A Study on the Safety and Immune Response of a Urinary Tract Infection (UTI) Vaccine in Adults 18-64 Years of Age and Clinical Efficacy in Females 18-64 Years of Age

Официальное название

A Seamless Phase 1/2, Observer-blind, Randomized, Placebo-controlled, Multicenter Study to Assess the Safety and Immunogenicity of a UTI Vaccine When Administered to Adults 18 Through 64 Years of Age and Clinical Efficacy When Administered to Females 18 Through 64 Years of Age

Обзор

The purpose of this study is to assess safety, reactogenicity, and immune response of the candidate UTI vaccine compared to placebo in adults between and including 18-64 years of age (YOA), and to perform a preliminary evaluation of clinical efficacy in females between and including 18-64 YOA.

Подробное описание

This clinical trial consists of 2 parts. Part 1 will consist of antigen dose-escalation (start with least dose with gradual increase in dose) Safety Lead-In (SLI) in healthy participants. Part 2 (Proof of Principle \[PoP\]) will start after the safety review of all safety data in Part 1 and will consist of participants with history of at least 1 episode of urine culture confirmed E. coli UTI in the last 12 months prior to the study intervention administration.

Вмешательства

• Комбинированный продукт Candidate UTI vaccine low dose formulation 1
  Candidate UTI vaccine low dose formulation 1 administered intramuscularly according to a 0, 2 months administration schedule.
• Комбинированный продукт Candidate UTI vaccine low dose formulation 2
  Candidate UTI vaccine low dose formulation 2 administered intramuscularly according to a 0, 2 months administration schedule.
• Комбинированный продукт Candidate UTI vaccine medium dose formulation 1
  Candidate UTI vaccine medium dose formulation 1 administered intramuscularly according to a 0, 2 months administration schedule.
• Комбинированный продукт Candidate UTI vaccine medium dose formulation 2
  Candidate UTI vaccine medium dose formulation 2 administered intramuscularly according to a 0, 2 months administration schedule.
• Комбинированный продукт Candidate UTI vaccine high dose formulation 1
  Candidate UTI vaccine high dose formulation 1 administered intramuscularly according to a 0, 2 months administration schedule.
• Комбинированный продукт Candidate UTI vaccine high dose formulation 2
  Candidate UTI vaccine high dose formulation 2 administered intramuscularly according to a 0, 2 months administration schedule.
• Комбинированный продукт Candidate UTI vaccine HTD formulation 2
  Candidate UTI vaccine HTD formulation 2 administered intramuscularly according to a 0, 2 months administration schedule.
• Комбинированный продукт Placebo
  Placebo administered intramuscularly according to a 0, 2 months administration schedule.

Первичные конечные точки

• Part 1 and 2: Number of participants reporting solicited administration site adverse events (AEs) [Срок оценки: During the 7 days follow-up period post-Dose 1 (study intervention administered at Day 1)]
• Part 1 and 2: Number of participants reporting solicited administration site AEs [Срок оценки: During the 7 days follow-up period post-Dose 2 (study intervention administered at Day 61)]
• Part 1 and 2: Number of participants reporting solicited systemic AEs [Срок оценки: During the 7 days follow-up period post-Dose 1 (study intervention administered at Day 1)]
• Part 1 and 2: Number of participants reporting solicited systemic AEs [Срок оценки: During the 7 days follow-up period post-Dose 2 (study intervention administered at Day 61)]
• Part 1 and 2: Number of participants reporting unsolicited AEs [Срок оценки: During the 30 days follow-up period post-Dose 1 (study intervention administered at Day 1)]
• Part 1 and 2: Number of participants reporting unsolicited AEs [Срок оценки: During the 30 days follow-up period post-Dose 2 (study intervention administered at Day 61)]
• Part 1 and 2: Number of participants reporting any immediate unsolicited AEs [Срок оценки: During the 60 minutes follow-up period post-Dose 1 (study intervention administered at Day 1)]
• Part 1 and 2: Number of participants reporting any immediate unsolicited AEs [Срок оценки: During the 60 minutes follow-up period post-Dose 2 (study intervention administered at Day 61)]
• Part 1 and 2: Number of participants reporting serious adverse events (SAEs) [Срок оценки: From Day 1 (Dose 1 administration) until Day 426 (end of follow-up)]
• Part 1 and 2: Number of participants reporting potential immune-mediated diseases (pIMDs) leading to study withdrawal [Срок оценки: From Day 1 (Dose 1 administration) until Day 426 (end of follow-up)]

Вторичные конечные точки (3)

• Part 2: IR of the total number of occurrences of urine culture confirmed UTIs due to E. coli in the investigational group compared to the IR in placebo group [Срок оценки: From 14 days (Day 75) up to 12 months (Day 426) post-Dose 2]
• Part 2: IR of the first occurrence of a urine culture confirmed UTI due to E. coli in the investigational group compared to the IR in placebo group [Срок оценки: From 14 days post-Dose 1 (Day 15) and up to the day before administration of Dose 2 (Day 60) or, for participants receiving only Dose 1, up to the end of the study (Day 426)]
• Part 2: IR of the total number of occurrences of urine culture confirmed UTIs due to E. coli in the investigational group compared to the IR in placebo group [Срок оценки: From 14 days post-Dose 1 (Day 15) and up to the day before administration of Dose 2 (Day 60) or, for participants receiving only Dose 1, up to the end of the study (Day 426)]

Критерии участия

Критерии включения

• Participants, who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Written informed consent obtained from the participant prior to performance of any study-specific procedure.
• Female participants of non-childbearing potential may be enrolled in the clinical study.
• Female participants of childbearing potential may be enrolled in the clinical 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 treatment period and for at least 1 month after completion of the study intervention administration series.
• Blood sample for simultaneous follicle stimulating hormone (FSH) and estradiol levels may be collected.

Additional inclusion criterion only for participants in Part 1 of the study (SLI):

• Female and male between and including 18 through 64 YOA at the time of ICF signature.
• Healthy participants, according to medical history, laboratory assessment and clinical examination at Screening Visit.

Additional inclusion criterion only for participants in Part 2 of the study (PoP):

• Females between and including 18 through 64 YOA at the time of ICF signature.
• Female participants with documented history of at least 1 episode of urine culture confirmed E. coli uncomplicated UTI in the last 12 months prior to study vaccine administration.

Критерии исключения

Medical conditions:

• History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention(s).
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• Hypersensitivity to latex.
• History of pIMD.
• Acute or chronic clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
• History of endocrinologic, hematologic, metabolic, urologic, dermatologic, or gastrointestinal conditions that, in the opinion of the investigator, places the participant at unacceptable risk or would make adhering to study procedures for the duration of the study difficult.
• Recurrent history or uncontrolled neurological disorders or any neuroinflammatory (including, but not limited to demyelinating disorders, encephalitis or myelitis of any origin), congenital neurological conditions, encephalopathies, or seizures.
• 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.
• Condition that in the judgment of the investigator would make intramuscular injection unsafe.
• Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study.

Additional exclusionary medical conditions only for participants in Part 1 of the study (SLI):

• Any clinically significant hematologic and/or biochemical laboratory abnormality at Screening Visit.

Additional exclusionary medical conditions only for participants in Part 2 of the study (PoP):

• The participant has UTI that is known or suspected to be due to fungal, parasitic, or viral pathogens; or known or suspected to be due to Pseudomonas aeruginosa or any Enterobacter species.
• The participant has symptoms known or suspected to be caused by another disease process, such as asymptomatic bacteriuria, overactive bladder, chronic incontinence, or chronic interstitial cystitis, that may interfere with the clinical efficacy assessments.
• The participant has an anatomical or physiological anomaly that predisposes the participant to UTIs or may be a source of persistent bacterial colonization, including calculi, obstruction or stricture of the urinary tract, primary renal disease or neurogenic bladder, or the participant has a history of anatomical or functional abnormalities of the urinary tract.
• The participant has an indwelling catheter, nephrostomy, ureteral stent, or other foreign material in the urinary tract.
• The participant who, in the opinion of the investigator, has an otherwise complicated UTI or has an active upper UTI.
• Use of any investigational or non-registered product (drug, vaccine or invasive medical device) other than the study intervention(s) during the period beginning 30 days before the first dose of study intervention(s) (Day -29 to Day 1), or their planned use during the study period.
• Previous administration of a vaccine or immunostimulant targeting rUTI.
• Participants currently on a prophylactic agent for rUTI (including antibiotics, methenamine, D-mannose).
• Planned administration and/or administration of a vaccine not foreseen by the study protocol in the period starting 15 days before the first dose and ending 15 days after the last dose of study intervention(s) administration.
• Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 90 days before the study intervention or planned administration during the study period.
• Chronic administration of immune-modifying drugs (defined as more than 14 consecutive days in total) and/or planned use of long-acting immune modifying treatments at any time up to the end of the study.

• Up to 3 months prior to the study intervention administration:
• For corticosteroids, this will mean prednisone equivalent >=20 mg/day for adult participants. Inhaled and topical steroids are allowed.
• Up to 3 months prior to study intervention administration: long-acting immune-modifying drugs including among others immunotherapy (e.g., TNF-inhibitors), monoclonal antibodies, antitumoral medication.
• 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.
• Female participant planning to become pregnant or planning to discontinue contraceptive precautions before 1 month after completion of the study intervention administration series.
• History of chronic alcohol consumption and/or drug abuse, based on investigator judgment.
• Persons under guardianship or trusteeship.
• Persons deprived of liberty.
• Any study personnel or their immediate dependents, family, or household members.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Тройное слепое

Основная цель

Профилактика

Центры проведения

США · 6 центров

• GSK Investigational Site — Lenexa
• GSK Investigational Site — Secaucus
• GSK Investigational Site — Rochester
• GSK Investigational Site — Weatherford
• GSK Investigational Site — Seattle
• GSK Investigational Site — Wenatchee

ЮАР · 2 центра

• GSK Investigational Site — Johannesburg
• GSK Investigational Site — Soshanguve

Идентификаторы

NCT: NCT06702449 · 219685

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗