Chronic Spontaneous Urticaria
Conditions
Keywords
LOU064, CSU, Treatment algorithm, UAS7, UCT7, sgH1-AH, omalizumab, remibrutinib
Brief summary
The purpose of this open-label study is to assess the efficacy and safety of a novel treatment algorithm for sequencing remibrutinib and omalizumab in the treatment of adult participants with chronic spontaneous urticaria (CSU) who are inadequately controlled by second-generation H1-antihistamines (sgH1-AH).
Detailed description
This is a global, multi-center, open-label study, investigating a remibrutinib- and omalizumab-based treatment algorithm in adult patients with CSU inadequately controlled by sgH1-AH, to achieve fast and well-controlled disease within 24 weeks.
Interventions
DRUGRemibrutinib
Remibrutinib 25 mg twice a day.
DRUGOmalizumab
Omalizumab 300 mg every 4 weeks.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Male and female adults (age ≥18 years) at the time of signing the informed consent. 2. CSU duration for ≥2 months prior to screening (defined as the onset of CSU determined by the Investigator based on all available supporting documentation). 3. Diagnosis of CSU inadequately controlled by sgH1-AH at baseline defined as: * The presence of itch and hives for ≥6 consecutive weeks prior to screening despite the use of sgH1-AH during this time period. * UAS7 score (range: 0-42) ≥16. 4. Documentation of hives within two months prior to baseline (either at screening and/or at baseline; or documented in the participant's medical history). 5. Willing and able to complete an Urticaria Patient Daily Diary (UPDD) for the duration of the study and adhere to the study protocol. 6. Participants must not have had more than one missing UPDD entry (either morning or evening) in the 7 days prior to enrollment (Day 1). Key
Exclusion criteria
1. Previous use of remibrutinib, other Bruton's tyrosine kinase (BTK) inhibitors or prior exposure to biologics with any effect in CSU (e.g., ligelizumab, omalizumab, dupilumab, barzolvolimab). 2. 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, gastrointestinal, or hematological disorders, 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 by the participant. 3. Significant bleeding risk or coagulation disorders. 4. History of gastrointestinal bleeding, e.g., in association with use of nonsteroidal anti-inflammatory drugs (NSAIDs), that was clinically relevant (e.g., where intervention was indicated or requiring hospitalization or blood transfusion). 5. Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel up to 75mg/d. The use of dual anti-platelet therapy (e.g., acetylsalicylic acid + clopidogrel) is prohibited. 6. Requirement for anticoagulant medication (for example, warfarin or Novel Oral Anti- Coagulant - NOAC). 7. 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 1.5x upper limit of normal (ULN) or international normalized ratio (INR) of more than 1.5 at screening. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants achieving Urticaria Activity Score over 7 days (UAS7) ≤6 (yes/no) | Week 24 | UAS7 is a validated patient-reported measure of chronic spontaneous urticaria disease activity over 7 days. It is calculated as the sum of the weekly Hives Severity Score (HSS7) and the weekly Itch Severity Score (ISS7) and ranges from 0 to 42. Lower scores indicate lower disease activity / better disease control, and a score of ≤6 indicates well-controlled disease. HSS7 and ISS7 are each derived from daily diary entries over the 7 days preceding the visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants achieving UAS7 ≤6 (yes/no) | Weeks 16 and 20 | UAS7 is calculated as the sum of the HSS7 and ISS7 and ranges from 0 to 42. Lower scores indicate lower disease activity / better disease control, and a score of ≤6 indicates well-controlled disease. HSS7 and ISS7 are each derived from daily diary entries over the 7 days preceding the visit. |
| Proportion of participants achieving UAS7 =0 (yes/no) | Weeks 16, 20, and 24 | UAS7 is calculated as the sum of the HSS7 and ISS7 and ranges from 0 to 42, with 0 indicating no urticaria activity over the 7-day assessment period and higher scores indicating worse disease activity. |
| Proportion of participants achieving Angioedema Activity Score over 7 days (AAS7) =0. | Weeks 16, 20, and 24 | AAS7 is a validated tool assessing angioedema activity, recorded once daily in the evening in the eDiary. If no angioedema is reported on a given day, the daily score is 0. Weekly AAS7 scores range from 0 to 105, with higher scores indicating greater angioedema severity; therefore, 0 represents absence of angioedema. |
| Proportion of participants achieving of Dermatology Life Quality Index (DLQI) =0/1 | Weeks 16, 20, and 24 | DLQI is a 10-item dermatology-specific quality-of-life instrument assessing the impact of skin disease over the previous 7 days. The total score ranges from 0 to 30, with higher scores indicating worse disease-related quality of life. A score of 0-1 corresponds to no effect on the participant's life. |
| Incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) | From Day 1 until at least 4 weeks after the last administration of remibrutinib and at least 16 weeks after the last administration of omalizumab | To evaluate the safety and tolerability of LOU064. |
| Proportion of participants achieving UAS7 ≤6 under the treatment algorithm compared with historical omalizumab (300 mg every 4 weeks) data. | Weeks 16, 20, and 24 | UAS7 is calculated as the sum of the HSS7 and ISS7 and ranges from 0 to 42. Lower scores indicate lower disease activity / better disease control, and a score of ≤6 indicates well-controlled disease. HSS7 and ISS7 are each derived from daily diary entries over the 7 days preceding the visit. |
| Proportion of participants achieving UAS7 =0 under the treatment algorithm compared with historical omalizumab (300 mg every 4 weeks) data. | Weeks 16, 20, and 24 | UAS7 is calculated as the sum of the HSS7 and ISS7 and ranges from 0 to 42, with 0 indicating no urticaria activity over the 7-day assessment period and higher scores indicating worse disease activity. |
Contacts
CONTACTNovartis Pharmaceuticals
Outcome results
None listed