Clinical trial NCT02078674: A(H7N9) VLP Antigen Dose-Ranging Study With Matrix-M1™ Adjuvant
Official title: A Phase I/II Randomized, Observer-Blinded, Dose-Ranging Study to Evaluate the Immunogenicity and Safety of Monovalent A/Anhui/1/13 (H7N9) Virus-Like Particle (VLP) Avian Influenza Antigen (Recombinant) in Healthy Adults With and Without Matrix-M1™
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Influenza (Pandemic)
Keywords: H7N9
Lead sponsor: Novavax
Sponsor class: INDUSTRY
Collaborators: name: Department of Health and Human Services
First posted: 2014-03-05
Enrollment: 610
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: 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 to 64 years old. Randomization will be stratified by age (18 to 49 years and 50 to 64 years) and by prior influenza immunization within the past three months. Subjects 18 to 49 years of age will comprise \~67% of subjects in each treatment group, and the balance will comprise subjects 50 to 64 years.

Each subject will receive two identical IM doses of test article 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:

1. Healthy adult male or female, 18 to 64 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 child-bearing potential must have a negative urine pregnancy test prior to each vaccination, and 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 will be excluded if they meet any of the following criteria:

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.
   * Acute or chronic illnesses or conditions which may be reasonably predicted to become symptomatic if treatment were withdrawn or interrupted are exclusionary, even if stable.
   * Note that illnesses or conditions may be exclusionary, even if otherwise stable and clinically minor, due to therapies used to treat them (see exclusion criteria 3, 5, 8, 9).
2. Any grade 1 or higher (as based on the Toxicity Grading Scale \[TGS\]) abnormality in ALT, AST, alkaline phosphatase, total bilirubin, blood urea nitrogen, or creatinine levels.
3. Any grade 2 or higher (as based on the TGS) vital sign or clinical laboratory abnormality not specified in criterion 2 above. Note that any abnormal vital sign may be repeated at the Investigator's discretion.
4. Participation in research involving investigational product (drug / biologic / device) within 45 days before planned date of first vaccination.
5. History of a serious reaction to prior influenza vaccination.
6. History of Guillain-Barré Syndrome (GBS) within 6 weeks following a previous influenza vaccine.
7. Received any vaccine in the 4 weeks preceding the study vaccination; or any A(H7N9) avian influenza vaccine at any time.
8. Any known or suspected immunosuppressive condition, acquired or congenital, as determined by history and/or physical examination.
9. 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 ≥10mg of prednisone per day or equivalent. The use of topical, inhaled, and nasal glucocorticoids will be permitted.
10. Administration of immunoglobulins and/or any blood products within the 3 months preceding the administration of the study vaccine or during the study.
11. 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).
12. Known disturbance of coagulation.
13. Women who are pregnant or breastfeeding, or plan to become pregnant during the study.
14. Suspicion or recent history (within one year of planned vaccination) of alcohol or other substance abuse.

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: Walnut Creek
country: United States
facility: Diablo Clinical Research
state: California
city: Miami
country: United States
facility: Miami Research Associates
state: Florida
city: Meridian
country: United States
facility: Advanced Clinical Research
state: Idaho
city: Endwell
country: United States
facility: Regional Clinical Research, Inc.
state: New York
city: Mt. Pleasant
country: United States
facility: Coastal Carolina Research
state: South Carolina
Study officials:
affiliation: Novavax, Inc.
name: D. Nigel Thomas, Ph. D.
role: STUDY_DIRECTOR
References: