Resumen

The purpose of this study was 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.

Descripción detallada

This was a global Phase III multi-centered, randomized,double-blind, parallel-group, placebo-controlled study investigating the safety, tolerability, and efficacy of remibrutinib (25 mg b.i.d.) in adult patients with CSU inadequately controlled by second generation H1-antihistamines (H1-AHs). The study consisted of four periods, the total study duration was up to 60 weeks: Screening period of up to 4 weeks, Double-blind placebo-controlled treatment period of 24 weeks, Open-label treatment period with remibrutinib period of 28 weeks, and treatment-free follow-up period of 4 weeks. The planned sample size was approximately 450 patients randomized in 2:1 ratio to remibrutinib or placebo arm (300 in the remibrutinib arm and 150 in placebo arm).

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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).

Criterios de exclusión

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

Ubicaciones

Novartis Investigative Site

CABA, Buenos Aires, Argentina

Novartis Investigative Site

CABA, Buenos Aires, Argentina

Novartis Investigative Site

La Plata, Buenos Aires, Argentina

Novartis Investigative Site

Buenos Aires, Nueve De Julio, Argentina

Novartis Investigative Site

Santa Fe, Rosario, Argentina

Novartis Investigative Site

Rosario, Santa Fe Province, Argentina

Novartis Investigative Site

Bahía Blanca, Argentina

Novartis Investigative Site

Capital Federal, Argentina

Novartis Investigative Site

Santa Fe, Argentina

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

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

LOU064 25 mg (b.i.d)

Placebo

LOU064 25 mg (b.i.d) as a tablet.

Ubicaciones

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Patrocinadores