Clinical trial NCT02342249: Study of Acute Uncomplicated Seasonal Influenza A in Adult Subjects
Official title: A Phase 2b, Randomized, Double-Blind, Placebo Controlled, Parallel-Group, Multicenter Study of 2 Dose Levels of VX 787 Administered as Monotherapy and One Dose Level of VX-787 Administered in Combination With Oseltamivir for the Treatment of Acute Uncomplicated Seasonal Influenza A in Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza A
Keywords: Influenza A
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
Collaborators: name: Janssen Pharmaceuticals
First posted: 2015-01-19
Enrollment: 292
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the antiviral effect, as measured by viral titer in nasal secretions in adults with acute uncomplicated seasonal influenza A following administration of VX-787.


Eligibility criteria: Inclusion Criteria: Part A

1. Willing and able to comply with the NP swab procedure
2. Subject will sign and date an informed consent form (ICF)
3. Presenting to the clinic with symptoms suggestive of a diagnosis of acute influenza. Symptoms include oral temperature ≥38°C (100.4°F) within the prior 24 hours, at least 1 respiratory symptom AND at least 1 systemic symptom.
4. Understand that no study treatment will be provided to subjects in Part A but that they are free to receive any treatment considered appropriate by their physician

Part B

1. Willing and able to comply with study requirements including treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures
2. Subject will sign and date an ICF
3. Present to the clinic with symptoms suggestive of a diagnosis of acute influenza. Symptoms include documented oral temperature ≥38°C (100.4°F) any time during the screening process, at least 1 respiratory symptom AND at least 1 systemic symptom, both scored as at least "moderate".
4. The time of onset of flu-like symptoms to the time anticipated for the start of treatment must be ≤48 hours. Onset of symptoms is defined as the first time (within 1 hour) the subject becomes aware of respiratory or systemic symptoms compatible with the flu or experiences an oral temperature ≥38°C (100.4°F)
5. Positive Rapid Influenza Diagnostic Test for influenza type A
6. Body mass index (BMI) of 18.0 to 33.0 kg/m2, inclusive, and a total body weight \>50 kg

Exclusion Criteria: Part B

1. History of any illness or any clinical condition that, in the opinion of the investigator or the subject's general practitioner, might confound the results of the study or pose an additional risk in administering study drug(s) to the subject.
2. Any condition possibly affecting drug absorption (e.g., gastrectomy, cholecystectomy, or other gastrointestinal tract surgery, except appendectomy).
3. Immunized (intranasal or injected vaccine) against influenza in the 6 months before study entry.
4. At Screening, an ECG that is abnormal and deemed by the investigator(s) to be clinically significant.
5. For female subjects: Pregnant or nursing subjects and female subjects of childbearing potential who are unwilling or unable to use an acceptable method of contraception as outlined in this protocol.
6. For male subjects, unwilling to comply with contraception requirements as outlined in the study protocol.
7. Blood donation (of approximately 1 pint \[500 mL\] or more) within 56 days before the first study drug dose.
8. Use of the following medications:

   * Influenza antiviral medication (oseltamivir, zanamivir, rimantidine, or amantadine) within 14 days or ribavirin within 6 months of screening.
   * Substrates of OATP1B1 and/or OATP1B3, including atrasentan, bosentan, ezetimibe, glyburide, irinotecan, repaglinide, rifampin, telmisartan, valsartan, and olmesartan, from Day 1 through the last dose of study drug. "Statins" (i.e., HMG CoA reductase inhibitors) may be continued, but subjects should be cautioned and observed for potential "statin"-related toxicity. Alternatively, subjects can abstain from statins for the duration of study drug dosing.
   * Strong inhibitors or inducers of CYP3A metabolism, including carbamazepine, clarithromycin, HIV and HCV protease inhibitors, itraconazole, ketoconazole, nefazodone, phenytoin, posaconazole, rifampin, St. John's wort, telithromycin, and voriconazole from 2 weeks prior to the first dose of study drug until the last PK sample is collected on Day 8.
   * An investigational drug or device 30 days before the first dose of study drug, 5 half lives before the first dose of study drug, or time determined by local requirements, whichever is longest.
9. History of excessive alcohol consumption.
10. History of known or current usage of drugs of abuse.
11. Hospitalized subjects and subjects with bacterial infections requiring systemic antibacterial agents at the time of screening.

Primary outcomes:
measure: Area under the curve (AUC) of the log10 Nasal Viral Load on Day 8
timeFrame: Day 8
Secondary outcomes:
measure: Time to Resolution of Influenza Symptoms After Initiation of Study Drug
timeFrame: Baseline up to Day 14
measure: Safety and tolerability based on assessment of adverse events, clinical laboratory assessments, 12-lead electrocardiograms (ECGs), and vital signs
timeFrame: Day 14
measure: Antiviral effect and viral kinetics composite
timeFrame: Days 1 - 8
measure: Clinical composite symptom scores
timeFrame: Day 14
measure: Pharmacokinetic parameters of VX787, as determined by population analysis
timeFrame: Day 14
measure: Viral sequence analysis to monitor for emergence of viral variants resistant to VX 787 and to oseltamivir
timeFrame: Day 14
Other outcomes:
Locations:
city: Athens
country: United States
state: Alabama
city: Birmingham
country: United States
state: Alabama
city: Gulf Shores
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state: Alabama
city: Huntsville
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state: Alabama
city: Scottsboro
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state: Alabama
city: Harrisburg
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state: Arkansas
city: Phoenix
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state: Arkansas
city: Anaheim
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state: California
city: Burbank
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state: California
city: Canoga Park
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state: California
city: Chula Vista
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city: Encino
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city: Fresno
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city: Huntington Beach
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city: La Mesa
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city: Lomita
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state: California
city: Long Beach
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city: Norwalk
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city: Oakland
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city: Oceanside
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city: Paramount
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city: San Diego
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city: Santa Monica
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city: Clearwater
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city: Coral Gables
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city: New Port Richey
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city: Pembroke Pines
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city: Worcester
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city: Niles
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city: Troy
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city: Saint Louis
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city: Fremont
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city: Berlin
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city: Brooklyn
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city: Rochester
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city: Rosedale
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state: New York
city: Advance
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state: North Carolina
city: Hickory
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city: Morehead City
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city: Morganton
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city: Salisbury
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city: Dayton
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state: Rhode Island
city: Johnston
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city: Greer
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city: Laurens
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city: Mount Pleasant
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city: Rock Hill
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city: Simpsonville
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city: Rapid City
country: United States
state: South Dakota
city: Bristol
country: United States
state: Tennessee
city: Amarillo
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city: Arlington
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state: Texas
city: Austin
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city: Baytown
country: United States
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city: Carrollton
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city: Corpus Christi
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Humble
country: United States
state: Texas
city: Katy
country: United States
state: Texas
city: Plano
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Tomball
country: United States
state: Texas
city: Clinton
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: South Jordan
country: United States
state: Utah
city: Alexandria
country: United States
state: Virginia
city: La Crosse
country: United States
state: Wisconsin
city: Milwaukee
country: United States
state: Wisconsin
city: Borgerhout
country: Belgium
city: Linkebeek
country: Belgium
city: Massemen
country: Belgium
city: Wichelen
country: Belgium
city: Sofia
country: Bulgaria
city: Veliko Turnovo
country: Bulgaria
city: Calgary
country: Canada
state: Alberta
city: West Vancouver
country: Canada
state: British Columbia
city: Mount Pearl
country: Canada
state: Newfoundland and Labrador
city: Brampton
country: Canada
state: Ontario
city: NewMarket
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Mirabel
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Saint-Jerome
country: Canada
state: Quebec
city: Trois-Rivières
country: Canada
state: Quebec
city: Paide
country: Estonia
city: Saku
country: Estonia
city: Tallinn
country: Estonia
city: Tartu
country: Estonia
city: Voru
country: Estonia
city: Berlin
country: Germany
city: Essen
country: Germany
city: Goch
country: Germany
city: Hamburg
country: Germany
city: Stuhr
country: Germany
city: Balvi
country: Latvia
city: Daugavpils
country: Latvia
city: Jekabpils
country: Latvia
city: Jelgava
country: Latvia
city: Kuldiga
country: Latvia
city: Lielvarde
country: Latvia
city: Riga
country: Latvia
city: Toa Baja
country: Puerto Rico
city: Boksburg
country: South Africa
city: Breyten
country: South Africa
city: Cape Town
country: South Africa
city: Durban
country: South Africa
city: Johannesburg
country: South Africa
city: Kempton Park
country: South Africa
city: Krugersdorp
country: South Africa
city: Middelburg
country: South Africa
city: Moloto
country: South Africa
city: Pretoria
country: South Africa
city: Thabazimbi
country: South Africa
city: Van Der Bijl Park
country: South Africa
city: Worcester
country: South Africa
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Finberg RW, Lanno R, Anderson D, Fleischhackl R, van Duijnhoven W, Kauffman RS, Kosoglou T, Vingerhoets J, Leopold L. Phase 2b Study of Pimodivir (JNJ-63623872) as Monotherapy or in Combination With Oseltamivir for Treatment of Acute Uncomplicated Seasonal Influenza A: TOPAZ Trial. J Infect Dis. 2019 Mar 15;219(7):1026-1034. doi: 10.1093/infdis/jiy547.