What is the mechanism of action of this treatment?

The most common treatments for Chronic Rhinosinusitis (CRS) target key cytokines involved in the inflammatory response. Tezepelumab, for example, inhibits thymic stromal lymphopoietin (TSLP), reducing inflammation and improving symptoms. Other treatments, such as IL-5 inhibitors (mepolizumab, benralizumab) and IL-4/IL-13 blockers (dupilumab), also reduce type 2 inflammation. These therapies are crucial for CRS patients as they address the underlying inflammation, leading to better symptom control and enhanced quality of life.

What side effects are associated with this type of intervention?

Common treatments for Chronic Rhinosinusitis, particularly those involving monoclonal antibodies like Tezepelumab, often have side effects such as injection site reactions, headache, and nasopharyngitis. More serious but less frequent side effects can include hypersensitivity reactions, increased risk of infections, and potential exacerbation of pre-existing conditions.

What prior FDA approvals exist?

Prior FDA approvals for the treatment of Chronic Rhinosinusitis with Nasal Polyposis include biologics such as Dupilumab and Omalizumab. Dupilumab is a monoclonal antibody that inhibits IL-4 and IL-13 signaling, reducing inflammation. Omalizumab targets IgE, which plays a role in allergic responses. Both drugs are used to manage severe cases of chronic rhinosinusitis with nasal polyposis by modulating the immune response, similar to the mechanism of action of Tezepelumab, which inhibits TSLP to reduce inflammation.

What other types of research exist?

Promising alternatives to Tezepelumab for Chronic Rhinosinusitis with Nasal Polyposis include Dupilumab and Omalizumab. Dupilumab is a monoclonal antibody that inhibits IL-4 and IL-13 signaling, reducing inflammation. Omalizumab targets IgE, which plays a role in allergic responses. Both have shown efficacy in reducing nasal polyp size and improving symptoms in clinical trials.

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Monoclonal Antibodies

Tezepelumab for Chronic Rhinosinusitis with Nasal Polyps (WAYPOINT Trial)

Phase 3

Waitlist Available

Led By Joseph K Han, MD

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Documented treatment of nasal polyposis exacerbation with SCS for at least 3 consecutive days or one IM depo-injectable dose (or contraindications/intolerance to) within the past 12 months prior to Visit 1 but not within the last 3 months prior to Visit 1 and/or any history of NP surgery (or contraindications/intolerance to)

Severity consistent with need for surgery as defined by total NPS ≥ 5 (≥ 2 for each nostril) at screening, as determined by the central reader

Must not have

Regular use of decongestants (topical or systematic) at enrolment is not allowed unless used for endoscopic procedure

Use of immunosuppressive medication (including but not limited to: methotrexate, troleandomycin, cyclosporine, azathioprine, mycophenolate, tacrolimus, gold, penicillamine, sulfasalazine, hydroxychloroquine, systemic corticosteroids or any experimental anti-inflammatory therapy) within 3 months prior to Visit 1 and during the study period. Systemic corticosteroid use is defined as treatment with a burst of systemic corticosteroids for at least 3 consecutive days or a single IM depo-injectable dose of corticosteroids (considered equivalent to a 3-day burst of systemic corticosteroids)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up over 52 weeks

Awards & highlights

Pivotal Trial

Summary

This trial is testing an injectable medication called tezepelumab in adults with severe sinus inflammation and nasal polyps. The medication aims to reduce swelling and polyp growth by calming the immune system. Tezepelumab has been previously studied and shown to improve outcomes in patients with severe, uncontrolled asthma.

Who is the study for?

This trial is for people with severe chronic rhinosinusitis and nasal polyps, who've had symptoms like runny nose or loss of smell for over 8 weeks. They should have a history of sinus issues needing steroids or surgery but haven't used certain meds in the last 3 months. Those recently vaccinated for COVID-19 or with other serious lung conditions can't join.

What is being tested?

The study tests Tezepelumab's effectiveness and safety against a placebo in participants with severe sinus issues due to nasal polyps. It's randomized, meaning participants are put into the Tezepelumab or placebo group by chance, and double-blind so neither doctors nor patients know who gets what.

What are the potential side effects?

While specific side effects aren't listed here, common ones from similar treatments include injection site reactions, headache, fatigue, and potential worsening of existing allergies or asthma. Participants will be monitored closely for any adverse reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I've been treated for nasal polyps with steroids or had surgery for it in the last year, but not in the last 3 months.

Select...

My nose problem is severe enough to need surgery, based on a specific test score.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I do not regularly use decongestants, except for endoscopic procedures.

Select...

I haven't taken any immunosuppressive drugs in the last 3 months.

Select...

I have no major health issues affecting my lungs except for asthma.

Select...

I have not had sinus surgery in the last 6 months or any that altered the side wall of my nose.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to week 52

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to week 52

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to week 52 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Nasal Polyp-Quality of Life Compared with Placebo

Nasal Polyposis Surgery and/or Receiving Systemic Corticosteroids for Nasal Polyposis

Nasal Polyposis Symptom Diary Total Symptom Score

+1 more

Other study objectives

Asthma Control in Participants with Comorbid Asthma and Aspirin Exacerbated Respiratory Disease (AERD)/Nonsteroidal Anti-Inflammatory Drug Exacerbated Respiratory Disease (NSAID-ERD)

Immunogenicity anti-drug antibodies

Loss of Smell

+7 more

Side effects data

From 2020 Phase 3 trial • 1061 Patients • NCT03347279

21%

Nasopharyngitis

11%

Upper respiratory tract infection

Headache

Bronchitis bacterial

Bronchitis

Urinary tract infection

Sinusitis

Back pain

Arthralgia

Influenza like illness

Hypertension

Gastroenteritis

Viral upper respiratory tract infection

Pharyngitis

Rhinitis

Asthma

Rhinitis allergic

100%

80%

60%

40%

20%

Study treatment Arm

Placebo

Tezepelumab 210mg Q4W

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: TezepelumabExperimental Treatment1 Intervention

Tezepelumab subcutaneous injection, in an accessorized pre-filled syringe.

Group II: PlaceboPlacebo Group1 Intervention

Placebo subcutaneous injection, in an accessorized pre-filled syringe.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Experimental: Tezepelumab

2019

Completed Phase 3

~1520

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Chronic Rhinosinusitis (CRS) target key cytokines involved in the inflammatory response. Tezepelumab, for example, inhibits thymic stromal lymphopoietin (TSLP), reducing inflammation and improving symptoms. Other treatments, such as IL-5 inhibitors (mepolizumab, benralizumab) and IL-4/IL-13 blockers (dupilumab), also reduce type 2 inflammation. These therapies are crucial for CRS patients as they address the underlying inflammation, leading to better symptom control and enhanced quality of life.

Pathways analysis of molecular markers in chronic sinusitis with polyps.