Study of Remibrutinib (LOU064) Efficacy and Safety and Exploration of Its Mechanism of Action in Participants With Chronic Urticaria

NCT06865651 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: CLOU064M121012024-516355-41
• Study Type: interventional
• Target: 44
• Locations: 5 countries
• Sites: 17

Brief Summary

The purpose of this study is to explore the effect and Mechanism of Action (MoA) of remibrutinib (LOU064) vs. placebo on clinical outcomes in participants with Chronic Urticaria (CU), including both Chronic Spontaneous Urticaria (CSU) and Chronic Inducible Urticaria (CINDU).

Conditions

Chronic Urticaria (CU): Chronic Inducible Urticaria (CINDU) and Chronic Spontaneous Urticaria (CSU)

Keywords

Remibrutinib; LOU064; Chronic urticaria; CINDU; CSU; Symptomatic dermographism; Cold urticaria; Cholinergic urticaria; Heat urticaria; Solar urticaria; Delayed pressure urticaria; Aquagenic urticaria; Contact urticaria

Outcome Measures

Primary Outcomes (2)

• Absolute change from baseline in the weekly most bothersome symptom Numeric Rating Scale (NRS) score on the Urticaria Symptom Daily Diary (USDD)

  To investigate the efficacy of remibrutinib versus placebo for the most bothersome symptom in CINDU patients. The USDD was developed to assess daily exposure and avoidance of triggers, severity of urticaria symptoms (including NRS for pain itch and burning). On the first day of completion, the participants will be asked which symptom (itch, pain, and burning) is the most bothersome symptom of urticaria.

  Baseline, Week 6

• Absolute change from baseline in Urticaria Control Test 7 (UCT7) weekly scores

  To investigate the impact of remibrutinib versus placebo on urticaria symptom control. The UCT is a 4-item PRO measure developed to assess disease control in patients with CU specifically CINDU and CSU. It has a 7-day recall period and participants respond with how much they were bothered by their urticaria symptoms, what is the impact on QoL, how often the treatment did not control their urticaria and their overall perception of disease control. Each question can be scored on a scale from 0 to 4 and the overall score ranges from 0 (no control) to 16 (maximum control). The cut-off value for disease control was established at 12. Participants with a score above 12 are considered controlled. A minimally important difference of 3 points was validated as reflective of a clinically relevant change of control.

  Baseline, Week 6

Secondary Outcomes (4)

• Absolute change from baseline in Urticaria Control test 7 (UCT7) weekly scores

  Baseline, Week 2 and Week 12

• Dermatology Life Quality Index (DLQI) response defined as DLQI= 0-1

  Week 2, Week 6 and Week 12

• Absolute change from baseline in USDD weekly component scores; this includes the change in itch, pain and burning numeric rating scale (NRS) from baseline.

  Baseline, Week 2, Week 6 and Week 12

• Number of Participants With Adverse Events of Special Interest (AESI)

  17 weeks

Study Arms (4)

LOU064-CINDU

EXPERIMENTAL

Diagnosis of Chronic Inducible Urticaria (CINDU), symptoms of symptomatic dermographism urticaria, cold urticaria, cholinergic urticaria, heat urticaria, solar urticaria, urticaria as diagnosed by pressure, evidence of urticaria after exposure to water, evidence of urticaria following contact to identified material causing urticaria symptoms.

Drug: Remibrutinib

LOU064-CSU

EXPERIMENTAL

Diagnosis of Chronic Spontaneous Urticaria (CSU) not adequately controlled

Drug: Remibrutinib

Placebo-CINDU

PLACEBO COMPARATOR

Diagnosis of Chronic Inducible Urticaria (CINDU), symptoms of symptomatic dermographism urticaria, cold urticaria, cholinergic urticaria, heat urticaria, solar urticaria, urticaria as diagnosed by pressure, evidence of urticaria after exposure to water, evidence of urticaria following contact to identified material causing urticaria symptoms.

Drug: Placebo

Placebo-CSU

PLACEBO COMPARATOR

Diagnosis of Chronic Spontaneous Urticaria (CSU) not adequately controlled

Drug: Placebo

Interventions

Remibrutinib DRUG

tablets

Also known as: LOU064

LOU064-CINDU; LOU064-CSU

Placebo DRUG

tablets

Placebo-CINDU; Placebo-CSU

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent must be obtained prior to participation in the study.
• Male and female participants ≥ 18 years of age at the time of signing of the informed consent forms.
• CINDU patients: Confirmed diagnosis of CINDU with a duration of ≥ 4 months (defined as onset of CINDU with supporting documentation (e.g. medical record, clinical history, photographs) and inadequate control with H1-AH at local label approved doses at the time of randomization. The response to the provocation test for each CINDU subtype is required before randomization (either during screening or prior to randomization on Day 1):
• CINDU patients: Patients should be symptomatic for their most bothersome symptom as assessed with the USDD during baseline with a NRS score of 3 or more
• CSU patients: Diagnosis of CSU (acc. to Zuberbier et al 2022c) not adequately controlled with H1-AH at approved doses alone for at least 4 weeks prior to randomization, as defined by all of the following:
• UAS7 score (range 0-42) ≥ 16 and HSS7 (range 0-21) ≥ 8 during 7 days prior to randomization
• CSU for ≥ 6 months
• Participants must be willing and able to attend the protocol defined test procedure throughout the study.

You may not qualify if:

• Diseases, other than CSU or CINDU, with urticaria or angioedema symptoms including but not limited to:
• urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa),
• food allergies yielding urticaria symptoms when the allergen is not avoided by the dietary habits of the participant
• hereditary or acquired angioedema.
• CINDU patients only: To prevent any confounding effect of CSU symptoms, the CINDU study population will consist of participants with predominant CINDU and should not have a significant share of CSU symptoms (that might make the assessment of CINDU symptoms difficult) as per the investigator's judgement.
• CSU patients only: Patients should have no relevant inducible urticaria trigger
• 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, etc.) or skin diseases associated with only wheals and no itch e.g asymptomatic dermographism
• Known or suspected ongoing, chronic or recurrent infectious disease including but not limited to opportunistic infections (e.g., tuberculosis, atypical mycobacterioses, listeriosis or aspergillosis) and/or known positivity for Human Immunodeficiency Virus (HIV) infection.
• Evidence of an ongoing Hepatitis C infection (defined by the detection at screening of Hepatitis C virus antibodies (anti-HCVAb) and hepatitis C ribonucleic acid (HCV-RNA) in participants who are positive for anti-HCVAb) and/or an ongoing Hepatitis B infection (defined by the detection of Hepatitis B virus surface antigen (HBsAg) and/or hepatitis B virus (HBV)-DNA at screening; participants who are positive for anti-hepatitis B core (HBc) antibodies but who are negative for antibodies against HBsAg and HBV-DNA can be included into the study if they agree to monitoring for HBsAg and HBV-DNA reactivation).
• Major surgery within 8 weeks prior to screening or planned surgery for the duration of the study.
• Evidence of clinically significant cardiovascular (such as but not limited to myocardial infarction, unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, arrhythmia and uncontrolled hypertension within 12 months prior to Screening), 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.
• Uncontrolled disease states, such as asthma, or inflammatory bowel disease, or any other disease where flares are commonly treated with oral or parenteral corticosteroids.
• History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 5 years (except for basal cell carcinoma or actinic keratosis that have been treated with no evidence of recurrence in the past 3 months, carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed).
• History or presence of impaired renal function as indicated by clinically significantly abnormal creatinine or BUN values, or abnormal urinary constituents (e.g. proteinuria, hematuria)
• Evidence of urinary obstruction, or difficulty in voiding at screening

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (17)

Ziaderm Research LLC

North Miami Beach, Florida, 33162, United States

RECRUITING

Endeavor Health

Glenview, Illinois, 60077, United States

RECRUITING

Novartis Investigative Site

Grenoble, 38043, France

RECRUITING

Novartis Investigative Site

Montpellier, 34295, France

RECRUITING

Novartis Investigative Site

Paris, 75970, France

RECRUITING

Novartis Investigative Site

Pierre-Bénite, 69495, France

RECRUITING

Novartis Investigative Site

Dresden, Saxony, 01307, Germany

RECRUITING

Novartis Investigative Site

Berlin, 13353, Germany

RECRUITING

Novartis Investigative Site

Mainz, 55131, Germany

WITHDRAWN

Novartis Investigative Site

Tübingen, 72076, Germany

RECRUITING

Novartis Investigative Site

Poznan, 61-731, Poland

RECRUITING

Novartis Investigative Site

Rzeszów, 35 055, Poland

RECRUITING

Novartis Investigative Site

Warsaw, 02-962, Poland

RECRUITING

Novartis Investigative Site

Barcelona, Catalonia, 08003, Spain

RECRUITING

Novartis Investigative Site

Pamplona, Navarre, 31008, Spain

RECRUITING

Novartis Investigative Site

Alicante, 03010, Spain

RECRUITING

Novartis Investigative Site

Madrid, 28006, Spain

RECRUITING

MeSH Terms

Conditions

Chronic Urticaria; Chronic Inducible Urticaria; Familial dermographism; Cold Urticaria; Urticaria, Solar

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; Photosensitivity Disorders

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2025
• First Posted: March 10, 2025
• Study Start: May 22, 2025
• Primary Completion (Estimated): August 23, 2027
• Study Completion (Estimated): September 28, 2027
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

PL (3); US (2); ES (4); FR (4); DE (4)