Long-term Remibrutinib for Chronic Hives

Recruiting at 252 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

695 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests remibrutinib, a medication for adults with chronic hives not helped by standard treatments. It aims to see if remibrutinib can reduce symptoms by blocking signals that cause hives. Remibrutinib is a highly selective, oral medication that has shown promising efficacy and safety in treating chronic spontaneous urticaria.

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.

What data supports the effectiveness of the drug Remibrutinib for chronic hives?

Research shows that Remibrutinib, a drug that targets specific proteins in the body, has been effective in controlling symptoms of chronic hives in patients who did not respond to standard antihistamine treatments. It has demonstrated a favorable safety profile and sustained efficacy over a 52-week period. ^{1 2 3 4 5}

Is Remibrutinib safe for long-term use in humans?

Remibrutinib, also known as LOU064, has shown a favorable safety profile in studies for chronic spontaneous urticaria, with research indicating it is generally safe for long-term use in humans. ^{1 2 3 6 7}

How is the drug Remibrutinib different from other treatments for chronic hives?

Remibrutinib is unique because it is an oral medication that specifically targets Bruton tyrosine kinase, offering fast disease control for chronic hives in patients who do not respond to standard antihistamines. ^{1 2 3 7 8}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Remibrutinib demonstrates favorable safety profile and sustained efficacy in chronic spontaneous urticaria over 52 weeks. [2023]

2. England pubmed.ncbi.nlm.nih.gov

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

3. United States pubmed.ncbi.nlm.nih.gov

Remibrutinib, a novel BTK inhibitor, demonstrates promising efficacy and safety in chronic spontaneous urticaria. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Combination therapy with omalizumab and an immune-suppressive agent for resistant chronic spontaneous rrticaria - A real-life experience. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Omalizumab in patients with chronic spontaneous urticaria: a systematic review and GRADE assessment. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Efficacy of oral tofacitinib in refractory chronic spontaneous urticaria and urticarial vasculitis. [2023]

7. France pubmed.ncbi.nlm.nih.gov

[Omalizumab for the treatment of chronic urticaria: Real-life findings]. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Omalizumab Drug Survival in Chronic Urticaria: A Retrospective Multicentric French Study. [2023]