Phase III, Multicenter Study to Evaluate the Safety, immune response, and effectiveness of Two Doses of aH5N1 vaccine when Administered to Adult and Elderly Subjects With and Without Underlying Diseases.

• Register: EUCTR
• Last refreshed on: 4 August 2015
• Main ID: EUCTR2011-003603-37-DE
• Date of registration: 18/12/2013
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Phase III, Multicenter Study to Evaluate the Safety, immune response, and effectiveness of Two Doses of aH5N1 vaccine when Administered to Adult and Elderly Subjects With and Without Underlying Diseases.
• Scientific title: Phase III, Stratified, Randomized, Controlled, Observer-Blind, Multicenter Study to Evaluate the Safety, Tolerability, and Immunogenicity of Two Doses of aH5N1 when Administered to Adult and Elderly Subjects With and Without Underlying Medical Conditions.
• Date of first enrolment: 04/02/2014
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-003603-37
• 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: yes Placebo: no Other: yes Other specify the comparator: Fluad Number of treatment arms in the trial: 2

Countries of recruitment

Germany

Contacts

• Name: Global Clinical Operations Lead
• Affiliation: Novartis Influenza Vaccines

• Name: Global Clinical Operations Lead
• Affiliation: Novartis Influenza Vaccines

Key inclusion & exclusion criteria

Inclusion criteria:
In order to participate in this study, all subjects must meet ALL of the following inclusion criteria in the “all subjects” section and ALL of the inclusion criteria in the respective section for their underlying health status:
All subjects
1. Male and female individuals 18 years of age and older at the time of enrollment who are mentally competent, willing and able to understand the nature and risks of the proposed study, and able to sign the consent form prior to study entry;
2. Individuals with a projected life expectancy of 12 months or longer;
3. Individuals who are able to comply with all study procedures and requirements;

Subjects with underlying medical conditions only
4. Individuals with at least one of the following medical conditions:
a. Documented underlying chronic respiratory medical condition: Chronic pulmonary disease. Classification of severity of COPD will be based on utilization of the 2013 Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, including evaluation of force expiratory volume (FEV1) within 3 months prior to enrollment. Eligible subjects must be classified with either GOLD 2 (moderate) or GOLD 3 (severe) impairment for enrollment (GOLD, 2013),
b. Underlying cardiovascular medical condition:
i. Documented myocardial infarction (confirmed by at least two of the
following: symptoms, ECG changes, biochemical markers, (echocardiogram finding)
ii. Documented congestive heart failure with New York Heart Association (NYHA) functional classification Class II or III,
c. Documented peripheral vascular disease including Rutherford symptom score of 2 (moderate claudication) or higher,
d. Documented diabetes mellitus with hemoglobin A1c =7 to <10% within 3 months prior to enrollment,
e. Documented moderate to severe renal impairment as reflected by glomerular filtration rate (GFR) of <60 mL/min/1.73 m2 within 3 months prior to enrollment OR currently receiving hemodialysis treatments;
5. A CCI score of 6 or below (section 3.2.2);

Healthy subjects only
6. Individuals who are in good health as determined by the outcome of medical history, physical assessment, and clinical judgment of the Investigator.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 270
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 270

Exclusion criteria:
All subjects
1. Individuals who are not able to follow all the required study procedures for the whole period of the study;
2. Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the Investigator, may interfere with the subject’s ability to participate in the study;Note: Concomitant participation in an observational study (not involving drugs, vaccines, or medical devices) is acceptable;
3. Individuals who are hospitalized or residing in a nursing care facility;
4. Individuals who are planning to change their home address due to relocation during the course of the trial and may become unavailable for follow-up;
5. Individuals with any fatal prognosis of an underlying medical condition (<12 months life expectancy);
6. Individuals with any progressive or severe neurologic disorder, seizure disorder, or history of Guillain-Barré syndrome;
7. Individuals with known human immunodeficiency virus (HIV) infection or HIVrelated disease;
8. Individuals who have received other nonstudy vaccines within 7 days of either day 1 or day 22 vaccination;
9. Individuals who have ever received an H5N1 vaccine;
10. Individuals who are receiving another investigational product within 30 days prior to day 1 or before completion of the safety Follow-up Period in another study and who are unwilling to refuse participation in another clinical study at any time during the conduct of this study
11. Individuals with a history of any anaphylaxis, serious vaccine reactions, or hypersensitivity to any of the following: influenza viral proteins, excipient(s) of the study or reference vaccine (see section 5.0), eggs (including ovalbumin), or chicken protein;
12. Individuals with history of (or current) drug or alcohol abuse that, in the Investigator’s opinion, would interfere with the safety of the subject or the evaluation of study objectives;
13. Individuals who will undergo surgery planned during the study period that, in the Investigator’s opinion, would interfere with the study visit schedule;
14. Individual who is a member of the research staff or has relatives who are members of the research staff (research staff are individuals with direct contact with study subjects or study site personnel who have access to any study document containing subject information, including receptionists, persons scheduling appointments or making
screening calls, regulatory specialists, or laboratory technicians). Hospital personnel, health care professionals, and their relatives who are not involved in this clinical study are allowed for inclusion;
15. Female subjects of childbearing potential who are sexually active and have not used for at least 2 months prior to study entry one or more of the following acceptable contraceptive methods:
- Hormonal contraceptive (oral, injection, transdermal patch, implant, cervical ring),
- Barrier (condom with or without spermicide or diaphragm with spermicide) each and every time during intercourse,
- Intrauterine device,
- Monogamous relationship with vasectomized partner (partner must have been vasectomized for at least 6 months prior to the subject’s study entry),
- Abstinence, if not sexually active, at least 2 months before the study entry and at least 2 months after the study entry (through day 60 of study participation);
16. Female subjects of childbearing potential who have a positive pregnancy test prior to study entry, who are nursing (breastfeeding), or who are sex

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

Health Condition(s) or Problem(s) studied

Pandemic Influenza
MedDRA version: 18.0 Level: LLT Classification code 10070436 Term: H5N1 influenza System Organ Class: 100000004862

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Intervention(s)

Trade Name: Aflunov
Product Name: Aflunov
Pharmaceutical Form: Suspension for injection in pre-filled syringe

Trade Name: Fluad
Product Name: Fluad
Pharmaceutical Form: Suspension for injection in pre-filled syringe

Primary Outcome(s)

Primary end point(s): Primary Immunogenicity Endpoint:
? Percentage of subjects achieving seroconversion (defined as HI =1:40 for subjects who were seronegative at baseline [day 1 HI titer <1:10] or a minimum 4-fold increase in HI titer for subjects who were seropositive at baseline [day 1 HI titer =1:10]) on day 43
? Geometric mean ratios (GMRs) on day 43/day 1, as determined by HI assay
? Percentage of subjects with an HI titer =1:40 on day 43

Primary Safety Endpoint:
? Percentages of subjects with solicited local, solicited systemic, and other AEs that occur within 7 days following each vaccination and calculated for 4 time intervals after vaccination: 30 minutes, 6 hours through 3 days, 4 days through 7 days, and 6 hours through 7 days
? Percentages of subjects with any unsolicited AEs reported within 21 days after each vaccination within each vaccine group
? Percentages of subjects reporting SAEs, NOCDs, medically attended AEs, AESIs, AEs leading to withdrawal from the study, and concomitant medications associated with these events, as collected from day 1 through day 202

Solicited local AEs will include injection-site erythema, injection-site induration, injection-site ecchymosis, and injection-site pain; solicited systemic AEs will include loss of appetite, nausea, fatigue, generalized myalgia, generalized arthralgia, headache, shivering/chills, vomiting, diarrhea, and body temperature =38.0°C (as measured orally).

Secondary Objective: Secondary Immunogenicity Objectives:
To evaluate homologous antibody responses to aH5N1 vaccine 3 weeks after first vaccination (day 22) according to CHMP immunogenicity criteria in adult and elderly subjects who are healthy or with underlying medical condition, as measured by HI assay.

To evaluate homologous antibody responses to aH5N1 vaccine 3 weeks after first and second vaccinations (day 22 and day 43) according to CHMP immunogenicity criteria in adult and elderly subjects who are healthy or with underlying medical condition, as measured by serial radial haemolysis (SRH) assay.

Main Objective: Primary Immunogenicity Objective:
To evaluate homologous antibody responses to aH5N1 vaccine 3 weeks after second vaccination (day 43) according to CHMP immunogenicity criteria1 in adult (18 through 60 years of age) and elderly (=61 years of age) subjects who are healthy or with underlying medical condition, as measured by hemagglutination inhibition (HI) assay.

Primary Safety Objective:
To evaluate in pooled age groups 18 years of age and older solicited and unsolicited adverse events in adults and elderly subjects who are healthy or with underlying medical condition who have received aTIV or aH5N1 vaccine.

Timepoint(s) of evaluation of this end point: Primary Immunogenicity Endpoint: 3 weeks after second vaccination (day 43) by HI
Primary Safety Endpoint: all timepoints

Secondary Outcome(s)

Secondary end point(s): Secondary Immunogenicity Endpoints:
? Geometric mean titers (GMTs) at the following time points: day 1, day 22 (3 weeks after the first vaccination), day 43 (3 weeks after the second vaccination) as determined by HI and SRH
? GMRs, calculated as follows: day 22/day 1 as determined by HI and day 22/day 1, day 43/day 1 as determined by SRH
? Percentage of subjects achieving seroconversion (defined as HI =1:40 for subjects who were seronegative at baseline [day 1 HI titer <1:10] or a minimum 4 fold increase in HI titer for subjects who were seropositive at baseline [day 1 HI titer =1:10]) on days 22
? Percentage of subjects with an HI titer =1:40 on days 1 and 22
? Percentage of subjects achieving seroconversion (defined as SRH area =25 mm2 for subjects who were seronegative at baseline [day 1 SRH area =3.997 mm2] or a significant increase [at least 50% increase] in SRH area for subjects who were seropositive at baseline [SRH area >3.997 mm2]) on days 22, 43
? Percentage of subjects with geometric mean area =25 mm2 on days 1, 22, 43

Timepoint(s) of evaluation of this end point: three weeks after first vaccination (day 22) by HI
three weeks after first and second vaccinations (day 22 and day 43) by SRH

Secondary ID(s)

V87_25

Source(s) of Monetary Support

Novartis Pharma Services AG