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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04882124

Collaborator

(none)

300

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Disease, Chronic Obstructive	Drug: CSJ117 Drug: Placebo	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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)

Actual Study Start Date :

Sep 24, 2021

Anticipated Primary Completion Date :

Aug 25, 2023

Anticipated Study Completion Date :

Aug 25, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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 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
Response in SGRQ-C in total score decrease from baseline [Baseline, 12 weeks]
To assess the number of patients who responded to treatment
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
Time to COPD exacerbations via EXACT [12 weeks]
Time to COPD exacerbations based on EXACT.
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
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.
Accumulation ratio (Racc) of CSJ117 [12 weeks]
To assess PK parameters of CSJ117 based on total serum concentrations.
Measuring anti-drug antibodies [12 weeks]
To assess the immunogenicity of CSJ117

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Andalusia	Alabama	United States	36420
2	Novartis Investigative Site	Riverside	California	United States	92506
3	Novartis Investigative Site	Westminster	California	United States	92683
4	Novartis Investigative Site	Altamonte Springs	Florida	United States	32701
5	Novartis Investigative Site	Greenacres City	Florida	United States	33467
6	Novartis Investigative Site	Louisville	Kentucky	United States	40215
7	Novartis Investigative Site	Crowley	Louisiana	United States	70526
8	Novartis Investigative Site	New Orleans	Louisiana	United States	70115
9	Novartis Investigative Site	Zachary	Louisiana	United States	70791
10	Novartis Investigative Site	Columbia	Missouri	United States	65203
11	Novartis Investigative Site	Saint Charles	Missouri	United States	63301
12	Novartis Investigative Site	Saint Louis	Missouri	United States	63141
13	Novartis Investigative Site	Charlotte	North Carolina	United States	28277
14	Novartis Investigative Site	Gastonia	North Carolina	United States	28054
15	Novartis Investigative Site	Huntersville	North Carolina	United States	28078
16	Novartis Investigative Site	Shelby	North Carolina	United States	28150
17	Novartis Investigative Site	Union	South Carolina	United States	29379
18	Novartis Investigative Site	Boerne	Texas	United States	78006
19	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1122AAK
20	Novartis Investigative Site	Westmead	New South Wales	Australia	2145
21	Novartis Investigative Site	South Brisbane	Queensland	Australia	4101
22	Novartis Investigative Site	Clayton	Victoria	Australia	3168
23	Novartis Investigative Site	Malvern East	Victoria	Australia	3145
24	Novartis Investigative Site	Jette	Brussel	Belgium	1090
25	Novartis Investigative Site	Bruxelles		Belgium	1000
26	Novartis Investigative Site	Erpent		Belgium	5100
27	Novartis Investigative Site	Sainte Foy	Quebec	Canada	G1V 4G5
28	Novartis Investigative Site	St-Charles-Borromee	Quebec	Canada	J6E 2B4
29	Novartis Investigative Site	Ostrava Poruba	Czech Republic	Czechia	708 68
30	Novartis Investigative Site	Teplice	Czech Republic	Czechia	415 01
31	Novartis Investigative Site	Cesky Krumlov		Czechia	381 01
32	Novartis Investigative Site	Tours Cedex 9	Indre Et Loire	France	37044
33	Novartis Investigative Site	Grenoble Cedex 9		France	38043
34	Novartis Investigative Site	Lyon Cedex 04		France	69317
35	Novartis Investigative Site	Marseille		France	13915
36	Novartis Investigative Site	Pessac Cedex		France	33604
37	Novartis Investigative Site	Berlin		Germany	10119
38	Novartis Investigative Site	Berlin		Germany	12159
39	Novartis Investigative Site	Frankfurt		Germany	60596
40	Novartis Investigative Site	Leipzig		Germany	04207
41	Novartis Investigative Site	Leipzig		Germany	D-04299
42	Novartis Investigative Site	Leipzig		Germany	D-04347
43	Novartis Investigative Site	Balassagyarmat		Hungary	2660
44	Novartis Investigative Site	Budapest		Hungary	1121
45	Novartis Investigative Site	Godollo		Hungary	2100
46	Novartis Investigative Site	Szeged		Hungary	6722
47	Novartis Investigative Site	Haifa		Israel	3436212
48	Novartis Investigative Site	Jerusalem		Israel	91031
49	Novartis Investigative Site	Jerusalem		Israel	9112001
50	Novartis Investigative Site	Rehovot		Israel	76100
51	Novartis Investigative Site	Nagoya	Aichi	Japan	457-8511
52	Novartis Investigative Site	Naka-gun	Ibaraki	Japan	319-1113
53	Novartis Investigative Site	Chuo ku	Tokyo	Japan	104-0031
54	Novartis Investigative Site	Toshima	Tokyo	Japan	170-0003
55	Novartis Investigative Site	Osaka		Japan	531-0073
56	Novartis Investigative Site	Iloilo City		Philippines	5000
57	Novartis Investigative Site	Iloilo		Philippines	5000
58	Novartis Investigative Site	Manila		Philippines	1000
59	Novartis Investigative Site	Manila		Philippines	1003
60	Novartis Investigative Site	Grudziadz		Poland	86-300

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Novartis Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT04882124

Other Study ID Numbers:

CCSJ117B12201

First Posted:

May 11, 2021

Last Update Posted:

Aug 23, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Novartis Pharmaceuticals

Chronic Obstructive Pulmonary Disease

COPD

CSJ117

Additional relevant MeSH terms:

Lung Diseases

Pulmonary Disease, Chronic Obstructive

Study Results

No Results Posted as of Aug 23, 2022