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

NCT02935673 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: CR1082172016-001653-4064041575RSV2003
• Study Type: interventional
• Target: 49
• Locations: 19 countries
• Sites: 109

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.

Conditions

Respiratory Syncytial Viruses

Outcome Measures

Primary Outcomes (7)

• Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 at Day 1

  Cmax is the maximum observed plasma concentration of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.

  Day 1

• Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 at Day 5

  Cmax is the maximum observed plasma concentration of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.

  Day 5

• Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24h]) of JNJ-63549109 at Day 1

  AUC(0-24) is the area under the plasma concentration-time curve from time 0 to 24 hours after dosing of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.

  Day 1

• Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24h]) of JNJ-63549109 at Day 5

  AUC(0-24) is the area under the plasma concentration-time curve from time 0 to 24 hours after dosing of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.

  Day 5

• Trough Observed Plasma Concentration (Ctrough) of JNJ-63549109 at Day 1

  Ctrough is the trough observed plasma concentration of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.

  Day 1

• Trough Observed Plasma Concentration (Ctrough) of JNJ-63549109 at Day 5

  Ctrough is the trough observed plasma concentration of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.

  Day 5

• 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])

  RSV RNA viral load in log10 copies/milliliter/day (log10 copies/mL/day) was measured in mid-turbinate nasal swabs and in endotracheal samples (obtained from intubated participants or via suction through tracheostomy or other sampling methods) using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Due to early termination of study, the analysis was not conducted as planned. Instead, using the same specification as for the primary analysis, a comparison was made on the AUC(1-7) days of pooled active treatment groups versus pooled placebo. The comparison was done as planned using a mixed model for repeated measures, using all available viral load data of baseline up to and including Day 7. The model computes the AUC at group level based on all available data, taking missing data into account under the missing at random assumption. The table reports the planned difference versus (pooled) placebo. No adjustment for multiplicity was applied.

  Day 1 (Baseline) to 7

Secondary Outcomes (34)

• Number of Participants With Adverse Events (AEs)

  Up to 28 Days

• Number of Participants With Vital Sign Abnormalities

  Up to 28 Days

• Number of Participants With QT Interval Abnormalities

  Up to 28 Days

• Number of Participants With Clinical Laboratory Abnormalities

  Up to 28 Days

• Time of Hospital Stay From Study Treatment Initiation to Discharge

  From study treatment initiation to discharge (Up to 28 Days)

Study Arms (3)

Regimen A (Placebo)

EXPERIMENTAL

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.

Drug: Placebo

Regimen B (low-dose lumicitabine)

EXPERIMENTAL

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.

Drug: lumicitabine

Regimen C (High-dose lumicitabine)

EXPERIMENTAL

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.

Drug: lumicitabine

Interventions

lumicitabine DRUG

Oral administration of lumicitabine as tablet.

Also known as: ALS-8176/JNJ-64041575

Regimen B (low-dose lumicitabine); Regimen C (High-dose lumicitabine)

Placebo DRUG

Oral administration of matching placebo.

Regimen A (Placebo)

Eligibility Criteria

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

You may qualify if:

• 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

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 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (109)

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Fresno, California, United States

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Orange, California, United States

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Stanford, California, United States

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Eustis, Florida, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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St Louis, Missouri, United States

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Butte, Montana, United States

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Rochester, New York, United States

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Syracuse, New York, United States

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Bahía Blanca, Argentina

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Barrio Parque Velez Sarfield, Argentina

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Buenos Aires, Argentina

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Ciudad de Buenos Aires, Argentina

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Ciudad de La Plata, Argentina

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Córdoba, Argentina

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La Plata, Argentina

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Rosario, Argentina

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Cairns, Australia

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Geelong, Australia

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Melbourne, Australia

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South Brisbane, Australia

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Sydney, Australia

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Bruges, Belgium

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Lier, Belgium

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Belo Horizonte, Brazil

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Passo Fundo, Brazil

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Porto Alegre, Brazil

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Ribeirão Preto, Brazil

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São Paulo, Brazil

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Kozloduy, Bulgaria

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Petrich, Bulgaria

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Rousse, Bulgaria

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Sofia, Bulgaria

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Veliko Tarnovo, Bulgaria

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Hamilton, Ontario, Canada

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Toronto, Ontario, Canada

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Colombes, France

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Dijon, France

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La Tronche, France

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Limoges, France

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Lyon, France

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Morlaix, France

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Nantes, France

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Paris, France

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Poitiers, France

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Suresnes, France

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Tours, France

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Marburg, Germany

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Witten, Germany

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Fukuoka, Japan

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Fukushima, Japan

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Funaishikawa, Japan

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Gifu, Japan

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Gunma, Japan

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Hamamatue, Japan

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Isahaya, Japan

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Izumo, Japan

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Kitakyushu, Japan

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Kobe, Japan

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Nagasaki, Japan

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Nagoya, Japan

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Osaka, Japan

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Ōta-ku, Japan

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Sendai, Japan

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Seto, Japan

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Shiogama, Japan

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Tanabe, Japan

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Tokyo, Japan

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Tsu, Japan

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Uruma, Japan

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Johor Bharu, Malaysia

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Kuala, Malaysia

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Kuala Lumpur, Malaysia

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Kuching, Malaysia

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Malacca, Malaysia

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Miri, Malaysia

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Taiping, Malaysia

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Cuernavaca, Mexico

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Guadalajara, Mexico

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México, Mexico

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Monterrey, Mexico

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Leiden, Netherlands

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Utrecht, Netherlands

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Bialystok, Poland

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Chęciny, Poland

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Mrozy, Poland

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Proszowice, Poland

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Bucheon-si, South Korea

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Daegu, South Korea

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Gwangju, South Korea

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Incheon, South Korea

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Seongnam, South Korea

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Seoul, South Korea

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Elche, Spain

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Granada, Spain

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Madrid, Spain

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Santiago de Compostela, Spain

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Vigo, Spain

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Gothenburg, Sweden

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Malmo, Sweden

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Umeå, Sweden

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Uppsala, Sweden

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Kaohsiung City, Taiwan

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New Taipei City, Taiwan

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Tainan, Taiwan

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Taipei, Taiwan

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London, United Kingdom

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Southampton, United Kingdom

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Limitations and Caveats

As the study was stopped prematurely the planned final analyses were adapted. Due to small number of participants in Part 2, it was decided to pool the data from the 3 parts of the study to perform an evaluation of selected planned analyses only.

Results Point of Contact

• Title: Medical Leader
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: October 14, 2016
• First Posted: October 17, 2016
• Study Start: October 25, 2016
• Primary Completion: July 17, 2018
• Study Completion: July 17, 2018
• Last Updated: December 24, 2019
• Results First Posted: December 24, 2019

Record last verified: 2019-12

Locations

ES (5); NL (2); KR (6); PL (4); BU (5); AU (5); AR (8); MY (7); SE (4); BR (5); ME (4); FR (11); US (10); DE (2); BE (2); GB (2); JP (21); CA (2); TW (4)