A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Inhaled CHF6333 After Single Doses in Healthy Volunteers and After Single and Repeated Doses in Subjects With Bronchiectasis

NCT06166056 | Recruiting Phase 1

• 1 other identifier: CLI-06333CA1-01
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 9

Brief Summary

The aim of this clinical trial is to assess the safety of:

• single doses of the study drug CHF6333 in Healthy Volunteers (HVs) and in subjects with Bronchiectasis (BE) - Part I
• repeated doses of the study drug CHF6333 in subjects with BE - Part II

Conditions

Bronchiectasis

Outcome Measures

Primary Outcomes (13)

• Safety and tolerability of single ascending doses of CHF6333 in HVs and a single dose in subjects with BE (Part I), and repeated doses in subjects with BE (Part II), in terms of AEs

  Through study completion. Part I: an average of 12 weeks and 8 weeks respectively for HVs and BE subjects. Part II: an avarage of 26 weeks

• Safety and tolerability of single ascending doses of CHF6333 in HVs and a single dose in subjects with BE (Part I), and repeated doses in subjects with BE (Part II), in terms of vital signs

  Arterial blood pressure (SBP and DBP)

  Part I:screening, day(D)-1, D1(from pre-dose until 96hrs post-dose HV, 6hrs post-dose BE), 14 to 21D post-dose.Part II:screening, D-1, D1 and 27(from pre-dose until 6hrs post-dose), D28(from pre-dose until 2hrs post-dose), 14 to 21D after last dose

• heart rate (HR)

  Safety and tolerability of single ascending doses of CHF6333 in HVs and a single dose in subjects with BE (Part I), and repeated doses in subjects with BE (Part II).

  Part I: at day1 from pre-dose until 24hrs post-dose. Part II: at day1 and 27 from pre-dose until 8hrs post-dose

• Safety and tolerability of single ascending doses of CHF6333 in HVs and a single dose in subjects with BE (Part I), and repeated doses in subjects with BE (Part II), in terms of 12-Lead ECG parameters from Holter: PR interval

  Part I HVs only and Part II

  Part I: at day1 from pre-dose until 24hrs post-dose. Part II: at day1 and 27 from pre-dose until 8hrs post-dose

• Safety and tolerability of single ascending doses of CHF6333 in HVs and a single dose in subjects with BE (Part I), and repeated doses in subjects with BE (Part II), in terms of 12-Lead ECG parameters from Holter: QRS interval

  Part I HVs only and Part II

  Part I: at day1 from pre-dose until 24hrs post-dose. Part II: at day1 and 27 from pre-dose until 8hrs post-dose

• Safety and tolerability of single ascending doses of CHF6333 in HVs and a single dose in subjects with BE (Part I), and repeated doses in subjects with BE (Part II), in terms of 12-Lead ECG parameters from Holter: Fridericia-corrected QT interval (QTcF)

  Part I HVs only and Part II

  Part I: at day1 from pre-dose until 24hrs post-dose. Part II: at day1 and 27 from pre-dose until 8hrs post-dose

• Safety and tolerability of single ascending doses of CHF6333 in HVs and a single dose in subjects with BE (Part I), and repeated doses in subjects with BE (Part II), in terms of lung function parameters: FEV1

  Part I: screening, day-1, day1 (from pre-dose until 24hrs post-dose for HVs and 6hrs post-dose for BE. Part II: screening, day-1, day1 and 27 (from pre-dose until 6hrs post-dose), day 28 (from pre-dose until 2hrs post-dose

• Safety and tolerability of single ascending doses of CHF6333 in HVs and a single dose in subjects with BE (Part I), and repeated doses in subjects with BE (Part II), in terms of lung function parameters: FVC

  Part I: screening, day-1, day1 (from pre-dose until 24hrs post-dose for HVs and 6hrs post-dose for BE. Part II: screening, day-1, day1 and 27 (from pre-dose until 6hrs post-dose), day 28 (from pre-dose until 2hrs post-dose

• Safety and tolerability of single ascending doses of CHF6333 in HVs and a single dose in subjects with BE (Part I), and repeated doses in subjects with BE (Part II), in terms of lung function parameters: FEV1/FVC ratio

  Part I: screening, day-1, day1 (from pre-dose until 24hrs post-dose for HVs and 6hrs post-dose for BE. Part II: screening, day-1, day1 and 27 (from pre-dose until 6hrs post-dose), day 28 (from pre-dose until 2hrs post-dose

• Safety and tolerability of single ascending doses of CHF6333 in HVs and a single dose in subjects with BE (Part I), and repeated doses in subjects with BE (Part II), in terms of lung function parameters: FEV1 percentage of predicted

  Part I: screening, day-1, day1 (from pre-dose until 24hrs post-dose for HVs and 6hrs post-dose for BE. Part II: screening, day-1, day1 and 27 (from pre-dose until 6hrs post-dose), day 28 (from pre-dose until 2hrs post-dose

• Number of participants with clinical laboratory tests: Haematology

  Safety and tolerability of single ascending doses of CHF6333 in HVs and a single dose in subjects with BE (Part I), and repeated doses in subjects with BE (Part II), in terms of clinical laboratory tests: Haematology

  Part I: screening, day-1 and day5 (pre-dose) for HVs/FU for BE. Part II: screening, day-1 and 27 (pre-dose)

• Number of participants with clinical laboratory tests: Biochemistry

  Safety and tolerability of single ascending doses of CHF6333 in HVs and a single dose in subjects with BE (Part I), and repeated doses in subjects with BE (Part II), in terms of clinical laboratory tests: Biochemistry

  Part I: screening, day-1 and day5 (pre-dose) for HVs/FU for BE. Part II: screening, day-1 and 27 (pre-dose)

• Number of participants with clinical laboratory tests: Urinalysis

  Safety and tolerability of single ascending doses of CHF6333 in HVs and a single dose in subjects with BE (Part I), and repeated doses in subjects with BE (Part II), in terms of clinical laboratory tests: Urinalysis

  Part I: screening, day-1 and day 5 (pre-dose) for HVs/FU for BE. Part II: screening, day-1 and 27 (pre-dose)

Secondary Outcomes (11)

• Pharmacokinetic variables in plasma in HVs only (Part I), in terms of Area Under the Curve

  Day 1: from pre-dose until 96 hours post-dose

• Pharmacokinetic variables in plasma in HVs only (Part I): Maximum concentration (Cmax)

  Day1: from pre-dose until 96 hours post-dose

• Pharmacokinetic variables in plasma in HVs only (Part I): Time to maximum concentration (tmax)

  Day1: from pre-dose until 96 hours post-dose

• Pharmacokinetic variables in plasma in HVs only (Part I): Terminal half-life (t½)

  Day 1: from pre-dose until 96 hours post-dose

• Pharmacokinetic variables in plasma in HVs only (Part I): Clearance (CL/F)

  Day 1: from pre-dose until 96 hours post-dose

Study Arms (2)

Experimental: CHF6333

EXPERIMENTAL

CHF6333 active (Part I - SAD): once daily inhaled single dose of CHF6333 at each period (three dose levels for HVs and one dose level for BE subjects). CHF6333 active (Part II - MD): once daily inhaled multiple dose of CHF6333 for 28 days consecutive days (two dose levels for BE subjects).

Drug: CHF6333

Placebo comparator: CHF6333 Placebo

PLACEBO COMPARATOR

CHF6333 placebo (Part I - SAD): once daily inhaled single dose of placebo matching CHF6333 at each period. CHF6333 placebo (Part II - MD): once daily inhaled multiple dose of placebo matching CHF6333 for 28 days consecutive days.

Drug: CHF6333 Placebo

Interventions

CHF6333 DRUG

CHF6333 Part I SAD; CHF6333 Part II MD.

Experimental: CHF6333

CHF6333 Placebo DRUG

Placebo Part I SAD; Placebo Part II MD.

Placebo comparator: CHF6333 Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated informed consent obtained prior to any study-related procedure;
• Healthy male or female subject ≥18 and ≤60 years of age at screening;
• Ability to understand the study procedures and the risks involved, and to be trained to use inhalers correctly and to generate sufficient peak inspiratory flow (PIF) (at least 40 L/min) using the In-Check Dial set as per "GenuAir" inhaler resistance, at screening;
• Body mass index (BMI) ≥18 and ≤35 kg/m2 at screening;
• Non-smokers or ex-smokers who smoked \<5 pack-years and stopped smoking \>1 year prior to screening;
• Good physical and mental status, determined via assessment of medical history and clinical examination, at screening and prior to randomisation;
• Vital signs within normal limits at screening and prior to randomisation: diastolic blood pressure (DBP) ≥40 and ≤89 mmHg, and systolic blood pressure (SBP) ≥90 and ≤139 mmHg; body temperature \<37.5°C;
• Triplicate 12-lead electrocardiogram (ECG) considered as normal (40 ≤ heart rate ≤110 bpm, 120 ms ≤ PR ≤210 ms, QRS ≤120 ms, Fridericia corrected QT interval \[QTcF\] ≤450 ms for males and QTcF ≤470 ms for females) at screening and prior to randomisation;
• Lung function measurements within limits at screening and prior to randomisation: forced expiratory volume in 1 second (FEV1) \>80% predicted and FEV1/forced vital capacity (FVC) ratio \>0.70;
• Male subjects willing to use a male condom throughout the study if they have women of childbearing potential (WOCBP) partners; male subjects with non-WOCBP partners or who are sterile do not have contraception requirements;
• Female subjects (if WOCBP) and/or their partners (if fertile) must be willing to use a highly effective birth control method, preferably with low user dependency, throughout the study; female subjects who are non-WOCBP or who have non-fertile partners do not have contraception requirements.

You may not qualify if:

• Participation in another clinical study where investigational drug was received and the last investigations were performed less than 3 months prior to randomisation;
• Clinically relevant and uncontrolled respiratory, cardiac, hepatic, gastrointestinal, renal, endocrine, hematologic, metabolic, neurological, or psychiatric disorders that may interfere with successful completion of this protocol, according to the investigator's judgment;
• Clinically relevant abnormal laboratory values at screening suggesting an unknown disease and requiring further clinical investigation or which may impact the safety of the subject or the evaluation of the results of the study, according to the investigator's judgment;
• History of respiratory diseases;
• Positive human immunodeficiency virus (HIV) 1 or HIV2 serology results at screening;
• Hepatitis serology results which indicate acute or chronic hepatitis B (HB) or hepatitis C virus (HCV) at screening;
• Documented coronavirus disease 2019 (COVID-19) diagnosis within 2 weeks prior to screening or prior to randomisation, or associated complications/symptoms, which have not resolved within 2 weeks prior to screening;
• Blood donation or blood loss (equal or more than 450 mL) less than 2 months prior to screening or prior to randomisation;
• Abnormal liver enzymes at screening or prior to randomisation (alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] or bilirubin: \>1.5× upper limit of normal \[ULN\]);
• Positive urine test for cotinine at screening or prior to randomisation;
• Documented history of alcohol abuse within 12 months prior to screening or a positive alcohol breath test at screening or prior to randomisation;
• Documented history of drug abuse within 12 months prior to screening or a positive urine drug screen at screening or prior to randomisation;
• Treatment with prohibited concomitant medications or if the subject is expected to take prohibited concomitant medications during the study;
• Presence of any current infection, or previous infection that resolved less than 7 days prior to screening or prior to randomisation;
• Known intolerance and/or hypersensitivity to any of the excipients contained in the formulation used in the study;

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (9)

Royal Papworth Hospital NHS Foundation Trust, Cambridge Centre for Lung Infection

Cambridge, United Kingdom

RECRUITING

Tayside Medical Science Centre, Ninewells Hospital & Medical School

Dundee, United Kingdom

RECRUITING

NHS Lothian

Edinburgh, United Kingdom

RECRUITING

Glasgow Royal Infirmary

Glasgow, United Kingdom

RECRUITING

The Leeds Teaching Hospitals NHS Trust, Saint James's University Hospital

Leeds, United Kingdom

WITHDRAWN

Royal Bromptom Hospital (NHS Guy's and Thomas')

London, United Kingdom

RECRUITING

Manchester University NHS Foundation Trust

Manchester, United Kingdom

RECRUITING

Medicines Evaluation Unit (MEU)

Manchester, United Kingdom

RECRUITING

University Hospital Southampton NHS Foundation Trust

Southampton, United Kingdom

RECRUITING

MeSH Terms

Conditions

Bronchiectasis

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases

Study Officials

• James D. Chalmers

  School of Medicine, University of Dundee, UK

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chiesi Clinical Trial info

CONTACT

+39 0521 2791; Clinicaltrials_info@chiesi.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part I: randomised, double-blind, placebo-controlled, single ascending dose, alternating cross-over design in HV and single dose in subjects with BE. Part II: randomised, double-blind, placebo-controlled, repeated-dose, 3-way cross-over design in subjects with BE.

Study Record Dates

• First Submitted: November 22, 2023
• First Posted: December 12, 2023
• Study Start: November 29, 2023
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (9)