A Randomised, Double-blind, Placebo-controlled Phase IIb Trial to Test FLU-v Vaccine

NCT02962908 | Completed Phase 2 Results

• 2 other identifiers: FLU-v 0032015-001932-38
• Study Type: interventional
• Target: 175
• Locations: 1 country
• Sites: 1

Brief Summary

FLU-v is a vaccine that aims to protect against a wide range of flu viruses. The purpose of this study is to measure the immune responses induced by FLU-v vaccine. This study will look at how safe FLU-v is when administered and how successful it is in preventing flu or reducing the severity of the flu symptoms. The study requires 222 healthy volunteers 18-60 years old. Participation in the study will take a maximum of 7 months and consists of 5 visits. During visit 1, subjects will be examined by a doctor to make sure they are eligible to enter the study. A 15ml blood sample (a tablespoon) will be taken to check general health followed by a general physical exam. Medical history and some personal information will be collected. Subjects that have received the traditional flu vaccine in the past 6 months, and those females who are pregnant or breastfeeding will not be allowed in the study. Subjects of childbearing age must agree to use effective contraceptive methods. At visit 2, subjects will be randomly allocated to one of the four treatment groups summarised below:

• Treatment 1: FLU-v (test vaccine) at the start of the study (Day 0) and then again 21 days later
• Treatment 2: FLU-v (test vaccine) with an additional substance added \[known as Montanide ISA 51\] which improves the effect of the test vaccine. Injection will be given on Day 0 and then Placebo (no test vaccine) alone 21 days later
• Treatment 3: Placebo (no test vaccine) injection on Day 0 and then 21 days later
• Treatment 4: Placebo (no test vaccine) with an additional substance added \[known as Montanide ISA 51\] on Day 0 and then Placebo (no test vaccine) alone 21 days later Treatment will be injected under the skin in the upper arm on day 0 (visit 2) and 21 days later (visit 3). Blood samples will be taken before treatment (day 0), and on days 42 (visit 4) and 180 (visit 5) to the immune responses induced by the vaccine. Subjects will be asked to complete a diary card to write down any side effects that they may experience after vaccination. Subjects will also be asked to complete another diary card to document any flu-like symptoms experienced between December 2016 and March 2017, this time is officially considered as the flu season. During this period, if the subject experiences flu-like symptoms, a collection of a nose and tonsil swab will be arranged by the study site to confirm whether they have the flu or not.

Conditions

Influenza

Keywords

broad; universal; vaccine; influenza; peptide; Tcell; UNISEC

Outcome Measures

Primary Outcomes (7)

• CD4+ and CD8+ Th1 Cellular Immunogenicity on Day 42

  Comparison of the TH1 response in the treatment arms compared to placebo from baseline to day 42 following vaccination, calculated as the median fold change in the number of CD4+ and CD8+ T cells positive for IFN-gamma, TNF-alpha, IL-2 and CD107a. Fold change is calculated as the number of cells on day 42 divided by number of cells on day 0.

  day 0 to day 42

• CD4+ and CD8+ Th1 Cellular Immunogenicity on Day 180

  Comparison of the TH1 response in the treatment arms compared to placebo from baseline to day 180 following vaccination, calculated as the median fold change in the number of CD4+ and CD8+ T cells positive for IFN-gamma, TNF-alpha, IL-2 and CD107a. Fold change is calculated as the number of cells on day 180 divided by number of cells on day 0.

  Day 0 to day 180

• Percentage of TH1 Cytokine Responders (Responders Defined as Those With >2 Fold Median Increase From Baseline in CD4+ and CD8+ T-cells Positive for Particular Cytokine)

  To compare the number of subjects that showed at least a two-fold increase on day 42 and day 180 following vaccination in the number of CD4+and CD8+ T-cells secreting TH1 cytokines in all groups.

  prevaccination, day 42 (21 days after last vaccination) and day 180.

• Percentage of CD4+ and CD8+ TH1 Cytokine Responders Determined by Mixture Models for Single-cell Assays (MIMOSA)

  To compare the number of subjects identified as responders for cytokine markers as determined by MIMOSA analysis (Responders based on a false discovery rate derived P-value \<0.05).

  day 0 to day 42 and day 180

• IFN-gamma Responses Measured by ELISA

  Median fold change in IFN-gamma secretion from PBMCs stimulated in vitro with FLU-v antigens. IFN-gamma secretion was measured by ELISA.Fold change was measured as secretion on day 42 divided by secretion on day 0, and secretion on day 180 divided by secretion on day 0.

  day 0 to day 42, day 0 to day 180

• Percentage of Responders on Day 42 and Day 180 for IFNgamma Secretion by PBMCs

  Responders were defined as subjects having at least a two-fold increase in the amount of IFNg secreted on day 42 and day 180 compared the amount secreted on day 0. IFNg was measured by ELISA

  prevaccination (day 0) to postvaccination (day 42 and day 180)

• Solicited AEs

  To evaluate the solicited AEs in all subjects

  until 21 days after the last dosing of the study vaccine

Secondary Outcomes (2)

• Antibody Responses to FLU-v

  prevaccination, day 42 (21 days after last vaccination) and day 180.

• Th2 Cytokine Responses (IL-4)

  prevaccination, day 42 (21 days after last vaccination) and day 180.

Other Outcomes (4)

• Unsolicited AEs and SAEs

  From the start of the vacciantion until study completion for each subject, approximately no more than 7 months

• Percentage of Participants Who Tested Positive for Influenza Strains

  For up to 4 months during the influenza season

• Severity of Symptoms in RT-PCR Influenza-confirmed Subjects.

  Symptoms experienced during an influenza infection episode, approximately 7-10 days.

Study Arms (4)

Group 1

EXPERIMENTAL

(n=74): FLU-v on Day 0 and Day 21

Biological: FLU-v

Group 2

EXPERIMENTAL

(n=74): adjuvanted FLU-v on Day 0, saline (0.5mL) on Day 21

Biological: adjuvanted FLU-v; Biological: Saline

Group 3

PLACEBO COMPARATOR

(n=37): saline solution (0.5ml) on Day 0 and Day 21

Biological: Saline

Group 4

PLACEBO COMPARATOR

(n=37): Adjuvanted placebo on Day 0, saline (0.5mL) on Day 21

Biological: Saline; Biological: Adjuvanted placebo

Interventions

FLU-v BIOLOGICAL

Subcutaneous injection in the upper arm with 500 ug of FLU-v as 0.5ml suspension in 0.01M HCl and 0.01M NaOH

Group 1

adjuvanted FLU-v BIOLOGICAL

Subcutaneous injection in the upper arm with 500ug of FLU-v emulsified in 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Group 2

Saline BIOLOGICAL

Subcutaneous injection in the upper arm with 0.5ml of saline

Also known as: NaCl

Group 2; Group 3; Group 4

Adjuvanted placebo BIOLOGICAL

Subcutaneous injection in the upper arm with an emulsion made with 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Group 4

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males or healthy non-pregnant females (as indicated by a negative blood pregnancy test done during the screening visit) between the ages of 18 and 60 years, inclusive;
• Women of childbearing potential (not surgically sterile or postmenopausal for greater than or equal to one year) and men must agree to practice appropriate contraception (a combination of barrier and hormonal methods for women and a condom for men) from screening and until at least 30 days (up to Study Day 51 for females) and 90 days (up to Study Day 111 for males), after the last vaccination.
• A subject is in good health, as determined by a comprehensive clinical assessment {vital signs (heart rate, blood pressure, oral temperature)}, blood chemistry test (electrolytes, renal/kidney function, liver function, C-reactive protein, complete blood count), medical history, general physical examination, self-reported illness} and the clinical judgment of the investigator;
• Able to understand and comply with planned study procedures;
• Provides signed informed consent form

You may not qualify if:

• Has a known allergy to any of the components of the vaccine.
• Has a history of severe reaction following immunization.
• Persons with immune deficiency/disorder, whether due to genetic defect, immunodeficiency disease, or immunosuppressive therapy.
• Women who have a positive pregnancy test during the screening visit or who are breastfeeding.
• Has a history of any of the following (reported by subjects):
• Acute disseminated encephalomyelitis (ADEM);
• Neoplastic disease - current or previous;
• Asthma or severe allergic disease;
• Bleeding disorders
• Chronic Hepatitis B and/or C infection;
• Chronic liver disease;
• Diabetes mellitus;
• Guillain-Barré syndrome;
• HIV;
• Rheumatoid arthritis or other autoimmune diseases;

Sponsors & Collaborators

• PepTcell Limited: lead
• Seventh Framework Programme: collaborator
• University of Groningen: collaborator
• University Medical Center Groningen: collaborator
• Robert Koch Institut: collaborator
• Norwegian Institute of Public Health: collaborator

Study Sites (1)

Isala

Zwolle, 8025 AB, Netherlands

Location

Related Publications (6)

• 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

• 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, 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

• 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

• 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

• Pleguezuelos O, Dille J, de Groen S, Oftung F, Niesters HGM, Islam MA, Naess LM, Hungnes O, Aldarij N, Idema DL, Perez AF, James E, Frijlink HW, Stoloff G, Groeneveld P, Hak E. Immunogenicity, Safety, and Efficacy of a Standalone Universal Influenza Vaccine, FLU-v, in Healthy Adults: A Randomized Clinical Trial. Ann Intern Med. 2020 Apr 7;172(7):453-462. doi: 10.7326/M19-0735. Epub 2020 Mar 10.

  PMID: 32150750 RESULT

Related Links

• End of project reporting for the UNISEC Consortium

MeSH Terms

Conditions

Influenza, Human

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

Recruitment stopped early at 175 subjects instead of 222. Dropout rate was lower than anticipated (4% vs 20%). The number of participants recruited was considered to be sufficient to provide statistically significant data in the primary endpoints.

Results Point of Contact

• Title: Dr Olga Pleguezuelos, Chief Scientific Officer
• Organization: PepTcell Ltd (trading as SEEK)

olga.pleguezuelos@seekacure.com

+44 020 7153 6601

Study Officials

• Paul Groeneveld, PhD

  Isala

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: November 7, 2016
• First Posted: November 15, 2016
• Study Start: August 1, 2016
• Primary Completion: July 18, 2017
• Study Completion: July 18, 2017
• Last Updated: September 16, 2020
• Results First Posted: April 8, 2019

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)