A Trial of a Peptide-based Group A Streptococcal (GAS) Vaccine Candidate in Healthy Individuals.

NCT04882514 | Completed Phase 1 DMC

• 1 other identifier: Pro00089919
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the safety and antibody (germ fighters) response of experimental (investigational) vaccine candidates against the germ group A streptococcus when injected into the arm of healthy adults.

Conditions

Group A Streptococcal Infection

Outcome Measures

Primary Outcomes (1)

• Adverse Events

  Safety is the primary outcome, and will be measured by assessing the clinical symptoms and signs at each study visit and completing standard lab parameters (hematological and biochemical) as well as performing echocardiograms to assess for mitral regurgitation

  6 months after last dose of vaccine is administered

Secondary Outcomes (1)

• Immunogenicity

  6 months after last dose of vaccine is administered

Study Arms (3)

Vaccine p*17-K4S2 (50 µg/mL) Vaccine

EXPERIMENTAL

To evaluate the safety and immunogenicity of p\*17-CRM197 (25µg) + K4S2-CRM197 (6.25µg): TOTAL 31.25 µg

Biological: p*17-K4S2

J8-K4S2 (100 µg/mL ) Vaccine

EXPERIMENTAL

To evaluate the safety and immunogenicity J8-CRM197 (50µg) + K4S2-CRM197 (6.25µg): TOTAL 56.25 µg

Biological: J8-K4S2

Rabavert Vaccine

SHAM COMPARATOR

Comparator vaccine (RABAVERT)

Biological: Rabavert vaccine

Interventions

p*17-K4S2 BIOLOGICAL

Administer p\*17-K4S2 25 μg vaccine at 0, 3, and 6 weeks and evaluate the safety and antibody levels for a total of 6 months after the last injection. All vaccines will be administered intramuscularly

Vaccine p*17-K4S2 (50 µg/mL) Vaccine

J8-K4S2 BIOLOGICAL

Administer a vaccination schedule of J8-K4S2 50μg vaccine at 0, 3, and 6 weeks and evaluate the safety and antibody levels for a total of 6 months after the last injection. All vaccines will be administered intramuscularly

J8-K4S2 (100 µg/mL ) Vaccine

Rabavert vaccine BIOLOGICAL

Administer the standard Rabavert vaccine at 0, 3, and 6 weeks and evaluate the safety and antibody levels for a total of 6 months after the last injection. All vaccines will be administered intramuscularly. The Rabavert vaccine will be used as a control comparator as it has a similar approved dosing schedule to the investigational vaccines.

Rabavert Vaccine

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Able to understand the purpose and the procedures involved in this study and sign the informed consent form.
• Male or non-pregnant female adults, 18-45 years of age inclusive.
• Non-smoker and in good general health, as determined by medical screening evaluation, performed by PI or delegated sub-investigator no greater than 28 days before the first dose in the form of medical history, clinical laboratory tests and physical examination.
• Normal Electrocardiogram (ECG).
• Echocardiogram (ECHO) that is normal or with findings that are considered trivial and clinically insignificant such as 'Clinically insignificant/trivial mitral regurgitation
• Women must agree not to become pregnant during the trial. If they are sexually active, they must use an effective method of birth control, e.g. insertable, injectable, transdermal, or combination oral contraceptive approved by Health Canada combined with a barrier contraceptive and have negative results on a serum or urine pregnancy test done before administration of study medication.
• Intention to reside in the geographical area for next 10 months and not intending to travel overseas for at least 30 days following the last study vaccine administration.
• Agree not to participate in any other clinical trial during the trial.
• Agree not to donate blood for the duration of the trial.
• Agree to restrain from intensive physical exercise i.e. exercise that varies significantly from an everyday exercise routine, 3 days before and after (± 3 days) administration of each dose, including each interim visit for blood sample collection.
• Up to date on seasonal influenza vaccine and recommended COVID-19 vaccines and booster doses at the time of study enrolment.

You may not qualify if:

• Personal or family history of post-streptococcal disease (rheumatic fever or glomerulonephritis), or collagen-vascular disease
• Evidence of increased cardiovascular disease risk (defined as \>10%, 10- year risk using Framingham score - see Appendix 5). Risk factors include sex, age, systolic blood pressure (mm Hg), smoking status, body mass index (BMI, kg/m2), reported diabetes status and blood pressure
• Previous use of phentermine (appetite suppressant of the amphetamine and phenethylamine class), fenfluramine or dexfenfluramine known as Fen-Phen, anti-obesity medications (possible association with cardiac valvular abnormalities);
• Clinical diagnosis or evidence of recent group A streptococcal infection as measured by anti-streptolysin O or anti-DNase B levels exceeding 200 units;
• Positive group A streptococcus throat culture at screening or rapid antigen test on day of study product administration;
• Presence of significant acute infection requiring systemic antibiotic treatment within the 14 days prior to each product administration;
• Pregnant or breast feeding (all women will have a negative pregnancy test result prior to each study product administered);
• Immunized or intent to immunize with any vaccine or investigational agents within 30 days prior to enrolment through to 30 days following the last study vaccine administration, with the exception of licensed inactivated influenza vaccines and COVID-19 vaccines;
• Past significant reaction following any previous vaccination;
• History of hypersensitivity to any diphtheria toxoid or CRM197 containing vaccine;
• Presence of acute infectious disease or fever (e.g., sub-lingual temperature 38.5°C) within the five days prior to study product administration;
• Presence of current or suspected serious chronic diseases such as cardiac or autoimmune disease (HIV or other immunodeficiencies), insulin dependent diabetes, progressive neurological disease, severe malnutrition, acute or progressive hepatic disease, acute or progressive renal disease, psoriasis, rheumatoid arthritis, asthma, epilepsy or obsessive-compulsive disorder, skin carcinoma excluding non-spreadable skin cancers such as basal cell and squamous cell carcinoma;
• Evidence and any history of leukaemia, lymphoma, or neoplasm;
• Presence or suspicion of impaired immune system function. Currently receiving or having within the past three years received immunosuppressive therapy, including systemic steroids, ACTH or inhaled steroids in dosages that are associated with hypothalamic-pituitary-adrenal axis suppression, such as 1mg/kg/day of prednisone or its equivalent or chronic use of inhaled high potency corticosteroids \[budesonide 800 µg per day or fluticasone 750 µg\];
• Received blood, blood products or a parenteral immunoglobulin preparation in the past 12 weeks;

Sponsors & Collaborators

• University of Alberta: lead
• Griffith University: collaborator

Study Sites (1)

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Related Publications (1)

• Meier-Stephenson V, Hawkes MT, Burton C, Calcutt A, Davis C, Dooley J, Good M, Houghton M, Keeffe E, Kim K, Lepletier A, O'Neil C, Ogbuehi I, Ozberk V, Pandey M, Reynolds S, Seth A, Stokes W, Tse-Chang A, Tyrrell B, Tyrrell DL, Tyrrell GJ, Yaskina M. A phase 1 randomized controlled trial of a peptide-based group A streptococcal vaccine in healthy volunteers. Trials. 2024 Nov 19;25(1):781. doi: 10.1186/s13063-024-08634-4.

  PMID: 39563457 DERIVED

MeSH Terms

Conditions

Streptococcal Infections

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Vanessa Meier-Stephenson, MD, PhD

  University of Alberta

  PRINCIPAL INVESTIGATOR

• Michael Good, MD, PhD

  Griffith University

  PRINCIPAL INVESTIGATOR

• Michael Houghton, PhD

  University of Alberta

  PRINCIPAL INVESTIGATOR

• Lorne Tyrrell, MD PhD

  University of Alberta

  PRINCIPAL INVESTIGATOR

• Michael Hawkes, MD, PhD

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Stage 1: The investigators will verify the immediate safety of the J8-K4S2 and p\*17-K4S2 vaccines using a test dose in 10 volunteers. If there are no safety concerns following the Stage 1 challenge, the study will proceed to a phase 2 double-blind randomized clinical trial. The Rabavert vaccine will be used as a comparator against the 2 investigational arms.

Study Record Dates

• First Submitted: May 6, 2021
• First Posted: May 12, 2021
• Study Start: November 7, 2022
• Primary Completion: May 12, 2025
• Study Completion: May 12, 2025
• Last Updated: May 28, 2025

Record last verified: 2025-05

Locations

CA (1)