Clinical trial NCT06036927: A Clinical Study of TQC2731 Injection in the Treatment of Chronic Rhinosinusitis With Nasal Polyps
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Sinusitis
Nasal Polyps
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-09-14
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* Presence of conditions/concomitant diseases that affect the evaluation of efficacy, such as:

  1. Posterior nostril polyps;
  2. Deviation of the nasal septum resulted in obstruction of at least one nostril;
  3. Acute sinusitis, nasal infection, or upper respiratory tract infection had occurred 2 weeks before screening, screening period or mediation period;
  4. Drug induced rhinitis;
  5. 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;
  6. Imaging suspected or confirmed fungal sinusitis;
  7. NPS cannot be evaluated due to nasal surgery to alter the structure of the lateral nasal wall;
  8. 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:

  1. 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.);
  2. 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.);
  3. Received systemic glucocorticoids within 28 days before the study;
  4. Glucocorticoid-eluting nasal stents were used within 6 months before the study;
  5. Immune globulin or blood products therapy were used within 28 days before the study;
  6. Received or planned to receive live attenuated vaccine within 28 days before or during the study period;
  7. 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);
  8. 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:

  1. White cell count\<3.5 x 10\^9/L;
  2. Aspartate aminotransferase (AST) \> 2.5 x upper limits of normal (ULN);
  3. Alanine aminotransferase (ALT) \> 2.5 x ULN;
  4. Total bilirubin \> 2 x ULN;
  5. Creatine phosphokinase (CPK)\> 2 x ULN;
  6. 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.

Primary outcomes:
measure: Nasal Polyp Score (NPS)
timeFrame: Baseline up to 24 weeks
Secondary outcomes:
measure: Nasal congestion score (NCS)
timeFrame: Baseline up to 24 weeks
measure: Anosmia Score
timeFrame: Baseline up to 24 weeks
measure: Total symptom score (TSS)
timeFrame: Baseline up to 24 weeks
measure: Visual analogue scale (VAS) for sinusitis
timeFrame: Baseline up to 24 weeks
measure: Nasal polyp (NP) surgery time
timeFrame: Baseline up to 32 weeks
measure: Nasal polyp (NP) surgery ratio
timeFrame: Baseline up to 32 weeks
measure: Time of Systemic glucocorticoids (SCS) remedial treatment
timeFrame: Baseline up to 32 weeks
measure: Ratio of Systemic glucocorticoids (SCS) treatment
timeFrame: Baseline up to 32 weeks
measure: Lund Mackay (LMK) score
timeFrame: Baseline up to 24 weeks
measure: Incidence of Adverse event (AE)
timeFrame: Baseline up to 32 weeks
measure: Severity of AE
timeFrame: Baseline up to 32 weeks
measure: Peak concentration (Cmax)
timeFrame: 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.
measure: Trough concentration (Cmin)
timeFrame: 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.
measure: Time to Peak concentration (Tmax)
timeFrame: 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.
measure: Area under the concentration time curve (AUC0-t)
timeFrame: 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.
measure: Maximum plasma concentration at steady state (Css-max)
timeFrame: 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.
measure: Minimum plasma concentration at steady state (Css-min)
timeFrame: 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.
measure: Plasma concentration at steady state (Css-av)
timeFrame: 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.
measure: Time to Peak concentration at steady state (Tss-max)
timeFrame: 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.
measure: Area under the concentration time curve (AUC0-t) at steady state
timeFrame: 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.
measure: Half life (t1/2)
timeFrame: 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.
measure: Apparent volume distribution (Vd/F)
timeFrame: 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.
measure: Plasma clearance (CL/F)
timeFrame: 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.
measure: Anti-drug antibody (ADA)
timeFrame: Within 1 hour before administration on Day 1, Day 169, Day 224, during withdrawal
measure: Neutralizing antibody (Nab)
timeFrame: Within 1 hour before administration on Day 1, Day 169, Day 224, during withdrawal
Other outcomes:
Locations:
city: Wuhu
country: China
facility: The First Affiliated Hospital of Wannan Medical College
state: Anhui
city: Guangzhou
country: China
facility: ZhuJiang Hospital of Southern Medical University
state: Guangdong
city: Jieyang
country: China
facility: Jieyang People's Hospital
state: Guangdong
city: Zhuhai
country: China
facility: The Fifth Affiliated Hospital Sun Yat-sen University
state: Guangdong
city: Zunyi
country: China
facility: Affiliated Hospital of Zunyi Medical University
state: Guizhou
city: Cangzhou
country: China
facility: Cangzhou Central Hospital
state: Hebei
city: Hohhot
country: China
facility: Affiliated Hospital of Inner Mongolia Medical University
state: Inner Mongolia
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Dalian
country: China
facility: Affiliated Zhongshan Hospital Of Dalian University
state: Liaoning
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Weifang
country: China
facility: Weifang Second People's Hospital
state: Shandong
city: Shanghai
country: China
facility: Eye & ENT Hospital of Fudan University
state: Shanghai
city: Chengdu
country: China
facility: Chengdu Second People's Hospital
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Ürümqi
country: China
facility: The First Affiliated Hospital of Xinjiang Medical University
state: Xinjiang Uygur Autonomous Region
Study officials:
References: