Clinical trial NCT05048342: A Safety and Efficacy Study of Remibrutinib in the Treatment of CSU in Japanese Adults Inadequately Controlled by H1-antihistamines
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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)
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-09-17
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion criteria:

* 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)

Exclusion criteria:

* 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

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events
timeFrame: Baseline up to 30 days after last dose of study medication, assessed up to approximately 56 weeks
Secondary outcomes:
measure: Mean Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12
timeFrame: Baseline, Week 12
measure: Number of Participants Who Achieved Disease Activity Control (UAS7 =< 6) at Week 12
timeFrame: Week 12
measure: Number of Participants Who Achieved Complete Absence of Hives and Itch (UAS7 = 0) at Week 12
timeFrame: Week 12
measure: Change From Baseline in Weekly Itch Severity Score (ISS7) at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Weekly Hives Severity Score (HSS7) at Week 12
timeFrame: Baseline, Week 12
measure: Number of Participants Who Achieved Early Onset of Disease Activity Control (UAS7 =< 6) at Week 2
timeFrame: Week 2
measure: Number of Participants Who Achieved Dermatology Life Quality Index (DLQI) = 0-1 at Week 12
timeFrame: Week 12
measure: Mean Cumulative Number of Weeks With Disease Activity Control (UAS7 =< 6) up to Week 12
timeFrame: Up to Week 12
measure: Mean Cumulative Number of Angioedema Occurrence-free Weeks (AAS7 = 0 Response) up to Week 12
timeFrame: Up to Week 12
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Urayasu
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Izumiotsu
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Neyagawa
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Sakai
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Takatsuki
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Izumo-city
country: Japan
facility: Novartis Investigative Site
state: Shimane
city: Itabashi-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Minato
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Ota-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Fukuoka
country: Japan
facility: Novartis Investigative Site
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Osaka
country: Japan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: