Investigate the Safety, Tolerability and Pharmacokinetics of CHF6523 in Healthy and in COPD Subjects

NCT04032535 | Completed Phase 1

• 2 other identifiers: CLI-06523AA1-012018-004162-34
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to investigate the safety, tolerability and pharmacokinetics of inhaled CHF6523 DPI in healthy male subjects first and then in COPD subjects after single or repeated dosesof CHF6523. As an exploratory assessment, the anti-inflammatory effect of CHF6523 in COPDsubjects will be evaluated.

Conditions

COPD

Keywords

anti-inflamatory; PI3K; Sputum; COPD; inhaled

Outcome Measures

Primary Outcomes (1)

• Treatment Emergent Adverse Events (TEAEs)

  The number of events and the number and percentage of subjects experiencing TEAEs, treatment emergent ADRs, serious TEAEs, non-serious TEAEs, severe TEAEs, TEAEs leading to discontinuation of study drug and TEAEs leading to death will be presented by treatment.

  Up to 4 weeks

Secondary Outcomes (2)

• Pharmacokinetics: AUC0-24h,

  On Day 1 at pre-dose,10, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose.

• Cardiac Safety

  At screening visit and on Day 1 at pre-dose, 10, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose and at 24 hours post dose;

Other Outcomes (2)

• Concentration of sputum biomarkers in COPD patients

  On Day 1 at pre-dose and on Day 28 after the dose

• Concentration of blood biomarkers in COPD patients

  On Day 1 at pre-dose and on Day 28 after the dose

Study Arms (3)

SAD

EXPERIMENTAL

Single Ascending Dose of 2 cohorts: Cohort A will be administered three ascending dose levels: 0.2 mg (dose 1), 2 mg (anticipated dose 3), 8 mg (anticipated dose 5) or placebo; Cohort B will be administered three ascending dose levels: 1 mg (anticipated dose 2), 4 mg (anticipated dose 4), 14 mg (anticipated dose 6, maximum dose) or placebo.

Drug: CHF6523

MAD

EXPERIMENTAL

Multiple Ascending Dose of 4 cohorts: Cohort A will be administered with 2 mg (anticipated dose 1) or placebo; Cohort B will be administered with 4 mg (anticipated dose 2) or placebo; Cohort C will be administered with 8 mg (anticipated dose 3) or placebo; Cohort D will be administered with 12 mg (anticipated dose 4) or placebo;

Drug: CHF6523

2way crossover

EXPERIMENTAL

Two 28-day treatment periods (Period 1 and Period 2), separated each by 32 days (up to 40 days) wash-out period, in crossover design. The treatment period will consist in repeated administrations of CHF 6523 at one dose level or placebo.

Drug: CHF6523

Interventions

CHF6523 DRUG

CHF6523 is a PI3K inhibitor (phosphoinositide3-kinase)

2way crossover; MAD; SAD

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject's written informed consent obtained prior to any study-related procedures;
• Male and female aged ≥40 years;
• A female is eligible to enter the study if she is of non-childbearing potential i.e.
• physiologically incapable of becoming pregnant (e.g. postmenopausal women defined as being amenorrheic for ≥12 consecutive months without an alternative medical cause. If indicated, as per investigator's request, post-menopausal status may be confirmed by follicle-stimulating hormone levels, according to local laboratory ranges) or women permanently sterilized (e.g. bilateral oophorectomy, hysterectomy or bilateral salpingectomy or non-fertile partner). Women physiologically capable of becoming pregnant \[i.e. women of childbearing potential (WOCBP)\] are eligible to enter the study if they have negative pregnancy test at screening and are fulfilling one of the following criteria:
• WOCBP with fertile male partners;
• WOCBP with non-fertile male partners;
• Male fulfilling one of the following criteria:
• Male with non-pregnant WOCBP partners;
• Male with pregnant WOCBP partner;
• Subject with an established diagnosis of COPD (according to GOLD guidelines, update 2019 \[7\]) at least 12 months prior to the screening visit;
• Subject with a smoking history of at least 10 pack-years \[pack-years=number of cigarettes per day x number of years/20\]. Current and ex- smokers are eligible. (Smoking cessation must be at least 6 months prior to the screening. If the subjects undergo smoking cessation therapy, it must be completed 6 months prior to the screening visit);
• Subject with a BMI in the range of 19-32 kg/m2 extremes included;
• Subject with a post-bronchodilator FEV1 ≥30% and ≤70% of the subject normal predicted value and a post-bronchodilator FEV1/FVC ratio \<0.70 measured 10-15 minutes after 400 μg (4 puffs x 100 μg) of salbutamol pMDI. If this criterion is not met at screening, the test could be repeated once prior to randomisation visit;
• Subject with at least one COPD exacerbation \[i.e. resulting in the use of systemic (oral/IV/IM) corticosteroids and/or antibiotics or visit to an emergency department or hospitalisation\] in the 12 months preceding the screening visit;
• Subject on maintenance dual therapy with LABA/LAMA fixed combination within at least 2 months prior to screening visit;

You may not qualify if:

• Pregnant or lactating female subject;
• Subject with a current diagnosis of asthma;
• Subject who have received or are planned to receive any type of vaccination within 3 weeks of their first dose of investigational product;
• Subject with a COPD exacerbation \[i.e. resulting in the use of systemic (oral/IV/IM) corticosteroids and/or antibiotics or visit to an emergency department or hospitalisation\] or a lower respiratory tract infection within 6 weeks prior to screening visit or between screening and randomisation;
• Subject on any maintenance therapy other than LABA/LAMA fixed combination within 2 months prior to screening visit;
• Subject receiving treatment with one or more drugs, and related time windows, listed in the prohibited medication section (see section 5.2.2);
• Subject requiring long-term (at least 12 hours daily) oxygen therapy for chronic hypoxemia;
• Subject participating to a pulmonary rehabilitation programme or completing such a programme within the last 6 weeks prior to screening visit;
• Subject with known respiratory disorders other than COPD that in investigator's opinion would affect efficacy and safety evaluation or place the subject at risk.
• This can include but is not limited to known -1 antitrypsin deficiency, active tuberculosis, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension and interstitial lung disease;
• Subject having lung cancer or a history of lung cancer;
• Subject with active cancer or a history of cancer (other than lung) with less than 5 years disease free survival time (whether or not there is evidence of local recurrence or metastases). Localized carcinoma e.g. basal cell carcinoma (without metastases), in situ carcinoma of the cervix adequately treated is acceptable;
• Subject with a known history of intolerance/hypersensitivity to any of the excipients/components contained in any of the formulations used in the trial;
• Subject with a diagnosis of depression associated with suicidal ideation or behavior or with a diagnosis of generalised anxiety disorder that in the investigator's opinion would place the subject at risk;
• Subject who has known history of clinically significant cardiovascular conditions such as, but not limited to, unstable or acute ischemic heart disease within one year prior to screening visit, NYHA Class III/IV heart failure, known history of sustained and non-sustained cardiac arrhythmias or history of atrial fibrillation diagnosed in the last 6 months prior to screening visit and not controlled with therapy rate control strategy;

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (1)

Richmond Pharmacology

London, United Kingdom

Location

Related Publications (1)

• Govoni M, Bassi M, Girardello L, Lucci G, Rony F, Charretier R, Galkin D, Faietti ML, Pioselli B, Modafferi G, Benfeitas R, Bonatti M, Miglietta D, Clark J, Pedersen F, Kirsten AM, Beeh KM, Kornmann O, Korn S, Ludwig-Sengpiel A, Watz H. CHF6523 data suggest that the phosphoinositide 3-kinase delta isoform is not a suitable target for the management of COPD. Respir Res. 2024 Oct 19;25(1):380. doi: 10.1186/s12931-024-02999-5.

  PMID: 39427187 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Respiratory Aspiration

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiration Disorders

Study Officials

• Jorg Taubel, MD

  Richmond Pharmacology Limited

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: SAD and MAD in healthy volunteers plus 2way crossover in COPD patients

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: July 25, 2019
• Study Start: July 24, 2019
• Primary Completion: December 5, 2022
• Study Completion: December 5, 2022
• Last Updated: February 13, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)