Remibrutinib for Hives

Not currently recruiting at 160 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: Biologics, Anti-coagulants

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 11

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness and safety of remibrutinib for individuals with chronic spontaneous urticaria (CSU), commonly known as hives, that are not well-controlled by regular allergy medications (H1-antihistamines). Participants will receive either remibrutinib, a placebo, or omalizumab (an injectable medication) to determine which works best over time. The trial targets those who have experienced itchy hives for at least six months despite using allergy medications. Individuals with persistent hives and itchiness that haven't improved with typical treatments may find this trial suitable. As a Phase 3 trial, it represents the final step before FDA approval, offering a chance to contribute to potentially groundbreaking treatment advancements.

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 mentions that in the extension phase, treatment will be with remibrutinib only, without any background therapy. 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 maintains a strong safety record from past studies. In trials involving individuals with chronic spontaneous urticaria (CSU), remibrutinib was generally well-tolerated. Unwanted effects were uncommon, and the treatment appeared safe even over extended periods, up to a year.

Reports from these studies indicate that most side effects were mild. Participants experienced improvements without serious safety concerns. Remibrutinib targets specific proteins involved in immune responses, reducing the risk of severe side effects.

For those considering joining a trial, these findings suggest that remibrutinib offers a promising option with a reassuring safety profile. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Remibrutinib is unique because it targets Bruton's tyrosine kinase (BTK), a new approach in treating hives compared to standard treatments like antihistamines and omalizumab, which focus on different pathways. Researchers are excited because by directly inhibiting BTK, remibrutinib could effectively reduce inflammation and itching more precisely and potentially more quickly than existing options. This novel mechanism of action paves the way for possibly more efficient management of chronic spontaneous urticaria, offering hope for those not fully benefiting from current therapies.

What evidence suggests that this trial's treatments could be effective for chronic spontaneous urticaria?

Research has shown that remibrutinib, a treatment under study in this trial, holds promise for people with chronic spontaneous urticaria (CSU), a condition causing itchy hives. In earlier studies, this oral medication significantly improved itching and hives within 12 weeks. Patients experienced quick and lasting relief for up to a year. The treatment is generally safe, making remibrutinib a potentially effective option for those whose symptoms aren't controlled by standard antihistamines. ^{5 6 7 8 9}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

Adults over 18 with chronic spontaneous urticaria (CSU) not well-controlled by antihistamines can join. They must have had hives and itching for at least 6 weeks despite treatment, and be able to keep a daily diary of their symptoms without missing more than one entry in the week before starting.

Inclusion Criteria

I have had itch and hives for 6 weeks or more, even while using allergy medication.

Your UAS7 score, ISS7 score and HSS7 score were all at least 16, 6 and 6 respectively during the week leading up to randomization.

You are prepared to fulfill the demands of the UPDD over the course of the research and abide by its regulations.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

1 visit (in-person)

Core Phase Treatment

Participants receive either remibrutinib, omalizumab, or placebo in a double-blind, double-dummy setup for 52 weeks

52 weeks

Regular visits every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks for non-extension participants, 4 weeks for extension participants

2 visits (in-person)

Open-label Extension

Optional phase where participants receive open-label remibrutinib for 52 weeks

52 weeks

Regular visits every 4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Omalizumab
• Placebo to omalizumab
• Placebo to remibrutinib
• Remibrutinib

Trial Overview The trial is testing Remibrutinib's effectiveness compared to a placebo and Omalizumab as an active control. Participants will take Remibrutinib or its placebo twice daily for 24 weeks, or Omalizumab every four weeks for 52 weeks.

How Is the Trial Designed?

Group I: Remibrutinib Experimental Treatment 1 Intervention

Participants will receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 52 weeks.

Group II: Omalizumab Active Control 1 Intervention

participants will receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d. for 52 weeks.

Group III: Placebo to remibrutinib Placebo Group 1 Intervention

Participants will receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants will receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w.

Group IV: Placebo to omalizumab Placebo Group 1 Intervention

Participants will receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants will receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d.

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 study of 11 patients with chronic spontaneous urticaria, 9 achieved complete resolution of symptoms after treatment with omalizumab, with an average time to remission of 9.3 weeks.

Omalizumab was found to be safe, as no side effects were reported during the treatment, indicating its potential as an effective option for patients unresponsive to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omalizumab for urticaria treatment in clinical practice: a case series. Lesiak, A., Bednarski, IA., Maćkowska, A., et al.[2022]

Omalizumab is an effective add-on therapy for patients with chronic spontaneous urticaria, significantly reducing itching and hives severity, and improving quality of life compared to placebo in well-controlled trials lasting 12 to 24 weeks.

The treatment is generally well tolerated, with adverse events similar in frequency and severity to those experienced by placebo recipients, primarily involving mild to moderate headaches and upper respiratory infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omalizumab: a review of its use in patients with chronic spontaneous urticaria. McCormack, PL.[2021]

A study involving 6038 patients showed that nearly all individuals starting treatment with omalizumab had previously used multiple asthma medications, indicating that they were likely experiencing severe asthma symptoms despite existing treatments.

A significant number of new omalizumab users had recent asthma-related emergency room visits (up to 36% in Medicaid) or hospitalizations, highlighting the need for effective management in patients with moderate to severe persistent allergic asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concomitant asthma medication use in patients receiving omalizumab: results from three large insurance claims databases. Lafeuille, MH., Duh, MS., Zhang, J., et al.[2015]

Omalizumab has a favorable safety profile, with a low incidence of anaphylaxis (0.14%) in treated patients, comparable to control patients (0.07%), and no measurable anti-omalizumab antibodies were found in treated individuals.

The drug has been shown to be effective for patients with moderate-to-severe allergic asthma, and clinical data do not indicate an increased risk of serious side effects like malignant neoplasia or thrombocytopenia, even after long-term use of up to 4 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of omalizumab. Corren, J., Casale, TB., Lanier, B., et al.[2023]

Omalizumab, a monoclonal antibody used to treat IgE-mediated diseases, has a low incidence of anaphylaxis, reported in only 0.1% of asthma patients during clinical trials and estimated at 0.2% in post-marketing studies.

A post-marketing study found no correlation between anaphylaxis or skin test reactions and the presence of IgE antibodies to omalizumab, suggesting that the risk of anaphylaxis may not be related to the drug's immunogenicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of IgE Antibodies to Omalizumab (Xolair®) and Their Potential Correlation to Anaphylaxis. Baker, DL., Nakamura, GR., Lowman, HB., et al.[2018]

Omalizumab treatment in 15 asthmatic volunteers for 12 weeks significantly reduced the production of Th2 cytokines (like IL-4 and IL-13) and chemokines (like IL-8) from basophils, which are important in allergic asthma.

The reduction in cytokine release was reversible, returning to baseline levels after stopping omalizumab, indicating that the drug works by suppressing the FcepsilonRI-mediated response in basophils, while histamine release remained unaffected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced FcepsilonRI-mediated release of asthma-promoting cytokines and chemokines from human basophils during omalizumab therapy. Oliver, JM., Tarleton, CA., Gilmartin, L., et al.[2021]

Omalizumab is an effective treatment for moderate to severe asthma in patients over 12 years old who have a positive allergy test and are symptomatic despite using inhaled corticosteroids.

It has a low incidence of side effects, making it a relatively safe option, although it is quite expensive and requires dosage adjustments based on body weight and IgE levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omalizumab: a recombinant humanized monoclonal IgE-blocking antibody. Scheinfeld, N.[2015]

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/37866460/

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.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0091674925010334

Remibrutinib in chronic spontaneous urticaria: 52-Week ... Remibrutinib, an oral, highly selective Bruton's tyrosine kinase inhibitor, demonstrated significant improvements in disease activity over ...

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. 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 ...

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 ...

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

Remibrutinib in Chronic Spontaneous Urticaria Remibrutinib, an oral, highly selective Bruton's tyrosine kinase inhibitor, showed efficacy and favorable safety in phase 2b trials. Data from ...

8. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05048342

A Safety and Efficacy Study of Remibrutinib in ... The purpose of this study was to evaluate the safety, tolerability and efficacy of remibrutinib (LOU064) in adult Japanese patients chronic spontaneous ...

9. 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.