Safety and Immunogenicity of PanBlok Influenza Vaccine in Healthy Adults

• Sponsor: Protein Sciences Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01147068
• Collaborator: (none)
• Enrollment: 392
• Locations: 4
• Arms: 7
• Duration (Months): 16
• Patients Per Site: 98
• Patients Per Site Per Month: 6.1

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the safety and immunogenicity of a recombinant hemagglutinin (rHA) influenza vaccine derived from A/Indonesia/05/2005 (H5N1) administered at 4 dose levels in adjuvanted (GLA-SE) rHA formulations and 2 dose levels in unadjuvanted rHA formulations.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Biological: 0.5mL Intramuscular Injection	Phase 1/Phase 2

Detailed Description

All currently licensed influenza vaccines in the United States are produced in embryonated hen's eggs. There are several well-recognized disadvantages to the use of eggs as the substrate for influenza vaccine. Eggs require specialized manufacturing facilities and could be difficult to scale up rapidly in response to an emerging need such as a pandemic. It is usually necessary to adapt candidate vaccine viruses for high-yield growth in eggs, a process that can be time consuming, is not always successful, and can select receptor variants that may have suboptimal immunogenicity. In addition, agricultural diseases that affect chicken flocks, and that might be an important issue in a pandemic due to an avian influenza virus strain, could easily disrupt the supply of eggs for vaccine manufacturing. Therefore, development of alternative substrates for influenza vaccine production has been identified as a high-priority objective.

One potential alternative method for production of influenza vaccine is expression of the influenza virus hemagglutinin (HA) using recombinant DNA techniques. This alternative avoids dependence on eggs and is very efficient because of the high levels of protein expression under the control of the baculovirus polyhedrin promoter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 392 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Two-Part Placebo-Controlled Evaluation of the Safety and Immunogenicity of an A/Indonesia/5/05 Recombinant Hemagglutinin Influenza H5N1 Vaccine With and Without Glucopyranosyl Lipid A (GLA-SE) in Healthy Adults 18-49
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PanBlok 135µg No Adjuvant 135µg recombinant hemagglutinin, no adjuvant; Two 0.5 mL IM injections 21 days apart	Biological: 0.5mL Intramuscular Injection; 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle; Other Names: rHA recombinant hemagglutinin PanBlok
Experimental: PanBlok 45µg No Adjuvant 45µg recombinant hemagglutinin, no adjuvant; Two 0.5 mL IM injections 21 days apart	Biological: 0.5mL Intramuscular Injection; 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle; Other Names: rHA recombinant hemagglutinin PanBlok
Experimental: PanBlok 45µg and GLA 1.0µg, SE 2% 45µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart	Biological: 0.5mL Intramuscular Injection; 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle; Other Names: rHA recombinant hemagglutinin PanBlok
Experimental: PanBlok 15µg and GLA 1.0µg, SE 2% 15µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart	Biological: 0.5mL Intramuscular Injection; 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle; Other Names: rHA recombinant hemagglutinin PanBlok
Experimental: PanBlok 7.5µg and GLA 1.0µg, SE 2% 7.5µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart	Biological: 0.5mL Intramuscular Injection; 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle; Other Names: rHA recombinant hemagglutinin PanBlok
Experimental: PanBlok 3.8µg and GLA 1.0µg, SE 2% 3.8µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart	Biological: 0.5mL Intramuscular Injection; 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle; Other Names: rHA recombinant hemagglutinin PanBlok
Placebo Comparator: Placebo 0.9% Sodium Chloride; Two 0.5 mL IM injections 21 days apart	Biological: 0.5mL Intramuscular Injection; 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle; Other Names: rHA recombinant hemagglutinin PanBlok

Outcome Measures

Primary Outcome Measures

1. Evaluation of Immunogenicity Measured by Seroconversion Rates of PanBlok With and Without Adjuvant Compared to Placebo in Healthy Adults 18-49 Years of Age. [42 Days]

   Immunogenicity was assessed by measuring the percentage of subjects in each group exhibiting seroconversion on Day 42. The treatment groups that received adjuvanted rHA were evaluated against non-adjuvanted rHA and placebo groups for whether they demonstrated seroconversion rates and 95% confidence intervals that met regulatory criterion for licensure.

Secondary Outcome Measures

1. Evaluation and Comparison of Immunogenicity From Geometric Mean Titers of PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age. [Day 0, and Day 42]

   Immunogenicity was assessed by measuring the proportion of subjects that exhibited a geometric mean titer change from Day 0 to Day 42. The geometric mean titers from the PanBlok groups (with and without adjuvant)and placebo group were then compared.

2. Serologic Response Rates at Day 21 Using PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age [21 Days]

   Immunogenicity was assessed by measuring the seroconversion rates of subjects from Day 0 to Day 21 to determine and evaluate the immune response following a single dose of study vaccine. The results were compared using PanBlok with and without adjuvant and placebo in healthy adults

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 49 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Male or female aged 18-49 years.

• Give written informed consent to participate.

• Healthy, as determined by medical history, physical examination, vital signs, and clinical safety laboratory evaluation

• Females should fulfill one of the following criteria:

• At least one year post-menopausal;

• Surgically sterile;

• Will use oral, implantable, transdermal or injectable contraceptives for 30 days prior to first vaccination and until 28 days after the booster vaccination; or

• Willing to use another reliable form of contraception approved by the Investigator (e.g., intrauterine device (IUD), female condom, diaphragm with spermicide, cervical cap, use of condom by the sexual partner or a sterile sexual partner) for 30 days prior to first vaccination and until 28 days after the booster vaccination.

• Women of childbearing potential must have a negative urine pregnancy test within 24 hours preceding receipt of first and booster vaccinations

• Comprehension of the study requirements, expressed availability for the required study period, and ability to attend scheduled visits.

Exclusion Criteria:

• Persons under 18 years old or 50 years or older

• Persons with chronic illnesses such as cancer, diabetes, liver or kidney disease

• Persons taking medications or treatments that may adversely affect the immune system

• Persons with known allergy to eggs or other vaccine or adjuvant components

• Person currently pregnant, nursing mothers or planning a pregnancy within one month of vaccination

• Persons who have had a prior serious reaction to any influenza vaccine

• Persons with a known history of Guillain-Barré Syndrome

• Persons with a history of anaphylactic-type reaction to injected vaccines

• Persons with a history of drug or chemical abuse in the year preceding the study

• Persons who previously received an H5N1 influenza vaccine or who plan to receive an H5N1 influenza vaccine while participating in the study

• Persons who received a seasonal influenza vaccine six months prior to enrollment (may delay enrollment)

• Persons who received any other vaccine within one week prior to enrollment (may delay enrollment)

• Persons who have had a respiratory illness or illness with fever within three days of study enrollment (may delay enrollment)

• Persons currently participating in another research study involving any study medications (investigational drugs or vaccines).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vince and Associates Clinical Research	Overland Park	Kansas	United States	66210
2	Meridian Clinical Research	Omaha	Nebraska	United States	68134
3	University of Rochester	Rochester	New York	United States	14642
4	Benchmark Research	Fort Worth	Texas	United States	76135

Sponsors and Collaborators

• Protein Sciences Corporation

Investigators

• Principal Investigator: John Treanor, MD, University of Rochester

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Manon M.J. Cox, CEO, Protein Sciences Corporation
• ClinicalTrials.gov Identifier: NCT01147068
• Other Study ID Numbers: PSC22 GLA-SE
• First Posted: Jun 22, 2010
• Last Update Posted: Nov 26, 2012
• Last Verified: Oct 1, 2012

• Keywords provided by Manon M.J. Cox, CEO, Protein Sciences Corporation: Influenza
• Additional relevant MeSH terms: Influenza, Human; Hemagglutinins

Study Results

Participant Flow

Recruitment Details	Healthy adults 18-49 years of age were screened in participating outpatient clinics for eligibility within 30 days of randomization during the 2010 influenza season.
Pre-assignment Detail	Subjects whose laboratory values were exclusionary were not randomized. Women of child-bearing potential were required to have a negative pregnancy test.

Arm/Group Title	Placebo	PanBlok 135µg No Adjuvant	PanBlok 45µg No Adjuvant	PanBlok 45µg and GLA 1.0µg, SE 2%	PanBlok 15µg and GLA 1.0µg, SE 2%	PanBlok 7.5µg and GLA 1.0µg, SE 2%	PanBlok 3.8µg and GLA 1.0µg, SE 2%
Arm/Group Description	0.9% Sodium Chloride; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	135µg recombinant hemagglutinin, no adjuvant; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	45µg recombinant hemagglutinin, no adjuvant; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	45µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	15µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	7.5µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	3.8µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle
Period Title: Subjects That Received 1st Dose
STARTED	60	57	55	56	56	53	55
COMPLETED	60	57	55	56	56	53	55
NOT COMPLETED	0	0	0	0	0	0	0
Period Title: Subjects That Received 1st Dose
STARTED	60	57	55	56	56	53	55
COMPLETED	59	52	52	56	55	51	55
NOT COMPLETED	1	5	3	0	1	2	0
Period Title: Subjects That Received 1st Dose
STARTED	60	57	55	56	56	53	55
COMPLETED	59	56	55	54	56	52	54
NOT COMPLETED	1	1	0	2	0	1	1

Baseline Characteristics

Arm/Group Title	Placebo	PanBlok 135µg No Adjuvant	PanBlok 45µg No Adjuvant	PanBlok 45µg and GLA 1.0µg, SE 2%	PanBlok 15µg and GLA 1.0µg, SE 2%	PanBlok 7.5µg and GLA 1.0µg, SE 2%	PanBlok 3.8µg and GLA 1.0µg, SE 2%	Total
Arm/Group Description	0.9% Sodium Chloride; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	135µg recombinant hemagglutinin, no adjuvant; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	45µg recombinant hemagglutinin, no adjuvant; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	45µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	15µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	7.5µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	3.8µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	Total of all reporting groups
Overall Participants	60	57	55	56	56	53	55	392
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	32.0	30.0	32.0	31.0	33.5	27.0	33.0	32.2
Sex: Female, Male (Count of Participants)
Female	33 55%	35 61.4%	32 58.2%	30 53.6%	43 76.8%	34 64.2%	25 45.5%	232 59.2%
Male	27 45%	22 38.6%	23 41.8%	26 46.4%	13 23.2%	19 35.8%	30 54.5%	160 40.8%

Outcome Measures

1. Primary Outcome

Title	Evaluation of Immunogenicity Measured by Seroconversion Rates of PanBlok With and Without Adjuvant Compared to Placebo in Healthy Adults 18-49 Years of Age.
Description	Immunogenicity was assessed by measuring the percentage of subjects in each group exhibiting seroconversion on Day 42. The treatment groups that received adjuvanted rHA were evaluated against non-adjuvanted rHA and placebo groups for whether they demonstrated seroconversion rates and 95% confidence intervals that met regulatory criterion for licensure.
Time Frame	42 Days

Outcome Measure Data

Analysis Population Description

All randomized subjects who received study vaccine and had Day 0 and Day 42 efficacy data. The analysis results are generated by Southern Research Institute on the intention to treat efficacy population using whole virus.

Arm/Group Title	Placebo	PanBlok 135µg No Adjuvant	PanBlok 45µg No Adjuvant	PanBlok 45µg and GLA 1.0µg, SE 2%	PanBlok 15µg and GLA 1.0µg, SE 2%	PanBlok 7.5µg and GLA 1.0µg, SE 2%	PanBlok 3.8µg and GLA 1.0µg, SE 2%
Arm/Group Description	0.9% Sodium Chloride; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	135µg recombinant hemagglutinin, no adjuvant; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	45µg recombinant hemagglutinin, no adjuvant; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	45µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	15µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	7.5µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	3.8µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle
Measure Participants	57	54	54	54	56	53	53
Number (95% Confidence Interval) [percentage of participants]	0 0%	32 56.1%	15 27.3%	82 146.4%	75 133.9%	66 124.5%	72 130.9%

2. Secondary Outcome

Title	Evaluation and Comparison of Immunogenicity From Geometric Mean Titers of PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age.
Description	Immunogenicity was assessed by measuring the proportion of subjects that exhibited a geometric mean titer change from Day 0 to Day 42. The geometric mean titers from the PanBlok groups (with and without adjuvant)and placebo group were then compared.
Time Frame	Day 0, and Day 42

Outcome Measure Data

Analysis Population Description

All randomized subjects who received study vaccine and had Day 0 and Day 42 geometric mean titers. Analysis of results were generated by Southern Research Institute on the overall population using whole virus.

Arm/Group Title	Placebo	PanBlok 135µg No Adjuvant	PanBlok 45µg No Adjuvant	PanBlok 45µg and GLA 1.0µg, SE 2%	PanBlok 15µg and GLA 1.0µg, SE 2%	PanBlok 7.5µg and GLA 1.0µg, SE 2%	PanBlok 3.8µg and GLA 1.0µg, SE 2%
Arm/Group Description	0.9% Sodium Chloride; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	135µg recombinant hemagglutinin, no adjuvant; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	45µg recombinant hemagglutinin, no adjuvant; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	45µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	15µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	7.5µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	3.8µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle
Measure Participants	57	54	54	54	56	53	53
Day 0	NA	NA	NA	NA	NA	NA	NA
Day 42	NA	16.7	10.7	128.4	94.5	68.7	71.7

3. Secondary Outcome

Title	Serologic Response Rates at Day 21 Using PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age
Description	Immunogenicity was assessed by measuring the seroconversion rates of subjects from Day 0 to Day 21 to determine and evaluate the immune response following a single dose of study vaccine. The results were compared using PanBlok with and without adjuvant and placebo in healthy adults
Time Frame	21 Days

Outcome Measure Data

Analysis Population Description

All randomized subjects with Day 0 and Day 21 data analyzed by Cincinnati Children's Hospital Medical Center using the intent to treat population and CBER antigen.

Arm/Group Title	Placebo	PanBlok 135µg No Adjuvant	PanBlok 45µg No Adjuvant	PanBlok 45µg and GLA 1.0µg, SE 2%	PanBlok 15µg and GLA 1.0µg, SE 2%	PanBlok 7.5µg and GLA 1.0µg, SE 2%	PanBlok 3.8µg and GLA 1.0µg, SE 2%
Arm/Group Description	0.9% Sodium Chloride; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	135µg recombinant hemagglutinin, no adjuvant; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	45µg recombinant hemagglutinin, no adjuvant; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	45µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	15µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	7.5µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle	3.8µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle
Measure Participants	60	56	54	56	56	52	55
Number (95% Confidence Interval) [percentage of participants]	3 5%	4 7%	4 7.3%	11 19.6%	7 12.5%	8 15.1%	2 3.6%

Adverse Events

Time Frame	All Adverse Events - 28 days following immunization; Serious adverse events, adverse events of special interest, and new onset of chronic illnesses for duration of 12-month follow-up after immunization.
Arm/Group Title	Placebo		PanBlok 135µg No Adjuvant		PanBlok 45µg No Adjuvant		PanBlok 45µg and GLA 1.0µg, SE 2%		PanBlok 15µg and GLA 1.0µg, SE 2%		PanBlok 7.5µg and GLA 1.0µg, SE 2%		PanBlok 3.8µg and GLA 1.0µg, SE 2%
Arm/Group Description	0.9% Sodium Chloride; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle		135µg recombinant hemagglutinin, no adjuvant; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle		45µg recombinant hemagglutinin, no adjuvant; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle		45µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle		15µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle		7.5µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle		3.8µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart 0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle
All Cause Mortality
	Placebo		PanBlok 135µg No Adjuvant		PanBlok 45µg No Adjuvant		PanBlok 45µg and GLA 1.0µg, SE 2%		PanBlok 15µg and GLA 1.0µg, SE 2%		PanBlok 7.5µg and GLA 1.0µg, SE 2%		PanBlok 3.8µg and GLA 1.0µg, SE 2%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		PanBlok 135µg No Adjuvant		PanBlok 45µg No Adjuvant		PanBlok 45µg and GLA 1.0µg, SE 2%		PanBlok 15µg and GLA 1.0µg, SE 2%		PanBlok 7.5µg and GLA 1.0µg, SE 2%		PanBlok 3.8µg and GLA 1.0µg, SE 2%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/60 (1.7%)		2/57 (3.5%)		1/55 (1.8%)		1/56 (1.8%)		2/56 (3.6%)		0/53 (0%)		3/55 (5.5%)
Cardiac disorders
Costochondritis	0/60 (0%)	0	0/57 (0%)	0	0/55 (0%)	0	0/56 (0%)	0	0/56 (0%)	0	0/53 (0%)	0	1/55 (1.8%)	3
Gastrointestinal disorders
Incisional Hernia	0/60 (0%)	0	1/57 (1.8%)	2	0/55 (0%)	0	0/56 (0%)	0	0/56 (0%)	0	0/53 (0%)	0	0/55 (0%)	0
Abdominopelvic Mass	0/60 (0%)	0	1/57 (1.8%)	2	0/55 (0%)	0	0/56 (0%)	0	0/56 (0%)	0	0/53 (0%)	0	0/55 (0%)	0
Appendicitis	0/60 (0%)	0	0/57 (0%)	0	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	2	0/53 (0%)	0	0/55 (0%)	0
General disorders
Worsening of Right Ankle Instability	1/60 (1.7%)	1	0/57 (0%)	0	0/55 (0%)	0	0/56 (0%)	0	0/56 (0%)	0	0/53 (0%)	0	0/55 (0%)	0
Infections and infestations
Post-operative Infection	0/60 (0%)	0	0/57 (0%)	0	1/55 (1.8%)	3	0/56 (0%)	0	0/56 (0%)	0	0/53 (0%)	0	0/55 (0%)	0
Metabolism and nutrition disorders
Unspecified Protein Calorie Malnutrition	0/60 (0%)	0	1/57 (1.8%)	3	0/55 (0%)	0	0/56 (0%)	0	0/56 (0%)	0	0/53 (0%)	0	0/55 (0%)	0
Nervous system disorders
Seizure	0/60 (0%)	0	0/57 (0%)	0	0/55 (0%)	0	1/56 (1.8%)	1	0/56 (0%)	0	0/53 (0%)	0	0/55 (0%)	0
Reproductive system and breast disorders
Intrauterine Fetal Demise	0/60 (0%)	0	0/57 (0%)	0	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	2	0/53 (0%)	0	0/55 (0%)	0
Ovarian Cyst	0/60 (0%)	0	0/57 (0%)	0	0/55 (0%)	0	0/56 (0%)	0	0/56 (0%)	0	0/53 (0%)	0	1/55 (1.8%)	3
Respiratory, thoracic and mediastinal disorders
Left Upper Lobe Lung Nodule with Organizing Abscess	0/60 (0%)	0	0/57 (0%)	0	0/55 (0%)	0	0/56 (0%)	0	0/56 (0%)	0	0/53 (0%)	0	1/55 (1.8%)	3
Surgical and medical procedures
Fractured/Cracked Vertebrae	0/60 (0%)	0	0/57 (0%)	0	1/55 (1.8%)	3	0/56 (0%)	0	0/56 (0%)	0	0/53 (0%)	0	0/55 (0%)	0
Pinched nerve between C3-6	0/60 (0%)	0	0/57 (0%)	0	1/55 (1.8%)	3	0/56 (0%)	0	0/56 (0%)	0	0/53 (0%)	0	0/55 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		PanBlok 135µg No Adjuvant		PanBlok 45µg No Adjuvant		PanBlok 45µg and GLA 1.0µg, SE 2%		PanBlok 15µg and GLA 1.0µg, SE 2%		PanBlok 7.5µg and GLA 1.0µg, SE 2%		PanBlok 3.8µg and GLA 1.0µg, SE 2%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/60 (65%)		36/57 (63.2%)		33/55 (60%)		35/56 (62.5%)		40/56 (71.4%)		32/53 (60.4%)		38/55 (69.1%)
Blood and lymphatic system disorders
Blood Cholesterol Increased	6/60 (10%)	6	4/57 (7%)	4	7/55 (12.7%)	7	5/56 (8.9%)	5	5/56 (8.9%)	5	3/53 (5.7%)	3	9/55 (16.4%)	9
Lymphocytosis	2/60 (3.3%)	2	2/57 (3.5%)	2	0/55 (0%)	0	0/56 (0%)	0	2/56 (3.6%)	2	1/53 (1.9%)	1	0/55 (0%)	0
Cardiac disorders
Bradycardia	3/60 (5%)	3	0/57 (0%)	0	3/55 (5.5%)	3	0/56 (0%)	0	2/56 (3.6%)	2	0/53 (0%)	0	2/55 (3.6%)	2
General disorders
Pyrexia	0/60 (0%)	0	2/57 (3.5%)	2	0/55 (0%)	0	0/56 (0%)	0	2/56 (3.6%)	2	3/53 (5.7%)	3	0/55 (0%)	0
Fatigue	1/60 (1.7%)	1	0/57 (0%)	0	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	2/53 (3.8%)	2	0/55 (0%)	0
Hepatobiliary disorders
Alanine Aminotransferase Increased	1/60 (1.7%)	1	3/57 (5.3%)	3	1/55 (1.8%)	1	3/56 (5.4%)	3	2/56 (3.6%)	2	5/53 (9.4%)	5	3/55 (5.5%)	3
Aspartate Aminotransferase Increased	0/60 (0%)	0	1/57 (1.8%)	1	0/55 (0%)	0	3/56 (5.4%)	3	2/56 (3.6%)	2	0/53 (0%)	0	4/55 (7.3%)	4
Infections and infestations
Rhinitis	0/60 (0%)	0	0/57 (0%)	0	1/55 (1.8%)	1	0/56 (0%)	0	3/56 (5.4%)	3	0/53 (0%)	0	0/55 (0%)	0
Upper Respiratory Tract Infection	0/60 (0%)	0	0/57 (0%)	0	1/55 (1.8%)	1	1/56 (1.8%)	1	1/56 (1.8%)	1	3/53 (5.7%)	3	2/55 (3.6%)	2
Nasopharyngitis	0/60 (0%)	0	0/57 (0%)	0	1/55 (1.8%)	1	0/56 (0%)	0	2/56 (3.6%)	2	2/53 (3.8%)	2	1/55 (1.8%)	1
Sinusitis	2/60 (3.3%)	2	1/57 (1.8%)	1	1/55 (1.8%)	1	0/56 (0%)	0	0/56 (0%)	0	0/53 (0%)	0	2/55 (3.6%)	2
Injury, poisoning and procedural complications
Hand Fracture	0/60 (0%)	0	0/57 (0%)	0	0/55 (0%)	0	0/56 (0%)	0	0/56 (0%)	0	2/53 (3.8%)	2	0/55 (0%)	0
Joint Sprain	0/60 (0%)	0	0/57 (0%)	0	0/55 (0%)	0	0/56 (0%)	0	0/56 (0%)	0	2/53 (3.8%)	2	0/55 (0%)	0
Investigations
Blood Glucose Increased	4/60 (6.7%)	4	5/57 (8.8%)	5	4/55 (7.3%)	4	4/56 (7.1%)	4	4/56 (7.1%)	4	1/53 (1.9%)	1	3/55 (5.5%)	3
Mean Cell Haemoglobin Concentration Decreased	1/60 (1.7%)	1	2/57 (3.5%)	2	1/55 (1.8%)	1	4/56 (7.1%)	4	5/56 (8.9%)	5	1/53 (1.9%)	1	1/55 (1.8%)	1
Carbon Dioxide Decreased	2/60 (3.3%)	2	1/57 (1.8%)	1	1/55 (1.8%)	1	2/56 (3.6%)	2	3/56 (5.4%)	3	2/53 (3.8%)	2	2/55 (3.6%)	2
Gamma-Glutamyltransferase Increased	2/60 (3.3%)	2	2/57 (3.5%)	2	1/55 (1.8%)	1	2/56 (3.6%)	2	2/56 (3.6%)	2	3/53 (5.7%)	3	2/55 (3.6%)	2
Haemoglobin Decreased	2/60 (3.3%)	2	1/57 (1.8%)	1	0/55 (0%)	0	0/56 (0%)	0	3/56 (5.4%)	3	1/53 (1.9%)	1	0/55 (0%)	0
Neutrophil Count Increased	1/60 (1.7%)	1	0/57 (0%)	0	0/55 (0%)	0	0/56 (0%)	0	3/56 (5.4%)	3	0/53 (0%)	0	3/55 (5.5%)	3
White Blood Cell Count Increased	0/60 (0%)	0	4/57 (7%)	4	2/55 (3.6%)	2	3/56 (5.4%)	3	3/56 (5.4%)	3	2/53 (3.8%)	2	3/55 (5.5%)	3
Blood Creatinine Increased	5/60 (8.3%)	5	0/57 (0%)	0	4/55 (7.3%)	4	2/56 (3.6%)	2	2/56 (3.6%)	2	0/53 (0%)	0	0/55 (0%)	0
Blood Lactate Dehydrogenase Increased	3/60 (5%)	3	0/57 (0%)	0	0/55 (0%)	0	2/56 (3.6%)	2	1/56 (1.8%)	1	2/53 (3.8%)	2	2/55 (3.6%)	2
Blood Urea Nitrogen/Creatinine Ratio Decreased	5/60 (8.3%)	5	1/57 (1.8%)	1	1/55 (1.8%)	1	0/56 (0%)	0	2/56 (3.6%)	2	2/53 (3.8%)	2	1/55 (1.8%)	1
Haematocrit Decreased	0/60 (0%)	0	1/57 (1.8%)	1	0/55 (0%)	0	0/56 (0%)	0	2/56 (3.6%)	2	0/53 (0%)	0	0/55 (0%)	0
Blood Cholesterol Increased	6/60 (10%)	6	4/57 (7%)	4	7/55 (12.7%)	7	5/56 (8.9%)	5	5/56 (8.9%)	5	3/53 (5.7%)	3	9/55 (16.4%)	9
Haematocrit Increased	1/60 (1.7%)	1	1/57 (1.8%)	1	1/55 (1.8%)	1	2/56 (3.6%)	2	2/56 (3.6%)	2	1/53 (1.9%)	1	1/55 (1.8%)	1
Neutrophil Count Decreased	1/60 (1.7%)	1	0/57 (0%)	0	1/55 (1.8%)	1	0/56 (0%)	0	1/56 (1.8%)	1	2/53 (3.8%)	2	2/55 (3.6%)	2
Red Cell Distribution Width Increased	0/60 (0%)	0	1/57 (1.8%)	1	1/55 (1.8%)	1	2/56 (3.6%)	2	1/56 (1.8%)	1	1/53 (1.9%)	1	2/55 (3.6%)	2
Metabolism and nutrition disorders
Hyperglycaemia	1/60 (1.7%)	1	2/57 (3.5%)	2	1/55 (1.8%)	1	2/56 (3.6%)	2	2/56 (3.6%)	2	1/53 (1.9%)	1	2/55 (3.6%)	2
Hyperlipidaemia	0/60 (0%)	0	1/57 (1.8%)	1	0/55 (0%)	0	2/56 (3.6%)	2	0/56 (0%)	0	0/53 (0%)	0	3/55 (5.5%)	3
Hypertriglyceridaemia	0/60 (0%)	0	0/57 (0%)	0	0/55 (0%)	0	0/56 (0%)	0	2/56 (3.6%)	2	2/53 (3.8%)	2	0/55 (0%)	0
Nervous system disorders
Headache	1/60 (1.7%)	1	1/57 (1.8%)	1	0/55 (0%)	0	0/56 (0%)	0	0/56 (0%)	0	3/53 (5.7%)	3	0/55 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/60 (0%)	0	1/57 (1.8%)	1	0/55 (0%)	0	2/56 (3.6%)	2	4/56 (7.1%)	4	4/53 (7.5%)	4	0/55 (0%)	0
Oropharngeal Pain	1/60 (1.7%)	1	2/57 (3.5%)	2	0/55 (0%)	0	0/56 (0%)	0	2/56 (3.6%)	2	3/53 (5.7%)	3	2/55 (3.6%)	2
Nasal Congestion	1/60 (1.7%)	1	2/57 (3.5%)	2	0/55 (0%)	0	1/56 (1.8%)	1	2/56 (3.6%)	2	2/53 (3.8%)	2	0/55 (0%)	0

Limitations/Caveats

The absence of a treatment group receiving a SE- or GLA-alone adjuvanted vaccine formulation is a limitation to the study conclusion.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.