A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Lebrikizumab/LY3650150 in Participants With Chronic Rhinosinusitis With Nasal Polyps on Background Intranasal Corticosteroids
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 510
- 试验地点
- 382
- 主要终点
- Mean Change From Baseline (CFBL) in Participant Reported Nasal Congestion Score (NCS) Severity
研究概览
简要总结
The main purpose of this study is to evaluate the efficacy and safety of lebrikizumab in participants with chronic rhinosinusitis and nasal polyps treated with intranasal corticosteroids. The study will last about 18 months.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blind
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Physician-diagnosed chronic rhinosinusitis (CRS) with bilateral nasal polyps (NP).
- •Prior treatment with systemic corticosteroids (SCS) within the last 2 years (or a medical contraindication or intolerance to SCS), prior surgery for NP, or both.
- •Endoscopic bilateral NPS score of at least 5 out of 8, with a minimum score of 2 in each nasal cavity performed at screening and baseline.
- •Ongoing symptoms for at least 8 weeks prior to study entry (screening), including:
- •Nasal congestion with moderate or severe symptom severity (score 2 or 3) at screening and a weekly average severity score of at least 1 (range 0 to 3) at randomization, and
- •At least one other symptom, such as partial loss of smell (hyposmia), total loss of smell (anosmia), or anterior or posterior rhinorrhea.
- •Have concomitant asthma must be stable in the 3 months prior to screening using permitted regular asthma treatment.
- •Adolescent participants ≥12 to <18 years of age and weighing ≥40 kg at time of Visit 1.
排除标准
- •Have received a dose of lebrikizumab.
- •Have received treatment with any rescue medication and/or have the need for surgery for NP during screening and/or run-in period.
- •Allergen immunotherapy (subcutaneous immunotherapy [SCIT]/sublingual immunotherapy [SLIT]) initiated within 6 months prior to screening, that is not on a stable dose (3 months prior to screening).
- •Has received a biologic treatment approved for use in CRSwNP, asthma, or AD, even if administered to treat a different condition, within 4 months or 5 half-lives, whichever is longer, prior to screening.
- •Have received treatment with any biologic or systemic immunosuppressants for inflammatory disease or autoimmune disease prior to the baseline visit:
- •B cell-depleting biologics, including rituximab, within 6 months.
- •other biologics within 5 half-lives (if known) or 8 weeks, whichever is longer.
- •Systemic immunosuppressants within 4 weeks prior to baseline.
- •Have had any sinus intranasal surgery (including nasal polypectomy) within 6 months prior to screening
- •Have had prior sino-nasal surgery or sinus surgery changing lateral wall structure of the nose making it difficult to assess endoscopic NPS
- •Have a presence of any of the following conditions that may impact the assessment of endpoints at screening or baseline:
- •Nasal septal deviation occluding at least one nostril.
- •Antrochoanal polyps.
- •Acute sinusitis, acute nasal infection, or acute upper respiratory infection.
- •Ongoing rhinitis medicamentosa.
- •Presence of another diagnosis associated with NP (ie, eosinophilic granulomatosis with polyangiitis, granulomatosis with polyangiitis, Young's syndrome, primary ciliary dyskinesia, cystic fibrosis). Note: for adolescents, documentation for ruling out cystic fibrosis and primary ciliary dyskinesia is required.
- •A nasal cavity tumor (malignant or benign).
- •Evidence of fungal rhinosinusitis.
- •Have anosmia from COVID or any reason other than CRSwNP.
- •Participants with forced expiratory volume in 1 second (FEV1) 50% or less (of predicted normal) at screening.
- •Female participant who is pregnant, breastfeeding, or is planning to become pregnant, or to breastfeed during the study.
研究组 & 干预措施
Placebo Q2W/Q4W
Placebo will be given as SC injection. Participants will receive background therapy with INCS.
干预措施: Placebo (Drug)
Lebrikizumab Q2W/every 8 weeks (Q8W)
Lebrikizumab will be given as SC injection. Participants will receive background therapy with INCS.
干预措施: LY3650150 (Drug)
Placebo Q2W/Q4W
Placebo will be given as SC injection. Participants will receive background therapy with INCS.
干预措施: Standard therapy for INCS (Drug)
Lebrikizumab Q2W/every 8 weeks (Q8W)
Lebrikizumab will be given as SC injection. Participants will receive background therapy with INCS.
干预措施: Standard therapy for INCS (Drug)
Lebrikizumab every 2 weeks (Q2W)/ every 4 weeks (Q4W)
Lebrikizumab will be given as Subcutaneous (SC) injection. Participants will receive background therapy with intranasal corticosteroids (INCS).
Note: Enrollment of adolescents will be open-label, with all adolescents assigned to the lebrikizumab Q2W/Q4W treatment arm.
干预措施: LY3650150 (Drug)
Lebrikizumab every 2 weeks (Q2W)/ every 4 weeks (Q4W)
Lebrikizumab will be given as Subcutaneous (SC) injection. Participants will receive background therapy with intranasal corticosteroids (INCS).
Note: Enrollment of adolescents will be open-label, with all adolescents assigned to the lebrikizumab Q2W/Q4W treatment arm.
干预措施: Standard therapy for INCS (Drug)
结局指标
主要结局
Mean Change From Baseline (CFBL) in Participant Reported Nasal Congestion Score (NCS) Severity
时间窗: Baseline, Week 24
NCS severity is rated by study participants using a 4-point scale (range from 0 to 3), where 0 corresponds to no symptoms and 3 corresponds to severe symptoms. Study participants are asked to record the severity of nasal congestion for the previous 24 hours. This assessment will be collected in the participant eDiary.
Mean CFBL in Endoscopic Nasal Polyp Score (NPS)
时间窗: Baseline, Week 24
The endoscopic NPS is assessed by a centralized, blinded, independent review of nasal endoscopy video recordings. The total score is the sum of the right and left nasal cavity scores. For each nasal cavity, endoscopic NPS is graded based on polyp size from 0 to 4, where 0 = no polyps and 4 = large polyps.
次要结局
- Mean change in Opacification of Sinuses Measured by the Lund Mackay score (LMK)(Baseline, Week 24)
- Mean change in Forced Expiratory Volume in 1 Second (FEV1)(Baseline, Week 24)
- Mean CFBL in Severity of Loss of Smell(Baseline, Week 24)
- Mean CFBL in Postnasal Drip(Baseline, Week 24)
- Mean change in Opacification of Sinuses Measured by the Lund Mackay score (LMK)(Baseline, Week 24)
- Mean change in Forced Expiratory Volume in 1 Second (FEV1)(Baseline, Week 24)
- Mean CFBL in Severity of Loss of Smell(Baseline, Week 24)
- Mean CFBL in Postnasal Drip(Baseline, Week 24)
- Mean Change from Baseline by Visit for the 22-item Sino-nasal Outcome Test (SNOT-22)(Baseline, Week 24)
- Mean Change from Baseline by Visit for the Nasal Peak Inspiratory Flow (NPIF)(Baseline, Week 24)