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

NCT03502694 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: CR1083782017-001696-2264041575MPN2001
• Study Type: interventional
• Target: N/A
• Locations: 16 countries
• Sites: 112

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.

Conditions

Metapneumovirus

Outcome Measures

Primary Outcomes (1)

• Area Under the Concentration-Time Curve (AUC) of Human Metapneumovirus (hMPV) Viral Load

  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.

  Baseline up to Day 7

Secondary Outcomes (41)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  Up to 28 days

• 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 Vital Signs/Peripheral Capillary Oxygen Saturation (SpO2) Reading as a Measure of Safety and Tolerability

  Up to 28 days

• Number of Participants with an Abnormal Electrocardiogram (ECG) Reading as a Measure of Safety and Tolerability

  Up to 28 days

• Number of Participants with Clinical Laboratory Abnormalities as a Measure of Safety and Tolerability

  Up to 28 days

Study Arms (3)

Regimen A (Low-Dose Lumicitabine)

EXPERIMENTAL

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).

Drug: Lumicitabine; Drug: Placebo

Regimen B (High-Dose Lumicitabine)

EXPERIMENTAL

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).

Drug: Lumicitabine; Drug: Placebo

Regimen C (Placebo)

PLACEBO COMPARATOR

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).

Drug: Placebo

Interventions

Lumicitabine DRUG

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

Also known as: JNJ-64041575, ALS-008176

Regimen A (Low-Dose Lumicitabine); Regimen B (High-Dose Lumicitabine)

Placebo DRUG

Participants will receive matching placebo tablets orally.

Regimen A (Low-Dose Lumicitabine); Regimen B (High-Dose Lumicitabine); Regimen C (Placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (112)

UCSF Fresno

Fresno, California, 93701, United States

Location

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

Long Beach, California, 90806, United States

Location

Lake Internal Medicine Associates

Eustis, Florida, 32726, United States

Location

Northwestern University - Northwestern Memorial Hospital - Infectious Disease Center

Chicago, Illinois, 60611, United States

Location

St Michaels Medical Center

Newark, New Jersey, 07102, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Marshfield Clinic

Marshfield, Wisconsin, 54449, United States

Location

Hospital Regional Español

Bahía Blanca, 8000, Argentina

Location

Hospital Interzonal General de Agudos Dr. Jose Penna

Bahía Blanca, B8001DDU, Argentina

Location

Hospital Italiano de Buenos Aires

Buenos Aires, C1199ABD, Argentina

Location

CEMIC Saavedra

Ciudad de Buenos Aires, 1431, Argentina

Location

Hospital Italiano de La Plata

Ciudad de La Plata, B1900AX, Argentina

Location

Hospital Rawson

Córdoba, 5000, Argentina

Location

Hospital Privado-Universitario de Cordoba

Córdoba, X5016KEH, Argentina

Location

Instituto Medico Platense

La Plata, B1900Avg, Argentina

Location

Queen Elizabeth Hospital

Adelaide, 5011, Australia

Location

Flinders Medical Centre

Adelaide, 5042, Australia

Location

Princess Alexandra Hospital

Brisbane, 4102, Australia

Location

Barwon Health - University Hospital Geelong

Geelong, 3220, Australia

Location

Royal Melbourne Hospital

Melbourne, 3050, Australia

Location

Mater Hospital Brisbane

South Brisbane, 4101, Australia

Location

Westmead Hospital

Sydney, 2145, Australia

Location

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

Porto Alegre, 90610-000, Brazil

Location

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

Ribeirão Preto, 14015-130, Brazil

Location

Hospital Sirio Libanes

São Paulo, 01308-050, Brazil

Location

Hospital Alemão Oswaldo Cruz

São Paulo, 01421-000, Brazil

Location

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

São Paulo, 05403-000, Brazil

Location

MHAT 'Sv. Ivan Rilski' Kozloduy EOOD

Kozloduy, 3320, Bulgaria

Location

Specialized Hospital for Active Treatment of Pulmonary Diseases - Pernik

Pernik, 2000, Bulgaria

Location

Specialized Hospital for Active Treatment of Pulmonary Diseases - Troyan EOOD

Troyan Municipality, 5600, Bulgaria

Location

MHAT Dr Stefan Cherkezov

Veliko Tarnovo, 5000, Bulgaria

Location

CHU Rouen

Bois-Guillaume, 76230, France

Location

CHU caen

Caen, 14033, France

Location

Hôpital Louis Mourier

Colombes, 92700, France

Location

APHP - Hopital Henri Mondor

Créteil, 94000, France

Location

CHU Dijon

Dijon, 21079, France

Location

CHU Grenoble

La Tronche, 38700, France

Location

CHU Nîmes

Nîmes, 30900, France

Location

Hopital Saint-Louis

Paris, 75010, France

Location

Hôpital Tenon

Paris, 75020, France

Location

CHU la milétrie

Poitiers, 86021, France

Location

CHU Saint-etienne

Saint-Priest-en-Jarez, 42270, France

Location

Hopital Foch

Suresnes, 92150, France

Location

Centre Hospitalier Universitaire de Tours

Tours, 37044, France

Location

Fukuoka University Hospital

Fukuoka, 814-0180, Japan

Location

National Hospital Organization Ibarakihigashi

Funaishikawa, 319-1113, Japan

Location

Ogaki Municipal Hospital

Gifu, 503-8502, Japan

Location

National Hospital Organization Tenryu Hospital

Hamamatue, 434-8511, Japan

Location

Japanese Red Cross Nagasaki Genbaku Isahaya Hospital

Isahaya, 859-0497, Japan

Location

Shimane University Hospital

Izumo, 693-8501, Japan

Location

Shinkomonji hospital

Kitakyushu, 800-0057, Japan

Location

Kobe City Medical Center General Hospital

Kobe, 650-0047, Japan

Location

Japanese Red Cross Society Nagano Hospital

Nagano, 380-8582, Japan

Location

Nagasaki University Hospital

Nagasaki, 852-8501, Japan

Location

National Hospital Organization Higashinagoya National Hospital

Nagoya, 465-8620, Japan

Location

Rinku General Medical Center

Osaka, 598-8577, Japan

Location

SUBARU Health Insurance Society Ota Memorial Hospital

Ōta-ku, 373-8585, Japan

Location

Tohoku Medical And Pharmaceutical University Hospital

Sendai, 983-8512, Japan

Location

Saka General Hospital

Shiogama, 985-8506, Japan

Location

National Hospital Organization Tokyo National Hospital

Tokyo, 204-8585, Japan

Location

Okinawa Prefectural Chubu Hospital

Uruma, 904-2293, Japan

Location

Okitama Public General Hospital

Yamagata, 992-0601, Japan

Location

Shimonoseki City Hospital

Yamaguchi, 750-0041, Japan

Location

Shin Yukuhashi Hospital

Yukuhashi, 824-0026, Japan

Location

Hospital Sultanah Bahiyah

Alor Star, 5460, Malaysia

Location

Hospital Pulau Pinang

George Town, 10990, Malaysia

Location

Hospital Raja Perempuan Zainab Ii

Kota Bharu, 15586, Malaysia

Location

University Malaya Medical Centre

Kuala Lumpur, 59120, Malaysia

Location

Sarawak General Hospital

Kuching, 93586, Malaysia

Location

Hospital Miri

Miri, 98000, Malaysia

Location

Hospital Taiping

Taiping, 34000, Malaysia

Location

UMCG

Groningen, 9713 GZ, Netherlands

Location

UMC Utrecht

Utrecht, 3584 CX, Netherlands

Location

Gelre Ziekenhuizen Zutphen

Zutphen, 7207 AE, Netherlands

Location

10 Wojskowy Szpital Kliniczny z Poliklinika

Bydgoszcz, 85-681, Poland

Location

Wojewódzki Szpital Specjalistyczny im. św. Rafała w Czerwonej Górze

Chęciny, 26-060, Poland

Location

SSZZOZ im. dr Teodora Dunina w Rudce

Mrozy, 05-320, Poland

Location

Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc w Olsztynie

Olsztyn, 10-357, Poland

Location

Samodzielny Publiczny Zespół Opieki Zdrowotnej w Proszowicach

Proszowice, 32-100, Poland

Location

State Health Care Institution 'Engels city hospital #2'

Engel's, 413124, Russia

Location

Saint-Petersburg State Health Care Institution 'Vvedenskaya Hospital'

Saint Petersburg, 191180, Russia

Location

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

Saint Petersburg, 195067, Russia

Location

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

Saint Petersburg, 196247, Russia

Location

Regional State Health Care Institution 'Clinical Hospital #1'

Smolensk, 214006, Russia

Location

Siberian State Medical University

Tomsk, 634050, Russia

Location

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

Voronezh, 394006, Russia

Location

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

Yaroslavl, 150003, Russia

Location

Soonchunhyang University Bucheon Hospital

Bucheon-si, 14584, South Korea

Location

Yeungnam University Medical Center

Daegu, 42415, South Korea

Location

Gachon University Gil Hospital

Incheon, 21565, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, 13620, South Korea

Location

Kangnam Sacred Heart Hospital

Seoul, 07441, South Korea

Location

Korea University Guro Hospital

Seoul, 08308, South Korea

Location

Hosp. Gral. Univ. de Elche

Elche, 03203, Spain

Location

Hosp. Univ. de La Princesa

Madrid, 28006, Spain

Location

Hosp. Univ. 12 de Octubre

Madrid, 28041, Spain

Location

Hosp. Univ. La Paz

Madrid, 28046, Spain

Location

Hosp. Clinico Univ. de Santiago

Santiago de Compostela, 15706, Spain

Location

Hosp. Alvaro Cunqueiro

Vigo, 36312, Spain

Location

Sahlgrenska University Hospital

Gothenburg, 41685, Sweden

Location

Skanes universitetssjukhus

Malmo, 20502, Sweden

Location

Norrlands Universitetssjukhus

Umeå, 90185, Sweden

Location

Akademiska Sjukhuset

Uppsala, 75185, Sweden

Location

Kaohsiung Veterans General Hospital

Kaohsiung City, 81362, Taiwan

Location

Far Eastern Memorial Hospital

New Taipei City, 22060, Taiwan

Location

Taipei Medical University Shuang Ho Hospital

New Taipei City, 23561, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

Taipei Municipal Wanfang Hospital

Taipei, 11696, Taiwan

Location

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

Chernivtsi, 58000, Ukraine

Location

Ivano-Frankivsk Regional Clinical Hospital

Ivano-Frankivsk, 76006, Ukraine

Location

Kharkiv National Medical University, Regional Clinical Infectious Hospital

Kharkiv, 61000, Ukraine

Location

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

Vinnytsia, 21021, Ukraine

Location

MeSH Terms

Interventions

4'-chloromethyl-2'-deoxy-3',5'-di-O-isobutyryl-2'-fluorocytidine

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2018
• First Posted: April 19, 2018
• Study Start: November 5, 2018
• Primary Completion: April 30, 2019
• Study Completion: October 28, 2020
• Last Updated: November 15, 2018

Record last verified: 2018-11

Locations

UA (4); RU (8); KR (6); NL (3); PL (5); TW (5); BU (4); MY (7); JP (20); ES (6); US (7); BR (5); SE (4); AR (8); FR (13); AU (7)