Trial Outcomes & Findings for The AdAPT Trial; Adenovirus After Allogeneic Pediatric Transplantation (NCT NCT03339401)

Last Updated: 2021-01-25

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

29 participants

Primary outcome timeframe

From randomization to 16 weeks post-randomization

Results posted on

2021-01-25

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	20	9
Overall Study COMPLETED	11	5
Overall Study NOT COMPLETED	9	4

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Death	2	1
Overall Study Withdrawal by Subject	2	0
Overall Study Study terminated	4	3
Overall Study Investigator Decision	1	0

Baseline Characteristics

The AdAPT Trial; Adenovirus After Allogeneic Pediatric Transplantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Brincidofovir n=20 Participants 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.	Standard of Care n=9 Participants 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.	Total n=29 Participants Total of all reporting groups
Age, Categorical <=18 years	20 Participants n=39 Participants	9 Participants n=41 Participants	29 Participants n=35 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Age, Categorical >=65 years	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Age, Continuous	5.1 years STANDARD_DEVIATION 4.05 • n=39 Participants	5.9 years STANDARD_DEVIATION 4.18 • n=41 Participants	5.3 years STANDARD_DEVIATION 4.04 • n=35 Participants
Sex: Female, Male Female	8 Participants n=39 Participants	5 Participants n=41 Participants	13 Participants n=35 Participants
Sex: Female, Male Male	12 Participants n=39 Participants	4 Participants n=41 Participants	16 Participants n=35 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=39 Participants	0 Participants n=41 Participants	1 Participants n=35 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=39 Participants	8 Participants n=41 Participants	26 Participants n=35 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=39 Participants	1 Participants n=41 Participants	2 Participants n=35 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Race (NIH/OMB) Asian	1 Participants n=39 Participants	1 Participants n=41 Participants	2 Participants n=35 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=39 Participants	0 Participants n=41 Participants	1 Participants n=35 Participants
Race (NIH/OMB) Black or African American	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Race (NIH/OMB) White	17 Participants n=39 Participants	4 Participants n=41 Participants	21 Participants n=35 Participants
Race (NIH/OMB) More than one race	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=39 Participants	4 Participants n=41 Participants	5 Participants n=35 Participants
Region of Enrollment United States	4 participants n=39 Participants	2 participants n=41 Participants	6 participants n=35 Participants
Region of Enrollment United Kingdom	12 participants n=39 Participants	5 participants n=41 Participants	17 participants n=35 Participants
Region of Enrollment Italy	0 participants n=39 Participants	1 participants n=41 Participants	1 participants n=35 Participants
Region of Enrollment France	3 participants n=39 Participants	0 participants n=41 Participants	3 participants n=35 Participants
Region of Enrollment Germany	1 participants n=39 Participants	1 participants n=41 Participants	2 participants n=35 Participants
Adenovirus in plasma	20 Participants n=39 Participants	9 Participants n=41 Participants	29 Participants n=35 Participants

PRIMARY outcome

Timeframe: From randomization to 16 weeks post-randomization

Population: The time-averaged area under the concentration-time curve for plasma adenovirus (AdV) viremia was not calculated because many of the viral response data were arbitrarily truncated/censored and individual subject AdV viremia profiles cannot be reported due to concerns with patient confidentiality.

Outcome measures

Outcome data not reported

Adverse Events

Brincidofovir

Serious events: 15 serious events

Other events: 20 other events

Deaths: 4 deaths

Standard of Care

Serious events: 6 serious events

Other events: 9 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Chimerix, Inc.

Phone: 919-806-1074

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Within 12 months after the end of the Study at all sites, if no publication of the overall multi-center results has been made, institutions are entitled to publish their locally obtained results, provided the Sponsor is given opportunity to review and comment. Institution publication may be delayed up to an additional 3 months to allow Sponsor to seek patent protection.
Publication restrictions are in place

Restriction type: OTHER

Measure	Brincidofovir n=20 participants at risk 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.	Standard of Care n=9 participants at risk 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.
Infections and infestations Bacteraemia	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Infections and infestations Device related infection	10.0% 2/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Infections and infestations Device related sepsis	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Infections and infestations Enterococcal bacteraemia	0.00% 0/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	11.1% 1/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Infections and infestations Gastroenteritis viral	0.00% 0/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	11.1% 1/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Infections and infestations Human herpesvirus 6 infection	0.00% 0/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	11.1% 1/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Infections and infestations Influenza	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Infections and infestations Lower respiratory tract infection fungal	0.00% 0/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	11.1% 1/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Infections and infestations Parainfluenzae virus infection	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Infections and infestations Pneumonia cytomegaloviral	0.00% 0/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	11.1% 1/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Infections and infestations Rhinovirus infection	10.0% 2/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Infections and infestations Sepsis	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Infections and infestations Viral upper respiratory tract infection	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Investigations Astrovirus test positive	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Investigations Blood creatinine abnormal	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Investigations Body temperature increased	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Metabolism and nutrition disorders Hyperkalaemia	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	11.1% 1/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Nervous system disorders Encephalopathy	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Product Issues Device dislocation	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Renal and urinary disorders Acute kidney injury	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	11.1% 1/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Blood and lymphatic system disorders Evans Syndrome	0.00% 0/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	11.1% 1/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Blood and lymphatic system disorders Haemolytic anaemia	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Blood and lymphatic system disorders Haemolytic uraemic syndrome	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Cardiac disorders Cardiac tamponade	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Cardiac disorders Pericardial effusion	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Gastrointestinal disorders Abdominal distension	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Gastrointestinal disorders Abdominal pain	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Gastrointestinal disorders Diarrhoea	0.00% 0/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	11.1% 1/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Gastrointestinal disorders Gastric haemorrhage	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Gastrointestinal disorders Gastrointestinal haemorrhage	10.0% 2/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Gastrointestinal disorders Vomiting	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
General disorders Pyrexia	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	33.3% 3/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Gastrointestinal disorders Unevaluable event	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Hepatobiliary disorders Venoocclusive liver disease	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Infections and infestations Adenovirus infection	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Respiratory, thoracic and mediastinal disorders Hypoxia	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	0.00% 0/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.
Respiratory, thoracic and mediastinal disorders Respiratory failure	5.0% 1/20 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.	11.1% 1/9 • From randomization to 16 weeks post-randomization. Note: Other Adverse Events includes non-serious and serious adverse events.