Clinical trial NCT03502694: Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of Oral Lumicitabine Regimens in Hospitalized Adult Participants Infected With Human Metapneumovirus
Official title: A Phase 2b, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of Orally Administered Lumicitabine (JNJ-64041575) Regimens in Hospitalized Adult Subjects Infected With Human Metapneumovirus
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Metapneumovirus
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2018-04-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Area Under the Concentration-Time Curve (AUC) of Human Metapneumovirus (hMPV) Viral Load
timeFrame: Baseline up to Day 7
Secondary outcomes:
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: Up to 28 days
measure: 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
timeFrame: Up to 28 days
measure: Number of Participants with an Abnormal Vital Signs/Peripheral Capillary Oxygen Saturation (SpO2) Reading as a Measure of Safety and Tolerability
timeFrame: Up to 28 days
measure: Number of Participants with an Abnormal Electrocardiogram (ECG) Reading as a Measure of Safety and Tolerability
timeFrame: Up to 28 days
measure: Number of Participants with Clinical Laboratory Abnormalities as a Measure of Safety and Tolerability
timeFrame: Up to 28 days
measure: Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109
timeFrame: 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
measure: Concentration at 12 Hours Postdose (C12h) of JNJ-63549109
timeFrame: Days 1, 2, and 5/6: 12 hours postdose
measure: Area Under the Plasma Concentration-Time Curve (AUC) of JNJ-63549109
timeFrame: 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
measure: Ordinal Scale
timeFrame: Day of last dose (Day 5 or Day 6)
measure: Length of Hospital Stay from Admission to Discharge
timeFrame: From admission to discharge (Up to 28 days)
measure: Length of Hospital Stay from Admission to Readiness for Discharge
timeFrame: From admission to readiness for discharge discharge (Up to 28 days)
measure: Length of Hospital Stay from Study Treatment Initiation to Discharge
timeFrame: From study treatment initiation to discharge (Up to 28 days)
measure: Length of Hospital Stay from Study Treatment Initiation to Readiness for Discharge
timeFrame: From study treatment initiation to readiness for discharge (Up to 28 days)
measure: Percentage of Participants Requiring Admission to the Intensive Care Unit (ICU)
timeFrame: Up to 28 days
measure: Duration of ICU Stay
timeFrame: Up to 28 days
measure: Percentage of Participants Requiring Oxygen Supplementation/Noninvasive Mechanical Ventilation Support
timeFrame: Up to 28 days
measure: Duration of Oxygen Supplementation/Noninvasive Mechanical Ventilation Support
timeFrame: Up to 28 days
measure: Percentage of Participants Requiring Invasive Mechanical Ventilation Support
timeFrame: Up to 28 days
measure: Duration of Invasive Mechanical Ventilation Support
timeFrame: Up to 28 days
measure: Time to no Longer Requiring Supplemental Oxygen
timeFrame: Up to 28 days
measure: Time to Clinical Stability
timeFrame: Up to 28 days
measure: Number of Hours from Initiation of Study Treatment Until SpO2 is Greater Than or equal to (>=) 93 Percent (%) on Room air
timeFrame: Up to 28 days
measure: Time for Respiratory Rate to Return to Pre-hMPV Infection Status
timeFrame: Up to 28 days
measure: Time for Peripheral Capillary Oxygen Saturation (SpO2) Return to Pre-hMPV Infection Status
timeFrame: Up to 28 days
measure: Time for Body Temperature to Return to Pre-hMPV Infection Status
timeFrame: Up to 28 days
measure: Percentage of Enrolled Participants Who Require Hydration and/or Feeding by Intravenous (IV) Catheter or Nasogastric Tube
timeFrame: Up to 28 days
measure: Number of Participants With Bacterial Superinfections Reported as AEs
timeFrame: Up to 28 days
measure: Number of Participants With Treatment-Emergent Complications
timeFrame: Up to 28 days
measure: Change From Baseline in the National Early Warning Score (NEWS) Over Time
timeFrame: Baseline up to 28 days
measure: Number of Participants With All-Cause Mortality
timeFrame: Up to 28 days
measure: Time to Return to Pre-hMPV Infection Functional Status (Katz Activities of Daily Living [ADL] score)
timeFrame: Up to 28 Days
measure: hMPV Viral Load Over Time
timeFrame: Up to 28 days
measure: Peak hMPV Viral Load
timeFrame: Up to 28 days
measure: Time to Peak hMPV Viral Load
timeFrame: Up to 28 days
measure: Rate of Decline of hMPV Viral Load
timeFrame: Up to 28 days
measure: Time to hMPV Ribonucleic Acid (RNA) Being Undetectable
timeFrame: Up to 28 days
measure: Percentage of Participants With Undetectable hMPV Viral Load at Each Timepoint
timeFrame: From Day 1 to Day 7 and on Day 10, Day 14, and Day 28
measure: AUC of hMPV Viral Load From Baseline up to Day 10
timeFrame: Baseline up to Day 10
measure: AUC of hMPV Viral Load from Baseline up to Day 14
timeFrame: Baseline up to Day 14
measure: 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
timeFrame: Baseline Until 1 day After the Last Dose of Study Drug (approximately up to 12 days)
measure: Number of Participants With Postbaseline Changes in the hMPV Polymerase Lgene and Other Regions of the hMPV Genome Compared With Baseline Sequences
timeFrame: Up to 28 days
Other outcomes:
Locations:
city: Fresno
country: United States
facility: UCSF Fresno
state: California
city: Long Beach
country: United States
facility: MemorialCare Research Miller Children's and Women's Hospital Long Beach
state: California
city: Eustis
country: United States
facility: Lake Internal Medicine Associates
state: Florida
city: Chicago
country: United States
facility: Northwestern University - Northwestern Memorial Hospital - Infectious Disease Center
state: Illinois
city: Newark
country: United States
facility: St Michaels Medical Center
state: New Jersey
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Marshfield
country: United States
facility: Marshfield Clinic
state: Wisconsin
city: Bahia Blanca
country: Argentina
facility: Hospital Interzonal General de Agudos Dr. Jose Penna
city: Bahía Blanca
country: Argentina
facility: Hospital Regional Español
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Ciudad De Buenos Aires
country: Argentina
facility: CEMIC Saavedra
city: Ciudad De La Plata
country: Argentina
facility: Hospital Italiano de La Plata
city: Cordoba
country: Argentina
facility: Hospital Rawson
city: Cordoba
country: Argentina
facility: Hospital Privado-Universitario de Cordoba
city: La Plata
country: Argentina
facility: Instituto Medico Platense
city: Adelaide
country: Australia
facility: Queen Elizabeth Hospital
city: Adelaide
country: Australia
facility: Flinders Medical Centre
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
city: Geelong
country: Australia
facility: Barwon Health - University Hospital Geelong
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
city: South Brisbane
country: Australia
facility: Mater Hospital Brisbane
city: Sydney
country: Australia
facility: Westmead Hospital
city: Porto Alegre
country: Brazil
facility: Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul
city: Ribeirao Preto
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo
city: Sao Paulo
country: Brazil
facility: Hospital Alemão Oswaldo Cruz
city: Sao Paulo
country: Brazil
facility: Hospital Das Clinicas Da Faculdade De Medicina Da Universidade De Sao Paulo
city: São Paulo
country: Brazil
facility: Hospital Sirio Libanes
city: Kozloduy
country: Bulgaria
facility: MHAT 'Sv. Ivan Rilski' Kozloduy EOOD
city: Pernik
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Pulmonary Diseases - Pernik
city: Troyan
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Pulmonary Diseases - Troyan EOOD
city: Veliko Tarnovo
country: Bulgaria
facility: MHAT Dr Stefan Cherkezov
city: Bois Guillaume
country: France
facility: CHU Rouen
city: Caen
country: France
facility: CHU caen
city: Colombes
country: France
facility: Hôpital Louis Mourier
city: Créteil
country: France
facility: APHP - Hopital Henri Mondor
city: Dijon
country: France
facility: CHU Dijon
city: La Tronche
country: France
facility: CHU Grenoble
city: Nîmes
country: France
facility: CHU Nîmes
city: Paris
country: France
facility: Hopital Saint-Louis
city: Paris
country: France
facility: Hôpital Tenon
city: Poitiers
country: France
facility: CHU la milétrie
city: St Priest En Jarez
country: France
facility: CHU Saint-etienne
city: Suresnes
country: France
facility: Hopital Foch
city: Tours Cedex
country: France
facility: Centre Hospitalier Universitaire de Tours
city: Fukuoka
country: Japan
facility: Fukuoka University Hospital
city: Gifu
country: Japan
facility: Ogaki Municipal Hospital
city: Hamamatue
country: Japan
facility: National Hospital Organization Tenryu Hospital
city: Isahaya
country: Japan
facility: Japanese Red Cross Nagasaki Genbaku Isahaya Hospital
city: Izumo
country: Japan
facility: Shimane University Hospital
city: Kitakyusyu
country: Japan
facility: Shinkomonji hospital
city: Kobe-City
country: Japan
facility: Kobe City Medical Center General Hospital
city: Nagano
country: Japan
facility: Japanese Red Cross Society Nagano Hospital
city: Nagasaki
country: Japan
facility: Nagasaki University Hospital
city: Nagoya
country: Japan
facility: National Hospital Organization Higashinagoya National Hospital
city: Osaka
country: Japan
facility: Rinku General Medical Center
city: Ota
country: Japan
facility: SUBARU Health Insurance Society Ota Memorial Hospital
city: Sendai
country: Japan
facility: Tohoku Medical And Pharmaceutical University Hospital
city: Shiogama
country: Japan
facility: Saka General Hospital
city: Tokai-Mura
country: Japan
facility: National Hospital Organization Ibarakihigashi
city: Tokyo
country: Japan
facility: National Hospital Organization Tokyo National Hospital
city: Uruma
country: Japan
facility: Okinawa Prefectural Chubu Hospital
city: Yamagata
country: Japan
facility: Okitama Public General Hospital
city: Yamaguchi
country: Japan
facility: Shimonoseki City Hospital
city: Yukuhashi
country: Japan
facility: Shin Yukuhashi Hospital
city: Bucheon
country: Korea, Republic of
facility: Soonchunhyang University Bucheon Hospital
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Medical Center
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Hospital
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Kangnam Sacred Heart Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Alor Setar
country: Malaysia
facility: Hospital Sultanah Bahiyah
city: George Town
country: Malaysia
facility: Hospital Pulau Pinang
city: Kota Bharu
country: Malaysia
facility: Hospital Raja Perempuan Zainab Ii
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Kuching
country: Malaysia
facility: Sarawak General Hospital
city: Miri
country: Malaysia
facility: Hospital Miri
city: Taiping
country: Malaysia
facility: Hospital Taiping
city: Groningen
country: Netherlands
facility: UMCG
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Zutphen
country: Netherlands
facility: Gelre Ziekenhuizen Zutphen
city: Bydgoszcz
country: Poland
facility: 10 Wojskowy Szpital Kliniczny z Poliklinika
city: Chęciny
country: Poland
facility: Wojewódzki Szpital Specjalistyczny im. św. Rafała w Czerwonej Górze
city: Mrozy
country: Poland
facility: SSZZOZ im. dr Teodora Dunina w Rudce
city: Olsztyn
country: Poland
facility: Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc w Olsztynie
city: Proszowice
country: Poland
facility: Samodzielny Publiczny Zespół Opieki Zdrowotnej w Proszowicach
city: Engels
country: Russian Federation
facility: State Health Care Institution 'Engels city hospital #2'
city: Smolensk
country: Russian Federation
facility: Regional State Health Care Institution 'Clinical Hospital #1'
city: St. Petersburg
country: Russian Federation
facility: Saint-Petersburg State Health Care Institution 'Vvedenskaya Hospital'
city: St. Petersburg
country: Russian Federation
facility: Clinical Infectious Diseases Hospital n. a. S.P. Botkin
city: St. Petersburg
country: Russian Federation
facility: Saint-Petersburg State Public Health Organization City Clinical Hospital #26
city: Tomsk
country: Russian Federation
facility: Siberian State Medical University
city: Voronezh
country: Russian Federation
facility: State Health Care Institution of Voronezh region 'Voronezh regional clinical infectious hospital'
city: Yaroslavl
country: Russian Federation
facility: Clinical Emergency Hospital n.a. N.V. Solovyev
city: Elche
country: Spain
facility: Hosp. Gral. Univ. de Elche
city: Madrid
country: Spain
facility: Hosp. Univ. de La Princesa
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Madrid
country: Spain
facility: Hosp. Univ. La Paz
city: Santiago De Compostela
country: Spain
facility: Hosp. Clinico Univ. de Santiago
city: Vigo
country: Spain
facility: Hosp. Alvaro Cunqueiro
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Malmö
country: Sweden
facility: Skanes universitetssjukhus
city: Umeå
country: Sweden
facility: Norrlands Universitetssjukhus
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: New Taipei
country: Taiwan
facility: Far Eastern Memorial Hospital
city: New Taipei
country: Taiwan
facility: Taipei Medical University Shuang Ho Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: Taipei Municipal Wanfang Hospital
city: Chernivtsi
country: Ukraine
facility: Bukovian State Medical University, Dept. of Infectious Disease and Epidemiology
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Regional Clinical Hospital
city: Kharkiv
country: Ukraine
facility: Kharkiv National Medical University, Regional Clinical Infectious Hospital
city: Vinnytsya
country: Ukraine
facility: Vinnytsia City Clinical Hospital #1, Department of Infectious Diseases #1
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: