Influenza
Conditions
Brief summary
This 2 arm study will evaluate the efficacy and safety of oseltamivir in the seasonal prophylaxis of influenza in immunocompromised participants (as represented by transplant recipients). Transplant recipients enrolled when influenza is circulating in the community will be randomized to receive oseltamivir syrup or capsules 30 milligrams (mg) to 75 mg daily (depending on body weight) or placebo for 12 weeks. Influenza symptoms and safety data will be recorded throughout the study.
Interventions
DRUGOseltamivir
Oseltamivir 30 mg to 75 mg capsule or suspension orally once daily for 12 weeks.
DRUGPlacebo
Placebo matched to oseltamivir capsule or suspension orally once daily for 12 weeks.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Negative rapid diagnostic test for influenza at baseline; * Immunocompromised participant (liver and/or kidney recipient or allogenic hematopoietic stem cell transplant).
Exclusion criteria
* Symptoms suggestive of influenza-like illness; but not limited to fever, cough, or nasal congestion; * Influenza vaccination in 6 weeks prior to randomization; * Positive rapid diagnostic test for influenza; * Solid organ transplant within 6 months of randomization; * Antiviral treatment for influenza in 2 weeks prior to randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Laboratory-Confirmed Clinical Influenza, ITT Population | From baseline up to 28 days after the last dose of study drug (maximum up to 112 days) | Laboratory-confirmed clinical influenza was defined as a fever (oral or otic temperature greater than \[\>\] 37.2 degrees Celsius \[°C\]) and a symptom score for cough and/or coryza (nasal congestion on the diary cards, where 0=absent, 1=mild, 2=moderate, and 3=severe) of 1, 2 or 3 on the same day as fever, and laboratory confirmation of influenza either by detection of viral shedding by viral culture from nasopharyngeal swabs within two days of fever and symptoms, and/or by 4-fold or greater increase in serum hemagglutination inhibition (HAI) titers measured from baseline to any point during the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Laboratory Confirmed Clinical Influenza, Intent-to-treat Virus Negative at Baseline (ITTNAB) Population | From baseline up to 28 days after the last dose of study drug (maximum up to 112 days) | Laboratory-confirmed clinical influenza was defined as a fever (oral or otic temperature greater than 37.2 °C) and a symptom score for cough and/or coryza (nasal congestion on the diary cards, where 0=absent, 1=mild, 2=moderate, and 3=severe) of 1, 2 or 3 on the same day as fever, and laboratory confirmation of influenza either by detection of viral shedding by viral culture from nasopharyngeal swabs within two days of fever and symptoms, and/or by 4-fold or greater increase in serum HAI titers measured from baseline to any point during the study. |
| Number of Participants With Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) Confirmed Clinical Influenza, ITT Population | From baseline up to 28 days after the last dose of study drug (maximum up to 112 days) | RT-PCR confirmed clinical influenza was defined as a confirmation of influenza by positive RT-PCR result within 2 days of symptoms/last dose from baseline to any point during the study. |
| Number of Participants With Laboratory Confirmed Clinical Influenza, Per Protocol (PP) Population | From baseline up to 28 days after the last dose of study drug (maximum up to 112 days) | Laboratory-confirmed clinical influenza was defined as a fever (oral or otic temperature greater than 37.2 °C) and a symptom score for cough and/or coryza (nasal congestion on the diary cards, where 0=absent, 1=mild, 2=moderate, and 3=severe) of 1, 2 or 3 on the same day as fever, and laboratory confirmation of influenza either by detection of viral shedding by viral culture from nasopharyngeal swabs within two days of fever and symptoms, and/or by 4-fold or greater increase in serum HAI titers measured from baseline to any point during the study. |
| Number of Participants With RT-PCR, or Serology/Viral Culture Confirmed Clinical Influenza, ITT Population | From baseline up to 28 days after the last dose of study drug (maximum up to 112 days) | RT-PCR, or serology/viral culture confirmed clinical influenza was defined as a confirmation of influenza by positive RT-PCR or culture within 2 days of symptoms/ last dose and/or positive serology result from baseline to any point during the study. |
| Number of Participants With RT-PCR, or Serology/Viral Culture Confirmed Clinical Influenza, ITTNAB Population | From baseline up to 28 days after the last dose of study drug (maximum up to 112 days) | RT-PCR, or serology/viral culture confirmed clinical influenza was defined as a confirmation of influenza by positive RT-PCR or culture within 2 days of symptoms/ last dose and/or positive serology result from baseline to any point during the study. |
| Number of Participants With RT-PCR Confirmed Clinical Influenza, ITTNAB Population | From baseline up to 28 days after the last dose of study drug (maximum up to 112 days) | RT-PCR confirmed clinical influenza was defined as a confirmation of influenza by positive RT-PCR result within 2 days of symptoms/last dose from baseline to any point during the study. |
Countries
Belgium, Canada, Czechia, Estonia, France, Germany, Hungary, Israel, Italy, Lithuania, Poland, Spain, United Kingdom, United States
Participant flow
Recruitment details
Out of total 477 participants who were randomized to receive study treatments, 2 participants were not included in the study population due to lack of efficacy data. Thus, results are reported only for 475 participants.
Pre-assignment details
One participant was randomized to placebo group but received oseltamivir for the first 9 weeks of the study. This participant was included in the placebo group in the Intention-to-treat (ITT) analysis population, but in the oseltamivir group in the safety analysis population.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo matched to oseltamivir capsule or suspension orally once daily for 12 weeks. | 237 |
| Oseltamivir Oseltamivir 30 mg to 75 mg capsule or suspension orally once daily for 12 weeks. | 238 |
| Total | 475 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Failure to Return | 6 | 2 |
| Overall Study | Refused Treatment | 6 | 2 |
Baseline characteristics
| Characteristic | Placebo | Total | Oseltamivir |
|---|---|---|---|
| Age, Continuous | 48.9 years STANDARD_DEVIATION 15.67 | 49.2 years STANDARD_DEVIATION 15.56 | 49.4 years STANDARD_DEVIATION 15.47 |
| Sex: Female, Male Female | 86 Participants | 160 Participants | 74 Participants |
| Sex: Female, Male Male | 151 Participants | 315 Participants | 164 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 40 / 237 | 42 / 238 |
| serious Total, serious adverse events | 23 / 237 | 18 / 238 |
Outcome results
Primary
Number of Participants With Laboratory-Confirmed Clinical Influenza, ITT Population
Laboratory-confirmed clinical influenza was defined as a fever (oral or otic temperature greater than \[\>\] 37.2 degrees Celsius \[°C\]) and a symptom score for cough and/or coryza (nasal congestion on the diary cards, where 0=absent, 1=mild, 2=moderate, and 3=severe) of 1, 2 or 3 on the same day as fever, and laboratory confirmation of influenza either by detection of viral shedding by viral culture from nasopharyngeal swabs within two days of fever and symptoms, and/or by 4-fold or greater increase in serum hemagglutination inhibition (HAI) titers measured from baseline to any point during the study.
Time frame: From baseline up to 28 days after the last dose of study drug (maximum up to 112 days)
Population: ITT population included all randomized participants who received at least 1 dose of study drug and had at least 1 post baseline efficacy assessment. Participants were analyzed as per initial randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Laboratory-Confirmed Clinical Influenza, ITT Population | 7 participants |
| Oseltamivir | Number of Participants With Laboratory-Confirmed Clinical Influenza, ITT Population | 5 participants |
Comparison: The null hypothesis tested was that there was no difference between the proportions of participants who met the primary endpoint in the two treatment groups.p-value: 0.77295% CI: [-2.3, 4.1]Fisher Exact
Secondary
Number of Participants With Laboratory Confirmed Clinical Influenza, Intent-to-treat Virus Negative at Baseline (ITTNAB) Population
Laboratory-confirmed clinical influenza was defined as a fever (oral or otic temperature greater than 37.2 °C) and a symptom score for cough and/or coryza (nasal congestion on the diary cards, where 0=absent, 1=mild, 2=moderate, and 3=severe) of 1, 2 or 3 on the same day as fever, and laboratory confirmation of influenza either by detection of viral shedding by viral culture from nasopharyngeal swabs within two days of fever and symptoms, and/or by 4-fold or greater increase in serum HAI titers measured from baseline to any point during the study.
Time frame: From baseline up to 28 days after the last dose of study drug (maximum up to 112 days)
Population: ITTNAB population was defined as the subset of the ITT population who were culture negative at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Laboratory Confirmed Clinical Influenza, Intent-to-treat Virus Negative at Baseline (ITTNAB) Population | 7 participants |
| Oseltamivir | Number of Participants With Laboratory Confirmed Clinical Influenza, Intent-to-treat Virus Negative at Baseline (ITTNAB) Population | 4 participants |
p-value: 0.38195% CI: [-1.7, 4.6]Fisher Exact
Secondary
Number of Participants With Laboratory Confirmed Clinical Influenza, Per Protocol (PP) Population
Laboratory-confirmed clinical influenza was defined as a fever (oral or otic temperature greater than 37.2 °C) and a symptom score for cough and/or coryza (nasal congestion on the diary cards, where 0=absent, 1=mild, 2=moderate, and 3=severe) of 1, 2 or 3 on the same day as fever, and laboratory confirmation of influenza either by detection of viral shedding by viral culture from nasopharyngeal swabs within two days of fever and symptoms, and/or by 4-fold or greater increase in serum HAI titers measured from baseline to any point during the study.
Time frame: From baseline up to 28 days after the last dose of study drug (maximum up to 112 days)
Population: Per-Protocol (PP) population was defined as the subset of the ITT population who did not have any major protocol violations which would impact the assessment of efficacy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Laboratory Confirmed Clinical Influenza, Per Protocol (PP) Population | 6 participants |
| Oseltamivir | Number of Participants With Laboratory Confirmed Clinical Influenza, Per Protocol (PP) Population | 4 participants |
p-value: 0.53495% CI: [-2.1, 4.5]Fisher Exact
Secondary
Number of Participants With Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) Confirmed Clinical Influenza, ITT Population
RT-PCR confirmed clinical influenza was defined as a confirmation of influenza by positive RT-PCR result within 2 days of symptoms/last dose from baseline to any point during the study.
Time frame: From baseline up to 28 days after the last dose of study drug (maximum up to 112 days)
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) Confirmed Clinical Influenza, ITT Population | 7 participants |
| Oseltamivir | Number of Participants With Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) Confirmed Clinical Influenza, ITT Population | 2 participants |
95% CI: [-0.6, 5.2]
Secondary
Number of Participants With RT-PCR Confirmed Clinical Influenza, ITTNAB Population
RT-PCR confirmed clinical influenza was defined as a confirmation of influenza by positive RT-PCR result within 2 days of symptoms/last dose from baseline to any point during the study.
Time frame: From baseline up to 28 days after the last dose of study drug (maximum up to 112 days)
Population: ITTNAB population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With RT-PCR Confirmed Clinical Influenza, ITTNAB Population | 7 participants |
| Oseltamivir | Number of Participants With RT-PCR Confirmed Clinical Influenza, ITTNAB Population | 1 participants |
95% CI: [0.1, 5.7]
Secondary
Number of Participants With RT-PCR, or Serology/Viral Culture Confirmed Clinical Influenza, ITTNAB Population
RT-PCR, or serology/viral culture confirmed clinical influenza was defined as a confirmation of influenza by positive RT-PCR or culture within 2 days of symptoms/ last dose and/or positive serology result from baseline to any point during the study.
Time frame: From baseline up to 28 days after the last dose of study drug (maximum up to 112 days)
Population: ITTNAB population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With RT-PCR, or Serology/Viral Culture Confirmed Clinical Influenza, ITTNAB Population | 8 participants |
| Oseltamivir | Number of Participants With RT-PCR, or Serology/Viral Culture Confirmed Clinical Influenza, ITTNAB Population | 4 participants |
95% CI: [-1.4, 5.1]
Secondary
Number of Participants With RT-PCR, or Serology/Viral Culture Confirmed Clinical Influenza, ITT Population
RT-PCR, or serology/viral culture confirmed clinical influenza was defined as a confirmation of influenza by positive RT-PCR or culture within 2 days of symptoms/ last dose and/or positive serology result from baseline to any point during the study.
Time frame: From baseline up to 28 days after the last dose of study drug (maximum up to 112 days)
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With RT-PCR, or Serology/Viral Culture Confirmed Clinical Influenza, ITT Population | 8 participants |
| Oseltamivir | Number of Participants With RT-PCR, or Serology/Viral Culture Confirmed Clinical Influenza, ITT Population | 5 participants |
95% CI: [-1.9, 4.6]