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

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)

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: CSJ117; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Novartis Investigative Site
• Canada
  • Quebec
    • Sainte Foy, Quebec, Canada, G1V 4G5
      • Novartis Investigative Site
• Czechia
  • Czech Republic
    • Ostrava Poruba, Czech Republic, Czechia, 708 68
      • Novartis Investigative Site
• Hungary
  • Balassagyarmat, Hungary, 2660
    • Novartis Investigative Site
  • Godollo, Hungary, 2100
    • Novartis Investigative Site
  • Szeged, Hungary, 6722
    • Novartis Investigative Site
• Japan
  • Aichi
    • Nagoya, Aichi, Japan, 457-8511
      • Novartis Investigative Site
  • Ibaraki
    • Naka-gun, Ibaraki, Japan, 319-1113
      • Novartis Investigative Site
• United States
  • Alabama
    • Andalusia, Alabama, United States, 36420
      • Novartis Investigative Site
  • Louisiana
    • Crowley, Louisiana, United States, 70526
      • Novartis Investigative Site
    • New Orleans, Louisiana, United States, 70115
      • Novartis Investigative Site
  • Missouri
    • Saint Charles, Missouri, United States, 63301
      • Novartis Investigative Site
    • Saint Louis, Missouri, United States, 63141
      • Novartis Investigative Site
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Novartis Investigative Site
    • Shelby, North Carolina, United States, 28150
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2021
• Primary Completion (Actual): September 15, 2022
• Study Completion (Actual): September 15, 2022

Study Registration Dates

• First Submitted: April 28, 2021
• First Submitted That Met QC Criteria: May 5, 2021
• First Posted (Actual): May 11, 2021

Study Record Updates

• Last Update Posted (Actual): November 28, 2022
• Last Update Submitted That Met QC Criteria: November 25, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: COPD; Chronic Obstructive Pulmonary Disease; CSJ117
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: CCSJ117B12201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No