Efficacy of FLU-v in an H1N1 Influenza Human Challenge Model

NCT03180801 | Completed Phase 2 Results

• 3 other identifiers: FLU-v-0042016-002134-742015-25472
• Study Type: interventional
• Target: 153
• Locations: 1 country
• Sites: 1

Brief Summary

FLU-v is a broad spectrum influenza vaccine that targets regions conserved among multiple influenza strains. FLU-v adjuvanted with Montanide ISA-51 was shown to be safe in previous trials. This study aims to assess efficacy of adjuvanted FLU-v vaccine in protecting healthy volunteers against an influenza challenge delivered intranasally under quarantine. Efficacy of FLU-v will be assessed by measuring the incidence and severity of the disease in the treatment groups compared to the placebo group. In addition, the immune responses of the volunteers to FLU-v will also be explored.

Conditions

Influenza

Keywords

broad; universal; vaccine; influenza; peptide; T cell; H1N1; human challenge

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Mild to Moderate Influenza Disease (MMID)

  To determine the effect of FLU-v on reducing the incidence of Mild to Moderate Influenza Disease (MMID) defined as detectable viral shedding by Luminex Respiratory Pathogen Panel Test (RPP) in the presence of at least one influenza symptom.

  From 24h post-viral inoculation (Day 1) until the end of the quarantine phase on Day 7

• Number of Treatment Emergent Adverse Events (TEAEs) Per Subject.

  To determine the number of TEAEs that were reported after the first administration of the vaccine until the end of the study (overall) and then separated into pre-inoculation (events reported from the time of first vaccination up to Day 0 prior to time of inoculation) and post-inoculation (Day 0 inoculation time through study completion).

  From the first vaccination on day -43 to the last follow up visit on day 63.

• Number of Subjects With Treatment Emergent Adverse Event Classified by Relatedness and Severity.

  Number of subjects with one or more AE are reported by severity (mild, moderate and severe) and relatedness to vaccine or challenge virus inoculation (definitely, probably, possibly, unlikely, not related).

  From the day of the first vaccination up to the end of the study on day +63.

Secondary Outcomes (8)

• Number of Subjects With Detectable Viral Shedding and Number of Subjects With Recorded Influenza Symptoms During the Quarantine Period.

  Quarantine period from day 1 to day 7 post-inoculation.

• Viral Shedding Duration

  starting from evening of Day 1 post-inoculation up to Day 7.

• Total Viral Shedding (Area Under the Curve)

  from the evening of Day 1 post-inoculation to the morning of Day 7 (last timepoint before expected quarantine discharge)

• Peak Viral Load

  from the evening of Day 1 post-inoculation to the morning of Day 7 (last timepoint before expected quarantine discharge)

• Duration of Influenza Symptoms

  from the evening of Day 1 post-inoculation to the morning of Day 7 (last timepoint before expected quarantine discharge)

Other Outcomes (1)

• Immunogenicity of FLU-v

  At pre-inoculation post-vaccination (Day -2), and post-influenza challenge (Day 35/Day 63)

Study Arms (3)

Group 1 adjuvanted placebo

PLACEBO COMPARATOR

0.5ml adjuvanted placebo on Day -43 and on Day -22 followed by influenza challenge on day 0

Biological: adjuvanted placebo; Other: Influenza challenge

Group 2 adjuvanted FLU-v one dose

EXPERIMENTAL

0.5ml (500mcg) adjuvanted FLU-v vaccine on Day -43 and adjuvanted placebo on Day -22 followed by influenza challenge on day 0

Biological: adjuvanted FLU-v; Biological: adjuvanted placebo; Other: Influenza challenge

Group 3 adjuvanted FLU-v two doses

EXPERIMENTAL

0.5ml (500mcg) adjuvanted FLU-v vaccine on Day -43 and on Day -22 followed by influenza challenge on day 0

Biological: adjuvanted FLU-v; Other: Influenza challenge

Interventions

adjuvanted FLU-v BIOLOGICAL

Subcutaneous injection in the upper arm with 500mcg of FLU-v as 0.5ml emulsion in 0.25ml of WFI and 0.25ml of adjuvant Montanide ISA-51

Group 2 adjuvanted FLU-v one dose; Group 3 adjuvanted FLU-v two doses

adjuvanted placebo BIOLOGICAL

Subcutaneous injection in the upper arm with 0.5ml emulsion made of 0.25ml of WFI and 0.25ml of adjuvant Montanide ISA-51

Group 1 adjuvanted placebo; Group 2 adjuvanted FLU-v one dose

Influenza challenge OTHER

On day 0, administration with an intranasal sprayer of 1ml of PBS containing 10(7) TCID50 of Influenza A 2009 H1N1 human virus manufactured under GMP in certified Vero cells.

Group 1 adjuvanted placebo; Group 2 adjuvanted FLU-v one dose; Group 3 adjuvanted FLU-v two doses

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males and females aged ≥18 and ≤55 years of age at the point of enrolment.
• Willingness to remain in isolation for the duration of viral shedding and to comply with all study requirements.
• The following criteria are applicable to subjects in a heterosexual relationship and female subjects in a same sex relationship (i.e., the criteria do not apply to male subjects in a same sex relationship):
• True abstinence- when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g. calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception).
• Two forms of effective contraceptive methods among (between) the couple, which are defined as:
• For males: condom with spermicidal foam/gel/film/cream, sterilisation (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate. This applies only to males participating in the study).
• For females:
• Women no longer of child bearing potential (post-menopausal females are defined as having a history of amenorrhea for at least 2 years, otherwise they should have documented status as being surgically sterile or post hysterectomy. The latter applies only to females participating in the study). If of childbearing potential, then acceptable forms of contraception include:
• Established (a minimum of 2 weeks prior to admission) use of oral, injected or implanted hormonal methods of contraception.
• Placement of an intrauterine device (IUD) or intrauterine system (IUS).
• Barrier methods of contraception or occlusive cap (diaphragm or cervical/vault caps), both with one of the following - spermicidal foam/gel/film/cream/suppository.
• The longevity of contraception is as follows:
• Males:
• Comply with agreed contraception at entry to quarantine, and continuing until 90 days after the date of viral challenge/last dosing with IMP (whichever occurs last).
• Must not donate sperm following discharge from quarantine until 90 days after the date of viral challenge/last dosing with IMP (whichever occurs last).

You may not qualify if:

• A documented medical history for a minimum of the last 2 years prior to inoculation.
• Any subjects who have smoked 10 pack years at any time. Of those subjects that have smoked less than 10 pack years at any time, a subject will be excluded: If regular smokers (e.g., smoking every day) at the time of enrolment. If current casual smoker or use of smoking / nicotine-related products, they must agree to refrain from smoking during the in-patient stay
• Presence of self-reported or medically documented significant medical condition including but not limited to:
• Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, cardiac surgery, ischemic heart disease, known anatomic defects).
• Chronic medical conditions requiring close medical follow-up or hospitalisation during the past 5 years (e.g., insulin dependent diabetes mellitus, renal dysfunction, haemoglobinopathies).
• Immunosuppression, or immunodeficiency or ongoing malignancy.
• Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy, stroke, seizures).
• Post infectious or post vaccine neurological sequelae.
• Hyperlipidemia requiring medical therapy per current American College of Cardiology (ACC) and American Heart Association (AHA) guidelines published in 2013.
• Individual with body mass index (BMI) \<18 and \>35.
• Acute illness within 7 days of first vaccine administration day
• Clinically significant abnormal electrocardiogram (ECG) and/or parameters, as determined by the Investigator
• Subjects with clinically significant abnormal systolic and diastolic blood pressure or clinically significant abnormal pulse rate.
• Subject has abnormal pulmonary function as measured by spirometry defined as a forced vital capacity or forced expiratory volume in 1 second (FEV1) \< 80% of predicted or peripheral arterial oxygen saturation (SpO2) \< 92% on room air.
• Known allergy to treatments for influenza (including but not limited to oseltamivir, nonsteroidals).

Sponsors & Collaborators

• PepTcell Limited: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

hVIVO Services Limited

London, E1 2AX, United Kingdom

Location

Related Publications (7)

• Stoloff GA, Caparros-Wanderley W. Synthetic multi-epitope peptides identified in silico induce protective immunity against multiple influenza serotypes. Eur J Immunol. 2007 Sep;37(9):2441-9. doi: 10.1002/eji.200737254.

  PMID: 17668898 BACKGROUND

• Pleguezuelos O, Robinson S, Stoloff GA, Caparros-Wanderley W. Synthetic Influenza vaccine (FLU-v) stimulates cell mediated immunity in a double-blind, randomised, placebo-controlled Phase I trial. Vaccine. 2012 Jun 29;30(31):4655-60. doi: 10.1016/j.vaccine.2012.04.089. Epub 2012 May 8.

  PMID: 22575166 BACKGROUND

• Pleguezuelos O, Robinson S, Fernandez A, Stoloff GA, Mann A, Gilbert A, Balaratnam G, Wilkinson T, Lambkin-Williams R, Oxford J, Caparros-Wanderley W. A Synthetic Influenza Virus Vaccine Induces a Cellular Immune Response That Correlates with Reduction in Symptomatology and Virus Shedding in a Randomized Phase Ib Live-Virus Challenge in Humans. Clin Vaccine Immunol. 2015 Jul;22(7):828-35. doi: 10.1128/CVI.00098-15. Epub 2015 May 20.

  PMID: 25994549 BACKGROUND

• Pleguezuelos O, Robinson S, Fernandez A, Stoloff GA, Caparros-Wanderley W. Meta-Analysis and Potential Role of Preexisting Heterosubtypic Cellular Immunity Based on Variations in Disease Severity Outcomes for Influenza Live Viral Challenges in Humans. Clin Vaccine Immunol. 2015 Aug;22(8):949-56. doi: 10.1128/CVI.00101-15. Epub 2015 Jun 17.

  PMID: 26084515 BACKGROUND

• van Doorn E, Pleguezuelos O, Liu H, Fernandez A, Bannister R, Stoloff G, Oftung F, Norley S, Huckriede A, Frijlink HW, Hak E. Evaluation of the immunogenicity and safety of different doses and formulations of a broad spectrum influenza vaccine (FLU-v) developed by SEEK: study protocol for a single-center, randomized, double-blind and placebo-controlled clinical phase IIb trial. BMC Infect Dis. 2017 Apr 4;17(1):241. doi: 10.1186/s12879-017-2341-9.

  PMID: 28376743 BACKGROUND

• Memoli MJ, Czajkowski L, Reed S, Athota R, Bristol T, Proudfoot K, Fargis S, Stein M, Dunfee RL, Shaw PA, Davey RT, Taubenberger JK. Validation of the wild-type influenza A human challenge model H1N1pdMIST: an A(H1N1)pdm09 dose-finding investigational new drug study. Clin Infect Dis. 2015 Mar 1;60(5):693-702. doi: 10.1093/cid/ciu924. Epub 2014 Nov 20.

  PMID: 25416753 BACKGROUND

• Ponne S, Kumar R, Vanmathi SM, Brilhante RSN, Kumar CR. Reverse engineering protection: A comprehensive survey of reverse vaccinology-based vaccines targeting viral pathogens. Vaccine. 2024 Apr 11;42(10):2503-2518. doi: 10.1016/j.vaccine.2024.02.087. Epub 2024 Mar 23.

  PMID: 38523003 DERIVED

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Dr Olga Pleguezuelos
• Organization: SEEK

olga.pleguezuelos@seekacure.com

+44 020 7153 6601

Study Officials

• Jeremy Dennison, Dr

  Hammersmith Medicines Research

  PRINCIPAL INVESTIGATOR

• Balpreet Matharu, Dr

  hVIVO Services Limited

  PRINCIPAL INVESTIGATOR

• Matthew J Memoli, M.D

  National Institute of Allergy and Infectious Diseases (NIAID)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2017
• First Posted: June 8, 2017
• Study Start: August 18, 2016
• Primary Completion: March 31, 2017
• Study Completion: May 25, 2017
• Last Updated: August 5, 2020
• Results First Posted: May 1, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)