A Phase 3 Study to Assess the Efficacy, Safety, and Immunogenicity of a Plant-Derived Quadrivalent VLP Influenza Vaccine in Adults 18-64 Years of Age

• Register: EUCTR
• Last refreshed on: 20 August 2018
• Main ID: EUCTR2017-001239-38-FI
• Date of registration: 20/06/2017
• Prospective Registration: Yes
• Primary sponsor: Medicago R&D Inc.
• Public title: A Phase 3 Study to Assess the Efficacy, Safety, and Immunogenicity of a Plant-Derived Quadrivalent VLP Influenza Vaccine in Adults 18-64 Years of Age
• Scientific title: A Randomized, Observer-blind, Placebo-controlled, Multicenter, Phase 3 Study to Assess the Efficacy, Safety, and Immunogenicity of a Plant-Derived Quadrivalent VLP Influenza Vaccine in Adults 18-64 Years of Age
• Date of first enrolment: 20/07/2017
• Target sample size: 10000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001239-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: Observer blind; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Finland, Germany, Philippines, Thailand, United Kingdom, United States

Contacts

• Name: Daniel Croteau
• Affiliation: Medicago R&D Inc

• Name: Daniel Croteau
• Affiliation: Medicago R&D Inc

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet all of the following inclusion criteria to be eligible for participation in this
study:
1. Subjects must be able to read, understand, and sign the informed consent form (ICF); complete study-related procedures; and communicate with the study staff at visits and by phone;
2. Subject must have a body mass index (BMI) below 40 kg/m2;
3. Subjects are considered by the Investigator to be reliable and likely to cooperate with the assessment procedures and be available for the duration of the study;
4. Male and female subjects must be 18 to 64 (has not yet had his/her 65th birthday) years of age, inclusive, at the Screening/Vaccination visit (Visit 1);
5. Subjects must be in good general health prior to study participation, with no clinically relevant abnormalities that could jeopardize subject safety or interfere with study assessments, as assessed by the Principal Investigator or sub-Investigator (there after referred as Investigator) and determined by medical history, physical examination, and vital signs;
Note: Subjects with a pre-existing chronic disease will be allowed to participate if the disease is stable and, according to the Investigator’s judgment, the condition is unlikely to confound the results of the study or pose additional risk to the subject by participating in the study. Stable disease is generally defined as no new onset or exacerbation of pre-existing chronic disease three months prior to vaccination. Based on the Investigator’s judgment, a subject with more recent stabilization of a disease could also be eligible.
6. Female subjects must have a negative urine pregnancy test result at the Screening/Vaccination visit (Visit 1);
7. Female subjects of childbearing potential must use an effective method of contraception for one month prior to vaccination and agree to continue employing adequate birth control measures for at least 60 days post-vaccination. Moreover, female subjects must have no plan to become pregnant for at least two months post-vaccination. Abstinent subjects should be asked what method(s) they would use should their circumstances change, and subjects without a well-defined plan should be excluded. The following relationship or methods of contraception are considered to be effective:
- Hormonal contraceptives (e.g. injectable, topical [patch], or estrogenic vaginal ring);
- Intra-uterine device with or without hormonal release;
- Male partner using a condom plus spermicide or sterilized partner (at least one year prior to vaccination);
- Credible self-reported history of heterosexual abstinence until at least 60 days postvaccination;
- Female partner;
8. Non-childbearing females are defined as:
- Surgically-sterile (defined as bilateral tubal ligation, hysterectomy or bilateral oophorectomy performed more than one month prior to vaccination); or
- Post-menopausal (absence of menses for 24 consecutive months and age consistent with natural cessation of ovulation).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10000
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
Subjects who meet any of the following criteria will be excluded from participating in this study:
1. Any subject whose medical condition(s) is sufficiently severe that annual influenza vaccination would be routinely recommended in the jurisdiction of recruitment;
2. According to the Investigator’s opinion, history of significant acute or chronic, uncontrolled medical or neuropsychiatric illness. ‘Uncontrolled’ is defined as:
- Requiring a new medical or surgical treatment during the three months prior to study vaccine administration unless the criteria outlined in inclusion criterion no. 5 can be met (i.e. the Investigator can justify inclusion based upon the innocuous nature of medical/surgical events and/or treatments);
- Requiring any significant change in a chronic medication (i.e. drug, dose, frequency) during the three months prior to study vaccine administration due to uncontrolled symptoms or drug toxicity unless the innocuous nature of the medication change meets the criteria outlined in inclusion criterion no. 5 and is appropriately justified by the Investigator.
3. Any medical or neuropsychiatric condition or any history of excessive alcohol use or drug abuse which, in the Investigator’s opinion, would render the subject unable to provide informed consent or unable to provide valid safety observations and reporting;
4. Any autoimmune disease other than hypothyroidism on stable replacement therapy (including, but not limited to rhematoid arthritis, systemic lupus erythematosus, Crohn’s disease, and inflammatory bowel disease) or any confirmed or suspected immunosuppressive condition or immunodeficiency including known or suspected human immunodeficiency virus (HIV), Hepatitis B or C infection, the presence of lymphoproliferative disease;
5. History of chronic pulmonary (including asthma, bronchopulmonary dysplasia, and cystic fibrosis) or cardiovascular (except isolated hypertension), renal, hepatic, neurologic, hematologic (including anemia and hemoglobinopathy), or metabolic disorders (including diabetes mellitus);
6. Because this is a placebo-controlled study, any subjects in close contact with individuals considered to be at high risk for developing influenza-related complications (individuals considered at high risk for complications include adults and children who have chronic pulmonary or cardiovascular [except isolated hypertension], renal, hepatic, neurologic, hematologic, or metabolic disorders [including diabetes mellitus]);
7. Administration or planned administration of any non-influenza vaccine within 30 days prior to randomization up to blood sampling on Day 21. Immunization on an emergency basis will be evaluated case-by-case by the Investigator;
8. Administration of any adjuvanted or investigational influenza vaccine within one year prior to randomization or planned administration prior to the completion of the study;
9. Administration of any ‘standard’, non-adjuvanted influenza vaccine (e.g. live attenuated trivalent/quadrivalent inactivated influenza vaccine or split trivalent/quadrivalent inactivated influenza vaccine administered by intranasal, intradermal, or IM route) within six months prior to randomization and up to completion of the study;
10. Use of any investigational or non-registered product within 30 days or five half-lives, whichever is longer, prior to randomization or planned use during the study period. Subjects may not participate in any other investigational or marketed drug study while pa

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Seasonal influenza
MedDRA version: 20.0 Level: PT Classification code 10022000 Term: Influenza System Organ Class: 10021881 - Infections and infestations

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Intervention(s)

Product Name: Quadrivalent VLP Influenza Vaccine
Pharmaceutical Form: Suspension for injection in pre-filled syringe
INN or Proposed INN: Quadrivalent VLP Influenza Vaccine
Other descriptive name: INFLUENZA VACCINE
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Intramuscular use

Primary Outcome(s)

Secondary Objective: Efficacy:
To evaluate the efficacy, relative to placebo, of a single dose of the Quadrivalent VLP Influenza Vaccine given at a dose of 30 µg/strain;
- Against any laboratory-confirmed influenza strain;
- Against laboratory-confirmed protocol-defined influenza-like illness (ILI) caused by vaccine-matched strains.
- As measured by the incidence of subjects presenting with symptoms of protocol-defined ILI, regardless of laboratory results.
Safety:
- To assess the safety and tolerability, relative to placebo, of a single dose of the Quadrivalent VLP Influenza Vaccine given at a dose of 30 µg/strain.
Immunogenicity:
- To assess, in a subset of 400 subjects, the immunogenicity of a single dose of Quadrivalent VLP Influenza Vaccine given at a dose of 30 µg/strain, as measured by hemagglutination inhibition (HI) assay, microneutralization (MN) assay, and single radial hemolysis (SRH) assay against homologous and heterologous (HI only) influenza strains.

Primary end point(s): Efficacy:
- Occurrences of laboratory-confirmed influenza illnesses (= 14 days post-vaccination) caused by influenza viral types/subtypes that are matched (and/or antigenically similar) to the strains covered in the vaccine formulation.

Timepoint(s) of evaluation of this end point: = 14 days post-vaccination

Main Objective: - To evaluate the efficacy, relative to placebo, of a single dose of the Quadrivalent VLP Influenza Vaccine given at a dose of 30 µg/strain, against laboratory-confirmed influenza caused by vaccine-matched strains.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Various times as detailed in the protocol

Secondary end point(s): Efficacy:
- Occurrences of laboratory-confirmed influenza illnesses (= 14 days post-vaccination) caused by any influenza viral types/subtypes (matched, mismatched, and un-typed);
- Occurrences of laboratory-confirmed influenza (according to protocol defined ILI) illnesses (= 14 days post-vaccination) caused by influenza viral types/subtypes that are matched (and/or antigenically similar) to the strains covered in the vaccine formulation;
- Occurrences of protocol-defined ILI = 14 days postvaccination (confirmed or not).
Safety:
- Percentage, intensity, and relationship to vaccination of immediate complaints (15 minutes post-vaccination);
- Percentage, intensity, and relationship to vaccination of solicited local and systemic signs and symptoms (for seven days following study vaccine administration);
- Percentage, intensity, and relationship of TEAEs for 21 days following study vaccine administration;
- Occurrences of deaths, SAEs, AEs leading to withdrawal, and NOCDs up to the end of the surveillance period.
Immunogenicity (subset of subjects):
- HI antibody response induced by the Quadrivalent VLP Influenza Vaccine against the homologous and heterologous influenza strains on Days 0 and 21 will be assessed in a subset of 400 subjects (300 who received the VLP vaccine and 100 who received the placebo). HI antibody titers will be analyzed using the following parameters: geometric mean titers (GMT), seroconversion (SC) rate, seroprotection (SP) rate, and geometric mean fold rise (GMFR);
- MN antibody response induced by the Quadrivalent VLP Influenza Vaccine against the homologous influenza strains on Days 0 and 21, in a subset of subjects, will be analyzed using the following parameters: GMT, SC rate, and GMFR;
- SRH antibody response induced by the Quadrivalent VLP Influenza Vaccine against the homologous strains on Days 0 and 21, will be analysed using the following parameters: geometric mean area (GMA), SC rate, SP rate, and GMFR.

Secondary ID(s)

2017-001239-38-DE

CP-PRO-QVLP-012

Source(s) of Monetary Support

Medicago R&D Inc.