Influenza A H3N2
Conditions
Brief summary
Phase 2 study, looking at the prophylactic efficacy, safety and tolerability to a repeated nasal dose of study drug after being infected with Influenza A/Perth/16/2009 (H3N2) virus.
Detailed description
Screening took place up to 90 days before quarantine. Volunteers completed an informed consent and underwent screening assessments to determine their eligibility. There were 2 study groups: Cohort A: (Sentinel): determined the Challenge Virus infection rate after inoculation with Influenza Virus on Day 0. There was 12 subjects (open label, no randomisation) invited to attend Quarantine on Day -2 or -1. Cohort B: Examined the prophylactic efficacy, safety and tolerability of PrEP-001 compared to placebo (randomised 1:1). Subjects attended on Day -4/-3, dosed with PrEP-001 or Placebo on Day -2 AND Day-1 and then challenged with virus (volume confirmed from Cohort A) on Day 0. Volunteers remained in quarantine unit for 8 days after inoculation. At day 28, end of study visit, volunteers seen and assessed by a study physician for well-being, on-going symptoms and adverse events.
Interventions
DRUGPrEP-001
OTHERPlacebo Comparator
Sponsors
Prep Biopharm Limited
Hvivo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Young healthy adults as determined by medical history, physical examination, serology (HIV and Hepatitis B and C) and clinical laboratory tests. * Female subjects were required to provide of a history of reliable contraceptive practice.
Exclusion criteria
* Subjects who have a significant history of any tobacco use at any time. * Any history or evidence of any clinically significant cardiovascular, dermatological gastrointestinal, endocrinological, haematological, hepatic, immunological, metabolic, urological, neurological, psychiatric, renal disease. * Abnormal ECG
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Efficacy Endpoint: The Area Under the Curve (AUC) of Total Symptom Score From Day 1 (Post Viral Challenge) to Day 8 (Quarantine Discharge). | 8 days | Area Under the Curve (AUC) of total symptom scores (upper respiratory tract (URT), lower respiratory tract (LRT) and systemic viral symptoms (SVS)). Total symptom scores (from the symptom diary card) were used to calculate the AUC. The time unit used was minutes. Thus, the AUC unit is the total symptom score multiplied by the time period from first to last assessment in minutes (i.e score\*mins). The minimum AUC value would be 0, for a subject who did not report any symptoms. The maximum AUC value is not provided as it would be theoretical only, with no real meaning in terms of severity. Higher scores indicate worse outcome than lower scores. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Efficacy Endpoint: Symptom Scores: Peak Symptoms Score | 8 days | Using the scheduled protocol assessments from Day 1 to Day 8, this endpoint represented the highest total symptom score (defined as the sum of all 10 individual composite symptoms). The minimum value, for subjects who had no symptoms, would be 0. The maximum value would be 30. Higher scores indicate worse outcome than lower scores. |
| Secondary Efficacy Endpoint: Incidence(s) of Illness and Infection: Viral Shedding | 8 days | The number of subjects with viral shedding. Viral shedding was measured by PCR, testing the nasopharyngeal swab samples. |
| Secondary Efficacy Endpoint: Incidence(s) of Illness and Infection: Seroconversion | 8 days | The number of subjects with seroconversion. Seroconversion was measured by the ratio of Influenza A/Perth/16/2009 (H3N2) virus antibodies at follow-up versus pre-dose. |
| Secondary Efficacy Endpoint: Viral Load Parameters: Area Under the Curve (AUC) of Viral Load, as Measured by Nasopharyngeal Swab RT-qPCR. | 8 days | Viral load data was supplied in Log10 Copies/mL. These values were used to calculate the Area Under the Curve (AUC) of Viral Load for each subject. |
| Secondary Efficacy Endpoint: Total Weight of Nasal Discharge Produced Post Viral Challenge to Quarantine Discharge | 8 days | Total weight of nasal discharge (in grams) was calculated as the sum of mucus weights taken from Day 1 (Post viral challenge) to Day 8 (Quarantine Discharge). |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Sentinel Group Sentinel group in which subjects received a challenge virus inoculum volume of 100uL on Day 0. | 11 |
| Cohort B: PrEP-001 PrEP-001 6400μg dose administered equally over both nostrils and on 2 consecutive days, using a single dose nasal powder device, as per randomisation schedule. | 27 |
| Cohort B: Placebo Nasal dose of placebo Comparator equally divided over both nostrils and on 2 consecutive days, using a single dose nasal powder device, as per randomisation schedule. | 28 |
| Total | 66 |
Baseline characteristics
| Characteristic | Cohort A: Sentinel Group | Cohort B: PrEP-001 | Cohort B: Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 27 Participants | 28 Participants | 66 Participants |
| Race/Ethnicity, Customized Asian or Asian British - Pakistani | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian - Other | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or Black British - African | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Mixed - White & Asian | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Mixed - White & Black Caribbean | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White British | 10 Participants | 23 Participants | 19 Participants | 52 Participants |
| Race/Ethnicity, Customized White Irish | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White Other | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment United Kingdom | 11 participants | 27 participants | 28 participants | 66 participants |
| Sex: Female, Male Female | 4 Participants | 8 Participants | 11 Participants | 23 Participants |
| Sex: Female, Male Male | 7 Participants | 19 Participants | 17 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 11 | 17 / 27 | 21 / 28 |
| serious Total, serious adverse events | 0 / 11 | 0 / 27 | 0 / 28 |
Outcome results
Primary
Primary Efficacy Endpoint: The Area Under the Curve (AUC) of Total Symptom Score From Day 1 (Post Viral Challenge) to Day 8 (Quarantine Discharge).
Area Under the Curve (AUC) of total symptom scores (upper respiratory tract (URT), lower respiratory tract (LRT) and systemic viral symptoms (SVS)). Total symptom scores (from the symptom diary card) were used to calculate the AUC. The time unit used was minutes. Thus, the AUC unit is the total symptom score multiplied by the time period from first to last assessment in minutes (i.e score\*mins). The minimum AUC value would be 0, for a subject who did not report any symptoms. The maximum AUC value is not provided as it would be theoretical only, with no real meaning in terms of severity. Higher scores indicate worse outcome than lower scores.
Time frame: 8 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Sentinel Group | Primary Efficacy Endpoint: The Area Under the Curve (AUC) of Total Symptom Score From Day 1 (Post Viral Challenge) to Day 8 (Quarantine Discharge). | 17956.5 score*mins | Standard Deviation 23780.83 |
| Cohort B: PrEP-001 | Primary Efficacy Endpoint: The Area Under the Curve (AUC) of Total Symptom Score From Day 1 (Post Viral Challenge) to Day 8 (Quarantine Discharge). | 4502.6 score*mins | Standard Deviation 6144.84 |
| Cohort B: Placebo | Primary Efficacy Endpoint: The Area Under the Curve (AUC) of Total Symptom Score From Day 1 (Post Viral Challenge) to Day 8 (Quarantine Discharge). | 9859.6 score*mins | Standard Deviation 12215.84 |
Secondary
Secondary Efficacy Endpoint: Incidence(s) of Illness and Infection: Seroconversion
The number of subjects with seroconversion. Seroconversion was measured by the ratio of Influenza A/Perth/16/2009 (H3N2) virus antibodies at follow-up versus pre-dose.
Time frame: 8 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: Sentinel Group | Secondary Efficacy Endpoint: Incidence(s) of Illness and Infection: Seroconversion | 9 Participants |
| Cohort B: PrEP-001 | Secondary Efficacy Endpoint: Incidence(s) of Illness and Infection: Seroconversion | 12 Participants |
| Cohort B: Placebo | Secondary Efficacy Endpoint: Incidence(s) of Illness and Infection: Seroconversion | 16 Participants |
Secondary
Secondary Efficacy Endpoint: Incidence(s) of Illness and Infection: Viral Shedding
The number of subjects with viral shedding. Viral shedding was measured by PCR, testing the nasopharyngeal swab samples.
Time frame: 8 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: Sentinel Group | Secondary Efficacy Endpoint: Incidence(s) of Illness and Infection: Viral Shedding | 7 Participants |
| Cohort B: PrEP-001 | Secondary Efficacy Endpoint: Incidence(s) of Illness and Infection: Viral Shedding | 13 Participants |
| Cohort B: Placebo | Secondary Efficacy Endpoint: Incidence(s) of Illness and Infection: Viral Shedding | 21 Participants |
Secondary
Secondary Efficacy Endpoint: Symptom Scores: Peak Symptoms Score
Using the scheduled protocol assessments from Day 1 to Day 8, this endpoint represented the highest total symptom score (defined as the sum of all 10 individual composite symptoms). The minimum value, for subjects who had no symptoms, would be 0. The maximum value would be 30. Higher scores indicate worse outcome than lower scores.
Time frame: 8 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Sentinel Group | Secondary Efficacy Endpoint: Symptom Scores: Peak Symptoms Score | 5.2 Score | Standard Deviation 5.88 |
| Cohort B: PrEP-001 | Secondary Efficacy Endpoint: Symptom Scores: Peak Symptoms Score | 1.7 Score | Standard Deviation 1.9 |
| Cohort B: Placebo | Secondary Efficacy Endpoint: Symptom Scores: Peak Symptoms Score | 3.3 Score | Standard Deviation 3.28 |
Secondary
Secondary Efficacy Endpoint: Total Weight of Nasal Discharge Produced Post Viral Challenge to Quarantine Discharge
Total weight of nasal discharge (in grams) was calculated as the sum of mucus weights taken from Day 1 (Post viral challenge) to Day 8 (Quarantine Discharge).
Time frame: 8 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Sentinel Group | Secondary Efficacy Endpoint: Total Weight of Nasal Discharge Produced Post Viral Challenge to Quarantine Discharge | 26.580 grams | Standard Deviation 49.5158 |
| Cohort B: PrEP-001 | Secondary Efficacy Endpoint: Total Weight of Nasal Discharge Produced Post Viral Challenge to Quarantine Discharge | 3.959 grams | Standard Deviation 5.1349 |
| Cohort B: Placebo | Secondary Efficacy Endpoint: Total Weight of Nasal Discharge Produced Post Viral Challenge to Quarantine Discharge | 13.414 grams | Standard Deviation 20.7986 |
Secondary
Secondary Efficacy Endpoint: Viral Load Parameters: Area Under the Curve (AUC) of Viral Load, as Measured by Nasopharyngeal Swab RT-qPCR.
Viral load data was supplied in Log10 Copies/mL. These values were used to calculate the Area Under the Curve (AUC) of Viral Load for each subject.
Time frame: 8 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Sentinel Group | Secondary Efficacy Endpoint: Viral Load Parameters: Area Under the Curve (AUC) of Viral Load, as Measured by Nasopharyngeal Swab RT-qPCR. | 33021.8 mins*log10 copy number/mL | Standard Deviation 19676.07 |
| Cohort B: PrEP-001 | Secondary Efficacy Endpoint: Viral Load Parameters: Area Under the Curve (AUC) of Viral Load, as Measured by Nasopharyngeal Swab RT-qPCR. | 23781.6 mins*log10 copy number/mL | Standard Deviation 14127.65 |
| Cohort B: Placebo | Secondary Efficacy Endpoint: Viral Load Parameters: Area Under the Curve (AUC) of Viral Load, as Measured by Nasopharyngeal Swab RT-qPCR. | 32944.4 mins*log10 copy number/mL | Standard Deviation 17059.07 |