Clinical Trial to Assess Safety and Immunogenicity of a Synthetic Vaccine Against Streptococcus Pyogenes

Phase I Clinical Trial for Assessment of Safety and Immunogenicity of a Synthetic Vaccine Against Streptococcus Pyogenes in Healthy Volunteers

This is a double-blind, randomized, placebo-controlled phase I clinical trial with dose-escalation of a synthetic vaccine against Streptococcus pyogenes. The active component of this vaccine candidate is a synthetic polypeptide named StreptInCor designed to elicit humoral and cell-mediated immune responses. The vaccine will be formulated with Aluminium hydroxide in three different doses of StreptInCor (50 µg, 100µg, 200 µg). The proposed vaccination schedule is three doses (0, 1, 6 months). The doses will be escalated for the next group after safety review.

Study Overview

• Status: Withdrawn
• Conditions: Rheumatic Fever
• Intervention / Treatment: Biological: Streptococcus pyogenes vaccine (50 µg); Biological: Streptococcus pyogenes vaccine (100 µg); Biological: Streptococcus pyogenes vaccine (200 µg); Other: Placebo

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers, both sex, aging 18 to 45 years;
• Availability for all procedures during the study period;
• Provide free informed consent to join the study

Exclusion Criteria:

• Diagnosis of concomitant infections or diseases that might affect immunity, including active HIV infection, hepatitis B, hepatitis C, diabetes mellitus, neoplasias, and autoimmune diseases;
• Previous or current diagnosis or family antecedent of rheumatic fever, chorea, obsessive-compulsive disorder or glomerulonephritis;
• Previous or current diagnosis of cardiac disease;
• Severe asma or Chronic obstructive pulmonary disease (COPD);
• Abnormal neurological clinical assessment, particularly chorea;
• Use of treatments that might affect the immunity in the last four weeks, including immunomodulators, corticosteroids (only systemic use equal or longer than two weeks), or antineoplastic agents;
• Use of treatments that might affect heart valves in the latest four weeks, including fenfluramine e dexfenfluramine;
• Kidney failure determined by creatinine clearance lower than 45 ml/min/1,73m²;
• History of intolerance or allergy to any component of investigational products, including antigen or adjuvant;
• Presence of abnormalities in heart valves or heart anatomy defined by echocardiogram;
• Electrocardiogram disturbances;
• Presence of cross-reactive antibodies against human tissues (heart, kidney, cartilage, brain) in screening tests;
• Evidence or suspicion of recent infection due to S. pyogenes assessed by clinical symptoms and negative rapid test for Streptococcus;
• Pregnancy, breastfeeding mother or intention to became pregnant during the study period;
• Any other condition that might affect the study process according to the investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo without active component
Experimental: Low-dose vaccine	Biological: Streptococcus pyogenes vaccine (50 µg); Vaccine containing 50 µg of StreptInCor synthetic peptide and Aluminium Hydroxide as adjuvant
Experimental: Mid-dose vaccine	Biological: Streptococcus pyogenes vaccine (100 µg); Vaccine containing 100 µg of StreptInCor synthetic peptide and Aluminium Hydroxide as adjuvant
Experimental: High-dose vaccine	Biological: Streptococcus pyogenes vaccine (200 µg); Vaccine containing 200 µg of StreptInCor synthetic peptide and Aluminium Hydroxide as adjuvant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Solicited and unsolicited adverse reactions	Frequency of solicited and unsolicited adverse reactions	Six months after last dose
Immune response to vaccine	Rate of seroconversion for vaccine epitopes	Six months after last dose

Collaborators and Investigators

• Sponsor: Butantan Institute
• Collaborators: InCor - Instituto do Coração - HCFMUSP.
• Investigators: Study Chair: Luiza Guilherme, PhD, InCor Heart Institute; Principal Investigator: Roney O Sampaio, MD, PhD, InCor Heart Institute

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2021
• Primary Completion (Anticipated): March 1, 2022
• Study Completion (Anticipated): October 1, 2023

Study Registration Dates

• First Submitted: June 24, 2019
• First Submitted That Met QC Criteria: June 24, 2019
• First Posted (Actual): June 26, 2019

Study Record Updates

• Last Update Posted (Actual): February 4, 2021
• Last Update Submitted That Met QC Criteria: February 2, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: vaccine; peptide; Streptococcus pyogenes
• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Rheumatic Fever; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: EGA-01-IB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No