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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06042478




Registration number
NCT06042478
Ethics application status
Date submitted
7/09/2023
Date registered
18/09/2023
Date last updated
28/06/2024

Titles & IDs
Public title
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.
Scientific 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.
Secondary ID [1] 0 0
2022-000518-32
Secondary ID [2] 0 0
CLOU064A2304
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Spontaneous Urticaria 0 0
Condition category
Condition code
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions
Inflammatory and Immune System 0 0 0 0
Allergies
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Remibrutinib
Treatment: Drugs - Placebo to remibrutinib
Treatment: Drugs - Placebo to omalizumab
Treatment: Drugs - Omalizumab

Experimental: Remibrutinib - Participants will receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 52 weeks.

Placebo comparator: Placebo to remibrutinib - Participants will receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants will receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w.

Placebo comparator: Placebo to omalizumab - Participants will receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants will receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d.

Active comparator: Omalizumab - participants will receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d. for 52 weeks.


Treatment: Drugs: Remibrutinib
Active treatment

Treatment: Drugs: Placebo to remibrutinib
Placebo followed by active treatment

Treatment: Drugs: Placebo to omalizumab
Placebo followed by active comparator

Treatment: Drugs: Omalizumab
Active comparator
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Absolute change from baseline in Weekly Urticaria Activity Score (UAS7)
Timepoint [1] 0 0
Week 12
Secondary outcome [1] 0 0
Achievement of UAS7=0 (yes/no)
Timepoint [1] 0 0
Week 12
Secondary outcome [2] 0 0
Improvement of severity of itch, assessed as absolute change from baseline in ISS7 score
Timepoint [2] 0 0
Week 12
Secondary outcome [3] 0 0
Improvement of severity of hives, assessed as absolute change from baseline in HSS7 score
Timepoint [3] 0 0
Week 12
Secondary outcome [4] 0 0
Occurrence of treatment-emergent adverse events and serious adverse events (SAEs)
Timepoint [4] 0 0
up to 68 weeks

Eligibility
Key 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).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/11/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
29/03/2027
Actual
Sample size
Target
468
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Woolloongabba
Recruitment hospital [2] 0 0
Novartis Investigative Site - Melbourne
Recruitment postcode(s) [1] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Buenos Aires
Country [2] 0 0
Argentina
State/province [2] 0 0
Santa Fe
Country [3] 0 0
Argentina
State/province [3] 0 0
Bahia Blanca
Country [4] 0 0
Argentina
State/province [4] 0 0
Caba
Country [5] 0 0
Argentina
State/province [5] 0 0
Capital Federal
Country [6] 0 0
Argentina
State/province [6] 0 0
Mendoza
Country [7] 0 0
Brazil
State/province [7] 0 0
RS
Country [8] 0 0
Brazil
State/province [8] 0 0
Sao Paulo
Country [9] 0 0
Brazil
State/province [9] 0 0
SP
Country [10] 0 0
Bulgaria
State/province [10] 0 0
Sofia
Country [11] 0 0
Bulgaria
State/province [11] 0 0
Varna
Country [12] 0 0
Canada
State/province [12] 0 0
Alberta
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario
Country [14] 0 0
Canada
State/province [14] 0 0
Quebec
Country [15] 0 0
Czechia
State/province [15] 0 0
Czech Republic
Country [16] 0 0
Czechia
State/province [16] 0 0
Plzen Bolevec
Country [17] 0 0
Czechia
State/province [17] 0 0
Prague 10
Country [18] 0 0
France
State/province [18] 0 0
Val De Marne
Country [19] 0 0
France
State/province [19] 0 0
Bobigny Cedex
Country [20] 0 0
France
State/province [20] 0 0
Clermont Ferrand
Country [21] 0 0
France
State/province [21] 0 0
La Rochelle
Country [22] 0 0
France
State/province [22] 0 0
La Tronche
Country [23] 0 0
France
State/province [23] 0 0
Nantes Cedex 1
Country [24] 0 0
France
State/province [24] 0 0
Nice
Country [25] 0 0
France
State/province [25] 0 0
Pierre Benite
Country [26] 0 0
France
State/province [26] 0 0
Rouen
Country [27] 0 0
Germany
State/province [27] 0 0
Bad Bentheim
Country [28] 0 0
Germany
State/province [28] 0 0
Berlin
Country [29] 0 0
Germany
State/province [29] 0 0
Bochum
Country [30] 0 0
Germany
State/province [30] 0 0
Dresden
Country [31] 0 0
Germany
State/province [31] 0 0
Frankfurt
Country [32] 0 0
Germany
State/province [32] 0 0
Freiburg
Country [33] 0 0
Germany
State/province [33] 0 0
Gottingen
Country [34] 0 0
Germany
State/province [34] 0 0
Halle
Country [35] 0 0
Germany
State/province [35] 0 0
Hamburg
Country [36] 0 0
Germany
State/province [36] 0 0
Heidelberg
Country [37] 0 0
Germany
State/province [37] 0 0
Leipzig
Country [38] 0 0
Germany
State/province [38] 0 0
Luebeck
Country [39] 0 0
Germany
State/province [39] 0 0
Muenchen
Country [40] 0 0
Germany
State/province [40] 0 0
Muenster
Country [41] 0 0
Germany
State/province [41] 0 0
Osnabrueck
Country [42] 0 0
Germany
State/province [42] 0 0
Stade
Country [43] 0 0
Germany
State/province [43] 0 0
Tuebingen
Country [44] 0 0
Hungary
State/province [44] 0 0
Kaposvar
Country [45] 0 0
India
State/province [45] 0 0
Gujarat
Country [46] 0 0
India
State/province [46] 0 0
Karnataka
Country [47] 0 0
India
State/province [47] 0 0
Maharashtra
Country [48] 0 0
India
State/province [48] 0 0
Rajasthan
Country [49] 0 0
India
State/province [49] 0 0
Telangana
Country [50] 0 0
India
State/province [50] 0 0
Uttarakhand
Country [51] 0 0
India
State/province [51] 0 0
New Delhi
Country [52] 0 0
Italy
State/province [52] 0 0
MI
Country [53] 0 0
Italy
State/province [53] 0 0
Roma
Country [54] 0 0
Korea, Republic of
State/province [54] 0 0
Gyeonggi Do
Country [55] 0 0
Korea, Republic of
State/province [55] 0 0
Busan
Country [56] 0 0
Korea, Republic of
State/province [56] 0 0
Seoul
Country [57] 0 0
Malaysia
State/province [57] 0 0
Johor
Country [58] 0 0
Malaysia
State/province [58] 0 0
Perak
Country [59] 0 0
Malaysia
State/province [59] 0 0
Selangor Darul Ehsan
Country [60] 0 0
Malaysia
State/province [60] 0 0
Wilayah Persekutuan
Country [61] 0 0
Malaysia
State/province [61] 0 0
Kuala Lumpur
Country [62] 0 0
Malaysia
State/province [62] 0 0
Penang
Country [63] 0 0
Netherlands
State/province [63] 0 0
Amsterdam
Country [64] 0 0
Netherlands
State/province [64] 0 0
Utrecht
Country [65] 0 0
Poland
State/province [65] 0 0
Gdansk
Country [66] 0 0
Poland
State/province [66] 0 0
Krosno
Country [67] 0 0
Poland
State/province [67] 0 0
Poznan
Country [68] 0 0
Poland
State/province [68] 0 0
Warszawa
Country [69] 0 0
Slovakia
State/province [69] 0 0
Bardejov
Country [70] 0 0
Slovakia
State/province [70] 0 0
Kezmarok
Country [71] 0 0
Slovakia
State/province [71] 0 0
Svidnik
Country [72] 0 0
Slovakia
State/province [72] 0 0
Trnava
Country [73] 0 0
Spain
State/province [73] 0 0
Andalucia
Country [74] 0 0
Spain
State/province [74] 0 0
Catalunya
Country [75] 0 0
Spain
State/province [75] 0 0
Comunidad Valenciana
Country [76] 0 0
Spain
State/province [76] 0 0
Madrid
Country [77] 0 0
Spain
State/province [77] 0 0
Las Palmas de Gran Canaria
Country [78] 0 0
Spain
State/province [78] 0 0
Valencia
Country [79] 0 0
Switzerland
State/province [79] 0 0
Geneve
Country [80] 0 0
Switzerland
State/province [80] 0 0
St Gallen
Country [81] 0 0
Switzerland
State/province [81] 0 0
Zuerich
Country [82] 0 0
Taiwan
State/province [82] 0 0
Taipei
Country [83] 0 0
Taiwan
State/province [83] 0 0
Taoyuan
Country [84] 0 0
Thailand
State/province [84] 0 0
Bangkok
Country [85] 0 0
Thailand
State/province [85] 0 0
Hat Yai
Country [86] 0 0
Thailand
State/province [86] 0 0
Phayathai
Country [87] 0 0
Thailand
State/province [87] 0 0
THA
Country [88] 0 0
Thailand
State/province [88] 0 0
Chiang Mai
Country [89] 0 0
Turkey
State/province [89] 0 0
TUR
Country [90] 0 0
Turkey
State/province [90] 0 0
Aydin
Country [91] 0 0
Turkey
State/province [91] 0 0
Denizli
Country [92] 0 0
Turkey
State/province [92] 0 0
Fatih-Istanbul
Country [93] 0 0
Turkey
State/province [93] 0 0
Sakarya

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT06042478
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
+41613241111
Fax 0 0
Email 0 0
novartis.email@novartis.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06042478