A(H7N9) VLP Antigen Dose-Ranging Study With Matrix-M1™ Adjuvant

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™

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.

Study Overview

• Status: Completed
• Conditions: Influenza (Pandemic)
• Intervention / Treatment: Biological: Placebo; Biological: Monovalent Avian Influenza VLP (H7N9); Biological: Matrix-M1™ adjuvant

• Study Type: Interventional
• Enrollment (Actual): 610
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research
  • Florida
    • Miami, Florida, United States, 33143
      • Miami Research Associates
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Advanced Clinical Research
  • New York
    • Endwell, New York, United States, 13760
      • Regional Clinical Research, Inc.
  • South Carolina
    • Mt. Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group A; Placebo	Biological: Placebo
EXPERIMENTAL: Group B; High dose Monovalent Avian Influenza VLP (H7N9); IM; Day 0 and Day 21	Biological: Monovalent Avian Influenza VLP (H7N9)
EXPERIMENTAL: Group C; High dose Monovalent Avian Influenza VLP (H7N9) with Low dose Matrix-M1™ adjuvant; IM; Day 0 and Day 21	Biological: Monovalent Avian Influenza VLP (H7N9); Biological: Matrix-M1™ adjuvant
EXPERIMENTAL: Group D; Intermediate dose Monovalent Avian Influenza VLP (H7N9) with Low dose Matrix-M1™ adjuvant; IM; Day 0 and Day 21	Biological: Monovalent Avian Influenza VLP (H7N9); Biological: Matrix-M1™ adjuvant
EXPERIMENTAL: Group E; Low dose Monovalent Avian Influenza VLP (H7N9) with Low dose Matrix-M1™ adjuvant; IM; Day 0 and Day 21	Biological: Monovalent Avian Influenza VLP (H7N9); Biological: Matrix-M1™ adjuvant
EXPERIMENTAL: Group F; High dose Monovalent Avian Influenza VLP (H7N9) with High dose Matrix-M1™ adjuvant; IM; Day 0 and Day 21	Biological: Monovalent Avian Influenza VLP (H7N9); Biological: Matrix-M1™ adjuvant
EXPERIMENTAL: Group G; Intermediate dose Monovalent Avian Influenza VLP (H7N9) with High dose Matrix-M1™ adjuvant; IM; Day 0 and Day 21	Biological: Monovalent Avian Influenza VLP (H7N9); Biological: Matrix-M1™ adjuvant
EXPERIMENTAL: Group H; Low dose Monovalent Avian Influenza VLP (H7N9) with High dose Matrix-M1™ adjuvant; IM; Day 0 and Day 21	Biological: Monovalent Avian Influenza VLP (H7N9); Biological: Matrix-M1™ adjuvant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of Safety	Counts (and percentages) of subjects with solicited local and systemic AEs over the seven days post-injection and all adverse events, solicited and unsolicited, including adverse changes in clinical laboratory parameters, over 42 days post-first injection. In addition, MAEs, SAEs, and SNMCs will be collected for one year.	Day 0 to Day 384
Immunogenicity as assessed by hemagglutination-inhibiting (HAI) antibody titers against the vaccine-homologous A/Anhui/1/13 (H7N9) virus.	Geometric mean titer (GMT) Geometric mean ratio (GMR) Seroconversion rate (SCR) Seroresponse rate (SRR)	Day 0 to Day 384

Secondary Outcome Measures

Outcome Measure	Time Frame
Immunogenicity as assessed by neuraminidase-inhibiting antibodies to N9.	Day 0 to Day 384

Collaborators and Investigators

• Sponsor: Novavax
• Collaborators: Department of Health and Human Services
• Investigators: Study Director: D. Nigel Thomas, Ph. D., Novavax, Inc.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (ACTUAL): July 1, 2015
• Study Completion (ACTUAL): July 1, 2015

Study Registration Dates

• First Submitted: March 3, 2014
• First Submitted That Met QC Criteria: March 3, 2014
• First Posted (ESTIMATE): March 5, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): September 23, 2016
• Last Update Submitted That Met QC Criteria: September 20, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: H7N9
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Influenza in Birds
• Other Study ID Numbers: FLU-MI7A-201