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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05030311




Registration number
NCT05030311
Ethics application status
Date submitted
19/08/2021
Date registered
1/09/2021
Date last updated
16/05/2024

Titles & IDs
Public title
A Phase 3 Study of Efficacy and Safety of Remibrutinib in the Treatment of CSU in Adults Inadequately Controlled by H1 Antihistamines
Scientific 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
Secondary ID [1] 0 0
2021-000471-37
Secondary ID [2] 0 0
CLOU064A2301
Universal Trial Number (UTN)
Trial acronym
REMIX-1
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 - LOU064 (blinded)
Treatment: Drugs - Placebo
Treatment: Drugs - LOU064 (open-label)

Experimental: Arm 1: LOU064 (blinded) - LOU064 (blinded) taken orally for 24 weeks, followed by LOU064 (open-label) taken orally open label for 28 weeks. Randomized in a 2:1 ratio (arm 1:arm 2).

Placebo Comparator: Arm 2: LOU064 placebo (blinded) - LOU064 placebo (blinded) taken orally for 24 weeks, followed by LOU064 (open-label) taken orally for 28 weeks. Randomized in a 2:1 ratio (arm 1:arm 2).


Treatment: Drugs: LOU064 (blinded)
LOU064 (blinded) active treatment

Treatment: Drugs: Placebo
Placebo

Treatment: Drugs: LOU064 (open-label)
LOU064 (open-label) active treatment
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from baseline in UAS7 (Scenario 1 with UAS7 as primary efficacy endpoint)
Timepoint [1] 0 0
12 weeks
Primary outcome [2] 0 0
Absolute change in ISS7 and absolute change in HSS7 (Scenario 2 with ISS7 and HSS7 as co-primary efficacy endpoints)
Timepoint [2] 0 0
12 weeks
Secondary outcome [1] 0 0
Change from baseline in UAS7 (only in scenario 2)
Timepoint [1] 0 0
12 weeks
Secondary outcome [2] 0 0
Sustained disease activity control (UAS7 =6)
Timepoint [2] 0 0
12 weeks
Secondary outcome [3] 0 0
Complete absence of hives and itch (UAS7 = 0)
Timepoint [3] 0 0
12 weeks
Secondary outcome [4] 0 0
Reduction of weekly ISS score (only in scenario 1)
Timepoint [4] 0 0
12 weeks
Secondary outcome [5] 0 0
Reduction of weekly HSS score (only in scenario 1)
Timepoint [5] 0 0
12 weeks
Secondary outcome [6] 0 0
Early onset of disease control (UAS7 = 6 at week 2)
Timepoint [6] 0 0
2 weeks
Secondary outcome [7] 0 0
Disease activity control (UAS7 = 6)
Timepoint [7] 0 0
12 weeks
Secondary outcome [8] 0 0
Achievement of DLQI = 0 - 1
Timepoint [8] 0 0
12 weeks
Secondary outcome [9] 0 0
Number of weeks without angioedema (AAS = 0)
Timepoint [9] 0 0
12 weeks
Secondary outcome [10] 0 0
Number of participants with Adverse Events
Timepoint [10] 0 0
56 weeks

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

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 administering 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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/11/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/01/2024
Sample size
Target
Accrual to date
Final
470
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Sydney
Recruitment hospital [2] 0 0
Novartis Investigative Site - East Melbourne
Recruitment hospital [3] 0 0
Novartis Investigative Site - Parkville
Recruitment postcode(s) [1] 0 0
2010 - Sydney
Recruitment postcode(s) [2] 0 0
3002 - East Melbourne
Recruitment postcode(s) [3] 0 0
3002 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
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Arkansas
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State/province [3] 0 0
California
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Colorado
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Florida
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Georgia
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United States of America
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Indiana
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United States of America
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Maryland
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United States of America
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Missouri
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United States of America
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Nebraska
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Ohio
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Oklahoma
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Texas
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Utah
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Washington
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Argentina
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Buenos Aires
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Nueve De Julio
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Rosario
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Santa Fe
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Bahia Blanca
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Argentina
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Capital Federal
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Pleven
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Sofia
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Bogota
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Czech Republic
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Olomouc
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Plzen
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France
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Reims
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Dalseo Gu
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San Juan
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Talas / Kayseri

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

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05030311
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries