Clinical Trial: Safety and Immunogenicity of Artificial Invaplex (Shigella Flexneri 2a InvaplexAR) Administered Intranasally to Healthy, Adult Volunteers

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase 1 Open-label, Dose Escalating Study of Artificial Shigella Flexneri 2a InvaplexAR Administered Intranasally to Healthy, Adult Volunteers to Evaluate Safety and Immunogenicity

Brief Summary: This study is an open-label, dose-escalating Phase 1 investigation of S. flexneri 2a InvaplexAR vaccine. A total of up to 40 subjects will receive one of four S. flexneri 2a InvaplexAR vaccine doses. The vaccine will be administered intranasally (without adjuvant).

Detailed Summary: The vaccine will be administered on Days 0,14, and 28. Volunteers (10 per group [8 minimum]) will receive the same dose at each vaccination dependent upon group assignment. Groups will be divided according to the table below. An interval no less than 1 week will separate the third dose of a group from the first dose of the next group (receiving an increased InvaplexAR dose). Blood, stool, and saliva specimens will be collected at pre-specified intervals to examine systemic and mucosal vaccine antigen-specific immune responses. Ocular tear samples will be collected in groups C and D. Vaccine safety will be actively monitored during vaccination and for 28 days following the third vaccine dose. The decision to advance to the next dose level is based on the safety assessment (not immunogenicity). A dose level with no occurrence of stopping criteria in the 7 days following the last vaccine dose will prompt moving to the next higher level. All safety data will be summarized and reviewed with the research monitor prior to dose escalation. In addition, a report of all safety data will be provided to the sponsor's safety office for informational purposes.
Sponsor: U.S. Army Medical Research and Materiel Command

Current Primary Outcome:

• Number of adverse events [ Time Frame: 270 days ]
  Solicited AE monitoring will survey and specifically inquire about symptoms including subjective and objective fever (oral temperature > 100.4°F), malaise, headache, rhinorrhea, epistaxis (nasal bleeding), nasal mucosal ulceration, nasal congestion, edema, nasal burning, nasal itching, nasal discharge, sore throat, post nasal drip, cough, sinus pain, sneezing, and itchy eyes.
• Antibody titers against immunizing antigens [ Time Frame: 56 days ]
  Serum samples will be assayed for antibody titers against immunizing antigens. Previously established high-titer specimens will be included on each plate to track day to day interassay variation. For each antigen, pre- and post-vaccination serum samples will be assayed side-by-side. The antibody titer assigned to each sample will represent the geometric mean of duplicate tests performed on 2 different days. Reciprocal endpoint titers < 5 will be assigned a value of 2.5 for computational purposes. Seroconversion will be defined as a > 4-fold increase in endpoint titer between pre-and post-vaccination samples AND a post-vaccination reciprocal titer >10.

Original Primary Outcome: Same as current

Current Secondary Outcome: Mucosal responses (Number of IgA Antibody Secreting Cells (ACS) and Antibody lymphocyte supernatant (ALS) responses). [ Time Frame: 56 days ]

Original Secondary Outcome: Same as current

Information By: U.S. Army Medical Research and Materiel Command

Dates:
Date Received: May 13, 2015
Date Started: October 1, 2015
Date Completion: March 2019
Last Updated: March 28, 2017
Last Verified: March 2017