Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of Oral Lumicitabine Regimens in Hospitalized Adult Participants Infected With Human Metapneumovirus

NCT ID: NCT03502694

Last Updated: 2018-11-15

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-05
• Study Completion Date: 2020-10-28

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.

Conditions

Metapneumovirus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Regimen A (Low-Dose 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).

Group Type: EXPERIMENTAL

Lumicitabine

Intervention Type: DRUG

Participants will receive loading dose and maintenance dose of lumicitabine tablets orally.

Placebo

Intervention Type: DRUG

Participants will receive matching placebo tablets orally.

Regimen B (High-Dose 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).

Group Type: EXPERIMENTAL

Lumicitabine

Intervention Type: DRUG

Participants will receive loading dose and maintenance dose of lumicitabine tablets orally.

Placebo

Intervention Type: DRUG

Participants will receive matching placebo tablets orally.

Regimen C (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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will receive matching placebo tablets orally.

Interventions

Lumicitabine

Participants will receive loading dose and maintenance dose of lumicitabine tablets orally.

Intervention Type: DRUG

Placebo

Participants will receive matching placebo tablets orally.

Intervention Type: DRUG

Other Intervention Names

JNJ-64041575, ALS-008176

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

UCSF Fresno

Fresno, California, United States

MemorialCare Research Miller Children's and Women's Hospital Long Beach

Long Beach, California, United States

Lake Internal Medicine Associates

Eustis, Florida, United States

Northwestern University - Northwestern Memorial Hospital - Infectious Disease Center

Chicago, Illinois, United States

St Michaels Medical Center

Newark, New Jersey, United States

SUNY Upstate Medical University

Syracuse, New York, United States

Marshfield Clinic

Marshfield, Wisconsin, United States

Hospital Regional Español

Bahía Blanca, , Argentina

Hospital Interzonal General de Agudos Dr. Jose Penna

Bahía Blanca, , Argentina

Hospital Italiano de Buenos Aires

Buenos Aires, , Argentina

CEMIC Saavedra

Ciudad de Buenos Aires, , Argentina

Hospital Italiano de La Plata

Ciudad de La Plata, , Argentina

Hospital Rawson

Córdoba, , Argentina

Hospital Privado-Universitario de Cordoba

Córdoba, , Argentina

Instituto Medico Platense

La Plata, , Argentina

Queen Elizabeth Hospital

Adelaide, , Australia

Flinders Medical Centre

Adelaide, , Australia

Princess Alexandra Hospital

Brisbane, , Australia

Barwon Health - University Hospital Geelong

Geelong, , Australia

Royal Melbourne Hospital

Melbourne, , Australia

Mater Hospital Brisbane

South Brisbane, , Australia

Westmead Hospital

Sydney, , Australia

Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul

Porto Alegre, , Brazil

Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo

Ribeirão Preto, , Brazil

Hospital Sirio Libanes

São Paulo, , Brazil

Hospital Alemão Oswaldo Cruz

São Paulo, , Brazil

Hospital Das Clinicas Da Faculdade De Medicina Da Universidade De Sao Paulo

São Paulo, , Brazil

MHAT 'Sv. Ivan Rilski' Kozloduy EOOD

Kozloduy, , Bulgaria

Specialized Hospital for Active Treatment of Pulmonary Diseases - Pernik

Pernik, , Bulgaria

Specialized Hospital for Active Treatment of Pulmonary Diseases - Troyan EOOD

Troyan Municipality, , Bulgaria

MHAT Dr Stefan Cherkezov

Veliko Tarnovo, , Bulgaria

CHU Rouen

Bois-Guillaume, , France

CHU caen

Caen, , France

Hôpital Louis Mourier

Colombes, , France

APHP - Hopital Henri Mondor

Créteil, , France

CHU Dijon

Dijon, , France

CHU Grenoble

La Tronche, , France

CHU Nîmes

Nîmes, , France

Hopital Saint-Louis

Paris, , France

Hôpital Tenon

Paris, , France

CHU la milétrie

Poitiers, , France

CHU Saint-etienne

Saint-Priest-en-Jarez, , France

Hopital Foch

Suresnes, , France

Centre Hospitalier Universitaire de Tours

Tours, , France

Fukuoka University Hospital

Fukuoka, , Japan

National Hospital Organization Ibarakihigashi

Funaishikawa, , Japan

Ogaki Municipal Hospital

Gifu, , Japan

National Hospital Organization Tenryu Hospital

Hamamatue, , Japan

Japanese Red Cross Nagasaki Genbaku Isahaya Hospital

Isahaya, , Japan

Shimane University Hospital

Izumo, , Japan

Shinkomonji hospital

Kitakyushu, , Japan

Kobe City Medical Center General Hospital

Kobe, , Japan

Japanese Red Cross Society Nagano Hospital

Nagano, , Japan

Nagasaki University Hospital

Nagasaki, , Japan

National Hospital Organization Higashinagoya National Hospital

Nagoya, , Japan

Rinku General Medical Center

Osaka, , Japan

SUBARU Health Insurance Society Ota Memorial Hospital

Ōta-ku, , Japan

Tohoku Medical And Pharmaceutical University Hospital

Sendai, , Japan

Saka General Hospital

Shiogama, , Japan

National Hospital Organization Tokyo National Hospital

Tokyo, , Japan

Okinawa Prefectural Chubu Hospital

Uruma, , Japan

Okitama Public General Hospital

Yamagata, , Japan

Shimonoseki City Hospital

Yamaguchi, , Japan

Shin Yukuhashi Hospital

Yukuhashi, , Japan

Hospital Sultanah Bahiyah

Alor Star, , Malaysia

Hospital Pulau Pinang

George Town, , Malaysia

Hospital Raja Perempuan Zainab Ii

Kota Bharu, , Malaysia

University Malaya Medical Centre

Kuala Lumpur, , Malaysia

Sarawak General Hospital

Kuching, , Malaysia

Hospital Miri

Miri, , Malaysia

Hospital Taiping

Taiping, , Malaysia

UMCG

Groningen, , Netherlands

UMC Utrecht

Utrecht, , Netherlands

Gelre Ziekenhuizen Zutphen

Zutphen, , Netherlands

10 Wojskowy Szpital Kliniczny z Poliklinika

Bydgoszcz, , Poland

Wojewódzki Szpital Specjalistyczny im. św. Rafała w Czerwonej Górze

Chęciny, , Poland

SSZZOZ im. dr Teodora Dunina w Rudce

Mrozy, , Poland

Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc w Olsztynie

Olsztyn, , Poland

Samodzielny Publiczny Zespół Opieki Zdrowotnej w Proszowicach

Proszowice, , Poland

State Health Care Institution 'Engels city hospital #2'

Engel's, , Russia

Saint-Petersburg State Health Care Institution 'Vvedenskaya Hospital'

Saint Petersburg, , Russia

Clinical Infectious Diseases Hospital n. a. S.P. Botkin

Saint Petersburg, , Russia

Saint-Petersburg State Public Health Organization City Clinical Hospital #26

Saint Petersburg, , Russia

Regional State Health Care Institution 'Clinical Hospital #1'

Smolensk, , Russia

Siberian State Medical University

Tomsk, , Russia

State Health Care Institution of Voronezh region 'Voronezh regional clinical infectious hospital'

Voronezh, , Russia

Clinical Emergency Hospital n.a. N.V. Solovyev

Yaroslavl, , Russia

Soonchunhyang University Bucheon Hospital

Bucheon-si, , South Korea

Yeungnam University Medical Center

Daegu, , South Korea

Gachon University Gil Hospital

Incheon, , South Korea

Seoul National University Bundang Hospital

Seongnam, , South Korea

Kangnam Sacred Heart Hospital

Seoul, , South Korea

Korea University Guro Hospital

Seoul, , South Korea

Hosp. Gral. Univ. de Elche

Elche, , Spain

Hosp. Univ. de La Princesa

Madrid, , Spain

Hosp. Univ. 12 de Octubre

Madrid, , Spain

Hosp. Univ. La Paz

Madrid, , Spain

Hosp. Clinico Univ. de Santiago

Santiago de Compostela, , Spain

Hosp. Alvaro Cunqueiro

Vigo, , Spain

Sahlgrenska University Hospital

Gothenburg, , Sweden

Skanes universitetssjukhus

Malmo, , Sweden

Norrlands Universitetssjukhus

Umeå, , Sweden

Akademiska Sjukhuset

Uppsala, , Sweden

Kaohsiung Veterans General Hospital

Kaohsiung City, , Taiwan

Far Eastern Memorial Hospital

New Taipei City, , Taiwan

Taipei Medical University Shuang Ho Hospital

New Taipei City, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

Taipei Municipal Wanfang Hospital

Taipei, , Taiwan

Bukovian State Medical University, Dept. of Infectious Disease and Epidemiology

Chernivtsi, , Ukraine

Ivano-Frankivsk Regional Clinical Hospital

Ivano-Frankivsk, , Ukraine

Kharkiv National Medical University, Regional Clinical Infectious Hospital

Kharkiv, , Ukraine

Vinnytsia City Clinical Hospital #1, Department of Infectious Diseases #1

Vinnytsia, , Ukraine

Countries

United States; Argentina; Australia; Brazil; Bulgaria; France; Japan; Malaysia; Netherlands; Poland; Russia; South Korea; Spain; Sweden; Taiwan; Ukraine

Other Identifiers

2017-001696-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

64041575MPN2001

Identifier Type: OTHER

Identifier Source: secondary_id

CR108378

Identifier Type: -

Identifier Source: org_study_id