A Clinical Study to Investigate Safety, Tolerability and Distribution of CHF 6333 After One or After Repeated Inhalation in Patients With Cystic Fibrosis (CF) and in Patients With Non Cystic Fibrosis (NCFB) Bronchiectasis

NCT04010799 | Completed Phase 1

• 2 other identifiers: CLI-06333AA1-162018-002508-15
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

CHF 6333 is a medicinal product on development for the treatment of cystic fibrosis and non-CF bronchiectasis and undergoing clinical testing. It has not yet been approved by the authorities for the treatment of these diseases. CHF6333 is an inhaled anti-inflammatory which mechanism of action is based on the inhibition of Human Neutrofil Elastase. The safety and tolerability of single and repeated ascending doses of inhaled CHF 6333 was previously investigated in healthy subjects: information was gathered on the uptake, distribution and excretion of the medicinal product being tested (pharmacokinetics). In this current clinical trial CHF 6333 will be tested in patients(CF and NCFB) for the first time. Three dose level will be tested during the first part of the study, as single administration. One repeated dose will be administered in the second part of the study.

Conditions

Cystic Fibrosis; Non-Cystic Fibrosis Bronchiectasis

Outcome Measures

Primary Outcomes (7)

• Adverse event

  Occurrence and severity of adverse events

  Part I: Baseline through end of treatment (up to a maximum of 30 days after last study drug intake) ; Part II Baseline through end of treatment (up to a maximum of 30 days after last study drug intake)

• Change in Vital signs

  Change in Systolic and Diastolic blood pressure

  Part I: Day 1 pre-dose up to 6 hours post dose. Part II: Day 1 and Day 7 pre dose up to 6 hours post dose

• Heart Rate

  Change in Heart Rate

  Part I: Day 1 pre dose up to 8 hours post dose. Part II: Day 1 and Day 7 pre dose up to 12 hours post dose

• PR interval

  Change in PR interval

  Part I: Day 1 pre dose up to 8 hours post dose. Part II: Day 1 and Day 7 pre dose up to 12 hours post dose

• QRS interval

  Change in QRS interval

  Part I: Day 1 pre dose up to 8 hours post dose. Part II: Day 1 and Day 7 pre dose up to 12 hours post dose

• QTCf interval

  Change in QTCf interval

  Part I: Day 1 pre dose up to 8 hours post dose. Part II: Day 1 and Day 7 pre dose up to 12 hours post dose

• FEV1

  Change in FEV1

  Part I: Day 1 pre dose up to 6 hours post dose. Part II: Day 1 and Day 7 pre dose up to 6 hours post dose. Day 2 -6: pre dose up to 2 hours post dose

Secondary Outcomes (6)

• AUC

  Part I: Day 1. Part II Day 1-7

• Cmax

  Part I: Day 1. Part II Day 1-7

• T max

  Part I: Day 1. Part II Day 1-7

• C24h

  Part II: Day 5 Day 6

• Rac

  Part II: Day 7

Study Arms (2)

CHF6333

EXPERIMENTAL

CHF6333 Active (part I - SAD). Once daily inhaled single dose of CHF6333 at each period (three dose level). CHF6333 Active (part II -MD). Once daily inhaled multiple dose of CHF6333 for 7 consecutive days.

Drug: CHF 6333

CHF6333 Placebo

PLACEBO COMPARATOR

Part I (SAD): Single dose of placebo matching CHF6333 at each period Part II (MD): Once daily multiple doses of placebo matching CHF6333 for 7 consecutive days

Drug: Placebo

Interventions

CHF 6333 DRUG

CHF 6333 - Part I - SAD CHF 6333 - Part II - MD

CHF6333

Placebo DRUG

Placebo - Part I - SAD Placebo Part II - MAD

CHF6333 Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• CF patients:
• Patient's written informed consent obtained prior to any study-related procedure;
• Male or female patient ≥ 18 years old with a confirmed historical diagnosis of cystic fibrosis;
• Ability to provide a spontaneous sputum sample at screening;
• Non- or ex-smokers who smoked \< 10 pack years and stopped smoking \> 1 year before screening visit;
• Patient in stable clinical condition and free from exacerbation for at least 4 weeks prior to screening and/or prior to randomisation;
• Patient on stable concomitant treatment regimen within 4 weeks prior to screening and/or prior to randomisation;
• Patient with pre-bronchodilator FEV1 ≥ 50% of predicted normal at screening and/or prior to randomisation;
• Vital signs within normal limits at screening and prior to randomisation;
• NCFB patients:
• Patient's written informed consent obtained prior to any study-related procedure;
• Male or female patient ≥ 18 years old with a diagnosis of Bronchiectasis confirmed by a historical Chest CT;
• Presence of clinically significant symptoms related to Bronchiectasis, such as daily cough that occurs over months or years, daily production of large amount of sputum, shortness of breath, wheezing chest pain;
• Ability to provide a spontaneous sputum sample at screening;
• Non- or ex-smokers who smoked \< 10 pack years and stopped smoking \> 1 year before screening visit;

You may not qualify if:

• Patient with BMI ≤ 17
• History of a clinically meaningful unstable or uncontrolled chronic comorbidity in the opinion of the Investigator;
• Unstable pulmonary status or symptomatic respiratory tract infection and related changes in therapy for pulmonary disease as per Investigator's judgment within 4 weeks before screening or prior to randomisation;
• Abnormal and clinically significant 12-lead ECG at screening or prior to randomisation;
• History of asthma based on objective evidence;
• History of malignancy, solid organ/haematological transplantation;
• Patient with evidence of active Nontuberculous Mycobacteria (NTM) and Tuberculous Mycobacteria (TM) infection or related bronchiectasis in the past 12 months;
• Patient with a positive test for active Allergic Bronchopulmonary Aspergillosis (ABPA) infection confirmed at screening or patient withABPA related bronchiectasis.
• Pregnant or lactating women.
• Patient on non-steroidal anti-inflammatory drugs (NSAIDs) within 4 weeks prior to screening or prior to randomization visit.
• Patient on cystic fibrosis transmembrane conductance regulator (CFTR) modulators and correctors if not on stable treatment regimen for at least 3 months prior to screening or prior to randomization.
• Positive HIV1 or HIV2 serology at screening; Positive results from the Hepatitis serology which indicates acute or chronic Hepatitis B or Hepatitis C at screening (i.e. positive HB surface antigen (HBsAg), HB core antibody (anti-HBc), HC antibody);
• NCFB Patients
• Patient with BMI ≤ 17
• History of a clinically meaningful unstable or uncontrolled chronic comorbidity in the opinion of the Investigator;

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (1)

IKF Institut für klinische Forschung Pneumologie

Frankfurt am Main, Germany

Location

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

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-dose escalation, cross-over design in one cohort of CF patients and in one cohort of NCFB patients. Part II: Randomised, double-blind, placebo-controlled, repeated-dose, parallel-group design in one cohort of CF patients and in one cohort of NCFB patients.

Study Record Dates

• First Submitted: June 10, 2019
• First Posted: July 8, 2019
• Study Start: May 27, 2019
• Primary Completion: March 8, 2021
• Study Completion: March 8, 2021
• Last Updated: March 30, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)