Clinical trial NCT06042478: Phase 3b Study to Assess the Efficacy, Safety, and Tolerability of Remibrutinib in Comparison to Placebo, With Omalizumab as Active Control, in Adult CSU Patients, Followed by an Open-label 52-week Optional Extension.
Official title: A Global, Multicenter, Randomized, Double-blind, Double-dummy, Parallel-group, Phase 3b Study to Assess the Efficacy, Safety, and Tolerability of Remibrutinib 25 mg b.i.d. in Comparison to Placebo With Omalizumab 300 mg Every 4 Weeks as Active Control Over 52 Weeks in Adult Patients With Chronic Spontaneous Urticaria Inadequately Controlled by Second Generation H1-antihistamines and an Open-label 52-week Optional Extension to Assess Long-term Efficacy, Safety and Tolerability of Remibrutinib 25 mg b.i.d.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Spontaneous Urticaria
Keywords: CSU
urticaria
LOU064
omalizumab
remibrutinib
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2023-09-18
Enrollment: 468
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible participants will be randomized to 1 of 4 treatment arms in a 2:1:1:2 ratio:

* Remibrutinib 25 mg b.i.d. arm: participants receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 52 weeks
* Placebo to remibrutinib arm: participants receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w.
* Placebo to omalizumab arm: participants receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d.
* Omalizumab 300 mg every 4 weeks arm: participants receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d. for 52 weeks.

All of the above arms are followed by an optional 52-week extension period where participants receive treatment with remibrutinib 25 mg b.i.d. for 52 weeks.
Primary purpose: TREATMENT

Brief summary: The purpose of the core phase of the trial is to assess the efficacy, safety and tolerability of remibrutinib (LOU064) 25 milligrams (mg) twice a day (b.i.d.) over placebo for 24 weeks and in comparison to omalizumab 300 mg every 4 weeks (q4w) for 52 weeks in participants with chronic spontaneous urticaria (CSU) inadequately controlled by H1-antihistamines (H1-AH).

The purpose of the open-label extension phase is to assess efficacy, safety and tolerability up to two years for patients treated with remibrutinib and patients transitioned from omalizumab to remibrutinib at Week 52. In the extension phase, treatment will be with remibrutinib only (i.e., no background therapy). The extension phase will also fulfill the Novartis commitment to provide post-trial access to participants of the previous core phase.

Detailed description: The study consists of 4 periods, and the total study duration is up to 112 weeks. Approximately 468 adult participants with CSU are expected to be randomized in the study.

Screening period: A screening period of up to 4 weeks will allow for the assessment of eligibility, determination of baseline disease activity and wash-out of prohibited medications.

Core Phase Treatment Period (52 weeks):

The treatment period will be double-dummy and double-blind, with placebo injections matching omalizumab 300 mg s.c. given to participants in the remibrutinib arm and placebo tablets matching remibrutinib 25 mg given to participants in the omalizumab arm (double-dummy). At the randomization visit, eligible participants will be randomized to one of four treatment arms.

Extension Phase Treatment Period (52 weeks): Optional open-label extension where patients receive treatment with open-label remibrutinib 25 mg, for 52 weeks.

Follow-up period:

For patients that do not enter the extension phase, there will be a 16-week, treatment-free, safety follow-up period.

Patients that enter extension phase will have a 4-week treatment-free safety follow-up period at the end of the extension phase.

All participants will be on a stable, local label-approved standard dose of a second-generation H1-AH ("background therapy") throughout the entire core phase (starting a minimum of 7 days prior to randomization until the end of the core phase).

In addition, to treat unbearable symptoms of CSU flare-ups, participants will be allowed to use a different second-generation H1-AH on an as-needed basis ("rescue therapy").

Eligibility criteria: Inclusion Criteria:

* Male and female adult participants ≥18 years of age at the time of signing the informed consent.
* CSU duration for ≥ 6 months prior to screening.
* 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.
* 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.
* 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:

* Prior exposure to ligelizumab, omalizumab and other biologics with any effect in CSU, including anti-IgE therapies.
* Significant bleeding risk or coagulation disorders.
* History of gastrointestinal bleeding.
* Requirement for anti-platelet or anti-coagulant medication.
* 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.
* Evidence of helminthic parasitic infection as evidenced by stools being positive for a pathogenic organism according to local guidelines.
* Documented history of anaphylaxis.
* Pregnant or nursing (lactating) women.

Primary outcomes:
measure: Absolute change from baseline in Weekly Urticaria Activity Score (UAS7)
timeFrame: Week 12
Secondary outcomes:
measure: Achievement of UAS7=0 (yes/no)
timeFrame: Week 12
measure: Improvement of severity of itch, assessed as absolute change from baseline in ISS7 score
timeFrame: Week 12
measure: Improvement of severity of hives, assessed as absolute change from baseline in HSS7 score
timeFrame: Week 12
measure: Occurrence of treatment-emergent adverse events and serious adverse events (SAEs)
timeFrame: up to 68 weeks
Other outcomes:
Locations:
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Santa Fe
city: Bahia Blanca
country: Argentina
facility: Novartis Investigative Site
city: Caba
country: Argentina
facility: Novartis Investigative Site
city: Capital Federal
country: Argentina
facility: Novartis Investigative Site
city: Mendoza
country: Argentina
facility: Novartis Investigative Site
city: Woolloongabba
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: RS
city: Alphaville Barueri
country: Brazil
facility: Novartis Investigative Site
state: Sao Paulo
city: Santo Andre
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sorocaba
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Varna
country: Bulgaria
facility: Novartis Investigative Site
city: Edmonton
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Hamilton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Hamilton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: London
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Niagara Falls
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Verdun
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: Brno
country: Czechia
facility: Novartis Investigative Site
city: Plzen Bolevec
country: Czechia
facility: Novartis Investigative Site
city: Praha 10
country: Czechia
facility: Novartis Investigative Site
city: Toulon Cedex 9
country: France
facility: Novartis Investigative Site
state: Val De Marne
city: Bobigny
country: France
facility: Novartis Investigative Site
city: Clermont Ferrand
country: France
facility: Novartis Investigative Site
city: Grenoble
country: France
facility: Novartis Investigative Site
city: La Rochelle
country: France
facility: Novartis Investigative Site
city: Nantes
country: France
facility: Novartis Investigative Site
city: Nice
country: France
facility: Novartis Investigative Site
city: Pierre Benite
country: France
facility: Novartis Investigative Site
city: Rouen
country: France
facility: Novartis Investigative Site
city: Frankfurt am Main
country: Germany
facility: Novartis Investigative Site
state: Hessen
city: Goettingen
country: Germany
facility: Novartis Investigative Site
state: Niedersachsen
city: Halle Saale
country: Germany
facility: Novartis Investigative Site
state: Sachsen-Anhalt
city: Leipzig
country: Germany
facility: Novartis Investigative Site
state: Sachsen
city: Bad Bentheim
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Bochum
country: Germany
facility: Novartis Investigative Site
city: Bochum
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Luebeck
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Osnabrueck
country: Germany
facility: Novartis Investigative Site
city: Stade
country: Germany
facility: Novartis Investigative Site
city: Tuebingen
country: Germany
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Kaposvar
country: Hungary
facility: Novartis Investigative Site
city: Pecs
country: Hungary
facility: Novartis Investigative Site
city: Ahmedabad
country: India
facility: Novartis Investigative Site
state: Gujarat
city: Bangalore
country: India
facility: Novartis Investigative Site
state: Karnataka
city: Mysore
country: India
facility: Novartis Investigative Site
state: Karnataka
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: Bikaner
country: India
facility: Novartis Investigative Site
state: Rajasthan
city: Hyderabad
country: India
facility: Novartis Investigative Site
state: Telangana
city: Dehradun
country: India
facility: Novartis Investigative Site
state: Uttarakhand
city: Belgavi
country: India
facility: Novartis Investigative Site
city: New Delhi
country: India
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Modena
country: Italy
facility: Novartis Investigative Site
state: MO
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Siena
country: Italy
facility: Novartis Investigative Site
state: SI
city: Ansan
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi Do
city: Busan
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Muar
country: Malaysia
facility: Novartis Investigative Site
state: Johor
city: Ipoh
country: Malaysia
facility: Novartis Investigative Site
state: Perak
city: Petaling Jaya
country: Malaysia
facility: Novartis Investigative Site
state: Selangor Darul Ehsan
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
state: Wilayah Persekutuan
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
city: Pulau Pinang
country: Malaysia
facility: Novartis Investigative Site
city: Wilayah Persekutuan
country: Malaysia
facility: Novartis Investigative Site
city: Cuauhtemoc
country: Mexico
facility: Novartis Investigative Site
state: Cdmx
city: Zapopan
country: Mexico
facility: Novartis Investigative Site
state: Jalisco
city: Villahermosa
country: Mexico
facility: Novartis Investigative Site
state: Tabasco
city: Merida
country: Mexico
facility: Novartis Investigative Site
state: Yucatan
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Krosno
country: Poland
facility: Novartis Investigative Site
city: Poznan
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Bardejov
country: Slovakia
facility: Novartis Investigative Site
city: Kezmarok
country: Slovakia
facility: Novartis Investigative Site
city: Svidnik
country: Slovakia
facility: Novartis Investigative Site
city: Trnava
country: Slovakia
facility: Novartis Investigative Site
city: Cordoba
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Granada
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Pozuelo de Alarcon
country: Spain
facility: Novartis Investigative Site
state: Madrid
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: Geneve 14
country: Switzerland
facility: Novartis Investigative Site
city: St Gallen
country: Switzerland
facility: Novartis Investigative Site
city: Zuerich
country: Switzerland
facility: Novartis Investigative Site
city: Zuerich
country: Switzerland
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taoyuan
country: Taiwan
facility: Novartis Investigative Site
city: Songkhla
country: Thailand
facility: Novartis Investigative Site
state: Hat Yai
city: Khon Kaen
country: Thailand
facility: Novartis Investigative Site
state: THA
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Chiang Mai
country: Thailand
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
state: TUR
city: Aydin
country: Turkey
facility: Novartis Investigative Site
city: Denizli
country: Turkey
facility: Novartis Investigative Site
city: Fatih-Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Sakarya
country: Turkey
facility: Novartis Investigative Site
city: Westbruy On Trym
country: United Kingdom
facility: Novartis Investigative Site
state: Bristol
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
state: West Yorkshire
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
city: Oxford
country: United Kingdom
facility: Novartis Investigative Site
city: Hanoi
country: Vietnam
facility: Novartis Investigative Site
city: Ho Chi Minh
country: Vietnam
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: