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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 April 2021
• Main ID: NCT04010799
• Date of registration: 10/06/2019
• Prospective Registration: No
• Primary sponsor: Chiesi Farmaceutici S.p.A.
• Public title: 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
• Scientific title: A Phase Ib, Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics of Inhaled CHF 6333 After Single and Repeated Ascending Doses in Patients Affected by Cystic Fibrosis and Non Cystic Fibrosis Bronchiectasis
• Date of first enrolment: May 27, 2019
• Target sample size: 68
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT04010799
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1

Countries of recruitment

Germany

Key inclusion & exclusion criteria

INCLUSION CRITERIA:

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;

- Patients in stable clinical condition and free from exacerbation since at least 4
weeks before screening and/or prior to randomisation;

- Patients 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 randomization visit;

- Vital signs within normal limits at screening and prior to randomisation

EXCLUSION CRITERIA CF Patients

- 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;

- 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
that results in active medical problem which may impact the safety of the patients as
per Investigator's judgment.

- History of malignancy, solid organ/haematological transplantation;

- Known diagnosis of cystic fibrosis. A negative sweat test is required at screening
(sweat chloride should be < 40 mmol/L);

- History of asthma based on objective evidence of the condition;

- Patient with primary diagnosis of COPD in the opinion of theInvestigator;

- Patient with rheumatoid factor positivity;

- 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 with ABPA related bronchiectasis;

- Patient with Connective Tissue Disease (CTD) related bronchiectasis;

- Diagnosis of common variable immunodeficiency (CVID);

- Patient on any antibiotics (except for stable macrolides treatment),oral, inhaled and
IV, within 4 weeks prior to screening or prior to randomisation;

- Patient on oral corticosteroids within 4 weeks prior to screening visit or prior to
randomization.

- Patient on non-steroidal anti-inflammatory drugs (NSAIDs) within 4 weeks prior to
screening or randomization visit.

- Patient on Carbocysteine and Mannitol treatment within 4 weeks before the screening or
randomization visit.

- Patient with traction bronchiectasis;

- Patient with any condition that prevent them to use inhaledantibiotics (including
patients who previously experienced adverse reaction to inhaled antibiotics;

- Patient treated with monoclonal antibodies (mAb);

- Pregnant or lactating women.

- 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), HBcore antibody (anti-HBc), HC antibody).



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Non-Cystic Fibrosis Bronchiectasis

Intervention(s)

Drug: CHF 6333

Drug: Placebo

Primary Outcome(s)

Heart Rate [Time Frame: 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 [Time Frame: 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]

Adverse event [Time Frame: 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)]

QTCf interval [Time Frame: 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 [Time Frame: 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]

PR interval [Time Frame: 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]

Change in Vital signs [Time Frame: 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]

Secondary Outcome(s)

Cmax [Time Frame: Part I: Day 1. Part II Day 1-7]

NE activity [Time Frame: Part I: Day -1 Day 1. Part II: Day -1 - 7]

AUC [Time Frame: Part I: Day 1. Part II Day 1-7]

T max [Time Frame: Part I: Day 1. Part II Day 1-7]

C24h [Time Frame: Part II: Day 5 Day 6]

Rac [Time Frame: Part II: Day 7]

Secondary ID(s)

2018-002508-15

CLI-06333AA1-16

Source(s) of Monetary Support

Please refer to primary and secondary sponsors