Safety and Immunogenicity of VAX125 Influenza Vaccine in Community-living Adults >= 65 Years of Age

• Sponsor: VaxInnate Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00966238
• Collaborator: (none)
• Enrollment: 120
• Locations: 3
• Arm: 1
• Duration (Months): 17.9
• Patients Per Site: 40
• Patients Per Site Per Month: 2.2

Study Details

Study Description

Brief Summary

A multi-center, open-label, escalating dose-ranging study to assess the safety, reactogenicity, and immunogenicity of four different VAX125 vaccine doses; 0.5 µg, 1.0 µg, 2.0 µg, or 3.0 µg, delivered i.m. as a single dose vaccination on Day 0. Hypothesis: VAX125 is safe and immunogenic at one or more of the doses tested.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Biological: VAX125	Phase 2

Detailed Description

A total of 80 community-living adults who are ≥65 years of age will be enrolled across the four dose groups. Following vaccination, each subject will remain at the study site for at least 30 minutes to be observed for any immediate reactogenicity complaints associated with the Day 0 vaccination. Subjects will also be evaluated during clinic visits on Study Days 1, 7, 14, and 28 following vaccination. In addition, a safety follow-up telephone contact will occur on post vaccination Day 3.

There will be 20 subjects per dose group. Up to 3 study sites will enroll 6-10 subjects per dose group over a two-day enrollment period. Progression to the next higher dose group will take place only if the Safety Monitoring Committee (SMC) assessment of the 30 (+15) minutes, Day 0, and Day 1 post vaccination safety data; Day 3 telephone report: and the Day 0 and Day 1 serum C-reactive protein (CRP) results concludes that the lower dose was well tolerated.

Study Design

• Study Type: Interventional
• Actual Enrollment: 120 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase II, Open-label, Escalating Dose-ranging Study to Evaluate the Safety and Immunogenicity of VAX125 Influenza Vaccine in Community-living Adults ≥65 Years of Age
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Apr 1, 2010
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VAX125 HA1 influenza vaccine	Biological: VAX125; STF2.HA1(SI) (VAX125), which is a recombinant fusion protein that consists of Salmonella typhimurium flagellin type 2 (STF2), a Toll-like receptor 5 (TLR5) ligand, fused at its C-terminus to the globular head domain of the hemagglutinin (HA) antigen of influenza A HA1 Solomon Islands (SI).

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Local and Systemic Immediate Reactogenicity Complaints [within 4 hours following vaccination]

Secondary Outcome Measures

1. Geometric Mean Hemagglutinin Inhibition (HAI) Antibody Titers [28 days after vaccination]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Adult men or women aged 65 or older; female subjects must be post menopausal.

• Live in the community, independently or in an assisted living environment

• Based on the results of the Short Portable Mental Status Questionnaire (SPMSQ), be rated as normal or have no greater than mild severity dementia.

• As defined by the Canadian Study of Health and Aging Clinical Frailty Scale (CSHA-CFS), fitness ranging from very fit to mildly frail; Classes 1 to 5 of 7.

• Healthy volunteers, as determined by medical history, physical examination (PE), vital signs, and clinical safety laboratory examinations.

• Able to comprehend the study requirements, agree to its provisions, have the ability to adhere to the provisions of the study, and give written informed consent prior to study entry.

• Willing to receive the unlicensed (VAX125) vaccine given as an i.m. injection.

• Willing to provide multiple blood specimens collected by venipuncture.

Exclusion Criteria:

• Persons who in the opinion of the Investigator, have a psychiatric illness, a chronic illness (e.g., diabetes or liver or kidney disease), or who are taking a concomitant therapy or have any other condition that would interfere with the subject's participation in the study or interpretation of the study results.

• Persons having cancer or have received treatment for cancer within three years (persons with a history of cancer who are disease-free without treatment for three years or more are eligible.

• Persons with impaired immune responsiveness (of any cause), including diabetes mellitus.

• Persons presently receiving or having a recent history of receiving (within the past six months) any medication or therapeutic modality that affects the immune system such as allergy shots, immune globulin, interferon, immunomodulators, radiation therapy, cytotoxic drugs or drugs known to be frequently associated with significant major organ toxicity, or systemic corticosteroids (oral or injectable). Inhaled and topical corticosteroids are allowed.

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

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

• Persons with a history of drug or chemical abuse in the year prior to screening.

• Persons currently participating in another research study involving study medications (drugs or vaccines) or who have participated within 30 days of vaccination.

• Persons who have received blood or blood products within eight weeks prior to vaccination or are planning to receive blood or blood products during the study period.

• Persons who have donated blood or blood products within eight weeks prior to vaccination or plan to donate at any time during the study.

• Persons with acute disease within 72 hours prior to vaccination defined as the presence of a moderate or severe illness as determined by the Investigator through medical history and physical examination. Vaccination can be delayed until the subject has recovered.

• Persons with significant cardiovascular disease e.g., New York Heart Associate (NYHA) Class 3 or 4 congestive heart failure; myocardial infarction within the past six months; unstable angina, coronary angioplasty within the past six months; uncontrolled ventricular cardiac arrhythmias; resting heart rate (HR) >100 beats per minute (bpm)

• Persons with a history of chronic obstructive pulmonary disease or history of other lung disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	JCCT	Lanexa	Kansas	United States	66219
2	Univ of Rochester	Rochester	New York	United States	14642
3	Coastal Carolina Research Center	Charleston	South Carolina	United States	29464

Sponsors and Collaborators

• VaxInnate Corporation

Investigators

• Study Director: David Taylor, MD, VaxInnate Corporation

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: VaxInnate Corporation
• ClinicalTrials.gov Identifier: NCT00966238
• Other Study ID Numbers: VAX125-02
• First Posted: Aug 26, 2009
• Last Update Posted: Oct 2, 2014
• Last Verified: Sep 1, 2014

• Keywords provided by VaxInnate Corporation: influenza; vaccine
• Additional relevant MeSH terms: Influenza, Human

Study Results

Participant Flow

Recruitment Details	Participants were recruited across 3 clinical sites.

Arm/Group Title	0.5 µg i.m.	1.0 µg i.m.	2.0 µg i.m.	3.0 µg i.m.	5.0 µg i.m.	8.0 µg i.m.
Arm/Group Description
Period Title: Overall Study
STARTED	20	20	20	20	20	20
COMPLETED	20	20	20	20	20	20
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	0.5 µg i.m.	1.0 µg i.m.	2.0 µg i.m.	3.0 µg i.m.	5.0 µg i.m.	8.0 µg i.m.	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	20	20	20	20	20	20	120
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
>=65 years	20 100%	20 100%	20 100%	20 100%	20 100%	20 100%	120 100%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	72.8 (6.12)	71.2 (4.65)	71.7 (4.16)	71.9 (4.28)	70.7 (4.07)	70.6 (4.91)	71.5 (4.71)
Sex: Female, Male (Count of Participants)
Female	10 50%	7 35%	10 50%	5 25%	12 60%	9 45%	53 44.2%
Male	10 50%	13 65%	10 50%	15 75%	8 40%	11 55%	67 55.8%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Local and Systemic Immediate Reactogenicity Complaints
Time Frame	within 4 hours following vaccination

Outcome Measure Data

Analysis Population Description

Immediate complaints were vaccination symptoms that were solicited and observed at 30 minutes (+15 minutes) and (±30 minutes) after the vaccination on Day 0.

Arm/Group Title	0.5 µg i.m.	1.0 µg i.m.	2.0 µg i.m.	3.0 µg i.m.	5.0 µg i.m.	8.0 µg i.m.
Arm/Group Description
Measure Participants	20	20	20	20	20	20
Redness	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Swelling	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Bruising	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Arm Pain	8 40%	8 40%	6 30%	7 35%	9 45%	11 55%
Headache	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Fatigue	0 0%	0 0%	1 5%	0 0%	0 0%	0 0%
Joint Pain	0 0%	0 0%	0 0%	0 0%	1 5%	1 5%
Muscle Aches	0 0%	0 0%	1 5%	0 0%	2 10%	1 5%
Chills	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Sweating	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

2. Secondary Outcome

Title	Geometric Mean Hemagglutinin Inhibition (HAI) Antibody Titers
Time Frame	28 days after vaccination

Outcome Measure Data

Analysis Population Description

The immunogenicity of the vaccine was evaluated by measuring the number of subjects who demonstrate seroconversion either by developing a measurable titer following vaccination or by showing a significant increase in HAI serum antibody titers post-vaccination.

Arm/Group Title	0.5 µg i.m.	1.0 µg i.m.	2.0 µg i.m.	3.0 µg i.m.	5.0 µg i.m.	8.0 µg i.m.
Arm/Group Description
Measure Participants	20	20	20	20	20	20
Baseline	27.32	27.32	24.62	50.98	18.59	30.31
Day 7	30.31	38.64	50.98	105.56	66.66	154.55
Day 14	42.87	77.27	69.64	160.00	230.44	234.25
Day 28	47.57	74.64	69.64	149.29	222.18	211.12

Adverse Events

Time Frame	Serious adverse events were collected for 1 year following vaccination. All adverse events were collected for 28 days following vaccination.
Arm/Group Title	0.5 µg i.m.		1.0 µg i.m.		2.0 µg i.m.		3.0 µg i.m.		5.0 µg i.m.		8.0 µg i.m.
Arm/Group Description
All Cause Mortality
	0.5 µg i.m.		1.0 µg i.m.		2.0 µg i.m.		3.0 µg i.m.		5.0 µg i.m.		8.0 µg i.m.
	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)
Serious Adverse Events
	0.5 µg i.m.		1.0 µg i.m.		2.0 µg i.m.		3.0 µg i.m.		5.0 µg i.m.		8.0 µg i.m.
	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	1/20 (5%)		1/20 (5%)		0/20 (0%)		1/20 (5%)		0/20 (0%)		0/20 (0%)
Hepatobiliary disorders
Cholelithiasis	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Reproductive system and breast disorders
Breast Cancer	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0
Respiratory, thoracic and mediastinal disorders
Non-small cell lung cancer	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0
Other (Not Including Serious) Adverse Events
	0.5 µg i.m.		1.0 µg i.m.		2.0 µg i.m.		3.0 µg i.m.		5.0 µg i.m.		8.0 µg i.m.
	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	0/20 (0%)		2/20 (10%)		0/20 (0%)		0/20 (0%)		0/20 (0%)		0/20 (0%)
Infections and infestations
Sinusitis	0/20 (0%)	0	2/20 (10%)	2	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0

Limitations/Caveats

[Not Specified]

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.