A phase I, double-blind, placebo-controlled, ascending single intravenous dose, safety, tolerability, pharmacokinetic and pharmacodynamic study in healthy participants and non-cystic fibrosis bronchiectasis patients colonized with pseudomonas aeruginosa administered INFEX702
- Conditions
- Respiratory infectionInfections and InfestationsHealthy participants and non-cystic fibrosis bronchiectasis patients colonized with pseudomonas aeruginosa
- Registration Number
- ISRCTN17978477
- Lead Sponsor
- Infex Therapeutics
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 44
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 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 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:
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 between 15 and 40 kg/m² (inclusive)
5. Weight less than or equal to 120kg
6. Proven diagnosis of Non-Cystic Fibrosis bronchiectasis as documented by computed tomography (CT) or high-resolution CT and as assessed by the investigator
7. History of 2 or more exacerbations treated with oral antibiotics OR 1 or more exacerbation requiring parenteral antibiotic treatment within 18 months prior to screening.
8. FEV1 =30% predicted at screening
9. A stable regimen of local standard treatment for BE (treatments unchanged for 28 days prior to randomization).
10. Colonised with P. aeruginosa, defined as 2 or more consecutive positive cultures, collected at least 1 month apart within the last 18 months, with last culture collected within the last 12 months. Respiratory samples used can include: expectorated sputum; deep throat cough swab; oro-pharyngeal swab; bronchoalveolar lavage.
11. Able to expectorate sputum on the majority of days
12. 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 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
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 (including vapes)
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 finding.
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, 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 (using a polymerase chain reaction test)within 72 hours prior to admission.
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 that have any known hypersensitivity to any of the e
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 day2. Physical examination findings follow up visit3. Safety laboratory tests (clinical chemistry, haematology, coagulation, Urinalysis) : Days -1, 1 ,2 ,3 ,5,8,15,22,29,36,43,57,71,99,follow up4. Vital sign measurements (blood pressure, heart rate, temperature, respiration rate and oxygen saturations) every study day5. Electrocardiogram (ECG) every study day6. Local tolerability (number of i.v. site reactions) (study days 1-3)
- Secondary Outcome Measures
Name Time Method