Efficacy of a Plant-derived Quadrivalent VLP Vaccine in the Elderly

• Sponsor: Medicago (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03739112
• Collaborator: (none)
• Enrollment: 12,793
• Locations: 104
• Arms: 2
• Actual Duration (Months): 8.8
• Patients Per Site: 123
• Patients Per Site Per Month: 13.9

Study Details

Study Description

Brief Summary

This Phase 3 study is intended to assess the relative efficacy of the Quadrivalent VLP Influenza Vaccine during the 2018-2019 influenza season compared to a licensed vaccine in elderly adults 65 years of age and older. One dose of Quadrivalent Virus-Like Particles (VLP) Influenza Vaccine (30 μg/strain) or of Comparator (15 ug/strain) will be administered to approximately 12,120 subjects.

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

Detailed Description

This randomized, observer-blind, active-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 2018-2019 influenza virus strains.

Approximately 12,120 healthy male and female subjects aged 65 years and older will be randomized in a 1:1 ratio into one of two parallel treatment groups, such that approximately 6,060 subjects will receive the Quadrivalent VLP Influenza Vaccine at a dose of 30 μg/strain and approximately 6,060 subjects will receive the comparator. Within the two treatment groups, subjects will be stratified by site and two age groups (65-74 years of age and 75 years of age and older in a 2:1 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: 12793 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This is a randomized, observer-blind, active comparator-controlled, multicenter, Phase 3 efficacy study.This is a randomized, observer-blind, active comparator-controlled, multicenter, Phase 3 efficacy study.
• Masking: Single (Outcomes Assessor)
• Masking Description: Surveillance personnel is blinded from IP injection
• Primary Purpose: Prevention
• Official Title: A Randomized, Observer-blind, Active Comparator-controlled, Multicenter, Phase 3 Study to Assess the Efficacy, Safety, and Immunogenicity of a Plant-derived Quadrivalent VLP Influenza Vaccine in Adults 65 Years of Age and Older
• Actual Study Start Date: Sep 18, 2018
• Actual Primary Completion Date: May 17, 2019
• Actual Study Completion Date: Jun 14, 2019

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
Active Comparator: Quadrivalent Comparator Vaccine Single dose - 15 ug/strain of Quadrivalent Comparator Vaccine	Biological: Quadrivalent Comparator Vaccine; Single dose of a 15 ug/strain of Quadrivalent Comparator Vaccine

Outcome Measures

Primary Outcome Measures

1. Occurrence of protocol-defined Influenza-Like Illnesses (ILI) cause by any influenza viral type/subtype [8 months]

   Occurrences of protocol-defined ILI due to laboratory-confirmed influenza viral type/sub-type (RT-PCR)

Secondary Outcome Measures

1. Occurrence of ILI cause by vaccine-matched strains [8 months]

   Occurrences of laboratory-confirmed ILI caused by influenza viral types/subtypes that are matched (and/or antigenically similar) to the strains covered in the vaccination formulation (RT-PCR and serotyping)

2. Occurrence of protocol-defined Respiratory Illnesses (RI) cause by vaccine-matched strains [8 months]

   Occurrences of laboratory-confirmed RI caused by vaccine-matched strains sequential RT-PCR and serotyping)

3. Occurrence of protocol-defined Respiratory Illnesses (RI) cause by any influenza viral types/subtypes [8 months]

   Occurrences of laboratory-confirmed RI caused by any influenza viral types/subtypes (sequential RT-PCR and serotyping)

4. Occurrences of ILI regardless of laboratory results [8 months]

   Occurrences of ILI post vaccination confirmed or not by laboratory testing

5. Occurrences of solicited local and systemic reactions recorded in Diary [15 minutes post-vaccination]

   Percentage, intensity, and relationship to vaccination of immediate complaints

6. Occurrences of solicited local and systemic reactions recorded in Diary [seven days following study vaccine administration]

   Percentage, intensity, and relationship to vaccination of solicited local and systemic signs and symptoms

7. Occurrences of unsolicited AEs up to 21 days post-vaccination [21 days following study vaccine administration]

   Percentage, intensity, and relationship of TEAEs

8. Occurrence of Serious Adverse Events (SAE) [8 months]

   Occurrences of death and SAEs

9. Occurrence of Adverse Events leading to withdrawal [8 months]

   Occurrences of AEs leading to withdrawal

10. Occurrence of New Onset of Chronic Disease (NOCD) [8 months]

    Occurrences of NOCDs

11. HI antibody response induced by QVLP against the homologous and heterologous influenza strains in a subset of 420 subjects [21 days following study vaccine administration]

    GMT of HI antibody

12. HI antibody response induced by QVLP against the homologous and heterologous influenza strains in a subset of 420 subjects [21 days following study vaccine administration]

    SC rate

13. HI antibody response induced by QVLP against the homologous and heterologous influenza strains in a subset of 420 subjects [21 days following study vaccine administration]

    SP rate

14. HI antibody response induced by QVLP against the homologous and heterologous influenza strains in a subset of 420 subjects [21 days following study vaccine administration]

    Geometric mean fold rise.

15. MN antibody response induced by QVLP against the homologous influenza strains in a subset of 420 subjects [21 days following study vaccine administration]

    GMT of MN antibody

16. MN antibody response induced by QVLP against the homologous influenza strains in a subset of 420 subjects [21 days following study vaccine administration]

    SC rate of MN antibody

17. MN antibody response induced by QVLP against the homologous influenza strains in a subset of 420 subjects [21 days following study vaccine administration]

    GMFR of MN antibody

18. SRH antibody response induced by QVLP against the homologous strains in a subset of 420 subjects [21 days following study vaccine administration]

    Geometric mean area (GMA) of SRH antibody

19. SRH antibody response induced by QVLP against the homologous strains in a subset of 420 subjects [21 days following study vaccine administration]

    SC rate of SRH antibody

20. SRH antibody response induced by QVLP against the homologous strains in a subset of 420 subjects [21 days following study vaccine administration]

    SP rate of SRH antibody

21. SRH antibody response induced by QVLP against the homologous strains in a subset of 420 subjects [21 days following study vaccine administration]

    GMFR of SRH antibody

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Subjects must have read, understood, and signed the informed consent form (ICF) prior to participating in the study; subjects must also complete study-related procedures and communicate with the study staff at visits and by phone during the study;

2. Subject must have a body mass index (BMI) ≤ 35 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 65 years of age and older at the Screening/Vaccination visit (Visit 1);

5. Subjects must be non-institutionalized (e.g. not living in rehabilitation centres or old-age homes; living in an elderly community is acceptable) and have no acute or evolving medical problems prior to study participation and 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.

Exclusion Criteria:

1. According to the Investigator's opinion, history of an ongoing acute or evolving medical or neuropsychiatric illness. 'Evolving' 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.

1. Any medical or neuropsychiatric condition or any history of excessive alcohol use or drug abuse that would render the subject unable to provide informed consent or unable to provide valid safety observations and reporting, including methadone (methadone as treatment for opioid dependence may be acceptable if the subject has been otherwise opioid-free for at least three years);

2. Any autoimmune disease other than hypothyroidism on stable replacement therapy (including, but not limited to rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, type 1 diabetes, 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;

3. Any history of status asthmaticus or ongoing serious problems with asthma, hospitalization for asthma control, or recurrent asthma episodes requiring medical attention in the last three years (one or more episodes per year);

4. 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;

5. Administration of any adjuvanted or investigational influenza vaccine within one year prior to randomization or planned administration prior to the completion of the study;

6. 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 [IM] route) within six months prior to randomization and up to completion of the study;

7. 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;

8. Treatment with systemic glucocorticoids at a dose exceeding 10 mg of prednisone (or equivalent) per day for more than seven consecutive days or for ten 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;

9. 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 100 mg/day]), and without a clinically apparent bleeding tendency are eligible. Subjects treated with new generation drugs that do not increase the risk of IM bleeding (e.g. clopidogrel) are also eligible;

10. History of allergy to any of the constituents of the Quadrivalent VLP Influenza Vaccine, any components of the active comparator quadrivalent vaccine, or tobacco;

11. History of anaphylactic allergic reactions to plants or plants components (including fruits and nuts);

12. Use of antihistamines within 48 hours prior to study vaccination;

13. Daily use of large doses of medication for pain control or inflammation (e.g. opioids, nonsteroidal anti-inflammatory drugs [NSAIDs]). Use of a singular regular dose either in the morning or at bedtime would not be exclusionary;

14. 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;

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

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

17. Subjects who have received a blood transfusion within 90 days prior to study vaccination;

18. Subjects with abnormal vital signs (systolic blood pressure [BP] ≥ 150 mmHg and/or diastolic BP ≥ 95 mmHg for individuals taking antihypertensive medication and ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg for individuals not taking antihypertensive medication; heart rate [HR] ≤ 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 HR ≤ 45 in highly trained athletes);

19. Presence of any febrile illness (including an oral temperature [OT] ≥ 38.0 ˚C within 24 hours prior to vaccination;

20. 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;

21. 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) of the Investigator or any employee of Medicago (or their family members);

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	(Site 225) Coastal Clinical Research	Mobile	Alabama	United States	36608
2	(Site 201) Clinical Research Consortium	Tempe	Arizona	United States	85003
3	(Site 213) Advanced Clinical Research	Banning	California	United States	92220
4	(Site 246) Paradigm Clinical Research / Pharmaseek	Redding	California	United States	96001
5	(Site 212) Benckmark Research	Sacramento	California	United States	95864
6	(Site 244) Paradigm Clinical Research Center Inc	San Diego	California	United States	92117
7	(Site 242) Paradigm Clinical Research Centers Inc	Wheat Ridge	Colorado	United States	80033
8	(Site 239) Alliance for Multispeciality Research	Coral Gables	Florida	United States	33134
9	(Site 222) Research Centers of America	Hollywood	Florida	United States	33024
10	(Site 221) St-Johns Center for Clinical Research	Ponte Vedra	Florida	United States	32081
11	(Site 231) QPS-MRA LLC	South Miami	Florida	United States	33143
12	(Site 251) Meridian Clinical Research	Richmond Hill	Georgia	United States	31324
13	(Site 240) Meridian Clinical Research LLC	Savannah	Georgia	United States	31406
14	(Site 223) Clinical Research Atlanta	Stockbridge	Georgia	United States	30281
15	(Site 249) Advanced Clinical Research	Meridian	Idaho	United States	83642
16	(Site 219) Heartland Research Associates LLC	Augusta	Kansas	United States	67010
17	(Site 234) Heartland Research Associates LLC	Newton	Kansas	United States	67114
18	(Site 215) Heartland Research Associates LLC	Wichita	Kansas	United States	67205
19	(Site 235) Heartland Research Associates LLC	Wichita	Kansas	United States	67207
20	(Site 241) Central Kentucky Reserach Associates	Lexington	Kentucky	United States	40509
21	(Site 203) Benchmark Research	Metairie	Louisiana	United States	70006
22	(Site 227) Sundande Clinical Research	Saint Louis	Missouri	United States	63141
23	(Site 226) Meridian Clinical Research LLC	Norfolk	Nebraska	United States	68701
24	(Site 211) Meridian Clinical Research	Omaha	Nebraska	United States	68134
25	(Site 209) United Medical Associates	Binghamton	New York	United States	13901
26	(Site 217) Regional Clinical Research inc	Endwell	New York	United States	13760
27	(Site 237) PMG Research of Cary LLC	Cary	North Carolina	United States	27518
28	(Site 230) PMG Research of Charlotte LLC	Charlotte	North Carolina	United States	28209
29	(Site 205) PMG Research of Rocky Mount LLC	Rocky Mount	North Carolina	United States	27804
30	(Site 236) PMG Research	Statesville	North Carolina	United States	28625
31	(Site 228) Research of Winston-Salem	Winston-Salem	North Carolina	United States	27103
32	(Site 233) Sterling Research Group	Cincinnati	Ohio	United States	45219
33	(Site 208) Sterling Research Group	Cincinnati	Ohio	United States	45246
34	(Site 245) Rapid Medical Research	Cleveland	Ohio	United States	44122
35	(Site 202) Aventiv Research Inc	Columbus	Ohio	United States	43213
36	(Site 207) Lynn Institute of Norman	Norman	Oklahoma	United States	73069
37	(Site 238) Tekton Research	Oklahoma City	Oklahoma	United States	73114
38	(Site 216) PMG Research of Charleston LLC	Mount Pleasant	South Carolina	United States	29464
39	(Site 248) Coastal Carolina Research Center	Mount Pleasant	South Carolina	United States	29464
40	(Site 201) Meridian Clinical Research	Dakota Dunes	South Dakota	United States	57049
41	(Site 247) New orleans Center for Clinical Research	Knoxville	Tennessee	United States	37920
42	(Site 206) Benchmark Research	Austin	Texas	United States	78705
43	(Site 218) Tekton Research Inc	Austin	Texas	United States	78745
44	(Site 214) Ventavia Research Group LLC	Fort Worth	Texas	United States	76104
45	(Site 224) Benchmark Research	Fort Worth	Texas	United States	76135
46	(Site 232) Benchmark Research	San Angelo	Texas	United States	76904
47	(Site 250) Clinical Trials of Texas Inc	San Antonio	Texas	United States	78229
48	(Site 204) Jean Brown Research	Salt Lake City	Utah	United States	84124
49	(Site 220) Advanced Clinical Research	West Jordan	Utah	United States	84088
50	(Site 229) Clinical Research Associates of Tidewater	Norfolk	Virginia	United States	23507
51	(Site 106) Colchester Research Group	Truro	Nova Scotia	Canada	B2N 1L2
52	(Site 113) Dawson Road Family Medical Clinic	Guelph	Ontario	Canada	N1H 1B1
53	(Site 110) Manna Research Inc.	Toronto	Ontario	Canada	M9W 4L6
54	(Site 103) Q & T Recherche Chicoutimi	Chicoutimi	Quebec	Canada	G7H 7Y8
55	(Site 105) Q & T Outaouais	Gatineau	Quebec	Canada	J8Y 6S8
56	(Site 107) Manna Research Inc.	Levis	Quebec	Canada	G6W 0M6
57	(Site 109) Manna Research Inc. (Mirabel)	Mirabel	Quebec	Canada	J7J 2K8
58	(Site 108) Manna Research	Pointe-Claire	Quebec	Canada	H9R 4S3
59	(Site 102) CHU de Québec - Université Laval	Québec City	Quebec	Canada	G1E 7G9
60	(site 101) Centre de Recherche St-Louis	Québec City	Quebec	Canada	G1W 4R4
61	(Site 110) Alpha Recherche Clinique	Québec City	Quebec	Canada	G3K 2P8
62	(Site 104) Q & T Recherche Sherbrooke	Sherbrooke	Quebec	Canada	J1J 2G2
63	(Site 112) Medexa Recherche	Victoriaville	Quebec	Canada	G6P 6P6
64	(Site 309) Espoo Vaccine Research Clinic	Espoo		Finland	02230
65	(Site 303) Helsinki South Vaccine Research Clinic	Helsinki		Finland	00100
66	(Site 308) Helsinki East Vaccine Research Center	Helsinki		Finland	00930
67	(Site 301) Jarvenpaa Vaccine Research Clinic	Järvenpää		Finland	04400
68	(Site 306) Kokkola Vaccine Research Clinic	Kokkola		Finland	67100
69	(Site 304) Oulu Vaccine Research Clinic	Oulu		Finland	90220
70	(Site 302) Tampere University Vaccine Research Center	Pori		Finland	28100
71	(Site 305) Seinaejoki Vaccine Research Clinic	Seinäjoki		Finland	60100
72	(Site 310) Tampere Vaccine Research Clinic	Tampere		Finland	33100
73	(Site 307) Turku Vaccine Research Center	Turku		Finland	20520
74	(Site 410) Emovis GmbH	Berlin		Germany	10629
75	(Site 418) Klinische Forschung Berlin GbR	Berlin		Germany	10787
76	(Site 422) Synexus Clinical Research GmbH	Berlin		Germany	12627
77	(Site 402) Synexus Clinical research GmbH	Bochum		Germany	44787
78	(Site 409) Gemeinschaftspraxis Dr. med Kleinecke-Pohl	Cologne		Germany	51069
79	(Site 401) Cardiologicum Dresden & Pirna	Dresden		Germany	01277
80	(Site 406) Diabetologische Germeinschafts praxis Faulman	Dresden		Germany	1279
81	(Site 405) Doktor Markus Faghih	Essen		Germany	45355
82	(Site 407) Klinisches Forschungszentrum Dr. Hagemann am Hausarztzer	Essen		Germany	45355
83	(Site 417) Medizentrum Essen-Borbeck	Essen		Germany	45355
84	(Site 414) Unterfrintroper Hausarztzentrum Klinische Forschung	Essen		Germany	45359
85	(SIte 404) Synexus Clinical Reserach GmbH	Frankfurt		Germany	60313
86	(Site 411) MedicoKIT GmbH	Goch		Germany	47574
87	(Site 425) Clinical Research Hamburg	Hamburg		Germany	22143
88	(Site 403) Praxis Dr. Med Cornelia Brauer	Hamburg		Germany	22415
89	(Site 408) Germeinsschaftspraxis Dr. med Christiane Klein/Minnich	Künzing		Germany	94550
90	(Site 421) SIBAmed Studienzentrum GmbH	Leipzig		Germany	01403
91	(Site 420) Synexus Clinical Research GmbH	Leipzig		Germany	04103
92	(Site 423) centrum fuer Diagnostik und Gesundheit	Munich		Germany	80809
93	(Site 413) Dr. Ingomar F.K. Naudts MD Office	Rodgau		Germany	63110
94	(Site 415) Praxisgemeinschaft Stuhr-Brinkum	Stuhr		Germany	28816
95	(Site 416) Praxis Dr. med Joachim Sauter	Wangen		Germany	88239
96	(Site 412) MALU-Medizinische Studien GmbH	Wardenburg		Germany	26203
97	(Site 424) Medislim GmbH	Weinheim		Germany	69469
98	(Site 603) Ramathibodi Hospital, Mahid - Division of Infectious Disease	Bangkok		Thailand	10160
99	(Site 606) Faculty of Tropical Medicine, Mahidol University	Bangkok		Thailand	10400
100	(Site 608) Phramongkutklao Hospital	Bangkok		Thailand	10400
101	(Site 609) Division of Tropical Pediatrics	Bangkok		Thailand	10400
102	(Site 601) Faculty of Medicine, Chiang Mai University	Chiang Mai		Thailand	50200
103	(Site 607) Srinagarind Hospital Khon Kaen University	Khon Kaen		Thailand	40002
104	(Site 605) Golden Jubilee Medical Center	Nakhon Pathom		Thailand

Sponsors and Collaborators

• Medicago

Investigators

• Study Chair: Sébastien Soucy, Director, Clinical Studies
• Study Director: Brian Ward, Medical Officer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Medicago
• ClinicalTrials.gov Identifier: NCT03739112
• Other Study ID Numbers: CP-PRO-QVLP-014
• First Posted: Nov 13, 2018
• Last Update Posted: Nov 2, 2020
• Last Verified: Oct 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Infections; Communicable Diseases; Virus Diseases; Respiratory Tract Infections; RNA Virus Infections; Respiratory Tract Diseases; Vaccines

Study Results

No Results Posted as of Nov 2, 2020