Respiratory infection Infections and Infestations Healthy participants and non-cystic fibrosis bronchiectasis patients colonized with pseudomonas aeruginosa
Conditions
Interventions
Current interventions as 01/05/2025:
The study will be conducted in two parts (Part A: Healthy participants and Part B: patients with non-cystic fibrosis bronchiectasis). Subjects will be randomised t
Sponsors
Infex Therapeutics
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 01/05/2025: Part A: 1. Provision of signed and dated, written informed consent prior to any study-specific procedures 2. Participants must be willing and able to comply with trial requirements 3. Males and females aged 18 to 55 years inclusive at the time of providing consent 4. BMI between 18 and 32 kg/m2 (inclusive) 5. Weight less than or equal to 120kg 6. In good health as determined by a responsible and qualified physician (including confirmation from GP) and determined by: 6.1. Medical history 6.2. Physical examination 6.3. Vital signs assessment 6.4. 12-lead electrocardiogram (ECG) 6.5. Clinical laboratory evaluations (congenital non-haemolytic hyperbilirubinaemia is acceptable). 7. The Over-Volunteering Prevention System (TOPS) registration completed, and no conflict found 8. Women of childbearing potential (WOCBP) and fertile male participants who are sexually active with WOCBP must agree to use two methods of contraception (see section 10.9.2 for details) and refrain from donating ova or sperm. The duration of contraception will be from the first administration of trial treatment, throughout trial and up to 4 months after dosing. Post-menopausal women defined as no menses for 12 months without an alternative medical cause. Part B: Participants must comply with all of the following inclusion criteria to be eligible for the study: 1. Provision of signed and dated, written informed consent prior to any study-specific procedures 2. Participants must be willing and able to comply with trial requirements. 3. Male and female patients of = 18 years of age at screening 4. BMI > 15.0 and < than or = 40.00 kg/m2 (inclusive) 5. Weight < than or = to 120 kg 6. Proven diagnosis of Non-Cystic Fibrosis bronchiectasis as documented by computed tomography (CT), or high-resolution CT reported by a radiologist and as assessed by the investigator 7. FEV1 = 50% predicted at screening 8. A stable regimen for the management of exacerbations and maintenance (treatments unchanged for 28 days prior to randomization). Patients are allowed to be on inhaled antibiotics and/or oral macrolide assuming it is stable therapy for at least 3 months prior to visit 1. 9. Clinical or microbiological evidence of exacerbation within 5 years and Microbiological culture positive or PCR positive for P. aeruginosa from one or more respiratory specimen(s) taken within 42 days of randomization. 10. Able to expectorate sputum on the majority of days 11. Women of childbearing potential (WOCBP defined as all women physiologically capable of becoming pregnant) and fertile male participants who are sexually active with WOCBP must agree to use two methods of contraception (see section 10.9.2 for details) and refrain from donating ova or sperm. The duration of contraception will be from the first administration of trial treatment, throughout trial and up to 4 months after the last dose. Post-menopausal women defined as no menses for 12 months without an alternative medical cause. Previous inclusion criteria: Part A: 1. Provision of signed and dated, written informed consent prior to any study-specific procedures 2. Participants must be willing and able to comply with trial requirements 3. Males and females aged 18 to 55 years inclusive at the time of providing consent 4. BMI between 18 and 32 kg/m² (inclusive) 5. Weight less than or equal to 120 kg 6. In good health as determined by a responsible and qualified physician (including confirmation fro
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 01/05/2025: Part A: 1. Female participants who are pregnant or currently lactating 2. Participants who do not agree, or whose partners of childbearing potential do not agree, to use appropriate contraception or to refrain from donating egg or sperm from the time of dosing until 4 months after the last dose of study drug. 3. Donated blood in the 3 months prior to screening, plasma in the 7 days prior to screening, platelets in the 6 weeks prior to screening (inclusion can be delayed under these circumstances) 4. Consume more than 28 units of alcohol per week or any significant history of alcohol/substance misuse as determined by the investigator 5. Current active smoker or ex-smoker (not stopped smoking within 4 weeks prior to Visit 1) with a history of smoking equivalent to >10 pack years 6. Unwilling to abstain from vigorous exercise for 48 hours prior to any study visit. 7. Unwilling to abstain from alcohol for 48 hours prior to any study visit. 8. Participants who have any clinically significant allergy or allergic condition as determined by the investigator (with the exception of non-active hay fever). 9. Participants who have any abnormality of vital signs prior to the first dose administration that, in the opinion of the investigator, would increase the risk of participating in the study. 10. Participants who have any clinically significant abnormal physical examination findings. 11. Participants who have any clinically significant 12-lead ECG abnormality that, in the opinion of the investigator, would increase the risk of participating in the study. This includes QTcB values >450ms (male) or >470ms (female), confirmed on triplicate ECG recordings from which the mean value will be derived. 12. Participants who have hepatitis B or C or are carriers of HBsAg or are carriers of HCV Ab or are positive for HIV 1/2 antibodies. 13. Any clinically significant abnormal finding on biochemistry, haematology, toxicology or serological blood tests, urinalysis, or clinical examination • N.B. In the event of clinically significant abnormal test results, confirmatory repeat tests will be requested. 14. Taking concomitant medications (with the exception of up to 2g paracetamol daily or the oral contraceptive pill) 15. Received any medication that has required dose adjustment (with the exception of the OCP or paracetamol) within 14 days prior to the first dose administration. 16. Received any non-prescribed systemic or topical medication (including vaccination), herbal remedy or vitamin/mineral supplementation within 14 days prior to the first dose administration (with the exception of paracetamol) 17. Participants who have a positive alcohol breath test or a positive urine drug screen (a repeat assessment is acceptable). 18. Positive for SARS-CoV-2 on day of admission Day (-1). 19. Participation in another interventional study within 3 months or 5 half-lives, whichever is longer 20. Clinically significant medical history in the opinion of the Investigator. 21. Previously received mAbs, immunoglobulin or any blood products within the last 6 months 22. History of immune complex disease 23. Any other condition or consideration that, in the opinion of the Investigator, would pose a health risk to the participant if they were enrolled in the study, or would otherwise interfere with the evaluation of the study aims 24. Previously enrolled in this study 25. Participants who have any known hypersensitivity to any of the ex
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 01/05/2025: Safety measured by: Incidence and severity of adverse events (AEs) Previous primary outcome measure: Timepoints for the evaluation of this end point for Part A would be the review of all available data per cohort (minimum subjects (6) - 96 hrs post dose) prior to dose escalation committee safety review. For Part B the review of all available safety data and tolerability data up to (and including) a minimum of 7 days (168 hours, D8) for each participant in each cohort prior to dose escalation committee safety review. Safety and tolerability measured by: 1. Incidence and severity of adverse events (AEs) every study day 2. Physical examination findings follow up visit 3. Safety laboratory tests (clinical chemistry, haematology, coagulation, Urinalysis) : Days -1, 1 ,2 ,3 ,5,8,15,22,29,36,43,57,71,99, follow up 4. Vital sign measurements (blood pressure, heart rate, temperature, respiration rate and oxygen saturations) every study day 5. Electrocardiogram (ECG) every study day 6. Local tolerability (number of i.v. site reactions) (study days 1-3) | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 01/05/2025: 1. Safety and tolerability measured by: 1.1. Physical examination findings Day 106 and follow-up visit Day 180 1.2. Safety laboratory tests (clinical chemistry, haematology, coagulation, urinalysis): Days -1, 1, 2, 3, 5, 8, 15, 22, 29, 36, 43, 57, 71, 99, 106 and day 180 follow-up 1.3. Vital sign measurements (blood pressure, heart rate, temperature, respiration rate and oxygen saturations) every study day 1.4. Electrocardiogram (ECG) every study day 1.5. Local tolerability (number of i.v. site reactions) (study days 1-3) Previous secondary outcome measures: Timepoints for the evaluation of this end point for Part A would be the review of all available data per cohort (minimum subjects (6) - 96 hrs post dose) prior to dose escalation committee review For Part B the review of all available safety data and tolerability data up to (and including) a minimum of 7 days (168 hours, D8) for each participant in each cohort prior to dose escalation committee review Pharmacokinetics of INFEX702 measured by calculating PK parameters from serum samples taken on every study day. Multiple samples will be taken on Day 1: 1. Area under the serum concentration-time curve from time 0 to infinity (AUC0-8) 2. Area under the serum concentration-time curve from time 0 to 28 days post dose (AUC0-28d) 3. Area under the serum concentration-time curve from time 0 to the last observed quantifiable concentration (AUC0-t) 4. Serum concentration observed at 28 days post dose (C28d) 5. Maximum observed serum concentration (Cmax) 6. Apparent terminal half-life (t1/2) 7. Time of last quantifiable concentration (tlast) 8. Time of occurrence of Cmax (tmax) | — |
Countries
England, United Kingdom
Contacts
Public ContactKerry Nield
Outcome results
None listed