Study to Evaluate Tezepelumab in Adults With Chronic Spontaneous Urticaria

(INCEPTION Trial)

Recruiting at 89 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Amgen

Must be taking: Second generation antihistamines

Must not be taking: Biologics, Systemic corticosteroids

Disqualifiers: Active skin diseases, Severe depression, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 25

Duration: 16 weeks

183 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you have been taking second generation H1-antihistamines (sgAH) for at least 3 consecutive days before the screening and continue using them. However, you must stop using certain other medications like biologic products and systemic corticosteroids at least 30 days before the screening.

What data supports the effectiveness of the drug Tezepelumab?

Research shows that Tezepelumab significantly reduces asthma attacks and improves lung function in people with severe, uncontrolled asthma. It has been well tolerated in studies, showing promise as a treatment option for asthma. ^{1 2 3 4 5}

Is Tezepelumab safe for humans?

Tezepelumab has been studied in several trials for conditions like severe asthma and atopic dermatitis, and it has shown an acceptable safety profile. In these studies, patients did not experience a higher rate of adverse reactions compared to those who received a placebo, and it was well tolerated in both healthy individuals and those with atopic dermatitis. ^{2 3 5 6 7}

How is the drug Tezepelumab different from other asthma treatments?

Tezepelumab is unique because it targets thymic stromal lymphopoietin (TSLP), a molecule involved in the inflammation process, making it effective for patients with severe asthma that is not controlled by other medications. It is administered as a subcutaneous injection by a healthcare provider, offering a new option for those with noneosinophilic inflammation. ^{1 2 3 5 8}

What is the purpose of this trial?

This trial is testing tezepelumab, a medication that helps reduce symptoms of hives. It targets patients with urticaria, aiming to improve their condition by blocking a protein that causes inflammation and allergic reactions. The goal is to see if it can lower their symptoms effectively.

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

Inclusion Criteria

Chronic spontaneous urticaria (CSU) diagnosis for ≥ 6 months at the time of screening.

CSU inadequately controlled by second generation H1-antihistamines (sgAH) at enrollment, as defined by all of the following: The presence of itch and hives for >= 6 consecutive weeks at any time prior to screening visit 2 Failure to respond to an sgAH (up to 4 times the approved dose) Urticaria Activity Score over 7 days (UAS7) (range 0-42) >= 16 and Hives Severity Score over 7 days (HSS7) (range 0-21) >= 8 during the 7 days prior to enrollment Participant with CSU who discontinued, is intolerant to, or was an inadequate responder to anti-IgE therapies despite being treated with omalizumab 300 mg every 4 weeks (Q4W) for 6 months or higher doses of omalizumab > 2 months or another anti-IgE therapy. Note: This criterion is only applicable for anti-IgE-experienced participants.

Subject must have been on a sgAH at approved or increased doses (up to 4x the approved dose) for treatment of CSU for at least 3 consecutive days immediately prior to the day -14 screening visit (screening visit 2) and must have documented current use on the day of screening visit 1

Exclusion Criteria

Prior/concomitant therapy, including but not limited to: Treatment with any biologic products (eg, omalizumab, ligelizumab) within 4 months or 5 half-lives (whichever is longer) prior to screening visit 1 Routine (daily or every other day for 5 or more consecutive days) use of systemic corticosteroids, systemic hydroxychloroquine, methotrexate, cyclosporine A, cyclophosphamide, tacrolimus, azathioprine, and mycophenolate mofetil within 30 days prior to screening visit 1. Major surgery within 8 weeks prior to screening visit 1 or planned inpatient surgery or hospitalization during the study period. Receipt of Ig or blood products within 30 days prior to screening visit 1. Vaccination with a live or attenuated vaccine within 30 days prior to screening visit 1. Receipt of COVID-19 vaccines and inactive/killed vaccinations (eg, inactive influenza) are allowed, provided the vaccinations are not administered within 7 days before or after any study dosing visit. Known hypersensitivity, including severe hypersensitivity reactions and/or history of anaphylactic shock, to any of the products or components to be administered during dosing or to products of similar chemical classes (ie, to murine, chimeric, or human antibodies).

History of a clinically significant infection within 28 days prior to day 1 that, in the opinion of the investigator or medical monitor, might compromise the safety of the participant in the study, interfere with evaluation of the investigational product, or reduce the participants ability to participate in the study.

Evidence of active tuberculosis (TB) (in the opinion of the investigator), either treated or untreated, or a positive purified protein derivative (PPD) or QuantiFERON-TB Gold Plus (QFT-Plus) test for TB during screening.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tezepelumab or placebo for chronic spontaneous urticaria

16 weeks

Visits at Weeks 1, 2, 4, 8, 12, and 16

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

Visits at Weeks 24 and 32

Treatment Details

Interventions

• Tezepelumab

Participant Groups

Group I: Group 7: Tezepelumab Dose 2 Experimental Treatment 1 Intervention

Participants previously treated with anti-IgE therapies will receive tezepelumab.

Group II: Group 6: Tezepelumab Dose 1 Experimental Treatment 1 Intervention

Participants previously treated with anti-IgE therapies will receive tezepelumab.

Group III: Group 4: Tezepelumab Dose 2 Experimental Treatment 1 Intervention

Participants naive to anti-IgE therapies will receive tezepelumab.

Group IV: Group 3: Tezepelumab Dose 1 Experimental Treatment 1 Intervention

Participants naive to anti-IgE therapies will receive tezepelumab.

Group V: Group 1: Omalizumab Active Control 1 Intervention

Participants naive to anti-IgE therapies will receive omalizumab.

Group VI: Group 5: Placebo Placebo Group 1 Intervention

Participants previously treated with anti-IgE therapies will receive a placebo.

Group VII: Group 2: Placebo Placebo Group 1 Intervention

Participants naive to anti-IgE therapies will receive a placebo.

Tezepelumab is already approved in United States, European Union for the following indications:

Approved in United States as Tezspire for:

• Severe asthma

Approved in European Union as Tezspire for:

• Severe asthma

Who Is Running the Clinical Trial?

Amgen

Lead Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Findings from Research

Tezepelumab significantly reduced annualized asthma exacerbation rates (AAER) by 66% to 78% in patients with perennial allergy and by 67% to 71% in those without, based on a study of 550 adults over 52 weeks.

The treatment also improved lung function (measured by prebronchodilator FEV1) and reduced type 2 biomarkers, demonstrating its efficacy in managing severe, uncontrolled asthma regardless of allergy status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma and Perennial Allergy. Corren, J., Ambrose, CS., Sałapa, K., et al.[2021]

Tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin, demonstrated linear pharmacokinetics and a long half-life of 19.9 to 25.7 days, indicating effective dosing intervals for asthma treatment.

The drug was well tolerated in phase I studies with no signs of immunogenicity, suggesting it is safe for use in healthy individuals and those with atopic dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety, and Tolerability of Tezepelumab (AMG 157) in Healthy and Atopic Dermatitis Adult Subjects. Parnes, JR., Sullivan, JT., Chen, L., et al.[2022]

Tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin, is being evaluated for its long-term safety and efficacy in patients with severe, uncontrolled asthma in the DESTINATION study, which includes participants from two previous phase 3 trials.

The study aims to assess not only the long-term tolerability and effect on asthma exacerbations over 104 weeks but also the clinical benefits after treatment cessation, providing insights into its potential as a corticosteroid-sparing therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DESTINATION: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the long-term safety and tolerability of tezepelumab in adults and adolescents with severe, uncontrolled asthma. Menzies-Gow, A., Ponnarambil, S., Downie, J., et al.[2021]

In the phase 3 NAVIGATOR study involving patients aged 12-80 with severe asthma, tezepelumab significantly improved various lung function parameters, including pre-bronchodilator FEV1 and forced vital capacity (FVC), compared to placebo over 52 weeks.

Improvements in lung function were observed as early as 1-2 weeks and were particularly pronounced in patients with a shorter disease duration and specific baseline lung function characteristics, indicating tezepelumab's efficacy in managing severe asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Tezepelumab on Lung Function in Patients With Severe, Uncontrolled Asthma in the Phase 3 NAVIGATOR Study. Menzies-Gow, A., Ambrose, CS., Colice, G., et al.[2023]

In a phase 2 trial involving 436 patients with uncontrolled moderate-to-severe asthma, tezepelumab significantly reduced the annualized rate of asthma exacerbations by 61% to 71% compared to placebo, demonstrating its efficacy in managing asthma symptoms.

Tezepelumab also improved lung function, as indicated by higher forced expiratory volume in 1 second (FEV1) across all dosing groups, with minimal adverse events leading to discontinuation, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tezepelumab in Adults with Uncontrolled Asthma. Corren, J., Parnes, JR., Wang, L., et al.[2022]

Tezepelumab, a monoclonal antibody approved for severe uncontrolled asthma, significantly improved forced expiratory volume (FEV1) by 0.15 L and reduced asthma exacerbation rates by 0.60 per year compared to placebo, based on a meta-analysis of six trials with 2667 patients.

The treatment was found to have an acceptable safety profile, with no higher incidence of adverse drug reactions compared to placebo, indicating it is a safe option for patients with severe asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tezepelumab for Patients with Severe Uncontrolled Asthma: A Systematic Review and Meta-Analysis. Zoumot, Z., Al Busaidi, N., Tashkandi, W., et al.[2022]

In a 52-week study involving 65 Japanese patients with severe uncontrolled asthma, tezepelumab was found to be safe and well-tolerated, with most adverse events being mild to moderate, and only one case leading to treatment discontinuation.

Tezepelumab significantly reduced asthma exacerbation rates (0.11 per patient-year) and improved lung function and asthma control, with a 71.4% responder rate at Week 52, indicating its efficacy in managing severe asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-year safety and tolerability of tezepelumab in Japanese patients with severe uncontrolled asthma: results of the NOZOMI study. Shinkai, M., Ebisawa, M., Fukushima, Y., et al.[2023]

Tezepelumab-ekko (Tezspire) is FDA-approved as an add-on maintenance therapy for individuals aged 12 and older with severe asthma that is not adequately controlled by existing medications.

The administration of Tezspire requires a healthcare provider to give it subcutaneously, highlighting the importance of professional oversight in its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tezspire Approved for Severe Asthma. Aschenbrenner, DS.[2023]

References

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

Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma and Perennial Allergy. [2021]

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

Pharmacokinetics, Safety, and Tolerability of Tezepelumab (AMG 157) in Healthy and Atopic Dermatitis Adult Subjects. [2022]

3. England pubmed.ncbi.nlm.nih.gov

DESTINATION: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the long-term safety and tolerability of tezepelumab in adults and adolescents with severe, uncontrolled asthma. [2021]

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

Effect of Tezepelumab on Lung Function in Patients With Severe, Uncontrolled Asthma in the Phase 3 NAVIGATOR Study. [2023]

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

Tezepelumab in Adults with Uncontrolled Asthma. [2022]

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

Tezepelumab for Patients with Severe Uncontrolled Asthma: A Systematic Review and Meta-Analysis. [2022]

7. England pubmed.ncbi.nlm.nih.gov

One-year safety and tolerability of tezepelumab in Japanese patients with severe uncontrolled asthma: results of the NOZOMI study. [2023]

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

Tezspire Approved for Severe Asthma. [2023]