Trial Outcomes & Findings for Lot-to-lot Consistency of a Plant-Derived Quadrivalent Virus-Like Particles Influenza Vaccine in Healthy Adults (NCT NCT03321968)

Participants were randomized in a 1:1:1 ratio to receive one of the three lots of the Quadrivalent Virus-Like Particles (VLP) Influenza Vaccine at a dose of 30 μg/strain.

Participants were healthy adults 18 to 49 years of age assessed during the 2016-2017 influenza season.

Lot-to-lot Consistency of a Plant-Derived Quadrivalent Virus-Like Particles Influenza Vaccine in Healthy Adults

The GMTs were measured using a HI assay for the homologous strains: A/California/7/2009 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008 (Victoria lineage), and B/Phuket/3073/2013 (Yamagata lineage). Lot-to-lot consistency was based on adjusted GMT ratio for pairwise comparisons of the lots (Lot 1 / Lot 2, Lot 1 / Lot 3, and Lot 2 / Lot 3).

The SC rate is the percentage of participants with either a ≥ 4-fold increase in reciprocal HI titers between Day 0 and Day 21 or a rise of undetectable HI titer (i.e. \<10) pre-vaccination (Day 0) to an HI titer of ≥40 on Day 21 post-vaccination. SC rate was measured using an HI assay for the homologous strains: A/California/7/2009 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008 (Victoria lineage), and B/Phuket/3073/2013 (Yamagata lineage).

The SP rate is the percentage of participants attaining a reciprocal HI titer of ≥ 40 on Day 21 (the percentage of vaccine recipients with a serum HI titer of at least 1:40 following vaccination). SP rate was measured using an HI assay for the homologous strains: A/California/7/2009 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008 (Victoria lineage), and B/Phuket/3073/2013 (Yamagata lineage).

GMFR, the geometric mean of the ratio of GMTs (Day 21/Day 0), was measured using an HI assay for the homologous strains: A/California/7/2009 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008 (Victoria lineage), and B/Phuket/3073/2013 (Yamagata lineage).

Immediate complaints were defined as any solicited local or systemic reactions. Solicited local reactions included: erythema, swelling, and pain at the injection site and solicited systemic reactions included: fever, headache, fatigue, muscle aches, joint aches, chills, a feeling of general discomfort, swelling in the axilla, and swelling in the neck.

Participants were monitored for both solicited local reactions (erythema, swelling, and pain at the injection site) and solicited systemic reactions (fever, headache, fatigue, muscle aches, joint aches, chills, a feeling of general discomfort, swelling in the axilla, and swelling in the neck). Any solicited local or systemic immediate complaint was also included.

Participants were monitored for both solicited local reactions (erythema, swelling, pain at the injection site) and solicited systemic reactions (fever, headache, fatigue, muscle aches, joint aches, chills, a feeling of general discomfort, swelling in the axilla, swelling in the neck). Any solicited local or systemic immediate complaint was also included. Intensity of solicited reactions graded as mild (1)-easily tolerated and does not interfere with usual activity; moderate (2)-interferes with daily activity, but the participant is still able to function; severe (3)-incapacitating and the participant is unable to work or complete usual activity or potentially life threatening;(4)-likely to be life-threatening if not treated in a timely manner, according to the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. The ≥severe events included severe and potentially life-threatening events.

Participants were monitored for both solicited local reactions (erythema, swelling, pain at the injection site) and solicited systemic reactions (fever, headache, fatigue, muscle aches, joint aches, chills, a feeling of general discomfort, swelling in the axilla, swelling in the neck). Intensity of solicited reactions was graded according to the FDA toxicity grade: mild (1); moderate (2); severe (3); (4)-likely to be life-threatening if not treated in a timely manner. Causal relationship with study vaccine was assessed as "definitely not related" (clearly not related),"probably not related" (no medical evidence),"possibly related"(reasonable possibility of cause and effect),"probably related"(plausible biologic mechanism and temporal relationship) or "definitely related"(direct cause and effect relationship). The ≥severe events included severe and "potentially life-threatening" and the related category included "possibly related", "probably related", and "definitely related."

Participants were monitored for unsolicited TEAEs. An adverse event (AE) or adverse experience was defined as any untoward medical occurrence in a participant or clinical investigation participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. An AE was considered treatment-emergent if it was aggravated in severity or frequency following the administration of the study vaccine, up to and including the last visit of the study.

The intensity of the unsolicited TEAEs was graded as mild (1)-easily tolerated and does not interfere with usual activity; moderate (2)-interferes with daily activity, but the participant is still able to function; severe (3)-incapacitating and the participant is unable to work or complete usual activity or potentially life threatening; (4)-likely to be life-threatening if not treated in a timely manner, according to the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. The ≥ Severe events included severe and potentially life-threatening events. AE and TEAEs are defined in outcome measure#9.

The intensity of the unsolicited TEAEs was graded as: mild (1), moderate (2), severe (3) or potentially life threatening (4). The causal relationship with the study vaccine was assessed as "definitely not related" (clearly not related),"probably not related" (no medical evidence), "possibly related" (reasonable possibility of cause and effect), "probably related" (plausible biologic mechanism and temporal relationship) or "definitely related" (direct cause and effect relationship). The ≥severe events included "severe" and "potentially life-threatening" and the related category included "possibly related", "probably related", and "definitely related." AE and TEAEs are defined in outcome measure #9.

The number of participants with an occurrence of death was assessed.

A serious adverse event (SAE) was considered to be any untoward medical occurrence (whether or not considered to be related to the study vaccine) that, at any dose results in death; is life-threatening (at the time of the event); requires inpatient hospitalization (≥ 24 hours) or prolongation of existing hospitalization (elective hospitalizations/procedures for pre-existing conditions that have not worsened are excluded); results in persistent or significant disability/incapacity; is a congenital abnormality/birth defect; or is another medically important event (e.g. any cases of newly diagnosed cancer). AE and TEAEs is defined in outcome measure #9.

An AE or adverse experience was defined as any untoward medical occurrence in a participant or clinical investigation participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. The number of participants with at least one adverse event leading to withdrawal was assessed.

All NOCDs that may plausibly have an allergic, autoimmune or inflammatory component were reported. Plausibility should be interpreted broadly; however, the only clear exceptions are degenerative conditions such as osteoarthritis, age-related physiologic changes and life-style diseases. In this context, most cancers, cardiac conditions and kidney diseases should be reported. NOCDs were collected from vaccination on Day 0 to the end of the Day 21 visit.