Chronic Spontaneous Urticaria MedDRA version: 20.0 Level: PT Classification code 10072757 Term: Chronic spontaneous urticaria System Organ Class: 10040785 - Skin and subcutaneous tissue disorders
Conditions
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants eligible for inclusion in this study must meet all of the following 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) Other protocol-defined inclusion criteria may apply. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 405 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
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, 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. where intervention was indicated or requiring hospitalization or blood transfusion) - Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel up to 75 mg/d. 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 Other protocol-defined exclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that remibrutinib is superior to placebo in CSU with respect to change from baseline in UAS7 at Week 12 (Scenario 1 with UAS7 as primary efficacy endpoint) or with respect to change from baseline in ISS7 and HSS7 at Week 12 (Scenario 2 with ISS7 and HSS7 as co-primary efficacy endpoints);Secondary Objective: To demonstrate: -that remibrutinib is superior to placebo in CSU with respect to change from baseline in UAS7 at Week 12 (only in scenario 2) -that a greater proportion of participants who are treated with remibrutinib compared to placebo-treated participants at Week 12: --achieve disease activity control (UAS7 = 6) --achieve complete absence of hives and itch (UAS7 = 0) -superiority of remibrutinib treated compared to placebo-treated participants at Week 12 with respect to (only in scenario 1): --reduction from baseline in the ISS7 --reduction from baseline in the HSS7 -that a greater proportion of participants who are treated with remibrutinib compared to placebo-treated participants: --achieve UAS7 = 6 at Week 2 --achieve DLQI = 0-1 at Week 12 -that remibrutinib treated compared to placebo treated participants over 12 weeks: --maintain disease activity control (defined as UAS7=6) for more weeks --have more angioedema occurrence-free weeks -the safety and tolerability;Primary end point(s): Absolute change from baseline in UAS7 (only in scenario 1) Absolute change from baseline in ISS7 (only in scenario 2) Absolute change from baseline in HSS7 (only in scenario 2) ;Timepoint(s) of evaluation of this end point: Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Absolute change from baseline in UAS7 (only in scenario 2) - Achievement of UAS7= 6 (yes/no) at Week 12; - Achievement of UAS7 = 0 (yes/no) at Week 12; - Improvement of severity of itch, assessed as absolute change from baseline in ISS7 score at Week 12 (only in scenario 1); - Improvement of severity of hives, assessed as absolute change from baseline in HSS7 score at Week 12 (only in scenario 1); - Achieving early onset of disease activity control, as defined as achievement of UAS7= 6 (yes/no) at Week 2; - No impact on participants' dermatology-quality of life, as defined by achievement of DLQI = 0-1 (yes/no) at Week 12; - Achieving sustained disease activity control, assessed as cumulative number of weeks with an UAS7=6 response between baseline and Week 12; - Number of weeks without angioedema, assessed by the cumulative number of weeks with an AAS7= 0 response between baseline and Week 12; - Occurrence of treatment emergent adverse events and serious adverse events during the study;Timepoint(s) of evaluation of this end point: Week 12; Week 2 for achieving early onset of disease activity control, defined as achievement of UAS7= 6 (yes/no) | — |
Countries
Austria, Brazil, Canada, China, Denmark, Germany, India, Malaysia, Poland, Russian Federation, Slovakia, South Africa, Switzerland, Taiwan, Thailand, United Kingdom, United States, Viet Nam
Contacts
Public ContactDRA information desk
Novartis Slovakia s.r.o.
Outcome results
None listed