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

Phase 2

Completed

• Conditions: Pulmonary Disease, Chronic Obstructive
• Interventions: Drug: CSJ117; Drug: Placebo

• Registration Number: NCT04882124
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2021-04-28
• Study First Submitted QC: 2021-05-05
• Study First Posted: 2021-05-11
• Study Start: 2021-09-24
• Primary Completion: 2022-09-15
• Study Completion: 2022-09-15
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-25
• Last Update Posted: 2022-11-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 38

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CSJ117 8mg	CSJ117	Intervention: Drug: CSJ117
CSJ117 4mg	CSJ117	Intervention: Drug: CSJ117
CSJ117 Placebo	Placebo	Intervention: Drug: Placebo

Primary Outcome Measures

Name	Time	Method
Change from baseline in E-RS score	Baseline, 12 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Change from baseline in SGRQ-C score	Baseline, 12 weeks	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.
Response in E-RS in total score decrease from baseline	Baseline, 12 weeks	To assess the number of patients who responded to treatment
Response in CAT in total score decrease from baseline	Baseline, 12 weeks	To assess the number of patients who responded to treatment
Change from baseline in CAT score	Baseline, 12 weeks	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.
Change from baseline in trough FEV1 after 2, 6, and 12 weeks of treatment	Baseline, 2, 6 and 12 weeks	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.
Puffs of rescue medication per day	12 weeks	To assess use of rescue medication
Rate and severity of COPD exacerbations via HCRU	12 weeks	Rate and severity of COPD exacerbations based on the Health Care Resource Utilization (HCRU).
Pre-dose trough concentration (Ctrough) of CSJ117	12 weeks	To assess pharmacokinetic (PK) parameters of CSJ117 based on total serum concentrations.
Response in SGRQ-C in total score decrease from baseline	Baseline, 12 weeks	To assess the number of patients who responded to treatment
Rate and severity of COPD exacerbations via EXACT	12 weeks	Rate and severity of COPD exacerbations based on the Exacerbations of chronic obstructive pulmonary disease tool (EXACT).
Time to COPD exacerbations via HCRU	12 weeks	Time to COPD exacerbations based on HCRU
Measuring anti-drug antibodies	12 weeks	To assess the immunogenicity of CSJ117
Time to COPD exacerbations via EXACT	12 weeks	Time to COPD exacerbations based on EXACT.
Accumulation ratio (Racc) of CSJ117	12 weeks	To assess PK parameters of CSJ117 based on total serum concentrations.

Trial Locations

Locations (1)

Novartis Investigative Site; 🇯🇵 Naka-gun, Ibaraki, Japan