Clinical trial NCT05507567: Safety, Tolerability and Prophylactic Antiviral Activity of Neumifil Against Influenza Via a Human Viral Challenge Model
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza Viral Infections
Keywords: Influenza
Human Challenge
Prophylaxis
Lead sponsor: Pneumagen Ltd.
Sponsor class: INDUSTRY
First posted: 2022-08-19
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double-blind, Placebo-controlled study
Primary purpose: PREVENTION

Brief summary: 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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Written informed consent signed and dated by the participant and the investigator obtained before any assessment is performed.
2. Adult male or female aged between 18 and 55 years old, inclusive, on the day prior to signing the consent form.
3. A total body weight ≥50 kg and body mass index (BMI) ≥18 kg/m2 and ≤35kg/m2.
4. 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.
5. Participants will have a documented medical history either prior to entering the study or following medical history review with the study physician at screening.
6. Agree to use highly effective contraception
7. Serosuitable for the challenge virus

Exclusion Criteria:

1. 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.
2. 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.
3. Any participants who have smoked ≥ 10 pack years at any time.
4. Females who are pregnant or breastfeeding
5. 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.
6. Venous access deemed inadequate for the phlebotomy and cannulation demands of the study.
7. 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
8. 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.
9. 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.
10. 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.
11. Use or anticipated use during the conduct of the study of concomitant medications
12. 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

14. A FEV1 \<80%, a FVC \<80% predicted, or an FEV1/FVC ratio \<0.7. 15. Positive HIV, hepatitis B virus, or hepatitis C virus test.

Primary outcomes:
measure: Incidence of Symptomatic Influenza Infection
timeFrame: Day 1 to Day 8
measure: Severity of Symptoms
timeFrame: Day 1 to Day 8
Secondary outcomes:
measure: Area Under the Curve (AUC) Over Time of Total Symptom Score (TSS)
timeFrame: Day 1 to Day 8
measure: Viral Shedding Over Time
timeFrame: Day 1 (pm) to Day 8 (am)
measure: Viral Shedding Over Time
timeFrame: Day 1 (pm) to Day 8 (am)
measure: Weight of Nasal Discharge
timeFrame: Day 1 (am) to Day 8 (am)
measure: Nasal Discharge
timeFrame: Day 1 (am) to Day 8 (am)
measure: Adverse Events, Solicited
timeFrame: From intake of first dose of IMP (Day -3) up to 12 hours post the last IMP dose (Day -1)
measure: Adverse Events, Unsolicited
timeFrame: From intake of first dose of IMP on Day -3 to Day 28
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: hVIVO Services Limited
Study officials:
affiliation: gkitson@propharmapartners.com
name: Geoff Kitson
role: STUDY_DIRECTOR
References: