Comparison of the Safety of Flublok® Versus Licensed IIV in Healthy, Medically Stable Adults ≥ 50 Years of Age

• Sponsor: Protein Sciences Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01825200
• Collaborator: (none)
• Enrollment: 2,640
• Locations: 14
• Arms: 2
• Duration (Months): 2
• Patients Per Site: 188.6
• Patients Per Site Per Month: 94.1

Study Details

Study Description

Brief Summary

The hypothesis for this trial is that the incidence of a pre-defined composite of common systemic hypersensitivity adverse events for Flublok recipients is non-inferior to that reported for licensed IIV recipients. Another hypothesis is that the safety and reactogenicity of Flublok is clinically acceptable, i.e. consistent with the overall safety profiles previously observed with Flublok and with the licensed comparator.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Biological: Flublok; Biological: Afluria	Phase 3

Detailed Description

The Advisory Committee on Immunization Practices (ACIP) recommends that all people aged 6 months and older be immunized to prevent influenza. Currently the only approved influenza vaccine across the entire age group is inactivated influenza vaccine (IIV). A Biologics Licensing Application (BLA) for Flublok was approved by the FDA for influenza immunization of adults 18-49 years of age. Additional safety and, ultimately efficacy, data is needed to support use in adults ≥50 years of age, an important age group as adults ≥65 years of age are among those at increased risk of influenza complications.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2640 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Comparison of the Safety of Flublok® Versus Licensed Inactivated Influenza Vaccine in Healthy, Medically Stable Adults ≥ 50 Years of Age
• Study Start Date: Mar 1, 2013
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Flublok Flublok containing 3x45µg (135µg total) of recombinant hemagglutinin (rHA) derived from influenza A/H1N1 and A/H3N2 and influenza B viruses in a total volume of 0.5 mL	Biological: Flublok; A Biologics Licensing Application (BLA) for Flublok was approved by the FDA for influenza immunization of adults 18-49 years of age. Flublok is produced using recombinant technology under serum-free conditions.
Placebo Comparator: Afluria Afluria, containing 3x15µg (45µg total), of trivalent, inactivated influenza vaccine (licensed IIV) containing influenza antigen derived from A/H1N1 and A/H3N2 and influenza B viruses in a total volume of 0.5 mL	Biological: Afluria; Afluria is approved for use in persons 5 years of age and older and is produced by inactivation and disruption of live influenza virus grown in embryonated chicken eggs.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Common Hypersensitivity Reactions as Measure of Safety [30 Days]

   Number of participants who experience a pre-defined common systemic hypersensitivity adverse event, including rash, urticaria, swelling or edema through Day 30 post-vaccine administration.

Secondary Outcome Measures

1. Subjects With at Least One Unsolicited Adverse Event in the 30 Days Following Vaccine Administration [30 Days]

   Subjects with at least one serious adverse event and subjects with at least one medically-attended unsolicited adverse event occurring during the 30 days following vaccine administration

2. Number of Participants With Local and Systemic Events Reported as a Measure of Safety [7 Days]

   Number of solicited local and systemic events of reactogenicity reported with the help of a memory aid during the seven days following vaccine administration.

3. Subjects With at Least One Hypersensitivity Event Reported on Day 0 and Days 0-7 Following Vaccine Administration as a Measure of Safety [7 Days]

   Subjects with at least one pre-defined common systemic hypersensitivity adverse event, including rash, urticaria, swelling or non-dependent edema on Day 0 and for Days 0 to 7 following vaccine administration

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Ambulatory adults aged 50 years and older

2. Medically stable, as determined by medical history and targeted physical examination based on medical history, if appropriate

3. Able to understand and comply with planned study procedures

4. Provides written informed consent prior to initiation of any study procedure.

Exclusion Criteria:

1. Known contraindication to either study vaccine (see product package inserts)

2. Receipt of any other influenza or other vaccine within 30 days prior to enrollment in this study.

3. Receipt of any new medication within 30 days prior to enrollment in this study

4. Plans to participate in any investigation involving an investigational product during this study.

5. Pre-existence of atopic dermatitis or any other cutaneous disorder that could complicate the evaluation of potential primary endpoints.

6. Any clinical or social circumstance that in the opinion of the investigator could interfere with compliance with study procedures or interfere with the interpretation of clinical data.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Genova Clinical Research	Tucson	Arizona	United States	85704-1152
2	Clinical Research of South Florida	Coral Gables	Florida	United States	33134
3	Meridian Clinical Research	Savannah	Georgia	United States	31406
4	Heartland Research Associates, LLC	Wichita	Kansas	United States	67207
5	Benchmark Research	Metairie	Louisiana	United States	70006
6	Maine Research Associates, LLC	Auburn	Maine	United States	04210
7	Meridian Clinical Research	Omaha	Nebraska	United States	68164
8	Clinical Research Center of Nevada, LLC	Las Vegas	Nevada	United States	89104
9	Regional Clinical Research	Binghamton	New York	United States	13901
10	Wake Research	Raleigh	North Carolina	United States	27612
11	Rapid Medical Research, Inc.	Cleveland	Ohio	United States	44122
12	Research Across America	Dallas	Texas	United States	75234
13	Benchmark Research	Fort Worth	Texas	United States	76135
14	Benchmark Research	San Angelo	Texas	United States	76904

Sponsors and Collaborators

• Protein Sciences Corporation

Investigators

• Principal Investigator: Brandon Essink, MD, Meridian Clinical Research
• Principal Investigator: Paul Bradley, MD, Meridian Clinical Research
• Principal Investigator: William Seger, MD, Benchmark Research
• Principal Investigator: Darrell Herrington, DO, Benchmark Research
• Principal Investigator: George Bauer, MD, Benchmark Research
• Principal Investigator: Frank Eder, MD, Regional Clinical Research
• Principal Investigator: Treva Tyson, MD, Wake Research
• Principal Investigator: Bob Weiss, MD, Maine Research Associates, LLC
• Principal Investigator: Jeffrey Rosen, MD, Clinical Research of South Florida
• Principal Investigator: Joe Blumenau, MD, Research Across America
• Principal Investigator: Steven Folkerth, MD, Clinical Research Center of Nevada, LLC
• Principal Investigator: Leah Schmidt, DO, Genova Clinical Research
• Principal Investigator: Eric Sheldon, Miami Research Associates
• Principal Investigator: Alan C. Wine, MD, Rapid Medical Research, Inc.
• Principal Investigator: Terry Poling, MD, Heartland Research Associates, LLC

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Protein Sciences Corporation
• ClinicalTrials.gov Identifier: NCT01825200
• Other Study ID Numbers: PSC11
• First Posted: Apr 5, 2013
• Last Update Posted: Feb 18, 2015
• Last Verified: Jan 1, 2015

• Keywords provided by Protein Sciences Corporation: Influenza
• Additional relevant MeSH terms: Influenza, Human

Study Results

Participant Flow

Recruitment Details	Subjects were recruited at outpatient medical clinics over a period of five weeks.

Arm/Group Title	Flublok	Afluria
Arm/Group Description	Flublok containing 3x45µg (135µg total) of rHA0 derived from influenza A/H1N1 and A/H3N2 and influenza B viruses in a total volume of 0.5mL Flublok: A Biologics Licensing Application (BLA) for Flublok was approved by the FDA for influenza immunization of adults 18-49 years of age. Flublok is produced using recombinant technology under serum-free conditions.	Afluria, containing 3x15µg (45µg total), of trivalent, inactivated influenza vaccine (licensed IIV) containing influenza antigen derived from A/H1N1 and A/H3N2 and influenza B viruses in a total volume of 0.5mL Afluria: Afluria is approved for use in persons 5 years of age and older and is produced by inactivation and disruption of live influenza virus grown in embryonated chicken eggs.
Period Title: Overall Study
STARTED	1319	1321
COMPLETED	1314	1314
NOT COMPLETED	5	7

Baseline Characteristics

Arm/Group Title	Flublok	Afluria	Total
Arm/Group Description	Flublok containing 3x45µg (135µg total) of rHA0 derived from influenza A/H1N1 and A/H3N2 and influenza B viruses in a total volume of 0.5mL Flublok: A Biologics Licensing Application (BLA) for Flublok was approved by the FDA for influenza immunization of adults 18-49 years of age. Flublok is produced using recombinant technology under serum-free conditions.	Afluria, containing 3x15µg (45µg total), of trivalent, inactivated influenza vaccine (licensed IIV) containing influenza antigen derived from A/H1N1 and A/H3N2 and influenza B viruses in a total volume of 0.5mL Afluria: Afluria is approved for use in persons 5 years of age and older and is produced by inactivation and disruption of live influenza virus grown in embryonated chicken eggs.	Total of all reporting groups
Overall Participants	1314	1313	2627
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	64	64	64
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	672 51.1%	665 50.6%	1337 50.9%
>=65 years	642 48.9%	648 49.4%	1290 49.1%
Sex: Female, Male (Count of Participants)
Female	730 55.6%	725 55.2%	1455 55.4%
Male	584 44.4%	588 44.8%	1172 44.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	8 0.6%	6 0.5%	14 0.5%
Asian	7 0.5%	5 0.4%	12 0.5%
Native Hawaiian or Other Pacific Islander	1 0.1%	2 0.2%	3 0.1%
Black or African American	197 15%	212 16.1%	409 15.6%
White	1098 83.6%	1083 82.5%	2181 83%
More than one race	3 0.2%	5 0.4%	8 0.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	105 8%	99 7.5%	204 7.8%
Not Hispanic or Latino	1209 92%	1214 92.5%	2423 92.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	1314 100%	1313 100%	2627 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Common Hypersensitivity Reactions as Measure of Safety
Description	Number of participants who experience a pre-defined common systemic hypersensitivity adverse event, including rash, urticaria, swelling or edema through Day 30 post-vaccine administration.
Time Frame	30 Days

Outcome Measure Data

Analysis Population Description

The primary analysis population, includes all randomized subjects who received a dose of study vaccine and for whom some safety data were available after administration of vaccine. Subjects were analyzed according to the vaccine received, regardless of whether this was the treatment group to which they were randomized.

Arm/Group Title	Flublok	Afluria
Arm/Group Description	Flublok containing 3x45µg (135µg total) of rHA0 derived from influenza A/H1N1 and A/H3N2 and influenza B viruses in a total volume of 0.5mL Flublok: A Biologics Licensing Application (BLA) for Flublok was approved by the FDA for influenza immunization of adults 18-49 years of age. Flublok is produced using recombinant technology under serum-free conditions.	Afluria, containing 3x15µg (45µg total), of trivalent, inactivated influenza vaccine (licensed IIV) containing influenza antigen derived from A/H1N1 and A/H3N2 and influenza B viruses in a total volume of 0.5mL Afluria: Afluria is approved for use in persons 5 years of age and older and is produced by inactivation and disruption of live influenza virus grown in embryonated chicken eggs.
Measure Participants	1314	1313
Number [participants]	31 2.4%	21 1.6%

2. Secondary Outcome

Title	Subjects With at Least One Unsolicited Adverse Event in the 30 Days Following Vaccine Administration
Description	Subjects with at least one serious adverse event and subjects with at least one medically-attended unsolicited adverse event occurring during the 30 days following vaccine administration
Time Frame	30 Days

Outcome Measure Data

Analysis Population Description

The primary analysis population, includes all randomized subjects who received a dose of study vaccine and for whom some safety data were available after administration of vaccine. Subjects were analyzed according to the vaccine received, regardless of whether this was the treatment group to which they were randomized.

Arm/Group Title	Flublok	Afluria
Arm/Group Description	Flublok containing 3x45µg (135µg total) of rHA0 derived from influenza A/H1N1 and A/H3N2 and influenza B viruses in a total volume of 0.5mL Flublok: A Biologics Licensing Application (BLA) for Flublok was approved by the FDA for influenza immunization of adults 18-49 years of age. Flublok is produced using recombinant technology under serum-free conditions.	Afluria, containing 3x15µg (45µg total), of trivalent, inactivated influenza vaccine (licensed IIV) containing influenza antigen derived from A/H1N1 and A/H3N2 and influenza B viruses in a total volume of 0.5mL Afluria: Afluria is approved for use in persons 5 years of age and older and is produced by inactivation and disruption of live influenza virus grown in embryonated chicken eggs.
Measure Participants	1314	1313
Serious Adverse Events (SAEs)	5 0.4%	10 0.8%
Medically-Attended Unsolicited Adverse Events	53 4%	51 3.9%

3. Secondary Outcome

Title	Number of Participants With Local and Systemic Events Reported as a Measure of Safety
Description	Number of solicited local and systemic events of reactogenicity reported with the help of a memory aid during the seven days following vaccine administration.
Time Frame	7 Days

Outcome Measure Data

Analysis Population Description

The primary analysis population, includes all randomized subjects who received a dose of study vaccine and for whom some safety data were available after administration of vaccine. Subjects were analyzed according to the vaccine received, regardless of whether this was the treatment group to which they were randomized.

Arm/Group Title	Flublok	Afluria
Arm/Group Description	Flublok containing 3x45µg (135µg total) of rHA0 derived from influenza A/H1N1 and A/H3N2 and influenza B viruses in a total volume of 0.5mL Flublok: A Biologics Licensing Application (BLA) for Flublok was approved by the FDA for influenza immunization of adults 18-49 years of age. Flublok is produced using recombinant technology under serum-free conditions.	Afluria, containing 3x15µg (45µg total), of trivalent, inactivated influenza vaccine (licensed IIV) containing influenza antigen derived from A/H1N1 and A/H3N2 and influenza B viruses in a total volume of 0.5mL Afluria: Afluria is approved for use in persons 5 years of age and older and is produced by inactivation and disruption of live influenza virus grown in embryonated chicken eggs.
Measure Participants	1314	1313
Number [participants]	432 32.9%	480 36.6%

4. Secondary Outcome

Title	Subjects With at Least One Hypersensitivity Event Reported on Day 0 and Days 0-7 Following Vaccine Administration as a Measure of Safety
Description	Subjects with at least one pre-defined common systemic hypersensitivity adverse event, including rash, urticaria, swelling or non-dependent edema on Day 0 and for Days 0 to 7 following vaccine administration
Time Frame	7 Days

Outcome Measure Data

Analysis Population Description

The primary analysis population, includes all randomized subjects who received a dose of study vaccine and for whom some safety data were available after administration of vaccine. Subjects were analyzed according to the vaccine received, regardless of whether this was the treatment group to which they were randomized.

Arm/Group Title	Flublok	Afluria
Arm/Group Description	Flublok containing 3x45µg (135µg total) of rHA0 derived from influenza A/H1N1 and A/H3N2 and influenza B viruses in a total volume of 0.5mL Flublok: A Biologics Licensing Application (BLA) for Flublok was approved by the FDA for influenza immunization of adults 18-49 years of age. Flublok is produced using recombinant technology under serum-free conditions.	Afluria, containing 3x15µg (45µg total), of trivalent, inactivated influenza vaccine (licensed IIV) containing influenza antigen derived from A/H1N1 and A/H3N2 and influenza B viruses in a total volume of 0.5mL Afluria: Afluria is approved for use in persons 5 years of age and older and is produced by inactivation and disruption of live influenza virus grown in embryonated chicken eggs.
Measure Participants	1314	1313
Day 0	5 0.4%	3 0.2%
Days 0-7	25 1.9%	12 0.9%

Adverse Events

Time Frame	30 days following vaccine administration
Adverse Event Reporting Description	Adverse Events were reviewed by Investigators and by the Medical Monitor. Assessments of causality were conducted by both reviewers.
Arm/Group Title	Flublok		Afluria
Arm/Group Description	Flublok containing 3x45µg (135µg total) of rHA0 derived from influenza A/H1N1 and A/H3N2 and influenza B viruses in a total volume of 0.5mL Flublok: A Biologics Licensing Application (BLA) for Flublok was approved by the FDA for influenza immunization of adults 18-49 years of age. Flublok is produced using recombinant technology under serum-free conditions.		Afluria, containing 3x15µg (45µg total), of trivalent, inactivated influenza vaccine (licensed IIV) containing influenza antigen derived from A/H1N1 and A/H3N2 and influenza B viruses in a total volume of 0.5mL Afluria: Afluria is approved for use in persons 5 years of age and older and is produced by inactivation and disruption of live influenza virus grown in embryonated chicken eggs.
All Cause Mortality
	Flublok		Afluria
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Flublok		Afluria
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/1314 (0.4%)		10/1313 (0.8%)
Cardiac disorders
Myocardial Infarction	1/1314 (0.1%)	1	2/1313 (0.2%)	2
Hypertension	0/1314 (0%)	0	1/1313 (0.1%)	1
Endocrine disorders
Diabetic Ketoacidosis	0/1314 (0%)	0	1/1313 (0.1%)	1
Infections and infestations
Sepsis	0/1314 (0%)	0	2/1313 (0.2%)	2
Pneumonia	0/1314 (0%)	0	1/1313 (0.1%)	1
Appendicitis	0/1314 (0%)	0	1/1313 (0.1%)	1
Injury, poisoning and procedural complications
Alcoholic Hepatitis	1/1314 (0.1%)	1	1/1313 (0.1%)	1
Leg Fracture	0/1314 (0%)	0	1/1313 (0.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate Cancer	1/1314 (0.1%)	1	0/1313 (0%)	0
Salivary Gland Tumor	1/1314 (0.1%)	1	0/1313 (0%)	0
Nervous system disorders
Cerebellar Stroke Syndrome	0/1314 (0%)	0	1/1313 (0.1%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism	1/1314 (0.1%)	1	0/1313 (0%)	0
Other (Not Including Serious) Adverse Events
	Flublok		Afluria
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/1314 (1.5%)		16/1313 (1.2%)
Gastrointestinal disorders
Diarrhea	12/1314 (0.9%)	12	4/1313 (0.3%)	4
Nervous system disorders
Headache	8/1314 (0.6%)	8	12/1313 (0.9%)	12

Limitations/Caveats

Rash, urticaria, swelling and edema were self-reported by subjects and most were not observed by investigators. Review by independent experts indicated that 42 of 52 subject-reported events did not represent Type 1 (IgE-mediated) hypersensitivity.

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.