A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of Inactivated Influenza A/H5N1 Vaccine Administered Intradermally With or Without Topical Aldara(R) in Healthy Young Adults
Overview
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Occurrence of all SAEs
Overview
Brief Summary
Phase I randomized, double-blind, placebo-controlled trial in 50 males and non-pregnant females, 18 to 49 years old, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity, and immunogenicity of inactivated A/H5N1 influenza vaccine administered intradermally (ID) with topical Aldara or control cream as a 2-dose regimen. The vaccine will be administered using the MicronJet600(TM) device. Subjects will be assigned to 2 treatment arms (25 subjects per treatment arm). Group A will receive two doses of A/H5N1 IIV ID with pre-application of topical Aldara on Days 1 and 22. Group B will receive two doses of A/H5N1 IIV ID with pre-application of topical control cream on Days 1 and 22. The duration of this study will be approximately 20 months with patient participation duration approximately 7 months. The primary objectives of this study are: 1) to assess the safety and reactogenicity after 2 doses of A/H5N1 IIV vaccine containing 9 mcg HA per dose administered ID approximately 21 days apart with topical Aldara or control cream; 2) to assess the serum HAI antibody responses 21 days after receipt of the 2nd dose of A/H5N1 IIV administered ID at 9 mcg HA per dose with topical Aldara or control cream.
Detailed Description
This is a Phase I randomized, double-blind, placebo-controlled trial in 50 males and non-pregnant females, 18 to 49 years old, inclusive, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity, and immunogenicity of inactivated A/H5N1 influenza vaccine administered intradermally (ID) with topical Aldara or control cream as a 2-dose regimen. The vaccine will be administered using the MicronJet600(TM) device. Subjects will be assigned randomly to 1 of 2 treatment arms (25 subjects per treatment arm) to receive 2 doses of A/H5N1 IIV administered ID with topical Aldara or control cream. Group A will receive two doses of A/H5N1 IIV (9 mcg HA/dose) ID with pre-application of topical Aldara on Days 1 and 22. Group B will receive two doses of A/H5N1 IIV (9 mcg HA/dose) ID with pre-application of topical control cream on Days 1 and 22. The duration of this study will be approximately 20 months with patient participation duration approximately 7 months. The primary objectives of this study are: 1) to assess the safety and reactogenicity after 2 doses of A/H5N1 IIV vaccine containing 9 mcg HA per dose administered ID approximately 21 days apart with topical Aldara or control cream; 2) to assess the serum HAI antibody responses 21 days after receipt of the 2nd dose of A/H5N1 IIV administered ID at 9 mcg HA per dose with topical Aldara or control cream. The secondary objectives are: 1) to assess unsolicited non-serious adverse events (AEs) following receipt of 2 doses of A/H5N1 IIV administered ID approximately 21 days apart with topical Aldara or control cream; 2) to assess medically-attended adverse events (MAAEs) including new-onset chronic medical conditions (NOCMCs), and potentially immune mediated medical conditions (PIMMCs) following receipt of two doses of A/H5N1 IIV administered ID approximately 21 days apart with topical Aldara or control cream for six months after last vaccination; 3) to assess the serum neutralizing (Neut) antibody responses 21 days following receipt of the 1st and 2nd dose of A/H5N1 IIV administered ID with topical Aldara or control cream; 4) to assess the serum HAI antibody responses 21 days following receipt of the 1st dose of A/H5N1 IIV administered ID with topical Aldara or control cream; 5) to assess the serum HAI and Neut antibody responses 7 days following receipt of the 2nd dose of A/H5N1 IIV administered ID with topical Aldara or control cream.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 49 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Provide written informed consent prior to initiation of any study procedures.
- •Are able to understand and comply with planned study procedures and be available for all study visits.
- •Are males or non-pregnant females, 18 to 49 years old, inclusive.
- •Are in good health, as determined by vital signs (oral temperature, pulse, and blood pressure), medical history, and physical examination to ensure any existing medical diagnoses or conditions (except those exclusionary) are stable.
- •Stable chronic medical condition - no change in prescription medication, dose, or frequency of medication in the last 2 months (defined as 60 days) and health outcomes of the specific disease are considered to be within acceptable limits in the last 6 months (defined as 180 days). Any change that is due to change of health care provider, insurance company etc., or that is done for financial reasons, as long as in the same class of medication, will not be considered a violation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the site principal investigator or appropriate sub-investigator, will not be considered a violation of this inclusion criterion.
- •- Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site principal investigator or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity. Note: Topical, nasal, and inhaled medications (with the exception of steroids as outlined in the Subject Exclusion Criteria), vitamins, and contraceptives are permitted.
- •Oral temperature is less than 100.0 degrees F.
- •Pulse is 47 to 100 bpm, inclusive.
- •Systolic blood pressure is 85 to 150 mm Hg, inclusive.
- •Diastolic blood pressure is 55 to 95 mmHg, inclusive.
Exclusion Criteria
- •Have an acute illness, as determined by the site PI or appropriate sub-investigator, within 72 hours prior to study vaccination.
- •An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol.
- •Have any medical disease or condition that, in the opinion of the site PI or appropriate sub-investigator, is a contraindication to study participation.
- •Including acute or chronic medical disease or condition, defined as persisting for at least 90 days, that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this study.
- •Have immunosuppression as a result of an underlying illness or treatment, or use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study vaccination.
- •Have known active neoplastic disease or a history of any hematologic malignancy. Non-melanoma skin cancers that are not active are permitted.
- •Have known HIV, chronic hepatitis B virus, or chronic hepatitis C infection.
- •Have known hypersensitivity or allergy to eggs, egg or chicken protein, or other components of the study vaccine.
- •Have a history of severe reactions following previous immunization with licensed or unlicensed influenza vaccines.
- •Have a history of Guillain-Barré Syndrome.
Arms & Interventions
Group 1
0.1 ml of influenza A/H5N1 IIV vaccine (9 mcg HA) intradermally 15 minutes after the application of approximately 250 mg of Imiquimod (Aldara) cream topically (deltoid) on Day 1 and Day 22. N=25
Intervention: Imiquimod (Drug)
Group 1
0.1 ml of influenza A/H5N1 IIV vaccine (9 mcg HA) intradermally 15 minutes after the application of approximately 250 mg of Imiquimod (Aldara) cream topically (deltoid) on Day 1 and Day 22. N=25
Intervention: Influenza Virus Vaccine, Monovalent A/H5N1 A/Vietnam/1203/04 (Biological)
Group 2
0.1 ml of influenza A/H5N1 IIV vaccine (9 mcg HA) intradermally 15 minutes after the application of approximately 250 mg of Aqueous Cream B.P. (Control Cream) topically (deltoid) on Day 1 and Day 22. N=25
Intervention: Aqueous Cream B.P. (Other)
Group 2
0.1 ml of influenza A/H5N1 IIV vaccine (9 mcg HA) intradermally 15 minutes after the application of approximately 250 mg of Aqueous Cream B.P. (Control Cream) topically (deltoid) on Day 1 and Day 22. N=25
Intervention: Influenza Virus Vaccine, Monovalent A/H5N1 A/Vietnam/1203/04 (Biological)
Outcomes
Primary Outcomes
Occurrence of all SAEs
Time Frame: Day 1 through Day 202
Geometric mean titers (GMTs) of serum HAI antibodies
Time Frame: Day 43
Occurrence of solicited injection site AEs
Time Frame: Day 22 through Day 29
Occurrence of solicited systemic AEs
Time Frame: Day 22 through Day29
Occurrence of study vaccine-related SAEs
Time Frame: Day 1 through Day 202
Percentage of subjects achieving a serum HAI antibody titer of 40 or greater against the A/H5N1 antigen contained in the study vaccine
Time Frame: Day 43
Percentage of subjects achieving HAI seroconversion against study vaccine (pre-vaccination HAI titer <10 and post-vaccination HAI titer > / = 40 or pre-vaccination HAI titer > / =10 and a min 4-fold rise in post-vaccination HAI antibody titer
Time Frame: Day 43
Secondary Outcomes
- GMT of serum HAI antibody against the A/H5N1 antigen contained in the study vaccine(Day 22)
- GMT of serum Neut antibody against the A/H5N1 antigen contained in the study vaccine(Day 43)
- Occurrence of all unsolicited non-SAEs(Day 1 through Day 43)
- Occurrence of Medically-Attended Adverse Events (MAAEs), including New-Onset Chronic Medical Conditions (NOCMCs) and Potentially Immune-Mediated Medical Conditions (PIMMCs)(Day 1 through Day 202)
- Occurrence of study vaccine-related unsolicited non-serious AEs(Day 1 through Day 43)
- Percentage of subjects achieving a serum HAI antibody titer of 40 or greater against the A/H5N1 antigen contained in the study vaccine(Day 22)
- Percentage of subjects achieving a serum Neut antibody titer of 40 or greater against the A/H5N1 antigen contained in the study vaccine(Day 43)
- Percentage of subjects achieving HAI seroconversion against the A/H5N1 antigen contained in the study vaccine(Day 22)
- Percentage of subjects achieving Neut seroconversion (pre-vaccination Neut titer < 10 and post-vaccination Neut titer > / = 40 or pre-vaccination Neut titer > / = 10 and a min 4-fold rise in post-vaccination Neut antibody titer)(Day 43)
- Proportion of subjects with GMT of serum Neut antibody against the A/H5N1 antigen contained in the study vaccine(Day 29)
- Proportion of subjects with seroconversion against the A/H5N1 antigen contained in the study vaccine(Day 29)
- Proportion of subjects with titer of 40 or greater of serum HAI antibody against the A/H5N1 antigen contained in the study vaccine(Day 29)
- Proportion of subjects with titer of 40 or greater of serum Neut antibody against the A/H5N1 antigen contained in the study vaccine(Day 29)
- Secondary Proportion of subjects with GMT of serum HAI antibody against the A/H5N1 antigen contained in the study vaccine(Day 29)