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

Chronic Spontaneous Urticaria Clinical Trial

— BISCUIT  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05048342
• Other study ID #: CLOU064A1301
• Status: Completed
• Phase: Phase 3
• Start date: January 15, 2022
• Est. completion date: December 9, 2023

Study information

• Verified date: April 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and efficacy of remibrutinib (LOU064) in adult Japanese chronic spontaneous urticaria (CSU) participants inadequately controlled by second generation H1-antihistamines.

Description:

This is a Phase 3 multi-center, open-label, single arm study investigating the safety, tolerability and efficacy of remibrutinib in participants with CSU inadequately controlled by second generation H1-antihistamines. Inadequate control of CSU by second generation H1-antihistamines is 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

• Urticaria Activity Score (UAS7) score (range 0-42) ≥ 16, Itch Severity Score (ISS7) score (range 0-21) ≥ 6 and Hives Severity Score (HSS7) score (range 0-21) ≥ 6 during the 7 days prior to baseline (Day 1).

The study consists 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, and a treatment free follow-up period of 4 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: December 9, 2023
• Est. primary completion date: December 8, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Signed informed consent must be obtained prior to participation in the study.

• Male and female 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 baseline 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 baseline (Day 1)

• Documentation of hives within three months before baseline (either at screening and/or at baseline; 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 baseline (Day 1).

Exclusion Criteria:

• 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- nflammatory drugs (NSAID), that was clinically relevant (e.g., requiring hospitalization or blood transfusion)

• 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

Related Conditions & MeSH terms

• Chronic Spontaneous Urticaria
• Chronic Urticaria
• Urticaria

Intervention

Drug:
• LOU064
Arm 1: LOU064 (open label)

Locations

Country	Name	City	State
Japan	Novartis Investigative Site	Fukuoka
Japan	Novartis Investigative Site	Itabashi-ku	Tokyo
Japan	Novartis Investigative Site	Izumiotsu	Osaka
Japan	Novartis Investigative Site	Izumo-city	Shimane
Japan	Novartis Investigative Site	Minato	Tokyo
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Neyagawa	Osaka
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Ota-ku	Tokyo
Japan	Novartis Investigative Site	Sakai	Osaka
Japan	Novartis Investigative Site	Takatsuki	Osaka
Japan	Novartis Investigative Site	Urayasu	Chiba

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The number and the proportion of participants with treatment-emergent adverse event	To evaluate the overall safety data of remibrutinib in CSU patients assessed as treatment emergent adverse events during the study.	52 weeks
Secondary	Change from baseline in UAS7	To evaluate the efficacy of remibrutinib measured by absolute change from baseline in UAS7 at Week 12.	12 weeks
Secondary	Disease activity control (UAS7= 6)	To evaluate the efficacy of remibrutinib as measured by proportion of participants achieving disease activity control (UAS7 = 6) at Week 12.	12 weeks
Secondary	Complete absence of hives and itch (UAS7 = 0)	To evaluate the efficacy of remibrutinib as measured by Proportion of participants achieving complete absence of hives and itch (UAS7 = 0) at Week 12.	12 weeks
Secondary	Change from baseline in ISS7 score	To evaluate the efficacy of remibrutinib as measured by absolute change from baseline in ISS7 score at Week 12.	12 weeks
Secondary	Change from baseline in HSS7 score	To evaluate the efficacy of remibrutinib as measured by absolute change from baseline in HSS7 score at Week 12.	12 weeks
Secondary	Early onset of disease activity control (UAS7 = 6 at 2 weeks)	To evaluate the efficacy of remibrutinib as proportion of participants achieving disease activity control (UAS7 = 6) at Week 2	2 weeks
Secondary	Sustained disease activity control UAS7 = 6	To evaluate the efficacy of remibrutinib by achieving sustained disease activity control, assessed as cumulative number of weeks with an UAS7=6 response between baseline and Week 12.	12 weeks
Secondary	Achievement of Dermatology Life Quality Index (DLQI) = 0-1	To evaluate the efficacy of remibrutinib by assessing achievement of DLQI = 0-1 at Week 12.	12 weeks
Secondary	Number of weeks without angioedema (AAS = 0)	To evaluate the efficacy of remibrutinib assessed by the cumulative number of weeks with an AAS7= 0 response between baseline and Week 12.	12 weeks