A Randomized, Double-blind, Placebo-controlled, Phase 2a Study To Assess the Safety, Tolerability and Prophylactic Antiviral Activity of Neumifil Against Influenza, Via a Human Viral Challenge Model in Healthy Adult Participants
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 104
- 试验地点
- 1
- 主要终点
- Incidence of Symptomatic Influenza Infection
研究概览
简要总结
Study to assess the efficacy and safety of a multiple dose regimen and a single dose regimen of intranasal Neumifil, administered prior to challenge with Influenza virus in healthy adult participants
详细描述
This is a single-centre, randomized, double-blind, placebo-controlled study in healthy adult participants to assess the pre-exposure prophylactic antiviral activity of Neumifil via a human viral challenge model.
Participants will enter the quarantine unit on Day -4.
Participants will be randomized to receive either active (single dose), active (multiple dose) or placebo in a 3:3:4 ratio followed by influenza viral challenge on Day 0.
Participants will leave the unit on Day 8, provided that no virus is detected by a qualitative virus antigen test and the participant has no clinically significant symptoms. A final follow-up will be performed on Day 28.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Written informed consent signed and dated by the participant and the investigator obtained before any assessment is performed.
- •Adult male or female aged between 18 and 55 years old, inclusive, on the day prior to signing the consent form.
- •A total body weight ≥50 kg and body mass index (BMI) ≥18 kg/m2 and ≤35kg/m
- •In good health with no history, or current evidence, of clinically significant medical conditions, and no clinically significant test abnormalities that that will interfere with participant safety, as defined by medical history, physical examination, (including vital signs), ECG, and routine laboratory tests as determined by the investigator.
- •Participants will have a documented medical history either prior to entering the study or following medical history review with the study physician at screening.
- •Agree to use highly effective contraception
- •Serosuitable for the challenge virus
排除标准
- •History of, or currently active, symptoms or signs suggestive of upper or lower respiratory tract (URT, LRT) infection within 4 weeks prior to the first study visit.
- •Any history or evidence of any clinically significant or currently active cardiovascular, respiratory, dermatological, gastrointestinal, endocrinological, haematological, hepatic, immunological (including immunosuppression), metabolic, urological, renal, neurological, or psychiatric disease and/or other major disease that, in the opinion of the investigator, may interfere with a participant completing the study and necessary investigations. Includes a history of depression or anxiety.
- •Any participants who have smoked ≥ 10 pack years at any time.
- •Females who are pregnant or breastfeeding
- •Any history of anaphylaxis or history of severe allergic reactions to any foods, drugs, insect bites or stings or any known allergy to tetracycline antibiotics.
- •Venous access deemed inadequate for the phlebotomy and cannulation demands of the study.
- •a) Any significant abnormality altering the anatomy of the nose in a substantial way or nasopharynx that may interfere with the aims of the study and, in particular, any of the nasal assessments or viral challenge b) Any evidence of nasal inflammation or nasal polyps within the last month c) Any clinically significant history of epistaxis (large nosebleeds) within the last 3 months of the first study visit and/or history of being hospitalised due to epistaxis on any previous occasion.
- •d) Any nasal or sinus surgery within 3 months of the first study visit. Prior or Concomitant Medications and Assessments
- •a) Evidence of vaccinations within the 4 weeks prior to the planned date of first dosing with IMP.
- •b) Intention to receive any vaccination(s) before the last day of follow-up (with the exception of vaccinations recommended for COVID19 as defined by Medicines and Healthcare Regulatory Agency (MHRA)/government vaccination guidelines). No travel restrictions apply after the Day 28 (±3 days) follow-up visit.
- •c) Receipt of influenza vaccine (or another IMP relating to treatment of influenza) in the last 6 months prior to the planned date of viral challenge OR a diagnosis of influenza or influenza-like illness confirmed by a physician within the last 2 months prior to screening.
- •Receipt of blood or blood products, or loss (including blood donations) of 550 mL or more of blood during the 3 months prior to the planned date of first dosing with IMP or planned during the 3 months after the final follow-up visit.
- •a) Receipt of any investigational drug within 3 months (or 5 half-lives of the IMP used in the other study, whichever is greater), prior to the planned date of first dosing with IMP.
- •b) Receipt of 3 or more investigational drugs within the previous 12 months prior to the planned date of first dosing with IMP.
- •c) Prior inoculation with a virus from the same virus-family as the challenge virus.
- •d) Prior participation in another human viral challenge study with a respiratory virus in the preceding 3 months.
- •Use or anticipated use during the conduct of the study of concomitant medications
- •Confirmed positive test for drugs of misuse and cotinine on first study visit
- •13 Recent history or presence of alcohol addiction, or excessive use of alcohol
- •A FEV1 <80%, a FVC <80% predicted, or an FEV1/FVC ratio <0.
- •Positive HIV, hepatitis B virus, or hepatitis C virus test.
研究组 & 干预措施
Neumifil multiple dose prophylactic treatment
Neumifil intranasal spray administered as 3 single daily doses prior to viral challenge
干预措施: Neumifil (Drug)
Neumifil single dose prophylactic treatment
Neumifil intranasal spray administered as a single dose and blinded by placebo administered as two single daily doses. All administrations completed prior to viral challenge
干预措施: Neumifil (Drug)
Neumifil single dose prophylactic treatment
Neumifil intranasal spray administered as a single dose and blinded by placebo administered as two single daily doses. All administrations completed prior to viral challenge
干预措施: Placebo (Drug)
Placebo
Intranasal spray administered as 3 single daily doses prior to viral challenge
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of Symptomatic Influenza Infection
时间窗: Day 1 to Day 8
Number of subjects with quantifiable viral shedding on 2 consecutive days AND with any symptom score of grade 2 or greater at a single time point. Viral shedding was measured by RT-qPCR. Eleven symptoms were assessed by questionnaire and were graded on a scale of 0-3 (grade 0: no symptoms; grade 1: just noticeable; grade 2: clearly bothersome from time to time but does not interfere with me doing my normal daily activities; grade 3: quite bothersome most or all of the time, and it stops me participating in activities).
Severity of Symptoms
时间窗: Day 1 to Day 8
Change in Peak Total Symptom Score (TSS) as measured by graded symptom scoring system collected 3 times daily; symptom questionnaire was graded on a scale of 0-3 (grade 0: no symptoms; grade 1: just noticeable; grade 2: clearly bothersome from time to time but does not interfere with me doing my normal daily activities; grade 3: quite bothersome most or all of the time, and it stops me participating in activities).Lower score means better outcome. The range was 0 to 33.
次要结局
- Area Under the Curve (AUC) Over Time of Total Symptom Score (TSS)(Day 1 to Day 8)
- Viral Shedding Over Time(Day 1 (pm) to Day 8 (am))
- Weight of Nasal Discharge(Day 1 (am) to Day 8 (am))
- Nasal Discharge(Day 1 (am) to Day 8 (am))
- Adverse Events, Solicited(From intake of first dose of IMP (Day -3) up to 12 hours post the last IMP dose (Day -1))
- Adverse Events, Unsolicited(From intake of first dose of IMP on Day -3 to Day 28)