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

NCT05677451 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: CLOU064F123012022-502159-78-00
• Study Type: interventional
• Target: 100
• Locations: 17 countries
• Sites: 50

Brief Summary

The purpose of this trial is:

1. 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. 2.to collect long-term efficacy, safety and tolerability data on remibrutinib in adolescents after having completed 24 weeks of treatment
3. 3.to collect safety data in this population for up to three years after the last dose of study treatment

Conditions

Chronic Spontaneous Urticaria

Keywords

BTK inhibitor; Chronic spontaneous urticaria; Urticaria activity score; Hives severity score; Itch severity score

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  Baseline, Week 12

Secondary Outcomes (11)

• Cmax of remibrutinib

  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

  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

  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

  Baseline - Week 12

• Absolute change from baseline in HSS7

  Baseline - Week 12

Study Arms (2)

Arm 1: LOU064 (blinded)

EXPERIMENTAL

LOU064 (blinded) taken orally b.i.d. for 24 weeks, followed by LOU064 (open-label) taken orally b.i.d. for up to 6 cycles of 24 weeks.

Drug: LOU064 (blinded)

Arm 2: LOU064 placebo (blinded)

PLACEBO COMPARATOR

LOU064 placebo (blinded) taken orally b.i.d. for 24 weeks (randomized in a 2:1 ratio arm 1: arm 2)

Drug: placebo

Interventions

LOU064 (blinded) DRUG

LOU064 (blinded) active treatment

Also known as: remibrutinib

Arm 1: LOU064 (blinded)

placebo DRUG

matching active drug

Arm 2: LOU064 placebo (blinded)

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (50)

Kern Research

Bakersfield, California, 93301, United States

Location

Allergy and Asthma Medical Group and Research Center

San Diego, California, 92123, United States

Location

Pediatric Dermatology of Miami at the Pediatric CoE

Miami, Florida, 33156, United States

Location

Treasure Valley Medical Research

Boise, Idaho, 83706, United States

Location

Endeavor Health

Glenview, Illinois, 60077, United States

Location

Allergy and Asthma Specialist P S C

Owensboro, Kentucky, 42301, United States

Location

Toledo Institute of Clinical Research

Toledo, Ohio, 43617, United States

Location

Allergy Asthma and Clinical Research

Oklahoma City, Oklahoma, 73120, United States

Location

Allergy and Clinical Immunology Associates

Pittsburgh, Pennsylvania, 15241, United States

Location

RFSA Dermatology

San Antonio, Texas, 78213, United States

Location

Allergy Associates of Utah

Sandy City, Utah, 84093, United States

Location

Novartis Investigative Site

CABA, Buenos Aires, C1414AIF, Argentina

Location

Novartis Investigative Site

Rosario, Santa Fe Province, 2000, Argentina

Location

Novartis Investigative Site

CABA, C1181ACH, Argentina

Location

Novartis Investigative Site

San Miguel de Tucumán, T4000AXL, Argentina

Location

Novartis Investigative Site

Montreal, Quebec, H4A 3J1, Canada

Location

Novartis Investigative Site

Santiago, Santiago Metropolitan, 8420383, Chile

Location

Novartis Investigative Site

Guangzhou, Guangdong, 510091, China

Location

Novartis Investigative Site

Chengdu, Sichuan, 610041, China

Location

Novartis Investigative Site

Beijing, 100050, China

Location

Novartis Investigative Site

Beijing, 100069, China

Location

Novartis Investigative Site

Frankfurt am Main, Hesse, 60590, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Tübingen, 72076, Germany

Location

Novartis Investigative Site

Hong Kong, Hong Kong, 999077, Hong Kong

Location

Novartis Investigative Site

Hong Kong, 999077, Hong Kong

Location

Novartis Investigative Site

Florence, FI, 50139, Italy

Location

Novartis Investigative Site

Pavia, PV, 27100, Italy

Location

Novartis Investigative Site

Siena, SI, 53100, Italy

Location

Novartis Investigative Site

Kitakyushu, Fukuoka, 8078556, Japan

Location

Novartis Investigative Site

Kamimashi-gun, Kumamoto, 861-3106, Japan

Location

Novartis Investigative Site

Sakai, Osaka, 5938324, Japan

Location

Novartis Investigative Site

Izumo, Shimane, 6938501, Japan

Location

Novartis Investigative Site

Itabashi-ku, Tokyo, 1738610, Japan

Location

Novartis Investigative Site

Kuching, Sarawak, 93586, Malaysia

Location

Novartis Investigative Site

Utrecht, 3584 CX, Netherlands

Location

Novartis Investigative Site

Lodz, 90-436, Poland

Location

Novartis Investigative Site

Pretoria, Gauteng, 0181, South Africa

Location

Novartis Investigative Site

Cape Town, 7925, South Africa

Location

Novartis Investigative Site

Esplugues, Barcelona, 08950, Spain

Location

Novartis Investigative Site

Valencia, 46014, Spain

Location

Novartis Investigative Site

Songkhla, Hat Yai, 90110, Thailand

Location

Novartis Investigative Site

Bangkok, 10330, Thailand

Location

Novartis Investigative Site

Bangkok, 10700, Thailand

Location

Novartis Investigative Site

Istanbul, Fatih, 34093, Turkey (Türkiye)

Location

Novartis Investigative Site

Ankara, Sihhiye-Altindag, 06230, Turkey (Türkiye)

Location

Novartis Investigative Site

Adana, 01330, Turkey (Türkiye)

Location

Novartis Investigative Site

Peterborough, Cambridgeshire, PE3 9GZ, United Kingdom

Location

Novartis Investigative Site

Manchester, M13 9WL, United Kingdom

Location

Novartis Investigative Site

Southampton, SO16 6YD, United Kingdom

Location

MeSH Terms

Conditions

Chronic Urticaria

Interventions

remibrutinib

Condition Hierarchy (Ancestors)

Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2022
• First Posted: January 10, 2023
• Study Start: July 11, 2023
• Primary Completion (Estimated): November 3, 2026
• Study Completion (Estimated): March 30, 2032
• Last Updated: July 20, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share

Locations

CN (4); GB (3); MY (1); CL (1); TU (3); JP (5); HK (2); US (11); NL (1); PL (1); DE (3); TH (3); CA (1); ZA (2); AR (4); ES (2); IT (3)