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

NCT ID: NCT04035668

Last Updated: 2023-01-30

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

73 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-07-12

Study Completion Date

2021-11-23

Brief Summary

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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.

Detailed Description

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This study was planned as an adaptive Phase 2 randomized, double-blind, placebo-controlled, multi-center, integrated dose-ranging study to evaluate the safety and efficacy of multiple remibrutinib doses in patients with moderate to severe Sjögren's Syndrome.

Of the initially planned two parts, only Part 1 of the study was conducted. In Part 1, the highest expected biologically active single dose of remibrutinib (100 mg) was tested in two different dosing regimens, a once daily dose (qd) or twice daily dose (bid), and compared to the placebo group. Each patient in Part 1 of the study underwent a screening period of up to 6 weeks, a treatment period of 24 weeks, and a follow-up period of 30 days post-treatment before the End of Study (EOS) visit. The total duration for each patient in the study, including Screening, was up to 35 weeks. For the treatment period, patients were randomized in a 1:1:1 ratio to one of the 3 treatment groups: remibrutinib 100 mg bid, remibrutinib 100 mg qd and placebo.

Conditions

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Sjögren Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Remibrutinib 100 mg bid

Remibrutinib 100 mg twice daily (bid)

Group Type EXPERIMENTAL

Remibrutinib

Intervention Type 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.

Remibrutinib 100 mg qd

Remibrutinib 100 mg once daily (qd)

Group Type EXPERIMENTAL

Remibrutinib

Intervention Type 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.

Placebo

Intervention Type 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

Placebo group

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type 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.

Interventions

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Remibrutinib

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.

Intervention Type DRUG

Placebo

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.

Intervention Type DRUG

Other Intervention Names

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LOU064

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Boston, Massachusetts, United States

Site Status

Novartis Investigative Site

Woodville, South Australia, Australia

Site Status

Novartis Investigative Site

Hobart, Tasmania, Australia

Site Status

Novartis Investigative Site

Clayton, Victoria, Australia

Site Status

Novartis Investigative Site

Ghent, , Belgium

Site Status

Novartis Investigative Site

Sofia, , Bulgaria

Site Status

Novartis Investigative Site

Hefei, Anhui, China

Site Status

Novartis Investigative Site

Nanjing, Jiangsu, China

Site Status

Novartis Investigative Site

Chengdu, Sichuan, China

Site Status

Novartis Investigative Site

Glostrup Municipality, , Denmark

Site Status

Novartis Investigative Site

Berlin, , Germany

Site Status

Novartis Investigative Site

Debrecen, , Hungary

Site Status

Novartis Investigative Site

Sabadell, Barcelona, Spain

Site Status

Novartis Investigative Site

Vigo, Pontevedra, Spain

Site Status

Novartis Investigative Site

Valencia, Valencia, Spain

Site Status

Novartis Investigative Site

Barcelona, , Spain

Site Status

Novartis Investigative Site

Madrid, , Spain

Site Status

Novartis Investigative Site

Basel, , Switzerland

Site Status

Novartis Investigative Site

Lausanne, , Switzerland

Site Status

Novartis Investigative Site

Taichung, Taiwan ROC, Taiwan

Site Status

Novartis Investigative Site

Kaohsiung City, , Taiwan

Site Status

Novartis Investigative Site

Taichung, , Taiwan

Site Status

Novartis Investigative Site

Taichung, , Taiwan

Site Status

Novartis Investigative Site

Liverpool, , United Kingdom

Site Status

Novartis Investigative Site

Swindon, , United Kingdom

Site Status

Novartis Investigative Site

Tyne and Wear, , United Kingdom

Site Status

Countries

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United States Australia Belgium Bulgaria China Denmark Germany Hungary Spain Switzerland Taiwan United Kingdom

References

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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.

Reference Type DERIVED
PMID: 37932009 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=1361

A Plain Language Trial Summary is available on novctrd.com

Other Identifiers

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2018-004387-54

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLOU064E12201

Identifier Type: -

Identifier Source: org_study_id

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