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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05976243




Registration number
NCT05976243
Ethics application status
Date submitted
28/07/2023
Date registered
4/08/2023
Date last updated
28/06/2024

Titles & IDs
Public title
A Study to Investigate Efficacy, Safety, and Tolerability of Remibrutinib Compared With Placebo in Adults With CINDU Inadequately Controlled by H1-antihistamines
Scientific title
A 52-week Multi-center, Randomized, Double-blind, Placebo Controlled, Basket Study With an Open-label Extension to Investigate the Efficacy, Safety, and Tolerability of Remibrutinib (LOU064) in Chronic Inducible Urticaria (CINDU) in Adults Inadequately Controlled by H1-antihistamines
Secondary ID [1] 0 0
2023-505739-12
Secondary ID [2] 0 0
CLOU064M12301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Inducible 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
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Remibrutinib
Other interventions - Placebo

Experimental: Remibrutinib, symptomatic dermographism group - Remibrutinib oral twice daily in participants with symptomatic dermographism

Placebo comparator: Placebo, symptomatic dermographism group - Placebo oral twice daily, symptomatic dermographism

Experimental: Remibrutinib, cold urticaria group - Remibrutinib oral twice daily, cold urticaria

Placebo comparator: Placebo, cold urticaria group - Placebo oral twice daily, cold urticaria

Experimental: Remibrutinib, cholinergic urticaria group - Remibrutinib oral twice daily, cholinergic urticaria

Placebo comparator: Placebo, cholinergic urticaria - Placebo oral twice daily, cholinergic urticaria


Treatment: Drugs: Remibrutinib
Remibrutinib treated groups and arms

Other interventions: Placebo
Placebo treated groups and arms
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of participants with complete response in Total Fric Score; symptomatic dermographism
Timepoint [1] 0 0
Week 12
Primary outcome [2] 0 0
Proportion of participants with complete response in critical temperature threshold; cold urticaria
Timepoint [2] 0 0
Week 12
Primary outcome [3] 0 0
Proportion of participants with itch numerical rating scale =0; cholinergic urticaria
Timepoint [3] 0 0
Week 12
Secondary outcome [1] 0 0
Change from baseline in Total Fric score; symptomatic dermographism
Timepoint [1] 0 0
Week 12
Secondary outcome [2] 0 0
Change from baseline in criticial temperature threshold following Temptest; cold urticaria
Timepoint [2] 0 0
Week 12
Secondary outcome [3] 0 0
Change from baseline in itch numerical rating scale; cholinergic urticaria
Timepoint [3] 0 0
Week 12
Secondary outcome [4] 0 0
proportion of participants with Physician Global Assessment (PGA) severity of hives =0; cholinergic urticaria
Timepoint [4] 0 0
Week 12
Secondary outcome [5] 0 0
Proportion of participants with complete response in TFS; symptomatic dermographism
Timepoint [5] 0 0
Week 24
Secondary outcome [6] 0 0
Proportion of participants with complete response in Critical Temperature threshold; cold urticaria
Timepoint [6] 0 0
Week 24
Secondary outcome [7] 0 0
Proportion of participants with complete response in itch numerical rating scale; cholinergic urticaria
Timepoint [7] 0 0
Week 24
Secondary outcome [8] 0 0
Change from baseline in itch numerical rating scale in participants with symptomatic dermographism
Timepoint [8] 0 0
Week 12
Secondary outcome [9] 0 0
Change from baseline in itch numerical rating scale in participants with cold urticaria
Timepoint [9] 0 0
Week 12
Secondary outcome [10] 0 0
Proportion of participants with complete response in Total Fric score; symptomatic dermographism
Timepoint [10] 0 0
Week 2
Secondary outcome [11] 0 0
Proportion of participants with complete response in Critical Temperature Threshold; cold urticaria
Timepoint [11] 0 0
Week 2
Secondary outcome [12] 0 0
Proportion of participants with itch NRS=0; cholinergic urticaria
Timepoint [12] 0 0
Week 2
Secondary outcome [13] 0 0
Change from baseline in TFS in participants with symptomatic dermographism
Timepoint [13] 0 0
Week 2
Secondary outcome [14] 0 0
Change from baseline in Critical Temperature Threshold in participants with cold urticaria
Timepoint [14] 0 0
Week 2
Secondary outcome [15] 0 0
Change from baseline in itch NRS in participants with cholinergic urticaria
Timepoint [15] 0 0
Week 2
Secondary outcome [16] 0 0
Change from baseline in itch NRS in participants with symptomatic dermographism
Timepoint [16] 0 0
Week 2
Secondary outcome [17] 0 0
Change from baseline in itch NRS in participants with cold urticaria
Timepoint [17] 0 0
Week 2
Secondary outcome [18] 0 0
Proportion of participants with cholinergic urticaria with PGA=0
Timepoint [18] 0 0
Week 2
Secondary outcome [19] 0 0
Change from baseline in weekly most bothersome symptom NRS score on the USDD
Timepoint [19] 0 0
Week 12
Secondary outcome [20] 0 0
Proportion of participants with DLQI=0-1
Timepoint [20] 0 0
Week 12
Secondary outcome [21] 0 0
Occurrence of treatment emergent adverse events and serious adverse events during the study
Timepoint [21] 0 0
Week 52

Eligibility
Key inclusion criteria
Inclusion Criteria for core period:

1. Male and female participants =18 years of age at the time of signing of the ICFs
2. Confirmed CINDU diagnosis (as per guidelines) for symptomatic dermographism, cold urticaria or cholinergic urticaria for = 4 months (defined as onset of CINDU with supporting documentation (e.g medical record, clinical history, photographs)) and inadequate control with H1-AH at local label approved doses at the time of randomization
3. The following response to the provocation test for each subtype is required at the randomization visit :

* Symptomatic Dermographism: A Total Fric Score of =3 using the FricTest® 4.0 and a numerical rating scale score of =5 for itch after the provocation test.
* Cold Urticaria: A Critical Threshold Temperature of =15°C using the TempTest® 4.0 and a numerical rating scale score of =5 for itch after the provocation test.
* Cholinergic Urticaria: A physician global assessment of severity of hives = 2 using the Pulse-controlled ergometry test and a numerical rating scale score of =5 for itch after the provocation test.
4. Cold Urticaria: Positive ice-cube test resulting in hives at the provocation site for participants at Screening.
5. Cholinergic urticaria: Participants must show sweating in performing the pulse-controlled ergometry test on day of randomization. Participants with anhidrosis must not be included.

Inclusion criteria for the OLE:

1. Participants who have completed the Core period up to Week 52 and are willing to enter the OLE period
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria for core period:
* 1. Previous use of remibrutinib or other BTK inhibitors.
2. Participants who have concomitant CSU at screening. Participants with resolved CSU at the time of screening can be included in the study.
3. Participants who have a familial form (e.g familial cold autoinflammatory syndrome, familial cold urticaria) of the target CINDU that is being considered for the participant's inclusion in this study.
4. Participants having a more defined other form of inducible urticaria than the target CINDU that is being considered for the participant's inclusion in this study.
5. Diseases, other than chronic inducible urticaria, with urticaria or angioedema symptoms including but not limited to urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquired angioedema
6. 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, etc.) or skin diseases associated with only wheals and no itch e.g asymptomatic dermographism

There are no exclusion criteria for OLE

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
7/12/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2028
Actual
Sample size
Target
348
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 - Carlton
Recruitment hospital [3] 0 0
Novartis Investigative Site - Melbourne
Recruitment postcode(s) [1] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 0 0
3053 - Carlton
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Idaho
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Kentucky
Country [11] 0 0
United States of America
State/province [11] 0 0
Maryland
Country [12] 0 0
United States of America
State/province [12] 0 0
Nebraska
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Oklahoma
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
South Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Utah
Country [19] 0 0
Argentina
State/province [19] 0 0
Buenos Aires
Country [20] 0 0
Argentina
State/province [20] 0 0
Santa Fe
Country [21] 0 0
Canada
State/province [21] 0 0
Manitoba
Country [22] 0 0
Canada
State/province [22] 0 0
Ontario
Country [23] 0 0
Canada
State/province [23] 0 0
Quebec
Country [24] 0 0
China
State/province [24] 0 0
Fujian
Country [25] 0 0
China
State/province [25] 0 0
Guangdong
Country [26] 0 0
China
State/province [26] 0 0
Guangzhou
Country [27] 0 0
China
State/province [27] 0 0
Hunan
Country [28] 0 0
China
State/province [28] 0 0
Jiangsu
Country [29] 0 0
China
State/province [29] 0 0
Jilin
Country [30] 0 0
China
State/province [30] 0 0
Shandong
Country [31] 0 0
China
State/province [31] 0 0
Sichuan
Country [32] 0 0
China
State/province [32] 0 0
Xinjiang
Country [33] 0 0
China
State/province [33] 0 0
Zhejiang
Country [34] 0 0
China
State/province [34] 0 0
Beijing
Country [35] 0 0
China
State/province [35] 0 0
Chongqing
Country [36] 0 0
China
State/province [36] 0 0
Jinan
Country [37] 0 0
China
State/province [37] 0 0
Shanghai
Country [38] 0 0
China
State/province [38] 0 0
Tianjin
Country [39] 0 0
Hong Kong
State/province [39] 0 0
Hong Kong
Country [40] 0 0
Israel
State/province [40] 0 0
Haifa
Country [41] 0 0
Israel
State/province [41] 0 0
Jerusalem
Country [42] 0 0
Israel
State/province [42] 0 0
Kfar Saba
Country [43] 0 0
Israel
State/province [43] 0 0
Ramat Gan
Country [44] 0 0
Israel
State/province [44] 0 0
Tel Aviv
Country [45] 0 0
Japan
State/province [45] 0 0
Fukuoka
Country [46] 0 0
Japan
State/province [46] 0 0
Kumamoto
Country [47] 0 0
Japan
State/province [47] 0 0
Osaka
Country [48] 0 0
Japan
State/province [48] 0 0
Shimane
Country [49] 0 0
Japan
State/province [49] 0 0
Tokyo
Country [50] 0 0
Korea, Republic of
State/province [50] 0 0
Gyeonggi Do
Country [51] 0 0
Korea, Republic of
State/province [51] 0 0
Seoul
Country [52] 0 0
Malaysia
State/province [52] 0 0
Johor
Country [53] 0 0
Malaysia
State/province [53] 0 0
Perak
Country [54] 0 0
Malaysia
State/province [54] 0 0
Wilayah Persekutuan
Country [55] 0 0
Malaysia
State/province [55] 0 0
Penang
Country [56] 0 0
Singapore
State/province [56] 0 0
Singapore
Country [57] 0 0
Thailand
State/province [57] 0 0
Chiang Mai
Country [58] 0 0
Turkey
State/province [58] 0 0
Istanbul
Country [59] 0 0
Turkey
State/province [59] 0 0
Sakarya
Country [60] 0 0
Turkey
State/province [60] 0 0
Talas / Kayseri

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 3, parallel group, placebo-controlled, double-blind, confirmatory study in patients with CINDU, with an optional Open-label Extension (OLE).

The purpose of the core period (52 weeks of treatment) of this study is to evaluate the efficacy, safety, and tolerability of remibrutinib (LOU064) vs. placebo in adults suffering from CINDU inadequately controlled by H1-antihistamines (H1-AHs).

The purpose of the OLE period is to collect long-term efficacy, safety, and tolerability data on remibrutinib in participants after having completed the Core period
Trial website
https://clinicaltrials.gov/study/NCT05976243
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
1-888-669-6682
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/NCT05976243