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

Sponsor

Medicago (Industry)

Overall Status

Completed

CT.gov ID

NCT03301051

Collaborator

(none)

10,137

Enrollment

Locations

Arms

9.4

Actual Duration (Months)

138.9

Patients Per Site

14.8

Patients Per Site Per Month

Study Details

Study Description

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 Virus-Like Particles (VLP) Influenza Vaccine (30 μg/strain) or of placebo will be administered to approximately 10,000 subjects.

Condition or Disease	Intervention/Treatment	Phase
Virus Diseases RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections	Biological: Quadrivalent VLP Vaccine Biological: Placebo	Phase 3

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 subjects 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 subjects will receive the Quadrivalent VLP Influenza Vaccine at a dose of 30 μg/strain and approximately 5,000 subjects will receive the placebo. Within the two treatment groups, subjects 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).

Subjects 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

10137 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

A Randomized, Observer-blind, Placebo-controlled, Multicenter, Phase 3 Study to Assess the Efficacy, Safety, and Immunogenicity of a Plant-Derived Quadrivalent Virus-Like Particles Influenza Vaccine in Adults 18-64 Years of Age

Actual Study Start Date :

Aug 31, 2017

Actual Primary Completion Date :

May 2, 2018

Actual Study Completion Date :

Jun 12, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Quadrivalent VLP Vaccine Single dose - 30 µg/strain of Quadrivalent VLP Vaccine	Biological: Quadrivalent VLP Vaccine Single dose of a 30 µg/strain of Quadrivalent VLP Vaccine Other Names: 30 µg/strain of Quadrivalent VLP Vaccine
Placebo Comparator: Placebo Single dose - Placebo	Biological: Placebo Single dose of a Placebo

Arm

Intervention/Treatment

Experimental: Quadrivalent VLP Vaccine

Single dose - 30 µg/strain of Quadrivalent VLP Vaccine

Biological: Quadrivalent VLP Vaccine

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

Other Names:

30 µg/strain of Quadrivalent VLP Vaccine

Placebo Comparator: Placebo

Single dose - Placebo

Biological: Placebo

Single dose of a Placebo

Outcome Measures

Primary Outcome Measures

Time of occurence of protocol-defined respiratory illness due to laboratory-confirmed influenza caused by vaccine matched strains. [8 months]

Secondary Outcome Measures

Time of occurence of protocol-defined respiratory illness due to any laboratory-confirmed influenza strains. [8 months]
Number of subjects with solicited local and systemic reactions, unsolicited adverse events, serious adverse events and New Onset Chronic Diseases. [8 months]
Immunogenicity evaluated by the humoral immune response (HI, MN, and SRH assays) and the CMI response [21 days after injection]
• 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 or placebo, as measured by hemagglutination inhibition (HI) assay, microneutralization (MN) assay, and single radial hemolysis (SRH) assay against homologous and heterologous (HI only) influenza strains.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 64 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be eligible for participation in this study; no protocol waivers are allowed:

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;
Subject must have a body mass index (BMI) below 40 kg/m2;
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;
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);
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 (thereafter 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.
Female subjects must have a negative urine pregnancy test result at the Screening/Vaccination visit (Visit 1);
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. 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).

Exclusion Criteria:

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

Any subject 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:

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.

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;
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 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]), ;
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. Subjects 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. Subjects 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;
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);
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 subject 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;
Planned use of influenza antiviral treatment medication before the collection of nasopharyngeal swabs (e.g. oseltamivir, zanamivir, rapivab);
Have a rash, dermatological condition, tattoos, muscle mass, or any other abnormalities at the injection site that may interfere with injection site reaction rating;
Subjects who have received a blood transfusion within 90 days prior to study vaccination;
Any female subject who has a positive or doubtful pregnancy test result prior to vaccination or who is lactating;
Subjects 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 subject 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);
Presence of any febrile illness (including an oral temperature ≥ 38.0 ˚C within 24 hours prior to vaccination. Such subjects may be re-evaluated for enrolment after resolution of illness;
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;

Subjects 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;
Subjects with a history of Guillain-Barré Syndrome.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 222	Mobile	Alabama	United States	36608
2	Site 210	Anaheim	California	United States	92801
3	Site 223	Milford	Connecticut	United States	06460
4	Site 217	Coral Gables	Florida	United States	33134
5	Site 220	Hollywood	Florida	United States	33024
6	Site 212	South Miami	Florida	United States	33143
7	Site 203	Savannah	Georgia	United States	31406
8	Site 218	Stockbridge	Georgia	United States	30281
9	Site 206	Wichita	Kansas	United States	67025
10	Site 202	Metairie	Louisiana	United States	70006
11	Site 225	Saint Louis	Missouri	United States	63141
12	Site 224	Norfolk	Nebraska	United States	68701
13	Site 208	Omaha	Nebraska	United States	63134
14	Site 213	Las Vegas	Nevada	United States	89104
15	Site 205	Binghamton	New York	United States	13901
16	Site 228	Endwell	New York	United States	13760
17	Site 216	Charlotte	North Carolina	United States	28209
18	Site 221	Charlotte	North Carolina	United States	28277
19	Site 227	Winston-Salem	North Carolina	United States	27103
20	Site 201	Columbus	Ohio	United States	43123
21	Site 207	Dakota Dunes	South Dakota	United States	57049
22	Site 209	Bristol	Tennessee	United States	37260
23	Site 204	Austin	Texas	United States	78705
24	Site 229	Austin	Texas	United States	78745
25	Site 226	Fort Worth	Texas	United States	76104
26	Site 219	Fort Worth	Texas	United States	76135
27	Site 214	Salt Lake City	Utah	United States	84124
28	Site 211	West Jordan	Utah	United States	84088
29	Site 230	Norfolk	Virginia	United States	23507
30	Site 105	Halifax	Nova Scotia	Canada
31	Site 106	Truro	Nova Scotia	Canada
32	Site 107	Brampton	Ontario	Canada
33	Site 110	Sudbury	Ontario	Canada
34	Site 108	Toronto	Ontario	Canada
35	Site 109	Mirabel	Quebec	Canada
36	Site 103	Pierrefonds	Quebec	Canada
37	Site 101	Quebec City	Quebec	Canada
38	Site 102	Quebec City	Quebec	Canada
39	Site 104	Sherbrooke	Quebec	Canada
40	Site 306	Espoo		Finland
41	Site 305	Helsinki		Finland
42	Site 310	Helsinki		Finland
43	Site 304	Jarvenpaa		Finland
44	Site 309	Kokkola		Finland
45	Site 307	Oulu		Finland
46	Site 303	Pori		Finland
47	Site 308	Seinäjoki		Finland
48	Site 301	Tampere		Finland
49	Site 302	Turku		Finland
50	Site 402	Berlin		Germany
51	Site 403	Berlin		Germany
52	Site 406	Berlin		Germany
53	Site 401	Essen		Germany
54	Site 404	Essen		Germany
55	Site 405	Hamburg		Germany
56	Site 701	Manila		Philippines
57	Site 703	Manila		Philippines
58	Site 702	Muntinlupa		Philippines
59	Site 704	Muntinlupa		Philippines
60	Site 705	Muntinlupa		Philippines
61	Site 706	Pasay		Philippines
62	Site 605	Bangkok Noi		Thailand
63	Site 601	Bangkok		Thailand
64	Site 603	Bangkok		Thailand
65	Site 604	Bangkok		Thailand
66	Site 606	Bangkok		Thailand
67	Site 607	Bangkok		Thailand
68	Site 602	Chiang Mai		Thailand
69	Site 510	Corby		United Kingdom
70	Site 507	Kent		United Kingdom
71	Site 506	Northwood		United Kingdom
72	Site 508	Romford		United Kingdom
73	Site 509	Shipley		United Kingdom