Safety and Immunogenicity of Artificial Invaplex (Shigella Flexneri 2a InvaplexAR)

NCT ID: NCT02445963

Last Updated: 2021-02-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-01
• Study Completion Date: 2016-05-13

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 Description

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.

Conditions

Shigellosis; Bacillary Dysentery

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

10 μg S. flexneri 2a Invaplex

10 subjects vaccinated on days 0, 14, 28

Group Type: ACTIVE_COMPARATOR

Shigella flexneri 2a InvaplexAR

Intervention Type: BIOLOGICAL

The investigational product is S. flexneri 2a InvaplexAR. The product is composed of three individual components IpaB, IpaC, and LPS. The components were assembled into the high molecular weight S. flexneri 2a InvaplexAR complex and subsequently purified by ion-exchange chromatography yielding a bulk lot.

50 μg S. flexneri 2a Invaplex

10 subjects vaccinated on days 0, 14, 28

Group Type: ACTIVE_COMPARATOR

Shigella flexneri 2a InvaplexAR

Intervention Type: BIOLOGICAL

The investigational product is S. flexneri 2a InvaplexAR. The product is composed of three individual components IpaB, IpaC, and LPS. The components were assembled into the high molecular weight S. flexneri 2a InvaplexAR complex and subsequently purified by ion-exchange chromatography yielding a bulk lot.

250 μg S. flexneri 2a Invaplex

10 subjects vaccinated on days 0, 14, 28

Group Type: ACTIVE_COMPARATOR

Shigella flexneri 2a InvaplexAR

Intervention Type: BIOLOGICAL

The investigational product is S. flexneri 2a InvaplexAR. The product is composed of three individual components IpaB, IpaC, and LPS. The components were assembled into the high molecular weight S. flexneri 2a InvaplexAR complex and subsequently purified by ion-exchange chromatography yielding a bulk lot.

500 μg S. flexneri 2a Invaplex

10 subjects vaccinated on days 0, 14, 28

Group Type: ACTIVE_COMPARATOR

Shigella flexneri 2a InvaplexAR

Intervention Type: BIOLOGICAL

The investigational product is S. flexneri 2a InvaplexAR. The product is composed of three individual components IpaB, IpaC, and LPS. The components were assembled into the high molecular weight S. flexneri 2a InvaplexAR complex and subsequently purified by ion-exchange chromatography yielding a bulk lot.

Interventions

Shigella flexneri 2a InvaplexAR

The investigational product is S. flexneri 2a InvaplexAR. The product is composed of three individual components IpaB, IpaC, and LPS. The components were assembled into the high molecular weight S. flexneri 2a InvaplexAR complex and subsequently purified by ion-exchange chromatography yielding a bulk lot.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Healthy, adult, male or female, age 18 to 45 years (inclusive) at the time of enrollment.
• Completion and review of comprehension test (achieved > 70% accuracy).
• Signed informed consent document.
• Available for the required follow-up period and scheduled clinic visits.
• Women: Negative pregnancy test with understanding (through informed consent process) to not become pregnant nor to breastfeed during the study or within 3 months following last vaccination

Exclusion Criteria

• Health problems (for example, chronic medical conditions such as psychiatric conditions, diabetes mellitus, hypertension, or any other conditions that might place the subjects at increased risk of adverse events)- study clinicians, in consultation with the PI, will use clinical judgment on a case-by-case basis to assess safety risks under this criterion. The PI will consult with the Research Monitor as appropriate.
• Clinically significant abnormalities on physical examination (chronic sinusitis or seasonal rhinitis) which compromise identification and interpretation of potential vaccine associated adverse effects.
• Use of immunosuppressive and/or immunomodulative drugs such as corticosteroids or chemotherapeutics that may influence antibody development.
• Immunosuppressive illnesses (including IgA deficiency defined by serum IgA below level of detection or <7mg/dL).
• Participation in research involving another investigational product (defined as receipt of an investigational product or exposure to an invasive investigational device) 30 days before planned date of first vaccination or anytime throughout the duration of the study until the last study safety visit.
• Positive blood test for HBsAG, HCV, HIV-1/HIV-2.
• Clinically significant abnormalities on basic laboratory screening.
• Presence of significant unexplained laboratory abnormalities that in the opinion of the PI may potentially confound the analysis of the study results.
• Current smoker or smoker in past 1 year ('smoker' defined as daily cigarette, cigar, or pipe use for a period of at least 1 month).

Research specific

• Structural abnormalities on sinus/nasal cavity examination.
• Rhinoplasty.
• Nasal polyps.
• Nasal ulcers.
• Deviated nasal septum. This question is being used to determine whether the volunteer has a clinically significant deviated septum that causes nasal obstruction (thereby causing difficulty breathing), interferes with normal sinus drainage, or obscures visualization of the posterior nasal cavity complicating examination and safety monitoring..
• Chronic sinusitis/rhinitis.
• Current or planned use of nasal topical corticosteroids and/or nasal spray medications in the 4 weeks prior to dosing or during the study vaccination period.
• Current or recent history (in the past 5 years) of reactive airway disease (asthma), chronic obstructive pulmonary disease, or chronic bronchitis.
• History of Bell's palsy.
• Chronic use (weekly or more often) of anti-diarrheal, anti-constipation, or antacid therapy (excluding use associated with spicy meals).
• Abnormal stool pattern (fewer than 3 stools per week or more than 3 stools per day) on a regular basis; loose or liquid stools on other than an occasional basis.
• Personal or family history of inflammatory arthritis.
• Positive blood test for HLA-B27.
• History of allergy to any vaccine.

Prior Exposure to Shigella

• Serum IgG titer ≥ 2500 to Shigella flexneri 2a LPS.
• History of microbiologically confirmed Shigella infection in the past 3 years.
• Received previous experimental Shigella vaccine or live Shigella challenge.
• Travel to countries with symptoms of travelers' diarrhea where Shigella or other enteric infections are endemic (most of the developing world) within the past 6 months prior to dosing.
• Occupation involving handling of Shigella bacteria currently, or in the past 3 years.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

U.S. Army Medical Research and Development Command

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christopher Duplessis, MD, MPH, MS

Role: PRINCIPAL_INVESTIGATOR

Enteric Diseases Department Naval Medical Research Center

Locations

Walter Reed Army Institute of Research, Clinical Trials Center

Silver Spring, Maryland, United States

Countries

United States

References

Duplessis C, Clarkson KA, Ross Turbyfill K, Alcala AN, Gutierrez R, Riddle MS, Lee T, Paolino K, Weerts HP, Lynen A, Oaks EV, Porter CK, Kaminski R. GMP manufacture of Shigella flexneri 2a Artificial Invaplex (InvaplexAR) and evaluation in a Phase 1 Open-label, dose escalating study administered intranasally to healthy, adult volunteers. Vaccine. 2023 Oct 6;41(42):6261-6271. doi: 10.1016/j.vaccine.2023.08.051. Epub 2023 Sep 2.

Reference Type: DERIVED

PMID: 37666695 (View on PubMed)

Other Identifiers

A-18716

Identifier Type: OTHER

Identifier Source: secondary_id

NMRC.2015.0003

Identifier Type: OTHER

Identifier Source: secondary_id

S-15-19

Identifier Type: -

Identifier Source: org_study_id