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

Phase 1

Withdrawn

• Conditions: Rheumatic Fever
• Interventions: Biological: Streptococcus pyogenes vaccine (50 µg); Biological: Streptococcus pyogenes vaccine (100 µg); Biological: Streptococcus pyogenes vaccine (200 µg); Other: Placebo

• Registration Number: NCT03998592
• Lead Sponsor: Butantan Institute

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-06-24
• Study First Submitted QC: 2019-06-24
• Study First Posted: 2019-06-26
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-02
• Last Update Posted: 2021-02-04
• Study Start: 2021-05
• Primary Completion: 2022-03
• Study Completion: 2023-10

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low-dose vaccine	Streptococcus pyogenes vaccine (50 µg)	-
Mid-dose vaccine	Streptococcus pyogenes vaccine (100 µg)	-
High-dose vaccine	Streptococcus pyogenes vaccine (200 µg)	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Solicited and unsolicited adverse reactions	Six months after last dose	Frequency of solicited and unsolicited adverse reactions
Immune response to vaccine	Six months after last dose	Rate of seroconversion for vaccine epitopes