Safety, Tolerability and Prophylactic Antiviral Activity of Neumifil Against Influenza Via a Human Viral Challenge Model

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 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

Study Overview

• Status: Completed
• Conditions: Influenza Viral Infections
• Intervention / Treatment: Drug: Neumifil; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, E1 2AX
    • hVIVO Services Limited

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neumifil multiple dose prophylactic treatment; Neumifil intranasal spray administered as 3 single daily doses prior to viral challenge	Drug: Neumifil; Liquid for intranasal spray administration
Experimental: 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	Drug: Neumifil; Liquid for intranasal spray administration; Drug: Placebo; Liquid for intranasal spray administration
Placebo Comparator: Placebo; Intranasal spray administered as 3 single daily doses prior to viral challenge	Drug: Placebo; Liquid for intranasal spray administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Symptomatic Influenza Infection	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).	Day 1 to Day 8
Severity of Symptoms	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.	Day 1 to Day 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve (AUC) Over Time of Total Symptom Score (TSS)	Participants completed a self-assessment symptom score 3 times daily, 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. Range 0 to 33	Day 1 to Day 8
Viral Shedding Over Time	Measurement of influenza viral load (VL) area under the curve (VL-AUC) of quantifiable measurements by RT-qPCR in nasal samples. The AUC is expressed as the log to the base 10 copies in a mL of nasal fluid multiplied by the time in days [(log10 copies/mL)*day]. The higher the viral load AUC, by PCR, the worse the outcome.	Day 1 (pm) to Day 8 (am)
Viral Shedding Over Time	Measurement of influenza viral load (VL) in nasal samples over time (VL-AUC) measured by viral culture. Nasal secretions were cultured and the Tissue Culture Infectious Dose (TCID50) calculated. The AUC of log to the base 10 of the TCID50 in each mL of nasal secretions, multiplied by the time in days [(log10 TCID50/mL)*day] was calculated. The higher the viral load AUC by culture, the worse the outcome.	Day 1 (pm) to Day 8 (am)
Weight of Nasal Discharge	Measurement of total weight of mucus produced by participants. The total weight of used tissues was measured to assess the weight of mucus produced. The greater the weight of the tissues the more mucus produced and the worse the outcome.	Day 1 (am) to Day 8 (am)
Nasal Discharge	The number of tissues used by participants were counted. The greater the number of tissues used the worse the outcome.	Day 1 (am) to Day 8 (am)
Adverse Events, Solicited	Number of participants reporting a solicited adverse event during the treatment period of IMP	From intake of first dose of IMP (Day -3) up to 12 hours post the last IMP dose (Day -1)
Adverse Events, Unsolicited	Number of participants reporting treatment emergent adverse events, unsolicited	From intake of first dose of IMP on Day -3 to Day 28

Collaborators and Investigators

• Sponsor: Pneumagen Ltd.
• Investigators: Study Director: Geoff Kitson, gkitson@propharmapartners.com

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2022
• Primary Completion (Actual): May 4, 2023
• Study Completion (Actual): May 4, 2023

Study Registration Dates

• First Submitted: August 17, 2022
• First Submitted That Met QC Criteria: August 17, 2022
• First Posted (Actual): August 19, 2022

Study Record Updates

• Last Update Posted (Actual): October 28, 2024
• Last Update Submitted That Met QC Criteria: October 24, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Influenza; Prophylaxis; Human Challenge
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Respiratory Tract Diseases; Influenza, Human; Virus Diseases
• Other Study ID Numbers: PNG-NMF-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No