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

NCT04035668 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: CLOU064E122012018-004387-54
• Study Type: interventional
• Target: 73
• Locations: 12 countries
• Sites: 26

Brief Summary

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

Conditions

Sjögren Syndrome

Keywords

LOU064; remibrutinib; Sjogren Syndrome; Dry Eye Syndromes; Pathological Processes; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Lacrimal Apparatus Diseases; Eye Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) Total Score at Week 24

  ESSDAI is a validated disease outcome measure for Sjögren's Syndrome. The instrument contains 12 organ-specific domains contributing to disease activity: constitutional, lymphadenopathy, glandular, articular, cutaneous, pulmonary, renal, muscular, peripheral nervous system, central nervous system, hematological and biological. For each domain, features of disease activity were scored according to their severity. These scores were summed across the 12 domains in a weighted manner to provide the total score. ESSDAI total score ranges from 0 to 123 with higher values indicating more disease activity. A negative change from baseline indicates improvement. The baseline value is defined as the last assessment performed prior to administration of the first dose of study treatment. A mixed effect model for repeated measurements (MMRM) was fitted to the changes from baseline in ESSDAI for all post-baseline time points up to Week 24. Values estimated from the model are presented in this table.

  Baseline, Week 24

Secondary Outcomes (16)

• Change From Baseline in ESSDAI Total Score Over Time

  Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 and Week 20

• Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) Total Score Over Time

  Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24

• Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Total Score Over Time

  Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24

• Change From Baseline in EuroQual 5 Dimensions (EQ-5D) VAS Score Over Time

  Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24

• Change From Baseline in Physician Global Assessment Scale (PhGA) Score Over Time

  Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24

Study Arms (3)

Remibrutinib 100 mg bid

EXPERIMENTAL

Remibrutinib 100 mg twice daily (bid)

Drug: Remibrutinib

Remibrutinib 100 mg qd

EXPERIMENTAL

Remibrutinib 100 mg once daily (qd)

Drug: Remibrutinib; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Placebo group

Drug: Placebo

Interventions

Remibrutinib DRUG

Remibrutinib 100 mg was administered orally as two 50 mg hard gelatin capsules. Patients in the remibrutinib 100 mg bid dose group took 2 capsules of active medication in the morning and 2 capsules of active medication in the evening. Patients in the remibrutinib 100 mg qd dose group took 2 capsules of active medication in the morning and 2 capsules of the placebo in the evening.

Also known as: LOU064

Remibrutinib 100 mg bid; Remibrutinib 100 mg qd

Placebo DRUG

Placebo was administered orally as two hard gelatin capsules. Patients in the placebo dose group took 2 capsules of placebo in the morning and 2 capsules of placebo in the evening.

Placebo; Remibrutinib 100 mg qd

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (26)

Novartis Investigative Site

Boston, Massachusetts, 02111, United States

Location

Novartis Investigative Site

Woodville, South Australia, 5011, Australia

Location

Novartis Investigative Site

Hobart, Tasmania, 7000, Australia

Location

Novartis Investigative Site

Clayton, Victoria, 3168, Australia

Location

Novartis Investigative Site

Ghent, 9000, Belgium

Location

Novartis Investigative Site

Sofia, 1612, Bulgaria

Location

Novartis Investigative Site

Hefei, Anhui, 230001, China

Location

Novartis Investigative Site

Nanjing, Jiangsu, 210008, China

Location

Novartis Investigative Site

Chengdu, Sichuan, 610041, China

Location

Novartis Investigative Site

Glostrup Municipality, 2600, Denmark

Location

Novartis Investigative Site

Berlin, 10117, Germany

Location

Novartis Investigative Site

Debrecen, 4032, Hungary

Location

Novartis Investigative Site

Sabadell, Barcelona, 08208, Spain

Location

Novartis Investigative Site

Vigo, Pontevedra, 36200, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46010, Spain

Location

Novartis Investigative Site

Barcelona, 08041, Spain

Location

Novartis Investigative Site

Madrid, 28041, Spain

Location

Novartis Investigative Site

Basel, 4031, Switzerland

Location

Novartis Investigative Site

Lausanne, 1011, Switzerland

Location

Novartis Investigative Site

Taichung, Taiwan ROC, 40201, Taiwan

Location

Novartis Investigative Site

Kaohsiung City, 81346, Taiwan

Location

Novartis Investigative Site

Taichung, 40447, Taiwan

Location

Novartis Investigative Site

Taichung, 40705, Taiwan

Location

Novartis Investigative Site

Liverpool, L9 7AL, United Kingdom

Location

Novartis Investigative Site

Swindon, SN3 6BB, United Kingdom

Location

Novartis Investigative Site

Tyne and Wear, NE29 8NH, United Kingdom

Location

Related Publications (1)

• Dorner T, Kaul M, Szanto A, Tseng JC, Papas AS, Pylvaenaeinen I, Hanser M, Abdallah N, Grioni A, Santos Da Costa A, Ferrero E, Gergely P, Hillenbrand R, Avrameas A, Cenni B, Siegel RM. Efficacy and safety of remibrutinib, a selective potent oral BTK inhibitor, in Sjogren's syndrome: results from a randomised, double-blind, placebo-controlled phase 2 trial. Ann Rheum Dis. 2024 Feb 15;83(3):360-371. doi: 10.1136/ard-2023-224691.

  PMID: 37932009 DERIVED

Related Links

• A Plain Language Trial Summary is available on novctrd.com

MeSH Terms

Conditions

Sjogren's Syndrome; Dry Eye Syndromes; Pathologic Processes; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Lacrimal Apparatus Diseases; Eye Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Interventions

remibrutinib

Condition Hierarchy (Ancestors)

Arthritis, Rheumatoid; Skin and Connective Tissue Diseases; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2019
• First Posted: July 29, 2019
• Study Start: July 12, 2019
• Primary Completion: November 23, 2021
• Study Completion: November 23, 2021
• Last Updated: January 30, 2023
• Results First Posted: December 20, 2022

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share

Locations

AU (3); DE (1); ES (5); US (1); HU (1); CH (2); DK (1); GB (3); BU (1); BE (1); TW (4); CN (3)