Clinical trial NCT05030311: A Phase 3 Study of Efficacy and Safety of Remibrutinib in the Treatment of CSU in Adults Inadequately Controlled by H1 Antihistamines
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Phase 3 Study of Remibrutinib (LOU064) to Investigate the Efficacy, Safety and Tolerability for 52 Weeks in Adult Chronic Spontaneous Urticaria (CSU) Patients Inadequately Controlled by H1-antihistamines
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Spontaneous Urticaria
Keywords: BTK inhibitor
Chronic spontaneous urticaria
Urticaria activity score
Hives severity score
Itch severity score
CSU
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-09-01
Enrollment: 470
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to establish the efficacy, safety, and tolerability of remibrutinib (LOU064) in adult participants suffering from chronic spontaneous urticaria (CSU) inadequately controlled by H1-antihistamines in comparison to placebo.

Detailed description: This was a global Phase III multi-centered, randomized,double-blind, parallel-group, placebo-controlled study investigating the safety, tolerability, and efficacy of remibrutinib (25 mg b.i.d.) in adult patients with CSU inadequately controlled by second generation H1-antihistamines (H1-AHs). The study consisted of four periods, the total study duration was up to 60 weeks: Screening period of up to 4 weeks, Double-blind placebo-controlled treatment period of 24 weeks, Open-label treatment period with remibrutinib period of 28 weeks, and treatment-free follow-up period of 4 weeks. The planned sample size was approximately 450 patients randomized in 2:1 ratio to remibrutinib or placebo arm (300 in the remibrutinib arm and 150 in placebo arm).

Eligibility criteria: Inclusion Criteria:

* Signed informed consent must be obtained prior to participation in the study.
* Male and female adult 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 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-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 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).
* 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 randomization (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-inflammatory 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

Primary outcomes:
measure: Change From Baseline in Weekly Urticaria Score (UAS7) at Week 12 (Scenario 1 With UAS7 as Primary Efficacy Endpoint)
timeFrame: Baseline, Week 12
measure: Change From Baseline in Weekly Itch Severity Score (ISS7) at Week 12 (Scenario 2 With ISS7 and HSS7 as Co-primary Efficacy Endpoints)
timeFrame: Baseline, Week 12
measure: Change From Baseline in Weekly Hives Severity Score (HSS7) at Week 12 (Scenario 2 With ISS7 and HSS7 as Co-primary Efficacy Endpoints)
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Number of Patients Who Achieved Disease Activity Control (UAS7 ≤6)
timeFrame: Week 12
measure: Number of Patients Who Achieved Complete Absence of Hives and Itch (UAS7 = 0)
timeFrame: Week 12
measure: Number of Patients With Early Onset of Disease Control (UAS7 ≤ 6 at Week 2)
timeFrame: Week 2
measure: Cumulative Number of Weeks With Disease Activity Control (UAS7 <= 6) up to Week 12
timeFrame: up to Week 12
measure: Number of Patients Who Achieved DLQI = 0 - 1
timeFrame: Week 12
measure: Cumulative Number of Weeks Without Angioedema (AAS7 = 0)
timeFrame: Up to Week 12
measure: Number of Participants With Adverse Events
timeFrame: On-treatment adverse events are reported from first dose of study medication up to 28 days after last dose of study medication, for a timeframe up to approximately 56 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Novartis Investigative Site
state: Alabama
city: North Little Rock
country: United States
facility: Novartis Investigative Site
state: Arkansas
city: Bakersfield
country: United States
facility: Novartis Investigative Site
state: California
city: Lancaster
country: United States
facility: Novartis Investigative Site
state: California
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: Redwood City
country: United States
facility: Novartis Investigative Site
state: California
city: Denver
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Aventura
country: United States
facility: Novartis Investigative Site
state: Florida
city: Greenacres City
country: United States
facility: Finlay Medical Research
state: Florida
city: Sarasota
country: United States
facility: Novartis Investigative Site
state: Florida
city: Tallahassee
country: United States
facility: Novartis Investigative Site
state: Florida
city: Albany
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Woodstock
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Evansville
country: United States
facility: Novartis Investigative Site
state: Indiana
city: Chevy Chase
country: United States
facility: Novartis Investigative Site
state: Maryland
city: Saint Louis
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Lincoln
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facility: Novartis Investigative Site
state: Nebraska
city: Athens
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Columbus
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Toledo
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facility: Novartis Investigative Site
state: Ohio
city: Tulsa
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: Austin
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facility: Novartis Investigative Site
state: Texas
city: El Paso
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facility: Novartis Investigative Site
state: Texas
city: San Antonio
country: United States
facility: Novartis Investigative Site
state: Texas
city: Sandy
country: United States
facility: Novartis Investigative Site
state: Utah
city: Bellingham
country: United States
facility: Novartis Investigative Site
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: La Plata
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
state: Nueve De Julio
city: Santa Fe
country: Argentina
facility: Novartis Investigative Site
state: Rosario
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Santa Fe
city: Bahia Blanca
country: Argentina
facility: Novartis Investigative Site
city: Capital Federal
country: Argentina
facility: Novartis Investigative Site
city: Santa Fe
country: Argentina
facility: Novartis Investigative Site
city: Sydney
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: East Melbourne
country: Australia
facility: Novartis Investigative Site
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city: Parkville
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facility: Novartis Investigative Site
state: Victoria
city: Pleven
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facility: Novartis Investigative Site
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country: Bulgaria
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city: Barranquilla
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facility: Novartis Investigative Site
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city: Barranquilla
country: Colombia
facility: Novartis Investigative Site
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city: Brno
country: Czechia
facility: Novartis Investigative Site
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city: Olomouc
country: Czechia
facility: Novartis Investigative Site
state: CZE
city: Plzen
country: Czechia
facility: Novartis Investigative Site
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country: Czechia
facility: Novartis Investigative Site
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country: France
facility: Novartis Investigative Site
city: Bordeaux Cedex
country: France
facility: Novartis Investigative Site
city: Nice
country: France
facility: Novartis Investigative Site
city: Pierre Benite
country: France
facility: Novartis Investigative Site
city: Reims
country: France
facility: Novartis Investigative Site
city: Rouen
country: France
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city: Debrecen
country: Hungary
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state: Hajdu Bihar
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Szeged
country: Hungary
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city: New Delhi
country: India
facility: Novartis Investigative Site
state: Delhi
city: Nagpur
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Nagpur
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Nashik
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Hyderabad
country: India
facility: Novartis Investigative Site
state: Telangana
city: Varanasi
country: India
facility: Novartis Investigative Site
state: Uttar Pradesh
city: Kolkata
country: India
facility: Novartis Investigative Site
state: West Bengal
city: Belgavi
country: India
facility: Novartis Investigative Site
city: Chandigarh
country: India
facility: Novartis Investigative Site
city: Ancona
country: Italy
facility: Novartis Investigative Site
state: AN
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Pisa
country: Italy
facility: Novartis Investigative Site
state: PI
city: Torino
country: Italy
facility: Novartis Investigative Site
state: TO
city: Obihiro
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Yokohama
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Kamimashi-gun
country: Japan
facility: Novartis Investigative Site
state: Kumamoto
city: Takatsuki
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Koto
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Fukuoka
country: Japan
facility: Novartis Investigative Site
city: Hiroshima
country: Japan
facility: Novartis Investigative Site
city: Daegu
country: Korea, Republic of
facility: Novartis Investigative Site
state: Dalseo Gu
city: Hwaseong si
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi Do
city: Suwon si
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi Do
city: Gwangju
country: Korea, Republic of
facility: Novartis Investigative Site
city: Incheon
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Ciudad de Mexico
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Novartis Investigative Site
state: Jalisco
city: Villahermosa
country: Mexico
facility: Novartis Investigative Site
state: Tabasco
city: Carolina
country: Puerto Rico
facility: Novartis Investigative Site
city: San Juan
country: Puerto Rico
facility: Novartis Investigative Site
city: Izhevsk
country: Russian Federation
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Alicante
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Las Palmas de Gran Canaria
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Valencia
country: Spain
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Aydin
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Kayseri
country: Turkey
facility: Novartis Investigative Site
city: Sakarya
country: Turkey
facility: Novartis Investigative Site
city: Samsun
country: Turkey
facility: Novartis Investigative Site
city: Talas Kayseri
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: