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Chronic Spontaneous UrticariaPhase 3BISCUITNCT05048342

A Safety and Efficacy Study of Remibrutinib in the Treatment of CSU in Japanese Adults Inadequately Controlled by H1-antihistamines

A Phase 3 study testing LOU064 in people with Chronic Spontaneous Urticaria, run by Novartis Pharmaceuticals at 13 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study was to evaluate the safety, tolerability and efficacy of remibrutinib (LOU064) in adult Japanese patients chronic spontaneous urticaria (CSU), who remain symptomatic despite treatment by H1-antihistamine (H1-AH) at locally label approved doses, for a duration of 52 weeks of treatment with… Read more about this study

Who is it for?
Ages 18 to 100 years
Conditions the study is for
Chronic Spontaneous Urticaria
What is being tested?
LOU064
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
71 participants
Where
13 sitesJapan
Study dates
15 Jan 2022to 9 Dec 2023
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 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed informed consent was required to be obtained prior to participation in the study.
  • Male and female patients >= 18 years of age at the time of screening
  • 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-AHs at the time of baseline (Day 1) defined as:
  • The presence of itch and hives for >= 6 consecutive weeks prior to screening despite the use of second generation H1-AHs 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 baseline (Day 1)
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  • Documentation of hives within three months before baseline (either at screening and/or at baseline; or documented in the patients' medical history)
  • Willing and able to complete an UPDD for the duration of the study and adhere to the study protocol
  • Patients were required to not have more than one missing UPDD entry (either morning or evening) in the 7 days prior to baseline (Day 1)

Who cannot join

  • Patients 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 angioedema, 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 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 patient, interfere with the interpretation of the study results or otherwise preclude participation or protocol adherence of the patient
  • Significant bleeding risk or coagulation disorders
  • History of gastrointestinal bleeding, e.g., in association with use of nonsteroidal anti-inflammatory drugs, that was clinically relevant (e.g., for which intervention was indicated or 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 up to 75 mg/d. 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)
  • History or current hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis or hepatic failure or AST/ALT levels of more than 1.5 × ULN or International Normalized Ratio (INR) of more than 1.5 at screening

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

Japan13 sites

  • Novartis Investigative Site

    Fukuoka, 811-1302

  • Novartis Investigative Site

    Izumiōtsu, Osaka, 595-0025

  • Novartis Investigative Site

    Izumo, Shimane, 693 8501

  • Novartis Investigative Site

    Minato, Tokyo, 108-0014

  • Novartis Investigative Site

    Nagoya, Aichi-ken, 454-0012

  • Novartis Investigative Site

    Neyagawa, Osaka, 572-0838

  • Novartis Investigative Site

    Osaka, 554 0014

  • Novartis Investigative Site

    Osaka, 558-0003

  • Novartis Investigative Site

    Ōta-ku, Tokyo, 143-0023

  • Novartis Investigative Site

    Sakai, Osaka, 593-8324

  • Novartis Investigative Site

    tabashi City, Tokyo, 173-8610

  • Novartis Investigative Site

    Takatsuki, Osaka, 569-0824

  • Novartis Investigative Site

    Urayasu, Chiba, 279-0011

Other trials in Japan

About this study

Official title: A Multicenter, Open-label Phase 3 Study of Remibrutinib (LOU064) to Investigate the Safety, Tolerability and Efficacy for 52 Weeks in Adult Japanese Chronic Spontaneous Urticaria Patients Inadequately Controlled by H1-antihistamines

The purpose of this study was to evaluate the safety, tolerability and efficacy of remibrutinib (LOU064) in adult Japanese patients chronic spontaneous urticaria (CSU), who remain symptomatic despite treatment by H1-antihistamine (H1-AH) at locally label approved doses, for a duration of 52 weeks of treatment with remibrutinib and a post-treatment follow-up period of up to 4 weeks.

Read the detailed description

The study consisted of three periods, the total study duration is up to 60 weeks: screening period of up to 4 weeks, open-label treatment period of 52 weeks (remibrutinib 25 mg b.i.d.), and a treatment free follow-up period of 4 weeks.

It was planned to include approximately 70 patients in the study; 71 patients were enrolled and included in the analyses.

Being tested
LOU064
Keywords
Bruton Tyrosine Kinase (BTK) inhibitor, Chronic Spontaneous Urticaria (CSU), Urticaria Activity Score (UAS), Weekly Urticaria Activity Score (UAS7), Hives Severity Score (HSS), Weekly Hives Severity Score (HSS7), Itch Severity Score (ISS), Weekly Itch Severity Score (ISS7), Angioedema Activity Score (AAS), Weekly Angioedema Activity Score (AAS7), Dermatology Life Quality Index (DLQI)
Medical subject headings
Chronic Urticaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LOU064Drug

    Also called remibrutinib

    Each patient took one film-coated tablet in the morning and one film-coated tablet in the evening (except the morning dose at the PK sampling visits, which were to be taken on site during the visit).

Study groups in NCT05048342
Study groupRoleWhat they receive
LOU064 25 mg b.i.d.ExperimentalPatients were treated with remibrutinib 25 mg bis in die/twice a day (b.i.d.). LOU064 open-label treatment taken orally for 52 weeks.
Receives: Drug: LOU064

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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 30 days after the last study treatment, or events present prior to the first dose of treatment which increased in severity based on preferred term within 30 days after the last study treatment.

    Measured: Baseline up to 30 days after last dose of study medication, assessed up to approximately 56 weeks

Secondary outcomes (9)

  1. Mean Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12

    Change from Baseline in Weekly Urticaria Activity Score (UAS7) was assessed to evaluate the efficacy of Remibrutinib in Chronic Spontaneous Urticaria (CSU) patients. The Weekly Urticaria Activity Score (UAS7) is the sum of the Weekly Hives Severity Score (HSS7) and the Weekly Itch Severity Score (ISS7). The possible range of the weekly UAS7 score is 0 - 42 (highest hives and itch severity).

    Measured: Baseline, Week 12

  2. 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).

    Measured: Week 12

  3. 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).

    Measured: Week 12

  4. Change From Baseline in Weekly Itch Severity Score (ISS7) at 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).

    Measured: Baseline, Week 12

  5. Change From Baseline in Weekly Hives Severity Score (HSS7) at 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).

    Measured: Baseline, Week 12

  6. 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).

    Measured: Week 2

  7. 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 as follows: 0-1 (No effect on patient's life), 2-5 (Small effect on patient's life), 6-10 (Moderate effect on patient's life), 11-20 (Very large effect on patient's life), 21-30 (Extremely large effect on patient's life).

    Measured: Week 12

  8. 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).

    Measured: Up to Week 12

  9. 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).

    Measured: Up to Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Sep 2021
  2. Study start15 Jan 2022
  3. Primary completion8 Dec 2023
  4. Study completion9 Dec 2023

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
71 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05048342
Sponsor's protocol ID
CLOU064A1301
Acronym
BISCUIT
Status last verified
Apr 2025
First submitted
8 Sep 2021
Last updated
8 Apr 2025
Data monitoring committee
Yes
FDA-regulated drug
No
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

  • Hayama K, Chinuki Y, Yagami A, Kume A, Morita A, Miyazu S, Lheritier K, Jaskiewicz L, Haemmerle S, Hide M. Remibrutinib Showed a Favorable Safety Profile and Sustained Efficacy in Japanese Patients with Chronic Spontaneous Urticaria Over 52 Weeks. Dermatol Ther (Heidelb). 2026 Mar;16(3):1707-1721. doi: 10.1007/s13555-026-01666-5. Epub 2026 Feb 19.

    PubMed 41712058

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing LOU064 in people with Chronic Spontaneous Urticaria, run by Novartis Pharmaceuticals at 13 sites in Japan.

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 13 sites in Japan. 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. 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 22 Nov 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?

Number of Participants With Treatment Emergent Adverse Events (time frame: Baseline up to 30 days after last dose of study medication, assessed up to approximately 56 weeks). 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 NCT05048342, 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 8 Apr 2025.

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