A Controlled Study to Evaluate the Safety and Immunogenicity of StreptAnova™ in Healthy Adults

A Phase I, Randomized, Observer-blind, Comparator-controlled, Study of the Safety and Immunogenicity of StreptAnova™ Vaccine in Healthy Adults Age ≥ 18 - 50 Years

This is a single-centered trial of a group A streptococcal (GAS) vaccine, StreptAnova™. The study is designed to assess safety and immunogenicity of three doses (0, 1, 6 months) of one dosage (600 µg protein) in healthy adults 18 through 50 years of age.

This is a single-centered trial of a group A streptococcal (GAS) vaccine, StreptAnova™, to be performed in Canada. It will be randomized, observer-blinded, and comparator controlled. The study is designed to assess safety and immunogenicity of three doses (0, 1, 6 months) of one dosage (600 µg protein) in healthy adults 18 through 50 years of age.

A comparator vaccine is included at 2:1 ratio (StreptAnova™ to comparator). Assignment to StreptAnova™ or comparator vaccine will be both randomized and observer-blinded. Three (3) 0.6 mL doses (600 µg protein) of StreptAnova™ or 0.5 mL doses of comparator will be administered on days 0, 30 and 180 (N= 30 StreptAnova™, 15 comparator); each subject will receive three doses of the same treatment.

Forty-five subjects will be enrolled. At each vaccine dose, detailed safety data will be collected from the first 15 randomized subjects until seven days after administration and used to determine whether to proceed to immunizing the 30 remaining subjects. Detailed safety data will be collected from the remaining 30 randomized subjects until seven days after administration and used to determine whether to proceed to immunizing the first 15 randomized subjects at the next dose.

Treatments will be followed by standard clinical parameters for evaluating the safety of a biologic/vaccine product including standardized methods for local and systemic vaccine reactions, repeated vital signs and physical examinations, 12-month follow-up (6 months post-dose 3) for adverse events and concomitant medication changes, and monitoring of clinical laboratory values as clinically indicated.

Inclusion Criteria:

• Male and female healthy adults ages 18 to 50 years inclusive;
• Good general health as determined by screening evaluation no greater than 42 days before the first immunization;
• For women of childbearing age, use of adequate birth control from enrollment until 180 days after the last injection;
• Written informed consent, after reading the consent form and having adequate opportunity to discuss the study with an investigator or a qualified designee.

Exclusion Criteria:

• Presence of any febrile illness or any known or suspected acute illness on the day of any first immunization;
• Any chronic illness, whether or not active treatment is required;
• Any immunodeficiency (congenital or acquired);
• Any history of cardiac pathology (acquired or severe/persistent congenital);
• Any history of congenital malformation syndromes associated with congenital heart disease (syndrome complexes, e.g. VATER association; chromosomal disorders, e.g. Down's Syndrome; teratogenic agents, e.g. fetal alcohol syndrome; others, e.g. Noonan's);
• Any history of clinical manifestations of auto-immune or systemic diseases (inflammatory disorders, e.g. JRA, SLE, Kawasaki disease; inborn errors of metabolism, e.g. Fabry; connective tissue disorders, e.g. Marfan syndrome; neuromuscular disorders, e.g. Friedreich ataxia; endocrine-metabolic disorders, e.g. hypothyroidism; hematologic disorders, e.g. sickle cell anemia);
• Any history of acute rheumatic fever (ARF), post-streptococcal glomerulonephritis (PSGN), undiagnosed acute self-limiting polyarthritis (swelling, heat, redness or tenderness or pain and limitation of motion in >2 joints), or chorea (purposeless, involuntary rapid movements of the trunk and/or extremities);
• Any previous echocardiogram suggestive of cardiac pathology;
• Any immediate family history (parents, siblings) of ARF, PSGN, self-limiting polyarthritis, chorea, or a collagen-vascular disease such as Lupus or Sjögren's syndrome;
• Receipt of systemic glucocorticoids (a dose ≥ 20 mg/day prednisone or equivalent) within one month, or any other cytotoxic or immunosuppressive drug within six months;
• Receipt of any investigational drug within six months, or prior participation in a clinical trial of a group A streptococcal vaccine;
• Receipt of blood products or immunoglobulin (IVIg or IMIg) within three (3) months of study entry/baseline serologic evaluation;
• Any physical findings suggestive of acute or chronic illness;
• History of receiving Adriamycin or other chemotherapy;
• Use of any of the following diet pills: fenfluramine, phentermine, or dexfenfluramins (also known as Pondimin, Redux, Adipex, or Fastin);
• History of sensitivity to any component of study vaccines;
• Evidence of tissue cross-reactive antibodies to human heart, joint cartilage, kidney, cerebral cortex or basal ganglia by indirect fluorescent antibody assay at pre-vaccination screening;
• Repeatable clinical laboratory abnormalities (blood or urine), as defined by lab normal ranges. To exclude transient abnormalities, the investigator may repeat a test up to twice, and if the repeat test is normal, subject may be enrolled;
• Echocardiographic finding of valvular dysfunction (stenosis, leaflet thickening or nodules, restricted leaflet mobility, or prolapse), LV dysfunction, atrial or ventricular enlargement, mild or greater mitral regurgitation or aortic insufficiency, moderate or greater tricuspid regurgitation or pulmonic insufficiency, pericardial effusion, or other cardiac pathology as identified by echocardiologist*;
• Receipt of any vaccines within 2 weeks of Dose 1;
• Clinically significant abnormality on screening electrocardiogram*
• Pregnancy or breastfeeding.