Safety and immune response testing of a 4-component Strep A vaccine with Alum or AS37 in healthy 18–25-year-olds

A Phase 1 Randomized, Placebo-controlled, Observer-blind Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of the GSK 4-component Vaccine Against Group A Streptococcus Pyogenes (Strep A) With Alum or AS37 in Healthy Adults 18 to 25 Years of Age in Australia

This will test three dose levels of two new Strep A vaccine formulations (one with Alum, one with AS37) in healthy 18–25-year-olds to see if they are safe and trigger immune responses.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 108 (estimated)
• Ages: 18 Years to 25 Years
• Sex: All
• Sponsor: GlaxoSmithKline (industry)
• Drugs / interventions: infliximab, prednisone
• Locations: 2 sites (Botany, New South Wales and 1 other locations)
• Trial ID: NCT07085702 on ClinicalTrials.gov

What this trial studies

This first-in-human Phase 1 trial gives healthy adults aged 18–25 three doses of a 4-component Strep A vaccine formulated with either aluminum hydroxide (Alum) or the AS37 adjuvant. Low, medium, and high dose levels for each formulation will be administered in sequence with monitoring between cohorts for immediate reactions and other safety signals. Participants will record reactogenicity (including via electronic diaries) and provide blood samples to measure antibody responses. Results will define tolerability and preliminary immunogenicity to guide dose selection for later-phase trials.

Who should consider this trial

Good fit: Healthy male or female adults aged 18–25 who can comply with study visits and procedures and meet screening criteria, including nonchildbearing status or agreed contraception for women of childbearing potential.

Not a fit: People outside the 18–25 age range, pregnant or breastfeeding women, or those with significant medical conditions or immunosuppression are unlikely to receive benefit from this Phase 1 trial.

Why it matters

Potential benefit: If successful, this vaccine could prevent Strep A infections and reduce complications such as invasive disease and post-infectious sequelae.

How similar studies have performed: This specific 4-component Strep A vaccine is being tested in humans for the first time, though aluminum adjuvants and newer adjuvants like AS37 have been used successfully in other vaccine development programs.

Eligibility criteria

Inclusion Criteria:

* Participants, who, in the opinion of the Investigator, can and will comply with the requirements of the protocol (e.g., completion of electronic diaries \[eDiaries\], return for follow-up visits).
* Written or witnessed/thumb-printed informed consent obtained from the participant prior to performance of any study-specific procedure.
* Healthy participants as established by medical history, clinical examination, and laboratory assessments.
* Satisfies all screening requirements.
* Male and female participants between and including 18 and 25 years of age at the time of informed consent.
* Female participants of nonchildbearing potential may be enrolled in the study. Nonchildbearing potential is defined as premenarche, postmenopause, or had current bilateral tubal ligation or occlusion, hysterectomy, or bilateral ovariectomy.
* Female participants who are of childbearing potential may be enrolled in the study if the participant:

  * has practiced adequate contraception for 1 month prior to study intervention administration, and
  * has a negative pregnancy test on the day of study intervention administration, and
  * has agreed to continue adequate contraception during the entire study intervention administration period and for 1 month after completion of the study intervention administration series.
* Male participants who are sexually active with a female partner of childbearing potential are eligible to participate if they agree to have their partner use a highly effective method of contraception for 1 month prior to the first study intervention administration until 1 month after completion of the study intervention administration series.
* Male participants must refrain from donating sperm for 1 month prior to the first study intervention administration until 1 month after completion of the study intervention administration series.
* Participants seronegative for human immunodeficiency virus (HIV), hepatitis B, and hepatitis C at Screening.

Exclusion Criteria:

* History of rheumatic fever or rheumatic heart disease during the lifetime of the participant as confirmed during interview with the participant or as documented in medical records.
* Recent history of pharyngitis in the last four (4) weeks will be excluded. These participants can be rescreened once the recent pharyngitis passes the 4-weeks period. Participants with symptoms of acute pharyngitis at Screening will be tested with a Strep A rapid antigen test. Those with positive results will be excluded.
* Progressive, unstable, or uncontrolled clinical conditions.
* History (known or suspected) of any reaction or hypersensitivity likely to be exacerbated by any component of the study interventions.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* Hypersensitivity (e.g., allergy) to medicinal products or medical equipment anticipated to be used in this study.
* Clinical conditions that represents a contraindication for IM vaccination or blood draws.
* Any behavioral or cognitive impairment or psychiatric disease that, in the opinion of the Investigator, may interfere with the participant's ability to participate in the study.
* Acute disease and/or fever (defined as temperature \>=38.0°C) at the time of enrollment.
* Any Grade \>=2 and/or clinically significant hematological and/or biochemical laboratory abnormality.
* Any echocardiographic/Doppler Echo findings consistent with carditis at Screening.
* Recurrent history or uncontrolled neurological disorders or seizures.
* Medical history or family history of autoimmune disease and other pIMDs.
* Family history of acute rheumatic fever.
* Acute or chronic illness, or clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality.
* Any other clinical condition that might pose additional risk to the participant due to participation in the study.
* Administration of long-acting immune-modifying drugs (e.g., infliximab) at any time prior to the administration of the first dose of study intervention(s) or planned administration during the study period.
* Prior receipt of an experimental Strep A vaccine.
* Use of any investigational or nonregistered product (drug, vaccine, or medical device) other than the study interventions during the period starting 30 days before the first dose of study intervention (Day -30 to Day 1), or their planned use during the study period.
* Receipt of a vaccine not foreseen by the study protocol administered during the period starting at 21 days before the first dose of study intervention (28 days before the first dose, in case of live vaccines) and ending after the last dose of study intervention administration.
* Administration of immunoglobulins and/or any blood products or plasma derivatives, or bone marrow transplantation, during the period starting 3 months before administration of the first dose of study intervention(s) or planned administration during the study period.
* Chronic administration (defined as \>14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first dose of study intervention. For corticosteroids, this means prednisone equivalent \>=20 mg/day for adult participants. Inhaled, topical, intra-articular, and intranasal steroids are allowed.
* Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention (drug, vaccine, or invasive medical device).
* Pregnant or lactating female participant.
* Participant who is planning to become pregnant or planning to discontinue contraceptive precautions.
* History of or current chronic alcohol consumption and/or drug abuse.
* Any study personnel or their immediate dependents, family, or household members.

Where this trial is running

Botany, New South Wales and 1 other locations

• GSK Investigational Site — Botany, New South Wales, Australia (RECRUITING)
• GSK Investigational Site — Camberwell, Victoria, Australia (RECRUITING)

Study contacts

• Principal investigator: King C Cheung — Emeritus Research
• Study coordinator: US GSK Clinical Trials Call Center

Conditions: Streptococcal Infections, Strep A, Streptococcus pyogenes, Safety, Reactogenicity, Immunogenicity, Healthy Adults, Australia