Study of Effect of CSJ117 on Symptoms, Pharmacodynamics and Safety in Patients With COPD

Study Overview
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Brief Summary
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This is a Phase 2 study in patients with chronic obstructive pulmonary disease (COPD) to assess the efficacy, pharmacodynamics (PD), pharmacokinetics (PK), and safety of two dose levels of CSJ117 in comparison to placebo. For this, the impact of CSJ117 on disease symptom burden and lung function will be explored.

Detailed Description
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This is a randomized, participant- and investigator-blinded, placebo-controlled, parallel group, multicenter study with two fixed-dose levels of CSJ117 (4 mg, 8 mg) administered once-daily via oral inhalation over 12 weeks in participants with COPD, prone for exacerbations and symptomatic at baseline despite background maintenance triple therapy (inhaled corticosteroids/long acting beta-2 agonist/long acting muscarinic antagonist (ICS/LABA/LAMA) combination, standard of care in this population) for at least three months prior to screening. The study will include: Screening period of up to 2 weeks to assess eligibility. Run-in period of 4 weeks where participants will be placed on fixed-dose triple background therapy (ICS/LABA/LAMA) that will be used until the patient's last study treatment. Treatment period of 12 weeks. Participants will be stratified by eosinophil levels and then randomized 1:1:1 to either 4 mg CSJ117, 8 mg CSJ117, or placebo. Follow-up period of 55 days following the last dose of study drug. The primary objective of the study is to assess the effect of CSJ117 on disease/symptom burden after 12 weeks of treatment.

Official Title
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A 12-week Randomized, participant-and Investigator-blinded, Placebo-controlled, Parallel Group Study to Explore the Efficacy, Pharmacodynamics, Safety, and Pharmacokinetics of Two Doses of Inhaled CSJ117 in Adults With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: CSJ117
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female COPD patients aged ≥40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure Current or ex-smokers who have a smoking history of at least 10 pack years Patients who have been treated with a triple combination of LABA/LAMA/ICS for the last 3 months prior to screening Patients with a documented diagnosis of COPD for at least 1 year prior to screening visit Exclusion Criteria: Patients with a past or current medical history of asthma Patients who have had a COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization, or a respiratory tract infection in the 4 weeks prior to screening, or hospitalization between screening and prior to treatment. Use of other investigational drugs (approved or unapproved) within 30 days or 5 half-lives prior to screening, or until the expected pharmacodynamic effect has returned to baseline (e.g., biologics), whichever is longer; or longer if required by local regulations Pregnant or nursing (lactating) women, and women of childbearing potential not willing to use acceptable effective methods of contraception during study participation Patients with a body mass index (BMI) of more than 40 kg/m2 Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CSJ117 8mg<br>Intervention: Drug: CSJ117 | Drug: CSJ117<br>* CSJ117 (4 mg and 8 mg) inhaled once daily for 12 weeks. Delivered via Concept1 device.<br>|
| Experimental: CSJ117 4mg<br>Intervention: Drug: CSJ117 | Drug: CSJ117<br>* CSJ117 (4 mg and 8 mg) inhaled once daily for 12 weeks. Delivered via Concept1 device.<br>|
| Placebo Comparator: CSJ117 Placebo<br>Intervention: Drug: Placebo | Drug: Placebo<br>* Placebo inhaled once daily for 12 weeks. Delivered via Concept1 device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in E-RS score | The Evaluating Respiratory Symptoms (E-RS) scale is based on the 11 respiratory symptom items included in the EXACT Tool (a validated 14-item electronic questionnaire). These 11 items generate a total score of 0-40, with higher scores indicating more severe respiratory symptoms. | Baseline, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in CAT score | The COPD assessment test (CAT) is a short instrument used to quantify the symptom burden of COPD and will be used to assess the health status of participants. The assessment consists of 8 items, each presented as a semantic 6-point differential scale, providing a total score out of 40. A higher score indicates a worse health status. | Baseline, 12 weeks | 
| Change from baseline in SGRQ-C score | The St. George Respiratory Questionnaire for COPD patients Specific Version (SGRQ-C) contains 40 items divided into two parts covering three aspects of health related to COPD: symptoms, activity and impacts. Total score ranges between 0 and 100, with higher scores indicating greater impairment of health status. | Baseline, 12 weeks | 
| Response in E-RS in total score decrease from baseline | To assess the number of patients who responded to treatment | Baseline, 12 weeks | 
| Response in CAT in total score decrease from baseline | To assess the number of patients who responded to treatment | Baseline, 12 weeks | 
| Response in SGRQ-C in total score decrease from baseline | To assess the number of patients who responded to treatment | Baseline, 12 weeks | 
| Change from baseline in trough FEV1 after 2, 6, and 12 weeks of treatment | Forced expiratory volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. | Baseline, 2, 6 and 12 weeks | 
| Puffs of rescue medication per day | To assess use of rescue medication | 12 weeks | 
| Time to COPD exacerbations via EXACT | Time to COPD exacerbations based on EXACT. | 12 weeks | 
| Rate and severity of COPD exacerbations via EXACT | Rate and severity of COPD exacerbations based on the Exacerbations of chronic obstructive pulmonary disease tool (EXACT). | 12 weeks | 
| Time to COPD exacerbations via HCRU | Time to COPD exacerbations based on HCRU | 12 weeks | 
| Rate and severity of COPD exacerbations via HCRU | Rate and severity of COPD exacerbations based on the Health Care Resource Utilization (HCRU). | 12 weeks | 
| Pre-dose trough concentration (Ctrough) of CSJ117 | To assess pharmacokinetic (PK) parameters of CSJ117 based on total serum concentrations. | 12 weeks | 
| Accumulation ratio (Racc) of CSJ117 | To assess PK parameters of CSJ117 based on total serum concentrations. | 12 weeks | 
| Measuring anti-drug antibodies | To assess the immunogenicity of CSJ117 | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Obstructive Pulmonary Disease, COPD, CSJ117