Safety Study of a Plant-based H5 Virus-Like Particles (VLP) Vaccine in Healthy Adults

Phase 1 Single Centre, Double-blind, Randomized, Placebo-controlled, Dose-escalation Study of Plant-based H5 VLP (Virus-like Particles), (H5N1) Pandemic Influenza Vaccine Adjuvanted With Aluminium Hydroxide and Administered to Healthy Adults 18-60 Years of Age

The primary objective is to assess the safety and tolerability of two consecutive doses of plant-based H5 VLP, (H5N1) pandemic influenza vaccine combined with Alhydrogel®, given 21 days apart, at three dose levels: 5µg, 10µg and 20µg., compared to the placebo, and combined with Alhydrogel®.

Study Overview

• Status: Completed
• Conditions: RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases
• Intervention / Treatment: Biological: H5 VLP pandemic influenza vaccine 5 µg; Biological: H5 VLP pandemic influenza vaccine 10 µg; Biological: H5 VLP pandemic influenza vaccine 20 µg; Biological: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Pierrefonds, Quebec, Canada, H9H 4Y6
      • MUHC Vaccine Study Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female adults, 18 to 60 years of age
• Healthy as judged by the Principal Investigator (PI) and determined by medical history, physical examination, vital signs, screening laboratories and medical history conducted no more than 30 days prior to study vaccine administration
• BMI of ≥18 and ≤29
• Comprehension of the study requirements, expressed availability for the required study period and ability to attend scheduled visits
• Accessible by telephone on a consistent basis
• In the opinion of the Investigator, competence and willingness to provide written, informed consent for participation after reading the informed consent form. The subject must have adequate opportunity to discuss the study with an Investigator or qualified designee
• If female and capable of child-bearing, have a negative urine pregnancy test result at study entry and agree to employ adequate birth control measures for the duration of the study

Exclusion Criteria:

• Presence of significant acute or chronic, uncontrolled medical or neuropsychiatric illness. "Uncontrolled" is defined as:

  1. Requiring a new medical or surgical treatment within one month prior to study vaccine administration
  2. Requiring a change in medication dosage in one month prior to test article administration due to uncontrolled symptoms or drug toxicity (elective dosage adjustments in stable subjects are acceptable), or
  3. Hospitalization or an event fulfilling the definition of a serious adverse event within one month prior to test article administration
• Any medical or neuropsychiatric condition which, in the Investigator's opinion, would render the subject incompetent to provide informed consent or unable to provide valid safety observations and reporting
• Any confirmed or suspected immunosuppressive condition or immunodeficiency including history of human immunodeficiency virus (HIV) infection or presence of lymphoproliferative disease
• Presence of any febrile illness, oral temperature of >38.0 C within 24 hours of test article administration. Such subjects may be re-evaluated for enrolment after resolution of illness
• History of autoimmune disease
• Administration of any vaccine (including any other influenza vaccine) within a 30 day period prior to study enrolment, or planned administration within the period from the first vaccination up to blood sampling at Day 42 or within 30 days prior to blood sampling at Day 228. Immunization on an emergency basis of a tetanus and diphtheria toxoids adsorbed for adult use (Td) will be allowed provided the vaccine is not administered within two weeks prior to test article administration. Receipt of any other emergency immunizations (e.g. rabies) will result in a case-by-case review of continued participation.
• Use of any investigational or non-registered product within 90 days prior to study enrolment or planned use during the study period. Subjects may not participate in any other drug study while participating in this study
• Treatment with systemic glucocorticoids at a dose exceeding ≥ 10 mg of prednisone per day, or equivalent for more than 7 consecutive days or for 10 or more days in total, within one month of first test article administration, or any other cytotoxic or immunosuppressant drug or any immune globulin preparation within three months of vaccination. Nasal or inhaled glucocorticoids are allowed
• Any significant disorder of coagulation or treatment with coumadin derivatives or heparin. Persons receiving prophylactic anti-platelet medications, e.g., low-dose aspirin, and without a clinically apparent bleeding tendency are eligible
• History of previous H5N1 vaccination
• History of allergy to any of the constituents of H5 VLP (H5N1) study vaccine, Alhydrogel® (aluminium hydroxide), or the phosphate buffer.
• History of severe allergic reactions or anaphylaxis
• History of tobacco allergy
• Have received a blood transfusion or immunoglobulins within 90 days of study entry
• If female, and of childbearing potential, has not been consistently using effective birth control for the 28 days prior to study entry. An example of highly effective birth control is oral contraceptives, hormone implants, abstinence (confirmed by Investigator), or male condom plus spermicide. All female subjects, regardless of birth control history must provide a urine sample for pregnancy screening. Effective birth control must be used for the duration of the study. The subject must have no plan to become pregnant during the study period. Females who are post-menopausal (no spotting at all) for at least two (2) years will not require a urine pregnancy test.
• Among female subjects, either known pregnancy or urine beta-human chorionic gonadotropin (ß-hCG) test results consistent with pregnancy prior to test article administration on Day 0
• Female subjects who are lactating
• Vital sign abnormalities: systolic blood pressure ≥150 mmHg, diastolic blood pressure ≥90 mmHg, resting pulse rate <40 bpm or >100 bpm
• Cancer or treatment for cancer within 3 years of test article administration. Persons with a history of cancer who are disease-free without treatment for 3 years or more are eligible. Persons with treated and uncomplicated basal cell carcinoma of the skin are eligible.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: H5 VLP vaccine 5 µg	Biological: H5 VLP pandemic influenza vaccine 5 µg; 0.5 mL, IM, 2 injections 21 days apart
Active Comparator: H5 VLP vaccine 10 µg	Biological: H5 VLP pandemic influenza vaccine 10 µg; 0.5 mL, IM, 2 injections 21 days apart
Active Comparator: H5 VLP vaccine 20 µg	Biological: H5 VLP pandemic influenza vaccine 20 µg; 0.5 mL, IM, two injections 21 days apart
Placebo Comparator: Placebo (Formulation buffer)	Biological: Placebo; 0.5 mL, IM, two injections 21 days apart

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety will be evaluated through reported adverse events, physical examination findings; clinical laboratory results and vital signs.	21 days

Secondary Outcome Measures

Outcome Measure	Time Frame
The secondary objective is to evaluate the immunogenicity of two consecutive doses of plant-based H5 VLP vaccine combined with Alhydrogel®, at three dose levels: 5µg, 10µg and 20µg, compared to the placebo, combined with Alhydrogel®.	21days after each vaccination and 6-month after boost injection

Collaborators and Investigators

• Sponsor: Medicago
• Investigators: Principal Investigator: Brian Ward, MD, MUHC Vaccine Study Centre

Publications and helpful links

General Publications

• Landry N, Ward BJ, Trepanier S, Montomoli E, Dargis M, Lapini G, Vezina LP. Preclinical and clinical development of plant-made virus-like particle vaccine against avian H5N1 influenza. PLoS One. 2010 Dec 22;5(12):e15559. doi: 10.1371/journal.pone.0015559.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: September 24, 2009
• First Submitted That Met QC Criteria: September 24, 2009
• First Posted (Estimate): September 25, 2009

Study Record Updates

• Last Update Posted (Estimate): November 4, 2010
• Last Update Submitted That Met QC Criteria: November 2, 2010
• Last Verified: April 1, 2010

More Information

Terms related to this study

• Keywords: influenza; H5N1; pandemic vaccine; Virus Like Particle (VLP)
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; RNA Virus Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: Medicago H5VLP-001