Efficacy of MVA-NP+M1 in the Influenza H3N2 Human Challenge Model

NCT03883113 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: FLU010
• Study Type: interventional
• Target: 145
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase 2, single center, randomized, double blind study evaluating the safety, efficacy, and immunogenicity of MVA NP+M1 in the H3N2 human influenza challenge model; on healthy adult volunteers.

Conditions

Influenza

Outcome Measures

Primary Outcomes (1)

• Degree of Nasopharyngeal Viral Shedding as Determined by Quantitative Polymerase Chain Reaction qPCR

  Measure of nasopharyngeal viral shedding during challenge; recorded as viral area under curve (vAUC) as determined by quantitative real time polymerase chain reaction (qRT-PCR). vAUC is calculated by plotting the log viral particles number/ml for each time point against time and is using the trapezoidal rule.

  Throughout 9 days (Day2, Day3, Day4, Day5, Day6, Day7, Day8, Day9, Day10) after viral Inoculation (Day1) of the challenge phase. Nasal swabs taken twice a day (b.i.d) at least 8 hours apart.

Secondary Outcomes (17)

• Number and Percentage of Virologically Confirmed Influenza-Like Illness

  9 days from day 2 to day 10

• Percentage of Participants With Attack Rate of Challenge Agent (qRT-PCR)

  9 days from day 2 to day 10

• Percentage of Participants With Quantitative Culture Attack Rate of Challenge Agent (qCulture)

  9 days from day 2 to day 10

• Time to Start of Viral Shedding (qPCR) From Virus Inoculation

  9 days from day 2 to day 10

• Time to Start of Viral Shedding (qCulture) From Virus Inoculation

  9 days from day 2 to day 10

Other Outcomes (4)

• Severity of Individual Symptoms for MVA-NP+M1 vs. Placebo

  11 days

• Total Symptom Score Time to Start, Time to Peak and Duration

  11 days

• Correlation of T Cell Phenotypes With Illness Outcomes

  3 months

Study Arms (2)

MVA-NP+M1 & H3N2 Challenge Virus

EXPERIMENTAL

Vaccination administered: MVA-NP+M1 (IM injection, 0.5 ml, 1.5 x10\^8 pfu.); Challenge Virus administered: H3N2 (nasal spray, 0.5 ml, 1.0x10\^6 TCID50/ml)

Biological: MVA-NP+M1; Biological: H3N2 (A/Belgium/2417/2015)

Saline Placebo & H3N2 Challenge Virus

PLACEBO COMPARATOR

Vaccination administered: Sodium Chloride (IM injection, 0.5 ml, 0.9%); Challenge Virus administered: H3N2 (nasal spray, 0.5 ml, 1.0x10\^6 TCID50/ml)

Biological: Saline; Biological: H3N2 (A/Belgium/2417/2015)

Interventions

MVA-NP+M1 BIOLOGICAL

Trial Vaccine

MVA-NP+M1 & H3N2 Challenge Virus

Saline BIOLOGICAL

Sodium Chloride Placebo

Saline Placebo & H3N2 Challenge Virus

H3N2 (A/Belgium/2417/2015) BIOLOGICAL

Challenge Agent

MVA-NP+M1 & H3N2 Challenge Virus; Saline Placebo & H3N2 Challenge Virus

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.
• Non-smokers or those who stopped smoking ≥ 3 months prior to screening 1 visit.
• Willingness to remain in isolation for the duration of the study.
• A female participant is eligible for this study if she is not pregnant or breast feeding and 1 of the following:
• Of non-childbearing potential (i.e., women who have had a hysterectomy or tubal ligation or are postmenopausal, as defined by no menses in greater than or equal to 1 year).
• Of childbearing potential but has been and agrees to continue practicing highly effective contraception or abstinence (if this is the preferred and usual lifestyle of the participant) from 6 months prior to vaccination to 6 months after administration of the influenza challenge virus. Highly effective methods of contraception include 1 or more of the following:
• i. male partner who is sterile (vasectomised) prior to the female participants entry into the study and is the sole sexual partner for the female participant; ii. hormonal (oral, intravaginal, transdermal, implantable or injectable); iii. an intrauterine hormone-releasing system (IUS); iv. an intrauterine device (IUD) with a documented failure rate of \< 1%; v. bilateral tubal occlusion.
• Pre-challenge serum microneutralization test (MNT) against A/Belgium/4217/2015 (H3N2) challenge strain \< 20.

You may not qualify if:

• BMI \< 19 and \> 32.
• Presence of any significant acute or chronic, uncontrolled medical (or psychiatric) illness including a history of chronic respiratory illness.
• History of seasonal hay fever or a clinically significant seasonal allergic rhinitis (SAR), including the use of symptomatic prescription only medication and non-prescription medication.
• History or evidence of autoimmune disease or known immunodeficiency of any cause - with the exception of atopic dermatitis/eczema and atopic rhinitis.
• Any history of anaphylaxis in reaction to vaccination or history of allergic reactions likely to be exacerbated by any component of the vaccine.
• History of lung disease (Asthma, COPD).
• Current smokers or those who stopped smoking \< 3months prior to screening 1 visit.
• Positive diagnostic tests for HIV, Hepatitis B or Hepatitis C indicating active infection.
• Evidence of drug abuse or a positive urine drug screen or alcohol breath test.
• Chronic use of any medication or other product (prescription or over-the-counter), for symptoms of rhinitis or nasal congestion or for any chronic nasopharyngeal complaint, or chronic use of any intranasal medication for any indication that has not ceased within 30 days prior to screening 1.
• Receipt of any investigational drug within 3 months prior to vaccination, or prior participation in a clinical trial of any influenza vaccine, or any investigational vaccine or experimental influenza viral challenge delivered directly to the respiratory tract within 1 year prior to challenge.
• Receipt of the 2018/2019 seasonal flu vaccine.
• Receipt of any live vaccines within the 4 weeks prior to vaccination.
• Any laboratory test which is abnormal and which is deemed by the Investigator(s) to be clinically significant.
• Receipt of any systemic chemotherapy agent at any time.

Sponsors & Collaborators

• Barinthus Biotherapeutics: lead

Study Sites (1)

SGS Life Sciences, Clinical Pharmacology Unit (CPU)

Antwerp, 2060, Belgium

Location

Related Publications (1)

• Evans TG, Castellino F, Kowalik Dobczyk M, Tucker G, Walley AM, Van Leuven K, Klein J, Rutkowski K, Ellis C, Eagling-Vose E, Treanor J, van Baalen C, Filkov E, Laurent C, Thacker J, Asher J, Donabedian A. Assessment of CD8+ T-cell mediated immunity in an influenza A(H3N2) human challenge model in Belgium: a single centre, randomised, double-blind phase 2 study. Lancet Microbe. 2024 Jul;5(7):645-654. doi: 10.1016/S2666-5247(24)00024-7. Epub 2024 May 7.

  PMID: 38729196 DERIVED

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

Results Point of Contact

• Title: Tom Evans, MD
• Organization: Vaccitech Ltd.

enquiries@vaccitech.co.uk

+44 01865 591 445

Study Officials

• Robin Rogiers, MD

  SGS S.A.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• 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: February 21, 2019
• First Posted: March 20, 2019
• Study Start: June 3, 2019
• Primary Completion: December 16, 2019
• Study Completion: April 17, 2020
• Last Updated: March 18, 2021
• Results First Posted: March 18, 2021

Record last verified: 2021-03

Locations

BE (1)