LOUiSSe: A Phase 2 Study to Evaluate the Safety and Efficacy of LOU064 in Patients With Moderate to Severe Sjögren's Syndrome

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04035668

Collaborator

(none)

252

Enrollment

Locations

Arms

60.3

Anticipated Duration (Months)

8.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

LOU064 is an oral Bruton's tyrosine kinase (BTK) inhibitor. This study is an adaptive phase 2 study designed to establish safety and efficacy and characterize the dose-response of LOU064 in subjects with moderate to severe Sjögren's syndrome.

Condition or Disease	Intervention/Treatment	Phase
Sjögren Syndrome	Drug: LOU064 Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

252 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Other

Official Title:

An Adaptive Phase 2 Randomized Double-blind, Placebo-controlled Multi-center Study to Evaluate the Safety and Efficacy of Multiple LOU064 Doses in Patients With Moderate to Severe Sjögren's Syndrome (LOUiSSe)

Actual Study Start Date :

Jul 12, 2019

Anticipated Primary Completion Date :

Jun 19, 2024

Anticipated Study Completion Date :

Jul 19, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LOU064 Dose 1 high orally	Drug: LOU064 10mg hard gelatin capsules 25mg hard gelatin capsules 50mg hard gelatin capsules
Experimental: LOU064 Dose 2 high orally	Drug: LOU064 10mg hard gelatin capsules 25mg hard gelatin capsules 50mg hard gelatin capsules
Experimental: LOU064 Dose 3 middle orally	Drug: LOU064 10mg hard gelatin capsules 25mg hard gelatin capsules 50mg hard gelatin capsules
Experimental: LOU064 Dose 4 low orally	Drug: LOU064 10mg hard gelatin capsules 25mg hard gelatin capsules 50mg hard gelatin capsules
Placebo Comparator: Placebo 0 mg orally	Drug: Placebo 0mg hard gelatin capsule

Outcome Measures

Primary Outcome Measures

Change in EULAR Sjögren's syndrome disease activity index (ESSDAI) at week 24 [Week 24]
Efficacy (Clinical Outcome Measures)

Secondary Outcome Measures

Change from baseline in ESSDAI over time [Baseline, week 2, week 4, week 8, week 12, week 16 and week 20]
Efficacy (Clinical Outcome Measures)
Change in EULAR Sjögren's Syndrome Patient Reported intensity (ESSPRI) over time [24 weeks]
Efficacy (Patient Reported Outcomes)
Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) over time [24 weeks]
Efficacy (Patient Reported Outcomes)
Change from baseline in quality of life as assessed by EQ-5D over time [24 weeks]
Efficacy (Patient Reported Outcomes)
Change from baseline in quality of life as assessed by PhGA over time [24 weeks]
Efficacy (Patient Reported Outcomes)
Occurrence of treatment emergent Adverse Events [34 weeks]
Safety
PK parameters: area under the curve (AUC) [24 weeks]
Pharmacokinetics
PK parameters: Cmax [24 weeks]
Pharmacokinetics
PK parameters: Tmax [24 weeks]
Pharmacokinetics
PK parameters: mean residence time (MRT) [24 weeks]
Pharmacokinetics

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of SjS according to the 2016 ACR/EULAR criteria
Screening ESSDAI (based on weighted score) ≥ 5 derived from 8 domains
Screening ESSPRI ≥ 5
Seropositive for anti-Ro/SSA antibodies at or within 3 months prior to screening
Unstimulated salivary flow > 0 mL/min.

Exclusion Criteria:

Sjögren's Syndrome overlap syndromes with another autoimmune disease as primary illness
DMARDs or kinase inhibitors within 3 months prior to baseline above certain doses OR maintained during study
Rituximab or other B cell depleting drug within 12 months of Screening .
Current use of prednisone or equivalent > 15mg/d or dose change within 2 weeks prior to Screening
Use of medication known to cause, as a major side effect, dry mouth / eyes
HIV, Hepatitis C, Hepatitis B, known or suspected history of an ongoing, chronic or recurrent infectious disease such as tuberculosis

Other protocol-defined inclusion/exclusion criteria may apply at the end

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Boston	Massachusetts	United States	02111
2	Novartis Investigative Site	Oklahoma City	Oklahoma	United States	73104
3	Novartis Investigative Site	San Antonio	Texas	United States	78284
4	Novartis Investigative Site	Woodville	South Australia	Australia	5011
5	Novartis Investigative Site	Hobart	Tasmania	Australia	7000
6	Novartis Investigative Site	Clayton	Victoria	Australia	3168
7	Novartis Investigative Site	Gent		Belgium	9000
8	Novartis Investigative Site	Sofia		Bulgaria	1612
9	Novartis Investigative Site	Hefei	Anhui	China	230001
10	Novartis Investigative Site	Nanjing	Jiangsu	China	210008
11	Novartis Investigative Site	Chengdu	Sichuan	China	610041
12	Novartis Investigative Site	Glostrup		Denmark	2600
13	Novartis Investigative Site	Berlin		Germany	10117
14	Novartis Investigative Site	Debrecen		Hungary	4032
15	Novartis Investigative Site	Sabadell	Barcelona	Spain	08208
16	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46010
17	Novartis Investigative Site	Vigo	Pontevedra	Spain	36200
18	Novartis Investigative Site	Barcelona		Spain	08041
19	Novartis Investigative Site	Madrid		Spain	28041
20	Novartis Investigative Site	Basel		Switzerland	4031
21	Novartis Investigative Site	Lausanne		Switzerland	1011
22	Novartis Investigative Site	Taichung	Taiwan ROC	Taiwan	40201
23	Novartis Investigative Site	Kaohsiung		Taiwan	81346
24	Novartis Investigative Site	Taichung		Taiwan	40447
25	Novartis Investigative Site	Taichung		Taiwan	40705
26	Novartis Investigative Site	Taoyuan		Taiwan	33305
27	Novartis Investigative Site	Liverpool		United Kingdom	L9 7AL
28	Novartis Investigative Site	Newcastle upon Tyne		United Kingdom	NE1 4LP
29	Novartis Investigative Site	Swindon		United Kingdom	SN3 6BB
30	Novartis Investigative Site	Tyne And Wear		United Kingdom	NE29 8NH