Study of Safety of CSJ117 in Participants With Moderate to Severe Uncontrolled Asthma

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04946318
• Collaborator: (none)
• Enrollment: 325
• Locations: 62
• Arms: 6
• Anticipated Duration (Months): 12
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to provide safety and tolerability, pharmacokinetics and immunogenicity data for multiple CSJ117 doses inhaled once daily compared with placebo, in adult asthma participants treated with medium or high dose ICS plus LABA alone or with additional asthma controllers (additional controllers allowed: LTRA, LAMA, Theophylline and its derivatives), who have completed the prior phase llb study CCSJ117A12201C (NCT04410523).

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: CSJ117; Drug: Placebo	Phase 2

Detailed Description

This is a 12/24-week Phase llb, multicenter, multi-national, double-blind, randomized, parallel-arm, placebo-controlled extension study to evaluate the safety and tolerability, pharmacokinetics and immunogenicity of 5 dose levels of CSJ117 in adult asthma participants treated with medium or high dose ICS plus LABA alone or with additional asthma controllers (allowed: LTRA, LAMA, theophylline or its derivatives), who have completed the prior core phase llb study CCSJ117A12201C (NCT04410523). The study will include the following three parts:

A Screening period of up to 3 days to assess eligibility.

A Treatment period of 12 or 24 weeks. There are two scenarios on when a participant can enroll into the extension study depending on when the study site is activated for the extension study CCSJ117A12201E1:

• A 24 week treatment period: Participants on each of the five treatment arms (CSJ117 0.5 to 8 mg) or placebo of the core study CCSJ117A12201C, who will enter the extension study after the last Treatment period visit (week 12) of the core study, will be randomized in a 1:1 ratio to continue on their previously assigned CSJ117 dose or placebo from CCSJ117A12201C for 24 weeks, or to first go through a 12-week "washout period" receiving placebo (for the blinding purpose) and then restart on their previously assigned CSJ117 dose or placebo from CCSJ117A12201C for 12 weeks.

• A 12 week treatment period: Participants on each of the five treatment arms (CSJ117 0.5 to 8 mg) or placebo of the core study CCSJ117A12201C, who will enter the extension study after the last Follow-up visit (week 24) of the core study, will restart on their previously assigned CSJ117 dose or placebo from CCSJ117A12201C for 12 weeks.

A Follow-up period of 12 weeks, study drug free, following the last dose of study drug.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 325 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A 24-week, Multicenter, Randomized, Double-blind, Parallel-arm, Placebo-controlled Extension Study to Assess the Safety of CSJ117, When Added to Existing Standard of Care Asthma Therapy in Patients ≥18 Years of Age
• Actual Study Start Date: Sep 8, 2021
• Actual Primary Completion Date: Jul 14, 2022
• Anticipated Study Completion Date: Sep 8, 2022

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 24-week Placebo Participants who will enter the extension study after the last treatment visit (week 12) of the core study and will be treated with Placebo inhaled once daily for 24 weeks	Drug: CSJ117; CSJ117 (0.5 mg, 1mg, 2mg, 4 mg and 8 mg) capsules for inhalation once daily delivered via Concept1 inhalation device for 12 or 24 weeks.; Drug: Placebo; Placebo inhaled once daily for 12 or 24 weeks. Delivered via Concept1 device.
Placebo Comparator: 12-week wash out + 12-week Placebo Participants who will enter the extension study after the last treatment visit (week 12) of the core study and will be treated with Placebo inhaled once daily for 12 weeks "washout period" and Placebo inhaled once daily for 12 weeks	Drug: CSJ117; CSJ117 (0.5 mg, 1mg, 2mg, 4 mg and 8 mg) capsules for inhalation once daily delivered via Concept1 inhalation device for 12 or 24 weeks.
Placebo Comparator: 12-week Placebo Participants who will enter the extension study after the last follow-up visit (week 24) of the core study will be treated with Placebo inhaled once daily for 12 weeks	Drug: CSJ117; CSJ117 (0.5 mg, 1mg, 2mg, 4 mg and 8 mg) capsules for inhalation once daily delivered via Concept1 inhalation device for 12 or 24 weeks.
Experimental: 24-week CSJ117 Participants who will enter the extension study after the last treatment visit (week 12) of the core study and will be treated once daily for 24 weeks with the same dose of CSJ117 they received in the core study. CSJ117 (0.5 mg, 1 mg, 2 mg, 4 mg and 8 mg) inhaled once daily for 24 weeks.	Drug: CSJ117; CSJ117 (0.5 mg, 1mg, 2mg, 4 mg and 8 mg) capsules for inhalation once daily delivered via Concept1 inhalation device for 12 or 24 weeks.
Experimental: 12-week wash out + 12-week CSJ117 Participants who will enter the extension study after the last treatment visit (week 12) of the core study and will be treated with Placebo inhaled once daily for 12 weeks "washout period" and then they will be treated once daily for 12 weeks with the same dose of CSJ117 they received in the core study. CSJ117 (0.5 mg, 1 mg, 2 mg, 4 mg and 8 mg) inhaled once daily for 12 weeks.	Drug: CSJ117; CSJ117 (0.5 mg, 1mg, 2mg, 4 mg and 8 mg) capsules for inhalation once daily delivered via Concept1 inhalation device for 12 or 24 weeks.
Experimental: 12-week CSJ117 Participants who will enter the extension study after the last follow-up visit (week 24) of the core study will be treated with once daily for 12 weeks with the same dose of CSJ117 they received in the core study. CSJ117 (0.5 mg, 1 mg, 2 mg, 4 mg and 8 mg) inhaled once daily for 24 weeks.	Drug: CSJ117; CSJ117 (0.5 mg, 1mg, 2mg, 4 mg and 8 mg) capsules for inhalation once daily delivered via Concept1 inhalation device for 12 or 24 weeks.

Outcome Measures

Primary Outcome Measures

1. Number of treatment emergent adverse events (AEs) and serious adverse events (SAEs) [From start of treatment in the core study and until 30 days after end of treatment in the extension study. Up to 40 weeks.]

   Number of treatment emergent AEs, AEs leading to study treatment discontinuation, SAEs and SAEs leading to study treatment discontinuation. Treatment emergent AEs and SAEs will be counted from first day of treatment of the core study (CCSJ117A12201C) and until 30 days after last day of treatment in the extension study. For participants who will enter the extension study after the last follow-up visit (week 24) of the core study, AEs (if any) occurring from week 4 to week 12 of the drug free follow-up period will not be counted as treatment emergent AEs.

2. Number of treatment emergent participant deaths and participant hospitalizations [From start of treatment in the core study and until 30 days after end of treatment in the extension study. Up to 40 weeks.]

   Number of treatment emergent participant deaths and participant hospitalizations (any visit to the hospital requiring an overnight stay or an emergency room visit greater than 24 hours). Treatment emergent participant deaths and participant hospitalizations will be counted from first day of treatment of the core study (CCSJ117A12201C) and until 30 days after last day of treatment in the extension study. For participants who will enter the extension study after the last follow-up visit (week 24) of the core study, participant deaths and hospitalizations (if any) occurring from week 4 to week 12 of the drug free follow-up period will not be counted as treatment emergent participant deaths and hospitalizations.

Secondary Outcome Measures

1. Trough plasma concentration (Ctrough) at Steady State [Participants entering directly after completion of study treatment of core study: Weeks 2, 4, 8, 12, 14, 16, 20, 24, 26, 28 and 36; Participants entering directly after completion of the core study Follow-up period: Weeks 2, 4, 8, 12, 14, 16 and 24.]

   Ctrough measured during the treatment period and the follow up period.

2. Terminal Elimination half-life (T1/2) at Steady State [Participants entering directly after completion of study treatment of core study: Weeks 2, 4, 8, 12, 14, 16, 20, 24, 26, 28 and 36; Participants entering directly after completion of the core study Follow-up period: Weeks 2, 4, 8, 12, 14, 16 and 24.]

   Terminal Elimination half-life (T1/2) measured during the treatment period and the follow up period.

3. Change from baseline in Anti-drug immune response [Participants entering directly after completion of study treatment of core study: Weeks 2, 4, 8, 12, 14, 16, 20, 24, 26, 28 and 36; Participants entering directly after completion of the core study Follow-up period: Weeks 2, 4, 8, 12, 14, 16 and 24.]

   The change from baseline in Anti-Drug Antibodies (ADA) titers during the treatment period and the follow up period.

4. Change from baseline in Fractional exhaled Nitric Oxide (FeNO) levels [Participants entering directly after completion of study treatment of core study: Weeks 2, 4, 8, 12, 14, 16, 20, 24, 26, 28 and 36; Participants entering directly after completion of the core study Follow-up period: Weeks 2, 4, 8, 12, 14, 16 and 24.]

   The change from baseline (same as in the core study CSJ117A12201C) in the observed values in FeNO (including all scheduled post-baseline visits with FeNO data).

5. CSJ117 serum concentration [Participants entering directly after completion of study treatment of core study: Weeks 2, 4, 8, 12, 14, 16, 20, 24, 26, 28 and 36; Participants entering directly after completion of the core study Follow-up period: Weeks 2, 4, 8, 12, 14, 16 and 24.]

   Measurement of the total CSJ117 serum concentration during the treatment period and the follow up period.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• All participants must have been treated with a fixed dose combination of fluticasone propionate/salmeterol in one of two doses in stable dose alone or with additional controllers at label approved dosage (allowed only: LTRA, LAMA, Theophylline or its derivatives).

• Participants completing the Treatment period and Follow-up period of study CSJ117A12201C and continuing with study CCSJ117A12201E1 must have completed the Treatment period of CSJ117A12201C (i.e. did not discontinue blinded study treatment prematurely) and Follow-up period of study CSJ117A12201C.

Exclusion Criteria:

• Participants who were enrolled into prior study CSJ117A12201C and developed a significant and/or permanent health condition during the prior study.

• Participants who experienced a serious and drug-related AE in the prior study CSJ117A12201C.

• Participants receiving any prohibited medications.

• Participants with a history or current diagnosis of ECG abnormalities.

• Pregnant or nursing (lactating) women.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Bakersfield	California	United States	93301
2	Novartis Investigative Site	Huntington Beach	California	United States	92647
3	Novartis Investigative Site	Los Angeles	California	United States	90017
4	Novartis Investigative Site	Los Angeles	California	United States	90025
5	Novartis Investigative Site	Denver	Colorado	United States	80206
6	Novartis Investigative Site	Marietta	Georgia	United States	30060
7	Novartis Investigative Site	White Marsh	Maryland	United States	21162
8	Novartis Investigative Site	Oklahoma City	Oklahoma	United States	73120
9	Novartis Investigative Site	Greenville	South Carolina	United States	29607
10	Novartis Investigative Site	Boerne	Texas	United States	78006
11	Novartis Investigative Site	McKinney	Texas	United States	75069
12	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1122AAK
13	Novartis Investigative Site	Ranelagh, Partido De Berazate	Buenos Aires	Argentina	1884
14	Novartis Investigative Site	Rosario	Santa Fe	Argentina	S2000JKR
15	Novartis Investigative Site	San Miguel de Tucuman	Tucuman	Argentina	4000
16	Novartis Investigative Site	Mendoza		Argentina	5500
17	Novartis Investigative Site	Parana		Argentina	3100
18	Novartis Investigative Site	Erpent		Belgium	5100
19	Novartis Investigative Site	Ruse		Bulgaria	7002
20	Novartis Investigative Site	Stara Zagora		Bulgaria	6000
21	Novartis Investigative Site	Burlington	Ontario	Canada	L7N 3V2
22	Novartis Investigative Site	Etobicoke	Ontario	Canada	M9V 4B4
23	Novartis Investigative Site	Montreal	Quebec	Canada	H2V 2K1
24	Novartis Investigative Site	Teplice	CZE	Czechia	415 01
25	Novartis Investigative Site	Lovosice		Czechia	41002
26	Novartis Investigative Site	Bamberg		Germany	96049
27	Novartis Investigative Site	Berlin		Germany	10119
28	Novartis Investigative Site	Berlin		Germany	10717
29	Novartis Investigative Site	Berlin		Germany	10969
30	Novartis Investigative Site	Berlin		Germany	12159
31	Novartis Investigative Site	Frankfurt		Germany	60596
32	Novartis Investigative Site	Leipzig		Germany	D-04299
33	Novartis Investigative Site	Leipzig		Germany	D-04347
34	Novartis Investigative Site	Witten		Germany	58452
35	Novartis Investigative Site	Balassagyarmat		Hungary	2660
36	Novartis Investigative Site	Godollo		Hungary	2100
37	Novartis Investigative Site	Komarom		Hungary	2900
38	Novartis Investigative Site	Yokohama-city	Kanagawa	Japan	223-0059
39	Novartis Investigative Site	Osaka city	Osaka	Japan	530 0001
40	Novartis Investigative Site	Chuo ku	Tokyo	Japan	104-0031
41	Novartis Investigative Site	Chuo-ku	Tokyo	Japan	103-0003
42	Novartis Investigative Site	Chuo-ku	Tokyo	Japan	103-0028
43	Novartis Investigative Site	Kodaira	Tokyo	Japan	187-0024
44	Novartis Investigative Site	Setagaya-Ku	Tokyo	Japan	157-0072
45	Novartis Investigative Site	Setagaya-ku	Tokyo	Japan	158-0097
46	Novartis Investigative Site	Toshima ku	Tokyo	Japan	170 0003
47	Novartis Investigative Site	Toshima	Tokyo	Japan	170-0003
48	Novartis Investigative Site	Osaka		Japan	531-0073
49	Novartis Investigative Site	Osaka		Japan	551-0032
50	Novartis Investigative Site	Riga	LV	Latvia	1038
51	Novartis Investigative Site	Daugavpils		Latvia	LV-5417
52	Novartis Investigative Site	Riga		Latvia	LV 1002
53	Novartis Investigative Site	Iloilo City		Philippines	5000
54	Novartis Investigative Site	Iloilo		Philippines	5000
55	Novartis Investigative Site	Manila		Philippines	1003
56	Novartis Investigative Site	Krakow		Poland	30033
57	Novartis Investigative Site	Lodz		Poland	90 153
58	Novartis Investigative Site	Poznan		Poland	60-693
59	Novartis Investigative Site	Poznan		Poland	60-823
60	Novartis Investigative Site	Saratov		Russian Federation	410012
61	Novartis Investigative Site	St Petersburg		Russian Federation	194354
62	Novartis Investigative Site	Levice		Slovakia	93401

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04946318
• Other Study ID Numbers: CCSJ117A12201E1; 2020-002341-42
• First Posted: Jun 30, 2021
• Last Update Posted: Aug 11, 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: No
• Keywords provided by Novartis Pharmaceuticals: CSJ, GINA 2019, Safety
• Additional relevant MeSH terms: Asthma

Study Results

No Results Posted as of Aug 11, 2022