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

NCT03301051 | Completed Phase 3 Results FDA Drug

• 1 other identifier: CP-PRO-QVLP-012
• Study Type: interventional
• Target: 10,160
• Locations: 7 countries
• Sites: 73

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

Conditions

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

Keywords

Influenza; Human; RNA Virus Infections; Efficacy; Immunologic; Immunogenic Factors; Physiological Effects of Drug; Virus Diseases; Orthomyxoviridae Infections; Infection; Vaccine; Safety; Plant-made; Virus-like Particle; Hemagglutinin; Quadrivalent Influenza Vaccine

Outcome Measures

Primary Outcomes (1)

• Number of Occurrences of Protocol-Defined Respiratory Illness Caused by Vaccine-Matched Influenza Strains

  Occurrences of protocol-defined respiratory illness caused by vaccine-matched influenza strains were assessed. The vaccine-matched strains included: H1N1 (A/Michigan/45/2015); H3N2 (A/Hong Kong/4801/2014); B/Brisbane (B/Brisbane/60/2008); and B/Phuket (B/Phuket/3073/2013A). The protocol-defined respiratory illness was determined by the occurrence of at least 1 of the following respiratory symptoms: sneezing, stuffy nose, sore throat, cough, sputum production, wheezing, or difficulty breathing. Occurrences of all matched strains are reported.

  Day 14 (post-vaccination) up to ~8 months

Secondary Outcomes (26)

• Number of Occurrences of Protocol-Defined Respiratory Illness Cases Caused by Any Laboratory Confirmed Influenza Strain

  Day 14 (post-vaccination) up to ~8 months

• Number of Occurrences of Laboratory-Confirmed Protocol-Defined Influenza-Like Illness (ILI) Caused by Vaccine-Matched Influenza Strains

  Day 14 (post-vaccination) up to ~8 months

• Number of Occurrences of Laboratory-Confirmed ILI Caused by Any Influenza Strain

  Day 14 (post-vaccination) up to ~8 months

• Number of Occurrences of Protocol-Defined ILI Cases

  Day 14 (post-vaccination) up to ~8 months

• Number of Participants With at Least One Immediate Complaint

  15 minutes post vaccination

Study Arms (2)

Quadrivalent VLP Vaccine

EXPERIMENTAL

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

Biological: Quadrivalent VLP Vaccine

Placebo

PLACEBO COMPARATOR

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

Biological: Placebo

Interventions

Quadrivalent VLP Vaccine BIOLOGICAL

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

Quadrivalent VLP Vaccine

Placebo BIOLOGICAL

Single dose of a Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participants must have a body mass index (BMI) below 40 kg/m\^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;
• 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.
• Female participants must have a negative urine pregnancy test result at the Screening/Vaccination visit (Visit 1).
• 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;
• 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).

You may not qualify if:

• Participants who meet any of the following criteria will be excluded from participating in this study; no protocol waivers are allowed:
• 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;
• According to the Investigator's opinion, history of significant acute or chronic, uncontrolled medical or neuropsychiatric illness. 'Uncontrolled' is defined as:
• 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;
• 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;
• 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);
• 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 \[including diabetes mellitus\]).
• 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;
• Administration of any adjuvanted or investigational influenza vaccine within one year prior to randomization or planned administration prior to the completion of the study;
• 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;
• 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;
• 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;
• 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;
• History of allergy to any of the constituents of the Quadrivalent VLP Influenza Vaccine or tobacco;
• History of anaphylactic allergic reactions to plants or plants components;

Sponsors & Collaborators

• Medicago: lead

Study Sites (73)

Site 222

Mobile, Alabama, 36608, United States

Location

Site 210

Anaheim, California, 92801, United States

Location

Site 223

Milford, Connecticut, 06460, United States

Location

Site 217

Coral Gables, Florida, 33134, United States

Location

Site 220

Hollywood, Florida, 33024, United States

Location

Site 212

South Miami, Florida, 33143, United States

Location

Site 203

Savannah, Georgia, 31406, United States

Location

Site 218

Stockbridge, Georgia, 30281, United States

Location

Site 206

Wichita, Kansas, 67025, United States

Location

Site 202

Metairie, Louisiana, 70006, United States

Location

Site 225

St Louis, Missouri, 63141, United States

Location

Site 224

Norfolk, Nebraska, 68701, United States

Location

Site 208

Omaha, Nebraska, 63134, United States

Location

Site 213

Las Vegas, Nevada, 89104, United States

Location

Site 205

Binghamton, New York, 13901, United States

Location

Site 228

Endwell, New York, 13760, United States

Location

Site 216

Charlotte, North Carolina, 28209, United States

Location

Site 221

Charlotte, North Carolina, 28277, United States

Location

Site 227

Winston-Salem, North Carolina, 27103, United States

Location

Site 201

Columbus, Ohio, 43123, United States

Location

Site 207

Dakota Dunes, South Dakota, 57049, United States

Location

Site 209

Bristol, Tennessee, 37260, United States

Location

Site 204

Austin, Texas, 78705, United States

Location

Site 229

Austin, Texas, 78745, United States

Location

Site 226

Fort Worth, Texas, 76104, United States

Location

Site 219

Fort Worth, Texas, 76135, United States

Location

Site 214

Salt Lake City, Utah, 84124, United States

Location

Site 211

West Jordan, Utah, 84088, United States

Location

Site 230

Norfolk, Virginia, 23507, United States

Location

Site 105

Halifax, Nova Scotia, Canada

Location

Site 106

Truro, Nova Scotia, Canada

Location

Site 107

Brampton, Ontario, Canada

Location

Site 110

Greater Sudbury, Ontario, Canada

Location

Site 108

Toronto, Ontario, Canada

Location

Site 109

Mirabel, Quebec, Canada

Location

Site 103

Pierrefonds, Quebec, Canada

Location

Site 101

Québec, Quebec, Canada

Location

Site 102

Québec, Quebec, Canada

Location

Site 104

Sherbrooke, Quebec, Canada

Location

Site 306

Espoo, Finland

Location

Site 305

Helsinki, Finland

Location

Site 310

Helsinki, Finland

Location

Site 304

Jarvenpaa, Finland

Location

Site 309

Kokkola, Finland

Location

Site 307

Oulu, Finland

Location

Site 303

Pori, Finland

Location

Site 308

Seinäjoki, Finland

Location

Site 301

Tampere, Finland

Location

Site 302

Turku, Finland

Location

Site 402

Berlin, Germany

Location

Site 403

Berlin, Germany

Location

Site 406

Berlin, Germany

Location

Site 401

Essen, Germany

Location

Site 404

Essen, Germany

Location

Site 405

Hamburg, Germany

Location

Site 702

City of Muntinlupa, Philippines

Location

Site 704

City of Muntinlupa, Philippines

Location

Site 705

City of Muntinlupa, Philippines

Location

Site 701

Manila, Philippines

Location

Site 703

Manila, Philippines

Location

Site 706

Pasay, Philippines

Location

Site 601

Bangkok, Thailand

Location

Site 603

Bangkok, Thailand

Location

Site 604

Bangkok, Thailand

Location

Site 606

Bangkok, Thailand

Location

Site 607

Bangkok, Thailand

Location

Site 605

Bangkok Noi, Thailand

Location

Site 602

Chiang Mai, Thailand

Location

Site 510

Corby, United Kingdom

Location

Site 507

Gillingham, United Kingdom

Location

Site 506

Northwood, United Kingdom

Location

Site 508

Romford, United Kingdom

Location

Site 509

Shipley, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 33065035 RESULT

MeSH Terms

Conditions

Virus Diseases; RNA Virus Infections; Respiratory Tract Diseases; Respiratory Tract Infections; Influenza, Human; Orthomyxoviridae Infections; Infections

Results Point of Contact

• Title: Medical Director
• Organization: Medicago

clinicaltrialinquiries@medicago.com

+1 418-658-9393

Study Officials

• Medical Director

  Medicago

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Observer-blind
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2017
• First Posted: October 4, 2017
• Study Start: August 31, 2017
• Primary Completion: May 2, 2018
• Study Completion: May 9, 2018
• Last Updated: August 14, 2023
• Results First Posted: August 14, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (10); US (29); DE (6); PH (6); TH (7); GB (5); FI (10)