(n=74): adjuvanted FLU-v on Day 0, saline (0.5mL) on Day 21

(n=37): saline solution (0.5ml) on Day 0 and Day 21

(n=37): Adjuvanted placebo on Day 0, saline (0.5mL) on Day 21

FLU-v on Day 0 and Day 21
FLU-v: Subcutaneous injection in the upper arm with 500 ug of FLU-v as 0.5ml suspension in 0.01M HCl and 0.01M NaOH

2x Non-adjuvanted FLU-v

adjuvanted FLU-v on Day 0, saline (0.5mL) on Day 21
adjuvanted FLU-v: Subcutaneous injection in the upper arm with 500ug of FLU-v emulsified in 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection
Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

1x Adjuvanted FLU-v

saline solution (0.5ml) on Day 0 and Day 21
Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Non-adjuvanted Placebo

Adjuvanted placebo on Day 0, saline (0.5mL) on Day 21
Saline: Subcutaneous injection in the upper arm with 0.5ml of saline
Adjuvanted placebo: Subcutaneous injection in the upper arm with an emulsion made with 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Adjuvanted Placebo

Total

Sex: Female, Male

Race/Ethnicity, Customized

Subjects were asked whether they had received previous influenza vaccinations and whether it was within 2 years or more from joining the trial.

previous influenza vaccination

Serum samples were collected at screening (summer-autumn 2016) and later analysed for pre-existing neutralising antibodies against the main influenza strains that circulated in the Netherlands during the influenza season of 2016-2017 (B/Phuket/3073/2013, B/Brisbane/60/2008, A/Hong Kong/5738/2014 (H3N2) and A/Michigan/45/15 (H1N1)). The number of subjects with a HA titer for A strains ≥ 40 and with HA ≥ 80 for B strains was recorded in each group.

HAI titer at screening

To compare the number of subjects that showed at least a two-fold increase on day 42 and day 180 following vaccination in the number of CD4+T-cells secreting TH1 cytokines in all groups.

Percentage of CD4+ TH1 Cytokine Responders

Responders were defined as subjects having at least a two-fold increase in the amount of IFNg secreted on day 42 and day 180 compared the amount secreted on day 0. IFNg was measured by ELISA

Percentage of Responders on Day 42 and Day 180 for IFNgamma Secretion by PBMCs

To evaluate the solicited AEs in all subjects

Solicited AEs

To evaluate the level of TH2 cytokines (IL-4) from baseline in all groups 42 and 180 days following FLU-v vaccination.

Th2 Cytokine Responses (IL-4)

To evaluate the humoral immune responses specific to FLU-v from baseline in all groups 42 and 180 days following FLU-v vaccination. Specific FLU-v IgG antibodies were measured by ELISA. The geometric mean for each treatment group was provided.

Antibody Responses to FLU-v

To evaluate unsolicited AEs and SAEs in all subjects

Unsolicited AEs and SAEs

To evaluate the change from baseline in cellular immune responses based on additional CMI assays such as ELISPOT (Enzyme-Linked ImmunoSpot) in all groups at 42 and 180 days following FLU-v vaccination

Immune Responses Measured by IFNgamma/Granzyme B ELISPOT

During the influenza season (Dec 2016 to March 2017), fully vaccinated subjects will contact the trial center immediately if they feel unwell for 24h, with a sudden onset of flu-like symptoms. The medical staff will arrange for a nasopharyngeal swab to be performed if the subject has at least one respiratory (cough, sore throat, shortness of breath, runny nose, stuffy nose, sneezing and earache) and one systemic symptom (fever, malaise, headache and myalgia (muscle and joint pain). Swabs should be taken from the reported subjects within 3 days from the trial center being contacted or within 4 days of the onset of symptoms, whatever time is shorter.

Percentage of Participants Who Tested Positive for Influenza Strains

Subjects recorded daily influenza symptoms from December 2016 up to March 2017. Subjects with a sudden onset of at least one respiratory and one systemic symptom were swabbed. If the results were positive for influenza then the symptoms were included in the analysis. The duration of symptoms was recorded as the number of symptomatic days during the influenza episode. Fever (≥38oC), malaise, headache, myalgia (muscle and joint pain), cough, sore throat, shortness of breath, runny nose, stuffy nose, sneezing and earache were scored on a severity scale of 0 to 3 (0: no symptom, 1: mild, 2: moderate, 3: severe). The daily severity score was the sum of the severity score for all symptoms listed above on a single day. The total score was the sum of all daily scores during the influenza episode. The peak score was the highest daily score during the influenza episode. The average score was the total score divided by the number of days the influenza episode lasted.

Severity of Symptoms in RT-PCR Influenza-confirmed Subjects.

Subjects recorded daily influenza symptoms from December 2016 up to March 2017. Subjects with a sudden onset of at least one respiratory and one systemic symptom were swabbed. If the results were positive for influenza then the symptoms were included in the analysis. The duration of symptoms was recorded as the number of symptomatic days during the influenza episode. The following symptoms were recorded: fever (≥38oC), malaise, headache, myalgia (muscle and joint pain), cough, sore throat, shortness of breath, runny nose, stuffy nose, sneezing and earache.

Duration of Influenza Symptoms in RT-PCR Confirmed Infected Subjects.

Overall Study

Dr Olga Pleguezuelos, Chief Scientific Officer

Influenza

Subcutaneous injection in the upper arm with 500 ug of FLU-v as 0.5ml suspension in 0.01M HCl and 0.01M NaOH

FLU-v

Subcutaneous injection in the upper arm with 500ug of FLU-v emulsified in 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

adjuvanted FLU-v

Subcutaneous injection in the upper arm with 0.5ml of saline

Saline

Subcutaneous injection in the upper arm with an emulsion made with 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Adjuvanted placebo

Website for the Consortium Universal Influenza Vaccine Secure

Isala

A Randomised, Double-blind, Placebo-controlled Phase IIb Trial to Test FLU-v Vaccine

A Randomised, Double-blind, Placebo-controlled, Single-centre Phase IIb Trial as Part of the EU-funded UNISEC Project to Assess the Immunogenicity and Safety of Different Formulations and Dosing Regimens of FLU-v Vaccine in Healthy Adults

PepTcell Limited

Seventh Framework Programme

University of Groningen

University Medical Center Groningen

Robert Koch Institut

Norwegian Institute of Public Health

Typical pre-operative intervention including injectable local anesthetic into the inferior and middle turbinates followed by topical anesthetic on soaked cottonoids or pledgets placed in the nasal cavity floor, medial to the middle turbinate, behind the uncinate process will be performed. Using endoscopy, the nasal passage is located. Under endoscopic visualization, the microdebrider will be utilized to perform 1) excision of the concha bullosa, 2) maxillary antrostomy, and 3) submucosal cauterization of the turbinates. Suction/irrigation will be utilized as necessary.

Typical pre-operative intervention including injectable local anesthetic into the inferior and middle turbinates followed by topical anesthetic on soaked cottonoids or pledgets placed in the nasal cavity floor, medial to the middle turbinate, behind the uncinate process will be performed. Using endoscopy, the nasal passage is located. Under endoscopic visualization, the Gold Laser will be utilized to perform 1) excision of the concha bullosa, 2) maxillary antrostomy, and 3) submucosal cauterization of the turbinates. Suction/irrigation will be utilized as necessary. If the Investigator determines that the sinus is not sufficiently dilated or cannot be accessed, the need for and the type of additional treatment will be at the discretion of the Investigator.

Sinusitis

Under endoscopic visualization, the Gold Laser will be utilized to perform 1) excision of the concha bullosa, 2) maxillary antrostomy, and 3) submucosal cauterization of the turbinates. Suction/irrigation will be utilized as necessary.

Gold Laser

Under endoscopic visualization, the microdebrider will be utilized to perform 1) excision of the concha bullosa, 2) maxillary antrostomy, and 3) submucosal cauterization of the turbinates.

Microdebridement

Sinus Surgery [Internet]. Pensacola: Medical Energy Inc.; c2015 [cited 2016 March 24]

Winters R, Knight Worley N. Gold Laser Resection of the Concha Bullosa: Description of a New Technique. Otolaryngology. 2012; 2:2.

Lethbridge-Cejku M, Rose D, Vickerie J. Summary health statistics for US adults: National Health Interview Survey, 2004. Vital Health Stat. 2006;10:19-22.

Stavem K, Rossberg E, Larsson P. Reliability, validity and responsiveness of a Norwegian Version of the Chronic Sinusitis Survey. BMC Ear, Nose and Throat Disorders. 2006; 6:9.

1. Ware, JE. The SF-36 Health Survey Manual and Interpretation Guide. Nimrod Press, Boston 1993; pp 10-14

Texas Tech University Health Sciences Center

Gold Laser Vs. Micro-Debriders for Functional Endoscopic Sinus Surgery

Comparing Post-Operative Outcomes Between Gold Laser and Micro-Debriders for Functional Endoscopic Sinus Surgery (FESS) in Patients With Chronic Sinusitis

Comparison will be made of change in patient-reported quality of life (QOL) as measured by Total CSS score at 2 weeks, 8 weeks, and 24 weeks postoperatively for subjects randomized to micro-debridement versus gold laser.

Comparison will be made of change in patient-reported quality of life (QOL) as measured by rhinosinusitis disability index (RSDI) total, physical, functional, and emotional sub-scores at 2 weeks, 8 weeks, and 24 weeks postoperatively for subjects randomized to microdebridement versus gold laser

Comparison will be made of medication type (name), dosage, frequency, and route of administration at 8 weeks and 24 weeks postoperatively (days of oral antibiotics, oral steroids, topical intranasal steroid sprays, topical and nasal anti-histamines) for subjects randomized to microdebridement versus gold laser.

Comparison will be made of missed days at work/school and unscheduled medical care visits due to sinusitis at 8 weeks and 24 weeks postoperatively for subjects randomized to microdebridement versus gold laser.

Comparison will be made of patient reported pre-post-enrollment sinus infections and patient-reported sinus infection severity for subjects randomized to microdebridement versus gold laser

granuloma/céphalée

A Randomised, Double-blind, Placebo-controlled Phase IIb Trial to Test FLU-v Vaccine

Gold Laser Vs. Micro-Debriders for Functional Endoscopic Sinus Surgery

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