Clinical trial NCT04035668: A Phase 2 Study to Evaluate the Safety and Efficacy of LOU064 in Patients With Moderate to Severe Sjögren's Syndrome
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-07-29
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) Total Score at Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Change From Baseline in ESSDAI Total Score Over Time
timeFrame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 and Week 20
measure: Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) Total Score Over Time
timeFrame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Total Score Over Time
timeFrame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24
measure: Change From Baseline in EuroQual 5 Dimensions (EQ-5D) VAS Score Over Time
timeFrame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24
measure: Change From Baseline in Physician Global Assessment Scale (PhGA) Score Over Time
timeFrame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: From first dose of study treatment up 30 days after last dose (Week 29)
measure: Maximum Observed Blood Concentration (Cmax) of Remibrutinib at Week 4
timeFrame: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4
measure: Maximum Observed Blood Concentration (Cmax) of Remibrutinib at Week 24
timeFrame: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24
measure: Time to Reach Maximum Observed Blood Concentration (Tmax) of Remibrutinib at Week 4
timeFrame: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4
measure: Time to Reach Maximum Observed Blood Concentration (Tmax) of Remibrutinib at Week 24
timeFrame: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24
measure: Area Under the Blood Concentration-time Curve Within a Dosing Interval (Tau) at Steady-state (AUCtau) of Remibrutinib at Week 4
timeFrame: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4
measure: Area Under the Blood Concentration-time Curve Within a Dosing Interval (Tau) at Steady-state (AUCtau) of Remibrutinib at Week 24
timeFrame: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24
measure: Area Under the Blood Concentration-time Curve From Time Zero to 4 Hours Post-dose (AUC0-4h) of Remibrutinib at Week 4
timeFrame: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4
measure: Area Under the Blood Concentration-time Curve From Time Zero to 4 Hours Post-dose (AUC0-4h) of Remibrutinib at Week 24
timeFrame: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24
measure: Elimination Half-life (T1/2) of Remibrutinib at Week 4
timeFrame: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4
measure: Elimination Half-life (T1/2) of Remibrutinib at Week 24
timeFrame: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24
Other outcomes:
Locations:
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Woodville
country: Australia
facility: Novartis Investigative Site
state: South Australia
city: Hobart
country: Australia
facility: Novartis Investigative Site
state: Tasmania
city: Clayton
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Hefei
country: China
facility: Novartis Investigative Site
state: Anhui
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Glostrup
country: Denmark
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Sabadell
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Vigo
country: Spain
facility: Novartis Investigative Site
state: Pontevedra
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Basel
country: Switzerland
facility: Novartis Investigative Site
city: Lausanne
country: Switzerland
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
state: Taiwan ROC
city: Kaohsiung
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Liverpool
country: United Kingdom
facility: Novartis Investigative Site
city: Swindon
country: United Kingdom
facility: Novartis Investigative Site
city: Tyne And Wear
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: