Dose Escalating Study of Intramuscular Invaplex[AR-DETOX]

NCT03869333 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: CVIA 064
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

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.

Conditions

Diarrhea

Keywords

Shigella flexneri 2a; Enteric; Shigella

Outcome Measures

Primary Outcomes (5)

• Percentage of Participants With Adverse Events

  All adverse events (AEs) were assessed for severity by the investigator according to the following scale: Grade 1 (Mild): Does not interfere with routine activities, minimal level of discomfort; Grade 2 (Moderate): Interferes with routine activities, moderate level of discomfort; Grade 3 (Severe): Unable to perform routine activities, significant level of discomfort; Grade 4 (Potentially life-threatening): Hospitalization or ER visit for potentially life-threatening event. An AE was considered "serious" if it resulted in any of the following outcomes: * Death * Life-threatening AE * Inpatient hospitalization or prolongation of existing hospitalization * Persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions * Congenital anomaly/birth defect. The Investigator assessed the relationship of each adverse event to study drug.

  From first dose up to 28 days following the third immunization (71 days)

• Number of Participants With Solicited Adverse Events Up to 7 Days After Dose 1

  The solicited AEs for this study included: * Site pain * Site tenderness * Swelling * Induration (determined by investigator exam) * Site redness * Pruritus * Fever * Nausea * Vomiting * Abdominal pain * Diarrhea (loose stools) * Appetite change * Fatigue * Headache * Myalgias (general pain or soreness in muscles) * Arthralgias (general pain in joints) * Malaise

  7 days after the first immunization (Days 1 to 7)

• Number of Participants With Solicited Adverse Events Up to 7 Days After Dose 2

  The solicited AEs for this study included: * Site pain * Site tenderness * Swelling * Induration (determined by investigator exam) * Site redness * Pruritus * Fever * Nausea * Vomiting * Abdominal pain * Diarrhea (loose stools) * Appetite change * Fatigue * Headache * Myalgias (general pain or soreness in muscles) * Arthralgias (general pain in joints) * Malaise

  7 days after the second immunization (Days 22 to 28)

• Number of Participants With Solicited Adverse Events After Dose 3

  The solicited AEs for this study included: * Site pain * Site tenderness * Swelling * Induration (determined by investigator exam) * Site redness * Pruritus * Fever * Nausea * Vomiting * Abdominal pain * Diarrhea (loose stools) * Appetite change * Fatigue * Headache * Myalgias (general pain or soreness in muscles) * Arthralgias (general pain in joints) * Malaise

  7 days after the third immunization (Days 43 to 49)

• Number of Participants With Unsolicited Adverse Events After Each Dose

  Dose 1: Days 1 to 21; Dose 2: Days 22 to 42; Dose 3: Days 43 to 71

Secondary Outcomes (12)

• Geometric Mean Titer (GMT) of Serum Immunoglobulin A (IgA) Antibodies to Invaplex

  Days 1 (Baseline), 22, 43, 50, 57 and 71.

• Geometric Mean Titer (GMT) of Serum Immunoglobulin G (IgG) Antibodies to Invaplex

  Days 1 (Baseline), 22, 43, 50, 57 and 71.

• Geometric Mean Titer (GMT) of Immunoglobulin A Antibodies to Invaplex in α4β7+ Antibody in Lymphocyte Supernatant (ALS)

  Days 1 (Baseline), 8, 29, and 50

• Geometric Mean Titer of Immunoglobulin G Antibodies to Invaplex in α4β7+ Antibody in Lymphocyte Supernatant

  Days 1 (Baseline), 8, 29, and 50

• Percentage of Participants With a ≥ 4-fold Increase in Serum IgA Antibodies From Baseline

  Days 1 (Baseline), 22 43, 50, 57 and 71

Study Arms (4)

Invaplex[AR-Detox] 2.5 μg

EXPERIMENTAL

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

Biological: Invaplex[AR-DETOX]

Invaplex[AR-Detox] 10 μg

EXPERIMENTAL

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

Biological: Invaplex[AR-DETOX]

Invaplex[AR-Detox] 25 μg

EXPERIMENTAL

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

Biological: Invaplex[AR-DETOX]

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Invaplex[AR-DETOX] BIOLOGICAL

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

Invaplex[AR-Detox] 10 μg; Invaplex[AR-Detox] 2.5 μg; Invaplex[AR-Detox] 25 μg

Placebo OTHER

Saline

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• Serum immunoglobulin G (IgG) titer \> 2500 to Shigella flexneri 2a lipopolysaccharide antigen (LPS).
• History of microbiologically confirmed Shigella infection.

Sponsors & Collaborators

• PATH: lead

Study Sites (1)

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

Silver Spring, Maryland, 20910, United States

Location

MeSH Terms

Conditions

Diarrhea; Dysentery, Bacillary

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Dysentery; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Results Point of Contact

• Title: Rahsan Erdem
• Organization: PATH

rerdem@path.org

+1 202 540 4546

Study Officials

• Ramiro Gutierrez, MD, MPH

  Naval Medical Research Center (NMRC)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2019
• First Posted: March 11, 2019
• Study Start: March 18, 2019
• Primary Completion: June 12, 2020
• Study Completion: June 12, 2020
• Last Updated: July 29, 2021
• Results First Posted: July 29, 2021

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)