NCT04783389终止2 期
A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate CBP-201 in Adult Patients With Chronic Rhinosinusitis With Nasal Polyps
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 40
- 试验地点
- 68
- 主要终点
- Change in Endoscopic Nasal Polyp Score (NPS)
研究概览
简要总结
This study will evaluate the effect of CBP-201, rademikibart, in adult patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP).
详细描述
This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the effect of CBP-201 on a background of mometasone furoate nasal spray (MFNS) in reducing endoscopic nasal polyp score (NPS) and nasal congestion/obstruction score (NCS) severity in eligible patients with CRSwNP whose disease remains inadequately controlled despite daily treatment with intranasal corticosteroid (INCS) therapy in comparison to placebo. CBP-201 is administered as a subcutaneous (SC) injection. The study is divided into a treatment period of 24 weeks and a follow-up period of 8 weeks.
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)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Female and male patients aged ≥ 18 and ≤ 75 years at the time of screening.
- •Patients who are diagnosed with chronic rhinosinusitis with bilateral polyps despite treatment with systemic corticosteroid within the past 2 years and/or medical contraindication/intolerance to systemic corticosteroids. The polyps have a minimum bilateral nasal polyps score (NPS) of 5 out of a maximum score of 8 with at least a score of 2 for each nostril at screening and baseline evaluated by endoscopy.
- •Nasal congestion/blockade/obstruction with moderate or severe symptom severity (Nasal Congestion Score of > 2) at screening and a weekly average severity of > 1 at time of randomization.
- •Patients using a documented stable dose of nasal mometasone at least 200 mcg/day, or an equivalent daily dose of another inhaled nasal corticosteroid (INCS), for at least 28 days before randomization and willing to continue the dose for the duration of the study. Note: For patients who are using an alternative INCS product other than mometasone furoate nasal spray (MFNS) prior to the screening visit, the investigator must switch the patient to MFNS at V
- •Patients willing to enter Patient Diary daily symptom assessments and maintain stable dosing with MFNS with a compliance of at least 70% in the 7 days preceding randomization. Note: Patients must use nasal mometasone at least 200 mcg/day, or equivalent, for at least 28 days before randomization, which can include days prior to screening with supportive documentation. Run-in can be 7-31 days with the compliance determined in the week prior to dosing.
- •Male patients who are non-sterilized and sexually active with a female partner of childbearing potential agree to use highly effective contraception from randomization until 8 weeks after last dose.
- •Female patients of childbearing potential who are sexually active with a nonsterilized male partner should have a confirmed negative serum beta-human chorionic gonadotropin test at Visit 1 and agrees to use highly effective contraception from signing of informed consent throughout the duration of the study and for 8 weeks after last dose.
- •Patient is able to understand and willing to sign the informed consent form (ICF) prior to any study related procedures being performed.
- •Willing and able to comply with all study visits and study-related procedures, in the opinion of the Investigator.
排除标准
- •A patient who meets any of the following criteria will be ineligible to participate in this study:
- •Patients unable to use MFNS.
- •Patients who are taking or have taken the following prohibited therapies as specified:
- •Systemic steroids within 28 days prior to screening,
- •Other nonbiologic investigational drugs within 60 days (or 5 half-lives, whichever is longer) of screening,
- •Intranasal corticosteroid drops or corticosteroid-administering devices (eg, OptiNose device or stents) within 28 days prior to screening,
- •Non-steroidal immunosuppressants (eg, cyclosporine, methotrexate, azathioprine, mycophenolate, sirolimus, tacrolimus) within 60 days or 5 half-lives, whichever is longer, of screening,
- •Any monoclonal antibody therapy (eg, benralizumab, mepolizumab, omalizumab, reslizumab, dupilumab) or investigational biologic drug for asthma or other diseases within 60 days or 5 half-lives, whichever is longer, of screening,
- •Leukotriene antagonists/modifiers within 7 days prior to screening for patients who were not on continuous treatment for ≥ 30 days prior to screening,
- •Allergen immunotherapy for patients who were not on maintenance treatment for at least 90 days prior to screening
- •Patients who did not respond favorably to previous dupilumab treatment (eg, therapy failure or patient experienced an adverse reaction to treatment).
- •Patients who have undergone any nasal surgery (including polypectomy) within 6 months before screening; or have a history of sinus or nasal surgery modifying the structure of the nose such that assessment of NPS is not possible, or have had uncontrolled epistaxis requiring surgical or procedural intervention, including nasal packing.
- •Patients with conditions/concomitant diseases making them non evaluable at screening or for the primary efficacy endpoint such as: antrochoanal polyps, nasal septal deviation that would occlude at least 1 nostril, acute sinusitis, nasal infection or upper respiratory infection at screening or within 2 weeks before screening, ongoing rhinitis medicamentosa; known or suspected diagnosis of cystic fibrosis; chronic granulomatous disease and granulomatous vasculitis, granulomatosis with polyangiitis (Wegener's Granulomatosis), eosinophilic granulomatous with polyangiitis (Churg-Strauss syndrome), Young's syndrome, primary dyskinetic ciliary syndromes (eg, Kartagener's syndrome) or other dyskinetic ciliary syndromes.
- •Signs or a CT scan suggestive of Allergic Fungal Rhinosinusitis.
- •Patients with co-morbid asthma are excluded if:
- •Forced Expiratory Volume in 1 second (FEV1) ≤ 50% of normal predicted value OR
- •An exacerbation within 90 days prior screening that required hospitalization (> 24 hours) OR
- •Are on a daily dose of inhaled corticosteroids (ICS) higher than 1000 mcg fluticasone or the equivalent.
- •Known or suspected history of immunosuppression, including history of invasive opportunistic infections, such as aspergillosis, coccidioidomycosis, histoplasmosis, human immunodeficiency virus (HIV), listeriosis, pneumocystosis, or tuberculosis, despite infection resolution; or unusually frequent, recurrent or prolonged infections. Tuberculosis testing would be performed on a country-by-country basis according to local guidelines if required by regulatory authorities or ethics committees.
- •Patients who have active Hepatitis B, Hepatitis C or HIV infections as determined by positive results at Screening for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb); or hepatitis C (HCV) antibody; or positive HIV serology. Note: Patients who test positive for HBvAb, negative for HBsAg and subsequently confirmed positive for HBsAb, indicating resolved natural infection (confirmed by negative HBV-DNA), may participate. Patients with positive HCV may participate if subsequent viral load is confirmed negative.
- •A helminth parasitic infection diagnosed within 24 weeks prior to the date of informed consent that has not been treated, or has failed to respond to, standard of care therapy.
- •Evidence of infection requiring treatment with systemic antibacterials, antivirals, antifungals, antiparasitics, or antiprotozoals within 7 days before baseline, or viral infections within 14 days before screening that may not have received antiviral treatment.
- •Live, attenuated vaccinations within 28 days prior to screening or planned live, attenuated vaccinations during the study.
- •Pregnant or intent to become pregnant during the study, or breast-feeding women.
- •Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the investigator and may affect the safety of the patient throughout the study, or influence the findings of the studies or their interpretations, or impede the patient's ability to complete the entire duration of study.
- •Any clinically significant abnormal findings in physical examination, vital signs, safety lab tests during screening/run-in period, which in the opinion of the investigator, may put the patient at risk because of their participation in the study, or may influence the results of the study, or the patient's ability to complete entire duration of the study.
- •Have any of the following laboratory abnormalities at Screening:
- •Eosinophils >1500 cells/mm3 (or 1.5 x 10E9/L)
- •Platelets <100000 cells/mm3 (or 100 x 10E9/L)
- •Creatine phosphokinase (CPK) > 10 upper limit of normal (ULN)
- •Alanine aminotransferase (ALT) > 2.5 times the ULN
- •Aspartate aminotransferase (AST) ≥ 2.5 times the ULN
- •Bilirubin ≥ 2 times the ULN
- •History of alcohol or drug abuse within 12 months prior to the date informed consent.
- •An allergy to L-histidine, trehalose or Tween (polysorbate) 80 or a history of a systemic hypersensitivity reaction, other than localized injection site reaction, to any biologic drug.
- •Plans to undergo any surgical procedure requiring general anesthesia during the study.
- •History of cancer: Patients who have had basal cell carcinoma, localized squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided that the patient is in remission and curative therapy was completed at least 12 months prior to the date informed consent. Note: Patients who have had other malignancies are eligible provided that the patient is in remission and curative therapy was completed at least 5 years prior to the date of informed consent.
研究组 & 干预措施
CBP-201 Dose 1
Experimental
CBP-201 Dose 1 subcutaneous (SC) injection.
干预措施: CBP-201 (Drug)
CBP-201 Dose 2
Experimental
CBP-201 Dose 2 subcutaneous (SC) injection.
干预措施: CBP-201 (Drug)
Placebo
Placebo Comparator
Placebo subcutaneous (SC) injection.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Endoscopic Nasal Polyp Score (NPS)
时间窗: From Baseline to Week 24
Change from baseline at Week 24 in endoscopic Nasal Polyp Score (NPS). Endoscopic NPS is assessed by central clinical specialist assessment of video recordings of nasal endoscopy. NPS is graded based on polyp size (recorded as the sum of the right and left nostril scores with a range of 0 to 8; higher scores indicate worse status). The scoring for each nostril is as follows: 0 No polyps, 1 Small polyps in the middle meatus not reaching below the inferior border of the middle turbinate, 2 Polyps reaching below the lower border of the middle turbinate, 3 Large polyps reaching the lower border of the inferior turbinate or large polyps medial to the middle turbinate (i.e., reaching below the middle turbinate), 4 Large polyps causing complete obstruction of the inferior nasal cavity (i.e., touching the floor of the nose). The most improvement improvement possible from baseline would be -8 and the max worsening possible is +8.
Change in Average Daily Nasal Congestion Score (NCS)
时间窗: From Baseline to Week 24
Change from baseline at Week 24 in average daily Nasal Congestion Score (NCS). Daily NCS wase assessed by patient diary from screening and throughout the study by using a 0 to 3 categorical scale for severity of symptoms from none to severe over the past 24 hours. The patient diary prompt: "How would you rate nasal congestion over the last 24 hours?" The answers are: 0 None,1 Minor, 2 Moderate, 3 Severe. The lowest possible weekly average is 0 and the highest possible is 3. The higher the NCS score, the worse the symptoms. Change from baseline in weekly average score is the outcome. Maximal improvement in NCS would be -3 and maximal worsening would be +3.
次要结局
- Change in Percentage of Maxillary Sinus Volume Occupied by Disease(From Baseline to Week 24)
- Change in University of Pennsylvania Smell Identification Test (UPSIT)(From Baseline to Week 24)
- Change in Visual Analogue Scale for Rhinosinusitis (VAS-RS)(From Baseline to Week 24)
- Change in Total Nasal Symptom Score (TNSS)(From Baseline to Week 24)
- Change in 22-item Sinonasal Outcome Test (SNOT-22)(From Baseline to Week 24)
- Change in Average Daily Anterior Rhinorrhea Score(From Baseline to Week 24)
- Change in Average Daily Posterior Rhinorrhea Score(From Baseline to Week 24)
- Change in Average Daily Loss of Smell Score(From Baseline to Week 24)
- Change in Daily Subject-assessed Nasal Peak Inspiratory Flow (NPIF)(From Baseline to Week 24)
- Change From Baseline in Blood Level of IgE(From Baseline to Week 32)
- Change From Baseline in Peripheral Eosinophil Counts(From Baseline to Week 32)
- Change From Baseline in Eosinophil Cationic Protein (ECP)(From Baseline to Week 32)
- Change From Baseline in Thymus and Activation-regulated Chemokine (TARC)(From Baseline to Week 32)
- Change From Baseline in Eotaxin-3(From Baseline to Week 32)
- Change From Baseline in Periostin(From Baseline to Week 32)
研究者
研究点 (68)
Loading locations...
相似试验
已完成
2 期
A Study to Assess the Efficacy and Safety of CBP-201 in Adult Subjects With Moderate to Severe Atopic DermatitisModerate-to-severe Atopic DermatitisNCT04444752Suzhou Connect Biopharmaceuticals, Ltd.226
已完成
2 期
Efficacy and Safety of Different Doses of BIRB 796 BS in Patients With Active Rheumatoid ArthritisArthritis, RheumatoidNCT02209779Boehringer Ingelheim167
已完成
2 期
Efficacy and Safety of CBP-201 in Patients With Moderate to Severe Persistent Asthma With Type 2 InflammationModerate to Severe Persistent AsthmaNCT04773678Suzhou Connect Biopharmaceuticals, Ltd.322
进行中（未招募）
2 期
A Study of Efficacy and Safety of Rosnilimab in Subjects with Moderate to Severe Rheumatoid Arthritis (RENOIR)Rheumatoid ArthritisNCT06041269AnaptysBio, Inc.420
终止
3 期
An Efficacy and Safety Study of Rimonabant for Treatment of Nonalcoholic Steatohepatitis (NASH) in Patients With Type 2 DiabetesFatty LiverNCT00577148Sanofi89