24 Weeks Double-blind Randomized Placebo-controlled Trial to Evaluate Efficacy, PK, Safety of LOU064 in Adolescents (12 - <18) With CSU and Inadequate Response to H1-antihistamine Followed by Optional 3 Years Open-label Extension and an Optional 3 Years Safety Long-term Treatment-free Follow-up

Chronic Spontaneous Urticaria Clinical Trial

Official title:

A Double-blind, Randomized, Placebo-controlled Trial to Evaluate the Efficacy, Pharmacokinetics and Safety of Remibrutinib (LOU064) for 24 Weeks in Adolescents From 12 to Less Than 18 Years of Age With Chronic Spontaneous Urticaria Inadequately Controlled by H1-antihistamines Followed by an Optional Open-label Extension for up to Another 3 Years and an Optional Safety Long-term Treatment-free Follow-up Period for up to an Additional 3 Years

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05677451
• Other study ID #: CLOU064F12301
• Secondary ID: 2022-502159-7820
• Status: Recruiting
• Phase: Phase 3
• Start date: July 11, 2023
• Est. completion date: January 22, 2032

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this trial is: 1. to assess the efficacy, pharmacokinetics, and safety of remibrutinib vs. placebo in adolescents from 12 to < 18 years of age suffering from chronic spontaneous urticaria inadequately controlled by H1-antihistamines 2. to collect long-term efficacy, safety and tolerability data on remibrutinib in adolescents after having completed 24 weeks of treatment 3. to collect safety data in this population for up to three years after the last dose of study treatment

Description:

This trial consists of 3 different periods: 1. the "core period", which is randomized and double-blind, during which 2/3 participants will receive remibrutinib and 1/3 will receive placebo for 24 weeks. Total duration: approximately 32 weeks (10 site visits). 2. an optional "open-label extension (OLE) period" proposed to all participants who completed 24 weeks of treatment of the "core period" and all scheduled assessments planned at week 24 visit . Depending on their CSU symptoms (as assessed by the doctor), participants will either receive remibrutinib for 24 weeks, or enter an observational treatment-free period for 1 year. If the CSU symptoms return during the observational period, the participants can switch to the treatment period at any time (decided by the doctor). At the end of the 24-week treatment period, if CSU is controlled, participants will enter the 1-year observational period, otherwise, they can continue with another cycle of 24-week remibrutinib treatment. The number of remibrutinib treatment or observational cycles will be limited to 6 times each. Total duration: from 1 year to approximately 3 years, and number of visits: from 3 to 15 (depending on the CSU symptoms). 3. an optional "long-term treatment-free follow-up period" proposed to all participants who completed at least 4 months treatment in the "OLE period". No treatment will be given. Duration: 3 years with 1 site visit and up to 4 phone call follow-up visits. The primary clinical question of interest is what is the effect of remibrutinib treatment versus placebo on the change from baseline in UAS7, ISS7 and HSS7 scores after 12 weeks of treatment

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: January 22, 2032
• Est. primary completion date: November 21, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 17 Years

Eligibility

Key Inclusion Criteria:

• Male and female adolescent participants aged >= 12 to < 18 years of age at the time of signing the informed consent
• 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-AH 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-AH during this time period according to local treatment guidelines
• 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)
• Documentation of hives within three months before randomization (either at screening and/or at randomization; or documented in the participants' medical history)

Key Exclusion criteria:

• Previous use of remibrutinib or other BTK inhibitors
• Significant bleeding risk or coagulation disorders
• History of gastrointestinal bleeding
• 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
• History or current hepatic disease
• Evidence of clinically significant cardiovascular, 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
• History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes
• 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 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 Other protocol-defined inclusion/exclusion criteria may apply.

Related Conditions & MeSH terms

• Chronic Spontaneous Urticaria
• Chronic Urticaria
• Urticaria

Intervention

Drug:
• LOU064 (blinded)
LOU064 (blinded) active treatment
• placebo
matching active drug

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Canada	Novartis Investigative Site	Montreal	Quebec
Chile	Novartis Investigative Site	Santiago
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Guangdong	Guangzhou
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Tuebingen
Hong Kong	Novartis Investigative Site	Hong Kong
Italy	Novartis Investigative Site	Bari
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Parma	PR
Italy	Novartis Investigative Site	Pavia	PV
Italy	Novartis Investigative Site	Trieste	TS
Japan	Novartis Investigative Site	Itabashi-ku	Tokyo
Japan	Novartis Investigative Site	Kamimashi-gun	Kumamoto
Malaysia	Novartis Investigative Site	Kuching	Sarawak
Netherlands	Novartis Investigative Site	Deventer
Netherlands	Novartis Investigative Site	Utrecht
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Olsztyn
Poland	Novartis Investigative Site	Warszawa
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
South Africa	Novartis Investigative Site	Pretoria	Gauteng
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Esplugues De Llobregat	Barcelona
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkoknoi	Bangkok
Turkey	Novartis Investigative Site	Adana
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Istanbul
United States	Kern Research	Bakersfield	California
United States	Treasure Valley Medical Research	Boise	Idaho
United States	Pediatric Dermatology of Miami at the Pediatric CoE	Coral Gables	Florida
United States	Northshore University Health System .	Glenview	Illinois
United States	Allergy Associates of Utah	Murray	Utah
United States	Allergy Asthma and Clinical Research	Oklahoma City	Oklahoma
United States	Allergy and Asthma Specialist P S C Main Center	Owensboro	Kentucky
United States	Allergy and Clinical Immunology Ass	Pittsburgh	Pennsylvania
United States	RFSA Dermatology	San Antonio	Texas
United States	Novartis Investigative Site	Seattle	Washington
United States	Toledo Institute of Clinical Research	Toledo	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Chile,  China,  Germany,  Hong Kong,  Italy,  Japan,  Malaysia,  Netherlands,  Poland,  Singapore,  South Africa,  Spain,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in UAS7	The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42. Complete UAS7 response is UAS7 = 0.; Negative change from baseline indicates improvement.	Baseline, week 12
Primary	Change fron baseline in ISS7	Itch Severity Score (ISS) scale is 0 to 3. Score (ISS7) is derived by adding up average daily scores of 7 days preceding visit. Possible range of weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate).; Negative change from baseline indicates improvement.	Baseline, Week 12
Primary	Change from baseline in HSS7	Hives Severity Score (HSS) scale is 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. Possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None 1 - Mild (1-6 hives/12 hours) 2 - Moderate (7-12 hives/12 hours) 3 - Severe (>12 hives/12 hours).; Negative change from baseline indicates improvement.	Baseline, Week 12
Secondary	Cmax of remibrutinib	The maximum (peak) observed blood drug concentration after single dose administration	At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake
Secondary	Tmax of remibrutinib	The time to reach maximum (peak) blood drug concentration after single dose administration	At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake
Secondary	AUClast of remibrutinib	The Area Under the Curve (AUC) from pre-dose to the last measurable concentration sampling time	At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake
Secondary	Absolute change from baseline in ISS7	Itch Severity Score (ISS) scale is 0 to 3. Score (ISS7) is derived by adding up average daily scores of 7 days preceding visit. Possible range of weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate).; Negative change from baseline indicates improvement.	Baseline - Week 12
Secondary	Absolute change from baseline in HSS7	Hives Severity Score (HSS) scale is 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. Possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None 1 - Mild (1-6 hives/12 hours) 2 - Moderate (7-12 hives/12 hours) 3 - Severe (>12 hives/12 hours).; Negative change from baseline indicates improvement.	Baseline - Week 12
Secondary	Achievement of UAS7 = 6 (yes/no)	Disease activity control is defined as UAS7 = 6. The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42.	Week 12 and over time
Secondary	Achievement of UAS7 = 0 (yes/no)	Complete absence of hives and itch is defined as UAS7 = 0. The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42.	Week 12 and over time
Secondary	Absolute change from baseline in CDLQI score	The Children Dermatology life Quality Index (CDLQI) score range is 0 to 30, with 0 (meaning no impact of skin disease on quality of life) to 30 (meaning maximum impact on quality of life).	Week 12
Secondary	Number of weeks without angioedema, assessed by the cumulative number of weeks with an AAS7 = 0 response	Angioedema Activity Score (AAS7) is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-105 where higher scores indicate increased angioedema activity.	baseline - Week 12
Secondary	Occurrence of treatment-emergent adverse events (AE) and serious adverse events (SAE) during the core period	To demonstrate the safety and tolerability of remibrutinib by assessing occurrence of treatment emergent adverse events and serious adverse events during the core period of the study.	28 weeks
Secondary	Occurrence of treatment emergent AEs, and SAEs during the Open Label Extension (OLE) period	To demonstrate the safety and tolerability of remibrutinib by assessing occurrence of treatment emergent adverse events and serious adverse events during the OLE period of the study.	3 years