Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of Oral Lumicitabine Regimens in Hospitalized Adult Participants Infected With Human Metapneumovirus
- Registration Number
- NCT03502694
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to determine in hospitalized adult participants infected with human metapneumovirus (hMPV - a virus closely related to respiratory syncytial virus (RSV) and has been identified as an important cause of acute respiratory infections, affecting all age groups) the dose-response relationship of multiple regimens of lumicitabine on antiviral activity based on nasal hMPV shedding using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assay.
- Detailed Description
The study consists of 3 phases: screening phase, treatment phase (Day 1 to Day 5/6 \[depending on timing of loading dose\]), and follow-up phase of 28 days post randomization. Participants will have assessments at Days 7, 10, 14, and 28 to evaluate safety, efficacy, and pharmacokinetics (PK). The primary hypothesis of study is a positive dose-response relationship of active treatment on average hMPV viral load area under concentration versus time curve (AUC) over 7 days, meaning that either average AUC on pooled active treatments is lower than on placebo, or average AUC on high active dose is lower than average AUC on placebo using multiple contrast testing. Based on review of PK, efficacy and safety data, Independent Data Monitoring Committee (IDMC) may recommend modifications to study design that is changes in dose and treatment duration.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- Participants hospitalized (or in Emergency room prior to hospitalization) at the time of randomization and unlikely to be discharged for the first 24 hours after randomization
- Participants diagnosed with human metapneumovirus (hMPV) infection using a rapid polymerase chain reaction (PCR)-based molecular diagnostic assay, with or without coinfection with another respiratory pathogen (respiratory virus or bacteria)
- Participants with an acute respiratory illness with signs and symptoms consistent with a viral infection (for example, fever, cough, nasal congestion, runny nose, sore throat, myalgia, lethargy, shortness of breath, or wheezing) with onset less than or equal to (<=)5 days from the anticipated time of randomization
- With the exception of the symptoms related to hMPV infection, participants must be medically stable on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening. If there are abnormalities, they must be consistent with the underlying illness in the study population, and/or the hMPV infection. This determination must be recorded in the participant's source documents and initialed by the investigator
- A woman must have a negative urine pregnancy test (beta-human chorionic gonadotropin [b-hCG]) at screening
- Participants who are not expected to survive for more than 48 hours
- Participants who have had major thoracic or abdominal surgery in the 6 weeks prior to randomization
- Participants who are considered by the investigator to be immunocompromised within the past 12 months, whether due to underlying medical condition (for example, malignancy or genetic disorder) or medical therapy (for example, medications other than corticosteroids for the treatment of chronic obstructive pulmonary disease (COPD) or asthma exacerbations, chemotherapy, radiation, stem cell or solid organ transplant)
- Participants undergoing peritoneal dialysis, hemodialysis, or hemofiltration or with an estimated glomerular filtration rate (GFR, determined by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) of (<) 60 milliliters per minute (mL/min) per 1.73 meter square (m^2)
- Participants with a known history of human immunodeficiency virus (HIV) or chronic viral hepatitis
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Regimen A (Low-Dose Lumicitabine) Placebo Participants will receive a single 750 milligram (mg) loading dose (LD) (Dose 1) of lumicitabine and matching placebo followed by nine 250 mg tablets as maintenance doses (MDs) (Doses 2 to 10) of lumicitabine and matching placebo administered twice daily during Day 1 to Day 5/6 (depending on the timing of the LD). Regimen C (Placebo) Placebo Participants will receive a placebo LD (Dose 1) followed by nine MDs (Doses 2 to 10) of matching placebo, administered twice daily during Day 1 to Day 5/6 (depending on the timing of the LD). Regimen B (High-Dose Lumicitabine) Placebo Participants will receive a single 1000 mg LD (Dose 1) of lumicitabine followed by nine 500 mg tablets as MDs (Doses 2 to 10) of lumicitabine and matching placebo tablet, administered twice daily during Day 1 to Day 5/6 (depending on the timing of the LD). Regimen A (Low-Dose Lumicitabine) Lumicitabine Participants will receive a single 750 milligram (mg) loading dose (LD) (Dose 1) of lumicitabine and matching placebo followed by nine 250 mg tablets as maintenance doses (MDs) (Doses 2 to 10) of lumicitabine and matching placebo administered twice daily during Day 1 to Day 5/6 (depending on the timing of the LD). Regimen B (High-Dose Lumicitabine) Lumicitabine Participants will receive a single 1000 mg LD (Dose 1) of lumicitabine followed by nine 500 mg tablets as MDs (Doses 2 to 10) of lumicitabine and matching placebo tablet, administered twice daily during Day 1 to Day 5/6 (depending on the timing of the LD).
- Primary Outcome Measures
Name Time Method Area Under the Concentration-Time Curve (AUC) of Human Metapneumovirus (hMPV) Viral Load Baseline up to Day 7 The AUC of hMPV ribonucleic acid (RNA) logarithm base 10 (log10) viral load (measured by quantitative real time reverse transcriptase polymerase chain reaction \[qRT-PCR\] in the mid-turbinate nasal swab specimens) is estimated by analyzing mean log10 viral load values over time using a restricted maximum likelihood based repeated measures approach.
- Secondary Outcome Measures
Name Time Method Number of Participants with Adverse Events as a Measure of Safety and Tolerability Up to 28 days An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Number of Participants with an Abnormal Electrocardiogram (ECG) Reading as a Measure of Safety and Tolerability Up to 28 days Number of participants with abnormal twelve-lead ECG will be reported.
Length of Hospital Stay from Study Treatment Initiation to Discharge From study treatment initiation to discharge (Up to 28 days) The length of hospital stay from study treatment initiation to discharge will be reported.
Percentage of Enrolled Participants Who Require Hydration and/or Feeding by Intravenous (IV) Catheter or Nasogastric Tube Up to 28 days The percentage of enrolled participants who require hydration and/or feeding by intravenous (IV) catheter or nasogastric tube will be reported.
Number of Participants With Treatment-Emergent Complications Up to 28 days The number of participants with treatment-emergent complications, including cardiovascular events and cerebrovascular events (for example, myocardial infarction, congestive heart failure exacerbation, arrhythmia, stroke) or Clostridium difficile-associated diarrhea, will be reported.
Time to Peak hMPV Viral Load Up to 28 days Time to peak viral load as measured by qRT-PCR will be reported.
AUC of hMPV Viral Load in Participants Assigned to a Longer Dosing Duration From Baseline Until 1 day After the Last Dose of Study Drug Baseline Until 1 day After the Last Dose of Study Drug (approximately up to 12 days) If dosing duration is increased by the Independent Data Monitoring Committee (IDMC), the AUC of hMPV viral load (measured by qRT-PCR in the mid-turbinate nasal swab specimens) will be estimated by analyzing mean log10 viral load values over time using a restricted maximum likelihood based repeated measures approach.
Number of Participants With Postbaseline Changes in the hMPV Polymerase Lgene and Other Regions of the hMPV Genome Compared With Baseline Sequences Up to 28 days Number of participants will be assessed for postbaseline changes in the hMPV polymerase Lgene (only if no mutations are seen in the Lgene) and other regions of the hMPV genome compared with baseline sequences.
Length of Hospital Stay from Study Treatment Initiation to Readiness for Discharge From study treatment initiation to readiness for discharge (Up to 28 days) The length of hospital stay from study treatment initiation to readiness for discharge will be reported.
Number of Participants with an Abnormal Vital Signs/Peripheral Capillary Oxygen Saturation (SpO2) Reading as a Measure of Safety and Tolerability Up to 28 days Number of participants with abnormal vital signs (including body temperature, heart rate, respiratory rate, systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\]), and SpO2 measurements will be reported.
Number of Participants with Clinical Laboratory Abnormalities as a Measure of Safety and Tolerability Up to 28 days Number of participants with clinical laboratory abnormalities (clinical laboratory tests include the following: hematology panel, serum chemistry panel, urinalysis, estimated glomerular filtration rate (GFR), urine pregnancy test (women only), and serum procalcitonin levels) will be reported.
Area Under the Plasma Concentration-Time Curve (AUC) of JNJ-63549109 Dose 1: 0.5 to 1 hour postdose, and 2 to 3 hours postdose; Dose 2: predose, and 3 to 6 hours postdose; Dose 3 and 10: predose AUC is defined as area under plasma concentration-time curve.
Length of Hospital Stay from Admission to Readiness for Discharge From admission to readiness for discharge discharge (Up to 28 days) The length of hospital stay from admission to readiness for discharge will be reported.
Percentage of Participants Requiring Admission to the Intensive Care Unit (ICU) Up to 28 days The percentage of enrolled participants requiring admission to the ICU will be reported.
Duration of ICU Stay Up to 28 days In the event that a participant requires admission to the ICU, the duration for how long the participant remained in the ICU will be measured.
Percentage of Participants Requiring Oxygen Supplementation/Noninvasive Mechanical Ventilation Support Up to 28 days The percentage of enrolled participants requiring oxygen supplementation/noninvasive mechanical ventilation support (for example \[eg\], nasal cannula, face mask, continuous positive airway pressure, bilevel positive airway pressure) above pre-hMPV infection status will be reported.
Number of Participants with an Abnormal Physical Examination Findings (Height, Body Weight, Respiratory System, Nose, Ear, Throat, Facial and Neck Lymph Nodes, and Skin Examination) as a Measure of Safety and Tolerability Up to 28 days Number of participants with an abnormal physical examination will be reported. A complete physical examination (including all body systems, height \[only at screening\], and body weight measurement) or a directed physical examination including respiratory system, nose, ear, throat, facial and neck lymph nodes, and skin examination will be performed.
Length of Hospital Stay from Admission to Discharge From admission to discharge (Up to 28 days) The length of hospital stay from admission to discharge will be reported.
Duration of Oxygen Supplementation/Noninvasive Mechanical Ventilation Support Up to 28 days The duration of oxygen supplementation/noninvasive mechanical ventilation support (eg, nasal cannula, face mask, continuous positive airway pressure, bilevel positive airway pressure) above pre-hMPV infection status will be measured.
Percentage of Participants Requiring Invasive Mechanical Ventilation Support Up to 28 days The percentage of enrolled participants requiring invasive mechanical ventilation support (eg, endotracheal-mechanical ventilation or mechanical ventilation via tracheostomy) above pre-hMPV infection status will be reported.
Time to no Longer Requiring Supplemental Oxygen Up to 28 days The time to which a participant no longer requires supplemental oxygen will be measured.
Time for Peripheral Capillary Oxygen Saturation (SpO2) Return to Pre-hMPV Infection Status Up to 28 days The time for SpO2 to return to pre-hMPV infection status will be recorded.
Time for Body Temperature to Return to Pre-hMPV Infection Status Up to 28 days The time for body temperature to return to pre-hMPV infection status will be recorded.
Change From Baseline in the National Early Warning Score (NEWS) Over Time Baseline up to 28 days The NEWS scoring system measures acute-illness severity using 7 physiological parameters (respiration rate, oxygen saturation, supplementary oxygen requirement, temperature, systolic blood pressure, heart rate, and level of consciousness). Each parameter is scored between 0 and 3 compared to normal ranges, with higher scores indicating greater severity. The total score is the sum of the individual physiological parameter values and ranges between 0 (least severe) and 21 (most severe).
Number of Participants With All-Cause Mortality Up to 28 days Number of participants will be assessed for all-cause mortality.
Time to hMPV Ribonucleic Acid (RNA) Being Undetectable Up to 28 days Time to hMPV RNA being undetectable as measured by qRT-PCR.
Percentage of Participants With Undetectable hMPV Viral Load at Each Timepoint From Day 1 to Day 7 and on Day 10, Day 14, and Day 28 Percentage of participants with undetectable viral load at each time point will be reported.
hMPV Viral Load Over Time Up to 28 days Viral load over time will be measured in mid-turbinate nasal swabs (obtained from non-intubated participants) or in mid-turbinate nasal swabs and endotracheal samples (obtained from intubated participants or via suction through tracheostomy or other sampling methods) by qRT-PCR.
Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 Dose 1: 0.5 to 1 hour postdose, and 2 to 3 hours postdose; Dose 2: predose, and 3 to 6 hours postdose; Dose 3 and 10: predose The Cmax is the maximum observed plasma concentration of JNJ-63549109. JNJ-63549109 is the metabolite of lumicitabine.
Concentration at 12 Hours Postdose (C12h) of JNJ-63549109 Days 1, 2, and 5/6: 12 hours postdose The C12h is the predicted concentration of JNJ-63549109 at 12 hours postdose.
Ordinal Scale Day of last dose (Day 5 or Day 6) The ordinal scale will be used to assess participant's status and consists of 6 categories that are exhaustive, mutually exclusive, and ordered, where: 1) Death, 2) Admitted to intensive care unit (ICU), 3) Non-ICU hospitalization requiring supplemental oxygen, 4) Non-ICU hospitalization not requiring supplemental oxygen, 5) Not hospitalized, unable to resume normal activities, 6) Not hospitalized, resumption of normal activities.
Duration of Invasive Mechanical Ventilation Support Up to 28 days The duration of invasive mechanical ventilation support (eg, endotracheal-mechanical ventilation or mechanical ventilation via tracheostomy) above pre-hMPV infection status will be measured.
Time to Return to Pre-hMPV Infection Functional Status (Katz Activities of Daily Living [ADL] score) Up to 28 Days Katz activities of daily living will assess questions related to Bathing, Dressing, Toileting, Transferring, Continence and Feeding. For the six individual activities, a score of 1 indicates independence, and a score of 0 indicates dependence. Total score will be calculated by adding the scores of all six activities and ranges from 0 high (participant independent) to 6 low (participant very dependent).
Peak hMPV Viral Load Up to 28 days Peak viral load over time will be measured by qRT-PCR.
Rate of Decline of hMPV Viral Load Up to 28 days Rate of decline in hMPV viral load during treatment as measured by qRT-PCR will be reported.
Time to Clinical Stability Up to 28 days Time to clinical stability is defined as the time at which the following criteria are all met: normalization of blood oxygen level (return to baseline; by pulse oximetry) without requirement of supplemental oxygen beyond baseline level, normalization of oral feeding, normalization of respiratory rate and normalization of heart rate.
Number of Hours from Initiation of Study Treatment Until SpO2 is Greater Than or equal to (>=) 93 Percent (%) on Room air Up to 28 days The number of hours until SpO2 is \>= 93% on room air among participants who were not on supplemental oxygen prior to onset of respiratory symptoms will be recorded.
Time for Respiratory Rate to Return to Pre-hMPV Infection Status Up to 28 days The time for respiratory rate to return to pre-hMPV infection status will be recorded.
Number of Participants With Bacterial Superinfections Reported as AEs Up to 28 days The number of participants with bacterial superinfections, as defined by the investigator based on clinical judgment and/or increasing procalcitonin levels, reported as AEs will be reported.
AUC of hMPV Viral Load From Baseline up to Day 10 Baseline up to Day 10 The AUC of hMPV RNA log10 viral load (measured by qRT-PCR in the mid-turbinate nasal swab specimens) is estimated by analyzing mean log10 viral load values over time using a restricted maximum likelihood based repeated measures approach.
AUC of hMPV Viral Load from Baseline up to Day 14 Baseline up to Day 14 The AUC of hMPV RNA log10 viral load (measured by qRT-PCR in the mid-turbinate nasal swab specimens) is estimated by analyzing mean log10 viral load values over time using a restricted maximum likelihood based repeated measures approach.
Trial Locations
- Locations (112)
Hôpital Tenon
🇫🇷Paris, France
MemorialCare Research Miller Children's and Women's Hospital Long Beach
🇺🇸Long Beach, California, United States
Lake Internal Medicine Associates
🇺🇸Eustis, Florida, United States
Hospital Italiano de Buenos Aires
🇦🇷Buenos Aires, Argentina
Hospital Privado-Universitario de Cordoba
🇦🇷Cordoba, Argentina
Hospital Rawson
🇦🇷Cordoba, Argentina
Instituto Medico Platense
🇦🇷La Plata, Argentina
Queen Elizabeth Hospital
🇦🇺Adelaide, Australia
Princess Alexandra Hospital
🇦🇺Brisbane, Australia
Flinders Medical Centre
🇦🇺Adelaide, Australia
Royal Melbourne Hospital
🇦🇺Melbourne, Australia
Mater Hospital Brisbane
🇦🇺South Brisbane, Australia
Barwon Health - University Hospital Geelong
🇦🇺Geelong, Australia
Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul
🇧🇷Porto Alegre, Brazil
Westmead Hospital
🇦🇺Sydney, Australia
Hospital Alemão Oswaldo Cruz
🇧🇷Sao Paulo, Brazil
Hospital Das Clinicas Da Faculdade De Medicina Da Universidade De Sao Paulo
🇧🇷Sao Paulo, Brazil
CHU Rouen
🇫🇷Bois Guillaume, France
CHU caen
🇫🇷Caen, France
Hôpital Louis Mourier
🇫🇷Colombes, France
Hopital Saint-Louis
🇫🇷Paris, France
APHP - Hopital Henri Mondor
🇫🇷Créteil, France
CHU Grenoble
🇫🇷La Tronche, France
CHU Dijon
🇫🇷Dijon, France
CHU Saint-etienne
🇫🇷St Priest En Jarez, France
CHU la milétrie
🇫🇷Poitiers, France
Centre Hospitalier Universitaire de Tours
🇫🇷Tours Cedex, France
Hopital Foch
🇫🇷Suresnes, France
Shinkomonji hospital
🇯🇵Kitakyusyu, Japan
Japanese Red Cross Society Nagano Hospital
🇯🇵Nagano, Japan
Rinku General Medical Center
🇯🇵Osaka, Japan
Tohoku Medical And Pharmaceutical University Hospital
🇯🇵Sendai, Japan
National Hospital Organization Tokyo National Hospital
🇯🇵Tokyo, Japan
Soonchunhyang University Bucheon Hospital
🇰🇷Bucheon, Korea, Republic of
Shin Yukuhashi Hospital
🇯🇵Yukuhashi, Japan
Yeungnam University Medical Center
🇰🇷Daegu, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam, Korea, Republic of
Gachon University Gil Hospital
🇰🇷Incheon, Korea, Republic of
Kangnam Sacred Heart Hospital
🇰🇷Seoul, Korea, Republic of
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Sultanah Bahiyah
🇲🇾Alor Setar, Malaysia
Hospital Pulau Pinang
🇲🇾George Town, Malaysia
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
Hospital Raja Perempuan Zainab Ii
🇲🇾Kota Bharu, Malaysia
Sarawak General Hospital
🇲🇾Kuching, Malaysia
UMCG
🇳🇱Groningen, Netherlands
10 Wojskowy Szpital Kliniczny z Poliklinika
🇵🇱Bydgoszcz, Poland
Wojewódzki Szpital Specjalistyczny im. św. Rafała w Czerwonej Górze
🇵🇱Chęciny, Poland
Regional State Health Care Institution 'Clinical Hospital #1'
🇷🇺Smolensk, Russian Federation
Siberian State Medical University
🇷🇺Tomsk, Russian Federation
Hosp. Univ. 12 de Octubre
🇪🇸Madrid, Spain
State Health Care Institution of Voronezh region 'Voronezh regional clinical infectious hospital'
🇷🇺Voronezh, Russian Federation
Hosp. Univ. de La Princesa
🇪🇸Madrid, Spain
Hosp. Gral. Univ. de Elche
🇪🇸Elche, Spain
Clinical Emergency Hospital n.a. N.V. Solovyev
🇷🇺Yaroslavl, Russian Federation
Hosp. Univ. La Paz
🇪🇸Madrid, Spain
Hosp. Clinico Univ. de Santiago
🇪🇸Santiago De Compostela, Spain
Hosp. Alvaro Cunqueiro
🇪🇸Vigo, Spain
Sahlgrenska University Hospital
🇸🇪Göteborg, Sweden
Norrlands Universitetssjukhus
🇸🇪Umeå, Sweden
Akademiska Sjukhuset
🇸🇪Uppsala, Sweden
Skanes universitetssjukhus
🇸🇪Malmö, Sweden
Kaohsiung Veterans General Hospital
🇨🇳Kaohsiung, Taiwan
Far Eastern Memorial Hospital
🇨🇳New Taipei, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
Taipei Medical University Shuang Ho Hospital
🇨🇳New Taipei, Taiwan
Ivano-Frankivsk Regional Clinical Hospital
🇺🇦Ivano-Frankivsk, Ukraine
Vinnytsia City Clinical Hospital #1, Department of Infectious Diseases #1
🇺🇦Vinnytsya, Ukraine
UCSF Fresno
🇺🇸Fresno, California, United States
Northwestern University - Northwestern Memorial Hospital - Infectious Disease Center
🇺🇸Chicago, Illinois, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Marshfield Clinic
🇺🇸Marshfield, Wisconsin, United States
Shimane University Hospital
🇯🇵Izumo, Japan
Saka General Hospital
🇯🇵Shiogama, Japan
National Hospital Organization Ibarakihigashi
🇯🇵Tokai-Mura, Japan
Hospital Taiping
🇲🇾Taiping, Malaysia
Gelre Ziekenhuizen Zutphen
🇳🇱Zutphen, Netherlands
CHU Nîmes
🇫🇷Nîmes, France
Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo
🇧🇷Ribeirao Preto, Brazil
Hospital Sirio Libanes
🇧🇷São Paulo, Brazil
National Hospital Organization Tenryu Hospital
🇯🇵Hamamatue, Japan
Specialized Hospital for Active Treatment of Pulmonary Diseases - Pernik
🇧🇬Pernik, Bulgaria
Fukuoka University Hospital
🇯🇵Fukuoka, Japan
Ogaki Municipal Hospital
🇯🇵Gifu, Japan
Taipei Municipal Wanfang Hospital
🇨🇳Taipei, Taiwan
MHAT Dr Stefan Cherkezov
🇧🇬Veliko Tarnovo, Bulgaria
Japanese Red Cross Nagasaki Genbaku Isahaya Hospital
🇯🇵Isahaya, Japan
National Hospital Organization Higashinagoya National Hospital
🇯🇵Nagoya, Japan
Saint-Petersburg State Public Health Organization City Clinical Hospital #26
🇷🇺St. Petersburg, Russian Federation
Hospital Italiano de La Plata
🇦🇷Ciudad De La Plata, Argentina
Specialized Hospital for Active Treatment of Pulmonary Diseases - Troyan EOOD
🇧🇬Troyan, Bulgaria
SUBARU Health Insurance Society Ota Memorial Hospital
🇯🇵Ota, Japan
Hospital Miri
🇲🇾Miri, Malaysia
UMC Utrecht
🇳🇱Utrecht, Netherlands
SSZZOZ im. dr Teodora Dunina w Rudce
🇵🇱Mrozy, Poland
State Health Care Institution 'Engels city hospital #2'
🇷🇺Engels, Russian Federation
Hospital Interzonal General de Agudos Dr. Jose Penna
🇦🇷Bahia Blanca, Argentina
Hospital Regional Español
🇦🇷Bahía Blanca, Argentina
CEMIC Saavedra
🇦🇷Ciudad De Buenos Aires, Argentina
MHAT 'Sv. Ivan Rilski' Kozloduy EOOD
🇧🇬Kozloduy, Bulgaria
Nagasaki University Hospital
🇯🇵Nagasaki, Japan
Okinawa Prefectural Chubu Hospital
🇯🇵Uruma, Japan
Shimonoseki City Hospital
🇯🇵Yamaguchi, Japan
Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc w Olsztynie
🇵🇱Olsztyn, Poland
Samodzielny Publiczny Zespół Opieki Zdrowotnej w Proszowicach
🇵🇱Proszowice, Poland
Saint-Petersburg State Health Care Institution 'Vvedenskaya Hospital'
🇷🇺St. Petersburg, Russian Federation
Clinical Infectious Diseases Hospital n. a. S.P. Botkin
🇷🇺St. Petersburg, Russian Federation
Kharkiv National Medical University, Regional Clinical Infectious Hospital
🇺🇦Kharkiv, Ukraine
St Michaels Medical Center
🇺🇸Newark, New Jersey, United States
Kobe City Medical Center General Hospital
🇯🇵Kobe-City, Japan
Okitama Public General Hospital
🇯🇵Yamagata, Japan
Bukovian State Medical University, Dept. of Infectious Disease and Epidemiology
🇺🇦Chernivtsi, Ukraine