A Phase 3 interventional study of LOU064 (blinded) and Placebo in Chronic Spontaneous Urticaria, sponsored by Novartis Pharmaceuticals. Completed at 122 sites in 18 countries. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2025-04-08.
Sponsored by Novartis Pharmaceuticals · Phase 3, Interventional, and Treatment
The purpose of this study was to establish the efficacy, safety, and tolerability of Remibrutinib 25 mg b.i.d. in adult patients suffering from chronic spontaneous urticaria (CSU) inadequately controlled by second generation H1-antihistamines (H1-AHs) in comparison to placebo.
The study consisted of four periods, the total study duration was up to 60 weeks: Screening period of up to 4 weeks, Double-blind placebo-controlled treatment period of 24 weeks, Open-label treatment period with Remibrutinib period of 28 weeks, and treatment free follow-up period of 4 weeks.
The design of this study was a replicate of another Phase III study, CLOU046A2301 (NCT05030311).
The study population consisted of female and male adult patients with CSU inadequately controlled by second generation H1-AHs at least at a locally label approved dose. All patients were on a stable, locally label approved dose of a second generation H1 AH (background therapy) throughout the entire study (starting a minimum of 7 days prior to randomization until the end of the study). To treat unbearable symptoms of CSU, patients were allowed to use another second generation H1-AH on an as-needed basis (rescue therapy). Eligible patients were randomly assigned to the treatment arms in a 2:1 ratio to remibrutinib or placebo arm (300 in the remibrutinib arm and 150 in placebo arm) and stratified based on prior exposure to anti-IgE biologics for CSU and geographic region.
An extension Phase IIIb study, CLOU064A2303B (NCT05513001), was initiated to allow CLOU064A2302 eligible patients to roll over after completion of the open-label treatment period.
There were two distinct testing strategies (scenario 1 with Weekly Urticaria Activity Score (UAS7) as the primary efficacy endpoint and scenario 2 with Weekly Itch Severity Score (ISS7) and Weekly Hives Severity Score (HSS7) as the co-primary efficacy endpoints) based on two primary objective scenarios related to regional regulatory precedent and Health Authorities' feedback.
237 studies on the registry are indexed under Urticaria; 26 are open to participants now.
This study's enrollment of 455 is above the median of 61 across 174 interventional studies indexed under Urticaria.
Browse Urticaria studies →Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.
Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.
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Key Inclusion Criteria:
Diagnosis of CSU inadequately controlled by second generation H1-antihistamines at the time of randomization defined as:
Key Exclusion Criteria:
LOU064A (blinded) taken orally b.i.d. for 24 weeks, followed by LOU064 (open- label) taken orally b.i.d. for 28 weeks. Randomised in 2:1 ratio (active vs placebo)
Drug: LOU064 (blinded) · Drug: LOU064 (open-label)
LOU064A placebo (blinded) taken orally for 24 weeks, followed by LOU064 (open-label) taken orally b.i.d. for 28 weeks. Randomised in 2:1 ratio (active vs placebo)
Drug: Placebo · Drug: LOU064 (open-label)
LOU064 (blinded) active treatment
Also known as: remibrutinib
Placebo
LOU064 (open-label) active treatment
Also known as: remibrutinib
Mean Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12 (Scenario 1 With UAS7 as Primary Efficacy Endpoint)
The Weekly Urticaria Activity Score (UAS7) is a simple scoring system to evaluate urticaria signs and symptoms. It is based on scoring wheals (hive severity score) and itch (itch severity score) separately on a scale of 0 (no signs/symptoms) to 3 (intense signs/symptoms) over 7 days. The final score is calculated by adding together the daily scores, which can range from 0 to 6, for 7 days. This results in a maximum total score of 42 (highest urticaria severity), and a minimum possible score of 0. This endpoint is a secondary endpoint for testing strategy Scenario 2 with Weekly Itch Severity Score (ISS7) and Weekly Hives Severity Score (HSS7) as co-primary efficacy endpoints).
Time frame: Baseline, Week 12
Mean Change From Baseline in Weekly Itch Severity Score (ISS7) at Week 12 (Scenario 2 With ISS7 and HSS7 as Co-primary Efficacy Endpoints)
The severity of the itch was recorded by the participant twice daily in their electronic Diary, on a scale of 0 (none) to 3 (severe). A weekly score (ISS7) was derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score was therefore 0 - 21 (highest itch severity). This endpoint is a secondary endpoint for testing strategy Scenario 1 with Weekly Urticaria Activity Score (UAS7) as the primary efficacy endpoint).
Time frame: Baseline, Week 12
Mean Change From Baseline in Weekly Hives Severity Score (HSS7) at Week 12 (Scenario 2 With ISS7 and HSS7 as Co-primary Efficacy Endpoints)
The hives (wheals) severity score, defined by number of hives, was recorded by the participant twice daily in their electronic Diary, on a scale of 0 (none) to 3 (\> 12 hives/12 hours). A weekly score (HSS7) was derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score was therefore 0 - 21 (highest hives activity). This endpoint is a secondary endpoint for testing strategy Scenario 1 with Weekly Urticaria Activity Score (UAS7) as the primary efficacy endpoint).
Time frame: Baseline, Week 12
Number of Participants Who Achieved Disease Activity Control (UAS7 =< 6) at Week 12
The percentage of patients achieving disease activity control (UAS7 =\< 6) at Week 12 was assessed to evaluate the efficacy of Remibrutinib in Chronic Spontaneous Urticaria (CSU) patients. The UAS7 is the sum of the Weekly Hives Severity Score (HSS7) and the Weekly Itch Severity Score (ISS7). The possible range of the UAS7 score is 0 - 42 (highest hives and itch severity).
Time frame: Week 12
Number of Participants Who Achieved Complete Absence of Hives and Itch (UAS7 = 0) at Week 12
The proportion of patients achieving complete absence of hives and itch (UAS7 = 0) at Week 12 was assessed to evaluate the efficacy of Remibrutinib in Chronic Spontaneous Urticaria (CSU) patients. The UAS7 is the sum of the Weekly Hives Severity Score (HSS7) and the Weekly Itch Severity Score (ISS7). The possible range of the UAS7 score is 0 - 42 (highest hives and itch severity).
Time frame: Week 12
Number of Participants Who Achieved Early Onset of Disease Activity Control (UAS7 =< 6) at Week 2
The percentage of patients achieving disease activity control (UAS7 =\< 6) at Week 2 was assessed to evaluate the efficacy of Remibrutinib in Chronic Spontaneous Urticaria (CSU) patients. The UAS7 is the sum of the Weekly Hives Severity Score (HSS7) and the Weekly Itch Severity Score (ISS7). The possible range of the UAS7 score is 0 - 42 (highest hives and itch severity).
Time frame: Week 2
Number of Participants Who Achieved Dermatology Life Quality Index (DLQI) = 0-1 at Week 12
The Dermatology Life Quality Index (DLQI) is a 10-item (grouped in 6 domains) dermatology-specific quality of life (QoL) measure. Participants are rating their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives thinking about the previous 7 days. An overall score is calculated and ranges from 0 to 30 (higher score meaning worse disease-related QoL). Domain scores are calculated for: Symptoms and Feelings (0-6), Daily Activities (0-6), Leisure (0-6), Work and School (0-3), Personal Relationships (0-6), Treatment (0-3). The overall DLQI score range was split into score bands and validated in terms of their meaning/relevance to patients overall DLQI = 0-1 means no effect on patient's life.
Time frame: Week 12
Mean Cumulative Number of Weeks With Disease Activity Control (UAS7 =< 6) up to Week 12
Maintaining disease activity control was assessed as cumulative number of weeks with an UAS7 =\< 6 response between baseline and Week 12. The UAS7 is the sum of the Weekly Hives Severity Score (HSS7) and the Weekly Itch Severity Score (ISS7). The possible range of the UAS7 score is 0 - 42 (highest hives and itch severity).
Time frame: Up to Week 12
Mean Cumulative Number of Angioedema Occurrence-free Weeks (AAS7 = 0 Response) up to Week 12
Angioedema occurrence was recorded once daily in the evening in the electronic Diary by the participant. Reporting the occurrence of angioedema was used as opening question for the assessment of the Angioedema Activity Score (AAS). The AAS consists of 5 questions with 4 answer options (scored 0-3) for each item, with a minimum score of 0 and a maximum score of 15 per day. The AAS score over 7 days (AAS7) ranges from 0 (no angioedema episodes) to 105 (highest angioedema severity).
Time frame: Up to Week 12
Number of Participants With Treatment Emergent Adverse Events
An adverse event (AE) is any untoward medical occurrence (e.g., any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product. Treatment emergent Adverse Event (TEAEs) in this study are events that started after the first dose of study treatment and until 28 days after the last dose of study treatment, or events present prior to the first dose of treatment which increased in severity based on preferred term within 28 days after the last study treatment.
Time frame: Baseline up to 28 days after last dose of study medication, assessed up to approximately 56 weeks
The study was conducted globally across 18 countries: Austria (1 center), Brazil (1 center), Canada (8 centers), China (16 centers), Denmark (2 centers), Germany (18 centers), India (10 centers), Malaysia (5 centers), Poland (5 centers), Russia (5 centers), Slovakia (4 centers), South Africa (3 centers), Switzerland (3 centers), Taiwan (2 centers), Thailand (4 centers), United Kingdom (3 centers), USA (30 centers), and Vietnam (2 centers).
| Milestone | LOU064 25 mg b.i.d. | Placebo |
|---|---|---|
| Started | 300 | 155 |
| Full analysis set (fas) | 297 | 153 |
| Safety set (saf) | 297 | 153 |
| Completed | 230 | 111 |
| Not completed | 70 | 44 |
| Withdrew: Adverse event | 12 | 7 |
| Withdrew: Pregnancy | 0 | 2 |
| Withdrew: Unsatisfactory therapeutic effect | 4 | 7 |
| Withdrew: Protocol deviation | 8 | 4 |
| Withdrew: Lost to follow-up | 1 | 3 |
| Withdrew: Physician decision | 7 | 2 |
| Withdrew: Patient decision | 38 | 19 |
The Weekly Urticaria Activity Score (UAS7) is a simple scoring system to evaluate urticaria signs and symptoms. It is based on scoring wheals (hive severity score) and itch (itch severity score) separately on a scale of 0 (no signs/symptoms) to 3 (intense signs/symptoms) over 7 days. The final score is calculated by adding together the daily scores, which can range from 0 to 6, for 7 days. This results in a maximum total score of 42 (highest urticaria severity), and a minimum possible score of 0. This endpoint is a secondary endpoint for testing strategy Scenario 2 with Weekly Itch Severity Score (ISS7) and Weekly Hives Severity Score (HSS7) as co-primary efficacy endpoints).
| Unit on a scale | LOU064 25 mg b.i.d. | Placebo |
|---|---|---|
| Mean Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12 (Scenario 1 With UAS7 as Primary Efficacy Endpoint) | -19.41 ± 0.702 | -11.73 ± 0.948 |
The severity of the itch was recorded by the participant twice daily in their electronic Diary, on a scale of 0 (none) to 3 (severe). A weekly score (ISS7) was derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score was therefore 0 - 21 (highest itch severity). This endpoint is a secondary endpoint for testing strategy Scenario 1 with Weekly Urticaria Activity Score (UAS7) as the primary efficacy endpoint).
| Unit on a scale | LOU064 25 mg b.i.d. | Placebo |
|---|---|---|
| Mean Change From Baseline in Weekly Itch Severity Score (ISS7) at Week 12 (Scenario 2 With ISS7 and HSS7 as Co-primary Efficacy Endpoints) | -8.95 ± 0.335 | -5.72 ± 0.454 |
The hives (wheals) severity score, defined by number of hives, was recorded by the participant twice daily in their electronic Diary, on a scale of 0 (none) to 3 (\> 12 hives/12 hours). A weekly score (HSS7) was derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score was therefore 0 - 21 (highest hives activity). This endpoint is a secondary endpoint for testing strategy Scenario 1 with Weekly Urticaria Activity Score (UAS7) as the primary efficacy endpoint).
| Unit on a scale | LOU064 25 mg b.i.d. | Placebo |
|---|---|---|
| Mean Change From Baseline in Weekly Hives Severity Score (HSS7) at Week 12 (Scenario 2 With ISS7 and HSS7 as Co-primary Efficacy Endpoints) | -10.47 ± 0.394 | -6.00 ± 0.531 |
The percentage of patients achieving disease activity control (UAS7 =\< 6) at Week 12 was assessed to evaluate the efficacy of Remibrutinib in Chronic Spontaneous Urticaria (CSU) patients. The UAS7 is the sum of the Weekly Hives Severity Score (HSS7) and the Weekly Itch Severity Score (ISS7). The possible range of the UAS7 score is 0 - 42 (highest hives and itch severity).
| Participants | LOU064 25 mg b.i.d. | Placebo |
|---|---|---|
| Number of Participants Who Achieved Disease Activity Control (UAS7 =< 6) at Week 12 | 139 | 30 |
The proportion of patients achieving complete absence of hives and itch (UAS7 = 0) at Week 12 was assessed to evaluate the efficacy of Remibrutinib in Chronic Spontaneous Urticaria (CSU) patients. The UAS7 is the sum of the Weekly Hives Severity Score (HSS7) and the Weekly Itch Severity Score (ISS7). The possible range of the UAS7 score is 0 - 42 (highest hives and itch severity).
| Participants | LOU064 25 mg b.i.d. | Placebo |
|---|---|---|
| Number of Participants Who Achieved Complete Absence of Hives and Itch (UAS7 = 0) at Week 12 | 83 | 10 |
The percentage of patients achieving disease activity control (UAS7 =\< 6) at Week 2 was assessed to evaluate the efficacy of Remibrutinib in Chronic Spontaneous Urticaria (CSU) patients. The UAS7 is the sum of the Weekly Hives Severity Score (HSS7) and the Weekly Itch Severity Score (ISS7). The possible range of the UAS7 score is 0 - 42 (highest hives and itch severity).
| Participants | LOU064 25 mg b.i.d. | Placebo |
|---|---|---|
| Number of Participants Who Achieved Early Onset of Disease Activity Control (UAS7 =< 6) at Week 2 | 89 | 9 |
The Dermatology Life Quality Index (DLQI) is a 10-item (grouped in 6 domains) dermatology-specific quality of life (QoL) measure. Participants are rating their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives thinking about the previous 7 days. An overall score is calculated and ranges from 0 to 30 (higher score meaning worse disease-related QoL). Domain scores are calculated for: Symptoms and Feelings (0-6), Daily Activities (0-6), Leisure (0-6), Work and School (0-3), Personal Relationships (0-6), Treatment (0-3). The overall DLQI score range was split into score bands and validated in terms of their meaning/relevance to patients overall DLQI = 0-1 means no effect on patient's life.
| Participants | LOU064 25 mg b.i.d. | Placebo |
|---|---|---|
| Number of Participants Who Achieved Dermatology Life Quality Index (DLQI) = 0-1 at Week 12 | 106 | 28 |
Maintaining disease activity control was assessed as cumulative number of weeks with an UAS7 =\< 6 response between baseline and Week 12. The UAS7 is the sum of the Weekly Hives Severity Score (HSS7) and the Weekly Itch Severity Score (ISS7). The possible range of the UAS7 score is 0 - 42 (highest hives and itch severity).
| Weeks | LOU064 25 mg b.i.d. | Placebo |
|---|---|---|
| Mean Cumulative Number of Weeks With Disease Activity Control (UAS7 =< 6) up to Week 12 | 4.50 ± 0.464 | 1.38 ± 0.216 |
Angioedema occurrence was recorded once daily in the evening in the electronic Diary by the participant. Reporting the occurrence of angioedema was used as opening question for the assessment of the Angioedema Activity Score (AAS). The AAS consists of 5 questions with 4 answer options (scored 0-3) for each item, with a minimum score of 0 and a maximum score of 15 per day. The AAS score over 7 days (AAS7) ranges from 0 (no angioedema episodes) to 105 (highest angioedema severity).
| Weeks | LOU064 25 mg b.i.d. | Placebo |
|---|---|---|
| Mean Cumulative Number of Angioedema Occurrence-free Weeks (AAS7 = 0 Response) up to Week 12 | 8.81 ± 0.308 | 6.68 ± 0.343 |
An adverse event (AE) is any untoward medical occurrence (e.g., any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product. Treatment emergent Adverse Event (TEAEs) in this study are events that started after the first dose of study treatment and until 28 days after the last dose of study treatment, or events present prior to the first dose of treatment which increased in severity based on preferred term within 28 days after the last study treatment.
| Participants | Double-blind Treatment Period: LOU064 25 mg b.i.d. | Double-blind Treatment Period: Placebo | LOU064 25 mg b.i.d. | Transitioned to LOU064 25 mg b.i.d. |
|---|---|---|---|---|
| Patients with at least one Adverse Event (AE) | 205 | 112 | 228 | 71 |
| Patients with serious or other significant events - Death | 0 | 0 | 0 | 0 |
| Patients with serious or other significant events - Non-fatal SAE(s) | 10 | 6 | 12 | 2 |
| Patients with serious or other significant events - Discontinued study treatment due to any AE(s) | 6 | 6 | 13 | 2 |
| Patients with serious or other significant events - Discontinued study treatment due to any SAE(s) | 0 | 1 | 1 | 0 |
Collected over On-treatment adverse events and deaths were reported from first dose of study medication up to 28 days after last dose of study medication, assessed up to approximately 56 weeks. Non-serious events are listed at a 3% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| LOU064 25 mg b.i.d. | 0/297 (0%) | 12/297 (4%) | 157/297 (52.9%) |
| Placebo | 0/153 (0%) | 6/153 (3.9%) | 66/153 (43.1%) |
| Transitioned to LOU064 25 mg b.i.d. | 0/129 (0%) | 2/129 (1.6%) | 40/129 (31%) |
| Event | LOU064 25 mg b.i.d. | Placebo | Transitioned to LOU064 25 mg b.i.d. |
|---|---|---|---|
| Large intestine polypGastrointestinal disorders | 0/297 | 0/153 | 1/129 |
| Cholecystitis acuteHepatobiliary disorders | 0/297 | 0/153 | 1/129 |
| Vestibular disorderEar and labyrinth disorders | 0/297 | 1/153 | 0/129 |
| Drug hypersensitivityImmune system disorders | 0/297 | 1/153 | 0/129 |
| AppendicitisInfections and infestations | 0/297 | 1/153 | 0/129 |
| PneumoniaInfections and infestations | 0/297 | 1/153 | 0/129 |
| Breast cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/297 | 1/153 | 0/129 |
| Chronic spontaneous urticariaSkin and subcutaneous tissue disorders | 0/297 | 1/153 | 0/129 |
| Arteriosclerosis coronary arteryCardiac disorders | 1/297 | 0/153 | 0/129 |
| Food poisoningGastrointestinal disorders | 1/297 | 0/153 | 0/129 |
| Event | LOU064 25 mg b.i.d. | Placebo | Transitioned to LOU064 25 mg b.i.d. |
|---|---|---|---|
| COVID-19Infections and infestations | 62/297 | 21/153 | 13/129 |
| NasopharyngitisInfections and infestations | 33/297 | 9/153 | 3/129 |
| Upper respiratory tract infectionInfections and infestations | 22/297 | 4/153 | 8/129 |
| HeadacheNervous system disorders | 22/297 | 8/153 | 1/129 |
| Suspected COVID-19Infections and infestations | 16/297 | 5/153 | 4/129 |
| HyperlipidaemiaMetabolism and nutrition disorders | 6/297 | 4/153 | 6/129 |
| UrticariaSkin and subcutaneous tissue disorders | 9/297 | 7/153 | 5/129 |
| PetechiaeSkin and subcutaneous tissue disorders | 13/297 | 0/153 | 5/129 |
| SinusitisInfections and infestations | 5/297 | 6/153 | 1/129 |
| Urinary tract infectionInfections and infestations | 11/297 | 4/153 | 3/129 |
| Age, Continuous(Years) | LOU064 25 mg b.i.d. | Placebo | Total |
|---|---|---|---|
| Mean | 41.9 ± 14.52 | 41.3 ± 14.58 | 41.7 ± 14.53 |
| Age, Customized(Participants) | LOU064 25 mg b.i.d. | Placebo | Total |
|---|---|---|---|
| >= 18 and < 65 years | 276 | 144 | 420 |
| >= 65 and < 85 years | 24 | 11 | 35 |
| Sex: Female, Male(Participants) | LOU064 25 mg b.i.d. | Placebo | Total |
|---|---|---|---|
| Female | 197 | 100 | 297 |
| Male | 103 | 55 | 158 |
| Race (NIH/OMB)(Participants) | LOU064 25 mg b.i.d. | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 130 | 72 | 202 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 7 | 3 | 10 |
| White | 159 | 79 | 238 |
| More than one race | 3 | 1 | 4 |
| Unknown or Not Reported | 1 | 0 | 1 |
Showing the first 100 of 122 sites across 18 countries.
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Plan to share: Yes — Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect 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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