Tezepelumab for Chronic Urticaria

(INCEPTION Trial)

No longer recruiting at 108 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called tezepelumab to determine if it can help adults with chronic spontaneous urticaria, a condition causing itchy hives without a known cause. The main goal is to see if tezepelumab can reduce the severity of these hives over a week. The trial includes several groups, with some receiving different doses of tezepelumab and others receiving a placebo (a non-active substance). Individuals who have had chronic hives for at least six months and haven't found relief from standard antihistamines might be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that tezepelumab has been studied for its safety in treating asthma. In these studies, participants generally tolerated it well, with most experiencing no serious problems. Any side effects were usually mild and manageable.

Other studies tested tezepelumab in healthy adults, and the results showed it was safe without causing serious health issues. This suggests that tezepelumab is likely safe for people in clinical trials.

Tezepelumab is currently being tested in a mid-stage trial. This phase focuses on assessing how well participants tolerate it and identifying any possible side effects. While there is already substantial safety information, researchers continue to gather more data. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for urticaria?

Tezepelumab is unique because it targets a specific part of the immune system involved in inflammation, called TSLP (thymic stromal lymphopoietin). This is different from most current treatments for chronic spontaneous urticaria, like antihistamines or omalizumab, which focus on blocking histamines or IgE antibodies. By acting on TSLP, tezepelumab may offer a new way to control symptoms for patients who don't respond well to existing therapies. Researchers are excited because this new approach could provide relief for those with difficult-to-treat cases.

What evidence suggests that this trial's treatments could be effective for improving Urticaria Activity Score?

Research has shown that tezepelumab, which participants in this trial may receive, effectively treats severe, uncontrolled asthma. Studies have found that it reduces hospital visits and improves symptoms compared to a placebo. In asthma patients, it significantly lowered the rate of flare-ups. Tezepelumab targets a protein involved in the body's immune response, which may help reduce symptoms in chronic spontaneous urticaria, a condition causing hives and itching. The positive results in asthma suggest it might also benefit those with chronic spontaneous urticaria. ^{4 6 7 8 9}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Tezepelumab

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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-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]

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 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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37015033/

Efficacy of Tezepelumab in Severe, Uncontrolled Asthma Tezepelumab reduced exacerbation-related hospitalization or emergency department visits and improved secondary outcomes compared with placebo ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1704064

Tezepelumab in Adults with Uncontrolled Asthma Treatment with tezepelumab resulted in significantly lower annualized rates of asthma exacerbations than the rate with placebo among patients ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05329194

Study Details | NCT05329194 | Effectiveness and Safety ... This is a multicenter, single-arm, open-label, Post-authorization, Phase 4 study to assess the effectiveness of tezepelumab in the United States (US)

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10419598/

The efficacy and safety of tezepelumab in the treatment of ... Tezepelumab effectively improved FEV1, reduced the disease symptom score, and decreased the risk of exacerbations in uncontrolled asthma patients.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0190962218330500

Tezepelumab, an anti–thymic stromal lymphopoietin ... Efficacy outcomes. At week 12, a numerically greater percentage of tezepelumab plus TCS-treated patients achieved an EASI50 response (64.7%) compared with ...

6. msds.amgen.com msds.amgen.com/tezspire-safety-datasheet

TEZSPIRE™ Tezepelumab has been classified per Amgen's Hazard Classification System as an Occupational Exposure Band 1 compound (1,000 µg/m3 - 5,000 µg/m3). local exhaust ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6766783/

Pharmacokinetics, Safety, and Tolerability of Tezepelumab ... Data from two double‐blind, placebo‐controlled clinical studies have shown tezepelumab to be a promising new treatment for asthma. In a proof‐of‐concept study, ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00757042

Safety Study of Tezepelumab (AMG 157) in Healthy Adults ... The purpose of the study is to evaluate the safety, tolerability, immunogenicity and pharmacokinetics of tezepelumab.

9. abmole.com abmole.com/literature/tezepelumab-msds.html?srsltid=AfmBOoqEMJ5RN-2_riRJRvHpxa1emIK8m0wxxaz3iJKPJVqKAZhsYMrY

Material Safety Data Sheet of Tezepelumab In case of Skin contact: Rinse skin thoroughly with large amounts of water. Remove contaminated clothing and shoes and call a physician. In case of Eye contact: ...