24 Weeks Double-blind Randomized Placebo-controlled Trial to Evaluate Efficacy, PK, Safety of LOU064 in Adolescents (12 - <18) With CSU and Inadequate Response to H1-antihistamine Followed by Optional 3 Years Open-label Extension and an Optional 3 Years Safety Long-term Treatment-free Follow-up

Phase 3Active Not RecruitingNCT05677451

Novartis Pharmaceuticals100 enrolled

Overview

The purpose of this trial is: 1. to assess the efficacy, pharmacokinetics, and safety of remibrutinib vs. placebo in adolescents from 12 to \< 18 years of age suffering from chronic spontaneous urticaria inadequately controlled by H1-antihistamines 2. to collect long-term efficacy, safety and tolerability data on remibrutinib in adolescents after having completed 24 weeks of treatment 3. to collect safety data in this population for up to three years after the last dose of study treatment

This trial consists of 3 different periods: 1. the "core period", which is randomized and double-blind, during which 2/3 participants will receive remibrutinib and 1/3 will receive placebo for 24 weeks. Total duration: approximately 32 weeks (10 site visits). 2. an optional "open-label extension (OLE) period" proposed to all participants who completed 24 weeks of treatment of the "core period" and all scheduled assessments planned at week 24 visit . Depending on their CSU symptoms (as assessed by the doctor), participants will either receive remibrutinib for 24 weeks, or enter an observational treatment-free period for 1 year. If the CSU symptoms return during the observational period, the participants can switch to the treatment period at any time (decided by the doctor). At the end of the 24-week treatment period, if CSU is controlled, participants will enter the 1-year observational period, otherwise, they can continue with another cycle of 24-week remibrutinib treatment. The number of remibrutinib treatment or observational cycles will be limited to 6 times each. Total duration: from 1 year to approximately 3 years, and number of visits: from 3 to 15 (depending on the CSU symptoms). 3. an optional "long-term treatment-free follow-up period" proposed to all participants who completed at least 4 months treatment in the "OLE period". No treatment will be given. Duration: 3 years with 1 site visit and up to 4 phone call follow-up visits. The primary clinical question of interest is what is the effect of remibrutinib treatment versus placebo on the change from baseline in UAS7, ISS7 and HSS7 scores after 12 weeks of treatment

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Eligibility

Sex: ALLMin age: 12 YearsMax age: 17 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Male and female adolescent participants aged \>= 12 to \< 18 years of age at the time of signing the informed consent * 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-AH 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-AH during this time period according to local treatment guidelines * 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) Key Exclusion criteria: * Previous use of remibrutinib or other BTK inhibitors * Significant bleeding risk or coagulation disorders * History of gastrointestinal bleeding * 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 * History or current hepatic disease * Evidence of clinically significant cardiovascular, 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 * History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes * 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 angioedema, 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 Other protocol-defined inclusion/exclusion criteria may apply.

Locations (50)

Kern Research

Bakersfield, California, United States

Allergy and Asthma Medical Group and Research Center

San Diego, California, United States

Pediatric Dermatology of Miami at the Pediatric CoE

Miami, Florida, United States

Treasure Valley Medical Research

Boise, Idaho, United States

Endeavor Health

Glenview, Illinois, United States

Outcomes

Primary Outcomes

Change from baseline in UAS7

The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42. Complete UAS7 response is UAS7 = 0. Negative change from baseline indicates improvement.

Time frame: Baseline, week 12

Change fron baseline in ISS7

Itch Severity Score (ISS) scale is 0 to 3. Score (ISS7) is derived by adding up average daily scores of 7 days preceding visit. Possible range of weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate). Negative change from baseline indicates improvement.

Time frame: Baseline, Week 12

Change from baseline in HSS7

Hives Severity Score (HSS) scale is 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. Possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None 1 - Mild (1-6 hives/12 hours) 2 - Moderate (7-12 hives/12 hours) 3 - Severe (\>12 hives/12 hours). Negative change from baseline indicates improvement.

Time frame: Baseline, Week 12

Secondary Outcomes

Cmax of remibrutinib

The maximum (peak) observed blood drug concentration after single dose administration

Time frame: At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake

Tmax of remibrutinib

The time to reach maximum (peak) blood drug concentration after single dose administration

Time frame: At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake

AUClast of remibrutinib

The Area Under the Curve (AUC) from pre-dose to the last measurable concentration sampling time

Time frame: At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake

Absolute change from baseline in ISS7

Time frame: Baseline - Week 12

Absolute change from baseline in HSS7

Time frame: Baseline - Week 12

Achievement of UAS7 ≤ 6 (yes/no)

Disease activity control is defined as UAS7 ≤ 6. The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42.

Time frame: Week 12 and over time

Achievement of UAS7 = 0 (yes/no)

Complete absence of hives and itch is defined as UAS7 = 0. The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42.

Time frame: Week 12 and over time

Absolute change from baseline in CDLQI score

The Children Dermatology life Quality Index (CDLQI) score range is 0 to 30, with 0 (meaning no impact of skin disease on quality of life) to 30 (meaning maximum impact on quality of life).

Time frame: Week 12

Number of weeks without angioedema, assessed by the cumulative number of weeks with an AAS7 = 0 response

Angioedema Activity Score (AAS7) is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-105 where higher scores indicate increased angioedema activity.

Time frame: baseline - Week 12

Occurrence of treatment-emergent adverse events (AE) and serious adverse events (SAE) during the core period

To demonstrate the safety and tolerability of remibrutinib by assessing occurrence of treatment emergent adverse events and serious adverse events during the core period of the study.

Time frame: 28 weeks

Occurrence of treatment emergent AEs, and SAEs during the Open Label Extension (OLE) period

To demonstrate the safety and tolerability of remibrutinib by assessing occurrence of treatment emergent adverse events and serious adverse events during the OLE period of the study.

Time frame: 3 years

24 Weeks Double-blind Randomized Placebo-controlled Trial to Evaluate Efficacy, PK, Safety of LOU064 in Adolescents (12 - <18) With CSU and Inadequate Response to H1-antihistamine Followed by Optional 3 Years Open-label Extension and an Optional 3 Years Safety Long-term Treatment-free Follow-up

Overview

Conditions

Interventions

Eligibility

Locations (50)

Outcomes

Primary Outcomes

Secondary Outcomes