Study Designed to Assess the Safety, Tolerability and PK of PTI-808 in Healthy Volunteers and in Adults With Cystic Fibrosis
- Conditions
- Cystic Fibrosis - CompleteHealthy Volunteer - Complete
- Interventions
- Registration Number
- NCT03251092
- Lead Sponsor
- Proteostasis Therapeutics, Inc.
- Brief Summary
Part 1 of this trial will enroll healthy volunteers into a single ascending dose (SAD), multiple ascending dose (MAD), and Food Effect (FE) treatment groups.
The SAD treatment group is comprised of at least 3 ascending dose level cohorts where healthy adult subjects will be randomized to receive a single dose of either PTI-808 or placebo and will be followed for 7 days post dose. A safety review committee (SRC) will convene after the completion of each cohort to evaluate safety and pharmacokinetic (PK) data.
Following the conclusion of the respective SAD level dose groups and after sufficient review of study data and approval by the SRC, a second set of healthy adult subjects will participate in an assigned MAD treatment group. The MAD treatment group is comprised of 3 ascending dose level cohorts where subjects will be randomized to receive either PTI-808 or placebo daily for 7 days and will be followed for 7 days after receiving the last dose.
Also following the conclusion of the respective SAD level dose groups, healthy adult subjects will participate in the FE treatment group.
Part 2 of this will enroll healthy volunteers to assess the safety, tolerability, and PK of PTI 808 co administered with PTI 801 and PTI 428 to HVs with daily dosing for 7 consecutive days.
Part 3 will enroll adult subjects with cystic fibrosis (CF) into a MAD treatment group consisting of 2 cohorts. Subjects will receive PTI-808 co-administered with PTI-801 and PTI-428. PTI-808 will be administered daily for 7 consecutive days followed by PTI-808 + PTI-801 + PTI-428 administered daily for 14 consecutive days.
Part 4 will enroll adult subjects with cystic fibrosis (CF) into 28-day cohorts. Subjects will receive PTI-808 co-administered with PTI-801 with or without PTI-428 versus matching placebo.
- Detailed Description
Part 1 of this trial will enroll healthy volunteers into a single ascending dose (SAD), multiple ascending dose (MAD), and Food Effect (FE) treatment groups.
The SAD treatment group is comprised of at least 3 ascending dose level cohorts where healthy adult subjects will be randomized to receive a single dose of either PTI-808 or placebo and will be followed for 7 days post dose.
The MAD treatment group is comprised of 3 ascending dose level cohorts where subjects will be randomized to receive either PTI-808 or placebo daily for 7 days and will be followed for 7 days after receiving the last dose.
Following the conclusion of the respective SAD level dose groups the food effect portion of the study will be initiated and subjects will be randomized to receive an initial single dose of PTI-808 either after an overnight fast of at least 10 hours (fasted group) or after an overnight fast of at least 10 hours followed the consumption of a high fat high calorie meal (fed group). After a 10 day washout period, subjects will cross over to the opposite group and receive a second dose of PTI-808. Subjects will be followed for up to 7 days following dosing.
Part 2 of this will enroll healthy volunteers to assess the safety, tolerability, and PK of PTI 808 co administered with PTI 801 and PTI 428 to HVs with daily dosing for 7 consecutive days.
Part 3 - Part 3 will enroll adult subjects with CF to assess the safety, tolerability, and PK of multiple ascending doses of PTI-808 co-administered with PTI-801 and PTI-428. Subjects will receive 7 days of PTI-808 or placebo followed by 14 days of PTI-808 or placebo co-administered with PTI-801+PTI-428 or matching placebos.
Part 4 - Part 4 will assess the safety, tolerability, PK, and the effects of PTI-808 co-administered with PTI-801 with or without PTI-428 over a 28-day treatment period in CF subjects who are either homozygous for the F508del CFTR genotype or are heterozygous for the F508del CFTR genotype. Subjects will be randomized to receive treatment with PTI-808 co-administered with PTI-801 with or without PTI-428 versus matching placebo.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 179
- Adults aged 18 to 55 years old, inclusive, at the time of informed consent
- Body mass index ≥18 and <30 kg/m2
- Subject must be a non-smoker and non-tobacco user for a minimum of 30 days prior to screening and for the duration of the study.
- Subject understands the full nature and purpose of the study, including possible risks and side effects, and is willing and able to comply with all compulsory study procedures and provides informed consent/permission prior to any study procedures being performed.
- Females of childbearing potential and males capable of fathering a child must meet the contraception requirements
Part 1 & Part 2
- History or current evidence of any clinically significant cardiac, endocrinologic, hematologic, hepatobiliary, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other major disease, as determined by the investigator
- Prolonged QT interval with Fridericia's correction >450 msec at screening
- Abnormal liver function as defined by aspartate transaminase (AST), alanine transaminase (ALT), or bilirubin >1.5× the upper limit of the normal range
- Abnormal renal function at screening defined as creatinine clearance <90 mL/min using the Cockroft-Gault equation
- Clinically significant screening results that would exclude subject from the study (e.g., medical histories, PE, ECGs, vital signs, and laboratory profiles) as deemed by the investigator
- Participation in another clinical study or treatment with an investigational agent within 30 days or five half-lives, whichever is longer, prior to Study Day 1
- History of cancer within the past 5 years (excluding non-melanoma skin cancer)
- History or current evidence of alcohol or drug abuse or dependence within 12 months of screening as determined by the investigator
- Positive urine screen for prohibited drugs (cocaine, cannabinoids, nicotine [urine cotinine is the detection mechanism for nicotine], opiates, barbiturates, amphetamines, and benzodiazepines) or positive alcohol test at screening
- Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody (HCVAb)
- Clinically significant infection within 3 months of screening as determined by the investigator
- Known or suspected hypersensitivity or idiosyncratic reaction to study medication or any components thereof
- Has donated blood within 3 months of screening or plans to donate blood within 3 months of study completion
- Pregnant or nursing women
- Any conditions that, in the opinion of the investigator, would make the subject unsuitable for enrollment or could interfere with the subject's participation in or completion of the study
- Use of prohibited medications within 14 days prior to dosing of study drug
Part 3 CF Inclusion Criteria:
- Confirmed diagnosis of CF with the F508del/F508del genotype
- Forced expiratory volume in 1 second (FEV1) 40-90% predicted, inclusive
- Non-smoker and non-tobacco user for a minimum of 30 days prior to screening
Part 3 CF Exclusion Criteria:
- Participation in another clinical trial or treatment with an investigational agent within 28 days or 5 half-lives, whichever is longer, prior to Study Day 1
- History of cancer within the past 5 years (excluding cervical cancer in situ with curative therapy for at least one year prior to screening and non-melanoma skin cancer)
- History of organ transplantation
- Hospitalization, sinopulmonary infection, CF exacerbation, or other clinically significant infection or illness (as determined by the investigator) requiring an increase or addition of medication, such as antibiotics or corticosteroids, within 14 days of Day 1
- Initiation of any new chronic therapy (e.g., ibuprofen, hypertonic saline, azithromycin, Pulmozyme®, Cayston®, TOBI®)) or any change in chronic therapy (excluding pancreatic enzyme replacement therapy) within 28 days prior to Day 1
- History or current evidence of alcohol or drug abuse or dependence within 12 months of screening as determined by the investigator
- Pregnant or nursing women
- Currently taking or has taken a CFTR modulator within 30 days prior to initial dose of study drugs
Part 4 CF Inclusion Criteria:
- Confirmed diagnosis of CF with either the F508del CFTR homozygous genotype on record or for heterozygote subjects, only one copy of the F508del CFTR mutation on record
- Forced expiratory volume in 1 second (FEV1) 40-90% predicted, inclusive
- Non-smoker and non-tobacco user for a minimum of 30 days prior to screening
Part 4 CF Exclusion Criteria:
- Participation in another clinical trial or treatment with an investigational agent within 28 days or 5 half-lives, whichever is longer, prior to Study Day 1
- History of cancer within the past 5 years (excluding cervical cancer in situ with curative therapy for at least one year prior to screening and non-melanoma skin cancer)
- History of organ transplantation
- Hospitalization, sinopulmonary infection, CF exacerbation, or other clinically significant infection or illness (as determined by the investigator) requiring an increase or addition of medication, such as antibiotics or corticosteroids, within 28 days of Day 1
- Initiation of any new chronic therapy (e.g., ibuprofen, hypertonic saline, azithromycin, Pulmozyme®, Cayston®, TOBI®)) or any change in chronic therapy (excluding pancreatic enzyme replacement therapy) within 28 days of Day 1
- History or current evidence of alcohol or drug abuse or dependence within 12 months of screening as determined by the investigator
- Pregnant or nursing women
- Currently taking or has taken a CFTR modulator within 14 days prior to the screening visit
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2 PTI-808 + PTI-801 + PTI-428 Active PTI-808 One cohort is planned where subjects will be randomized to either the triple active arm (dosed with PTI 808+PTI 801+PTI 428) OR placebo arm. Part 3 CF MAD PTI-808 + PTI-801 + PTI-428 PTI-808 In all cohorts in Part 3, subjects will be will be randomized to receive 7 days of PTI-808 or placebo followed by 14 days of co-administration of PTI-808+PTI-801+PTI-428 or matching placebos. A follow-up will occur on Day 28. FE PTI-808 Active PTI-808 Subjects will be randomized to Fed or Fasted on Days 1 and 12. Follow up visits will occur 7 days post Day 12 dose. SAD PTI-808 Placebo Placebo Three cohorts of SAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo. Part 2 dual active arm PTI-801+PTI-428+ PTI-808 placebo PTI-428 One cohort is planned where subjects are randomized to either 808 placebo + dual active arm (dosed with placebo matching PTI 808 plus PTI 801 + PTI 428) OR placebo arm. Part 2 matching Placebos Placebo In all three cohorts in part 2, subjects will be randomized to active drug or placebo. The placebo arm for all cohorts consists of placebo capsules matching PTI-808+PTI-801+PTI-428. SAD PTI-808 Active PTI-808 Three cohorts of SAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo. FE PTI-808 Placebo Placebo Subjects will be randomized to Fed or Fasted on Days 1 and 12. Follow up visits will occur 7 days post Day 12 dose. MAD PTI-808 Active PTI-808 Three cohorts of MAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo. Part 2 PTI-808 + PTI-801 + PTI-428 Active PTI-428 One cohort is planned where subjects will be randomized to either the triple active arm (dosed with PTI 808+PTI 801+PTI 428) OR placebo arm. Part 2 dual active arm PTI-801+PTI-428+ PTI-808 placebo Placebo One cohort is planned where subjects are randomized to either 808 placebo + dual active arm (dosed with placebo matching PTI 808 plus PTI 801 + PTI 428) OR placebo arm. Part 2 dual active arm PTI-801+PTI-808+PTI-428 placebo PTI-808 One cohort is planned where subjects are randomized to either 428 placebo + dual active arm (dosed with placebo matching PTI 428 plus PTI 808 and PTI 801) OR placebo arm. Part 3 CF MAD PTI-808 placebo+PTI-801 placebo+PTI-428 placebo Placebo In all cohorts in Part 3, subjects will be randomized to receive 7 days of PTI-808 or placebo followed by 14 days of co-administration of PTI-808+PTI-801+PTI-428 or matching placebos. A follow-up will occur on Day 28. MAD PTI-808 Placebo Placebo Three cohorts of MAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo. Part 4 CF PTI-808 + PTI-801 + PTI-428 PTI-808 In cohorts 3 \& 4 subjects will be randomized to receive PTI-808 + PTI-801 with or without PTI-428 or matching placebos. A follow-up will occur on Day 42. Part 4 CF PTI-808 placebo + PTI-801 placebo + PTI-428 placebo Placebo In cohorts 3 \& 4, subjects will be randomized to receive PTI-808 + PTI-801 with or without PTI-428 or matching placebos. A follow-up will occur on Day 42. Part 2 dual active arm PTI-801+PTI-808+PTI-428 placebo Placebo One cohort is planned where subjects are randomized to either 428 placebo + dual active arm (dosed with placebo matching PTI 428 plus PTI 808 and PTI 801) OR placebo arm. Part 3 CF MAD PTI-808 + PTI-801 + PTI-428 PTI-428 In all cohorts in Part 3, subjects will be will be randomized to receive 7 days of PTI-808 or placebo followed by 14 days of co-administration of PTI-808+PTI-801+PTI-428 or matching placebos. A follow-up will occur on Day 28. Part 4 CF PTI-808 + PTI-801 + PTI-428 PTI-428 In cohorts 3 \& 4 subjects will be randomized to receive PTI-808 + PTI-801 with or without PTI-428 or matching placebos. A follow-up will occur on Day 42. Part 4 CF PTI-808 + PTI-801 + PTI-428 placebo PTI-808 In cohorts 3 \& 4, subjects will be randomized to receive PTI-808 + PTI-801 with or without PTI-428 or matching placebos. A follow-up will occur on Day 42. Part 2 PTI-808 + PTI-801 + PTI-428 Active PTI-801 One cohort is planned where subjects will be randomized to either the triple active arm (dosed with PTI 808+PTI 801+PTI 428) OR placebo arm. Part 2 dual active arm PTI-801+PTI-808+PTI-428 placebo PTI-801 One cohort is planned where subjects are randomized to either 428 placebo + dual active arm (dosed with placebo matching PTI 428 plus PTI 808 and PTI 801) OR placebo arm. Part 3 CF MAD PTI-808 + PTI-801 + PTI-428 PTI-801 In all cohorts in Part 3, subjects will be will be randomized to receive 7 days of PTI-808 or placebo followed by 14 days of co-administration of PTI-808+PTI-801+PTI-428 or matching placebos. A follow-up will occur on Day 28. Part 4 CF PTI-808 + PTI-801 + PTI-428 PTI-801 In cohorts 3 \& 4 subjects will be randomized to receive PTI-808 + PTI-801 with or without PTI-428 or matching placebos. A follow-up will occur on Day 42. Part 4 CF PTI-808 + PTI-801 + PTI-428 placebo PTI-801 In cohorts 3 \& 4, subjects will be randomized to receive PTI-808 + PTI-801 with or without PTI-428 or matching placebos. A follow-up will occur on Day 42. Part 2 dual active arm PTI-801+PTI-428+ PTI-808 placebo PTI-801 One cohort is planned where subjects are randomized to either 808 placebo + dual active arm (dosed with placebo matching PTI 808 plus PTI 801 + PTI 428) OR placebo arm.
- Primary Outcome Measures
Name Time Method Part 1 SAD and MAD: ECGs Baseline to up to 14 days Safety and tolerability measure by number of subjects who experience potential clinically significant changes in ECGs
Part 1 SAD and MAD: Adverse Events Baseline to up to 14 days Safety and tolerability measure by number of subjects who experience adverse events
Part 1 SAD and MAD: Physical Exams Baseline to up to 14 days Safety and tolerability measure by number of subjects who experience potential clinically significant changes in physical examinations
Part 1 SAD and MAD: The number of subjects who experience potential clinically significant changes in vital signs Baseline to up to 14 days Safety and tolerability measure by number of subjects who experience potential clinically significant changes in vital signs
Part 1 SAD : AUC Through 24 hours post dose Area under the concentration-time curve from time 0 to 24 hours post dose (AUC 0-24) of single oral dose
Part 1 SAD and FE: AUC0 Through 72 hours post dose AUC from time 0 to time of last measurable concentration (AUC0-last) of single oral dose
Part 1 SAD and FE: AUC0-inf Through 72 hours post dose AUC from time 0 to infinity (AUC0-inf) of single dose
Part 1 MAD: t1/2 Through 72 hours post dose t1/2 of multiple oral dose
Part 1 MAD: Tmax Through 72 hours post dose Tmax of multiple oral doses
Part 1 MAD: Cmax Through 72 hours post last dose Cmax of multiple oral doses
Part 1 SAD and MAD: The number of subjects who experience potential clinically significant changes in safety labs Baseline to up to 14 days Safety and tolerability measure by number of subjects who experience potential clinically significant changes in safety labs
Part 1 SAD and FE: terminal half life Through 72 hours post dose Apparent terminal half-life (t1/2) of single oral dose
Part 1 SAD and FE : Tmax Through 72 hours post dose Time to reach maximum plasma concentration (Tmax) of single oral dose
Part 1 SAD and FE: Cmax Through 72 hours post dose Maximum plasma concentration (Cmax) of single oral dose
Part 1 MAD: AUC0-24 Through 24 hours post last dose AUC0-24 of multiple oral dose
Part 1 MAD: AUC0-last Through 72 hours post last dose AUC0-last of multiple oral doses
Part 1 MAD: Urine Through 24 hours post last dose Cumulative amount of PTI-808 excreted unchanged in urine (Ae) as appropriate of multiple oral doses
Part 1 MAD: CLR Through 24 hours post dose Renal clearance (CLR) of multiple oral doses
Part 2: Physical Exams Baseline up to 14 days Safety and tolerability measure by number of subjects who experience potential clinically significant changes in physical examinations
Part 2: ECGs Baseline up to 14 days Safety and tolerability measure by number of subjects who experience potential clinically significant changes in ECGs
Part 2: Safety Labs Baseline up to 14 days Safety and tolerability measure by number of subjects who experience potential clinically significant changes in safety labs
Part 2: Vitals Signs Baseline up to 14 days Measure by number of subjects who experience potential clinically significant changes in vital signs
Part 3 CF: Physical Exams Baseline up to 28 days Safety and tolerability measured by number of subjects who experience potential clinically significant changes in physical examinations
Part 3 CF: ECGs Baseline up to 28 days Safety and tolerability measured by number of subjects who experience potential clinically significant changes in ECGs
Part 3 CF: Safety Labs Baseline up to 28 days Safety and tolerability measured by number of subjects who experience potential clinically significant changes in safety labs
Part 3 CF: Vital Signs Baseline up to 28 days Measured by number of subjects who experience potential clinically significant changes in vital signs
Part 4 CF: Physical Exams Baseline up to 42 days Safety and tolerability measured by number of subjects who experience potential clinically significant changes in physical examinations
Part 4 CF: ECGs Baseline up to 42 days Safety and tolerability measured by number of subjects who experience potential clinically significant changes in ECGs
Part 4 CF: Safety Labs Baseline up to 42 days Safety and tolerability measured by number of subjects who experience potential clinically significant changes in safety labs
Part 4 CF: Vital Signs Baseline up to 42 days Safety and tolerability measured by number of subjects who experience potential clinically significant changes in physical examinations
- Secondary Outcome Measures
Name Time Method Part 2: Apparent terminal half life (t1/2) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428 Day 1 through Day 10 Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults
Part 2: Maximum plasma concentration (Cmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428 Day 1 through Day 10 Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults
Part 2: Time to reach maximum plasma concentration (Tmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428 Day 1 through Day 10 Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults
Part 2: AUC0-last of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428 Day 1 through Day 10 Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults
Part 2: AUC from time 0 to infinity (AUC0-inf) of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428 Day 1 through Day 10 Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults
Part 3 CF: Time to reach maximum plasma concentration (Tmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428 Day 1 through Day 22 Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in adults with CF
Part 3 CF: Maximum plasma concentration (Cmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428 Day 1 through Day 22 Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in adults with CF
Part 3 CF: AUC0-last of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428 Day 1 through Day 22 Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in adults with CF
Part 4 CF: Time to reach maximum plasma concentration (Tmax) of multiple oral doses of PTI 808 + PTI 801 co-administered with or without PTI 428 Day 1 through Day 28 Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 + PTI 801 is co administered with or with out PTI 428 in adults with CF
Part 4 CF: Maximum plasma concentration (Cmax) of multiple oral doses of PTI 808 + PTI 801 co-administered with or without PTI 428 Day 1 through 28 Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 + PTI 801 is co administered with or with out PTI 428 in adults with CF
Part 4 CF: AUC0-last of multiple oral doses when PTI 808 + PTI 801 is coadministered with or without PTI 428 in adults with CF Day 1 through 28 Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 + PTI 801 is co administered with or without PTI 428 in adults with CF
Part 4 CF: FEV1 Baseline through Day 42 Change in forced expiratory volume in one second (FEV1) over time
Part 4 CF Sweat Chloride Baseline through Day 42 Change in sweat chloride concentrations over time
Part 3 CF: FEV1 Baseline through Day 28 Change in forced expiratory volume in one second (FEV1) over time
Trial Locations
- Locations (48)
Banner University of Arizona Medical Center
🇺🇸Tucson, Arizona, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Michigan Medicine, University of Michigan
🇺🇸Ann Arbor, Michigan, United States
St. Paul's Hospital
🇨🇦Vancouver, British Columbia, Canada
McGill University Health Centre
🇨🇦Montréal, Quebec, Canada
University Hospital Cologne
🇩🇪Cologne, Germany
Harper University Hospital
🇺🇸Detroit, Michigan, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Centre hospitalier de l'Université de Montréal (CHUM)
🇨🇦Montréal, Quebec, Canada
Charité Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval
🇨🇦Québec, Canada
Hôpital Haut Lévêque
🇫🇷Pessac, Gironde, France
Hôpital Guillaume-et-René-Laennec
🇫🇷Nantes, Loire-Atlantique, France
Hôpital Cochin
🇫🇷Paris, France
Hôpital Maison Blanche Maladies respiratoires et allergologie
🇫🇷Reims, Marne, France
Hospices Civils de Lyon
🇫🇷Lyon, France
Universitätsklinikum Essen
🇩🇪Essen, Germany
Auckland Clinical Studies Ltd.
🇳🇿Grafton, Auckland, New Zealand
Central Florida Pulmonary Group
🇺🇸Altamonte Springs, Florida, United States
Children's Mercy
🇺🇸Kansas City, Missouri, United States
Billings Clinic
🇺🇸Billings, Montana, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Universitair ziekenhuis Brussel
🇧🇪Brussels, Belgium
John Hunter Hospital
🇦🇺Lambton, New South Wales, Australia
Hôpital Pasteur
🇫🇷Nice, Alpes-Maritimes, France
Klinikum der J.W. Goethe Universität
🇩🇪Frankfurt, Germany
Klinikum des Universität München
🇩🇪München, Germany
Stanford University Medical Center
🇺🇸Stanford, California, United States
Emory Children's Center
🇺🇸Atlanta, Georgia, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
ICON Early Phase Services
🇺🇸San Antonio, Texas, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
New York Medical College
🇺🇸Valhalla, New York, United States
National Jewish Health
🇺🇸Denver, Colorado, United States
University of Copenhagen Rigshospitalet
🇩🇰Copenhagen, Denmark
University Hospital Southampton
🇬🇧Southampton, United Kingdom
UZ Leuven
🇧🇪Leuven, Belgium
Birmingham Heartlands Hospital
🇬🇧Birmingham, West Midlands, United Kingdom
Western General Hospital
🇬🇧Edinburgh, Scotland, United Kingdom
Belfast City Hospital
🇬🇧Belfast, United Kingdom
Royal Devon and Exeter Hospital
🇬🇧Exeter, Devon, United Kingdom
King's College Hospital
🇬🇧London, United Kingdom