Influenza
Conditions
Keywords
Influenza treatment, pediatric, laninamivir
Brief summary
This Phase 1/2 protocol is designed to collect safety, tolerability and pharmacokinetic data of two doses of Laninamivir Octanoate in children and adolescents. The protocol will also explore virology and efficacy endpoints.
Detailed description
Approximately 48 subjects aged 5-17 years inclusive will be randomised into the study. Subjects with recent onset of presumptive influenza will have influenza A or B infection confirm by Rapid Antigen Test. The study will be conducted on an outpatient basis. The dose is administered in a single session in the clinic on Day 1. The subject will return to the clinic for assessments and follow up.
Interventions
Sponsors
Department of Health and Human Services
Biota Scientific Management Pty Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Subjects' parent/legally acceptable representative/guardian must give written informed consent to participate in the study and must understand the nature of the study and must be willing to comply with all protocol requirements. Subjects over 12 must provide assent to participate in the study and potential subjects below this age should provide assent if deemed appropriate to the maturity level of the subject or if required according to local guidance/regulations. * Males or females aged between 5 and 17 years inclusive, who weigh at least 15 kg at screening. * Confirmed influenza infection based on positive rapid antigen test (RAT) for Influenza A or B. * Fever, defined as either: 1. Otic temperature ≥38.0° C (100.4°F) at the screening visit, OR, 2. A history of fever within the 24 hours prior to the screening visit and has administered antipyretic(s) in the 6 hours prior to the screening visit. * Presence on the Screening questionnaire of, at least two, of the following influenza symptoms: 1. Non-productive Cough, of at least moderate severity, 2. Sore throat, of at least moderate severity, 3. Nasal congestion/runny nose, of at least moderate severity, 4. Headache, of at least moderate severity, 5. Muscle aches and pain, of at least moderate severity, 6. Feeling feverish, of at least moderate severity, 7. Low energy, tired, fatigue, of at least moderate severity; * Onset of illness no more than 40 hours before randomization, defined as: 1. time when the temperature was first measured as elevated ≥38.0°C (oral or otic) OR 2. time when the subject first experienced at least one influenza symptom (non-productive cough, sore throat or nasal congestion/runny nose, headache, muscle aches and pain, feeling feverish, or low energy/tired/fatigue) * In the Investigator's opinion able to complete the required inhalations of the investigational medicinal product.
Exclusion criteria
* Use of antiviral treatment for influenza (e.g., zanamivir, oseltamivir, peramivir, rimantadine, or amantadine) within 14 days prior to screening * Received influenza virus vaccine in the previous 3 weeks. * History or presence of clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, cystic fibrosis, or bronchiectasis) * Current asthma requiring treatment, or history of asthma requiring treatment in the last 5 years, or episode of wheezing in the 12 months prior to randomization. * History of congestive heart failure with symptoms consistent with New York Heart Association Class III or IV functional status. * Presence of an immune compromised status due to chronic illness, organ transplantation or use of daily systemic immunosuppressants * Presence of clinically significant signs of acute respiratory distress during screening. * Current use of inhaled medications (nasal or oral) or anticipated use of inhaled medications (nasal or oral) at any time during the study. * Current or a history of acute or chronic renal impairment/disease * Currently hospitalized or any planned hospitalizations within 1 month following the last dose of IMP. * Current clinical evidence of otitis, bronchitis, sinusitis, or pneumonia or active bacterial infection at any body site * Severe infection within 30 days prior to screening which required parenteral antibiotic use or hospitalization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate Time to First Alleviation of a Composite of Influenza Symptoms and Absence of Fever. | Subjects are assessed at clinic visits and followed up to 28-days post dose. | For subjects aged 5 through 12 years, the subject or parent/legal guardian completed the Canadian Acute Respiratory Illness and Flu Scale (CARIFS) symptom diary and measured otic body temperature twice a day, in the morning between 6 and 10AM and evening between 6 and 10PM, until the Day 10 visit. Subjects aged 13 through 17 years completed the Influenza Symptom Questionnaire (ISQ) themselves and measured otic body temperature twice a day, in the morning between 6 and 10AM and evening between 6 and 10PM, until the Day 10 visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate the Pharmacokinetic (PK) Profiles (Concentration) of the Prodrug, Laninamivir Octanoate, and Its Active Metabolite, Laninamivir, Following Administration of a Single Dose (20 or 40 mg) | Samples are collected at clinic visits over 5 days. | Pharmacokinetic parameters will be calculated and summarized, PK concentration data will add to population models. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 20mg Laninamivir Octanoate Dry Powder plus placebo
20 mg laninamivir octanoate
Placebo | 7 |
| 40mg Laninamivir Octanoate Dry Powder
40 mg laninamivir octanoate | 8 |
| Total | 15 |
Baseline characteristics
| Characteristic | 40mg Laninamivir Octanoate | 20mg Laninamivir Octanoate | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 8 Participants | 7 Participants | 15 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 9.8 years STANDARD_DEVIATION 2.82 | 8.3 years STANDARD_DEVIATION 3.77 | 9.1 years STANDARD_DEVIATION 3.26 |
| Region of Enrollment United States | 8 Participants | 7 Participants | 15 Participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 8 |
| other Total, other adverse events | 2 / 7 | 5 / 8 |
| serious Total, serious adverse events | 0 / 7 | 0 / 8 |
Outcome results
Primary
To Evaluate Time to First Alleviation of a Composite of Influenza Symptoms and Absence of Fever.
For subjects aged 5 through 12 years, the subject or parent/legal guardian completed the Canadian Acute Respiratory Illness and Flu Scale (CARIFS) symptom diary and measured otic body temperature twice a day, in the morning between 6 and 10AM and evening between 6 and 10PM, until the Day 10 visit. Subjects aged 13 through 17 years completed the Influenza Symptom Questionnaire (ISQ) themselves and measured otic body temperature twice a day, in the morning between 6 and 10AM and evening between 6 and 10PM, until the Day 10 visit.
Time frame: Subjects are assessed at clinic visits and followed up to 28-days post dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 20mg Laninamivir Octanoate | To Evaluate Time to First Alleviation of a Composite of Influenza Symptoms and Absence of Fever. | 85.1 hours | Standard Deviation 34.2 |
| 40mg Laninamivir Octanoate | To Evaluate Time to First Alleviation of a Composite of Influenza Symptoms and Absence of Fever. | 79.7 hours | Standard Deviation 29.8 |
Secondary
To Evaluate the Pharmacokinetic (PK) Profiles (Concentration) of the Prodrug, Laninamivir Octanoate, and Its Active Metabolite, Laninamivir, Following Administration of a Single Dose (20 or 40 mg)
Pharmacokinetic parameters will be calculated and summarized, PK concentration data will add to population models.
Time frame: Samples are collected at clinic visits over 5 days.
Population: Due to early study termination, no PK data were collected.