Clinical trial NCT02935673: 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
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 Regimens in Adult Subjects Hospitalized With Respiratory Syncytial Virus
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Respiratory Syncytial Viruses
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2016-10-17
Enrollment: 49
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 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.

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

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 at Day 1
timeFrame: Day 1
measure: Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 at Day 5
timeFrame: Day 5
measure: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24h]) of JNJ-63549109 at Day 1
timeFrame: Day 1
measure: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24h]) of JNJ-63549109 at Day 5
timeFrame: Day 5
measure: Trough Observed Plasma Concentration (Ctrough) of JNJ-63549109 at Day 1
timeFrame: Day 1
measure: Trough Observed Plasma Concentration (Ctrough) of JNJ-63549109 at Day 5
timeFrame: Day 5
measure: Least Square Mean Difference (Low and High Dose Lumicitabine Versus Placebo) of Respiratory Syncytial Virus (RSV) Ribonucleic Acid (RNA) Viral Load Area Under the Concentration-time Curve From Day 1 to 7 (AUC[1-7])
timeFrame: Day 1 (Baseline) to 7
Secondary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to 28 Days
measure: Number of Participants With Vital Sign Abnormalities
timeFrame: Up to 28 Days
measure: Number of Participants With QT Interval Abnormalities
timeFrame: Up to 28 Days
measure: Number of Participants With Clinical Laboratory Abnormalities
timeFrame: Up to 28 Days
measure: Time of Hospital Stay From Study Treatment Initiation to Discharge
timeFrame: From study treatment initiation to discharge (Up to 28 Days)
measure: Time of Hospital Stay From Admission to Discharge
timeFrame: From admission to discharge (Up to 28 Days)
measure: Time of Hospital Stay From Study Treatment Initiation to Readiness for Discharge
timeFrame: From study treatment initiation to readiness for discharge on Day 2 or up to Day 6 if hospitalization is prolonged
measure: Time of Hospital Stay From Admission to Readiness for Discharge
timeFrame: Up to 28 Days
measure: Number of Participants Who Required to be Admitted to the Intensive Care Unit (ICU) Since Initiation of Treatment
timeFrame: Up to 28 Days
measure: Duration of Intensive Care Unit Stay
timeFrame: Up to 28 Days
measure: Number of Participants Who Required Supplemental Oxygen
timeFrame: Up to 28 Days
measure: Time to End of Oxygen Supplementation
timeFrame: Up to 28 Days
measure: Time (Number of Hours) Until Peripheral Capillary Oxygen Saturation (SpO2) Greater Than or Equal to (>=) 93 Percent (%) on Room Air Among Participants Who Were Not on Supplemental Oxygen Prior to the Onset of Respiratory Symptoms
timeFrame: Up to 28 Days
measure: Time to Return to Pre-respiratory Syncytial Virus (Pre-RSV) Disease Level for Respiratory Rate
timeFrame: Up to 28 Days
measure: Time to Return to Pre-RSV Disease Level for Oxygen Saturation
timeFrame: Up to 28 Days
measure: Time to Return to Pre-RSV Disease Level for Body Temperature
timeFrame: Up to 28 Days
measure: Number of Participants Who Required Noninvasive Mechanical Ventilation Support
timeFrame: Up to 28 Days
measure: Time to End of Noninvasive Mechanical Ventilation Support
timeFrame: Up to 28 Days
measure: Number of Participants Who Required Invasive Mechanical Ventilation Support
timeFrame: Up to 28 Days
measure: Time to End of Invasive Mechanical Ventilation Support
timeFrame: Up to 28 Days
measure: Time to Return to Pre-RSV Functional Status as Assessed by KATZ Activities of Daily Living (ADL) Score
timeFrame: Up to 28 Days
measure: Number of Participants Who Required Hydration or Feeding by Intravenous (IV) Catheter or Nasogastric Tube
timeFrame: Up to 28 Days
measure: Time to Clinical Stability
timeFrame: Up to 28 Days
measure: Number of Participants in Each Ordinal Scale Category
timeFrame: Day 5/6 (Day of last study treatment)
measure: Number of Participants With All-Cause Mortality
timeFrame: Up to 28 Days
measure: RSV RNA Viral Load Over Time
timeFrame: Days 2, 3, 4, 5, 6, 7, 10, 14, and 28
measure: Peak Viral Load
timeFrame: Up to 28 Days
measure: Time to Peak Viral Load
timeFrame: Up to 28 Days
measure: Rate of Decline of Viral Load
timeFrame: Up to 28 Days
measure: Time to RSV RNA Viral Load Being Undetectable
timeFrame: Up to 28 Days
measure: Number of Participants With Undetectable Viral Load
timeFrame: Up to 28 Days
measure: RSV RNA Viral Load AUC up to Day 14
timeFrame: Up to Day 14
measure: RSV RNA Viral Load AUC in Participants Assigned to a Longer Dosing Duration
timeFrame: Up to 1 Day after the last dose of study drug
measure: Number of Participants With Postbaseline Changes in the RSV Polymerase L Gene and Other Regions of the RSV Genome Compared With Baseline Sequences
timeFrame: Baseline up to 28 Days
Other outcomes:
Locations:
city: Fresno
country: United States
state: California
city: Orange
country: United States
state: California
city: Stanford
country: United States
state: California
city: Eustis
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Saint Louis
country: United States
state: Missouri
city: Butte
country: United States
state: Montana
city: Rochester
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Bahia Blanca
country: Argentina
city: Barrio Parque Velez Sarfield
country: Argentina
city: Buenos Aires
country: Argentina
city: Ciudad de Buenos Aires
country: Argentina
city: Ciudad De La Plata
country: Argentina
city: Cordoba
country: Argentina
city: Córdoba
country: Argentina
city: La Plata
country: Argentina
city: Rosario
country: Argentina
city: Cairns
country: Australia
city: Geelong
country: Australia
city: Melbourne
country: Australia
city: South Brisbane
country: Australia
city: Sydney
country: Australia
city: Brugge
country: Belgium
city: Lier
country: Belgium
city: Belo Horizonte
country: Brazil
city: Passo Fundo
country: Brazil
city: Porto Alegre
country: Brazil
city: Ribeirao Preto
country: Brazil
city: Sao Paulo
country: Brazil
city: Kozloduy
country: Bulgaria
city: Petrich
country: Bulgaria
city: Ruse
country: Bulgaria
city: Sofia
country: Bulgaria
city: Veliko Tarnovo
country: Bulgaria
city: Hamilton
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Colombes
country: France
city: Dijon
country: France
city: La Tronche
country: France
city: Limoges
country: France
city: Lyon
country: France
city: Morlaix
country: France
city: Nantes
country: France
city: Paris
country: France
city: Poitiers
country: France
city: Suresnes
country: France
city: Tours
country: France
city: Marburg
country: Germany
city: Witten
country: Germany
city: Fukuoka
country: Japan
city: Fukushima
country: Japan
city: Gifu
country: Japan
city: Gunma
country: Japan
city: Hamamatue
country: Japan
city: Isahaya
country: Japan
city: Izumo
country: Japan
city: Kitakyusyu
country: Japan
city: Kobe-city,
country: Japan
city: Nagasaki
country: Japan
city: Nagoya
country: Japan
city: Osaka
country: Japan
city: Ota
country: Japan
city: Sendai
country: Japan
city: Seto
country: Japan
city: Shiogama
country: Japan
city: Tanabe
country: Japan
city: Tokai-mura
country: Japan
city: Tokyo
country: Japan
city: Tsu
country: Japan
city: Uruma
country: Japan
city: Bucheon
country: Korea, Republic of
city: Daegu
country: Korea, Republic of
city: Gwangju
country: Korea, Republic of
city: Incheon
country: Korea, Republic of
city: Seongnam
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Johor Bharu
country: Malaysia
city: Kuala Lumpur
country: Malaysia
city: Kuala
country: Malaysia
city: Kuching
country: Malaysia
city: Melaka
country: Malaysia
city: Miri
country: Malaysia
city: Taiping
country: Malaysia
city: Cuernavaca
country: Mexico
city: Guadalajara
country: Mexico
city: Mexico
country: Mexico
city: Monterrey
country: Mexico
city: Leiden
country: Netherlands
city: Utrecht
country: Netherlands
city: Białystok
country: Poland
city: Chęciny
country: Poland
city: Mrozy
country: Poland
city: Proszowice
country: Poland
city: Elche
country: Spain
city: Granada
country: Spain
city: Madrid
country: Spain
city: Santiago de Compostela
country: Spain
city: Vigo
country: Spain
city: Göteborg
country: Sweden
city: Malmö
country: Sweden
city: Umeå
country: Sweden
city: Uppsala
country: Sweden
city: Kaohsiung
country: Taiwan
city: New Taipei
country: Taiwan
city: Tainan
country: Taiwan
city: Taipei
country: Taiwan
city: London
country: United Kingdom
city: Southampton
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: