Health Condition 1: L508- Other urticaria
Conditions
Interventions
Intervention1: LOU064/remibrutinib: LOU064A (blinded) taken orally b.i.d. for 24 weeks, followed by LOU064 (open-label) taken orally open label for 28 weeks. Randomised in 2:1 ratio (active vs placebo
Sponsors
Novartis Healthcare Pvt Ltd
Eligibility
Inclusion criteria
Inclusion criteria: ?1,Signed informed consent must be obtained prior to participation in the study. ?2. Male and female adult participants =18 years of age. ?3. CSU duration for = 6 months prior to screening (defined as the onset of CSU determined by the investigator based on all available supporting documentation). ?4. 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-antihistaminesvduring 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) ?6. Documentation of hives within three months before randomization (either at screening and/or at randomization; or documented in the participants medical history). ?7. Willing and able to complete an Urticaria Patient Daily Diary (UPDD) for the duration of the study and adhere to the study protocol. ?8. 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
Exclusion criteria: 1.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 ? 2.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 ? 3.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 4.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 investigators 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 ? 5.Significant bleeding risk or coagulation disorders ?6. 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) ?7. 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. ?8. Requirement for anticoagulant medication (for example, warfarin or Novel Oral Anti-Coagulants (NOAC)) ?9. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To demonstrate that remibrutinib (25 mg b.i.d.) is superior to placebo in CSU with respect to change from baseline in UAS7 at Week 12Timepoint: Absolute change from baseline in UAS7 at Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| To demonstrate that a greater proportion of participants achieve disease activity control (UAS7 = 6) at Week 12 who are treated with remibrutinib (25 mg b.i.d.) compared to placebo-treated participantsTimepoint: Achievement of UAS7 = 6 (yes/no) at Week 12;To demonstrate that a greater proportion of participants achieve complete absence of hives and itch (UAS7 equals to 0) at Week 12 who are treated with remibrutinib (25 mg b.i.d.) compared to placebo-treated participantsTimepoint: Achievement of UAS7 equals to 0 (yes/no) at Week 12;To demonstrate the superiority of remibrutinib (25 mg b.i.d.) treated participants with respect to a reduction from baseline in the weekly itch severity score at Week 12 compared to placebotreated participantsTimepoint: Improvement of severity of itch, assessed as absolute change from baseline in ISS7 score at Week 12;To demonstrate the superiority of remibrutinib (25 mg b.i.d.) treated participants with respect to a reduction from baseline in the weekly hive severity score at Week 12 compared to placebotreated participantsTimepoint: Improvement of severity of hives, assessed as absolute change from baseline in HSS7 score at Week 12;To demonstrate that a greater proportion of participants achieve UAS7 = 6 at Week 2 who are treated with remibrutinib (25 mg b.i.d.) compared to placebo-treated participantsTimepoint: Achieving early onset of disease activity control, as defined as achievement of UAS7= 6 (yes/no) at Week 2;To demonstrate that a greater proportion of participants who are treated with remibrutinib (25 mg b.i.d.) achieve DLQI equal to 0-1 at Week 12 compared to placebotreated participantsTimepoint: No impact on participants dermatology-quality of life, as defined by achievement of DLQI equals to 0-1 (yes/no) at Week 12;To demonstrate that remibrutinib (25 mg b.i.d.) treated participants maintain disease activity control (defined as UAS7=6) for more weeks compared to placebo treated participa | — |
Countries
Argentina, Australia, Bulgaria, Colombia, Czech Republic, France, Hungary, India, Italy, Japan, Mexico, Portugal, Republic of Korea, Russian Federation, Spain, Taiwan, Turkey, United States of America
Contacts
Public ContactMurugananthan K
Novartis Healthcare PVT LTD
Outcome results
None listed