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

• ClinicalTrials.gov Identifier: NCT03450915
• Recruitment Status: Completed
• First Posted: March 1, 2018
• Results First Posted: September 13, 2021
• Last Update Posted: October 5, 2021
• Sponsor: BiondVax Pharmaceuticals ltd.
• Information provided by (Responsible Party): BiondVax Pharmaceuticals ltd.

Tracking Information

• First Submitted Date: February 8, 2018
• First Posted Date: March 1, 2018
• Results First Submitted Date: June 16, 2021
• Results First Posted Date: September 13, 2021
• Last Update Posted Date: October 5, 2021
• Actual Study Start Date: August 1, 2018
• Actual Primary Completion Date: July 2, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 17, 2021)

• Number of Participants With qRT-PCR or Culture-confirmed Influenza-like Illness [ Time Frame: From Day 14 post-second vaccination day to end of influenza season, an average of 4 months per participant per year ]
  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.
• Number of Participants With One or More Serious Adverse Events, New Onset Chronic Illness, and Non-solicited Adverse Events [ Time Frame: 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 ]
  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

Original Primary Outcome Measures (submitted: February 23, 2018)

• Clinical Efficacy: PCR and Culture Confirmed Influenza [ Time Frame: Up to 2 flu seasons (approximately 1.5 years) ]
  If a participant presents with ILI, then we will run Polymerase chain reaction (PCR). If the PCR is positive, then we will culture confirm. Outcome measure is percentage of PCR and culture confirmed influenza cases in the M-001 experimental group vs. placebo caused by any influenza A or B virus in association with Influenza-like illness (ILI) symptoms.
• Safety: Occurrence of vaccine-related serious adverse events (SAEs) [ Time Frame: 6 months ]
  Occurrence of vaccine-related serious adverse events (SAEs) such as solicited and unsolicited injection site and systemic reactogenicity events.

Current Secondary Outcome Measures (submitted: August 17, 2021)

• Number of Participants With Culture-confirmed Influenza Incidence [ Time Frame: From Day 14 post-second vaccination day to end of influenza season, an average of 4 months per participant per year ]
  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.
• Number of Participants With Reduction of Severity of qRT-PCR or Culture-confirmed Influenza [ Time Frame: From Day 14 post-second vaccination day to end of influenza season, an average of 4 months per participant per year ]
  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.
• Number of Participants With Influenza-like Illness Symptoms [ Time Frame: From Day 14 post-second vaccination day to end of influenza season, an average of 4 months per participant per year ]
  Assessment of number of participants having ILI symptoms in the experimental or control group

Original Secondary Outcome Measures (submitted: February 23, 2018)

• Clinical Efficacy: PCR Confirmed Influenza [ Time Frame: Up to 2 flu seasons (approximately 1.5 years) ]
  Percentage of PCR confirmed influenza cases in the M-001 experimental group vs. placebo
• Lot consistency [ Time Frame: 42 days ]
  Frequency of T-cell subsets from participants in the experimental group, expressing interferon gamma (IFN-g) in cluster of differentiation 4 (CD4+) peripheral blood mononuclear cells (PBMCs) after stimulation with M-001 16 days after the second dose of M-001 as compared to baseline.

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: February 23, 2018)

Reduced severity of illness [ Time Frame: Up to 2 flu seasons (approximately 1.5 years) ]

Average time to alleviation of each influenza symptom

Descriptive Information

• Brief Title: A Pivotal Trial to Assess the Safety and Clinical Efficacy of the M-001 as a Standalone Universal Flu Vaccine
• Official Title: 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).
• Brief Summary: 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.

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
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Experimental group: 2 immunizations with M-001 Control group: 2 injection of saline (placebo)

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

All parties are blinded except for the person who prepares the syringe for injection. The M-001 is cloudy white and its appearance is different from the transparent saline that is used for placebo. The person prepares the syringe with an opaque sticker that fully covers the syringe contents. People administering the syringe are not involved or present during syringe preparation, and are thus fully blinded.

Primary Purpose: Treatment

• Condition: Influenza

Intervention

• 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 Name: Multimeric-001
• Biological: Saline
  0.9% sodium chloride (NaCl)

Study Arms

• Experimental: M-001
  Participants will be vaccinated with 1mg dose of M-001 twice: Once at Day 0, and once at Day 21.
  Intervention: Biological: M-001
• Placebo Comparator: Saline
  Participants will be vaccinated with saline twice: Once at Day 0, and once at Day 21.
  Intervention: Biological: Saline

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 17, 2021): 12460
• Original Estimated Enrollment (submitted: February 23, 2018): 9630
• Actual Study Completion Date: October 23, 2020
• Actual Primary Completion Date: July 2, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Poland

Administrative Information

• NCT Number: NCT03450915
• Other Study ID Numbers: BVX-010
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: BiondVax Pharmaceuticals ltd.
• Study Sponsor: BiondVax Pharmaceuticals ltd.
• Collaborators: Not Provided

Investigators

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

• PRS Account: BiondVax Pharmaceuticals ltd.
• Verification Date: September 2021