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Group A Streptococcal InfectionPhase 1/2NCT04882514

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

A Phase 1/2 study testing p*17-K4S2, J8-K4S2 and Rabavert vaccine in people with Group A Streptococcal Infection, run by University of Alberta at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for
Group A Streptococcal Infection
What is being tested?
p*17-K4S2, J8-K4S2 and Rabavert vaccine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
30 participants
Where
1 siteCanada
Study dates
7 Nov 2022to 12 May 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 45 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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;
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  • 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;
  • Evidence of bleeding diathesis or any condition that may be associated with a prolonged bleeding time;
  • Known inherited genetic anomaly (known as cytogenic disorders) e.g., Down's syndrome;
  • Evidence of any condition that, in the opinion of the clinical investigator, might interfere with the evaluation of the study objectives or pose excessive risks to participants;
  • Findings of definite, probable, or possible rheumatic heart disease (RHD), definite or probable acute rheumatic fever (ARF).
  • Inadequate echocardiographic windows for assessment.
  • Echocardiographic findings such as: Cardiac Chambers: left ventricular dilatation (based on LV diameter > 29mm/m2 to BSA); left ventricular dysfunction (Ejection Fraction < 50%; left ventricular hypertrophy (LV wall thickness > 11mm); Right ventricular dysfunction or dilatation (Subjective assessment);
  • Cardiac Valves/Haemodynamic Findings: Clinically significant mitral regurgitation defined: at the discretion of the cardiologist and/or effective regurgitant orifice area of >10mm2; Any degree of valvular stenosis or left ventricular outflow tract obstruction; Pulmonary hypertension (defined as an estimated right ventricular systolic pressure of >30 mmHg, calculated using the peak tricuspid regurgitant jet velocity method);
  • Any aortic regurgitation;
  • Pericardium: greater than trivial pericardial fluid (trivial defined as < 5mm and not circumferential);
  • Pre-existing significant structural valve disease (for example, but not limited to bicuspid aortic valve regardless of haemodynamic effect, mitral valve prolapse regardless of severity of regurgitation, pulmonary stenosis);
  • Other significant congenital lesions (for example, but not limited to aortic coarctation, septal defect, excluding patent foramen ovale (NOTE: findings considered normal developmental variation, specifically including patient foramen ovale and prominent Eustachian valve will not be considered exclusion criteria;
  • Clinical or sub-clinical acute post-streptococcal glomerulonephritis (APSGN),
  • Clinically significant abnormal laboratory results e.g., CBC with differential and platelets, AST, ALT, creatinine, fasting blood sugar, electrolytes (including sodium, potassium, chloride, and bicarbonate);
  • The participant has a diagnosis of schizophrenia, bi-polar disease, or other severe (disabling) chronic psychiatric diagnosis;
  • The participant has been hospitalized within the past 5 years prior to enrollment for psychiatric illness, history of suicide attempt or confinement for danger to self or others;
  • The participant is receiving psychiatric drugs but their psychiatric conditions is not stabilized. Participants who are receiving a single antidepressant drug and are stable for at least 3 months prior to enrollment without decompensating are allowed enrollment into the study; *aripiprazole, clozapine, ziprasidone, haloperidol, molindone, loxapine, thioridazine, thiothixene, pimozide, fluphenazine, risperidone, mesoridazine, quetiapine, trifluoperazine, trifluopromazine, chlorprothixene, chlorpromazine, perphenazine, olanzapine, carbamazepine, divalproex sodium, lithium carbonate or lithium citrate. This is not an absolute contra-indication and clinician judgment will be used to assess the likelihood that this will compromise trial participation and follow-up.
  • The participant has a history of alcohol or drug abuse in the 5 years prior to enrollment. This is not an absolute contra-indication and clinician judgment will be used to assess the likelihood that this will compromise trial participation and follow-up.

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • University of Alberta Hospital

    Edmonton, Alberta, T6G 2B7

Other trials in Canada

About this study

Official title: A Randomized Double Blinded Within Dose, Controlled, Safety and Immunogenicity Study of GAS Vaccine Candidate in Healthy Individuals.

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.

Read the detailed description

Group A streptococcus (GAS) is a bacteria that cause a number of different infections that range from mild illnesses to deadly diseases. It is estimated 500,000 deaths occur worldwide each year from GAS. To address these high rates of disease, the investigators want to test a new potential vaccine for safety and immune response in healthy participants.

The investigators will verify the immediate safety of the J8-K4S2 and p*17-K4S2 vaccines using a test dose in 10 volunteers. With respect to J8-K4S2 vaccine, safety of one of the peptide components (J8) has previously been established. Therefore, The investigators will begin with a test dose of J8-K4S2. The first IM injection of J8-K4S2 will be administered to the first participant. The investigators will wait two days, assess safety, then administer J8-K4S2 to a second participant. The investigators will wait two days, assess safety, then administer J8-K4S2 to a third participant. This process will continue until 5 participants have received a test dose of J8- K4S2. If there are no safety concerns with the first 5 participants, the investigators will have shown the preliminary safety of the K4S2 component. If the J8-K4S2 vaccine is well-tolerated, second and third doses of J8-K4S2 will be administered at 3 and 6 weeks, testing the safety of repeated dosing.

The investigators will next administer p*17-K4S2 to a sixth participant, wait two days, assess safety, and administer p*17-K4S2 to a seventh participant. The investigators will wait two days, assess safety, then administer p*17-K4S2 to an eighth participant. This process will continue until 5 participants have received a test dose of p*17-K4S2. If there are no safety concerns, the investigators will have shown the preliminary safety of the p*17 component. If the p*17-K4S2 peptide vaccine is well-tolerated, second and third doses of p*17-K4S2 will be administered at 3 and 6 weeks, testing the safety of repeated dosing.

Following this stage 1 challenge, if no safety concerns arise, the study will proceed to stage 2, with randomized allocation to each arm for 20 more participants who will receive J8-K4S2 vaccine (n=5), p*17-K4S2 vaccine (n=5), and 10 who receive comparator (rabies) vaccine.

Being tested
p*17-K4S2, J8-K4S2, Rabavert vaccine
Medical subject headings
Streptococcal Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • p*17-K4S2Biological

    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

  • J8-K4S2Biological

    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

  • Rabavert vaccineBiological

    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.

Study groups in NCT04882514
Study groupRoleWhat they receive
Vaccine p*17-K4S2 (50 µg/mL) VaccineExperimentalTo evaluate the safety and immunogenicity of p*17-CRM197 (25µg) + K4S2-CRM197 (6.25µg): TOTAL 31.25 µg
Receives: Biological: p*17-K4S2
J8-K4S2 (100 µg/mL ) VaccineExperimentalTo evaluate the safety and immunogenicity J8-CRM197 (50µg) + K4S2-CRM197 (6.25µg): TOTAL 56.25 µg
Receives: Biological: J8-K4S2
Rabavert VaccineSham comparatorComparator vaccine (RABAVERT)
Receives: Biological: Rabavert vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 6 months after last dose of vaccine is administered

Secondary outcomes (1)

  1. Immunogenicity

    Antibody titre levels will be measured prior to each vaccine dose administered as well as 2 after the last dose and 6 months after the last dose

    Measured: 6 months after last dose of vaccine is administered

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 May 2021
  2. Study start7 Nov 2022
  3. Primary completion12 May 2025
  4. Study completion12 May 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04882514
Sponsor's protocol ID
Pro00089919
Status last verified
May 2025
First submitted
6 May 2021
Last updated
28 May 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 39563457

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing p*17-K4S2, J8-K4S2 and Rabavert vaccine in people with Group A Streptococcal Infection, run by University of Alberta at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse Events (time frame: 6 months after last dose of vaccine is administered). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04882514, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2025.

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