Immune Reponses to RSV B Challenge in Older Adults (A Controlled Human Infection Study With RSV in Older People-02)

Официальное название

CHIRP02 - Immune Reponses to RSV B Challenge in Older Adults (A Controlled Human Infection Study With RSV in Older People-02)

Обзор

This is a human challenge sequential cohort study involving healthy, non-smoking older adults aged 65-75 years. We aim to enrol 20 participants. There will be a sentinel cohort of 6 participants at the beginning of the study (Group 1). If no pausing rules are met, the remaining 14 participants will be enrolled for a total of 20 enrolled participants (Group 2). The study will consist of three main phases: (1) screening and baseline, (2) inoculation and quarantine, and (3) follow up. All participants will attend a screening visit for a comprehensive health assessment to confirm eligibility. If eligible, participants will take part in an inpatient stay in a quarantine unit, where they will be inoculated with 105 plaque-forming units of RSV B-I54 by intranasal drops. The inoculation dose has been determined in the earlier mentioned outpatient study of the same virus strain, in healthy young adults. Due to the older age range and potentially increased risk of more severe disease, participants will remain within the quarantine unit for 10-days post inoculation and will be closely monitored by clinical review and self-completed symptom diaries. Participants will undergo daily sample collection and will remain in quarantine until the discharge criteria are met at Day 10. After discharge, participants will attend follow-up visits at Day 14, Day 28, and Day 90. Participants in Group 2 will have an additional baseline visit at Day -14 where blood, respiratory (nose and throat) and lower airway (bronchoscopy) samples will be collected. Group 2 participants will also undergo a second bronchoscopy during the inpatient period and the third and final bronchoscopy at Day 28. Clinical outcomes will be determined by symptomatology and viral detection in nasal lavage using quantitative PCR. Based on the first-in-human RSV B characterisation study and recent elderly RSV A challenge data, we anticipate approximately 74% attack rate, with a range of mild-moderate symptoms in the infected individuals. Symptoms typically commence 3 days post-inoculation and worsen to peak around days 5-9 before rapidly resolving without treatment. Timing of viral shedding is expected to correlate closely with symptoms.

Вмешательства

• Биопрепарат RSV B
  RSV B challenge virus

Первичные конечные точки

• Number, frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) Adverse Events (AEs) from the viral challenge (Day 0) up to Day 28. [Срок оценки: 28 Days]
• Number, frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) Adverse Events (AEs) relating to the bronchoscopy sampling in those undergoing bronchoscopy procedures (Group 2) [Срок оценки: 28 Days]
• Occurrence of clinically significant abnormalities and changes from baseline in clinical laboratory tests up to and including Day [Срок оценки: 7 days]
• Occurrence of clinically significant abnormalities and changes from baseline in clinical measurements and assessments (physical examination, vital signs, ECG or Spirometry) from viral challenge (Day 0) up to Day 28. [Срок оценки: 28 Days]
• Infection rate in older adult participants after inoculation with a GMP wild-type RSV B [Срок оценки: 8 Days]

Вторичные конечные точки (11)

• RSV B viral dynamics in upper respiratory samples [Срок оценки: 8 Days]
• RSV B viral dynamics in upper respiratory samples [Срок оценки: 8 Days]
• RSV B viral dynamics in upper respiratory samples [Срок оценки: 8 Days]
• RSV B viral dynamics in upper respiratory samples [Срок оценки: 8 Days]
• RSV B viral dynamics in upper respiratory samples [Срок оценки: 8 Days]
• RSV disease after inoculation with a GMP wild-type RSV B strain [Срок оценки: 14 Days]
• RSV disease after inoculation with a GMP wild-type RSV B strain [Срок оценки: 14 Days]
• RSV disease after inoculation with a GMP wild-type RSV B strain [Срок оценки: 14 Days]
• RSV disease after inoculation with a GMP wild-type RSV B strain [Срок оценки: 8 Days]
• Systemic antibody response to challenge RSV B infection [Срок оценки: 28 Days]
• Systemic antibody response to challenge RSV B infection [Срок оценки: 28 Days]

Критерии участия

Критерии включения

• Aged between 65 to 75years (inclusive) at Day 0.
• Willing and able to commit to participation in the study.
• Adequate understanding of the study, the procedures involved, and able to provide written informed consent prior to any study procedures.
• In good health with no history of clinically significant medical conditions (as described in exclusion criteria) that would interfere with participant safety. A forced expiratory volume in 1 second (FEV1) and a forced vital capacity (FVC) <80% of predicted value calculated using ATS/ERS guidance.

Критерии исключения

• Any significant medical condition or prescribed drug deemed by the Investigator to deem the participant unsuitable for the study.
• History or evidence of any clinically significant or currently active:

• Cardiovascular, thromboembolic or cerebrovascular disease.
• Chronic respiratory disease (e.g. asthma, COPD, rhinitis, sinusitis, reactive airway disease, pulmonary hypertension or a chronic lung condition) in adulthood (a history of childhood asthma without respiratory disease in adulthood may be accepted at the PIs discretion).
• Significant or severe wheeze, or respiratory symptoms (including wheeze) which has ever resulted in hospitalisation.
• Known bronchial hyperactivity to viruses.
• Diabetes mellitus.
• Migraine with associated neurological symptoms such as hemiplegia or vision loss. Cluster headache/migraine or prophylactic treatment for migraine.
• History or evidence of autoimmune disease or known/suspected immunodeficiency of any cause, including asplenia or history of recurrent severe infections.
• Immunosuppression of any type.
• Known IgA deficiency, immotile cilia syndrome, or Kartagener's syndrome.
• Known coagulation disorder or anticoagulant therapy.
• Psychiatric illness including participants with a history of depression and/or anxiety with associated severe psychiatric comorbidities, for example psychosis. Consider exclusion in the following cases: Participants with history of anxiety-related symptoms of any severity within the last 2 years if the Generalized Anxiety Disorder-7 score is ≥4; Participants with a history of depression of any severity within the last 2 years if the Patient Health Questionnaire-9 score is ≥4; . Severe claustrophobia
• Other major disease that, in the opinion of the Investigator, could interfere with a participant completing the study and necessary investigations.
• Concurrent serious illness including history of malignancy that could interfere with the aims of the study or a participant completing the study.

Permissible stable conditions that are well controlled might not be exclusionary and will be assessed by the PI on a case-by-case basis. These include, but will not be limited to: well controlled Hypertension, Sensitive Bladder, Hiatus Hernia, Vitamin D Deficiency, Diverticulitis, Renal Calculi, Depression (well managed), Perioral Dermatitis, Hypercholesterolemia (diet or well medically controlled), Macular Degeneration, Mild Arthritis.

• Any significant abnormality altering the anatomy or function of the nose or nasopharynx in a substantial way, including nasopharyngeal malignancy, arterio-venous malformation, or undiagnosed nasopharyngeal mass.
• A history of clinically significant epistaxis (large nosebleeds) within 3 months of Day 0.
• Nasal or sinus surgery within 3 months of Day 0.
• Any anatomic or neurologic abnormality impairing the gag reflex or associated with increased risk of aspiration.
• Receipt of systemic glucocorticoids (in a dose ≥ 5 mg prednisone daily or equivalent) within one month, or any other cytotoxic or immunosuppressive drug within 6 months prior to Day 0.
• A history of inhaled bronchodilator or inhaled steroid use within the prior 12 months to Day -14.
• Receipt of any vaccine within 30 days of Day -14 or planned during the study period, until the last follow-up visit (Day 90).
• Participation in an investigational drug or device study within 3 months prior to Day 0.
• Receipt of blood or blood products, or loss (including blood donations) of 550 mL or more of blood during the 6 months prior to Day -14.
• History of difficult blood draw, syncope or poor tolerance of sampling procedures as assessed by clinical study team.
• History of anaphylaxis and/or a history of severe allergic reaction or significant intolerance to any food or drug, as assessed by the PI.
• Allergic symptoms present at baseline (at screening, day -14 or day 0).
• Clinically active rhinitis (including hay fever) or history of moderate to severe rhinitis, or history of seasonal allergic rhinitis likely to be active at the time of inclusion into the study and/or requiring regular nasal corticosteroids on an at least weekly basis, within 30 days of enrolment.
• Habitual use of any medication or other product (prescription or over the counter) for symptoms of rhinitis or nasal congestion the 3 months prior to Day -14.
• Receipt of RSV vaccine at any time or planned RSV vaccination in the 3 months following inoculation.
• Virologically confirmed RSV infection within 6 months of Day 0.
• Prior inoculation with a virus from the same virus family (Pneumoviridiae) as the challenge virus.
• Prior participation in another controlled human infection study with a respiratory virus in the preceding 6 months taken from the date of viral challenge in the previous study to the date of expected viral challenge in this study.
• Acute upper respiratory infection (URI or sinusitis) in the 6 weeks prior to Day-14 baseline visit.
• Presence of cold-like symptoms and/or fever (defined as participant presenting with a temperature reading of >37.9ºC) on Day -14, Day -1 or Day 0.
• A respiratory PCR test that is indicative of Influenza, RSV or other respiratory virus infection, including asymptomatic infections, determined by a test on admission to quarantine (Day -1).
• Clinically relevant abnormality on chest X-ray.
• A total body weight of ≤ 50kg and a Body Mass Index (BMI) ≤18 kg/m2 or ≥28 kg/m2.

• The upper limit of BMI may be increased to ≤ 30kg/m2 at the PI's discretion, in the case of physically fit muscular individual or other variation of normal).
• Any abnormal finding on screening safety blood tests deemed to be clinically significant by the Investigator including positive HIV, active/chronic hepatitis B or C test.
• Any ECG abnormality deemed to be clinically significant by the Investigator.
• Significant history or presence of drug or alcohol misuse.

• Participants will be required to have a negative urine drug test at screening. If positive, this will be exclusionary.
• Current use of more than 21 units alcohol per week, drug abuse, or regular use of sedatives, hypnotics, tranquilisers or any other addictive agent are exclusionary.
• Current use of any recreational drugs, including injected, taken through the nose or inhaled route.
• Regular smoking and/or vaping and/or using other nicotine-containing products in the past 3 months OR:

• >5 pack-year lifetime history by self-report (5 pack years is equivalent to one pack of 20 cigarettes per day for 5 years).
• Participants will be required to have a negative urine cotinine test at screening. If positive, this will be exclusionary.
• Those in close domestic contact (i.e. sharing a household with, caring for, or daily face to face contact) with children under 4 years, clinically vulnerable and/or immunosuppressed persons, or those with chronic respiratory disease for 30 days after RSV B inoculation.

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

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07713628 · 204808

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗