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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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).

Conditions
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Influenza

Intervention / Treatment
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* Biological: M-001
* Biological: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Able to comply with the trial procedures and be available for all study visits. 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). 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) Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to study vaccination. Exclusion Criteria: History of neurological symptoms or signs, or anaphylactic shock following administration of any vaccine. Known or suspected (or have a high risk of developing) impairment/alteration of immune function (excluding that normally associated with advanced age). 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 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. An acute illness, including an axillary temperature greater than 38 Celsius (38ºC), occurred within 1 week before first vaccination Positive positive urine pregnancy test prior to vaccination or women who are breastfeeding.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Experimental group: 2 immunizations with M-001 Control group: 2 injection of saline (placebo)
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Flu, vaccine, Influenza, universal, M-001, Multimeric-001