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

Study Overview
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Brief Summary
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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.

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

Conditions
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Rheumatic Fever

Intervention / Treatment
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* Biological: Streptococcus pyogenes vaccine (50 µg)
* Biological: Streptococcus pyogenes vaccine (100 µg)
* Biological: Streptococcus pyogenes vaccine (200 µg)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vaccine, peptide, Streptococcus pyogenes