Long-term Remibrutinib for Chronic Hives

Not currently recruiting at 304 trial locations

Overseen By Mark Scarupa

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must not be taking: Anti-platelets, Anticoagulants

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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to gather long-term data on the safety and effectiveness of remibrutinib for treating chronic spontaneous urticaria (CSU), a type of chronic hives that appear without an obvious cause. Participants will initially receive either the actual treatment or a placebo (a harmless pill with no effect), followed by further treatment or observation cycles. The trial suits those who have completed previous related studies on remibrutinib and do not have significant health issues like bleeding disorders or liver disease. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you require anti-platelet or anticoagulant medications.

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

Research has shown that remibrutinib, also known as LOU064, is generally safe based on previous studies. Many patients tolerated the treatment well, though some experienced side effects, which were usually mild. Common side effects included headaches and mild stomach issues, such as nausea.

Remibrutinib underwent testing for up to 52 weeks in people with chronic spontaneous urticaria (CSU), and the safety results remained consistent over time. This consistency suggests that remibrutinib is generally safe for long-term use in many people with CSU.

In summary, research indicates that most people tolerate remibrutinib well, and serious side effects are rare. However, since everyone can react differently to medications, discussing any concerns with the trial team is important. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for chronic hives?

Researchers are excited about Remibrutinib (LOU064) for chronic hives because it offers a novel approach compared to current treatments. Unlike standard options like antihistamines and corticosteroids, which primarily focus on symptom relief, Remibrutinib works by targeting the Bruton’s tyrosine kinase (BTK) enzyme. This novel mechanism of action could potentially provide more effective and longer-lasting relief from chronic hives. Additionally, the oral administration of Remibrutinib may offer a more convenient treatment option for patients compared to injectable therapies.

What evidence suggests that remibrutinib might be an effective treatment for chronic hives?

Research has shown that remibrutinib, which participants in this trial may receive, holds promise for treating chronic hives. In earlier studies, patients who took remibrutinib experienced significantly less itching and fewer hives by the 12th week. A detailed review also found that remibrutinib quickly relieves symptoms and is safe for individuals with severe cases of chronic hives. These findings suggest that remibrutinib could be a useful option for managing chronic hives. ^{1 3 5 6 7}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults over 18 who have chronic spontaneous urticaria (hives) and completed previous Phase 3 studies with Remibrutinib. Participants must be able to follow the study plan and visit schedule. Those with significant bleeding risks, coagulation disorders, liver disease, or other serious health issues that could affect safety or results are not eligible.

Inclusion Criteria

Written informed consent must be obtained before any assessment is performed.

Willing and able to adhere to the study protocol and visit schedule.

You have finished the previous main studies CLOU064A2301, CLOU064A2302, CLOU064A1301, CLOU064A2304, or CLOU064A2305 as per the rules.

Exclusion Criteria

I need medication to prevent blood clots.

I do not have major health issues that would affect my safety or participation in the study.

I have a high risk of bleeding or a blood clotting disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomized Withdrawal

Participants undergo a 24-week randomized withdrawal period with remibrutinib or placebo

24 weeks

Open-label Treatment

Participants receive open-label treatment with remibrutinib for 24 weeks if they relapse during the withdrawal phase

24 weeks

Long-term Open-label Treatment Cycles

Participants enter 24-week cycles of open-label treatment or observation, with up to 5 cycles

120 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LOU064
• Placebo

Trial Overview The trial is testing the long-term effects of Remibrutinib on hives. It's an extension study for those who finished earlier trials with this drug. Some will receive Remibrutinib openly while others will get it without knowing if it's the actual drug or a placebo.

How Is the Trial Designed?

Group I: Arm 3: LOU064 (Open Label) Experimental Treatment 1 Intervention

LOU064 (open-label) taken orally for 24 weeks per treatment cycle (Arm 3)

Group II: Arm 1: LOU064 (blinded) Experimental Treatment 2 Interventions

LOU064 (blinded) taken orally for 24 weeks, followed by cycles of either LOU064 (open-label) taken orally for a maximum of 5 cycles of 24 weeks each OR treatment-free observation cycles. Randomized in a 1:1 ratio (arm 1:arm 2)

Group III: Arm 2: LOU064 Placebo (blinded) Placebo Group 2 Interventions

LOU064 placebo (blinded) taken orally for 24 weeks, followed by cycles of either LOU064 (open-label) taken orally for a maximum of 5 cycles of 24 weeks each OR treatment-free observation cycles. Randomized in a 1:1 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]

Tofacitinib, a JAK1/3 inhibitor, showed significant improvement in patients with refractory chronic urticaria (CU) and urticarial vasculitis (UV), even after they had not responded to other treatments.

The use of tofacitinib allowed for the tapering and discontinuation of other medications like cyclosporine and antihistamines, suggesting it may be an effective new treatment option for difficult-to-treat cases of CU and UV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of oral tofacitinib in refractory chronic spontaneous urticaria and urticarial vasculitis. Mansouri, P., Mozafari, N., Chalangari, R., et al.[2023]

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]

In a study of 878 French patients with chronic urticaria, omalizumab (OMA) showed a longer drug survival rate compared to previous studies, with 50% of patients still on treatment 2.4 years after starting.

The main reason for discontinuing OMA was achieving well-controlled disease in 50% of patients, but many were able to restart treatment, indicating its effectiveness in managing chronic urticaria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omalizumab Drug Survival in Chronic Urticaria: A Retrospective Multicentric French Study. Litovsky, J., Hacard, F., Tétart, F., et al.[2023]

In a study of 23 patients with chronic urticaria who were unresponsive to standard treatments, omalizumab resulted in complete or significant remission in 83% of cases, with nearly half experiencing remission within 72 hours of the first injection.

While 52% of patients reported non-serious side effects, only one patient had to stop treatment due to adverse events, indicating that omalizumab is generally safe and effective for managing chronic urticaria in real-life settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Omalizumab for the treatment of chronic urticaria: Real-life findings]. Hamelin, A., Amsler, E., Mathelier-Fusade, P., et al.[2019]

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]

Citations

1. 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.

2. 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 ...

3. 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 ...

4. 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.

5. 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 ...

6. annallergy.org annallergy.org/article/S1081-1206(23)00712-3/fulltext

ANALYSIS OF SAFETY DATA OF REMIBRUTINIB FROM ... Here, we report the safety profile of remibrutinib from its completed Phase 2 clinical trials, including participants with long-term treatment.

7. 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 ...