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

NCT05048342 | Completed Phase 3 Results DMC

• 1 other identifier: CLOU064A1301
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 13

Brief 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 remibrutinib and a post-treatment follow-up period of up to 4 weeks.

Conditions

Chronic Spontaneous Urticaria

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)

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (9)

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

  Baseline, Week 12

• Number of Participants Who Achieved Disease Activity Control (UAS7 =< 6) at Week 12

  Week 12

• Number of Participants Who Achieved Complete Absence of Hives and Itch (UAS7 = 0) at Week 12

  Week 12

• Change From Baseline in Weekly Itch Severity Score (ISS7) at Week 12

  Baseline, Week 12

• Change From Baseline in Weekly Hives Severity Score (HSS7) at Week 12

  Baseline, Week 12

Study Arms (1)

LOU064 25 mg b.i.d.

EXPERIMENTAL

Patients were treated with remibrutinib 25 mg bis in die/twice a day (b.i.d.). LOU064 open-label treatment taken orally for 52 weeks.

Drug: LOU064

Interventions

LOU064 DRUG

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).

Also known as: remibrutinib

LOU064 25 mg b.i.d.

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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)

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (13)

Novartis Investigative Site

Nagoya, Aichi-ken, 454-0012, Japan

Location

Novartis Investigative Site

Urayasu, Chiba, 279-0011, Japan

Location

Novartis Investigative Site

Izumiōtsu, Osaka, 595-0025, Japan

Location

Novartis Investigative Site

Neyagawa, Osaka, 572-0838, Japan

Location

Novartis Investigative Site

Sakai, Osaka, 593-8324, Japan

Location

Novartis Investigative Site

Takatsuki, Osaka, 569-0824, Japan

Location

Novartis Investigative Site

Izumo, Shimane, 693 8501, Japan

Location

Novartis Investigative Site

Itabashi-ku, Tokyo, 173-8610, Japan

Location

Novartis Investigative Site

Minato, Tokyo, 108-0014, Japan

Location

Novartis Investigative Site

Ōta-ku, Tokyo, 143-0023, Japan

Location

Novartis Investigative Site

Fukuoka, 811-1302, Japan

Location

Novartis Investigative Site

Osaka, 554 0014, Japan

Location

Novartis Investigative Site

Osaka, 558-0003, Japan

Location

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Chronic Urticaria

Interventions

remibrutinib

Condition Hierarchy (Ancestors)

Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2021
• First Posted: September 17, 2021
• Study Start: January 15, 2022
• Primary Completion: December 8, 2023
• Study Completion: December 9, 2023
• Last Updated: April 8, 2025
• Results First Posted: November 22, 2024

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

JP (13)