Remibrutinib for Hives

Recruiting at 122 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

468 Participants Needed

Trial Summary

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.

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

Omalizumab (Xolair), a component of the treatment, has been shown to effectively reduce itching and the number and size of hives in patients with chronic spontaneous urticaria (a type of hives) when added to antihistamine therapy, improving patients' quality of life. ^{1 2 3 4 5}

Is Remibrutinib safe for humans?

Omalizumab, a treatment similar to Remibrutinib, has been generally well tolerated in clinical trials for conditions like chronic hives and asthma. Most side effects were mild or moderate, with headaches and upper respiratory infections being slightly more common. Anaphylaxis (a severe allergic reaction) was rare, occurring in about 0.1% to 0.2% of patients. ^{1 2 3 5 6}

How does the drug Remibrutinib differ from Omalizumab for treating hives?

Remibrutinib is a new treatment option for hives, while Omalizumab is an established drug that works by blocking IgE, a protein involved in allergic reactions. Remibrutinib's unique mechanism or benefits compared to Omalizumab are not detailed in the provided research, but it may offer an alternative for patients who do not respond to existing treatments. ^{1 2 3 5 7}

What is the purpose of this trial?

The purpose of the core phase of the trial is to assess the efficacy, safety and tolerability of remibrutinib (LOU064) 25 milligrams (mg) twice a day (b.i.d.) over placebo for 24 weeks and in comparison to omalizumab 300 mg every 4 weeks (q4w) for 52 weeks in participants with chronic spontaneous urticaria (CSU) inadequately controlled by H1-antihistamines (H1-AH). The purpose of the open-label extension phase is to assess efficacy, safety and tolerability up to two years for patients treated with remibrutinib and patients transitioned from omalizumab to remibrutinib at Week 52. In the extension phase, treatment will be with remibrutinib only (i.e., no background therapy). The extension phase will also fulfill the Novartis commitment to provide post-trial access to participants of the previous core phase.

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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, 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]

References

1. Poland pubmed.ncbi.nlm.nih.gov

Omalizumab for urticaria treatment in clinical practice: a case series. [2022]

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

Safety and tolerability of omalizumab. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Concomitant asthma medication use in patients receiving omalizumab: results from three large insurance claims databases. [2015]

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

Evaluation of IgE Antibodies to Omalizumab (Xolair®) and Their Potential Correlation to Anaphylaxis. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Reduced FcepsilonRI-mediated release of asthma-promoting cytokines and chemokines from human basophils during omalizumab therapy. [2021]

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

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