H5N1 With or Without Topical Aldara in Healthy Adults

NCT03472976 | Completed Phase 1 FDA Drug

• 2 other identifiers: 16-0050HHSN272201300015I
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Avian Influenza; Influenza Immunisation

Keywords

Healthy Young Adults; Immunogenicity; Inactivated Influenza A/H5N1 Vaccine; Phase I Clinical Trial; Reactogenicity; Safety; Topical Aldara(R)

Outcome Measures

Primary Outcomes (10)

• Geometric mean titers (GMTs) of serum HAI antibodies

  Day 1

• Geometric mean titers (GMTs) of serum HAI antibodies

  Day 43

• Occurrence of all SAEs

  Day 1 through Day 202

• Occurrence of solicited injection site AEs

  Day 1 through Day 8

• Occurrence of solicited injection site AEs

  Day 22 through Day 29

• Occurrence of solicited systemic AEs

  Day 1 through Day 8

• Occurrence of solicited systemic AEs

  Day 22 through Day29

• Occurrence of study vaccine-related SAEs

  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

  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

  Day 43

Secondary Outcomes (19)

• 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 1

• GMT of serum Neut 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

Study Arms (2)

Group 1

EXPERIMENTAL

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

Drug: Imiquimod; Biological: Influenza Virus Vaccine, Monovalent A/H5N1 A/Vietnam/1203/04

Group 2

EXPERIMENTAL

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

Other: Aqueous Cream B.P.; Biological: Influenza Virus Vaccine, Monovalent A/H5N1 A/Vietnam/1203/04

Interventions

Aqueous Cream B.P. OTHER

Aqueous Cream B.P. will be used as the control cream. An equivalent of 250mg of the cream will be applied and rubbed into the skin until it vanishes, on the deltoid area 5-15 minutes prior to vaccine administration.

Group 2

Imiquimod DRUG

Aldara (imiquimod 5%) cream is an immune response modifier for topical administration. 250 mg of the cream, equivalent to 12.5 mg of imiquimod will be applied and rubbed into the skin until it vanishes, on the deltoid area 5-15 minutes prior to vaccine administration.

Group 1

Influenza Virus Vaccine, Monovalent A/H5N1 A/Vietnam/1203/04 BIOLOGICAL

Inactivated monovalent subvirion H5N1 vaccine containing hemagglutinin (HA) of A/Vietnam/1203/04

Group 1; Group 2

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Women of childbearing potential must use an acceptable method of contraception from 30 days prior to vaccination until 60 days after the last study vaccination.
• \- Not sterilized via tubal ligation, bilateral oophorectomy, hysterectomy, or successful Essure(R) placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or \< 1 year of the last menses if menopausal).
• \-- Includes non-male sexual relationships, abstinence from sexual intercourse with a male partner, monogamous relationship with a vasectomized partner, male condoms with the use of applied spermicide, intrauterine devices, NuvaRing(R), and licensed hormonal methods such as implants, injectables or oral contraceptives ("the pill"). Method of contraception will be captured on the appropriate data collection form.
• Female subjects of childbearing potential must have a negative urine pregnancy test within 24 hours prior to study vaccination.
• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Baylor College of Medicine - Molecular Virology and Microbiology

Houston, Texas, 77030-3411, United States

Location

Related Publications (1)

• El Sahly HM, Atmar RL, Sendra E, Wegel A, Keitel WA. Topical Imiquimod Does Not Provide an Adjuvant Effect When Administered With Inactivated Influenza A/H5N1 Vaccine in Healthy Young Adults. J Infect Dis. 2021 Nov 22;224(10):1712-1719. doi: 10.1093/infdis/jiab206.

  PMID: 33852718 DERIVED

MeSH Terms

Conditions

Influenza in Birds; Influenza, Human

Interventions

Imiquimod; Influenza Vaccines

Condition Hierarchy (Ancestors)

Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Infections; Bird Diseases; Animal Diseases; Respiratory Tract Infections; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2018
• First Posted: March 21, 2018
• Study Start: June 13, 2018
• Primary Completion: March 4, 2019
• Study Completion: March 4, 2019
• Last Updated: February 24, 2020

Record last verified: 2018-08-14

Locations

US (1)