Clinical trial NCT05281523: Efficacy and Safety of Depemokimab (GSK3511294) in Participants With Chronic Rhinosinusitis With Nasal Polyps (ANCHOR-2)
Official title: A Randomised, Double-blind, Parallel Group Phase III Study to Assess the Efficacy and Safety of 100 mg SC Depemokimab in Patients With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) - ANCHOR-2 (depemokimAb iN CHrOnic Rhinosinusitis)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Nasal Polyps
Keywords: Depemokimab
GSK3511294
Chronic rhinosinusitis
Verbal response scale
Asthma Control Questionnaire
Lund Mackay computed tomography
Nasal polyps score
Nasal endoscopy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2022-03-16
Enrollment: 264
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will receive either depemokimab (GSK3511294) or placebo during the study.
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy and safety of depemokimab (GSK3511294) in participants with Chronic rhinosinusitis with nasal polyps (CRSwNP).


Eligibility criteria: Inclusion Criteria:

Inclusion Criteria:

* Participants with 18 years of age and older inclusive, at the time of signing the informed consent.
* Endoscopic bilateral NP score of at least 5 out of a maximum score of 8 (with a minimum score of 2 in each nasal cavity) assessed by the investigator.
* Participants who have had at least one of the following at Visit 1: Previous nasal surgery for the removal of NP; Have used at least three consecutive days of systemic corticosteroids in the previous 2 years for the treatment of NP; Medically unsuitable or intolerant to systemic corticosteroid.
* Participants (except for those in Japan) must be on daily treatment with intranasal corticosteroids (INCS) (including intranasal liquid steroid wash/douching) for at least 8 weeks prior to screening.
* Participants presenting with severe NP symptoms defined as symptoms of nasal congestion/blockade/obstruction with moderate or severe severity and loss of smell or rhinorrhea (runny nose) based on clinical assessment by the investigator.
* Presence of symptoms of chronic rhinosinusitis as described by at least 2 different symptoms for at least 12 weeks prior to Visit 1, one of which should be either nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior nasal drip), plus facial pain/pressure and/or reduction or loss of smell.
* Male or eligible female participants

Exclusion Criteria:

Exclusion Criteria:

* As a result of medical interview, physical examination, or screening investigation the physician responsible considers the participant unfit for the study.
* Cystic fibrosis.
* Antrochoanal polyps.
* Nasal cavity tumor (malignant or benign)
* Fungal rhinosinusitis
* Severe nasal septal deviation occluding one nostril preventing full assessment of nasal polyps in both nostrils.
* Participants who had a sino-nasal or sinus surgery changing the lateral wall structure of the nose making impossible the evaluation of nasal polyp score.
* Acute sinusitis or upper respiratory tract infection (URTI) at screening or in 2 weeks prior to screening.
* Ongoing rhinitis medicamentosa (rebound or chemical induced rhinitis).
* Participants who have had an asthma exacerbation requiring admission to hospital within 4 weeks of Screening.
* Participants who have undergone any intranasal and/or sinus surgery (for example polypectomy, balloon dilatation or nasal stent insertion) within 6 months prior to Visit 1; nasal biopsy prior to Visit 1 for diagnostic purposes only is excepted.
* Participants where NP surgery is contraindicated in the opinion of the Investigator.
* Participants with other conditions that could lead to elevated eosinophils such as hyper-eosinophilic syndromes including (but not limited to) eosinophilic granulomatosis with polyangiitis (EGPA) (formerly known as Churg-Strauss Syndrome) or Eosinophilic Esophagitis.
* Participants with a known, pre-existing parasitic infestation within 6 months prior to Visit 1.
* A known immunodeficiency (e.g. human immunodeficiency virus (HIV), other than that explained by the use of corticosteroids (CSs) taken as therapy for asthma.
* A current malignancy or previous history of cancer in remission for less than 12 months prior to screening.
* Liver Disease: Alanine aminotransferase (ALT) \>2 times upper limit normal (ULN); Total bilirubin \>1.5 times ULN (isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin less than \[\<\]35 percent \[%\]); Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice.
* Participants who have known, pre-existing, clinically significant cardiac, endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, hematological or any other system abnormalities that are uncontrolled with standard treatment.
* Participants with current diagnosis of vasculitis. Participants with high clinical suspicion of vasculitis at screening will be evaluated and current vasculitis must be excluded prior to enrollment.
* Hypersensitivity: Participants with allergy/intolerance to the excipients of depemokimab (GSK3511294) in a monoclonal antibody, or biologic.
* Participants that, according to the investigator's medical judgment, are likely to have active Coronavirus disease-2019 (COVID-19) infection must be excluded. Participants with known COVID-19 positive contacts within the past 14 days must be excluded for at least 14 days following the exposure during which the participant should remain symptom-free. Reported smell/ taste complications from COVID-19 must be used as exclusion.
* Participants that have been exposed to ionising radiation in excess of 10 millisievert (mSv) above background over the previous 3-year period as a result of occupational exposure or previous participation in research studies.
* Previously participated in any study with mepolizumab, reslizumab, or benralizumab and received study intervention (including placebo) within 12 months prior to Visit 1.
* Women who are pregnant or lactating or are planning on becoming pregnant during the study.

Primary outcomes:
measure: Change from Baseline in total endoscopic nasal polyps (NP) score at Week 52 (scores on a scale)
timeFrame: Baseline and at Week 52
measure: Change from Baseline in mean nasal obstruction score using verbal response scale (VRS) from Weeks 49 to 52 (scores on a scale)
timeFrame: Baseline and from Week 49 to Week 52
Secondary outcomes:
measure: Change from Baseline in mean symptom score for rhinorrhea (runny nose) using VRS (scores on a scale)
timeFrame: Baseline and from Week 49 to Week 52
measure: Change from Baseline in mean symptom score for loss of smell using VRS (scores on a scale)
timeFrame: Baseline and from Week 49 to Week 52
measure: Change from Baseline in Lund Mackay (LMK) computed tomography (CT) score (scores on a scale)
timeFrame: Baseline and at Week 52
measure: Change from Baseline in Sino-nasal Outcome Test (SNOT)-22 total score (scores on a scale)
timeFrame: Baseline and at Week 52
measure: Change from Baseline in mean nasal obstruction score using VRS from Weeks 21 to 24 (scores on a scale)
timeFrame: Baseline and from Week 21 to Week 24
measure: Change from Baseline in total endoscopic NP score at Week 26 (scores on a scale)
timeFrame: Baseline and at Week 26
measure: Time to first nasal surgery (actual or entry on waiting list) or disease-modulating medication for Chronic rhinosinusitis with nasal polyps (CRSwNP) up to Week 52
timeFrame: Up to Week 52
measure: Time to first nasal surgery (actual) or disease-modulating medication for CRSwNP up to Week 52
timeFrame: Up to Week 52
measure: Percentage of Participants requiring at least 1 course of systemic corticosteroids or disease-modulating medication for CRSwNP or nasal surgery (actual) during the Week 52 treatment period
timeFrame: Up to Week 52
measure: Change from Baseline in Asthma Control Questionnaire (ACQ-5) score (scores on a scale)
timeFrame: Baseline and at Week 52
Other outcomes:
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city: Jerez de la Frontera
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city: Madrid
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city: Madrid
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city: Madrid
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city: Pamplona
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city: Valladolid
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city: Zaragoza
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city: Goteborg
country: Sweden
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city: Lund
country: Sweden
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city: Stockholm
country: Sweden
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city: Stockholm
country: Sweden
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city: Ankara
country: Turkey
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city: CapaIstanbul
country: Turkey
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city: Izmir
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facility: GSK Investigational Site
city: Tekirdag
country: Turkey
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Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: