NCT00539981

Immunogenicity, Safety, Reactogenicity, Efficacy, Effectiveness and Lot Consistency of FluBlok

Completed Phase 3 Results posted Last updated 6 April 2022

What this trial tests

Phase 3 trial testing FluBlok® in Influenza in 4,648 participants. Completed in 28 May 2008.

Timeline

15 September 2007

Primary endpoint
28 May 2008

28 May 2008

Quick facts

Lead sponsor	Sanofi
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	prevention
Enrollment	4,648
Start date	15 September 2007
Primary completion	28 May 2008
Estimated completion	28 May 2008
Sites	24 locations across United States

Drugs / interventions tested

• FluBlok®
• Placebo

Conditions studied

• Influenza — all drugs for Influenza →

Sponsor

Sanofi — full company profile →

Who can join

Adults 18 to 49, any sex, with Influenza. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Reporting Solicited Injection Site (Local) Reactions Primary · Within 7 days post vaccination

Solicited reaction (reactogenicity event) was an adverse event (AE) that was pre-listed in electronic case report form(eCRF), considered to be related to vaccination and recorded by participant by means of memory aid. Injection sites reaction included pain,bruising,redness,swelling. Pain and bruising:Grade0: didn't have it at all; Grade1: noticed it, but it didn't interfere with usual activities at all; Grade2: had it, and it was bad enough to prevent a significant part of usual activities; Grade3: had it, and it prevented most or all of normal activities, or had to see a doctor for prescripti

Injection site pain- Grade 0

Group	Value	95% CI
FluBlok (Lots A, B, C)	1421
Placebo	2050

Injection site pain- Grade 1

Group	Value	95% CI
FluBlok (Lots A, B, C)	797
Placebo	177

Injection site pain- Grade 2

Group	Value	95% CI
FluBlok (Lots A, B, C)	52
Placebo	3

Injection site pain- Grade 3

Group	Value	95% CI
FluBlok (Lots A, B, C)	2
Placebo	1

Injection site bruising- Grade 0

Group	Value	95% CI
FluBlok (Lots A, B, C)	2197
Placebo	2172

Injection site bruising- Grade 1

Group	Value	95% CI
FluBlok (Lots A, B, C)	68
Placebo	57

Injection site bruising- Grade 2

Group	Value	95% CI
FluBlok (Lots A, B, C)	6
Placebo	1

Injection site bruising- Grade 3

Group	Value	95% CI
FluBlok (Lots A, B, C)	1
Placebo	1

Number of Participants Reporting Solicited Systemic Reactions Primary · Within 7 days post vaccination

Solicited reaction (reactogenicity event) was an AE that was pre-listed in eCRF, considered to be related to vaccination recorded by the participant by means of a memory aid between the day of vaccination (Day 0) and Day 7 post vaccination. Systemic events included fever, fatigue, shivering, joint pain, muscle pain, headache, and nausea. Fever: \>=100.4 degree Fahrenheit (ºF) to \<101.1ºF; \>=101.2ºF to \<102.2ºF; \>=102.2ºF; Fatigue, shivering, joint pain, muscle pain, headache and nausea: Grade 0: didn't have it at all; Grade 1: noticed it, but it didn't interfere with usual activities at al

Fever (>=100.4ºF)

Group	Value	95% CI
FluBlok (Lots A, B, C)	2238
Placebo	2188

Fever (>=100.4 to <101.1ºF)

Group	Value	95% CI
FluBlok (Lots A, B, C)	8
Placebo	5

Fever (>=101.2 to <102.2ºF)

Group	Value	95% CI
FluBlok (Lots A, B, C)	5
Placebo	6

Fever (>=102.2ºF)

Group	Value	95% CI
FluBlok (Lots A, B, C)	4
Placebo	1

Fatigue- Grade 0

Group	Value	95% CI
FluBlok (Lots A, B, C)	1932
Placebo	1898

Fatigue- Grade 1

Group	Value	95% CI
FluBlok (Lots A, B, C)	250
Placebo	256

Fatigue- Grade 2

Group	Value	95% CI
FluBlok (Lots A, B, C)	78
Placebo	66

Fatigue- Grade 3

Group	Value	95% CI
FluBlok (Lots A, B, C)	12
Placebo	11

Number of Participants Reporting Unsolicited Adverse Events Primary · From Day 0 (post-vaccination) through Day 28 post vaccination

An AE was defined as any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a study vaccine, whether or not considered to be related to the study vaccine. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination, ascertained during follow-up visit or telephone contact up to (and including) the Day 28 contact, whether reported spontaneously by the participant or in response to general questi

Group	Value	95% CI
FluBlok (Lots A, B, C)	61
Placebo	67

Lot Consistency: Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies Following FluBlok Vaccination Primary · Day 28 post vaccination

GMTs of anti-influenza antibodies were measured using a single radial immunodiffusion (SRID) assay for 3 strains: A/Solomon Islands \[H1N1\], A/Wisconsin \[H3N2\], and B/Malaysia. Titers were expressed in terms of 1/dilution.

A/Solomon Islands (H1N1)

Group	Value	95% CI
FluBlok: Lot A	346.15	291.96 – 410.41
FluBlok: Lot B	322.95	274.80 – 379.55
FluBlok: Lot C	381.00	321.79 – 451.10

A/Wisconsin (H3N2)

Group	Value	95% CI
FluBlok: Lot A	390.34	324.83 – 469.06
FluBlok: Lot B	192.25	159.59 – 231.59
FluBlok: Lot C	240.01	200.14 – 287.82

B/Malaysia

Group	Value	95% CI
FluBlok: Lot A	182.10	151.95 – 218.24
FluBlok: Lot B	205.95	174.16 – 243.55
FluBlok: Lot C	215.34	179.31 – 258.62

Percentage of Participants With Positive Cell Culture/Culture-Confirmed Influenza Like Illness as Defined by Centers for Disease Control and Prevention (CDC-ILI) Primary · 14 days post vaccination through and up to 6 months

CDC-defined ILI was defined as fever (body temperature \>=100ºF oral accompanied by cough and/or sore throat, on the same day or on consecutive days) due to strains represented in the vaccine.

Group	Value	95% CI
FluBlok (Lots A, B, C)	0.04
Placebo	0.2

Percentage of Participants With Seroprotection to Influenza Vaccine Antigens After Vaccination With FluBlok Secondary · 28 days post vaccination

Anti-influenza antibodies were measured using an HAI assay for 3 strains: A/Solomon Islands \[H1N1\], A/Wisconsin \[H3N2\] and B/Malaysia. Seroprotection was defined as a post-vaccination HAI antibody titer of \>=1:40.

A/Solomon Islands (H1N1)

Group	Value	95% CI
FluBlok (Lots A, B, C)	99	97.1 – 99.5

A/Wisconsin (H3N2)

Group	Value	95% CI
FluBlok (Lots A, B, C)	97	94.8 – 98.3

B/Malaysia

Group	Value	95% CI
FluBlok (Lots A, B, C)	96	94.0 – 97.8

Percentage of Participants With Seroconversion to Influenza Vaccine Antigens After Vaccination With FluBlok Secondary · 28 days post vaccination

Anti-influenza antibodies were measured using an HAI assay for 3 strains: A/Solomon Islands \[H1N1\], A/Wisconsin \[H3N2\] and B/Malaysia. Seroconversion was defined as a post-vaccination titer of \>=1:40 in participants with undetectable baseline antibody (HI titer = \<1:10) or a \>=4-fold rise in antibody in participants with a baseline titer of \>=1:10, with the achievement of post-vaccination titer of at least 1:40.

A/Solomon Islands (H1N1)

Group	Value	95% CI
FluBlok (Lots A, B, C)	78	73.5 – 81.5

A/Wisconsin (H3N2)

Group	Value	95% CI
FluBlok (Lots A, B, C)	81	77.1 – 84.6

B/Malaysia

Group	Value	95% CI
FluBlok (Lots A, B, C)	52	47.0 – 56.5

Adverse events — posted to ClinicalTrials.gov

Time frame: Unsolicited non-serious AEs: Day 0 to Day 28 post vaccination, Solicited reactions: within 7 days post vaccination, SAE: through the end of influenza season (up to 6 months). Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

FluBlok (Lots A, B, C)

Serious: 30/2344 (1%)

Deaths: 1/2344

Placebo

Serious: 34/2304 (1%)

Deaths: 1/2304

Serious adverse events (74 terms)

Reaction	System	FluBlok (Lots A, B, C)	Placebo
Depression	Psychiatric disorders	—	—
Appendicitis	Infections and infestations	—	—
Kidney infection	Infections and infestations	—	—
Dehydration	Metabolism and nutrition disorders	—	—
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	—	—
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Suicide attempt	Psychiatric disorders	—	—
Iron deficiency anaemia	Blood and lymphatic system disorders	—	—
Lymphadenopathy	Blood and lymphatic system disorders	—	—
Angina pectoris	Cardiac disorders	—	—
Myocardial infarction	Cardiac disorders	—	—
Pericardial effusion	Cardiac disorders	—	—
Sinus tachycardia	Cardiac disorders	—	—
Supraventricular tachycardia	Cardiac disorders	—	—
Rathke's cleft cyst	Congenital, familial and genetic disorders	—	—
Retinal haemorrhage	Eye disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Crohn's disease	Gastrointestinal disorders	—	—
Inflammatory bowel disease	Gastrointestinal disorders	—	—
Small intestinal obstruction	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Accidental death	General disorders	—	—
Chest pain	General disorders	—	—
Non-cardiac chest pain	General disorders	—	—
Biliary colic	Hepatobiliary disorders	—	—

Other adverse events (4 terms — click to expand)

Reaction	System	FluBlok (Lots A, B, C)	Placebo
Pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Headache	Nervous system disorders	—	—
Nasal congestion	Respiratory, thoracic and mediastinal disorders	—	—

Most-reported serious reactions: Depression, Appendicitis, Kidney infection, Dehydration, Intervertebral disc protrusion, Uterine leiomyoma, Suicide attempt, Iron deficiency anaemia.

Data from ClinicalTrials.gov NCT00539981 adverse events section.

Sponsor's own description

The purpose of this study was to evaluate a single dose of FluBlok in terms of safety, efficacy and effectiveness in prevention of influenza and influenza-like illness and assess clinical lot-to-lot consistency in manufacturing by evaluating and comparing the immunogenicity of three different lots of FluBlok in a subset of participants.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Age Dependence and Isotype Specificity of Influenza Virus Hemagglutinin Stalk-Reactive Antibodies in Humans.
   Nachbagauer R, Choi A, Izikson R, Cox MM, et al · · 2016 · cited 129× · PMID 26787832 · DOI 10.1128/mbio.01996-15
2. Analysis of Anti-Influenza Virus Neuraminidase Antibodies in Children, Adults, and the Elderly by ELISA and Enzyme Inhibition: Evidence for Original Antigenic Sin.
   Rajendran M, Nachbagauer R, Ermler ME, Bunduc P, et al · · 2017 · cited 124× · PMID 28325769 · DOI 10.1128/mbio.02281-16