Peptide-based GAS Vaccine for Streptococcal Infections

Overseen By Avi Seth

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Alberta

Must not be taking: Fen-Phen, Immunosuppressants, others

Disqualifiers: Cardiac disease, Autoimmune disease, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new vaccines to evaluate their safety and effectiveness in boosting the body's defenses against strep infections. Strep, short for group A streptococcus, is a bacterium that can cause throat infections and other illnesses. The trial includes two experimental vaccines, J8-K4S2 and p*17-K4S2, and one standard vaccine, Rabavert, for comparison. It seeks healthy non-smokers who have not had recent infections or participated in other clinical trials and who plan to remain in the area for the next 10 months. As a Phase 1 and Phase 2 trial, this research aims to understand how the vaccines work in people and measure their effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on psychiatric drugs, your condition must be stable for at least 3 months before joining the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the experimental vaccines J8-K4S2 and p*17-K4S2 appear safe. Early studies have not identified any major safety issues with the J8-K4S2 vaccine. Most participants tolerated it well, suggesting its safety for people. Similarly, preclinical tests for the p*17-K4S2 vaccine did not reveal any harmful effects on the heart or nervous system, indicating a positive safety profile.

Both vaccines remain in the early stages of human testing. Researchers continue to gather information, but so far, the vaccines seem well-tolerated. This is important for those considering joining a trial, as it suggests the vaccines are unlikely to cause serious harm. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard antibiotics used to treat streptococcal infections, the peptide-based vaccines J8-K4S2 and p*17-K4S2 target the bacteria directly by stimulating the immune system to recognize and fight the infection. These vaccines use a unique mechanism involving specific peptide sequences, J8 and p*17, combined with a carrier protein, CRM197, designed to trigger a strong immune response. Researchers are excited because these vaccines have the potential not only to treat but also to prevent streptococcal infections by training the immune system to recognize and attack the bacteria before illness occurs.

What evidence suggests that this trial's treatments could be effective for streptococcal infections?

Research has shown that the J8-K4S2 vaccine, one of the investigational treatments in this trial, is safe and can trigger an immune response in early trials. Initial studies found that this vaccine helps the body defend against Group A Streptococcus without causing major side effects. Similarly, the p*17-K4S2 vaccine, another treatment option in this trial, has demonstrated its ability to build protective immunity in both animals and early human tests. Preclinical data revealed strong immune responses, suggesting the vaccine could effectively prevent infections. Both vaccines have been well-tolerated, with no serious safety concerns reported so far. These results are encouraging steps toward a vaccine against Streptococcal infections. ^{1 2 4 6 7}

Who Is on the Research Team?

Michael Good, MD, PhD

Principal Investigator

Griffith University

Vanessa Meier-Stephenson, MD, PhD

Principal Investigator

University of Alberta

Michael Houghton, PhD

Principal Investigator

University of Alberta

Lorne Tyrrell, MD PhD

Principal Investigator

University of Alberta

Michael Hawkes, MD, PhD

Principal Investigator

University of Alberta

Are You a Good Fit for This Trial?

Healthy adults aged 18-45, non-smokers with good health as confirmed by medical screening. Participants must not be pregnant or breastfeeding, agree to use effective birth control, and have up-to-date vaccinations for influenza and COVID-19. They should not have a recent history of streptococcal infection or immunosuppressive therapy, nor plan to travel overseas soon after vaccination.

Inclusion Criteria

I am up to date with my flu and COVID-19 vaccines.

Agree not to donate blood for the duration of the trial

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

Exclusion Criteria

You have been diagnosed with severe mental health conditions like schizophrenia or bipolar disorder that significantly affect your daily life.

I have previously used appetite suppressants like phentermine or Fen-Phen.

I haven't needed antibiotics for a serious infection in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Safety Assessment

Initial safety of J8-K4S2 and p*17-K4S2 vaccines is assessed with test doses in small groups of participants

6 weeks

Multiple visits for each participant

Treatment

Participants receive repeated doses of J8-K4S2 or p*17-K4S2 vaccines, or a comparator rabies vaccine

6 weeks

3 visits (in-person) for each participant

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Regular visits for safety and immunogenicity assessments

What Are the Treatments Tested in This Trial?

Interventions

• J8-K4S2
• p*17-K4S2
• Rabavert vaccine

Trial Overview The trial is testing the safety and immune response of two experimental vaccines (p*17-K4S2, J8-K4S2) against Group A Streptococcus compared to an existing Rabavert vaccine. Healthy participants will receive injections in their arm and their antibody levels will be monitored.

How Is the Trial Designed?

Group I: Vaccine p*17-K4S2 (50 µg/mL) Vaccine Experimental Treatment 1 Intervention

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

Group II: J8-K4S2 (100 µg/mL ) Vaccine Experimental Treatment 1 Intervention

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

Group III: Rabavert Vaccine Placebo Group 1 Intervention

Comparator vaccine (RABAVERT)

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Griffith University

Collaborator

Trials

18

Recruited

22,900+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39563457/

A phase 1 randomized controlled trial of a peptide-based ... This Strep A vaccine clinical trial aims to investigate safety and immunogenicity of two novel conjugated peptide-based vaccines, J8-KS42 and p*17-K4S2.

2. nature.com nature.com/articles/s41541-023-00730-x

Update on the development of Group A Streptococcus ... The path to Group A Streptococcus vaccines: World Health Organization research and development technology roadmap and preferred product characteristics.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04882514?term=AREA%5BBasicSearch%5D(AREA%5BConditionSearch%5D(Streptococcal)%20AND%20AREA%5BLastUpdatePostDate%5D%20RANGE%5B2020-01-11,MAX%5D)&rank=8

A Trial of a Peptide-based Group A Streptococcal (GAS ... 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 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11577953/

A phase 1 randomized controlled trial of a peptide-based ... This Strep A vaccine clinical trial aims to investigate safety and immunogenicity of two novel conjugated peptide-based vaccines, J8-KS42 and p* ...

5. cdn.who.int cdn.who.int/media/docs/default-source/immunization/pdvac/pdvac-2022/gas_masterdeck.pdf?sfvrsn=856a654_2

WHO expert review of Group A Streptococcus vaccines. Initial preclinical efficacy and safety results and, in some cases, human safety and immunogenicity data, are encouraging. • Many candidates are ...

6. nature.com nature.com/articles/s41598-020-80508-6

Preclinical safety and immunogenicity of Streptococcus ... We have developed two candidate vaccines to protect against multiple strains of Strep A infections. The candidates are combinatorial synthetic peptide vaccines.

7. nccid.ca nccid.ca/debrief/group-a-streptococcus/

Group A Streptococcus Group A streptococcus (GAS) is responsible for a range of diseases in humans. These diseases include strep throat (acute pharyngitis) and skin and soft ...