Clinical Study in Children to Evaluate Efficacy, Safety and Immune Response of Investigational Flu Vaccine Compared to an Approved non-Flu Vaccine

• Register: EUCTR
• Last refreshed on: 10 December 2019
• Main ID: EUCTR2016-002883-15-ES
• Date of registration: 30/05/2017
• Prospective Registration: Yes
• Primary sponsor: Seqirus UK Limited
• Public title: Clinical Study in Children to Evaluate Efficacy, Safety and Immune Response of Investigational Flu Vaccine Compared to an Approved non-Flu Vaccine
• Scientific title: A Phase III/IV, Stratified, Randomized, Observer Blind, Multicenter Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of a Cell-Based Quadrivalent Subunit Influenza Virus Vaccine Compared to Non-Influenza Comparator Vaccine in Subjects >/=2 years to <18 Years of Age - A Phase III/IV Efficacy Study of QIVc in pediatric Subjects
• Date of first enrolment: 31/07/2017
• Target sample size: 6368
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002883-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: yes; Other trial design description: Observer-blind; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: Non-flu vaccine comparator and saline; 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): yes

Countries of recruitment

Australia, Estonia, Finland, Lithuania, Philippines, Poland, South Africa, Spain, Thailand

Contacts

• Name: Mirjam van Huffelen
• Affiliation: Seqirus UK Limited

• Name: Mirjam van Huffelen
• Affiliation: Seqirus UK Limited

Key inclusion & exclusion criteria

Inclusion criteria:
1. Males or females =2 years to <18 years of age on the day of first study vaccination;
2. Individual has and/or has (a) parent(s) or legal guardian(s) who has/have given informed consent/assent after the nature of the study has been explained in accordance with the practices described in protocol and according to local regulatory requirements;
3. If the individual is of an age where, according to local regulations, informed assent is required, that individual has provided assent to participate in the study.
4. Individual and individual’s parent or legal guardian can comply with study procedures and are available for follow-up;
5. Individual is in generally good health as per the Investigator’s medical judgement;
Are the trial subjects under 18? yes
Number of subjects for this age range: 6368
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Individual with clinical signs of and/or an oral temperature of = 100.4 F (38.0 degrees Celsius) within three days prior to vaccination;
2. Individuals with a known history of any anaphylaxis, serious vaccine reactions or hypersensitivity to any of the vaccine components described in investigator brochure, or having any of the contraindications listed in the package insert of the comparator vaccine;
3. Individuals with history of Guillain-Barré syndrome or other demyelinating diseases such as encephalomyelitis and transverse myelitis;
4. Female subject “of childbearing potential”, sexually active, and not used any of the “acceptable contraceptive method” for at least 2 months prior to study entry and intend to use until the end of subject participation;
5. Individual is pregnant or breast feeding female;
6. Individual and/or individual’ parent/guardians who are not able to comprehend or follow all required study procedures for the whole period of the study;
7. Individual has received prior Meningococcal ACWY vaccination that conflicts with national recommendations or local practices for timing of primary or booster vaccination
8. Individual has received influenza vaccination or has had documented influenza disease in the last 6 months;
9. Known or suspected congenital or acquired immunodeficiency; or receipt immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or systemic corticosteroid therapy (prednisone or equivalent) at any dose for more than 2 consecutive weeks (14 days) within the past 3months. Topical, inhaled and intranasal corticosteroids are permitted. Intermittent use (one dose in 30 days) of intra-articular corticosteroids is also permitted;
10. Administration of immunoglobulin and/or any blood products within the 3 months preceding vaccination, or planned administration during the study;
11. Individual has participated in any clinical trial with another investigational product 30 days prior to first study visit or intent to participate in another clinical study at any time during the conduct of this study. Concomitant participation in an observational study (not involving drugs, vaccines, or medical devices) is acceptable;
12. Medical conditions or treatments contraindicating intramuscular vaccination due to increased risk of bleeding. These may include known bleeding disorders (such as thrombocytopenia), or treatment with anticoagulants (such as warfarin) in the 3 weeks preceding vaccination. However, antiplatelet agents such as low-dose aspirin, ticlopidine (Ticlid) and clopidogrel (Plavix) are permitted;
13. Evidence, or history (within the previous 12 months) of drug or alcohol abuse;
14. Study personnel or immediate family members (brother, sister, child, parent), the spouse of study personnel or individuals who are financially or emotionally dependent on study staff
15. Participation in this trial in a prior season, if applicable.
16. Any clinical condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study


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

Health Condition(s) or Problem(s) studied

Profylaxis for Influenza virus
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 Influenza Vaccine cell-based (QIVc)
Product Code: QIVc
Pharmaceutical Form: Suspension for injection in pre-filled syringe
INN or Proposed INN: A/ (H1N1)-LIKE VIRUS ANTIGEN
Other descriptive name: A/ (H1N1)-LIKE VIRUS ANTIGEN
Concentration unit: µg microgram(s)
Concentration type: not less then
Concentration number: 15-
INN or Proposed INN: A/ (H3N2)-LIKE VIRUS ANTIGEN
Other descriptive name: A/ (H3N2)-LIKE VIRUS ANTIGEN
Concentration unit: µg microgram(s)
Concentration type: not less then
Concentration number: 15-
INN or Proposed INN: B/ -LIKE VIRUS ANTIGEN
Other descriptive name: B/ -LIKE VIRUS ANTIGEN
Concentration unit: µg microgram(s)
Concentration type: not less then
Concentration number: 15-
INN or Proposed INN: B/ -LIKE VIRUS ANTIGEN
Other descriptive name: B/ -LIKE VIRUS ANTIGEN
Concentration unit: µg microgram(s)
Concentration type: not less then
Concentration number: 15-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intramuscular use

Trade Name: Menveo
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: -
CAS Number: -
Current Sponsor code: -
Other descriptive name: MENINGOCOCCAL GROUP A, C, W135 AND Y CONJUGATE VACCINE
Concentration unit: ml millilitre(s)
Concentration type: equal
Concentration number: 0.5-

Primary Outcome(s)

Main Objective: - Primary Efficacy Objective(s):
To demonstrate absolute vaccine efficacy of QIVc versus a non-influenza comparator determined by first occurrence RT-PCR or culture confirmed influenza, due to any influenza Type A and B strain in subjects
In case of successful demonstration of the primary efficacy objective:
- Co-Primary Efficacy Objective(s):
To demonstrate absolute vaccine efficacy of QIVc versus a non-influenza comparator determined by first occurrence RT-PCR or culture confirmed influenza, due to any influenza Type A and B strain in subjects =2 years to <18 years of age.

Secondary Objective: The following secondary objectives will be evaluated in specific age cohorts:

*Efficacy:
Demonstrate absolute vaccine efficacy of QIVc determined in 4 ways:
1. determined by first occurrence RT-PCR or culture confirmed influenza, due to any influenza Type A and B strain.
2. determined by first occurrence RT-PCR influenza, due to any influenza Type A and B strain.
3. determined by first occurrence culture confirmed influenza, due to any influenza Type A and B strain.
4. determined by first occurrence culture confirmed influenza, caused by influenza strains antigenically matched
- Exploratory: To further characterize the efficacy of QIVc, with specific attention for all-cause mortality, pneumonia and otitis media.

*Immunogenicity:
To characterize the immunogenicity of QIVc by HI assay.
- Exploratory: Further characterize the immune response, additional immunogenicity analyses may be conducted such as MN.

*Safety:
Assess the safety and tolerability of QIVc.

Primary end point(s): - Primary Efficacy Endpoint(s)
The primary efficacy endpoint is the time from the last study vaccination to the onset of the first occurrence confirmed influenza by either RT-PCR-confirmed or culture-confirmed, due to any influenza Type A or B strain regardless of antigenic match to the strains selected for the seasonal vaccine, occurring >14 days after the last vaccination and until the end of the influenza season.

Timepoint(s) of evaluation of this end point: >14 days after the last vaccination and until the end of the influenza season.

Secondary Outcome(s)

Secondary end point(s): - Secondary Safety Endpoint(s)
Safety will be assessed by calculating:
* The percentage of subjects with solicited local and systemic adverse events for 7 days following vaccination at Day 1 (“previously vaccinated” subjects) or Day1 and Day 29, (“not previously vaccinated” subjects) in the QIVc group and the non-influenza comparator vaccine group.
* The percentage of subjects with all unsolicited AEs will be assessed from Day 1 to Day 22 for “previously vaccinated” subjects or Day 1 to Day 50 for “not previously vaccinated” subjects in the QIVc group and in non-influenza comparator vaccine group.
* Percentage of subjects with SAEs, AEs leading to withdrawal from the study and NOCDs reported during the subject’s entire participation in the study, i.e. from Day 1 to Day 181 (for “previously vaccinated” subjects) or to Day 209 (for “not previously vaccinated” subjects), or until the end of influenza season, whichever is longer, and all medications associated with these events.
* Percentage of subjects with medically-attended adverse events within 30 days after of first occurrence RT-PCR confirmed ILI.

- Secondary Efficacy Endpoint(s)
* The efficacy endpoint for secondary objective 1 is the time from the last study vaccination to the onset of the first occurrence confirmed influenza by either RT-PCR confirmed or culture-confirmed, due to any influenza Type A or B strain regardless of antigenic match to the strains selected for the seasonal vaccine, occurring at >14 days after the last vaccination and until the end of the influenza season.
* The efficacy endpoint for secondary objective 2 is the time from the last study vaccination to the onset of the first-occurrence confirmed influenza by RT-PCR confirmed, due to any influenza Type A or B strain regardless of antigen match to the strains selected for the seasonal vaccine, (occurring at >14 days after the last vaccination and until the end of the influenza season).
* The efficacy endpoint for secondary objective 3 is time from the last study vaccination to the onset of the first-occurrence confirmed influenza by culture confirmed, due to any influenza Type A or B strain regardless of antigenic match to the strains selected for the seasonal vaccine, (occurring at >14 days after the last vaccination and until the end of the influenza season).
* The efficacy endpoint for secondary objective 4 is the time from the last study vaccination to the onset of the first-occurrence confirmed influenza by culture-confirmed, due to influenza Type A or B strain antigenic matched to the strains selected for the seasonal vaccine, (occurring at >14 days after the last vaccination and until the end of the influenza season).

- Secondary Immunogenicity Endpoints
The measures for assessing immunogenicity as determined by HI are as follows:
* HI Geometric mean titers (GMTs) on Day 1 (all subjects), Day 22 (all “previously vaccinated” subjects receiving a single vaccine dose) or Days 29 and 50 (all “not previously vaccinated” subjects receiving 2 doses) for all 4 influenza strains.
* Percentage of subjects achieving seroconversion (defined as: either a prevaccination HI titer < 1:10 and a post-vaccination HI titer = 1:40 or a prevaccination HI titer = 1:10 and a = 4-fold increase in post-vaccination HI titer) on Day 22 (all “previously vaccinated” subjects receiving a single vaccine dose) or Days 29 and 50 (all “not previously vaccinated” subjects receiving 2 doses) for all 4 influenza strains.
* HI Geometric mean Ratio (GMR) of Day 22/Day 1 (all “previously vaccinated” subjects receiving a single vaccine dose) or Day 29/Day 1 and Day 50/Day 1 (all “not previously vaccinated” subjects receiving 2 doses) for all 4 influenza strains.
* Percentage of subjects with HI titer = 1:40 on Day 22 (all “previously vaccinated” subjects receiving a single vaccine dose) or Days 29 and 50 (all “not previously vaccinated” subjects receiving 2 doses) for all 4 influenza strains.

Timepoint(s) of evaluation of this end point: See above for specific timepoints per endpoint

Secondary ID(s)

2016-002883-15-LT

V130_12

Source(s) of Monetary Support

Seqirus UK Limited

Ethics review

Status: Approved
Approval date:
Contact: