Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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 : June 4, 2021
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 screening. 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, and through the assessment of symptoms.

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 : March 31, 2023
Estimated Study Completion Date : March 31, 2023

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
IPs less than 12 years old will receive either 2 mg/kg (if weight less than 20 kg) or 40 mg (if weight more than or equal to 20 kg) of Baloxavir Marboxil as oral suspension. IPs more than or equal to 12 years old 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
IPs less than 12 years old will receive placebo oral suspension and those above 12 years will receive placebo tablets. HHCs of IPs will not receive study medication.




Primary Outcome Measures :
  1. Virological Transmission by Day 5 [ Time Frame: Baseline to Day 5 (5 days) ]
    Defined as the percentage of Household Contacts (HHCs) who become Polymerase Chain Reaction Positive (PCR+) for Influenza by Day 5 post IP randomization. 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. Symptomatic Transmission by Day 5 [ Time Frame: Baseline to Day 5 (5 days) ]
    Defined as the percentage of HHCs who become PCR+ for Influenza by Day 5 post IP randomization and develop Influenza symptoms at any time during the study. 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.

  2. Virological Transmission at the Household Level by Day 5 [ Time Frame: Baseline to Day 5 (5 days) ]
    Defined as the percentage of households with at least one HHC who meets the primary endpoint.

  3. Symptomatic Transmission at the Household Level by Day 5 [ Time Frame: Baseline to Day 5 (5 days) ]
    Defined as the percentage of households with at least one HHC who meets the "Symptomatic transmission by Day 5 endpoint.

  4. Virological Transmission by Day 9 [ Time Frame: Baseline to Day 9 (9 days) ]
    Defined as the percentage of HHCs who become PCR+ for Influenza by Day 9 post IP randomization. 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.

  5. Symptomatic Transmission by Day 9 [ Time Frame: Baseline to Day 9 (9 Days) ]
    Defined as the percentage of HHCs who meet the "Virological transmission by Day 9" endpoint AND are symptomatic per the definition for symptoms in the "Symptomatic transmission by Day 5" endpoint.

  6. Any Virological Infection by Day 9 [ Time Frame: Baseline to Day 9 (9 Days) ]
    Defined as the percentage of HHCs who become PCR (+) for influenza (confirmed at central laboratory) by Day 9.

  7. Any Virological Infection at the Household Level by Day 9 [ Time Frame: Baseline to Day 9 (9 Days) ]
    Defined as the percentage of households with at least one HHC who meets the "Any virological infection by Day 9" endpoint.

  8. Any Symptomatic Infection by Day 9 [ Time Frame: Baseline to Day 9 (9 Days) ]
    Defined as the percentage of HHCs who meet the "Any virological infection by Day 9" endpoint AND are symptomatic per the definition for symptoms in the "Symptomatic transmission by Day 5" endpoint.

  9. Any Symptomatic Infection at the Household Level by Day 9 [ Time Frame: Baseline to Day 9 (9 Days) ]
    Defined as the percentage of households with at least one HHC who meets the "Any symptomatic infection by Day 9" endpoint.

  10. Percentage of IPs With Adverse Events (AEs) [ Time Frame: Baseline to Day 9 (≥12 years old) and Day 21 (<12 years old) ]
  11. 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.

  12. Change From Baseline in Work Productivity and Activity Impairment According to Work Productivity and Activity Impairment (WPAI) plus Classroom Impairement Questions Score (IPs only) [ 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:   5 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.
  • PCR (-) or antigen test (-) for SARS-CoV-2 based on cobas® SARS-CoV-2 Assay or other point-of-care / local laboratory result
  • 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: (1) No HHC is known to have been diagnosed with influenza or SARS-CoV-2 infection by a healthcare professional (HCP) in the past 4 weeks (2) All HHCs are expected to meet the key HHC inclusion criteria (3) >=2 HHCs are expected to participate in the full study who have not received the influenza vaccine within 6 months prior to screening.
  • Women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures specified in the protocol

All HHCs (Part 1):

  • PCR (-) or RIDT (-) based on cobas® influenza A/B Assay or other local point-of-care / local laboratory result.
  • PCR (-) or antigen test (-) for SARS-CoV-2 based on cobas® SARS-CoV-2 Assay or other POC / local laboratory result.
  • HHC lives with no HHC who will be present in the home at any time during the study and who meets any HHC exclusion criteria.
  • HHC lives with no HHC who does not meet HHC inclusion criteria 1.
  • HHC lives in a household where ≥2 HHCs meet all of the following: Start screening within 24 hours post IP randomization; Have NOT received the influenza vaccine within 6 months prior to screening; and Fulfill full study HHC inclusion criteria part 2.

Full study HHCs (part 2) intended for full study must meet the following additional criteria for study entry:

  • Agree to participate in the full study.
  • Able to comply with the study protocol per investigator judgment
  • 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.
  • In the 6 months prior to screening: a) Has not been diagnosed with influenza by a healthcare professional b) Has not received BXM, peramivir, laninamivir, oseltamivir, zanamivir, rimantadine, umifenovir, or amantadine.
  • Does not have a moderate or worse active infections OR infections requiring systemic (e.g., oral or intravenous) or otherwise internally administered (e.g., inhaled, intrathecal) antibiotic/antiviral/antifungal therapy, (topical therapies for mild external infections allowed).

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.
  • IP is ≥12 years old and unable to swallow tablets (not applicable to IPs 5 to 11 year olds who will receive oral suspension).
  • 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.
  • IP previously included in the study
  • IP lives with an HHC who, based on available information, meets the HHC exclusion criteria

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.
  • Diagnosed with influenza or SARS-CoV-2 infection by a healthcare professional in the past 4 weeks.
  • HHC who plans to arrive home after 24 hours post IP randomization to Day 9 and is not willing to be consented as soon as possible upon arrival.
  • HHC previously included in the study.

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 265 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: June 4, 2021
Last Verified: June 2021
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.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's 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
Baloxavir
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action