Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

Study to Assess the Efficacy of Baloxavir Marboxil Versus Placebo to Reduce Onward Transmission of Influenza A or B in Households

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03969212
Recruitment Status : Recruiting
First Posted : May 31, 2019
Last Update Posted : January 3, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
Otherwise healthy index patients (IP) are randomized to either baloxavir marboxil or placebo if their influenza symptoms onset was within 48 hours of screen. Their households are enrolled within 24 hours of randomization if at least 2 household contacts (HHC) have not received influenza vaccine within 6 months of screening and if all HHC screen negative for influenza infection. The main endpoints are assessed based on multiple respiratory swabs obtained from both IP and HHC up to 9 (+/-1) days post IP randomization.

Condition or disease Intervention/treatment Phase
Influenza Drug: Baloxavir Marboxil Drug: Placebo Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase IIIB, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Clinical Efficacy Study of Baloxavir Marboxil for the Reduction of Direct Transmission of Influenza From Otherwise Healthy Patients to Household Contacts
Actual Study Start Date : October 10, 2019
Estimated Primary Completion Date : May 24, 2020
Estimated Study Completion Date : June 6, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot

Arm Intervention/treatment
Experimental: Baloxavir Marboxil
Participants who are IPs will receive a single oral dose of baloxavir marboxil. HHCs of the IPs will not receive study medication.
Drug: Baloxavir Marboxil
Participants who are IPs will receive either 40 mg (if weight less than 80 kg) or 80 mg (if weight more than or equal to 80 kg) of Baloxavir Marboxil as tablets. HHCs of IPs will not receive study medication.
Other Name: Xofluza

Placebo Comparator: Placebo
Participants who are IPs will receive a single oral dose of placebo. HHCs of the IPs will not receive study medication.
Drug: Placebo
Participants who are IPs will receive a matching placebo as tablets. HHCs of IPs will not receive study medication.




Primary Outcome Measures :
  1. Percentage of Household Contacts (HHCs) who become Polymerase Chain Reaction Positive (PCR+) for Influenza by Day 5 Post IP Randomization [ Time Frame: Baseline to Day 5 (5 days) ]
    HHCs may be symptomatic or asymptomatic and their virus subtype must match that of the index patient (IP) in their household. The primary efficacy analysis population will consist of all enrolled unvaccinated HHCs of the randomized IPs.


Secondary Outcome Measures :
  1. Percentage of HHCs who become PCR+ for Influenza by Day 9 Post IP Randomization [ Time Frame: Baseline to Day 9 (9 days) ]
    HHCs must have their virus subtype match that of the IP, and include: (1) all HHC meeting primary endpoint, AND (2) all HHC cases detected after Day 5 Visit meeting the following criteria: (2a) included HHC case is in a household where another HHC has already met the primary endpoint, OR (2b) included HHC case is PCR (+) for influenza bearing treatment-emergent amino acid substitutions in the PA protein that have been associated with reduced susceptibility to baloxavir marboxil.

  2. Percentage of HHCs who become PCR+ for Influenza by Day 5 Post IP Randomization and Develop Influenza Symptoms at any Time During the Study [ Time Frame: Baseline to Day 5 (5 days) ]
    HHCs ≥12 years old were defined symptomatic if (1) presence of temperature ≥38.0 Celsius and one respiratory symptom (cough, sore throat, nasal congestion) or (2) presence of one respiratory symptom and one general systemic symptom (headache, feverishness or chills, muscle or joint pain, fatigue), with or without fever. HHCs ≥2 and <12 years old were defined symptomatic if presence of temperature ≥38.0 Celsius and cough, nasal congestion, or rhinorrhea. Note: For HHCs of any age, respiratory or general systemic symptoms had to be either (1) new, or (2) worsened versus baseline with baseline symptoms due to a pre-existing comorbidity. HHCs must have their virus subtype match that of the IP.

  3. Percentage of Households with At Least One HHC who Meets Primary Endpoint [ Time Frame: Baseline to Day 5 (5 days) ]
  4. Percentage of IPs With Adverse Events (AEs) [ Time Frame: Baseline to Day 9 (9 Days) ]
  5. Change from baseline in health-related quality of life according to EuroQol 5 dimensions 5 (EQ-5D-5L; Appendix 3) questionnaire at Day 3 and Day 9 Visits (IPs only) [ Time Frame: Baseline, Day 3 and Day 9 ]
    The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. An increase in the VAS score of 7 points or greater was defined as the threshold for a meaningful improvement.

  6. Change From Baseline in Work Productivity and Activity Impairment According to Work Productivity and Activity Impairment (WPAI) plus Classroom Impairement Questions Score [ Time Frame: Baseline and Day 9 ]
    The WPAI is a patient-reported measure which assesses the effect of general health and symptom severity on work productivity and regular activities. The General Health questionnaire asks participants to estimate the number of hours missed from work due to reasons related and unrelated to their health problems, as well as the total number of hours actually worked in the preceding 7-day period. The percentage of participants reporting that they were employed (working for pay) was assessed at baseline was assessed along with Absenteeism (work time missed), Presenteeism (impairment at work / reduced on-the-job effectiveness), Work productivity loss (overall work impairment / absenteeism plus presenteeism), and Activity Impairment.



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.


Layout table for eligibility information
Ages Eligible for Study:   12 Years to 64 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

Index Patients (IPs):

  • Able to comply with the study protocol per investigator judgment.
  • Diagnosed with acute influenza infection by investigator.
  • Polymerase chain reaction [PCR] (+) or Rapid Influenza Diagnostic Test [RIDT] (+) for influenza A/B based on cobas® influenza A/B Assay or other point-of-care / local laboratory results.
  • Presence of (a) fever (>=38.0 °C per tympanic or rectal thermometer; >=37.5 °C per axillary, oral or forehead/temporal thermometer) or (b) any influenza symptoms (cough, sore throat, nasal congestion, headache, feverishness or chills, muscle or joint pain, fatigue).
  • The time interval between the onset of fever or influenza symptoms and the pre-dose examinations is 48 hours or less.
  • IP lives in a household where: No household contact (HHC) known to have been diagnosed with influenza by a healthcare professional, all HHCs are expected to meet the key HHC inclusion criteria and none of the HHC exclusion criteria, >=2 HHCs are expected to participate in the full study who have not received the influenza vaccine within 6 months prior to screening.

All HHCs:

  • Willing to undergo screening visit as a scheduled/unscheduled visit after they return to the home if not at home at Day 0 Visit.
  • PCR (-) or RIDT (-) based on cobas® influenza A/B Assay or other local point-of-care / local laboratory result at Day 0 Visit.

HHC intended for full study must meet the following additional criteria for study entry:

  • No influenza symptoms within 7 days prior to screening. Alternatively, mild symptoms are permissible if determined by the investigator to be due to a pre-existing condition.
  • Temperature <38.0 °C (tympanic).
  • Will reside in the index patient's house for at least 7 of the next 9 days and will be present for scheduled study visits.
  • Willing and able to measure and record temperature, or have another household member perform the task on his or her behalf. Furthermore, a responsible adult will assume responsibility to oversee or perform this task on behalf of minors.
  • ≥2 HHC who have not been vaccinated within 6 months prior to screening are needed for household to be included)

EXCLUSION CRITERIA:

IPs:

  • IPs with severe influenza virus infection requiring inpatient treatment.
  • IPs judged by the investigator to be at high risk for complications of influenza.
  • IPs unable to swallow tablets.
  • IPs weighing less than 40 kg.
  • Women who are breastfeeding or have a positive pregnancy test in the pre-dose examinations.
  • IPs with concurrent (non-influenza) infections requiring systemic antimicrobial and/or antiviral therapy at the pre-dose examinations.
  • IPs who have received baloxavir marboxil, peramivir, laninamivir, oseltamivir, zanamivir, rimantadine, umifenovir or amantadine, or an investigational drug, within 30 days or 5 drug-elimination half-lives, whichever is longer, prior to screening.
  • IPs who have received an investigational monoclonal antibody for a viral disease in the last year.
  • Known hypersensitivity to baloxavir marboxil or the drug product excipients.

HHC:

  • Pregnant or within 2 weeks post-partum at screening.
  • Immunocompromised.
  • Less than 2 years old.
  • Who have received an investigational therapy within the 30 days or 5 drug elimination half-lives, whichever is longer, prior to 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): NCT03969212


Contacts
Layout table for location contacts
Contact: MV40618 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global-roche-genentech-trials@gene.com

Locations
Show Show 181 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Layout table for investigator information
Study Director: Clinical Trials Hoffmann-La Roche

Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03969212    
Other Study ID Numbers: MV40618
2018-004056-37 ( EudraCT Number )
First Posted: May 31, 2019    Key Record Dates
Last Update Posted: January 3, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche'Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Baloxavir
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action