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

Influenza Viral Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05507567
• Other study ID #: PNG-NMF-201
• Status: Completed
• Phase: Phase 2
• Start date: August 12, 2022
• Est. completion date: May 4, 2023

Study information

• Verified date: May 2023
• Source: Pneumagen Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 104
• Est. completion date: May 4, 2023
• Est. primary completion date: May 4, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Influenza Viral Infections
• Influenza, Human
• Virus Diseases

Intervention

Drug:
• Neumifil
Liquid for intranasal spray administration
• Placebo
Liquid for intranasal spray administration

Locations

Country	Name	City	State
United Kingdom	hVIVO Services Limited	London

Sponsors (1)

Lead Sponsor	Collaborator
Pneumagen Ltd.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the effect of Neumifil in reducing the incidence of symptomatic influenza infection compared to placebo	Incidence of 2 quantifiable qRT PCR samples on 2 consecutive days AND any symptoms of grade =2 at a single time point	Day 1 to Day 8
Primary	To evaluate the effect of Neumifil in reducing the severity of symptoms compared to placebo	Change in Peak Total Symptom Score as measured by graded symptom scoring system collected 3 times daily; symptom questionnaire will be 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.	Day 1 to Day 8
Secondary	To evaluate the effect of Neumifil in reducing symptoms compared to placebo	Participants will complete a self-assessment symptom diary card	Day 1 to Day 8
Secondary	To evaluate the antiviral effect of Neumifil in reducing or shortening viral shedding when compared to placebo	Measurement of influenza viral load and duration of quantifiable measurements in nasal samples by qRT-PCR and tissue culture	Day 1 to Day 8
Secondary	To evaluate the effect of Neumifil in reducing nasal discharge	Measurement of total weight of mucus produced and number of tissues used by participants	Day 1 to Day 8
Secondary	To evaluate the safety of intranasal doses of Neumifil compared to placebo	Occurrence of adverse events, solicited and unsolicited	to Day 28