LOU064 for Chronic Urticaria

Recruiting at 85 trial locations

Overseen By Novartis Pharmaceuticals

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: H1-antihistamines

Must not be taking: BTK inhibitors

Disqualifiers: Bleeding risk, Hepatic disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 14

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called remibrutinib for teens with chronic spontaneous urticaria, a condition causing constant itching and hives. The main goal is to assess the effectiveness and safety of remibrutinib compared to a placebo (a harmless pill with no active drug) over 24 weeks. The trial will also monitor long-term safety for up to three years. Teens who have had chronic urticaria for at least six months and find no relief from standard allergy medicines might be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially bringing a new treatment to market.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot use certain anti-platelet medications, except for low doses of acetylsalicylic acid or clopidogrel. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that remibrutinib, also known as LOU064, has been well-tolerated in previous studies. In these studies, individuals with conditions like chronic spontaneous urticaria (CSU) experienced quick relief from symptoms without major safety issues. One study found that remibrutinib reduced itching and hives by the 12th week. Another report showed that it remained safe and effective for up to 52 weeks. Overall, remibrutinib has consistently demonstrated a good safety record in treating CSU, making it a promising option for those whose urticaria doesn't improve with other treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chronic urticaria?

Most treatments for chronic urticaria, like antihistamines, focus on easing symptoms by blocking histamine, which often requires ongoing usage and doesn't address the underlying cause. But LOU064 works differently, targeting a specific kinase involved in immune responses, potentially offering a more direct approach to controlling the condition. Researchers are excited about LOU064 because it could provide longer-lasting relief and a new way to manage chronic urticaria by addressing the root of the problem rather than just the symptoms.

What evidence suggests that LOU064 might be an effective treatment for chronic urticaria?

Research shows that remibrutinib, also known as LOU064, greatly improves symptoms of chronic spontaneous urticaria, such as itching and hives, within 12 weeks. Previous studies found that patients felt relief quickly and that the treatment was generally safe. In this trial, participants in one arm will receive LOU064, while those in another arm will receive a placebo. This treatment offers promise for those who haven't found success with regular antihistamines. Taken by mouth, it is easy to use. Overall, remibrutinib has shown positive results in managing this condition. ^{1 2 3 4 6}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

Adolescents aged 12 to under 18 with chronic spontaneous urticaria (hives) not well-controlled by antihistamines can join. They must have had hives for at least six months and show certain scores on itch and hive severity scales. Those with liver disease, other skin conditions causing itching, or a history of severe allergic reactions to similar drugs cannot participate.

Inclusion Criteria

I have chronic hives and itching for over 6 weeks despite taking allergy medication.

You had hives in the last three months before joining the study.

Your skin condition scores are high in the 7 days before starting the study.

Exclusion Criteria

I only take low-dose aspirin or clopidogrel for my heart.

I do not have conditions like urticaria vasculitis or hereditary angioedema.

I have a history of liver disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Core Period

Randomized and double-blind phase where participants receive remibrutinib or placebo for 24 weeks

24 weeks

10 site visits

Open-label Extension (OLE) Period

Participants who completed the core period may enter an open-label extension, receiving remibrutinib or entering an observational period based on CSU symptoms

1 to 3 years

3 to 15 visits depending on CSU symptoms

Long-term Treatment-free Follow-up

Participants who completed at least 4 months in the OLE period enter a treatment-free follow-up

3 years

1 site visit and up to 4 phone call follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• LOU064
• placebo

Trial Overview The trial is testing the effectiveness of LOU064 (remibrutinib), a medication against placebo in adolescents who haven't responded well to antihistamines for their chronic hives. It includes an initial 24-week double-blind phase followed by up to three years where all participants may receive remibrutinib.

How Is the Trial Designed?

Group I: Arm 1: LOU064 (blinded) Experimental Treatment 1 Intervention

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.

Group II: Arm 2: LOU064 placebo (blinded) Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

In a phase 2b extension study involving 230 patients with chronic spontaneous urticaria (CSU), remibrutinib showed a favorable safety profile, with most adverse events being mild to moderate and not directly related to the treatment.

Remibrutinib provided significant and sustained efficacy, with 55.8% of patients achieving complete response (UAS7 = 0) and 68.0% achieving well-controlled disease (UAS7 ≤6) after 52 weeks of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remibrutinib demonstrates favorable safety profile and sustained efficacy in chronic spontaneous urticaria over 52 weeks. Jain, V., Giménez-Arnau, A., Hayama, K., et al.[2023]

In a phase 2b trial involving 311 patients with chronic spontaneous urticaria (CSU), remibrutinib demonstrated significant efficacy in reducing symptoms, with all doses showing improvement compared to placebo by week 4.

Remibrutinib was well-tolerated, with most adverse events being mild or moderate, indicating a favorable safety profile across various doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remibrutinib, a novel BTK inhibitor, demonstrates promising efficacy and safety in chronic spontaneous urticaria. Maurer, M., Berger, W., Giménez-Arnau, A., et al.[2023]

In a study of 159 chronic urticaria patients in Italy, those with chronic spontaneous urticaria (CSU) experienced significant improvements in quality of life after 24 months, with dermatology life quality index scores decreasing from 7.5 to 3.0.

The study highlighted that adherence to recommended treatments, particularly nonsedating H1-antihistamines, increased from 52.9% to 89.6%, suggesting that proper medication can lead to better management of CSU and reduced work productivity impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Socio-economic burden and resource utilisation in Italian patients with chronic urticaria: 2-year data from the AWARE study. Rossi, O., Piccirillo, A., Iemoli, E., et al.[2022]

In a real-life clinical analysis of 51 chronic urticaria patients, omalizumab demonstrated high efficacy, achieving complete remission in 83% of patients with chronic spontaneous urticaria (CSU) and 70% with chronic inducible urticaria (CindU).

Omalizumab was found to be safe, with rapid symptom relief occurring within the first week for 57% of CSU patients, and the treatment's effectiveness was not influenced by baseline IgE levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omalizumab is an effective and rapidly acting therapy in difficult-to-treat chronic urticaria: a retrospective clinical analysis. Metz, M., Ohanyan, T., Church, MK., et al.[2022]

Dupilumab shows promise as a long-term treatment for chronic spontaneous urticaria, with 67% of patients maintaining remission after stopping the therapy for up to 22 months.

This case series, involving six patients who previously did not respond to antihistamines or high-dose omalizumab, suggests that dupilumab may have disease-modifying effects in managing chronic spontaneous urticaria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of patients treated with dupilumab for chronic spontaneous urticaria: A case report. Abadeh, A., Lee, JK.[2022]

Urticaria is a complex condition with various subtypes, including spontaneous and physical urticarias, which require clear classification for effective diagnosis and treatment.

Non-sedating H1-antihistamines are the first-line treatment for urticaria, and current guidelines recommend increasing their dosage up to four times the standard amount for better symptom relief, with alternative therapies reserved for patients who do not respond to this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urticaria: current opinions about etiology, diagnosis and therapy. Zuberbier, T., Maurer, M.[2007]

Omalizumab 300 mg significantly reduced symptoms of chronic idiopathic urticaria (CIU) compared to placebo, with a notable decrease in urticarial activity scores and itch severity scores across multiple studies involving 1117 patients.

The treatment also increased the percentage of angioedema-free days, indicating its efficacy in managing symptoms that are resistant to conventional antihistamine treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omalizumab vs. placebo in the management of chronic idiopathic urticaria: a systematic review. Carrillo, DC., Borges, MS., García, E., et al.[2023]

Recent advances in the classification and management of chronic urticaria emphasize the use of non-sedating H1-antihistamines, which can be administered in standard doses or increased up to four times if necessary, improving patient care.

For patients who do not respond to H1-antihistamines, omalizumab has been identified as a safe and effective treatment option, providing a new avenue for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insights and advances in chronic urticaria: a Canadian perspective. Sussman, G., Hébert, J., Gulliver, W., et al.[2022]

In a study of 109 patients with chronic urticaria (CU) who did not respond to standard doses of nonsedating H1-antihistamines (nsAHs), increasing the dose of nsAHs 4-fold resulted in a higher rate of complete symptom control compared to using a combination of four different nsAHs (40.0% vs. 10.7%).

Both the 4-fold updosing of nsAHs and the combination treatment improved the rate of well-controlled cases of CU without significant adverse effects, but the updosing strategy was confirmed to be more effective for achieving complete control of symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Second-Line Treatments in Chronic Urticaria Refractory to Standard Dose Antihistamines. Kim, MA., Choi, JH., Shin, YS., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41005705/

A Systematic Review and Meta-Analysis Conclusion: Remibrutinib shows rapid symptom improvement with an acceptable safety profile in refractory CSU and appears to be a promising oral ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40043237/

Remibrutinib in Chronic Spontaneous Urticaria Treatment with oral remibrutinib resulted in a significant improvement in a composite measure of itching and hives at week 12.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06865651

NCT06865651 | Study of Remibrutinib (LOU064) Efficacy ... 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 ...

4. novartis.com novartis.com/clinicaltrials/study/nct06865651

Study of Remibrutinib (LOU064) Efficacy and Safety ... 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 ...

5. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2408792

Remibrutinib in Chronic Spontaneous Urticaria Treatment with oral remibrutinib resulted in a significant improvement in a composite measure of itching and hives at week 12.

6. jacionline.org jacionline.org/article/S0091-6749(23)01346-5/fulltext

Remibrutinib demonstrates favorable safety profile and ... Remibrutinib demonstrated a consistent favorable safety profile with fast and sustained efficacy for up to 52 weeks in patients with CSU. Key ...