of contraception while enrolled in the study and for at least 90 days after the last dose of BCV.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03339401


Locations
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Sponsors and Collaborators
Chimerix
  Study Documents (Full-Text)

Documents provided by Chimerix:
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Responsible Party: Chimerix
ClinicalTrials.gov Identifier: NCT03339401    
Other Study ID Numbers: CMX001-999
First Posted: November 13, 2017    Key Record Dates
Results First Posted: January 25, 2021
Last Update Posted: January 25, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Chimerix:
Adenovirus
Pediatric
Hematopoietic Cell Transplant
Brincidofovir
Standard of care
Additional relevant MeSH terms:
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Adenoviridae Infections
DNA Virus Infections
Virus Diseases