Sjögren SyndromePhase 2LOUiSSeNCT04035668
A Phase 2 Study to Evaluate the Safety and Efficacy of LOU064 in Patients With Moderate to Severe Sjögren's Syndrome
A Phase 2 study testing Remibrutinib in people with Sjögren Syndrome, run by Novartis Pharmaceuticals at 26 sites in 12 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Sjögren Syndrome
- What is being tested?
- Remibrutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 73 participants
- Where
- 26 sitesin 12 countries
- Study dates
- 12 Jul 2019to 23 Nov 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
26 sites in 12 countries.
26 sites in 12 countries
Spain5 sites
Novartis Investigative Site
Barcelona, 08041
Novartis Investigative Site
Madrid, 28041
Novartis Investigative Site
Sabadell, Barcelona, 08208
Novartis Investigative Site
Valencia, Valencia, 46010
Novartis Investigative Site
Vigo, Pontevedra, 36200
Taiwan4 sites
Novartis Investigative Site
Kaohsiung City, 81346
Novartis Investigative Site
Taichung, Taiwan ROC, 40201
Novartis Investigative Site
Taichung, 40447
Novartis Investigative Site
Taichung, 40705
Australia3 sites
Novartis Investigative Site
Clayton, Victoria, 3168
Novartis Investigative Site
Hobart, Tasmania, 7000
Novartis Investigative Site
Woodville, South Australia, 5011
China3 sites
Novartis Investigative Site
Chengdu, Sichuan, 610041
Novartis Investigative Site
Hefei, Anhui, 230001
Novartis Investigative Site
Nanjing, Jiangsu, 210008
United Kingdom3 sites
Novartis Investigative Site
Liverpool, L9 7AL
Novartis Investigative Site
Swindon, SN3 6BB
Novartis Investigative Site
Tyne and Wear, NE29 8NH
Switzerland2 sites
Novartis Investigative Site
Basel, 4031
Novartis Investigative Site
Lausanne, 1011
United States1 site
Novartis Investigative Site
Boston, Massachusetts, 02111
About this study
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)
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.
Read the 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.
- Conditions
- Sjögren Syndrome
- Being tested
- Remibrutinib, Placebo
- 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
- Medical subject headings
- Sjogren's Syndrome, Dry Eye Syndromes, Pathologic Processes, Arthritis, Joint Diseases, Musculoskeletal Diseases, Rheumatic Diseases, Xerostomia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RemibrutinibDrug
Also called LOU064
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Remibrutinib 100 mg bid | Experimental | Remibrutinib 100 mg twice daily (bid) Receives: Drug: Remibrutinib |
| Remibrutinib 100 mg qd | Experimental | Remibrutinib 100 mg once daily (qd) Receives: Drug: Remibrutinib; Drug: Placebo |
| Placebo | Placebo comparator | Placebo group Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Week 24
Secondary outcomes (16)
Change From Baseline in ESSDAI Total Score Over Time
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.
Measured: 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
ESSPRI is an established disease outcome measure for Sjögren's Syndrome. It consists of three domains of dryness, pain, and fatigue. The patient can assess the severity of symptoms they experience on a single 0-10 numerical scale for each of the three domains. The ESSPRI score is defined as the mean of scores from the three scales: (dryness + pain +fatigue) /3. ESSPRI total score ranges from 0 to 10 with higher values indicating more disease symptoms. 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 ESSPRI for all post-baseline time points up to Week 24. Values estimated from the model are presented in this table.
Measured: 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
FACIT-F v4 is a short, 13-item, easy-to-administer tool that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue was measured on a 5-point Likert scale (0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, 4 = very much). FACIT-F total score ranges from 0 to 52 with higher values indicating higher quality of life (less fatigue). A positive change from baseline is a favorable outcome.
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 FACIT-F for all post-baseline time points up to Week 24. Values estimated from the model are presented in this table.
Measured: 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
EQ-5D is a standardized instrument that measures the health-related quality of life. The EQ-5D consists of a descriptive system and a visual analog scale (VAS).The EQ-5D VAS records the patient's self-rated health on a vertical visual analogue scale with 0 representing 'Worst imaginable Health State' and 100 'Best imaginable Health State'. A positive change from baseline is a favorable outcome.
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 EQ-5D VAS score for all post-baseline time points up to Week 24. Values estimated from the model are presented in this table.
Measured: 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
The physician's global assessment scale was used for the Investigator to rate the disease activity of their patient using 100 mm visual analog scale (VAS) ranging from "no disease activity" (0) to "maximal disease activity" (100). 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 PhGA score for all post-baseline time points up to Week 24. Values estimated from the model are presented in this table.
Measured: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Number of participants with TEAEs and serious TEAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as TEAEs. TEAEs are defined as adverse events that started after the first dose of study medications or adverse events present prior to start of double-blind treatment but increased in severity.
The number of participants in each category is reported in the table.
Measured: From first dose of study treatment up 30 days after last dose (Week 29)
Maximum Observed Blood Concentration (Cmax) of Remibrutinib at Week 4
Remibrutinib was determined in whole blood by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1.0 ng/mL. Pharmacokinetic (PK) parameters were calculated based on remibrutinib blood concentrations by using the actual recorded sampling times and non-compartmental methods with Phoenix WinNonlin (version 8 or higher). Concentrations below the LLOQ were treated as zero. Cmax is defined as the maximum (peak) observed blood concentration following a dose.
Measured: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4
Maximum Observed Blood Concentration (Cmax) of Remibrutinib at Week 24
Remibrutinib was determined in whole blood by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1.0 ng/mL. Pharmacokinetic (PK) parameters were calculated based on remibrutinib blood concentrations by using the actual recorded sampling times and non-compartmental methods with Phoenix WinNonlin (version 8 or higher). Concentrations below the LLOQ were treated as zero. Cmax is defined as the maximum (peak) observed blood concentration following a dose.
Measured: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24
Time to Reach Maximum Observed Blood Concentration (Tmax) of Remibrutinib at Week 4
Remibrutinib was determined in whole blood by a validated LC-MS/MS method with a LLOQ of 1.0 ng/mL. Pharmacokinetic (PK) parameters were calculated based on remibrutinib blood concentrations by using the actual recorded sampling times and non-compartmental methods with Phoenix WinNonlin (version 8 or higher). Concentrations below the LLOQ were treated as zero. Tmax is defined as the time to reach maximum (peak) blood concentration following a dose.
Measured: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4
Time to Reach Maximum Observed Blood Concentration (Tmax) of Remibrutinib at Week 24
Remibrutinib was determined in whole blood by a validated LC-MS/MS method with a LLOQ of 1.0 ng/mL. Pharmacokinetic (PK) parameters were calculated based on remibrutinib blood concentrations by using the actual recorded sampling times and non-compartmental methods with Phoenix WinNonlin (version 8 or higher). Concentrations below the LLOQ were treated as zero. Tmax is defined as the time to reach maximum (peak) blood concentration following a dose.
Measured: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24
Area Under the Blood Concentration-time Curve Within a Dosing Interval (Tau) at Steady-state (AUCtau) of Remibrutinib at Week 4
Remibrutinib was determined in whole blood by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1.0 ng/mL. Pharmacokinetic (PK) parameters were calculated based on remibrutinib blood concentrations by using the actual recorded sampling times and non-compartmental methods with Phoenix WinNonlin (version 8 or higher). Concentrations below the LLOQ were treated as zero. AUCtau is defined as the area under the blood concentration-time curve calculated/extrapolated to the end of a dosing interval (tau) at steady-state. Tau was 24 hours for the qd dosing group and 12 hours for the bid dosing group. For the calculation of AUCtau, the pre-dose concentrations at Week 4 and Week 24 were duplicated as 24 hours and 12 hours concentrations for the qd and bid groups, respectively. The linear trapezoidal method was used for AUCtau calculation.
Measured: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4
Area Under the Blood Concentration-time Curve Within a Dosing Interval (Tau) at Steady-state (AUCtau) of Remibrutinib at Week 24
Remibrutinib was determined in whole blood by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1.0 ng/mL. Pharmacokinetic (PK) parameters were calculated based on remibrutinib blood concentrations by using the actual recorded sampling times and non-compartmental methods with Phoenix WinNonlin (version 8 or higher). Concentrations below the LLOQ were treated as zero. AUCtau is defined as the area under the blood concentration-time curve calculated/extrapolated to the end of a dosing interval (tau) at steady-state. Tau was 24 hours for the qd dosing group and 12 hours for the bid dosing group. For the calculation of AUCtau, the pre-dose concentrations at Week 4 and Week 24 were duplicated as 24 hours and 12 hours concentrations for the qd and bid groups, respectively. The linear trapezoidal method was used for AUCtau calculation.
Measured: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24
Area Under the Blood Concentration-time Curve From Time Zero to 4 Hours Post-dose (AUC0-4h) of Remibrutinib at Week 4
Remibrutinib was determined in whole blood by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1.0 ng/mL. Pharmacokinetic (PK) parameters were calculated based on remibrutinib blood concentrations by using the actual recorded sampling times and non-compartmental methods with Phoenix WinNonlin (version 8 or higher). Concentrations below the LLOQ were treated as zero. AUC0-4h is defined as the area under the blood concentration-time curve from time zero to 4 hours post-dose, which was the last sampling time. The linear trapezoidal method was used for AUC0-4h calculation.
Measured: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4
Area Under the Blood Concentration-time Curve From Time Zero to 4 Hours Post-dose (AUC0-4h) of Remibrutinib at Week 24
Remibrutinib was determined in whole blood by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1.0 ng/mL. Pharmacokinetic (PK) parameters were calculated based on remibrutinib blood concentrations by using the actual recorded sampling times and non-compartmental methods with Phoenix WinNonlin (version 8 or higher). Concentrations below the LLOQ were treated as zero. AUC0-4h is defined as the area under the blood concentration-time curve from time zero to 4 hours post-dose, which was the last sampling time. The linear trapezoidal method was used for AUC0-4h calculation.
Measured: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24
Elimination Half-life (T1/2) of Remibrutinib at Week 4
Remibrutinib was determined in whole blood by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1.0 ng/mL. Pharmacokinetic (PK) parameters were calculated based on remibrutinib blood concentrations by using the actual recorded sampling times and non-compartmental methods with Phoenix WinNonlin (version 8 or higher). Concentrations below the LLOQ were treated as zero. T1/2 is defined as the time taken for the blood concentration, as well as the amount of the drug in the body, to fall by one-half.
Measured: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4
Elimination Half-life (T1/2) of Remibrutinib at Week 24
Remibrutinib was determined in whole blood by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1.0 ng/mL. Pharmacokinetic (PK) parameters were calculated based on remibrutinib blood concentrations by using the actual recorded sampling times and non-compartmental methods with Phoenix WinNonlin (version 8 or higher). Concentrations below the LLOQ were treated as zero. T1/2 is defined as the time taken for the blood concentration, as well as the amount of the drug in the body, to fall by one-half.
Measured: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2019
- Study start12 Jul 2019
- Primary completion23 Nov 2021
- Study completion23 Nov 2021
Why it stopped: Sponsor's decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sjögren SyndromeStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 73 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04035668
- Sponsor's protocol ID
- CLOU064E12201
- Other IDs
- 2018-004387-54, 2018
- Acronym
- LOUiSSe
- Status last verified
- Jan 2023
- First submitted
- 8 Jul 2019
- Last updated
- 30 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Publications
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.
PubMed 37932009
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04035668
- Acronym / sponsor ID
- LOUiSSe / CLOU064E12201
- Conditions
- Sjögren Syndrome
- Keywords
- LOU064, remibrutinib, Sjogren Syndrome, Dry Eye Syndromes, Pathological Processes, Arthritis, Joint Diseases, Musculoskeletal Diseases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor's decision
- Enrolment
- 73 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 12 Jul 2019 (actual)
- Primary completion
- 23 Nov 2021 (actual)
- Study completion
- 23 Nov 2021 (actual)
- First posted
- 29 Jul 2019 (actual)
- Results
- Posted 20 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Remibrutinib 100 mg bid | Experimental | Drug: RemibrutinibRemibrutinib 100 mg twice daily (bid) |
| Remibrutinib 100 mg qd | Experimental | Drug: Remibrutinib, Drug: PlaceboRemibrutinib 100 mg once daily (qd) |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo group |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RemibrutinibAlso: LOU064Remibrutinib 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. | Drug | Remibrutinib 100 mg bid, Remibrutinib 100 mg qd |
| PlaceboPlacebo 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. | Drug | Placebo, Remibrutinib 100 mg qd |
Primary outcome
Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) Total Score at Week 24
Time frame: Baseline, 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.
16 secondary outcomes
Change From Baseline in ESSDAI Total Score Over Time
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Time frame: From first dose of study treatment up 30 days after last dose (Week 29)
Maximum Observed Blood Concentration (Cmax) of Remibrutinib at Week 4
Time frame: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4
Maximum Observed Blood Concentration (Cmax) of Remibrutinib at Week 24
Time frame: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24
Time to Reach Maximum Observed Blood Concentration (Tmax) of Remibrutinib at Week 4
Time frame: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4
Time to Reach Maximum Observed Blood Concentration (Tmax) of Remibrutinib at Week 24
Time frame: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24
Area Under the Blood Concentration-time Curve Within a Dosing Interval (Tau) at Steady-state (AUCtau) of Remibrutinib at Week 4
Time frame: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4
Area Under the Blood Concentration-time Curve Within a Dosing Interval (Tau) at Steady-state (AUCtau) of Remibrutinib at Week 24
Time frame: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24
Area Under the Blood Concentration-time Curve From Time Zero to 4 Hours Post-dose (AUC0-4h) of Remibrutinib at Week 4
Time frame: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4
Area Under the Blood Concentration-time Curve From Time Zero to 4 Hours Post-dose (AUC0-4h) of Remibrutinib at Week 24
Time frame: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24
Elimination Half-life (T1/2) of Remibrutinib at Week 4
Time frame: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 4
Elimination Half-life (T1/2) of Remibrutinib at Week 24
Time frame: pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose at Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37932009Dorner 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.
- A Plain Language Trial Summary is available on novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
26 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Remibrutinib in people with Sjögren Syndrome, run by Novartis Pharmaceuticals at 26 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in Spain, Taiwan, Australia, China, United Kingdom and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) Total Score at Week 24 (time frame: Baseline, Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04035668, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2023.