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Study of Acute Uncomplicated Seasonal Influenza A in Adult Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02342249
Recruitment Status : Completed
First Posted : January 19, 2015
Last Update Posted : June 14, 2017
Sponsor:
Collaborator:
Janssen Pharmaceuticals
Information provided by (Responsible Party):
Janssen Research & Development, LLC

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.

Condition or disease Intervention/treatment Phase
Influenza A Drug: VX-787 300 mg Drug: VX-787 600 mg Drug: Oseltamivir 75 mg Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 292 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : December 11, 2014
Actual Primary Completion Date : May 25, 2016
Actual Study Completion Date : May 25, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot
Drug Information available for: Oseltamivir

Arm Intervention/treatment
Placebo Comparator: VX-787 Placebo BID + Oseltamivir Placebo BID
Subjects will receive 10 doses of matching placebo of VX-787 and Oseltamivir twice daily (BID) with approximately 12 hour (+/- 2) intervals, over 5-6 days.
Drug: Placebo
Subjects will receive matching placebo of Oseltamivir

Active Comparator: VX-787 300 mg BID + Oseltamivir Placebo BID
Subjects will receive 10 doses of VX-787 300 milligram (mg) tablet along with matching placebo of Oseltamivir twice daily (BID) with approximately 12 hour (+/- 2) intervals, over 5-6 days.
Drug: VX-787 300 mg
A oral dose of 300 mg VX-787 tablet will be administered over 5-6 days.
Other Name: JNJ-63623872

Drug: Placebo
Subjects will receive matching placebo of Oseltamivir

Active Comparator: VX-787 600 mg BID + Oseltamivir Placebo BID
Subjects will receive 10 doses of VX-787 600 mg (2*300 mg tablets) along with matching placebo of Oseltamivir twice daily (BID) with approximately 12 hour (+/- 2) intervals, over 5-6 days.
Drug: VX-787 600 mg
A oral dose of VX-787 600 mg (formulated as 2*300 mg tablets) will be administered over 5-6 days.
Other Name: JNJ-63623872

Drug: Placebo
Subjects will receive matching placebo of Oseltamivir

Active Comparator: VX-787 600 mg BID + Oseltamivir 75 mg BID
Subjects will receive 10 doses of VX-787 600 mg tablets (2*300 mg tablets) along with 75 mg Oseltamivir capsule twice daily (BID) with approximately 12 hour (+/- 2) intervals, over 5-6 days.
Drug: VX-787 600 mg
A oral dose of VX-787 600 mg (formulated as 2*300 mg tablets) will be administered over 5-6 days.
Other Name: JNJ-63623872

Drug: Oseltamivir 75 mg
A oral dose of 75 mg Oseltamivir capsule will be administered over 5-6 days.




Primary Outcome Measures :
  1. Area under the curve (AUC) of the log10 Nasal Viral Load on Day 8 [ Time Frame: Day 8 ]
    Area under the curve (AUC) of the log10 nasal viral load is measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).


Secondary Outcome Measures :
  1. Time to Resolution of Influenza Symptoms After Initiation of Study Drug [ Time Frame: Baseline up to Day 14 ]
    Estimated acceleration factors expressed as the ratio of the time to resolution of influenza symptoms as compared to placebo time to negativity. Resolution of influenza symptoms was the time of the first of 3 evaluations (over 24 hours) in which all symptom scores for each of the 3 assessments are 0 or 1 for all 7 primary influenza symptoms (cough, sore throat, headache, nasal stuffiness, feverishness or chills, muscle or joint pain, and fatigue) of the Flu-iiQ^TM. The Flu-iiQ^TM questionnaire consists of 4 modules, including 1 module assessing influenza symptoms, 1 module assessing the impact of influenza on normal functioning, and 2 modules assessing the impact of influenza on the subject's emotional state. The Influenza Symptom assessment (Module 1) is scored on a 4 point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe) for each of 10 influenza symptoms.

  2. Safety and tolerability based on assessment of adverse events, clinical laboratory assessments, 12-lead electrocardiograms (ECGs), and vital signs [ Time Frame: Day 14 ]
  3. Antiviral effect and viral kinetics composite [ Time Frame: Days 1 - 8 ]

    Antiviral effect and viral kinetics in relation to:

    • Duration of viral shedding in nasal secretions by qRT-PCR and viral culture
    • AUC of the log10 viral load measured by viral culture
    • Peak viral shedding titer by qRT-PCR and viral culture.

  4. Clinical composite symptom scores [ Time Frame: Day 14 ]

    Clinical symptom scores

    • Composite symptom score AUC
    • Time to peak of composite symptom score,
    • Duration and time to resolution of composite symptom score from peak

  5. Pharmacokinetic parameters of VX787, as determined by population analysis [ Time Frame: Day 14 ]
    A population Pharmacokinetic Pharmacodynamic analysis of plasma concentration data of VX-787 will be performed using the nonlinear mixed effects modeling approach.

  6. Viral sequence analysis to monitor for emergence of viral variants resistant to VX 787 and to oseltamivir [ Time Frame: Day 14 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02342249


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Sponsors and Collaborators
Janssen Research & Development, LLC
Janssen Pharmaceuticals
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02342249     History of Changes
Other Study ID Numbers: CR107745
VX-787FLZ2001 ( Other Identifier: Janssen Research & Development, LLC )
VX14-787-103 ( Other Identifier: Janssen Research & Development, LLC )
2014-004068-39 ( EudraCT Number )
First Posted: January 19, 2015    Key Record Dates
Last Update Posted: June 14, 2017
Last Verified: June 2017

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Janssen Research & Development, LLC:
Influenza A

Additional relevant MeSH terms:
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Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Oseltamivir
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action