Clinical trial NCT04583280: A Study of Rilematovir in Infants and Children and Subsequently in Neonates Hospitalized With Acute Respiratory Tract Infection Due to Respiratory Syncytial Virus (RSV)
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Rilematovir in Infants and Children (≥28 Days to ≤5 Years of Age) and Subsequently in Neonates (<28 Days of Age), Hospitalized With Acute Respiratory Tract Infection Due to Respiratory Syncytial Virus (RSV)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Respiratory Tract Infections
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-10-12
Enrollment: 28
Sex: ALL
Minimum age (years): 1
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the efficacy of rilematovir compared to placebo treatment with respect to the clinical outcome on the RSV Recovery Scale (RRS).

Detailed description: Respiratory syncytial virus (RSV), a negative-stranded ribonucleic acid (RNA) virus belonging to the Pneumoviridae family, is considered the most important cause of acute lower respiratory tract infection (LRTI) in infants and young children. In most patients, RSV results in upper respiratory tract infection (URTI) eliciting "common cold"-like symptoms, which might last up to 2 weeks, and are usually self-limiting. RSV-related LRTI is a major cause of hospital admissions and death in young children worldwide. Rilematovir is an investigational, small molecule, RSV fusion inhibitor. This study aims to evaluate the efficacy and safety of rilematovir in hospitalized infants and children (greater than or equal to \[\>=\] 28 days to less than or equal to \[\<=\] 5 years) and, subsequent to completion of the neonatal substudy, in hospitalized neonates (born at term, less than \[\<\] 28 days of age) with RSV infection. The study will include a Screening Period, a Treatment Period, and a Follow-up Period. The total study duration for each participant will be approximately 36 days (Screening included). The efficacy assessments include evaluation under the RRS and the safety assessments include evaluations of physical examinations, vital signs, electrocardiograms, clinical laboratory tests, and adverse events.

Eligibility criteria: Inclusion criteria:

* The participant weighs within greater than or equal to (\>=) 2.4 kilograms (kg) and less than or equal to (\<=) 24.6 kg
* Each participant's parent(s) (preferably both if available or as per local requirements) or their legally acceptable representative(s) has/have signed an informed consent form (ICF) indicating that (s)he understands the purpose of, and procedures required for, the study; is willing for their child to participate in the study; with regards to the concomitant medication, the lifestyle consideration and study procedures and assessments to be performed by the parent(s)/caregiver(s) as well as those by the investigator/study site personnel
* The participant has an acute respiratory illness with at least 1 of the signs/symptoms within 24 hours prior to start of screening and at screening, as evaluated by the investigator in Upper respiratory tract infection: nasal congestion or rhinorrhea; and Lower respiratory tract infection: increased respiratory effort (as evidenced by subcostal, intercostal or tracheosternal retractions, grunting, head bobbing, nasal flaring, or tachypnea), wheezing, cough, cyanosis, or apnea; and systemic/general: feeding difficulties (defined as \<75 percent \[%\] intake of normal food amounts); dehydration; fever; disturbed sleep, or disturbed activity level (irritable/restless/agitated/less responsive). Cough or wheezing cannot be the only LRTI sign/symptom present, that is, at least one other LRTI sign/symptom needs to be present for eligibility
* The time of onset of RSV signs/symptoms to the anticipated time of randomization must be less than or equal to (\<=) 3 days. Onset of signs/symptoms is defined as the time of the day (or part of the day if time of the day cannot be specified) the parent(s)/caregiver(s) became aware of the first sign and/or symptom consistent with respiratory or systemic/general manifestation of signs/symptoms of RSV infection. The time of sign/symptom onset has to be assessed as accurately as possible
* Participants are otherwise healthy or have (a) risk factor(s) for severe RSV disease

Exclusion criteria:

* The participant has had either confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (test positive) during the four weeks prior to randomization, or close contact with a person with COVID-19 (test confirmed or suspected SARS CoV-2 infection) within 14 days prior to randomization
* Confirmed QT interval corrected for heart rate according to Fridericia's formula (QTcF) interval greater than (\>) 450 milliseconds (msec) per the machine read parameter result at screening. Presence of an abnormal QTcF interval should be confirmed by repeat electrocardiogram (ECG) recording during screening
* Known personal or family history of Long QT Syndrome or sudden cardiac death
* Presence of repetitive ventricular premature contractions (\>10/minutes \[min\]), second- or third-degree heart block, or complete or incomplete left bundle branch block, or complete right bundle branch block per the machine read ECG result at screening. Presence of any of the above abnormalities should be confirmed by repeat ECG recording during screening

Primary outcomes:
measure: Percentage of Participants by Respiratory Syncytial Virus (RSV) Recovery Scale (RRS) Category
timeFrame: Baseline to Day 8
Secondary outcomes:
measure: Percentage of Participants Clinically Resolved From RSV Disease Based on the Clinician Reported Outcome (ClinRO) Sign/Symptoms at Day 8
timeFrame: Day 8
measure: Time From First Study Dose to Resolution of Key RSV Signs/Symptoms Based on Observer Reported Outcome (ObsRO) After Free of Supplementation (Oxygen/Feeding/Hydration) for at Least 24 Hours
timeFrame: Up to Day 21
measure: Number of Participants With Post-baseline RSV-related Complications
timeFrame: Up to Day 35
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 1 up to Day 35
measure: Number of Participants With Abnormalities in Clinical Laboratory Values
timeFrame: Up to Day 35
measure: Number of Participants With Abnormalities in Electrocardiograms (ECGs)
timeFrame: Up to Day 35
measure: Number of Participants With Abnormalities in Vital Signs
timeFrame: Up to Day 35
measure: Percentage of Participants Requiring Intensive Care Unit (ICU) Stay After First Dose of Rilematovir
timeFrame: Up to Day 35
measure: Duration of ICU Stay
timeFrame: Up to Day 35
measure: Percentage of Participants Requiring Re-hospitalization for Respiratory/Other Reasons
timeFrame: Up to Day 35
measure: Percentage of Participants Requiring Oxygen Supplementation After First Dose of Rilematovir
timeFrame: Up to Day 35
measure: Duration of Oxygen Supplementation
timeFrame: Up to Day 35
measure: Percentage of Participants Requiring Hydration and/or Feeding by Intravenous (IV) Administration or Nasogastric Tube After First Dose of Rilematovir
timeFrame: Up to Day 35
measure: Duration of Supplemental Feeding/Hydration
timeFrame: Up to Day 35
measure: Number of Participants With Medical Encounters and Treatments
timeFrame: Up to Day 35
measure: RSV Viral Load at Baseline, Days 2, 3, 5, 8, 14 and 21
timeFrame: Baseline, Days 2, 3, 5, 8, 14 and 21
measure: Change From Baseline in RSV Viral Load at Days 2, 3, 5, 8, 14 and 21
timeFrame: Baseline, Days 2, 3, 5, 8, 14 and 21
measure: Percentage of Participants With Undetectable RSV Viral Load
timeFrame: Baseline, Days 2, 3, 5, 8, 14 and 21
measure: Plasma Concentrations of Rilematovir
timeFrame: 1 hour Post-dose (Day 1) and pre-dose (Day 2)
measure: Percentage of Participants With Acceptability and Palatability of the Rilematovir Formulation as Assessed by Parent(s)/Caregiver(s)
timeFrame: Day 8
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Arnold Palmer Hospital For Children
state: Florida
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Bronx
country: United States
facility: Jacobi Medical Center
state: New York
city: Memphis
country: United States
facility: Le Bonheur Children's Hospital
state: Tennessee
city: Tacoma
country: United States
facility: MultiCare Health Systems for Research and Innovation
state: Washington
city: Bahia Blanca
country: Argentina
facility: Hospital Interzonal General de Agudos Dr. Jose Penna
city: Bahía Blanca
country: Argentina
facility: Hospital Italiano Regional Del Sur
city: Buenos Aires
country: Argentina
facility: Hospital General de Niños Pedro de Elizalde
city: Pilar
country: Argentina
facility: Hospital Universitario Austral
city: Rio Cuarto
country: Argentina
facility: Instituto Medico Rio Cuarto
city: San Miguel de Tucuman
country: Argentina
facility: Clinica Mayo de UMCB
city: San Miguel de Tucumán
country: Argentina
facility: Hospital del Niño Jesús
city: Anderlecht
country: Belgium
facility: ULB Hôpital Erasme
city: Brugge
country: Belgium
facility: AZ Sint Jan Brugge Oostende AV
city: Brussel
country: Belgium
facility: UZ Brussel
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Leuven
country: Belgium
facility: UZ Leuven
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericordia de Belo Horizonte
city: Botucatu
country: Brazil
facility: Fundacao para o Desenvolvimento Medico Hospitalar (UNESP Botucatu)
city: Campinas
country: Brazil
facility: Sociedade Campineira de Educacao e Instrucao Hospital e Maternidade Celso Pierro
city: Curitiba
country: Brazil
facility: Nucleo de Pesquisa do Hospital Pequeno Princípe
city: Fortaleza
country: Brazil
facility: Secretaria da Saude do Estado do Ceara - Hospital Doutor Carlos Alberto Studart Gomes
city: Porto Alegre
country: Brazil
facility: Associacao Hospitalar Moinhos de Vento
city: Ribeirão Preto
country: Brazil
facility: Hospital Das Clinicas Da Faculdade De Medicina De RPUSP HCRP
city: Sao Paulo
country: Brazil
facility: Fundacao Jose Luiz Egydio Setubal
city: Votuporanga
country: Brazil
facility: Santa Casa de Misericórdia de Votuporanga
city: Plovdiv
country: Bulgaria
facility: UMHAT 'Sveti Georgi'-Plovdiv
city: Ruse
country: Bulgaria
facility: UMHAT 'Kanev' EAD
city: Sofia
country: Bulgaria
facility: Acibadem City Clinic Tokuda Hospital
city: Sofia
country: Bulgaria
facility: UMHAT 'Aleksandrovska' EAD
city: Sofia
country: Bulgaria
facility: SHATCD 'Prof. Ivan Mitev' EAD
city: Beijing
country: China
facility: Capital Institute of Pediatrics
city: Beijing
country: China
facility: Beijing Children's Hospital, Capital Medical University
city: Beijing
country: China
facility: Peking University Third Hospital
city: Chengdu
country: China
facility: West China Second University Hospital, Sichuan University
city: Guangzhou
country: China
facility: Guangzhou Women And Children's Medical Center
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Praha 10
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
city: Praha 4
country: Czechia
facility: Thomayerova nemocnice
city: Tallinn
country: Estonia
facility: Tallinn Children's Hospital
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Freiburg
country: Germany
facility: Universitätsklinik Freiburg
city: Wuppertal
country: Germany
facility: HELIOS Klinikum Wuppertal GmbH
city: Würzburg
country: Germany
facility: Universitatsklinikum Wurzburg
city: Budapest
country: Hungary
facility: Semmelweis Egyetem, II. sz. Gyermekgyógyászati Klinika
city: Budapest
country: Hungary
facility: Bethesda Gyermekkórház
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Győr
country: Hungary
facility: Petz Aladar Megyei Oktato Korhaz
city: Kecskemet
country: Hungary
facility: Bacs-kiskun Megyei Korhaz
city: Miskolc
country: Hungary
facility: Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem
city: Veszprém
country: Hungary
facility: Csolnoky Ferenc Korhaz
city: Beer-Sheba
country: Israel
facility: Soroka University Medical Center
city: Haifa
country: Israel
facility: Ruth Rappaport Children's Hospital, Rambam Health Care Campus
city: Petah Tikva
country: Israel
facility: Schneider Children's Medical Center
city: Ramat Gan
country: Israel
facility: Pediatrics B, Safra Children's Hospital, Tel Hashomer
city: Tel-Aviv
country: Israel
facility: Sourasky MC
city: Bologna
country: Italy
facility: A O U Sant Orsola Malpighi
city: Milan
country: Italy
facility: Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Pavia
country: Italy
facility: Department of Pediatrics University of Pavia, Policlinico San Matteo
city: Ponderano
country: Italy
facility: Ospedale degli Infermi
city: Fukui-shi
country: Japan
facility: Fukui Prefectural Hospital
city: Fukuyama
country: Japan
facility: Fukuyama City Hospital
city: Hioki
country: Japan
facility: Kagoshima Children's Hospital
city: Hokkaido
country: Japan
facility: Teine Keijinkai Hospital
city: Ishikawa
country: Japan
facility: National Hospital Organization Kanazawa Medical Center
city: Kitakyushu-shi
country: Japan
facility: Japan Community Health care Organization Kyushu Hospital
city: Kobe
country: Japan
facility: Kobe City Medical Center General Hospital
city: Kochi
country: Japan
facility: Kochi Health Sciences Center
city: Maebashi
country: Japan
facility: Maebashi Red Cross Hospital
city: Nagoya
country: Japan
facility: Kojunkai Daido Hospital
city: Niigata
country: Japan
facility: National Hospital Organization Niigata National Hospital
city: Oita
country: Japan
facility: National Hospital Organization Beppu Medical Center
city: Saitama
country: Japan
facility: National Hospital Organization Saitama National Hospital
city: Ureshino-shi
country: Japan
facility: National Hospital Organization Ureshino Medical Center
city: Yamanashi
country: Japan
facility: Yamanashi Prefectural Central Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: CHA Bundang Medical Center, CHA University
city: Seoul
country: Korea, Republic of
facility: Korea Institute of Radiological and Medical Sciences
city: Seoul
country: Korea, Republic of
facility: Nowon Eulji Medical Center, Eulji University
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Inje University Sanggye Paik Hospital
city: Riga
country: Latvia
facility: Children's Clinical University Hospital
city: Batu Caves
country: Malaysia
facility: Hospital Selayang
city: Bintulu
country: Malaysia
facility: Hospital Bintulu
city: Miri
country: Malaysia
facility: Hospital Miri
city: Sibu
country: Malaysia
facility: Hospital Sibu
city: Taiping
country: Malaysia
facility: Hospital Taiping
city: Ciudad de Mexico
country: Mexico
facility: Instituto Nacional de Pediatría
city: Ciudad De Mexico
country: Mexico
facility: Hospital Infantil de Mexico Federico Gomez
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr Jose Eleuterio Gonzalez
city: Monterrey
country: Mexico
facility: Centro Medico Zambrano Hellion
city: Panama
country: Panama
facility: Cevaxin Avenida Mexico
city: Krakow
country: Poland
facility: Krakowski Szpital Specjalistyczny im Jana Pawla II
city: Lodz
country: Poland
facility: Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im M Kopernika w Lodzi
city: Lublin
country: Poland
facility: Uniwersytecki Szpital Dzieciecy w Lublinie
city: Warszawa
country: Poland
facility: Dzieciecy Szpital Kliniczny im Jozefa Polikarpa Brudzinskiego
city: Banska Bystrica
country: Slovakia
facility: DFNsP Banska Bystrica
city: Bratislava
country: Slovakia
facility: Pediatric Pulmonology Clinic, University Hospital Bratislava
city: Badalona
country: Spain
facility: Hosp. Univ. Germans Trias I Pujol
city: Barakaldo
country: Spain
facility: Hosp. Univ. de Cruces
city: Córdoba
country: Spain
facility: Hosp Reina Sofia
city: Getafe
country: Spain
facility: Hosp. Univ. de Getafe
city: Madrid
country: Spain
facility: Hosp Univ Fund Jimenez Diaz
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Madrid
country: Spain
facility: Hosp. Univ. La Paz
city: Madrid
country: Spain
facility: Hosp. Univ. Hm Monteprincipe
city: Madrid
country: Spain
facility: Hosp. Univ. Severo Ochoa
city: Majadahonda
country: Spain
facility: Hosp. Univ. Pta. de Hierro Majadahonda
city: Mostoles
country: Spain
facility: Hosp. Puerta Del Sur
city: Pamplona
country: Spain
facility: Complejo Hosp. de Navarra
city: Pozuelo de Alarcón
country: Spain
facility: Hosp. Quiron Madrid Pozuelo
city: Santiago de Compostela
country: Spain
facility: Hosp. Clinico Univ. de Santiago
city: Stockholm
country: Sweden
facility: Astrid Lindgrens barnsjukhus Solna
city: Hsinchu
country: Taiwan
facility: Hsinchu MacKay Memorial Hospital
city: New Taipei City
country: Taiwan
facility: Taipei Medical University Shuang Ho Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital
city: Taoyuan City
country: Taiwan
facility: Chang Gung Medical Foundation
city: Bangkok
country: Thailand
facility: Tropical Medicine Hospital, Mahidol University
city: Bangkok
country: Thailand
facility: Siriraj Hospital Mahidol University
city: Chiang Mai
country: Thailand
facility: Maharaj Nakorn Chiangmai Hospital
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital
city: Nonthaburi
country: Thailand
facility: Bamrasnaradura Infectious Disease Institute
city: Pathumwan
country: Thailand
facility: Faculty of Medicine Chulalongkorn University
city: Adana
country: Turkey
facility: Cukurova University Medical Faculty Balcali Hospital
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: Ankara
country: Turkey
facility: Gazi University Medical Faculty
city: Istanbul
country: Turkey
facility: Istanbul University Istanbul Medical Faculty
city: Izmir
country: Turkey
facility: Ege University Medical Faculty
city: Sarıyer
country: Turkey
facility: Saglik Bilimleri University Sariyer Hamidiye Etfal Training and Research Hospital
city: Trabzon
country: Turkey
facility: Karadeniz Teknik University Medical Faculty
city: Dnipro
country: Ukraine
facility: MNPE City Children's Clinical Hospital № 6 of Dnipro City Council
city: Dnipro
country: Ukraine
facility: ME 'Dnipropetrovsk Regional Children's Clinical Hospital of Dnipropetrovsk Regional Council'
city: Kharkiv
country: Ukraine
facility: Kharkiv National Medical University on based CHPI Kharkiv Municipal Clinical Children's Hospital 16
city: Kryvyi Rih
country: Ukraine
facility: MUNICIPAL NON-PROFIT ENTERPRISE 'Kryvyi Rih CITY HOSPITAL №16' Kryvyi Rih CITY COUNCIL
city: Odessa
country: Ukraine
facility: Odessa Regional Child Hospital
city: Sumy
country: Ukraine
facility: SSU Division MU Ch of pediatrics of PGE with propedeutic pediatrics and children infections course
city: Sumy
country: Ukraine
facility: Sumy Regional Childrens Clinical Hospital
city: Vinnytsia
country: Ukraine
facility: Municipal institution 'Vinnytsia Regional Clinical Children's Infectious Diseases Hospital'
city: Zaporizhzhia
country: Ukraine
facility: MNPE Zaporizhzhya Regional Clinical Children's Hospital of Zaporizhzhya Regional Council
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: