Chronic Spontaneous UrticariaPhase 3REMIX-1NCT05030311
A Phase 3 Study of Efficacy and Safety of Remibrutinib in the Treatment of CSU in Adults Inadequately Controlled by H1 Antihistamines
A Phase 3 study testing LOU064 25 mg (b.i.d) and LOU064 25 mg (b.i.d) as a tablet. in people with Chronic Spontaneous Urticaria, run by Novartis Pharmaceuticals at 112 sites in 19 countries.
Trial summary
The purpose of this study was to establish the efficacy, safety, and tolerability of remibrutinib (LOU064) in adult participants suffering from chronic spontaneous urticaria (CSU) inadequately controlled by H1-antihistamines in comparison to placebo. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Spontaneous Urticaria
- What is being tested?
- LOU064 25 mg (b.i.d) and LOU064 25 mg (b.i.d) as a tablet.
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 470 participants
- Where
- 112 sitesin 19 countries
- Study dates
- 30 Nov 2021to 19 Jan 2024
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent must be obtained prior to participation in the study.
- Male and female adult participants ≥18 years of age.
- CSU duration for ≥ 6 months prior to screening (defined as the onset of CSU determined by the investigator based on all available supporting documentation).
- Diagnosis of CSU inadequately controlled by second generation H1 antihistamines at the time of randomization defined as:
- The presence of itch and hives for ≥6 consecutive weeks prior to screening despite the use of second generation H1-antihistamines during this time period
- UAS7 score (range 0-42) ≥16, ISS7 score (range 0-21) ≥ 6 and HSS7 score (range 0-21) ≥ 6 during the 7 days prior to randomization (Day 1)
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- Documentation of hives within three months before randomization (either at screening and/or at randomization; or documented in the participants medical history).
- Willing and able to complete an Urticaria Patient Daily Diary (UPDD) for the duration of the study and adhere to the study protocol.
- Participants must not have had more than one missing UPDD entry (either morning or evening) in the 7 days prior to randomization (Day 1).
Who cannot join
- Participants having a clearly defined predominant or sole trigger of their chronic urticaria (chronic inducible urticaria) including urticaria factitia (symptomatic dermographism), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic-, or contact-urticaria
- Other diseases with symptoms of urticaria or angioedema, including but not limited to urticaria vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary urticaria, or drug-induced urticaria
- Any other skin disease associated with chronic itching that might influence in the investigator's opinion the study evaluations and results, e.g. atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus or psoriasis
- Evidence of clinically significant cardiovascular (such as but not limited to myocardial infarction, unstable ischemic heart disease, New York heart association (NYHA) Class III/IV left ventricular failure, arrhythmia and uncontrolled hypertension within 12 months prior to Visit 1), neurological, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, hematological disorders, gastrointestinal disease or immunodeficiency that, in the investigator's opinion, would compromise the safety of the participant, interfere with the interpretation of the study results or otherwise preclude participation or protocol adherence of the participant
- Significant bleeding risk or coagulation disorders
- History of gastrointestinal bleeding, e.g. in association with use of nonsteroidal anti-inflammatory drugs (NSAID), that was clinically relevant (e.g. requiring hospitalization or blood transfusion)
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- Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel. The use of dual anti-platelet therapy (e.g. acetylsalicylic acid + clopidogrel) is prohibited.
- Requirement for anticoagulant medication (for example, warfarin or Novel Oral Anti-Coagulants (NOAC))
- History or current hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis or hepatic failure or Aspartate Aminotransferase (AST)/ Alanine Aminotransferase (ALT) levels of more than 1.5 x upper limit of normal (ULN) or International Normalized Ratio (INR) of more than 1.5 at screening
Trial locations and contacts
112 sites in 19 countries.
112 sites in 19 countries
United States26 sites
Novartis Investigative Site
Albany, Georgia, 31707
Novartis Investigative Site
Athens, Ohio, 45701
Novartis Investigative Site
Austin, Texas, 78759
Novartis Investigative Site
Aventura, Florida, 33180
Novartis Investigative Site
Bakersfield, California, 93301
Novartis Investigative Site
Bellingham, Washington, 98225
Novartis Investigative Site
Birmingham, Alabama, 35209
Novartis Investigative Site
Chevy Chase, Maryland, 20815
Novartis Investigative Site
Columbus, Ohio, 43235
Novartis Investigative Site
Denver, Colorado, 80230
Novartis Investigative Site
El Paso, Texas, 79924
Novartis Investigative Site
Evansville, Indiana, 47715
Finlay Medical Research
Greenacres City, Florida, 33467
Novartis Investigative Site
Lancaster, California, 93534
Novartis Investigative Site
Lincoln, Nebraska, 68510
Novartis Investigative Site
Los Angeles, California, 90025
Novartis Investigative Site
North Little Rock, Arkansas, 72117
Novartis Investigative Site
Redwood City, California, 94063
Novartis Investigative Site
San Antonio, Texas, 78213
Novartis Investigative Site
Sandy City, Utah, 84093
Novartis Investigative Site
Sarasota, Florida, 34233
Novartis Investigative Site
St Louis, Missouri, 63141
Novartis Investigative Site
Tallahassee, Florida, 32308
Novartis Investigative Site
Toledo, Ohio, 43617
Novartis Investigative Site
Tulsa, Oklahoma, 74136
Novartis Investigative Site
Woodstock, Georgia, 30188
Argentina9 sites
Novartis Investigative Site
Bahía Blanca, B8000JRB
Novartis Investigative Site
Buenos Aires, Nueve De Julio, B6500BWQ
Novartis Investigative Site
CABA, Buenos Aires, C1181ACH
Novartis Investigative Site
CABA, Buenos Aires, C1414AIF
Novartis Investigative Site
Capital Federal, C1023AAB
Novartis Investigative Site
La Plata, Buenos Aires, B1902COS
Novartis Investigative Site
Rosario, Santa Fe Province, S2000JKR
Novartis Investigative Site
Santa Fe, Rosario, S2000DBS
Novartis Investigative Site
Santa Fe, S3000FIL
India9 sites
Novartis Investigative Site
Belgavi, 590010
Novartis Investigative Site
Chandigarh, 160012
Novartis Investigative Site
Hyderabad, Telangana, 500004
Novartis Investigative Site
Kolkata, West Bengal, 700054
Novartis Investigative Site
Nagpur, Maharashtra, 440012
Novartis Investigative Site
Nagpur, Maharashtra, 440015
Novartis Investigative Site
Nashik, Maharashtra, 422005
Novartis Investigative Site
New Delhi, National Capital Territory of Delhi, 110 060
Novartis Investigative Site
Varanasi, Uttar Pradesh, 221005
South Korea9 sites
Novartis Investigative Site
Daegu, Dalseo Gu, 42602
Novartis Investigative Site
Gwangju, 61469
Novartis Investigative Site
Hwaseong-si, Gyeonggi-do, 18450
Novartis Investigative Site
Incheon, 405 760
Novartis Investigative Site
Seoul, 03080
Novartis Investigative Site
Seoul, 03722
Novartis Investigative Site
Seoul, 07061
Novartis Investigative Site
Seoul, 07441
Novartis Investigative Site
Suwon, Gyeonggi-do, 16499
Turkey (Türkiye)9 sites
Novartis Investigative Site
Aydin, 09100
Novartis Investigative Site
Istanbul, 34662
Novartis Investigative Site
Izmir, 35100
Novartis Investigative Site
Izmir, 35380
Novartis Investigative Site
Izmir, 35620
Novartis Investigative Site
Kayseri, 38070
Novartis Investigative Site
Sakarya, 54290
Novartis Investigative Site
Samsun, 55139
Novartis Investigative Site
Talas Kayseri, 38039
Japan7 sites
Novartis Investigative Site
Fukuoka, 819 0167
Novartis Investigative Site
Hiroshima, 734-8551
Novartis Investigative Site
Kamimashi-gun, Kumamoto, 861-3106
Novartis Investigative Site
Koto, Tokyo, 136-0074
Novartis Investigative Site
Obihiro, Hokkaido, 080 0013
Novartis Investigative Site
Takatsuki, Osaka, 569-8686
Novartis Investigative Site
Yokohama, Kanagawa, 220-6208
Spain7 sites
Novartis Investigative Site
Alicante, Valencia, 03010
Novartis Investigative Site
Barcelona, Catalonia, 08003
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Las Palmas de Gran Canaria, 35010
Novartis Investigative Site
Madrid, 280796
Novartis Investigative Site
Valencia, Valencia, 46015
Novartis Investigative Site
Valencia, 46026
France6 sites
Novartis Investigative Site
Antony, 92160
Novartis Investigative Site
Bordeaux, 33075
Novartis Investigative Site
Nice, 06000
Novartis Investigative Site
Pierre-Bénite, 69495
Novartis Investigative Site
Reims, 51100
Novartis Investigative Site
Rouen, 76031
Colombia4 sites
Novartis Investigative Site
Barranquilla, Atlántico, 080002
Novartis Investigative Site
Barranquilla, 080020
Novartis Investigative Site
Bogotá, 110221
Novartis Investigative Site
Medellín, Antioquia, 050010
Czechia4 sites
Novartis Investigative Site
Brno, Czech Republic, 656 91
Novartis Investigative Site
Olomouc, CZE, 779 00
Novartis Investigative Site
Pilsen, 305 99
Novartis Investigative Site
Prague, 150 06
Italy4 sites
Novartis Investigative Site
Ancona, AN, 60126
Novartis Investigative Site
Milan, MI, 20162
Novartis Investigative Site
Pisa, PI, 56124
Novartis Investigative Site
Torino, TO, 10128
Australia3 sites
Novartis Investigative Site
East Melbourne, Victoria, 3002
Novartis Investigative Site
Parkville, Victoria, 3050
Novartis Investigative Site
Sydney, New South Wales, 2010
Bulgaria3 sites
Novartis Investigative Site
Pleven, 5800
Novartis Investigative Site
Sofia, 1407
Novartis Investigative Site
Sofia, 1431
Hungary3 sites
Novartis Investigative Site
Debrecen, Hajdú-Bihar, 4026
Novartis Investigative Site
Debrecen, 4032
Novartis Investigative Site
Szeged, 6720
Mexico3 sites
Novartis Investigative Site
Guadalajara, Jalisco, 44130
Novartis Investigative Site
Mexico City, Mexico City, 06700
Novartis Investigative Site
Villahermosa, Tabasco, 86035
Puerto Rico2 sites
Novartis Investigative Site
Carolina, 00985
Novartis Investigative Site
San Juan, 00927
Taiwan2 sites
Novartis Investigative Site
Taipei, 10002
Novartis Investigative Site
Taipei, 11217
About this study
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Phase 3 Study of Remibrutinib (LOU064) to Investigate the Efficacy, Safety and Tolerability for 52 Weeks in Adult Chronic Spontaneous Urticaria (CSU) Patients Inadequately Controlled by H1-antihistamines
The purpose of this study was to establish the efficacy, safety, and tolerability of remibrutinib (LOU064) in adult participants suffering from chronic spontaneous urticaria (CSU) inadequately controlled by H1-antihistamines in comparison to placebo.
Read the detailed description
This was a global Phase III multi-centered, randomized,double-blind, parallel-group, placebo-controlled study investigating the safety, tolerability, and efficacy of remibrutinib (25 mg b.i.d.) in adult patients with CSU inadequately controlled by second generation H1-antihistamines (H1-AHs). 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 planned sample size was approximately 450 patients randomized in 2:1 ratio to remibrutinib or placebo arm (300 in the remibrutinib arm and 150 in placebo arm).
- Conditions
- Chronic Spontaneous Urticaria
- Being tested
- LOU064 25 mg (b.i.d), Placebo, LOU064 25 mg (b.i.d) as a tablet.
- Keywords
- BTK inhibitor, Chronic spontaneous urticaria, Urticaria activity score, Hives severity score, Itch severity score, CSU
- Medical subject headings
- Chronic Urticaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LOU064 25 mg (b.i.d)Drug
Also called remibrutinib
LOU064 25 mg was administered by oral route twice a day (b.i.d) as a tablet.
PlaceboDrug
Placebo
LOU064 25 mg (b.i.d) as a tablet.Drug
Also called remibrutinib
LOU064 25 mg was administered by oral route twice a day (b.i.d) as a tablet in open label phase.
| Study group | Role | What they receive |
|---|---|---|
| LOU064 25mg b.i.d. | Experimental | Patients initially randomized to Remibrutinib during the Double-blind treatment period and continued Remibrutinib during the Open-label treatment period (Up to Week 52) Receives: Drug: LOU064 25 mg (b.i.d); Drug: LOU064 25 mg (b.i.d) as a tablet. |
| Placebo | Placebo comparator | Patients initially randomized to Placebo (Up to Week 24) Receives: Drug: Placebo; Drug: LOU064 25 mg (b.i.d) as a tablet. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Weekly Urticaria 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).
Measured: Baseline, Week 12
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).
Measured: Baseline, Week 12
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.
Measured: Baseline, Week 12
Secondary outcomes (7)
Number of Patients Who Achieved Disease Activity Control (UAS7 ≤6)
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).
Measured: Week 12
Number of Patients Who Achieved Complete Absence of Hives and Itch (UAS7 = 0)
The number 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).
Measured: Week 12
Number of Patients With Early Onset of Disease 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).
Measured: Week 2
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).
Measured: up to Week 12
Number of Patients Who Achieved DLQI = 0 - 1
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.
Measured: Week 12
Cumulative Number of Weeks Without Angioedema (AAS7 = 0)
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).
Measured: Up to Week 12
Number of Participants With 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.
Measured: On-treatment adverse events are reported from first dose of study medication up to 28 days after last dose of study medication, for a timeframe up to approximately 56 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2021
- Study start30 Nov 2021
- Primary completion27 Dec 2023
- Study completion19 Jan 2024
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 (2)Papers the sponsor has linked to this study.
- Other trials for Chronic Spontaneous UrticariaStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 470 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
- NCT05030311
- Sponsor's protocol ID
- CLOU064A2301
- Other IDs
- 2022-001034-11
- Acronym
- REMIX-1
- Status last verified
- Apr 2025
- First submitted
- 19 Aug 2021
- Last updated
- 8 Apr 2025
- 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 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
Publications
Mosnaim G, Saini S, Lebwohl M, Thomsen SF, Reed J, Yang B, Fukunaga A, Jain V, Field C, Kuruvilla M, Martzloff ED, Seko N, Wang P, Haemmerle S, Metz M. Remibrutinib impact on disease control, sleep, and quality of life: Analysis of phase 3 REMIX-1/2. Ann Allergy Asthma Immunol. 2026 Jun 15:S1081-1206(26)00271-1. doi: 10.1016/j.anai.2026.06.011. Online ahead of print.
PubMed 42297099Metz M, Gimenez-Arnau A, Hide M, Lebwohl M, Mosnaim G, Saini S, Sussman G, Szalewski R, Haemmerle S, Lheritier K, Martzloff ED, Seko N, Wang P, Zharkov A, Maurer M; REMIX-1 and REMIX-2 Investigators; REMIX-1 Investigators; REMIX-2 Investigators. Remibrutinib in Chronic Spontaneous Urticaria. N Engl J Med. 2025 Mar 6;392(10):984-994. doi: 10.1056/NEJMoa2408792.
PubMed 40043237
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-blind, Placebo-controlled Phase 3 Study of Remibrutinib (LOU064) to Investigate the Efficacy, Safety and Tolerability for 52 Weeks in Adult Chronic Spontaneous Urticaria (CSU) Patients Inadequately Controlled by H1-antihistamines
- ClinicalTrials.gov ID
- NCT05030311
- Acronym / sponsor ID
- REMIX-1 / CLOU064A2301
- Conditions
- Chronic Spontaneous Urticaria
- Keywords
- BTK inhibitor, Chronic spontaneous urticaria, Urticaria activity score, Hives severity score, Itch severity score, CSU
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 470 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 30 Nov 2021 (actual)
- Primary completion
- 27 Dec 2023 (actual)
- Study completion
- 19 Jan 2024 (actual)
- First posted
- 1 Sep 2021 (actual)
- Results
- Posted 2 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to establish the efficacy, safety, and tolerability of remibrutinib (LOU064) in adult participants suffering from chronic spontaneous urticaria (CSU) inadequately controlled by H1-antihistamines in comparison to placebo.
Detailed description
This was a global Phase III multi-centered, randomized,double-blind, parallel-group, placebo-controlled study investigating the safety, tolerability, and efficacy of remibrutinib (25 mg b.i.d.) in adult patients with CSU inadequately controlled by second generation H1-antihistamines (H1-AHs). 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 planned sample size was approximately 450 patients randomized in 2:1 ratio to remibrutinib or placebo arm (300 in the remibrutinib arm and 150 in placebo arm).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LOU064 25mg b.i.d. | Experimental | Drug: LOU064 25 mg (b.i.d), Drug: LOU064 25 mg (b.i.d) as a tablet.Patients initially randomized to Remibrutinib during the Double-blind treatment period and continued Remibrutinib during the Open-label treatment period (Up to Week 52) |
| Placebo | Placebo comparator | Drug: Placebo, Drug: LOU064 25 mg (b.i.d) as a tablet.Patients initially randomized to Placebo (Up to Week 24) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Signed informed consent must be obtained prior to participation in the study.
- Male and female adult participants ≥18 years of age.
- CSU duration for ≥ 6 months prior to screening (defined as the onset of CSU determined by the investigator based on all available supporting documentation).
- Diagnosis of CSU inadequately controlled by second generation H1 antihistamines at the time of randomization defined as:
- The presence of itch and hives for ≥6 consecutive weeks prior to screening despite the use of second generation H1-antihistamines during this time period
Key exclusion criteria (9 listed)
- Participants having a clearly defined predominant or sole trigger of their chronic urticaria (chronic inducible urticaria) including urticaria factitia (symptomatic dermographism), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic-, or contact-urticaria
- Other diseases with symptoms of urticaria or angioedema, including but not limited to urticaria vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary urticaria, or drug-induced urticaria
- Any other skin disease associated with chronic itching that might influence in the investigator's opinion the study evaluations and results, e.g. atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus or psoriasis
- Evidence of clinically significant cardiovascular (such as but not limited to myocardial infarction, unstable ischemic heart disease, New York heart association (NYHA) Class III/IV left ventricular failure, arrhythmia and uncontrolled hypertension within 12 months prior to Visit 1), neurological, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, hematological disorders, gastrointestinal disease or immunodeficiency that, in the investigator's opinion, would compromise the safety of the participant, interfere with the interpretation of the study results or otherwise preclude participation or protocol adherence of the participant
- Significant bleeding risk or coagulation disorders
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 |
|---|---|---|
| LOU064 25 mg (b.i.d)Also: remibrutinibLOU064 25 mg was administered by oral route twice a day (b.i.d) as a tablet. | Drug | LOU064 25mg b.i.d. |
| PlaceboPlacebo | Drug | Placebo |
| LOU064 25 mg (b.i.d) as a tablet.Also: remibrutinibLOU064 25 mg was administered by oral route twice a day (b.i.d) as a tablet in open label phase. | Drug | LOU064 25mg b.i.d., Placebo |
Primary outcome
Change From Baseline in Weekly Urticaria Score (UAS7) at Week 12 (Scenario 1 With UAS7 as Primary Efficacy Endpoint)
Time frame: Baseline, Week 12
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).
Change From Baseline in Weekly Itch Severity Score (ISS7) at Week 12 (Scenario 2 With ISS7 and HSS7 as Co-primary Efficacy Endpoints)
Time frame: Baseline, Week 12
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).
Change From Baseline in Weekly Hives Severity Score (HSS7) at Week 12 (Scenario 2 With ISS7 and HSS7 as Co-primary Efficacy Endpoints)
Time frame: Baseline, Week 12
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.
7 secondary outcomes
Number of Patients Who Achieved Disease Activity Control (UAS7 ≤6)
Time frame: Week 12
Number of Patients Who Achieved Complete Absence of Hives and Itch (UAS7 = 0)
Time frame: Week 12
Number of Patients With Early Onset of Disease Control (UAS7 ≤ 6 at Week 2)
Time frame: Week 2
Cumulative Number of Weeks With Disease Activity Control (UAS7 <= 6) up to Week 12
Time frame: up to Week 12
Number of Patients Who Achieved DLQI = 0 - 1
Time frame: Week 12
Cumulative Number of Weeks Without Angioedema (AAS7 = 0)
Time frame: Up to Week 12
Number of Participants With Adverse Events
Time frame: On-treatment adverse events are reported from first dose of study medication up to 28 days after last dose of study medication, for a timeframe up to approximately 56 weeks
Results and safety
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Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42297099Mosnaim G, Saini S, Lebwohl M, Thomsen SF, Reed J, Yang B, Fukunaga A, Jain V, Field C, Kuruvilla M, Martzloff ED, Seko N, Wang P, Haemmerle S, Metz M. Remibrutinib impact on disease control, sleep, and quality of life: Analysis of phase 3 REMIX-1/2. Ann Allergy Asthma Immunol. 2026 Jun 15:S1081-1206(26)00271-1. doi: 10.1016/j.anai.2026.06.011. Online ahead of print.
- Derived from this study: PubMed 40043237Metz M, Gimenez-Arnau A, Hide M, Lebwohl M, Mosnaim G, Saini S, Sussman G, Szalewski R, Haemmerle S, Lheritier K, Martzloff ED, Seko N, Wang P, Zharkov A, Maurer M; REMIX-1 and REMIX-2 Investigators; REMIX-1 Investigators; REMIX-2 Investigators. Remibrutinib in Chronic Spontaneous Urticaria. N Engl J Med. 2025 Mar 6;392(10):984-994. doi: 10.1056/NEJMoa2408792.
- A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: 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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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
112 sites in 19 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing LOU064 25 mg (b.i.d) and LOU064 25 mg (b.i.d) as a tablet. in people with Chronic Spontaneous Urticaria, run by Novartis Pharmaceuticals at 112 sites in 19 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 9 inclusion and 9 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: finished, as of the sponsor's last update on 8 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 112 sites in United States, Argentina, India, South Korea, Turkey (Türkiye) and 14 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 2 Dec 2024). 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 Weekly Urticaria Score (UAS7) at Week 12 (Scenario 1 With UAS7 as Primary Efficacy Endpoint) (time frame: Baseline, Week 12). The study lists 3 primary outcomes in all. 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 NCT05030311, which also lists 2 linked publications.
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 8 Apr 2025.