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)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 264
- 试验地点
- 1
- 主要终点
- Change From Baseline in Total Endoscopic Nasal Polyps (NP) Score at Week 52 (Centrally Read)
研究概览
简要总结
This study will evaluate the efficacy and safety of depemokimab (GSK3511294) in participants with Chronic rhinosinusitis with nasal polyps (CRSwNP).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
This will be a double-blind study.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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
- •Women who are pregnant or lactating or are planning on becoming pregnant during the study.
研究组 & 干预措施
Depemokimab
Participants received a 100 milligram (mg) dose of depemokimab subcutaneous (SC) injection once every 26 weeks (week 0 and week 26) over a treatment period of 52-weeks. Participants were to be maintained on their existing baseline maintenance Chronic rhinosinusitis with nasal polyps (CRSwNP) standard of care (SOC) treatment throughout the study.
干预措施: Depemokimab (GSK3511294) (Biological)
Placebo
Participants received placebo SC injection once every 26 weeks (week 0 and week 26) over a treatment period of 52-weeks. Participants were to be maintained on their existing baseline maintenance CRSwNP SOC treatment throughout the study.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Total Endoscopic Nasal Polyps (NP) Score at Week 52 (Centrally Read)
时间窗: Baseline (Day 1) and at Week 52
Total endoscopic nasal polyps (NP) score evaluated the size and extent of nasal polyps via endoscopy. The assessments were performed by central video image recordings of nasal endoscopy. The right and left nostrils were scored from 0 to 4 (0 = No polyps; 1 = Small polyps in the middle meatus not reaching below the inferior border of the middle concha; 2 = Polyps reaching below the lower border of the middle turbinate; 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle concha; and 4 = Large polyps causing complete obstruction of the inferior meatus). The scores were graded based on NP size, recorded as sum of the right and left nostril scores and ranges from 0 (no polyps) to 8 (large polyps), calculated by summing the scores \[0 to 4\] in each nostril; with higher scores indicating worse status. Baseline was defined as Day 1 value. Change from Baseline = Post-baseline value minus Baseline value.
Change From Baseline in Mean Nasal Obstruction Score Using Verbal Response Scale From Weeks 49 Through to Week 52
时间窗: Baseline (Day 1) and from Week 49 to Week 52
This endpoint evaluated the change from baseline in the mean nasal obstruction score using a Verbal Response Scale (VRS) from Week 49 through to Week 52. Participants used a VRS to rate nasal obstruction severity, with scores averaged over the specified period to assess treatment impact on nasal obstruction symptoms. Participants were asked to indicate the severity of nasal obstruction at their worst over the last 24 hours using a 4-point VRS, with options of no symptoms, mild symptoms, moderate symptoms, and severe symptoms. This was scored on a scale ranging from 0 (no symptoms) to 3 (severe symptoms), with higher scores indicating worse status. Baseline was defined as the average score from 28 days of eDiary data collected prior to Day 1. Change from Baseline = Post-baseline value minus Baseline value.
次要结局
- Change From Baseline in Mean Symptom Score for Rhinorrhea (Runny Nose) Using Verbal Response Scale From Week 49 Through to Week 52(Baseline (Day 1) and from Week 49 to Week 52)
- Change From Baseline in Mean Symptom Score for Loss of Smell From Week 49 Through to Week 52(Baseline (Day 1) and from Week 49 to Week 52)
- Change From Baseline in Lund Mackay (LMK) Computed Tomography (CT) Score at Week 52(Baseline (Day 1) and at Week 52)
- Change From Baseline in Sino-nasal Outcome Test (SNOT)-22 Total Score at Week 52(Baseline (Day 1) and at Week 52)
- Change From Baseline in Mean Nasal Obstruction Score From Week 21 Through to Week 24(Baseline (Day 1) and from Week 21 to Week 24)
- Change From Baseline in Total Endoscopic Nasal Polyps Score at Week 26(Baseline (Day 1) and at Week 26)
- Percentage of Participants Requiring First Nasal Surgery (Actual or Entry on Waiting List) or Disease-Modulating Medication for Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) Up to Week 52(Up to Week 52)
- Percentage of Participants Requiring First Nasal Surgery (Actual) or Disease-Modulating Medication for CRSwNP up to Week 52(Up to Week 52)
- Percentage of Participants Requiring at Least One Course of Systemic Corticosteroids or Disease-Modulating Medication for CRSwNP or Nasal Surgery (Actual) During the Week 52 Treatment Period(Up to Week 52)
- Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Week 52(Baseline (Day 1) and at Week 52)