Study to Evaluate the Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of Orally Administered Lumicitabine Regimens in Adult Participants Hospitalized With Respiratory Syncytial Virus

NCT ID: NCT02935673

Last Updated: 2019-12-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-25
• Study Completion Date: 2018-07-17

Brief Summary

The purpose of this study is to characterize the Pharmacokinetic and to confirm the popPK model derived from healthy volunteers in hospitalized adults who are infected with respiratory syncytial virus (RSV) and to determine in adults who are hospitalized with respiratory syncytial virus (RSV) infection the dose response relationship of multiple regimens of lumicitabine on antiviral activity based on nasal RSV shedding using quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) assay.

Detailed Description

The study will be conducted in 3 phases: a screening phase, a treatment phase from Day 1 to Day 5/6 (depending on the timing of the loading dose), and a follow-up phase for a total of 28 days post randomization. Participants will have assessments completed at Day 7, Day 10, Day 14, and Day 28. Depending on discharge date, assessments will be completed either while hospitalized or during outpatient visits. The duration of the participant's participation will be approximately 28 days. The study will be performed in 2 parts. Participants will be randomly assigned to one of 2 treatment groups in part 1, and to one of 3 treatment groups in part 2. Treatment groups will be evaluated for PK and safety after a target of approximately 24 participants have been enrolled in part 1 and before initiating part 2 (approximately 90 participants in part 2). An Independent Data Monitoring Committee (IDMC) will be established to monitor the safety of participants and will review data in an unblinded manner on a regular basis to ensure the continuing safety of the participants enrolled in this study and to evaluate whether efficacy objectives are met. The committee will meet periodically to review interim data. Based on the recommendations of the IDMC following interim analyses/reviews, an increase in duration may be implemented.

Conditions

Respiratory Syncytial Viruses

Study Design

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

Study Groups

Regimen A (Placebo)

Participants of part 1 and part 2 will receive a single loading dose (LD) (Dose 1) followed by 9 maintenance doses (MDs) (Doses 2 to 10) of matching placebo, administered twice daily.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Oral administration of matching placebo.

Regimen B (low-dose lumicitabine)

Participants of part 1 and part 2 will receive a single 750 mg LD (Dose 1) followed by nine 250 mg MDs (Doses 2 to 10) of lumicitabine, administered twice daily.

Group Type: EXPERIMENTAL

lumicitabine

Intervention Type: DRUG

Oral administration of lumicitabine as tablet.

Regimen C (High-dose lumicitabine)

Participants of part 2 will receive a single 1000 mg LD (Dose 1) followed by nine 500 mg MDs (Doses 2 to 10) of lumicitabine, administered twice daily.

Group Type: EXPERIMENTAL

lumicitabine

Intervention Type: DRUG

Oral administration of lumicitabine as tablet.

Interventions

lumicitabine

Oral administration of lumicitabine as tablet.

Intervention Type: DRUG

Placebo

Oral administration of matching placebo.

Intervention Type: DRUG

Other Intervention Names

ALS-8176/JNJ-64041575

Eligibility Criteria

Inclusion Criteria

• 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
• Diagnosed with respiratory syncytial virus (RSV) infection based on polymerase chain reaction (PCR)-based assay with or without co infection with another respiratory pathogen (eg, influenza, human metapneumovirus, or bacteria)
• With the exception of the RSV disease, medically stable on the basis of medical history, physical examination, 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 RSV infection. This determination must be recorded in the participant's source documents and initialed by the investigator
• A woman must have a negative urine beta human chorionic gonadotropin at screening
• A woman must agree not to donate eggs (ova, oocytes) during the study and for at least 44 days after receiving the last dose of study drug
• Contraceptive use by women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies A woman must be of non-childbearing potential defined as either: a) Postmenopausal: a postmenopausal state is defined as more than (>) 45 years and no menses for 12 consecutive months without an alternative medical cause, OR Permanently sterile: permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures (without reversal operation), and bilateral oophorectomy. b) Of childbearing potential and, if heterosexually active, also included: practicing a highly effective method of contraception (failure rate of less than (<) 1percent (%) per year when used consistently and correctly)
• Participants must have a body weight of at least 50.0 kilogram, 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 immuno-compromised within the past 12 months, whether due to underlying medical condition (example, malignancy or genetic disorder) or medical therapy (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 with a known history of human immunodeficiency virus (HIV) or chronic viral hepatitis
• 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 1 or more of the following laboratory abnormalities at screening as defined by the Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity Table: Hemoglobin <9.5 gram per deciliter (g/dL), Platelet count <75,000 per millimeter cube (/mm^³), White blood cell count <1,000/mm^³, Absolute neutrophil count <1,000/mm^³

• 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

Fresno, California, United States

Orange, California, United States

Stanford, California, United States

Eustis, Florida, United States

Atlanta, Georgia, United States

Chicago, Illinois, United States

St Louis, Missouri, United States

Butte, Montana, United States

Rochester, New York, United States

Syracuse, New York, United States

Bahía Blanca, , Argentina

Barrio Parque Velez Sarfield, , Argentina

Buenos Aires, , Argentina

Ciudad de Buenos Aires, , Argentina

Ciudad de La Plata, , Argentina

Córdoba, , Argentina

La Plata, , Argentina

Rosario, , Argentina

Cairns, , Australia

Geelong, , Australia

Melbourne, , Australia

South Brisbane, , Australia

Sydney, , Australia

Bruges, , Belgium

Lier, , Belgium

Belo Horizonte, , Brazil

Passo Fundo, , Brazil

Porto Alegre, , Brazil

Ribeirão Preto, , Brazil

São Paulo, , Brazil

Kozloduy, , Bulgaria

Petrich, , Bulgaria

Rousse, , Bulgaria

Sofia, , Bulgaria

Veliko Tarnovo, , Bulgaria

Hamilton, Ontario, Canada

Toronto, Ontario, Canada

Colombes, , France

Dijon, , France

La Tronche, , France

Limoges, , France

Lyon, , France

Morlaix, , France

Nantes, , France

Paris, , France

Poitiers, , France

Suresnes, , France

Tours, , France

Marburg, , Germany

Witten, , Germany

Fukuoka, , Japan

Fukushima, , Japan

Funaishikawa, , Japan

Gifu, , Japan

Gunma, , Japan

Hamamatue, , Japan

Isahaya, , Japan

Izumo, , Japan

Kitakyushu, , Japan

Kobe, , Japan

Nagasaki, , Japan

Nagoya, , Japan

Osaka, , Japan

Ōta-ku, , Japan

Sendai, , Japan

Seto, , Japan

Shiogama, , Japan

Tanabe, , Japan

Tokyo, , Japan

Tsu, , Japan

Uruma, , Japan

Johor Bharu, , Malaysia

Kuala, , Malaysia

Kuala Lumpur, , Malaysia

Kuching, , Malaysia

Malacca, , Malaysia

Miri, , Malaysia

Taiping, , Malaysia

Cuernavaca, , Mexico

Guadalajara, , Mexico

México, , Mexico

Monterrey, , Mexico

Leiden, , Netherlands

Utrecht, , Netherlands

Bialystok, , Poland

Chęciny, , Poland

Mrozy, , Poland

Proszowice, , Poland

Bucheon-si, , South Korea

Daegu, , South Korea

Gwangju, , South Korea

Incheon, , South Korea

Seongnam, , South Korea

Seoul, , South Korea

Elche, , Spain

Granada, , Spain

Madrid, , Spain

Santiago de Compostela, , Spain

Vigo, , Spain

Gothenburg, , Sweden

Malmo, , Sweden

Umeå, , Sweden

Uppsala, , Sweden

Kaohsiung City, , Taiwan

New Taipei City, , Taiwan

Tainan City, , Taiwan

Taipei, , Taiwan

London, , United Kingdom

Southampton, , United Kingdom

Countries

United States; Argentina; Australia; Belgium; Brazil; Bulgaria; Canada; France; Germany; Japan; Malaysia; Mexico; Netherlands; Poland; South Korea; Spain; Sweden; Taiwan; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-001653-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

64041575RSV2003

Identifier Type: OTHER

Identifier Source: secondary_id

CR108217

Identifier Type: -

Identifier Source: org_study_id