Safety and Immunogenicity Study of IP-QSV Vaccine in Healthy Adults/Adolescents, Children and Infants

Официальное название

A Phase 1/2a, Randomized, Observer-blind, Age-descending, Dose Finding Study to Evaluate the Safety and Immunogenicity of Institut Pasteur Quadrivalent Shigella Vaccine (IP-QSV) for Intramuscular Administration in Healthy Adults/Adolescents, Children and Infants

Обзор

The goal of this phase 1/2a, randomized, observer-blind, age-descending, dose-finding trial is to evaluate the safety and immunogenicity of a quadrivalent synthetic oligosaccharide-based Shigella vaccine (adjuvanted IP-QSV) in adults, children, and infants in Mali. This first-in-human study is intended to obtain initial data on the safety of the adjuvanted IP-QSV vaccine and its effect on immune responses in a Shigella-endemic region.

Подробное описание

this is phase 1/2a, randomized, observer-blind, age-descending, dose-finding trial to evaluate the safety and immunogenicity of a quadrivalent synthetic oligosaccharide-based Shigella vaccine (adjuvanted IP-QSV) in adults, children, and infants in Mali

A total of 370 healthy participants aged 6 months to 45 years in Mali will be enrolled and randomly assigned in a 2:1 or 2:2:1 ratio. The study groups are as follow

* Group A (18-45 years): one dose of 30 µg IP / placebo in a 2:1 ratio * Group B (2-5 years): two doses of 10 µg IP / placebo administered 3 months apart in a 2:1 ratio * Group C (2-5 years): one dose of 30 µg IP / placebo in a 2:1 ratio * Group D (6-8 months): three doses of 2 µg IP / placebo administered at 3- and 6-month intervals in a 2:1 ratio * Group E (6-8 months): three doses of 10 µg IP or placebo administered at 3- and 6-month intervals in a 2:2:1 ratio * Group F (9-11 months): two doses of 10 µg IP / placebo administered 6 months apart in a 2:1 ratio * Group G (6-8 months): two doses of 30 µg IP or placebo administered 9 months apart in a 2:1 ratio.

The DSMB must review the safety data of each group and approve study continuation before investigational product administration of the next group is initiated.

Participants will attend between 5 and 11 scheduled study visits, including blood sampling for immunogenicity assessments and safety evaluations. Blood samples will be collected at screening and at multiple time points throughout the study to assess immune responses and overall health status. Baseline laboratory assessments will include HIV testing, hepatitis screening, complete blood counts, and renal and liver function tests. Women of childbearing potential will undergo pregnancy testing at screening.

Serious adverse events (SAEs) will be reported and followed until resolution or stabilization. Participants will be instructed to contact the study team immediately if they experience any serious adverse event.

The study will monitor for SAEs, including hospitalization, death, or significant disability, occurring during the study, regardless of whether they are considered related to the study vaccine. Immediate reactions occurring within 0.5 - 1 hours after vaccination will be monitored to detect allergic or other acute responses. Solicited mild to moderate adverse events, such as nausea, fever, and diarrhea, will be recorded for up to 7 days after each vaccination.

Вмешательства

• Биопрепарат 30μg IP-QSV
  A mix of the four synthetic OS-based conjugates, each independently targeting SF 2a, 3a, 6, or Sson, and using tetanus toxoid as carrier protein. 30 ㎍ of IP-QSV adjuvanted with Aluminum phosphate.
• Другое Placebo
  Sterile 0.9% sodium chloride.
• Биопрепарат 10μg IP-QSV
  A mix of the four synthetic OS-based conjugates, each independently targeting SF 2a, 3a, 6, or Sson, and using tetanus toxoid as carrier protein. 30 ㎍ of IP-QSV adjuvanted with Aluminum phosphate.
• Биопрепарат 2μg IP-QSV
  A mix of the four synthetic OS-based conjugates, each independently targeting SF 2a, 3a, 6, or Sson, and using tetanus toxoid as carrier protein. 30 ㎍ of IP-QSV adjuvanted with Aluminum phosphate.

Первичные конечные точки

• Serious adverse events (SAEs) and adverse events of special interest (AESIs) and medically attended adverse event (MAAE) [Срок оценки: through study completion, an average of 6 months]
• Immediate adverse events [Срок оценки: Within 30 minutes post each dose]
• Solicited adverse events [Срок оценки: Within 7 days post each dose]
• Unsolicited adverse events [Срок оценки: Within 28 days post each dose]
• GMT of serum IgG against SF 2a, SF3a, SF6 & Sson LPS at 4 weeks and at 6 months post primary IP administration of IP-QSV 2/10/30μg OS-equivalent dosages in infants aged 6-8 months [Срок оценки: Baseline, at 4 weeks, and at 6 months post primary IP administration series]
• Seroconversion of serum IgG against SF 2a, SF3a, SF6 & Sson LPS at 4 weeks and at 6 months post primary IP administration of IP-QSV 2/10/30μg OS-equivalent dosages in infants aged 6-8 months [Срок оценки: at 4 weeks and at 6 months post primary IP administration series]

Вторичные конечные точки (8)

• GMT of serum IgG against SF 2a, SF3a, SF6 & Sson LPS at 4 weeks and at 6 months post full IP administration of IP-QSV 2/10/30μg OS-equivalent dosages in infants aged 6-8 months [Срок оценки: Baseline, at 4 weeks, and at 6 months post full IP administration series]
• Seroconversion of serum IgG against SF 2a, SF3a, SF6 & Sson LPS at 4 weeks and at 6 months post full IP administration of IP-QSV 2/10/30μg OS-equivalent dosages in infants aged 6-8 months [Срок оценки: Baseline, at 4 weeks, and at 6 months post full IP administration series]
• GMT of serum IgG against SF 2a, SF3a, SF6 & Sson LPS at 4 weeks post each dose of full IP administration series and at 6 months post full IP administration of IP-QSV 10μg OS-equivalent dosages in infants aged 9-11 month [Срок оценки: Baseline and at post each dose of full IP administration series]
• Seroconversion of serum IgG against SF 2a, SF3a, SF6 & Sson LPS at 4 weeks post each dose of full IP administration series and at 6 months post full IP administration of IP-QSV 10μg OS-equivalent dosages in infants aged 9-11 months [Срок оценки: at post each dose of full IP administration series]
• GMT of SF2a, SF3a, SF6 & Sson -specific serum bactericidal antibodies (SBA) at 4 weeks and at 6 months post primary IP and full IP administration of IP-QSV 2/10/30μg OS-equivalent dosages in infants aged 6-11 months [Срок оценки: Baseline, at 4 weeks and at 6 months post primary and full IP administration series]
• Seroconversion of SF2a, SF3a, SF6 & Sson -specific serum bactericidal antibodies (SBA) at 4 weeks and at 6 months post primary IP and full IP administration of IP-QSV 2/10/30μg OS-equivalent dosages in infants aged 6-11 months [Срок оценки: at 4 weeks and at 6 months post primary and full IP administration series]
• GMT of serum IgG against SF2a, SF3a, SF6 & Sson LPS at 4 weeks post each dose of full IP administration series of IP-QSV 10/30μg OS-equivalent dosages in adults aged 18-45 years and children aged 2-5 years [Срок оценки: Baseline and at 4 weeks post each dose of full IP administration series]
• Seroconversion of serum IgG against SF2a, SF3a, SF6 & Sson LPS at 4 weeks post each dose of full IP administration of IP-QSV 10/30μg OS-equivalent dosages in adults aged 18-45 years and children aged 2-5 years [Срок оценки: at 4 weeks post each dose of full IP administration series]

Критерии участия

Критерии включения

• Individuals aged 18-45 years in Group A, 2-5 years in Groups B and C, 6-8 months in Groups D, E and G , and 9-11 months in Group F
• Participants/ Participants' Legally Acceptable representative (LAR) willing to provide written informed consent to participate in the study voluntarily
• Participants who can comply with the study requirements
• Individuals in good health as determined by the outcome of medical history, physical examination, and the clinical judgment of the investigator

Критерии исключения

• Known history or allergy to investigational vaccine components or other medications, or any other allergies deemed by the investigator to increase the risk of an adverse event if they were to participate in the trial
• Individuals with major congenital abnormalities, developmental disorders, genetic defects, or severe malnutrition, among other conditions which in the opinion of investigator may affect the participant's participation in the study
• Known history of immune function disorders including immunodeficiency diseases (known HIV infection¥ or other immune function disorders) which in the opinion of investigator may affect the participant's participation in the study or interfere with the assessment of the study objectives
• Use of systemic steroids within past 6 months (>10 mg/day prednisone equivalent for periods exceeding 2 consecutive weeks), or receive chemotherapy, radiation therapy or other immunosuppressive drugs within the past 6 months
• Any abnormality or chronic disease which in the opinion of the investigator might be detrimental for the safety of the participant and interfere with the assessment of the study objectives
• Individuals with behavioral or cognitive impairment or psychiatric disease or neural disorders that, in the opinion of the investigator, could interfere with the participant's ability to participate in the trial
• Individuals with splenectomy
• Individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time resulting in contraindication for IM injections/blood extractions
• Receipt of blood, blood-derived products, or immunoglobulin products in the past 3 months
• Individuals who have received other vaccines from 4 weeks prior to the first dose of investigational product administration or planned to receive any vaccine within 4 weeks post any dose of the investigational product
• Individuals with active or known previous culture-proven Shigella infection
• Individuals who have household contact with/and /or intimate exposure to an individual with laboratory confirmed Shigella infection
• Previous participation in any study in which a Shigella-vaccine candidate was administered
• Individuals with a history of severe diarrhea in the last 6 months requiring care at a medical facility lasting 24 hours or more
• Individuals with a history of clinically significant gastrointestinal disorders or with any history of frequent diarrhea, nausea or emesis, within the last 6 months
• Individuals aged below 5 years with Weight for Height Z score and/or Height for Age Z score of less than -3
• Any female participant who is lactating or pregnant#
• Females of childbearing potential who do not agree to use an effective birth control method\* for at least 4 weeks before the screening and up to 12 weeks after the investigational product administration
• Individuals enrolled in another clinical trial within 6 months prior to enrollment, concomitantly enrolled or scheduled to be enrolled in another trial during study period
• Individuals who are research staff involved with the clinical trial or household members of research staff
• As per Investigator's medical judgement, an individual could be excluded from the study despite meeting all inclusion/exclusion criteria mentioned above
• Special Conditions for Children Aged 24 Months and Below: For such children, additional exclusion criteria include difficult birth, resuscitation after suffocation, a history of neurological damage, premature birth (delivery before the 37th week of gestation), and low birth weight (less than 2500 grams)
• Clinically significant abnormal findings in blood tests during the screening

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

Четверное слепое

Основная цель

Профилактика

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07666750 · IVI IP QSV

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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