The AdAPT Trial; Adenovirus After Allogeneic Pediatric Transplantation (AdAPT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03339401
Recruitment Status : Recruiting
First Posted : November 13, 2017
Last Update Posted : July 30, 2018
Information provided by (Responsible Party):

Brief Summary:
This study is designed to assess the safety, overall tolerability, and antiviral activity of "short course" 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 will be evaluated, in which subjects randomized to BCV therapy are treated until AdV viremia is confirmed as undetectable or until a maximum of 16 weeks of therapy, whichever occurs first.

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 141 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : December 22, 2017
Estimated Primary Completion Date : September 21, 2019
Estimated Study Completion Date : February 21, 2020

Arm Intervention/treatment
Experimental: Brincidofovir (BCV)
Drug: Brincidofovir
Other Name: BCV

Standard of Care (SOC)
Other: Standard of Care
SOC per study center guidelines
Other Name: SOC

Primary Outcome Measures :
  1. Primary Outcome is the time-averaged area under the concentration-time curve (AAUC) for plasma AdV viremia (log10 copies/mL). [ Time Frame: randomization through16 weeks ]
    From randomization through Week 16, time-averaged area under the concentration-time curve (AAUC) for plasma AdV viremia (log10 copies/mL).

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Months to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Aged at least 2 months and less than 18-years-old on Day 1 AND
  2. Have received a T cell-depleted allogeneic (i.e., non-autologous) HCT within the previous 100 days.
  3. First detectable AdV DNA plasma viremia since the qualifying transplant occurred within 21 days prior to Day 1.
  4. AdV DNA plasma viremia of ≥ 1,000 copies/mL and rising, defined as two consecutive results ≥ 1,000 copies/mL from the designated central virology laboratory, with the second result being greater than the first.

Exclusion Criteria:

  1. Any 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 per day over baseline), unless attributed to AdV, within 7 days prior to Day 1
  3. NIH Stage 4 acute GVHD of the skin (i.e., generalized erythroderma with bullous formation) within 7 days prior to Day 1
  4. 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
  5. 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
  6. Active malignancy (with the exception of non-melanoma skin cancer), including relapse or progression of the underlying disease for which qualifying transplant was performed
  7. Use of vasopressors within 7 days prior to Day 1
  8. PT-INR > 2x upper limit of normal reference range (ULN) in the absence of anticoagulation within 7 days prior to Day 1
  9. 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
  10. 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
  11. ALT > 5x ULN, AST > 5x ULN, or total bilirubin > 3 mg/dL [SI: > 51 μmol/L] within 7 days prior to Day 1
  12. 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.]
  13. Females who are pregnant or breastfeeding or planning to become pregnant within 90 days after their last anticipated dose of BCV
  14. Receiving or anticipated to receive medications prohibited in the protocol.
  15. Hypersensitivity (not including renal dysfunction or eye disorder) to CDV or to BCV or its formulation excipients
  16. Participation in another interventional clinical trial unless prior approval has been received from the Chimerix Medical Monitor (or designee).
  17. Received any cell-based anti-AdV therapy within 6 weeks prior to Day 1 or previously received an anti-AdV vaccine at any time.

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 identifier (NCT number): NCT03339401

Contact: Garrett Nichols, MD, MS 919-287-6006

United States, California
Children's Hospital of Los Angeles Recruiting
Los Angeles, California, United States, 90027
Principal Investigator: Hisham Abdel-Azim, MD         
University of California San Francisco Recruiting
San Francisco, California, United States, 94143
Principal Investigator: Jasmeen Dara, MD         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Principal Investigator: Kathleen Mullane, DO         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Principal Investigator: Genovefa Papanicolaou, MD         
United States, North Carolina
Duke University Medical Center Not yet recruiting
Durham, North Carolina, United States, 27705
Principal Investigator: Vinod Prasad, MD         
United States, Ohio
Cincinnati Childrens Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Principal Investigator: Michael Grimley, MD         
United States, Pennsylvania
Children's Hospital of Philadelphia Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Principal Investigator: Nancy Bunin, MD         
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Principal Investigator: Gabriela Maron, MD         
United States, Washington
University of Washington-Seattle Childrens Hospital Recruiting
Seattle, Washington, United States, 98105
Principal Investigator: Janet Englund, MD         
Hopital Necker-Enfants Malades Recruiting
Paris, France, 75015
Principal Investigator: Stephane Blanche         
Hopital Universitaire Robert Debre Recruiting
Paris, France, 75019
Principal Investigator: Jean-Hugues Dalle         
Our Lady's Children Hospital Recruiting
Dublin, Ireland, D12 N512
Principal Investigator: Andrea Malone, MD         
Hospital Sant Joan de Deu Recruiting
Esplugues De Llobregat, Barcelona, Spain, 08950
Principal Investigator: Claudia Fortuny Guasch         
Hospital Infantil Universitario Nino Jesus Recruiting
Madrid, Spain, 28009
Principal Investigator: Miguel Diaz Perez         
United Kingdom
Royal Marsden Hospital Recruiting
Sutton, Surrey, United Kingdom, SM2 5PT
Principal Investigator: Mark Ethell         
Leeds Children's Hospital Recruiting
Leeds, West Yorkshire, United Kingdom, LS1 3EX
Principal Investigator: Rebecca James, MD         
Bristol Royal Hospital for Children Recruiting
Bristol, United Kingdom, BS2 8BJ
Principal Investigator: Ponni Sivaprakasam, MD         
Royal Hospital for Sick Children Recruiting
Glasgow, United Kingdom, G51 4TF
Principal Investigator: Brenda Gibson         
University College London Hospital Recruiting
London, United Kingdom, NW1 2BU
Principal Investigator: Rachael Hough, MD         
St Marys Hospital Recruiting
London, United Kingdom, W2 1NY
Principal Investigator: Jesus de la Fuente Pereda         
Great Ormond Street Hospital for Children Recruiting
London, United Kingdom, WCIN 3JH
Principal Investigator: Kanchan Rao         
Royal Manchester Childrens Hospital Recruiting
Manchester, United Kingdom, M13 9WL
Principal Investigator: Robert Wynn         
Sheffield Children's Hospital Recruiting
Sheffield, United Kingdom, S10 2TH
Principal Investigator: Katharine Patrick         
Sponsors and Collaborators

Responsible Party: Chimerix Identifier: NCT03339401     History of Changes
Other Study ID Numbers: CMX001-999
First Posted: November 13, 2017    Key Record Dates
Last Update Posted: July 30, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Adenoviridae Infections
DNA Virus Infections
Virus Diseases