A Pivotal Trial to Assess the Safety and Clinical Efficacy of the M-001 as a Standalone Universal Flu Vaccine

A Pivotal Multi-center, Randomized, Modified Double-blind, Placebo-controlled Phase 3 Trial to Assess the Safety and Clinical Efficacy of M-001 Influenza Vaccine Administered Intra-muscularly Twice in Older Adults and Elderly (≥50 Years).

The pivotal Phase 3 trial plans to enroll a total of approximately 12,460 participants aged 50+ over two years. Participants will be immunized twice with the M-001 universal influenza vaccine candidate or placebo and then followed for up to 2 seasons. The trial will evaluate the number of influenza cases in each group and the severity of illness during the follow up period.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: M-001; Biological: Saline

Detailed Description

The placebo-controlled pivotal clinical efficacy Phase 3 trial plans to enroll a total of approximately 12,460 participants over two years. Participants will be immunized twice with the M-001 influenza vaccine candidate or placebo. Influenza incidence and illness severity will be evaluated throughout the follow-up period of up to two years. Participants will be 50 years and older, with at least half over 65 years of age.

The trial is expected to take place in eastern European countries and begin prior to the 2018/19 Northern Hemisphere flu season.

• Study Type: Interventional
• Enrollment (Actual): 12460
• Phase: Phase 3

Contacts and Locations

Study Locations

• Poland
  • Kraków, Poland, 30348
    • Jagiellońskie Centrum Innowacji Sp.z o.o.
  • Ul. Bobrzyńskiego 14,
    • Kraków, Ul. Bobrzyńskiego 14,, Poland, 30-348
      • Jagiellońskie Centrum Innowacji Sp.z o.o.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female subjects 50 years of age (inclusive) or older, mentally competent, willing and able to give the written informed consent prior to study entry
2. Able to comply with the trial procedures and be available for all study visits.
3. Medically stable. (Subjects may have underlying chronic conditions such as hypertension, diabetes, ischemic heart disease, or hypothyroidism, as long as their symptoms/signs are controlled. If they are on medication for a condition, the medication dose must have been stable for at least 3 months preceding vaccination).
4. Women of childbearing potential (not surgically sterile or postmenopausal for greater than or equal to one year) and men must agree to practice adequate contraception (barrier or hormone methods or intra uterine device (IUD) for women and a condom for men) throughout the study treatment and for at least up to day 51 (for female) and day 111 (for male) of the trial (i.e. 30 (for female) and 90 (for male) days after the last dose of the IMP)
5. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to study vaccination.

Exclusion Criteria:

1. History of neurological symptoms or signs, or anaphylactic shock following administration of any vaccine.
2. Known or suspected (or have a high risk of developing) impairment/alteration of immune function (excluding that normally associated with advanced age).
3. Receipt of: a) Immunosuppressive drugs: i) systemic glucocorticoids >/= 10 mg prednisone per day ii) cytotoxic drugs b) Investigational drugs within 30 days before, or planned during, the study c) Blood products within 3 months before, or planned during, the study d) Influenza vaccine within 6 months before the study) Other vaccines within 30 days before, or planned during, the study
4. Any serious disease such as: cancer, autoimmune disease, advanced arteriosclerotic disease or complicated diabetes mellitus, chronic obstructive pulmonary disease (COPD) that requires oxygen therapy, acute or progressive hepatic disease, acute or progressive renal disease, or congestive heart failure, as judged by the PI.
5. An acute illness, including an axillary temperature greater than 38 Celsius (38ºC), occurred within 1 week before first vaccination
6. Positive positive urine pregnancy test prior to vaccination or women who are breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: M-001; Participants will be vaccinated with 1mg dose of M-001 twice: Once at Day 0, and once at Day 21.	Biological: M-001; A recombinant protein containing 9 conserved epitopes from Influenza A and B that are common to the vast majority of influenza viruses.; Other Names: Multimeric-001
PLACEBO_COMPARATOR: Saline; Participants will be vaccinated with saline twice: Once at Day 0, and once at Day 21.	Biological: Saline; 0.9% sodium chloride (NaCl)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With qRT-PCR or Culture-confirmed Influenza-like Illness	Prevention of influenza disease by comparing the occurrence of either qRT-PCR or culture confirmed influenza in the M-001 experimental group vs. placebo caused by any influenza A or B virus in association with a protocol defined Influenza Like Illness.	From Day 14 post-second vaccination day to end of influenza season, an average of 4 months per participant per year
Number of Participants With One or More Serious Adverse Events, New Onset Chronic Illness, and Non-solicited Adverse Events	Number of participants with one or more Serious Adverse Events, New Onset Chronic illness, and Non-solicited Adverse Events assessed during one flu season per participant	From Day 0 to end of study completion by participant which coincides with end of flu season in the respective year, an average of 4 months per participant per year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Culture-confirmed Influenza Incidence	Occurrence of culture confirmed influenza in the M-001 experimental group vs. placebo caused by any influenza A or B virus in association with a protocol defined Influenza Like Illness.	From Day 14 post-second vaccination day to end of influenza season, an average of 4 months per participant per year
Number of Participants With Reduction of Severity of qRT-PCR or Culture-confirmed Influenza	Assessed by reduction of severity of either qRT-PCR or culture-confirmed influenza illness by the reduction due to M-001 in the average number of days with respiratory or systemic symptoms during the first laboratory-confirmed influenza illness episode.	From Day 14 post-second vaccination day to end of influenza season, an average of 4 months per participant per year
Number of Participants With Influenza-like Illness Symptoms	Assessment of number of participants having ILI symptoms in the experimental or control group	From Day 14 post-second vaccination day to end of influenza season, an average of 4 months per participant per year

Collaborators and Investigators

• Sponsor: BiondVax Pharmaceuticals ltd.
• Investigators: Study Director: Tamar Ben-Yedidia, PhD, BiondVax Pharmaceuticals ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2018
• Primary Completion (ACTUAL): July 2, 2020
• Study Completion (ACTUAL): October 23, 2020

Study Registration Dates

• First Submitted: February 8, 2018
• First Submitted That Met QC Criteria: February 23, 2018
• First Posted (ACTUAL): March 1, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 5, 2021
• Last Update Submitted That Met QC Criteria: September 13, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: vaccine; Influenza; Flu; universal; M-001; Multimeric-001
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: BVX-010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No