Influenza
Conditions
Keywords
Challenge, oral vaccine
Brief summary
A Phase 2 Randomized, Placebo- and Active-Controlled, Human Influenza A/California/04/2009 (H1N1) Challenge Study Following Administration of an Oral H1N1 Hemagglutinin (HA) Adenoviral-Vector Based Seasonal Influenza Vaccine and dsRNA Adjuvant (VXA-A1.1) to Healthy Adult Volunteers.
Detailed description
This is a Phase 2 randomized, placebo- and active-controlled, two-part study in which healthy adult volunteers with low or undetectable pre-existing antibodies against A/California/7/2009(H1N1) pdm09-like virus will be challenged with an influenza A/H1N1 human challenge strain approximately 90 days after vaccination with a single dose of H1N1 HA Adenoviral-vector based seasonal influenza vaccine and dsRNA adjuvant (VXA-A1.1), an injectable QIV vaccine, and/or placebo. An independent Safety Monitoring Committee (SMC) will oversee the safety of the study. To accommodate the limited size of the isolation unit that will be utilized for the challenge and post-challenge sequestration period, subjects will move through the study (enrollment, vaccination and challenge) sequentially in a total of 6 cohorts. Each cohort will randomize 30 subjects to obtain approximately 25 subjects per cohort for the challenge phase. Subjects will be randomized in a ratio of 2:2:1 (VXA-A1.1: Quadrivalent Influenza Vaccine (QIV): Placebo. The study will be conducted in two parts. Part A: Subjects will be randomized in a double-blinded manner to receive a single administration of one of three treatment arms: * Arm 1: VXA-A1.1 oral vaccine + placebo Intramuscular (IM) * Arm 2: QIV (IM) injection + oral placebo * Arm 3: Placebo IM injection + oral placebo Subjects will return to the site for \ 8 visits and be contacted remotely at defined time points to be followed for immunogenicity and safety during study Part A. Part B: Subjects will be challenged with a wild-type influenza A H1 virus strain \ 90 days following vaccination. Blood samples will be collected to evaluate immunogenicity. Subjects will remain in the isolation unit for 6 to 9 days post-challenge. Following challenge, influenza symptoms and signs will be assessed during the sequestration period. Blood samples and nasopharyngeal swab samples will be collected. Vital signs will be measured every 4 hours during waking hours. After release from the isolation unit subjects will return to the site 30 days post-challenge. Part B will continue for purposes of collecting long term safety follow-up (serious adverse events (SAEs), AEs of special interest (AESIs) and any new onset of chronic illness (NOCI) via phone contacts through 1 year post-vaccination (Day 365).
Interventions
OTHERSaline Solution for Placebo IM Injection
BIOLOGICALVXA-A1.1
Enteric coated oral vaccine tablet
BIOLOGICALFluzone®
Fluzone Quadravalent (Fluzone®) influenza vaccine (QIV) suspension for intramuscular (IM) injection
OTHERPlacebo Tablets
Placebo tablets similar in size, color and number to the active oral tablet vaccine drug product
Sponsors
Biomedical Advanced Research and Development Authority
Vaxart
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Oral vaccination followed by viral challenge at 3 months post vaccination
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male or female volunteers aged 18 - 49 years, inclusive 2. Able to give written informed consent 3. Low pre-existing antibodies to the study vaccine 4. In general good health (no clinically significant health concerns) 5. Safety laboratory normal range or not clinically significant (NCS), with few exceptions 6. Body mass index (BMI) between 17 and 35 7. Comprehension of the study requirements with ability and willingness to complete all assessments and comply with scheduled visits and contacts 8. Female participants must have a negative pregnancy test at screening
Exclusion criteria
1. Receipt of any influenza vaccine within two years prior to study 2. Use of any investigational vaccine/adjuvanted vaccine within 8 weeks of study 3. Use of any investigational drug or device within 4 weeks of study 4. Use of any licensed vaccine within 30 days of study 5. Presence of significant uncontrolled medical or psychiatric illness within 3 months of study 6. Clinically significant and/or protocol defined ECG abnormality 7. Positive serology for HIV-1 or HIV-2, or HBsAg or HCV antibodies 8. Cancer, or treatment for cancer, within 3 years of study 9. History of drug, alcohol or chemical abuse within 1 year 10. Receipt of blood or blood products within 6 months of study 11. Donation of blood within 4 weeks of study 12. Presence of a fever ≥ 38ºC measured orally at baseline 13. Stool sample with occult blood at screening 14. Positive urine drug screen for drugs of abuse at screening 15. Positive breath or urine alcohol test at screening or baseline 16. Consistent/habitual smoking within 2 months prior to vaccination 17. History of serious reactions to any vaccination such as anaphylaxis, respiratory problems, Guillain-Barre syndrome, hives or abdominal pain 18. Asthma, bronchiectasis or chronic obstructive pulmonary disease 19. Any known allergy or intolerance to oseltamivir
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Influenza-like Clinical Illness and Laboratory Confirmed Infection Post Challenge With a Homologous A Strain Influenza Virus | Clinical Illness and/or laboratory confirmed infection occurring following viral challenge at 3 months post vaccination | The clinical efficacy of VXA-A1.1 to protect against illness caused by the homologous A strain influenza virus with challenge 3 months following a single immunization in comparison to placebo and QIV. Participants were evaluated for clinical signs and symptoms of influenza as well as for viral shedding via PCR for confirmation of infection. |
Countries
United States
Participant flow
Recruitment details
Between Aug 31, 2016, and Jan 23, 2017, 374 individuals were assessed for eligibility.
Participants by arm
| Arm | Count |
|---|---|
| Oral Vaccine (VXA-A1.1) Oral enteric coated vaccine tablets. Placebo (saline solution) IM injection was also administered in this arm.
VXA-A1.1: Enteric coated oral vaccine tablet
Saline Solution for Placebo IM Injection | 71 |
| QIV IM Injection A commercially available QIV was administered at the approved dose level as the active comparator. Oral placebo tablets were also administered in this arm.
Fluzone®: Fluzone Quadravalent (Fluzone®) influenza vaccine (QIV) suspension for intramuscular (IM) injection
Placebo Tablets: Placebo tablets similar in size, color and number to the active oral tablet vaccine drug product | 72 |
| Oral and IM Placebo Two forms of placebo (saline IM injection and oral placebo tablets) were administered in this arm.
Placebo Tablets: Placebo tablets similar in size, color and number to the active oral tablet vaccine drug product
Saline Solution for Placebo IM Injection | 36 |
| Total | 179 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Allocation and Follow-Up | Lost to Follow-up | 1 | 2 | 1 |
| Allocation and Follow-Up | Withdrawal by Subject | 1 | 0 | 0 |
| Challenge Phase Analysis | Lost to Follow-up | 0 | 0 | 1 |
| Challenge Phase Analysis | Withdrawal by Subject | 0 | 0 | 1 |
| Vaccination Phase Analysis | Biofire Positive | 5 | 5 | 0 |
| Vaccination Phase Analysis | Exlcuded by Investigator for Safety of Compliance | 2 | 3 | 2 |
| Vaccination Phase Analysis | Seasonal allergies | 0 | 1 | 0 |
| Vaccination Phase Analysis | Symptoms of Sinusitis | 1 | 0 | 0 |
| Vaccination Phase Analysis | Withdrawal by Subject | 3 | 7 | 2 |
Baseline characteristics
| Characteristic | Oral Vaccine (VXA-A1.1) | Total | Oral and IM Placebo | QIV IM Injection |
|---|---|---|---|---|
| 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 | 71 Participants | 179 Participants | 36 Participants | 72 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 24 Participants | 55 Participants | 10 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 47 Participants | 121 Participants | 26 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Hemagglutination Inhibition (HAI) Titer | 54 participants | 132 participants | 29 participants | 49 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 20 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 37 Participants | 7 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 6 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 45 Participants | 114 Participants | 24 Participants | 45 Participants |
| Sex: Female, Male Female | 29 Participants | 73 Participants | 15 Participants | 29 Participants |
| Sex: Female, Male Male | 42 Participants | 106 Participants | 21 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 71 | 0 / 72 | 0 / 36 |
| other Total, other adverse events | 15 / 71 | 11 / 72 | 4 / 36 |
| serious Total, serious adverse events | 0 / 71 | 0 / 72 | 0 / 36 |
Outcome results
Primary
Number of Subjects With Influenza-like Clinical Illness and Laboratory Confirmed Infection Post Challenge With a Homologous A Strain Influenza Virus
The clinical efficacy of VXA-A1.1 to protect against illness caused by the homologous A strain influenza virus with challenge 3 months following a single immunization in comparison to placebo and QIV. Participants were evaluated for clinical signs and symptoms of influenza as well as for viral shedding via PCR for confirmation of infection.
Time frame: Clinical Illness and/or laboratory confirmed infection occurring following viral challenge at 3 months post vaccination
Population: Subjects that did not complete the vaccination phase per protocol criteria, did not undergo viral challenge, did not have Biofire results positive for infections other than influenza or were discharged early from the isolation unit post challenge were excluded from the per protocol analysis set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Vaccine (VXA-A1.1) | Number of Subjects With Influenza-like Clinical Illness and Laboratory Confirmed Infection Post Challenge With a Homologous A Strain Influenza Virus | 17 Participants |
| QIV IM Injection | Number of Subjects With Influenza-like Clinical Illness and Laboratory Confirmed Infection Post Challenge With a Homologous A Strain Influenza Virus | 19 Participants |
| Oral and IM Placebo | Number of Subjects With Influenza-like Clinical Illness and Laboratory Confirmed Infection Post Challenge With a Homologous A Strain Influenza Virus | 15 Participants |