Development of an Intranasal Proteosome Influenza Vaccine

Study to Determine if Intranasal Proteosome-Adjuvanted Trivalent Influenza Vaccine is Safe, Immunogenic and Efficacious in the Influenza Human Viral Challenge Model

A study to compare multiple dosage regimes of a protesomal intranasal vaccine.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Placebo Protesomal Vaccine; Biological: Experimental: Protesomal Vaccine 1 x 30 µg; Biological: Experimental: Protesomal Vaccine 2 x 30 µg; Biological: Experimental: Protesomal Vaccine 2 x 15 µg

Detailed Description

A Proteosome-adjuvanted trivalent inactivated influenza vaccine (P-TIV) administered intra-nasally was shown to be effective, safe, well tolerated, immunogenic - in both systemic and mucosal compartments - and effective at preventing influenza illness.

In two separate studies using the Human Viral Challenge Model, subjects were selected for susceptibility to A/Panama/2007/1999 (H3N2) virus and then dosed with one of three regimens: (A/New Caledonia/20/1999 (H1N1), A/Panama/2007/1999 (H3N2), B/Victoria/504/2000 or B/Shangdong/7/1997) or placebo via a nasal spray. One or two doses were given, 14 days apart, before subjects were challenged with ~8.5 x 105 EID¬50 of A/Panama/2007/1999 (H3N2) virus. Immune responses to the vaccine antigens were measured, namely serum IgG (via the aemagglutination inhibition assay (HAI)) and nasal wash secretory IgA (sIgA) antibodies (via ELISA). Viral titres in nasal washes and symptoms of influenza illness were assessed after viral challenge and compared.

• Study Type: Interventional
• Enrollment (Actual): 174
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Young healthy adults as determined by medical history, physical examination, serology (HIV and Hepatitis B and C) and clinical laboratory tests.
• Female subjects were required to provide of a history of reliable contraceptive practice.
• Susceptibility to A/Panama/2007/1999 (H3N2) (a serum reciprocal HAI titre ≤10) was confirmed at screening. -

Exclusion Criteria:included;

• asthma,
• hypersensitivity to mercurials or chicken eggs,
• anatomic or neurologic abnormality impairing the gag reflex or contributing to aspiration, * chronic nasopharyngeal complaints,
• abnormal electrocardiogram (ECG),
• febrile illness or significant symptoms of upper respiratory infection on the day of vaccination or between admission to quarantine and administration of the challenge inoculum.
• Subjects using medication or other products for rhinitis or nasal congestion,
• Subject who had received systemic glucocorticoids within 1 month, or cytotoxic or immunosuppressive drugs within 6 months of the study start.
• Subjects agreed not to smoke during the quarantine phase.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Biological: Placebo Protesomal Vaccine; Intranasal vaccine Protesomal Vaccine; Other Names: Placebo
Experimental: Protesomal Vaccine 1 x 30 µg	Biological: Experimental: Protesomal Vaccine 1 x 30 µg; Experimental: Protesomal Vaccine 1 x 30 µg
Experimental: Protesomal Vaccine 2 x 30 µg	Biological: Experimental: Protesomal Vaccine 2 x 30 µg; Experimental: Protesomal Vaccine 2 x 30 µg
Experimental: Protesomal Vaccine 2 x 15 µg	Biological: Experimental: Protesomal Vaccine 2 x 15 µg; Experimental: Protesomal Vaccine 2 x 15 µg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Reduction in Influenza Like Illness in those with laboratory confirmed influenza	Within the duration of infection, approx 10 days

Collaborators and Investigators

• Sponsor: Hvivo
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Rob Lambkin-Williams, PhD, PI

Publications and helpful links

General Publications

• Lambkin-Williams R, Gelder C, Broughton R, Mallett CP, Gilbert AS, Mann A, He D, Oxford JS, Burt D. An Intranasal Proteosome-Adjuvanted Trivalent Influenza Vaccine Is Safe, Immunogenic & Efficacious in the Human Viral Influenza Challenge Model. Serum IgG & Mucosal IgA Are Important Correlates of Protection against Illness Associated with Infection. PLoS One. 2016 Dec 22;11(12):e0163089. doi: 10.1371/journal.pone.0163089. eCollection 2016.

Study record dates

Study Major Dates

• Study Start: January 1, 2002
• Primary Completion (Actual): January 1, 2004
• Study Completion (Actual): January 1, 2004

Study Registration Dates

• First Submitted: July 28, 2015
• First Submitted That Met QC Criteria: August 12, 2015
• First Posted (Estimate): August 13, 2015

Study Record Updates

• Last Update Posted (Estimate): August 13, 2015
• Last Update Submitted That Met QC Criteria: August 12, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: IDB 004 IDB 005