Clinical trial NCT02532283: A Study to Evaluate the Pharmacokinetics, Safety, and Antiviral Activity of JNJ-63623872 in Combination With Oseltamivir in Adult, and Elderly Hospitalized Participants With Influenza A Infection
Official title: A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Pharmacokinetics, Safety, and Antiviral Activity of JNJ-63623872 in Combination With Oseltamivir in Adult and Elderly Hospitalized Patients With Influenza A Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza A Virus
Keywords: Influenza A virus
JNJ-63623872
Oseltamivir
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2015-08-25
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
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 evaluate the Pharmacokinetic parameters of JNJ-63623872 in combination with oseltamivir in elderly participants (aged 65 to \<= 85 years) compared to adults (aged 18 to \<= 64 years) with influenza A infection.

Detailed description: This is a randomized (study medication assigned to participants by chance), double-blind (neither the researchers nor the participants know what treatment the participant is receiving), placebo-controlled, multicenter (when more than one hospital or medical school team work on a medical research study) study to evaluate the effect of JNJ-63623872 in combination with oseltamivir in participants with influenza A infection. The study consists of 3 Phases: Screening visit (1 Day), participants who meet all eligibility criteria will be randomized in a 2:1 ratio to receive study drug in double-blind treatment Phase (7 Days) and follow up Phase (21 Days). The duration of participation in the study for each participant is approximately 28 Days. Primarily Pharmacokinetic parameters of JNJ-63623872 will be measured. Participants' safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Participant requires hospitalization to treat influenza infection and/or to treat complications of influenza infection
* Participant tested positive for influenza A infection within 1 day of signing of the informed consent form (ICF)/assent form using a polymerase chain reaction (PCR)-based rapid molecular diagnostic assay
* Participants must be capable of swallowing study medication tablets and capsules
* Each participant (or their legally acceptable representative) must sign an ICF indicating that he or she understands the purpose of and procedures required for the study and is willing to participate in the study
* Participant must be willing and able to adhere to the prohibitions and restrictions specified in the protocol

Exclusion Criteria:

* Participant received more than 3 doses of the influenza antiviral medication oseltamivir, zanamivir, or peramivir since the start of the influenza symptoms, or ribavirin within 6 months prior to Screening
* Participant is unwilling to undergo regular nasal Mid-turbinate (MT) swabs or has any physical abnormality which limits the ability to collect regular nasal specimens
* Participant is immunocompromised, whether due to underlying medical condition (example, malignancy) or medical therapy (example, medications, chemotherapy, radiation, post-transplant)
* Participant is undergoing peritoneal dialysis, hemodialysis, or hemofiltration
* Participant has an estimated glomerular filtration rate (eGFR) less than or equal to (\<=)30 milliliter (mL)/minute (min)/1.73 meter\^2 (m\^2) according to the Modification of Diet in Renal Disease (MDRD) equation, assessed at Screening or based on the most recent clinically relevant creatinine value if available

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Pimodivir
timeFrame: Pre-dose, 1, 2, 4, 6, 8, 10 and 12 hours post-dose on Day 3
measure: Minimum Observed Plasma Concentration (Cmin) of Pimodivir
timeFrame: Pre-dose, 1, 2, 4, 6, 8, 10 and 12 hours post-dose on Day 3
measure: Area Under the Plasma Concentration-time Curve From Time of Administration to 12 Hours After Dosing (AUC [0-12]) of Pimodivir
timeFrame: Pre-dose, 1, 2, 4, 6, 8, 10 and 12 hours post-dose on Day 3
Secondary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious AEs (TESAEs)
timeFrame: Up to 28 Days
measure: Time to Influenza A Viral Negativity
timeFrame: Up to 14 Days
measure: Influenza Viral Load Over Time
timeFrame: Baseline, Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14
measure: Rate of Decline in Viral Load
timeFrame: Up to Day 7
measure: Area Under the Plasma Concentration-time Curve (AUC) of Viral Load
timeFrame: Baseline up to Day 8
measure: Percentage of Participants With Influenza Complications
timeFrame: Up to 28 Days
measure: Change From Baseline in Influenza Patient-Reported Outcome Questionnaire (FLU-PRO) Total Score
timeFrame: Baseline, Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, and 33
measure: Time to Improvement of Vital Signs
timeFrame: Up to 28 Days
measure: Time to Improvement of Respiratory Status
timeFrame: Up to 28 Days
measure: Percentage of Participants With Clinical Outcome Based on Ordinal Scale
timeFrame: Day 8
measure: Number of Participants With the Emergence of Drug Resistance Mutations With Oseltamivir (OST) and Pimodivir
timeFrame: Up to 28 Days
measure: Time to Return to Premorbid Functional Status
timeFrame: Up to Day 33
measure: Time to Hospital Discharge
timeFrame: Up to 28 Days
measure: Time to Return to Usual Health
timeFrame: Up to Day 33
measure: Time to Significant Reduction in FLU-PRO Influenza Symptom Severity
timeFrame: Up to Day 33
measure: Percentage of Participants With Significant Reduction in FLU-PRO All Influenza Symptoms (Mild or None for All Symptoms)
timeFrame: Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32 and 33
Other outcomes:
Locations:
city: Fresno
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Stanford
country: United States
state: California
city: Atlantis
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Detroit
country: United States
state: Michigan
city: Royal Oak
country: United States
state: Michigan
city: Troy
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Teaneck
country: United States
state: New Jersey
city: Winston-Salem
country: United States
state: North Carolina
city: Houston
country: United States
state: Texas
city: Cairns
country: Australia
city: South Brisbane
country: Australia
city: Westmead
country: Australia
city: Aalst
country: Belgium
city: Bruxelles
country: Belgium
city: Leuven
country: Belgium
city: Passo Fundo
country: Brazil
city: Porto Alegre
country: Brazil
city: Sao Paulo
country: Brazil
city: Hamilton
country: Canada
state: Ontario
city: Québec
country: Canada
state: Quebec
city: Dijon
country: France
city: Grenoble
country: France
city: Limoges
country: France
city: Lyon
country: France
city: Nantes
country: France
city: Paris
country: France
city: Poitiers
country: France
city: Rennes
country: France
city: Saint-Priest en Jarez
country: France
city: Tours Cedex 9
country: France
city: Donaustauf
country: Germany
city: Jena
country: Germany
city: Hong Kong
country: Hong Kong
city: Kota 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: Sungai Buloh
country: Malaysia
city: Taiping
country: Malaysia
city: Rotterdam
country: Netherlands
city: Utrecht
country: Netherlands
city: Zutphen
country: Netherlands
city: Hamilton
country: New Zealand
city: Singapore
country: Singapore
city: Alicante
country: Spain
city: Barcelona
country: Spain
city: Bizkaia
country: Spain
city: Elche
country: Spain
city: Granada
country: Spain
city: Madrid
country: Spain
city: Mataró
country: Spain
city: San Sebastián
country: Spain
city: Vigo
country: Spain
city: Malmö
country: Sweden
city: Umeå
country: Sweden
city: Uppsala
country: Sweden
city: Ankara
country: Turkey
city: Eskişehir
country: Turkey
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
city: Trabzon
country: Turkey
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: O'Neil B, Ison MG, Hallouin-Bernard MC, Nilsson AC, Torres A, Wilburn JM, van Duijnhoven W, Van Dromme I, Anderson D, Deleu S, Kosoglou T, Vingerhoets J, Rossenu S, Leopold L. A Phase 2 Study of Pimodivir (JNJ-63623872) in Combination With Oseltamivir in Elderly and Nonelderly Adults Hospitalized With Influenza A Infection: OPAL Study. J Infect Dis. 2022 Aug 12;226(1):109-118. doi: 10.1093/infdis/jiaa376.