NCT06036927已完成2 期
A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Clinical Trial to Evaluate the Efficacy, Safety and Pharmacokinetics of TQC2731 Injection in the Treatment of Chronic Sinusitis With Nasal Polyps.
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 16
- 主要终点
- Nasal Polyp Score (NPS)
研究概览
简要总结
This is a multicenter, randomized, double-blind, placebo-controlled Phase II clinical trial to evaluate the efficacy, safety and pharmacokinetics of TQC2731 injection in the treatment of Chronic Sinusitis with Nasal Polyps.
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
- •Subjects sign informed consent before study, fully understand the purpose, procedures and possible adverse reactions of the study;
- •Male and female, ≥18 years old and ≤ 75 years old;
- •Bilateral chronic rhinosinusitis with nasal polyps (CRSwNP) who met the diagnostic criteria of the Chinese Guidelines for the Diagnosis and Treatment of chronic rhinosinusitis (2018);
- •Received nasal polyp surgery or received systemic glucocorticoid treatment 2 years before screening;
- •Bilateral nasal polyp score (NPS) ≥5 and each nostril was scored ≥ 2 when screening and randomization;
- •Nasal congestion score (NCS) ≥2 when screening and randomization;
- •Persistent nasal leakage or smell decrease or loss last more than 8 weeks before screening;
- •Sinonasal outcome testing 22 (SNOT-22) score ≥ 30 when screening and randomization;
- •Subjects received steady dose of intranasal glucocorticoids (INCS) over 4 weeks before screening (subjects agree use Mometasone Furoate Aqueous Nasal Spray (MFNS) while studying);
- •Subjects with asthma start inhaled stable dose of glucocorticoid therapy over 4 weeks before screening, and are willing to keep the dose during whole study;
- •MFNS medication compliance ≥70%, subjects daily symptom assessment compliance ≥70% through Patient dairy;
- •Subjects agree to take effective non-pharmaceutical contraception from signing informed consent to 6 mouth after last administration.
排除标准
- •Presence of conditions/concomitant diseases that affect the evaluation of efficacy, such as:
- •Posterior nostril polyps;
- •Deviation of the nasal septum resulted in obstruction of at least one nostril;
- •Acute sinusitis, nasal infection, or upper respiratory tract infection had occurred 2 weeks before screening, screening period or mediation period;
- •Drug induced rhinitis;
- •Allergic granulomatous vasculitis (Churg-Strauss syndrome), granuloma with poly vasculitis (Wegener's granuloma), Young syndrome, Kartagener syndrome, or other dysphoric ciliary syndrome, with cystic fibrosis;
- •Imaging suspected or confirmed fungal sinusitis;
- •NPS cannot be evaluated due to nasal surgery to alter the structure of the lateral nasal wall;
- •Subjects with nasal malignancies and benign tumors (papilloma, blood furuncle, etc.)
- •Any type of active malignancy or a history of malignancy (Patient with basal cell carcinoma, skin localized squamous cell carcinoma or carcinoma in situ of cervix, can participate in the study if curative treatment was completed for more than 12 months prior to visit 1; Patients with other malignant tumors can participate in the study if curative therapy had been completed for at least 5 years prior to visit 1);
- •Active autoimmune disease (including but not limited to Hashimoto's thyroiditis, Graves disease, Inflammatory bowel disease, Primary biliary cholangitis, Systemic lupus erythematosus, Multiple sclerosis and other neuroinflammatory diseases, Psoriasis vulgaris, Rheumatoid arthritis);
- •Known or suspected history of immunosuppression, immune disorders, or immune disorders, including but not limited to invasive opportunistic infections (histoplasmosis, listeriosis, coccidioides, pulmonary cysticercosis disease, aspergillosis), even if the infection has been resolved;
- •Any intranasal and/or sinus surgery (including polypectomy) within 6 months before screening;
- •Uncontrolled epistaxis occurred within 2 months before screening;
- •A history of active pulmonary tuberculosis in the 12 months before screening;
- •Infection requiring treatment with systemic antibacterial, antiviral, antifungal, antiparasitic, or antiparasitic agents occurred within 14 days before screening;
- •Helminth parasite infection was diagnosed within 24 weeks prior to screening and had not received or failed to respond to standard treatment;
- •Leukotriene antagonists/modulators were used while screening (using a stable dose of leukotriene modulator for ≥30 days before screening was acceptable);
- •Regular use of decongestants (topical or systemic) before screening, except for short-term use for endoscopy;
- •Patients who received any of the following treatments before screening:
- •Received immunosuppressive therapy within the previous 8 weeks or five half-lives (whichever was longer), (including but not limited to cyclophosphamide, cyclosporine, interferon-γ, azathioprine, methotrexate, mycophenolate mofetil and tacrolimus, etc.);
- •Received monoclonal antibody therapy within the previous 8 weeks or five half-lives (whichever was longer), (Including but not limited to: benralizumab, mepolizumab, omalizumab, resveratrol, dupilumab, etc.);
- •Received systemic glucocorticoids within 28 days before the study;
- •Glucocorticoid-eluting nasal stents were used within 6 months before the study;
- •Immune globulin or blood products therapy were used within 28 days before the study;
- •Received or planned to receive live attenuated vaccine within 28 days before or during the study period;
- •Received allergen specific immunotherapy 6 mouth before screening (if started at 3 mouth before screening, being treated at a stable dose in 1 mouth before visit 1 and not expected to change during study, it would be acceptable);
- •Join any other clinical trials within 3 months;
- •Patients with concurrent asthma had any of the following conditions: forced expiratory volume in the first second (FEV1) ≤ 50% of the expected normal value, or acute exacerbation of asthma within 90 days prior to screening, requiring hospitalization (>24 hours), or taking a daily dose greater than 1000 μg of fluticasone or equivalent inhaled glucocorticoids (ICS);
- •Hepatitis B surface Antigen (HBsAg) positive, or Hepatitis B core antibody (HBcAb) positive and Hepatitis B virus deoxyribonucleic acid (HBV-DNA) positive, or anti-hepatitis C virus (Anti-HCV) positive and Hepatitis C virus ribonucleic acid (HCV-RNA) positive, or anti-human Immunodeficiency Virus (Anti-HIV) positive, or anti-treponema pallidum (Anti-TP) positive;
- •Any clinically significant abnormal findings, include physical examination, vital signs, 12-lead electrocardiogram, blood biochemistry, blood routine or urine routine, and investigator judged that participating in the trial may put the patient at risk, or may affect the study outcome or hinder the patient's ability to complete the entire study process;
- •Lab tests results were abnormal:
- •White cell count<3.5 x 10^9/L;
- •Aspartate aminotransferase (AST) > 2.5 x upper limits of normal (ULN);
- •Alanine aminotransferase (ALT) > 2.5 x ULN;
- •Total bilirubin > 2 x ULN;
- •Creatine phosphokinase (CPK)> 2 x ULN;
- •Creatinine >1.5 x ULN
- •Pregnant or lactating women;
- •A allergic history or allergic reaction to Mometasone furoate nasal spray (Nasonex®) or any component of TQC2731 injection;
- •A history of systemic allergy to any biologic drug (except local injection site reactions);
- •The subjects had poor compliance and were judged unable to complete the study;
- •Any medical or psychiatric disorder that was considered by the investigator or the sponsor medical reviewer to be likely to affect the safety of the subjects throughout the study or to prevent the subjects from completing the study or interfere with the interpretation of the results; including but not limited to cardiovascular, gastrointestinal, liver, kidney, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological diseases, psychiatric or major limb disorders etc.
研究组 & 干预措施
TQC2731 injection 210 mg
Experimental
TQC2731 injection 210 mg combined with Mometasone Furoate Aqueous Nasal Spray, 28 days as a treatment cycle.
干预措施: TQC2731 injection (Drug)
TQC2731 injection 420 mg
Experimental
TQC2731 injection 420 mg combined with Mometasone Furoate Aqueous Nasal Spray, 28 days as a treatment cycle.
干预措施: TQC2731 injection (Drug)
TQC2731 matching placebo
Placebo Comparator
TQC2731 matching placebo combined with Mometasone Furoate Aqueous Nasal Spray, 28 days as a treatment cycle.
干预措施: TQC2731 matching placebo (Drug)
结局指标
主要结局
Nasal Polyp Score (NPS)
时间窗: Baseline up to 24 weeks
NPS is the sum of the left and right nostril scores evaluated through nasal endoscopy, with a total score range of 0 to 8. NPS is based on polyp grading, with a score of 0-4 based on polyp grading.
次要结局
- Anosmia Score(Baseline up to 24 weeks)
- Total symptom score (TSS)(Baseline up to 24 weeks)
- Incidence of Adverse event (AE)(Baseline up to 32 weeks)
- Severity of AE(Baseline up to 32 weeks)
- Peak concentration (Cmax)(Before first administration, 1, 4, 8, 12, 24, 72, 120, 144, 168, 336 hours after first administration; before second, third, fourth and last administration; 1, 4, 8, 12, 24, 72, 168, 336, 672, 1008, 1344, 1992 hours after last administration.)
- Trough concentration (Cmin)(Before first administration, 1, 4, 8, 12, 24, 72, 120, 144, 168, 336 hours after first administration; before second, third, fourth and last administration; 1, 4, 8, 12, 24, 72, 168, 336, 672, 1008, 1344, 1992 hours after last administration.)
- Time to Peak concentration (Tmax)(Before first administration, 1, 4, 8, 12, 24, 72, 120, 144, 168, 336 hours after first administration; before second, third, fourth and last administration; 1, 4, 8, 12, 24, 72, 168, 336, 672, 1008, 1344, 1992 hours after last administration.)
- Area under the concentration time curve (AUC0-t)(Before first administration, 1, 4, 8, 12, 24, 72, 120, 144, 168, 336 hours after first administration; before second, third, fourth and last administration; 1, 4, 8, 12, 24, 72, 168, 336, 672, 1008, 1344, 1992 hours after last administration.)
- Maximum plasma concentration at steady state (Css-max)(Before first administration, 1, 4, 8, 12, 24, 72, 120, 144, 168, 336 hours after first administration; before second, third, fourth and last administration; 1, 4, 8, 12, 24, 72, 168, 336, 672, 1008, 1344, 1992 hours after last administration.)
- Minimum plasma concentration at steady state (Css-min)(Before first administration, 1, 4, 8, 12, 24, 72, 120, 144, 168, 336 hours after first administration; before second, third, fourth and last administration; 1, 4, 8, 12, 24, 72, 168, 336, 672, 1008, 1344, 1992 hours after last administration.)
- Plasma concentration at steady state (Css-av)(Before first administration, 1, 4, 8, 12, 24, 72, 120, 144, 168, 336 hours after first administration; before second, third, fourth and last administration; 1, 4, 8, 12, 24, 72, 168, 336, 672, 1008, 1344, 1992 hours after last administration.)
- Nasal congestion score (NCS)(Baseline up to 24 weeks)
- Visual analogue scale (VAS) for sinusitis(Baseline up to 24 weeks)
- Nasal polyp (NP) surgery time(Baseline up to 32 weeks)
- Nasal polyp (NP) surgery ratio(Baseline up to 32 weeks)
- Time of Systemic glucocorticoids (SCS) remedial treatment(Baseline up to 32 weeks)
- Ratio of Systemic glucocorticoids (SCS) treatment(Baseline up to 32 weeks)
- Lund Mackay (LMK) score(Baseline up to 24 weeks)
- Time to Peak concentration at steady state (Tss-max)(Before first administration, 1, 4, 8, 12, 24, 72, 120, 144, 168, 336 hours after first administration; before second, third, fourth and last administration; 1, 4, 8, 12, 24, 72, 168, 336, 672, 1008, 1344, 1992 hours after last administration.)
- Area under the concentration time curve (AUC0-t) at steady state(Before first administration, 1, 4, 8, 12, 24, 72, 120, 144, 168, 336 hours after first administration; before second, third, fourth and last administration; 1, 4, 8, 12, 24, 72, 168, 336, 672, 1008, 1344, 1992 hours after last administration.)
- Half life (t1/2)(Before first administration, 1, 4, 8, 12, 24, 72, 120, 144, 168, 336 hours after first administration; before second, third, fourth and last administration; 1, 4, 8, 12, 24, 72, 168, 336, 672, 1008, 1344, 1992 hours after last administration.)
- Apparent volume distribution (Vd/F)(Before first administration, 1, 4, 8, 12, 24, 72, 120, 144, 168, 336 hours after first administration; before second, third, fourth and last administration; 1, 4, 8, 12, 24, 72, 168, 336, 672, 1008, 1344, 1992 hours after last administration.)
- Plasma clearance (CL/F)(Before first administration, 1, 4, 8, 12, 24, 72, 120, 144, 168, 336 hours after first administration; before second, third, fourth and last administration; 1, 4, 8, 12, 24, 72, 168, 336, 672, 1008, 1344, 1992 hours after last administration.)
- Anti-drug antibody (ADA)(Within 1 hour before administration on Day 1, Day 169, Day 224, during withdrawal)
- Neutralizing antibody (Nab)(Within 1 hour before administration on Day 1, Day 169, Day 224, during withdrawal)
研究者
研究点 (16)
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