Dose Escalating Study of Intramuscular Invaplex[AR-DETOX]

NCT ID: NCT03869333

Last Updated: 2021-07-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-18
• Study Completion Date: 2020-06-12

Brief Summary

The main purpose of this study is to evaluate the safety of a Shigella flexneri 2a detoxified artificial invasin complex (Invaplex[AR-Detox]) vaccine candidate administered by intramuscular immunization.

Detailed Description

This is a randomized, double-blind, placebo-controlled, Phase 1 clinical trial in which a total of 60 volunteers will receive one of three doses of Invaplex[AR-DETOX] or placebo (saline). The vaccine will be administered via intramuscular (IM) injection on study days 1, 22, and 43. Each participant will receive the same formulation at each vaccination dependent upon group assignment. The study will be initiated with the lowest dose level (2.5 μg) and will proceed to the next highest dose in an escalating fashion. All safety data will be summarized and reviewed by the Protocol Safety Review Team (PSRT) prior to dose-escalation.

Specimens will be collected at prescribed intervals to examine systemic and mucosal immune responses. Vaccine safety will be actively monitored during vaccination and for 28 days following the third vaccine dose.

Conditions

Diarrhea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Invaplex[AR-Detox] 2.5 μg

Participants received an intramuscular injection of 2.5 μg Invaplex\[AR-DETOX\] vaccine on Days 1, 22, and 43.

Group Type: EXPERIMENTAL

Invaplex[AR-DETOX]

Intervention Type: BIOLOGICAL

Detoxified Shigella flexneri 2a Artificial Invasin Complex (Invaplex\[AR-Detox\]) Vaccine

Invaplex[AR-Detox] 10 μg

Participants received an intramuscular injection of 10 μg Invaplex\[AR-DETOX\] vaccine on Days 1, 22, and 43.

Group Type: EXPERIMENTAL

Invaplex[AR-DETOX]

Intervention Type: BIOLOGICAL

Detoxified Shigella flexneri 2a Artificial Invasin Complex (Invaplex\[AR-Detox\]) Vaccine

Invaplex[AR-Detox] 25 μg

Participants received an intramuscular injection of 25 μg Invaplex\[AR-DETOX\] vaccine on Days 1, 22, and 43.

Group Type: EXPERIMENTAL

Invaplex[AR-DETOX]

Intervention Type: BIOLOGICAL

Detoxified Shigella flexneri 2a Artificial Invasin Complex (Invaplex\[AR-Detox\]) Vaccine

Placebo

Participants received an intramuscular injection of placebo solution on Days 1, 22, and 43.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Saline

Interventions

Invaplex[AR-DETOX]

Detoxified Shigella flexneri 2a Artificial Invasin Complex (Invaplex\[AR-Detox\]) Vaccine

Intervention Type: BIOLOGICAL

Placebo

Saline

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Healthy, adult, male or female, age 18 to 50 years (inclusive) at the time of enrollment.
• Completion and review of comprehension test (achieved ≥ 70% accuracy, two attempts allowed).
• Provide written informed consent before initiation of any study procedures.
• Agrees to complete all study visits and procedures and to provide a screening stool sample.
• Women of childbearing capacity: Negative pregnancy test with understanding (through informed consent process) to not become pregnant during the study or within three (3) months following the last vaccine dose.

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 Principal Investigator (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.
• History of autoimmune disorders, cardiovascular and renal disease.
• Use of immunosuppressive medications (systemic corticosteroids or chemotherapeutics that may influence antibody development), or immunosuppressive illness, including immunoglobulin A (IgA) deficiency (defined by serum IgA < 7 mg/dL).
• Women who are pregnant or planning to become pregnant during the study period plus 3 months beyond the last vaccine dose and currently nursing women.
• 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 in-clinic study safety visit.
• Positive blood test for hepatitis B surface antigen (HBsAG), hepatitis C virus antibody (HCV Ab), human immunodeficiency virus (HIV)-1/HIV-2 antibody.
• Clinically significant abnormalities on basic laboratory screening tests.
• Systemic antimicrobial treatment (i.e., topical treatments are not an exclusion) within 1 week before administration of the first vaccine dose.
• Allergies that may increase the risk of adverse events (AEs).
• Regular use (weekly or more often) of antidiarrheal, anti-constipation, or antacid therapy.
• 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 an inflammatory arthritis.
• Positive blood test for human leukocyte antigen (HLA) B27 (associated with increased risk of reactive arthritis secondary to Shigella infection)
• History of allergy to any vaccine.
• Exclusionary skin disease history/findings that would confound assessment or prevent appropriate local monitoring of AEs, or possibly increase the risk of a local AE.
• Serum immunoglobulin G (IgG) titer > 2500 to Shigella flexneri 2a lipopolysaccharide antigen (LPS).
• History of microbiologically confirmed Shigella infection.
• Received previous licensed or experimental Shigella vaccine or live Shigella challenge.
• Travel to countries where Shigella or other enteric infections are endemic (most of the developing world) within two years prior to dosing (clinician judgement).
• Occupation involving handling of Shigella bacteria currently, or in the past 3 years.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

PATH

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ramiro Gutierrez, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Naval Medical Research Center (NMRC)

Locations

Walter Reed Army Institute of Research Clinical Trials Center (WRAIR CTC)

Silver Spring, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CVIA 064

Identifier Type: -

Identifier Source: org_study_id