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AdenovirusPhase 2AdAPTNCT03339401

The AdAPT Trial; Adenovirus After Allogeneic Pediatric Transplantation

A Phase 2 study testing Brincidofovir in people with Adenovirus, run by Jazz Pharmaceuticals at 36 sites in 9 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 2 months to 25 years
Conditions the study is for
Adenovirus
What is being tested?
Brincidofovir
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
36 sitesin 9 countries
Study dates
22 Dec 2017to 10 May 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 months to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
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  • 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:
  • 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
  • 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.

Who cannot join

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
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  • 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.
  • Concurrent HIV, active hepatitis B virus, or hepatitis C virus infection.
  • 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.
  • Estimated creatinine clearance <30 mL/min or use of renal replacement therapy within 7 days prior to Day 1.
  • Previous receipt of BCV at any time or receipt of CDV (IV or intravesicular) or letermovir within 48 hours prior to Day 1.
  • 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.

Trial locations and contacts

36 sites in 9 countries.

36 sites in 9 countries

United States11 sites
  • University of Chicago

    Chicago, Illinois, 60637

  • Cincinnati Childrens Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Duke University Medical Center

    Durham, North Carolina, 27705

  • Joseph M. Sanzari Childrens Hospital-Regional Cancer Care

    Hackensack, New Jersey, 07601

  • Children's Hospital of Los Angeles

    Los Angeles, California, 90027

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • University of California San Francisco

    San Francisco, California, 94143

  • University of Washington-Seattle Childrens Hospital

    Seattle, Washington, 98105

Other trials in United States

United Kingdom11 sites
  • Birmingham Childrens Hospital

    Birmingham, West Midlands, B4 6NH

  • Bristol Royal Hospital for Children

    Bristol, BS2 8BJ

  • Royal Hospital for Sick Children

    Glasgow, G51 4TF

  • Leeds Children's Hospital

    Leeds, West Yorkshire, LS1 3EX

  • University College London Hospital

    London, NW1 2BU

  • St Marys Hospital

    London, W2 1NY

  • Great Ormond Street Hospital for Children

    London, WCIN 3JH

  • Royal Manchester Childrens Hospital

    Manchester, M13 9WL

  • Newcastle-upon-Tyne Hospitals-Great Childrens Hospital

    Newcastle upon Tyne, Tyneside, NE1 4LP

  • Sheffield Children's Hospital

    Sheffield, S10 2TH

  • Royal Marsden Hospital

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

France3 sites
  • IHOPe-Institut d'Homatologie et d'Oncologie Pediatrique

    Lyon, 69008

  • Hopital Necker-Enfants Malades

    Paris, 75015

  • Hopital Universitaire Robert Debre

    Paris, 75019

Other trials in France

Germany3 sites
  • Charite Universitatsmedizin Berlin, Campus Virchow-Klinikum

    Berlin, 13353

  • Dr. von Haunersches Kinderspital, Abteilung fur Padiatrische

    München, Bavaria, 80337

  • Universitatsklinik fur Kinder-und Jugendmedizin

    Tübingen, Baden-Wurttemberg, 72076

Other trials in Germany

Italy2 sites
  • Fondazione MBBM-CTMO Pediatrico

    Monza, 20900

  • Ospedale Pediatrico Bambino Gesu

    Roma, 00165

Other trials in Italy

Netherlands2 sites
  • Leiden University Medical Center (LUMC)

    Leiden, 2333

  • Princess Maxima Center Utrecht

    Utrecht, 3584

Other trials in Netherlands

Spain2 sites
  • Hospital Sant Joan de Deu

    Esplugues de Llobregat, Barcelona, 08950

  • Hospital Infantil Universitario Nino Jesus

    Madrid, 28009

Other trials in Spain

Ireland1 site
  • Our Lady's Children Hospital

    Dublin, D12 N512

Other trials in Ireland

Poland1 site
  • Uniwerstytecki Azpital Kliniczny we Wroclawiu

    Wroclaw, Lower Silesian Voivodeship, 50-556

Other trials in Poland

About this study

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

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.

Read the 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).

Conditions
Adenovirus
Being tested
Standard of Care, Brincidofovir
Keywords
Adenovirus, Pediatric, Hematopoietic Cell Transplant, Brincidofovir, Standard of care
Medical subject headings
Adenoviridae Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Standard of CareOther

    Also called SoC

    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.

  • BrincidofovirDrug

    Also called BCV

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

Study groups in NCT03339401
Study groupRoleWhat they receive
BrincidofovirExperimentalBrincidofovir (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.
Receives: Drug: Brincidofovir
Standard of CareOtherLocal 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.
Receives: Other: Standard of Care

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time-averaged Area Under the Concentration-time Curve for Plasma Adenovirus Viremia (Log10 Copies/mL).

    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.

    Measured: From randomization to 16 weeks post-randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Nov 2017
  2. Study start22 Dec 2017
  3. Primary completion10 May 2019
  4. Study completion10 May 2019

Why it stopped: terminated due to low enrollment rate

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03339401
Sponsor's protocol ID
CMX001-999
Acronym
AdAPT
Status last verified
Jan 2021
First submitted
8 Nov 2017
Last updated
25 Jan 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Brincidofovir in people with Adenovirus, run by Jazz Pharmaceuticals at 36 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 36 sites in United States, United Kingdom, France, Germany, Italy and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time-averaged Area Under the Concentration-time Curve for Plasma Adenovirus Viremia (Log10 Copies/mL). (time frame: From randomization to 16 weeks post-randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jan 2021.

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