Clinical trial NCT01897701: A(H7N9) VLP Antigen Dose Ranging Study With Adjuvant 1
Official title: A Phase 1 Randomized, Observer-Blinded, Dose-Ranging Study to Evaluate the Immunogenicity and Safety of Monovalent A/Anhui/1/2013 (H7N9) Virus-Like Particle (VLP) Avian Influenza Antigen (Recombinant) in Healthy Adults With and Without Adjuvant 1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Avian Influenza
Keywords: H7N9
Lead sponsor: Novavax
Sponsor class: INDUSTRY
First posted: 2013-07-12
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a randomized, observer-blinded, placebo-controlled trial in adults ≥18 years old. Randomization will be stratified by age (18 to 49 years and ≥50 years) and by prior influenza immunization within the past three months. Proportions of subjects in the various strata will not be pre-specified; rather, the goal will be to achieve an approximately equal distribution of subjects with these characteristics across the various treatment groups.

Treatments will comprise two identical IM doses at a 21-day interval (Day 0 and Day 21), in alternate deltoids. For each subject, study follow-up will span approximately 385 days total, or approximately 13 months from the first dose.


Eligibility criteria: Inclusion Criteria:

Subjects must meet all of the following to be eligible for participation in the study:

1. Healthy adult male or female, ≥18 years of age,
2. Willing and able to give informed consent prior to study enrollment,
3. Able to comply with study requirements, and
4. Women of childbearing potential must have a negative urine pregnancy test prior to each vaccination, will be advised through the Informed Consent process to avoid becoming pregnant over the duration of the study, and must assert that they will employ an effective form of birth control for the duration of the study. Acceptable forms of birth control are: credible history of continuous abstinence from heterosexual activity or prior surgical sterilization, hormonal contraceptives (oral, injectable, implant, patch, ring), barrier contraceptives (condom or diaphragm), and intrauterine device (IUD). Women with an adequately documented history of surgical sterility, or ≥50 years of age and without menses for ≥ 1 year are exempt from urine pregnancy testing.

Exclusion Criteria:

Subjects meeting any of the following criteria are not eligible for participation in the study.

1. Any ongoing, symptomatic acute or chronic illness requiring medical or surgical care.

   * Asymptomatic conditions or findings (e.g., mild hypertension, dyslipidemia) that are not associated with evidence of end-organ damage are not exclusionary provided that they are being appropriately managed and are clinically stable (i.e., unlikely to result in symptomatic illness within the time-course of this study) in the opinion of the investigator.
   * Note that illnesses or conditions may be exclusionary, even if otherwise stable, due to therapies used to treat them (see exclusion criteria 2, 5, 7, 8).
2. Participation in research involving investigational product (drug / biologic / device) within 45 days before planned date of first vaccination.
3. History of a serious reaction to prior influenza vaccination.
4. History of Guillain-Barré Syndrome (GBS) within 6 weeks following a previous influenza vaccine.
5. Received any vaccine in the 4 weeks preceding the study vaccination; or any A(H7N9) avian influenza vaccine at any time.
6. Any known or suspected immunosuppressive condition, acquired or congenital, as determined by history and/or physical examination.
7. Chronic administration (defined as more than 14 continuous days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the administration of the study vaccine. An immunosuppressant dose of glucocorticoid will be defined as a systemic dose ≥10 mg of prednisone per day or equivalent. The use of topical, inhaled, and nasal glucocorticoids will be permitted.
8. Administration of immunoglobulins and/or any blood products within the 3 months preceding the administration of the study vaccine or during the study.
9. Acute disease at the time of enrollment (defined as the presence of a moderate or severe illness with or without fever, or an oral temperature \>38.0°C on the planned day of vaccine administration).
10. Known disturbance of coagulation.
11. Women who are pregnant or breastfeeding, or plan to become pregnant during the study.
12. Suspicion or recent history (within one year of planned vaccination) of alcohol or other substance abuse.
13. Any condition that in the opinion of the investigator would pose a health risk to the subject if enrolled or could interfere with evaluation of the vaccine or interpretation of study results (including neurologic or psychiatric conditions deemed likely to impair the quality of safety reporting).
14. Persons employed in a capacity that involves handling poultry or wild birds.

Primary outcomes:
measure: Assessment of Safety
timeFrame: Day 0 to Day 384
measure: Immunogenicity as assessed by hemagglutination-inhibiting (HAI) antibody titers against the vaccine-homologous A/Anhui/1/13 (H7N9) virus.
timeFrame: Day 0 to Day 384
Secondary outcomes:
measure: Immunogenicity as assessed by neuraminidase-inhibiting antibodies to N9.
timeFrame: Day 0 to Day 384
Other outcomes:
Locations:
city: Herston
country: Australia
facility: Q-Pharm Pty Limited
state: Queensland
city: Adelaide
country: Australia
facility: CMAX
state: South Australia
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
Study officials:
affiliation: Novavax, Inc.
name: D. Nigel Thomas, Ph.D.
role: STUDY_DIRECTOR
References:
citation: Fries LF, Smith GE, Glenn GM. A recombinant viruslike particle influenza A (H7N9) vaccine. N Engl J Med. 2013 Dec 26;369(26):2564-6. doi: 10.1056/NEJMc1313186. Epub 2013 Nov 13. No abstract available.