RECRUITING

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

Conditions

Chronic Urticaria (CU): Chronic Inducible Urticaria (CINDU) and Chronic Spontaneous Urticaria (CSU)Remibrutinib LOU064 Chronic urticaria CINDU CSU Symptomatic dermographism Cold urticaria Cholinergic urticaria Heat urticaria Solar urticaria Delayed pressure urticaria Aquagenic urticaria Contact urticaria

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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).

Official Title

A 12-week Randomized, Participant and Investigator-blinded, Placebo-controlled, Exploratory Study in Adult Participants With Chronic Urticaria to Assess the Efficacy and Safety and Explore the Mechanism of Action of Remibrutinib (LOU064)

Quick Facts

Study Start:2025-05-22

Study Completion:2027-07-27

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06865651

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 100 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Signed informed consent must be obtained prior to participation in the study. 2. Male and female participants ≥ 18 years of age at the time of signing of the informed consent forms. 3. 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): 4. 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 5. 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 6. Participants must be willing and able to attend the protocol defined test procedure throughout the study.	1. Participants who have a familial/hereditary form (e.g. familial cold autoinflammatory syndrome, familial cold urticaria) of the target CINDU that is being considered for the participant's inclusion in this study. 2. 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. 3. 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. 4. CSU patients only: Patients should have no relevant inducible urticaria trigger 5. 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 6. 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. 7. 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). 8. Major surgery within 8 weeks prior to screening or planned surgery for the duration of the study. 9. 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. 10. Uncontrolled disease states, such as asthma, or inflammatory bowel disease, or any other disease where flares are commonly treated with oral or parenteral corticosteroids. 11. 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). 12. 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 * Evidence of congenital renal abnormalities with known effect on renal function * Calculated eGFR \< 60 mL/min 13. Hematology parameters at screening: * Hemoglobin: \< 10 g/dL * Platelets: \< 100,000/mm3 * Leucocytes: \< 3,000/mm3 * Neutrophils:\< 1,500/mm3 14. 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 15. Use of other investigational drugs s within 5 half-lives or within 30 days (for small molecules) prior to Screening or until the expected pharmacodynamic (PD) effect has returned to baseline (for biologics), whichever is longer; or longer if required by local regulations 16. Contraindications to or hypersensitivity to remibrutinib (or its excipients or to drugs of similar chemical classes) or other substances provided to the subjects as rescue medication to control symptoms, such as antihistamines. 17. Participants taking prohibited therapies as listed in Section 6.6.2. In particular patients with pretreatment with remibrutinib or another BTK-inhibitor within 4 months prior to randomization. 18. History of live or live attenuated vaccine within 6 weeks prior to randomization or requirement to receive these vaccinations at any time during the study drug treatment. 19. Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel up to 75 mg/d which are allowed. The use of dual anti-platelet therapy (e.g., acetylsalicylic acid + clopidogrel) is prohibited. 20. Requirement for anticoagulant medication (for example, warfarin or Novel Oral Anti-Coagulants (NOAC)). 21. History of gastrointestinal bleeding, e.g., in association with use of nonsteroidal anti-inflammatory drugs (NSAID), that was clinically relevant (e.g., where intervention was indicated or requiring hospitalization or blood transfusion) 22. Significant bleeding risk or coagulation disorders. 23. Known history or evidence of ongoing alcohol or drug abuse within the last 6 months before randomization as per source records. 24. Pregnant or nursing (breast feeding) women. 25. Women of child-bearing potential, defined as fertile, following menarche and until becoming post-menopausal unless they are permanent sterile or they are using highly effective methods of contraception during dosing for 7 days after stopping study treatment. Highly effective contraception methods include: * Total abstinence (when this is in line with the preferred and usual lifestyle of the participant). Note that periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception * Bilateral oophorectomy with or without hysterectomy, total hysterectomy or bilateral salpingectomy at least six weeks prior to the first dose of study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered to be not of child-bearing potential. * Bilateral tubal occlusion, Bilateral tubal ligation (at least six weeks prior to the first dose of study treatment) * Male partner sterilization (vasectomy) of male partner(s) of the female participant at least six months prior to screening). The vasectomized male partner should be sole partner for that participant and received medical assessment of the surgical success. * Use of oral (estrogen and progesterone), injected, or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate \< 1%), for example hormone vaginal ring or transdermal hormone contraception.

Inclusion Criteria

Exclusion Criteria

1. Signed informed consent must be obtained prior to participation in the study.
2. Male and female participants ≥ 18 years of age at the time of signing of the informed consent forms.
3. 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):
4. 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
5. 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
6. Participants must be willing and able to attend the protocol defined test procedure throughout the study.

1. Participants who have a familial/hereditary form (e.g. familial cold autoinflammatory syndrome, familial cold urticaria) of the target CINDU that is being considered for the participant's inclusion in this study.
2. 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.
3. 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.
4. CSU patients only: Patients should have no relevant inducible urticaria trigger
5. 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
6. 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.
7. 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).
8. Major surgery within 8 weeks prior to screening or planned surgery for the duration of the study.
9. 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.
10. Uncontrolled disease states, such as asthma, or inflammatory bowel disease, or any other disease where flares are commonly treated with oral or parenteral corticosteroids.
11. 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).
12. 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
* Evidence of congenital renal abnormalities with known effect on renal function
* Calculated eGFR \< 60 mL/min
13. Hematology parameters at screening:
* Hemoglobin: \< 10 g/dL
* Platelets: \< 100,000/mm3
* Leucocytes: \< 3,000/mm3
* Neutrophils:\< 1,500/mm3
14. 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
15. Use of other investigational drugs s within 5 half-lives or within 30 days (for small molecules) prior to Screening or until the expected pharmacodynamic (PD) effect has returned to baseline (for biologics), whichever is longer; or longer if required by local regulations
16. Contraindications to or hypersensitivity to remibrutinib (or its excipients or to drugs of similar chemical classes) or other substances provided to the subjects as rescue medication to control symptoms, such as antihistamines.
17. Participants taking prohibited therapies as listed in Section 6.6.2. In particular patients with pretreatment with remibrutinib or another BTK-inhibitor within 4 months prior to randomization.
18. History of live or live attenuated vaccine within 6 weeks prior to randomization or requirement to receive these vaccinations at any time during the study drug treatment.
19. Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel up to 75 mg/d which are allowed. The use of dual anti-platelet therapy (e.g., acetylsalicylic acid + clopidogrel) is prohibited.
20. Requirement for anticoagulant medication (for example, warfarin or Novel Oral Anti-Coagulants (NOAC)).
21. History of gastrointestinal bleeding, e.g., in association with use of nonsteroidal anti-inflammatory drugs (NSAID), that was clinically relevant (e.g., where intervention was indicated or requiring hospitalization or blood transfusion)
22. Significant bleeding risk or coagulation disorders.
23. Known history or evidence of ongoing alcohol or drug abuse within the last 6 months before randomization as per source records.
24. Pregnant or nursing (breast feeding) women.
25. Women of child-bearing potential, defined as fertile, following menarche and until becoming post-menopausal unless they are permanent sterile or they are using highly effective methods of contraception during dosing for 7 days after stopping study treatment. Highly effective contraception methods include:
* Total abstinence (when this is in line with the preferred and usual lifestyle of the participant). Note that periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
* Bilateral oophorectomy with or without hysterectomy, total hysterectomy or bilateral salpingectomy at least six weeks prior to the first dose of study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered to be not of child-bearing potential.
* Bilateral tubal occlusion, Bilateral tubal ligation (at least six weeks prior to the first dose of study treatment)
* Male partner sterilization (vasectomy) of male partner(s) of the female participant at least six months prior to screening). The vasectomized male partner should be sole partner for that participant and received medical assessment of the surgical success.
* Use of oral (estrogen and progesterone), injected, or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate \< 1%), for example hormone vaginal ring or transdermal hormone contraception.

Contacts and Locations

Study Contact

Novartis Pharmaceuticals

CONTACT

1-888-669-6682

novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111

Study Locations (Sites)

Ziaderm Research LLC

North Miami Beach, Florida, 33162

United States

Endeavor Health

Glenview, Illinois, 60077

United States

Collaborators and Investigators

Sponsor: Novartis Pharmaceuticals

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-05-22

Study Completion Date2027-07-27

Study Record Updates

Study Start Date2025-05-22

Study Completion Date2027-07-27

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

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