Viral Respiratory Tract Infection
Conditions
Brief summary
This is a Phase 1, single-centre, randomised, placebo-controlled first in human study in healthy subjects. The study will assess the safety and tolerability of single-ascending (Part A) and multiple-ascending (Part B) doses of Neumifil, administered intranasally.
Detailed description
Part A will include up to 36 healthy subjects in up to 5 groups. 6 subjects will be enrolled in Groups A1-A3 and 9 subjects will be enrolled in Groups A4 and A5. All subjects will receive a single intranasal dose of Neumifil or placebo. In Groups A1-A3, 4 subjects will receive Neumifil and 2 will receive matching placebo. In Groups A4 and A5, 6 subjects will receive Neumifil and 3 will receive matching placebo. The planned dose levels are: 0.028 mg (Group A1), 0.085 mg (Group A2), 0.28 mg (Group A3), 0.885 mg (Group A4), and 2.8 mg (Group A5). Additional dose levels may be assessed in up to 2 optional groups of up to 9 subjects each (Groups A6 and A7). Subjects will be screened within 35 days before their dose of trial medication and reside at the Investigator site from the day before their dose (Day -1) until approximately 24 hours after dosing (Day 2). They will return for a follow-up visit on Day 8-9. Part B will include up to 24 healthy subjects in up to 3 groups of 8 subjects (Groups B1-B3). Subjects will receive once-daily intranasal doses of Neumifil or placebo for 7 days. In each group, 6 subjects will receive Neumifil and 2 subjects will receive matching placebo. The starting dose level (dose and dose regimen) for Group B1 will be decided after review of safety and tolerability data from at least 3 dose levels in Part A, and will be no higher than a dose that has previously been shown to cause no safety concerns in Part A . An additional dose level may be explored in 1 optional group of up to 8 subjects (Group B4). Subjects will be screened within 35 days before their dose of trial medication and reside. at the Investigator site from the day before their first dose (Day -1) until about 24 hours after their last dose (Day 8). Subjects will attend an outpatient visit on Days 15-16. They will return for a follow-up visit on Days 21-23. During the study, dose levels for study groups will be determined by a Safety Review Committee in accordance with criteria defined in the study protocol and the Investigator site operating procedures. Dose levels will only be increased if the safety and tolerability of previous dose levels are considered to be acceptable by the Safety Review Committee.
Interventions
DRUGNeumifil
Neumifil contains the active ingredient HEX17, a multivalent, glycan-targeting carbohydrate binding module (CBM). HEX17 CBM is suspended in an aqueous buffer solution containing 20 mM sodium phosphate, 50 mM NaCl (at pH 6.3), 5 % (v/v) glycerol and 0.5 % (v/v) polysorbate 80.
DRUGPlacebo
Aqueous buffer solution containing 20 mM sodium phosphate, 50 mM NaCl (at pH 6.3), 5 % (v/v) glycerol and 0.5 % (v/v) polysorbate 80.
Sponsors
Pneumagen Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Randomized, double-blind, placebo-controlled trial.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male or female volunteer, aged 18-60 years. 2. BMI (Quetelet index) in the range 18.0-30.9 kg/m2. 3. Able to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial. 4. Willingness to give written consent to participate after reading the information and consent form, and after having the opportunity to discuss the trial with the investigator or their delegate. 5. Agree to follow the contraception requirements of the trial 6. Agree not to donate blood or blood products during the study and for up to 3 months after the administration of the trial medication. 7. Spirometry readings (FEV1 and FVC) to be ≥ 80% of predicted value at the screening visit, calculated using National Health and Nutrition Examination Survey (NHANES) reference. If a subject's FEV1 or FVC is outside that range at the screening visit, the test may be repeated once on another day. 8. Registered with a General Practitioner (GP) in the UK (Part A only). 9. Willingness to give written consent to have data entered into The Overvolunteering Prevention System (TOPS).
Exclusion criteria
1. Woman who is pregnant or lactating, or pre-menopausal woman who is sexually active and not using a reliable method of contraception. 2. Clinically relevant abnormal medical history, physical findings, ECG, or laboratory values at the pre-trial screening assessment that in the opinion of the investigator could interfere with the objectives of the trial or the safety of the volunteer. 3. Presence or history of acute or chronic illness sufficient to invalidate the volunteer's participation in the trial or make it unnecessarily hazardous. 4. Presence or history of respiratory disease, including (but not limited to) asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, emphysema, requiring acute or chronic medication. 5. Presence of nasal polyps or significant nasal abnormalities. 6. Symptoms of respiratory illness (including, but not limited to, runny nose, sore throat, sneezing, coughing or wheezing) at the screening visit or before dosing on Day 1. 7. Tympanic temperature \> 37.5°C at the screening visit or before dosing on Day 1. 8. Impaired endocrine, thyroid, hepatic, respiratory or renal function, diabetes mellitus, coronary heart disease, or history of any psychotic mental illness. 9. History of psychiatric disease, as determine by the investigator. 10. History or presence of malignant disease. 11. Immune-suppressed status, resulting from either disease or medication, as determined by the investigator. 12. Presence or history of severe adverse reaction to any drug or the excipients of Neumifil. 13. Known allergy to tetracycline antibiotics. 14. Use of a prescription medicine (except HRT in female subjects), including oral contraceptives, during the 28 days before the first dose of trial medication, or use of an over-the-counter medicine, with the exception of acetaminophen (paracetamol) and vitamin or nutritional supplements, during the 7 days before the first dose of trial medication. 15. Receipt of an investigational product (including prescription medicines) as part of another clinical trial within the 3 months before admission to this study; in the follow-up period of another clinical trial at the time of screening for this study. 16. Receipt of a COVID-19 vaccine within 7 days before the first dose of trial medication, or anticipate receiving a COVID-19 vaccine within the 7 days after a (final) dose of trial medication. 17. Presence or history of drug or alcohol abuse, or regular intake of more than 14 units of alcohol weekly. 18. Use of cigarettes or nicotine-containing products during the 6 months before first dose of trial medication. 19. Blood pressure and heart rate in supine position at the screening examination outside the ranges: blood pressure 90-140 mm Hg systolic, 40-90 mm Hg diastolic; heart rate 40-100 beats/min. Triplicate measurements will be made (at least 2 min apart), and a mean value outside the above ranges will lead to exclusion. Repeat measurements (in triplicate) are permitted if values are borderline (ie values that are within 5 mm Hg for blood pressure or 5 beats/min for heart rate) or if requested by the investigator. Subjects can be included if the repeat value is within range or still borderline but deemed not clinically significant by the investigator. 20. QTcF value, of \> 450 msec (men) or \> 470 msec (women); or QRS duration ≥ 120 msec, measured on 12-lead ECG at the screening visit. Triplicate measurements will be made, and a mean value used to determine eligibility. A repeat (in triplicate) is also allowed on one occasion for determination of eligibility. 21. Possibility that the volunteer will not cooperate with the requirements of the protocol. 22. Positive test for hepatitis B surface antigen, hepatitis C or HIV. NOTE: participants with positive hepatitis C antibody owing to resolved disease can be included only if a hepatitis C ribonucleic acid (RNA) test is negative. 23. Positive test for SARS-CoV-2 (polymerase chain reaction; PCR) or suspected exposure to the SARS-CoV-19 virus during the 14 days before screening. 24. Loss of more than 400 mL blood during the 3 months before the trial, eg as a blood donor. 25. Objection by GP to volunteer entering trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part B:Clinically Significant Changes in Safety Tests | 14 days after last dose | Number of participants with clinically significant changes in: vital signs (heart rate, blood pressure, respiratory rate, pulse oximetry and temperature), 12-lead electrocardiogram (ECG), FEV1, FVC, physical examination, nasal examination, laboratory safety tests (haematology, biochemistry and urinalysis), tolerability questionnaire |
| Part A Treatment Emergent Adverse Events | 7 days | Number of participants with Treatment Emergent Adverse Events |
| Part B: Treatment Emergent Adverse Events | 14 days after last dose | Number of participants with Treatment Emergent Adverse Events |
| Part A: Clinically Significant Changes in Safety Tests | 7 days | Number of participants with clinically significant changes in:vital signs (heart rate, blood pressure, respiratory rate, pulse oximetry and temperature), 12-lead electrocardiogram (ECG), Forced expiratory volume in 1 second (FEV1), Forced vital capacity (FVC), physical examination, nasal examination, laboratory safety tests (haematology, biochemistry and urinalysis), tolerability questionnaire |
Other
| Measure | Time frame | Description |
|---|---|---|
| SARS-CoV-2 Infection Test | Screening, before first dose, Day 8 (Part B only), follow-up (Part A: Day 8 to 9); Part B: Day 21 to 23) | SARS-CoV-2 infection test |
| Part B: Immunoglobulin A and G (IgA and IgG) Concentrations | Blood samples before first dose, follow-up (Day 21 to 23) | Part B: Immunoglobulin A and G (IgA and IgG) concentrations specific for Neumifil |
| Part A: Plasma Concentration of Neumifil | Day 1 after single dose | Part A: Plasma concentration of Neumifil |
| Part B:Plasma Concentration of Neumifil | Day 1 after dosing, Day 7 | Part B:Plasma concentration of Neumifil |
Countries
United Kingdom
Participant flow
Recruitment details
This was a first in human study in healthy participants at a single site in the UK. The first participant was screened on 07 October 2021 and the last participant visit was on 05 April 2022.
Participants by arm
| Arm | Count |
|---|---|
| Part A Placebo All Groups Placebo will be administered intranasally using an Aptar deliver system. Each dose will consist of 0.5ml to each nostril. | 12 |
| Part A1 Neumifil 0.028mg Neumifil 0.028mg as a single dose administered intranasally using an Aptar delivery system. Each dose will consist of 0.5ml to each nostril. | 4 |
| Part A2 Neumifil 0.085mg Neumifil 0.085mg as a single dose administered intranasally using an Aptar delivery system. Each dose will consist of 0.5ml to each nostril. | 4 |
| Part A3 Neumifil 0.28mg Neumifil 0.028mg as a single dose administered intranasally using an Aptar delivery system. Each dose will consist of 0.5ml to each nostril. | 4 |
| Part A4 Neumifil 0.885mg Neumifil 0.085mg as a single dose administered intranasally using an Aptar delivery system. Each dose will consist of 0.5ml to each nostril. | 6 |
| Part A5 Neumifil 2.8mg Neumifil 2.8 mg as a single dose administered intranasally using an Aptar delivery system. Each dose will consist of 0.5ml to each nostril. | 6 |
| Part B Placebo All Groups Placebo will be administered intranasally once daily for 7 days using an Aptar delivery system. Each dose will consist of 0.5ml to each nostril. | 6 |
| Part B1 Neumifil 0.28mg Neumifil 0.28mg will be administered intranasally once daily for 7 days using an Aptar delivery system. Each dose will consist of 0.5ml to each nostril. | 6 |
| Part B2 Neumifil 0.885mg Neumifil 0.885mg will be administered intranasally once daily for 7 days using an Aptar delivery system. Each dose will consist of 0.5ml to each nostril. | 6 |
| Part B3 Neumifil 2.8mg Neumifil 2.8mg will be administered intranasally once daily for 7 days using an Aptar delivery system. Each dose will consist of 0.5ml to each nostril. | 6 |
| Total | 60 |
Baseline characteristics
| Characteristic | Part A Placebo All Groups | Part A1 Neumifil 0.028mg | Part A2 Neumifil 0.085mg | Part A3 Neumifil 0.28mg | Part A4 Neumifil 0.885mg | Part A5 Neumifil 2.8mg | Part B Placebo All Groups | Part B1 Neumifil 0.28mg | Part B2 Neumifil 0.885mg | Part B3 Neumifil 2.8mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 43.3 years STANDARD_DEVIATION 12.16 | 34.0 years STANDARD_DEVIATION 5.89 | 35.0 years STANDARD_DEVIATION 14.85 | 31.5 years STANDARD_DEVIATION 17.23 | 32.2 years STANDARD_DEVIATION 12.94 | 27.7 years STANDARD_DEVIATION 3.67 | 41.2 years STANDARD_DEVIATION 15.32 | 38.8 years STANDARD_DEVIATION 15.51 | 32.7 years STANDARD_DEVIATION 12.19 | 38.3 years STANDARD_DEVIATION 13.53 | 35.6 years STANDARD_DEVIATION 12.46 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 4 Participants | 4 Participants | 4 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 5 Participants | 6 Participants | 58 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United Kingdom | 12 participants | 4 participants | 4 participants | 4 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 60 participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 16 Participants |
| Sex: Female, Male Male | 9 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 4 Participants | 5 Participants | 5 Participants | 5 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 4 / 12 | 3 / 4 | 2 / 4 | 3 / 4 | 5 / 6 | 5 / 6 | 5 / 6 | 6 / 6 | 5 / 6 | 6 / 6 |
| serious Total, serious adverse events | 0 / 12 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Part A: Clinically Significant Changes in Safety Tests
Number of participants with clinically significant changes in:vital signs (heart rate, blood pressure, respiratory rate, pulse oximetry and temperature), 12-lead electrocardiogram (ECG), Forced expiratory volume in 1 second (FEV1), Forced vital capacity (FVC), physical examination, nasal examination, laboratory safety tests (haematology, biochemistry and urinalysis), tolerability questionnaire
Time frame: 7 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A Placebo All Groups | Part A: Clinically Significant Changes in Safety Tests | 0 Participants |
| Part A1 Neumifil 0.028mg | Part A: Clinically Significant Changes in Safety Tests | 0 Participants |
| Part A2 Neumifil 0.085mg | Part A: Clinically Significant Changes in Safety Tests | 0 Participants |
| Part A3 Neumifil 0.28mg | Part A: Clinically Significant Changes in Safety Tests | 0 Participants |
| Part A4 0.Neumifil 0.885mg | Part A: Clinically Significant Changes in Safety Tests | 0 Participants |
| Part A5 Neumifil 2.8mg | Part A: Clinically Significant Changes in Safety Tests | 0 Participants |
Primary
Part A Treatment Emergent Adverse Events
Number of participants with Treatment Emergent Adverse Events
Time frame: 7 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A Placebo All Groups | Part A Treatment Emergent Adverse Events | 4 Participants |
| Part A1 Neumifil 0.028mg | Part A Treatment Emergent Adverse Events | 3 Participants |
| Part A2 Neumifil 0.085mg | Part A Treatment Emergent Adverse Events | 2 Participants |
| Part A3 Neumifil 0.28mg | Part A Treatment Emergent Adverse Events | 3 Participants |
| Part A4 0.Neumifil 0.885mg | Part A Treatment Emergent Adverse Events | 5 Participants |
| Part A5 Neumifil 2.8mg | Part A Treatment Emergent Adverse Events | 5 Participants |
Primary
Part B:Clinically Significant Changes in Safety Tests
Number of participants with clinically significant changes in: vital signs (heart rate, blood pressure, respiratory rate, pulse oximetry and temperature), 12-lead electrocardiogram (ECG), FEV1, FVC, physical examination, nasal examination, laboratory safety tests (haematology, biochemistry and urinalysis), tolerability questionnaire
Time frame: 14 days after last dose
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A Placebo All Groups | Part B:Clinically Significant Changes in Safety Tests | 1 Participants |
| Part A1 Neumifil 0.028mg | Part B:Clinically Significant Changes in Safety Tests | 0 Participants |
| Part A2 Neumifil 0.085mg | Part B:Clinically Significant Changes in Safety Tests | 0 Participants |
| Part A3 Neumifil 0.28mg | Part B:Clinically Significant Changes in Safety Tests | 0 Participants |
Primary
Part B: Treatment Emergent Adverse Events
Number of participants with Treatment Emergent Adverse Events
Time frame: 14 days after last dose
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A Placebo All Groups | Part B: Treatment Emergent Adverse Events | 5 Participants |
| Part A1 Neumifil 0.028mg | Part B: Treatment Emergent Adverse Events | 6 Participants |
| Part A2 Neumifil 0.085mg | Part B: Treatment Emergent Adverse Events | 5 Participants |
| Part A3 Neumifil 0.28mg | Part B: Treatment Emergent Adverse Events | 6 Participants |
Other Pre-specified
Part A: Plasma Concentration of Neumifil
Part A: Plasma concentration of Neumifil
Time frame: Day 1 after single dose
Other Pre-specified
Part B: Immunoglobulin A and G (IgA and IgG) Concentrations
Part B: Immunoglobulin A and G (IgA and IgG) concentrations specific for Neumifil
Time frame: Blood samples before first dose, follow-up (Day 21 to 23)
Other Pre-specified
Part B:Plasma Concentration of Neumifil
Part B:Plasma concentration of Neumifil
Time frame: Day 1 after dosing, Day 7
Other Pre-specified
SARS-CoV-2 Infection Test
SARS-CoV-2 infection test
Time frame: Screening, before first dose, Day 8 (Part B only), follow-up (Part A: Day 8 to 9); Part B: Day 21 to 23)