Clinical trial NCT05677451: 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
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Spontaneous Urticaria
Keywords: BTK inhibitor
Chronic spontaneous urticaria
Urticaria activity score
Hives severity score
Itch severity score
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2023-01-10
Enrollment: 100
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Detailed 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

Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline in UAS7
timeFrame: Baseline, week 12
measure: Change fron baseline in ISS7
timeFrame: Baseline, Week 12
measure: Change from baseline in HSS7
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Cmax of remibrutinib
timeFrame: At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake
measure: Tmax of remibrutinib
timeFrame: At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake
measure: AUClast of remibrutinib
timeFrame: At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake
measure: Absolute change from baseline in ISS7
timeFrame: Baseline - Week 12
measure: Absolute change from baseline in HSS7
timeFrame: Baseline - Week 12
measure: Achievement of UAS7 ≤ 6 (yes/no)
timeFrame: Week 12 and over time
measure: Achievement of UAS7 = 0 (yes/no)
timeFrame: Week 12 and over time
measure: Absolute change from baseline in CDLQI score
timeFrame: Week 12
measure: Number of weeks without angioedema, assessed by the cumulative number of weeks with an AAS7 = 0 response
timeFrame: baseline - Week 12
measure: Occurrence of treatment-emergent adverse events (AE) and serious adverse events (SAE) during the core period
timeFrame: 28 weeks
measure: Occurrence of treatment emergent AEs, and SAEs during the Open Label Extension (OLE) period
timeFrame: 3 years
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: Kern Research
state: California
city: San Diego
country: United States
facility: Allergy and Asthma Medical Group and Research Center
state: California
city: Coral Gables
country: United States
facility: Pediatric Dermatology of Miami at the Pediatric CoE
state: Florida
city: Boise
country: United States
facility: Treasure Valley Medical Research
state: Idaho
city: Glenview
country: United States
facility: Endeavor Health
state: Illinois
city: Owensboro
country: United States
facility: Allergy and Asthma Specialist P S C
state: Kentucky
city: Toledo
country: United States
facility: Toledo Institute of Clinical Research
state: Ohio
city: Oklahoma City
country: United States
facility: Allergy Asthma and Clinical Research
state: Oklahoma
city: Pittsburgh
country: United States
facility: Allergy and Clinical Immunology Associates
state: Pennsylvania
city: San Antonio
country: United States
facility: RFSA Dermatology
state: Texas
city: Sandy
country: United States
facility: Allergy Associates of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Allergy and Asthma Rsch
state: Washington
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Santa Fe
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Guangdong
country: China
facility: Novartis Investigative Site
state: Guangzhou
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Frankfurt am Main
country: Germany
facility: Novartis Investigative Site
state: Hessen
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Tuebingen
country: Germany
facility: Novartis Investigative Site
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Pokfulam
country: Hong Kong
facility: Novartis Investigative Site
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Parma
country: Italy
facility: Novartis Investigative Site
state: PR
city: Pavia
country: Italy
facility: Novartis Investigative Site
state: PV
city: Siena
country: Italy
facility: Novartis Investigative Site
state: SI
city: Trieste
country: Italy
facility: Novartis Investigative Site
state: TS
city: Bari
country: Italy
facility: Novartis Investigative Site
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Kitakyushu
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Kamimashi-gun
country: Japan
facility: Novartis Investigative Site
state: Kumamoto
city: Sakai
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: Kuching
country: Malaysia
facility: Novartis Investigative Site
state: Sarawak
city: Deventer
country: Netherlands
facility: Novartis Investigative Site
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
city: Lodz
country: Poland
facility: Novartis Investigative Site
city: Olsztyn
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Pretoria
country: South Africa
facility: Novartis Investigative Site
state: Gauteng
city: Cape Town
country: South Africa
facility: Novartis Investigative Site
state: Western Cape
city: Esplugues De Llobregat
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Songkhla
country: Thailand
facility: Novartis Investigative Site
state: Hat Yai
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Adana
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Peterborough
country: United Kingdom
facility: Novartis Investigative Site
state: Cambridgeshire
city: Southampton
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: