Efficacy, Safety, and Immunogenicity of a Plant-Derived Quadrivalent Virus-Like Particles (VLPs) Influenza Vaccine in Adults

NCT ID: NCT03301051

Last Updated: 2023-08-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 10160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-31
• Study Completion Date: 2018-05-09

Brief Summary

This Phase 3 study is intended to assess the efficacy of the Quadrivalent VLP Influenza Vaccine during the 2017-2018 influenza season in healthy adults 18 to 64 years of age. One dose of Quadrivalent VLP Influenza Vaccine (30 μg/strain) or of placebo will be administered to approximately 10,000 participants

Detailed Description

This randomized, observer-blind, placebo-controlled multicenter, Phase 3 study will be conducted at multiple sites. The composition of the Quadrivalent VLP Influenza Vaccine to be used in this study includes a mix of recombinant H1, H3, and two B hemagglutinin proteins expressed as VLPs for the 2017-2018 influenza virus strains.

Approximately 10,000 healthy male and female participants aged 18 to 64 years will be randomized in a 1:1 ratio into one of two parallel treatment groups, such that approximately 5,000 participants will receive the Quadrivalent VLP Influenza Vaccine at a dose of 30 μg/strain and approximately 5,000 participants will receive the placebo. Within the two treatment groups, participants will be stratified by site and two age groups (18-49 years of age and 50-64 years of age in a 1:1 ratio).

Participants will participate in this study for approximately eight to ten months, during which a first visit will be scheduled on Day 0 for screening and vaccine administration.

Conditions

Virus Diseases; RNA Virus Infections; Respiratory Tract Diseases; Respiratory Tract Infections; Influenza

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Quadrivalent VLP Vaccine

Participants received one intramuscular (IM) injection of 0.5 mL of 30 μg/strain of the Quadrivalent VLP Influenza Vaccine on Day 0.

Group Type: EXPERIMENTAL

Quadrivalent VLP Vaccine

Intervention Type: BIOLOGICAL

Single dose of a 30 µg/strain of Quadrivalent VLP Vaccine

Placebo

Participants received one IM injection of 0.5 mL of placebo on Day 0.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Single dose of a Placebo

Interventions

Quadrivalent VLP Vaccine

Single dose of a 30 µg/strain of Quadrivalent VLP Vaccine

Intervention Type: BIOLOGICAL

Placebo

Single dose of a Placebo

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Participants must have a body mass index (BMI) below 40 kg/m^2;

2. Participants 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;

3. Participants must be in good general health prior to study participation, with no clinically relevant abnormalities that could jeopardize participant safety or interfere with study assessments, as assessed by the Principal Investigator or sub-Investigator (thereafter referred as Investigator) and determined by medical history, physical examination, and vital signs; Note: Participants 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 participant 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 participant with more recent stabilization of a disease could also be eligible.

4. Female participants must have a negative urine pregnancy test result at the Screening/Vaccination visit (Visit 1).

5. Female participants 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 participants must have no plan to become pregnant for at least two months post-vaccination. Abstinent participants should be asked what method(s) they would use should their circumstances change, and participants without a well-defined plan should be excluded. The following relationship or methods of contraception are considered to be effective:

• Hormonal contraceptives (e.g. oral, 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 vaginal intercourse abstinence until at least 60 days post-vaccination;
• Female partner;

6. 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).

Exclusion Criteria

Participants who meet any of the following criteria will be excluded from participating in this study; no protocol waivers are allowed:

1. Any participant whose medical condition(s) is sufficiently severe that annual influenza vaccination would be routinely recommended in the jurisdiction of recruitment, as per the Investigator's judgement;

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 participant 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 rheumatoid 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 participants 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 intramuscular 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. Participants may not participate in any other investigational or marketed drug study while participating in this study until after the study;

11. Treatment with systemic glucocorticoids at a dose exceeding 10 mg of prednisone (or equivalent) per day for more than seven consecutive days or for 10 or more days in total, within one month of study vaccine administration; any other cytotoxic or immunosuppressant drug, or any immunoglobulin preparation within three months of vaccination and until the completion of the study. Low doses of nasal or inhaled glucocorticoids are allowed. Topical steroids are permitted;

12. Any significant disorder of coagulation including, but not limited to, treatment with warfarin derivatives or heparin. Persons receiving prophylactic anti-platelet medications (e.g. low-dose aspirin [no more than 325 mg/day]), and without a clinically apparent bleeding tendency are eligible. Participants treated with new generation drugs that do not increase the risk of intramuscular bleeding (e.g. clopidogrel) are also eligible;

13. History of allergy to any of the constituents of the Quadrivalent VLP Influenza Vaccine or tobacco;

14. History of anaphylactic allergic reactions to plants or plants components;

15. Use of antihistamines with systemic absorption for more than 14 days in the four weeks prior to vaccination or use of antihistamines 48 hours prior to study vaccination (the use of topical antihistamines and nasal or inhaled steroids is acceptable);

16. Use of prophylactic medications (e.g. acetaminophen/paracetamol, aspirin, naproxen, or ibuprofen) within 24 hours of randomization to prevent or pre-empt symptoms due to vaccination. Any participant discovered to have taken a prophylactic medication to prevent or pre-empt symptoms due to vaccination within the 24 hours prior to planned randomization must be delayed until at least the 24 hours period is met;

17. Planned use of influenza antiviral treatment medication before the collection of nasopharyngeal swabs (e.g. oseltamivir, zanamivir, rapivab);

18. Have a rash, dermatological condition, tattoos, muscle mass, or any other abnormalities at the injection site that may interfere with injection site reaction rating;

19. Participants who have received a blood transfusion within 90 days prior to study vaccination;

20. Any female participant who has a positive or doubtful pregnancy test result prior to vaccination or who is lactating;

21. Participants with abnormal vital signs (systolic blood pressure [BP] > 140 mmHg and/or diastolic BP ≥ 90 mmHg, heart rate ≤ 45 beats/min and ≥ 100 beats/min) evaluated by an Investigator to be clinically significant. A participant with abnormal vital signs results may be included in the study based on Investigator's judgment (e.g. a resting hear rate ≤ 45 in highly trained athletes);

22. Presence of any febrile illness (including an oral temperature ≥ 38.0 ˚C within 24 hours prior to vaccination. Such participants may be re-evaluated for enrolment after resolution of illness;

23. Cancer or treatment for cancer within three years prior to study vaccine administration.

Persons with a history of cancer who are disease-free without treatment for three years or more are eligible. However, individuals with conditions such as treated and uncomplicated basal cell carcinoma of the skin or non-treated, non-disseminated local prostate cancer may be eligible;

24. Participants identified as an Investigator or employee of the Investigator or clinical site with direct involvement in the proposed study, or identified as an immediate family member (i.e. parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study or any employee of Medicago;

25. Participants with a history of Guillain-Barré Syndrome.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Medicago

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Medicago

Locations

Site 222

Mobile, Alabama, United States

Site 210

Anaheim, California, United States

Site 223

Milford, Connecticut, United States

Site 217

Coral Gables, Florida, United States

Site 220

Hollywood, Florida, United States

Site 212

South Miami, Florida, United States

Site 203

Savannah, Georgia, United States

Site 218

Stockbridge, Georgia, United States

Site 206

Wichita, Kansas, United States

Site 202

Metairie, Louisiana, United States

Site 225

St Louis, Missouri, United States

Site 224

Norfolk, Nebraska, United States

Site 208

Omaha, Nebraska, United States

Site 213

Las Vegas, Nevada, United States

Site 205

Binghamton, New York, United States

Site 228

Endwell, New York, United States

Site 216

Charlotte, North Carolina, United States

Site 221

Charlotte, North Carolina, United States

Site 227

Winston-Salem, North Carolina, United States

Site 201

Columbus, Ohio, United States

Site 207

Dakota Dunes, South Dakota, United States

Site 209

Bristol, Tennessee, United States

Site 204

Austin, Texas, United States

Site 229

Austin, Texas, United States

Site 226

Fort Worth, Texas, United States

Site 219

Fort Worth, Texas, United States

Site 214

Salt Lake City, Utah, United States

Site 211

West Jordan, Utah, United States

Site 230

Norfolk, Virginia, United States

Site 105

Halifax, Nova Scotia, Canada

Site 106

Truro, Nova Scotia, Canada

Site 107

Brampton, Ontario, Canada

Site 110

Greater Sudbury, Ontario, Canada

Site 108

Toronto, Ontario, Canada

Site 109

Mirabel, Quebec, Canada

Site 103

Pierrefonds, Quebec, Canada

Site 101

Québec, Quebec, Canada

Site 102

Québec, Quebec, Canada

Site 104

Sherbrooke, Quebec, Canada

Site 306

Espoo, , Finland

Site 305

Helsinki, , Finland

Site 310

Helsinki, , Finland

Site 304

Järvenpää, , Finland

Site 309

Kokkola, , Finland

Site 307

Oulu, , Finland

Site 303

Pori, , Finland

Site 308

Seinäjoki, , Finland

Site 301

Tampere, , Finland

Site 302

Turku, , Finland

Site 402

Berlin, , Germany

Site 403

Berlin, , Germany

Site 406

Berlin, , Germany

Site 401

Essen, , Germany

Site 404

Essen, , Germany

Site 405

Hamburg, , Germany

Site 702

City of Muntinlupa, , Philippines

Site 704

City of Muntinlupa, , Philippines

Site 705

City of Muntinlupa, , Philippines

Site 701

Manila, , Philippines

Site 703

Manila, , Philippines

Site 706

Pasay, , Philippines

Site 601

Bangkok, , Thailand

Site 603

Bangkok, , Thailand

Site 604

Bangkok, , Thailand

Site 606

Bangkok, , Thailand

Site 607

Bangkok, , Thailand

Site 605

Bangkok Noi, , Thailand

Site 602

Chiang Mai, , Thailand

Site 510

Corby, , United Kingdom

Site 507

Gillingham, , United Kingdom

Site 506

Northwood, , United Kingdom

Site 508

Romford, , United Kingdom

Site 509

Shipley, , United Kingdom

Countries

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

References

Ward BJ, Makarkov A, Seguin A, Pillet S, Trepanier S, Dhaliwall J, Libman MD, Vesikari T, Landry N. Efficacy, immunogenicity, and safety of a plant-derived, quadrivalent, virus-like particle influenza vaccine in adults (18-64 years) and older adults (>/=65 years): two multicentre, randomised phase 3 trials. Lancet. 2020 Nov 7;396(10261):1491-1503. doi: 10.1016/S0140-6736(20)32014-6. Epub 2020 Oct 13.

Reference Type: RESULT

PMID: 33065035 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CP-PRO-QVLP-012

Identifier Type: -

Identifier Source: org_study_id