A 12 Weeks,Multi-center,Randomized,Double-blind,Placebo-controlled Phase II Study to Evaluate the Efficacy and Safety of LP-003 in Adult Patients With Inadequately Controlled Moderate to Severe Seasonal Allergic Rhinitis Despite the Current Recommended Therapies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 180
- 试验地点
- 17
- 主要终点
- Mean nasal symptom score
研究概览
简要总结
Allergic rhinitis (AR) affects large population worldwide, the most commonly used medication include anti-histamine, nasal spray and anti-LTRAs inhibitors (leukotriene receptor antagonists), Even after those first-line treatment, there is still a large number of patient (~20%) are not well/adequately controlled. Anti-IgE antibody has been approved to treat moderate to severe AR by PMDA/Japan in 2020, demonstrating the efficacy of IgE blockade in the treatment of allergic rhinitis. The current study presents a novel anti-IgE antibody (LP-003) with higher affinity to IgE, stronger efficacy and longer half-life.
详细描述
The purpose of this study was to evaluate the efficacy and safety of LP-003 in combination with SoC (nasal corticosteroids and/or anti-histamine) in adult patients with Moderate to Severe Seasonal Allergic Rhinitis, whose symptoms were inadequately controlled despite the current recommended therapies (nasal corticosteroids and/or anti-histamine) in the previous 2 pollen seasons.
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)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 to 65 years at the screening period
- •Patients who met the diagnostic criteria of allergic rhinitis in Chinese Guidelines for the Diagnosis and Treatment of Allergic Rhinitis (revised edition, 2022) : a. Clinical symptoms: more than 2 (including 2 items) symptoms of sneezing, rhinorrhea, nasal congestion, nasal itching and other symptoms appear, which last or accumulate for more than 1h per day and may be accompanied by ocular symptoms such as itchy eyes/ tearing/ redness and burning heat sensation; b. Physical signs: pale, edema of the nasal mucosa and nasal watery discharge; c. Allergen detection: positive of at least 1 allergen skin prick test(SPT) and/or serum-specific IgE within 1 year before enrollment, or nasal provocation test positive
- •Had inadequately controlled symptoms (≥TNSS score of 6 and ≥ nasal congestion score of 2) of seasonal allergic rhinitis in last two years despite the use of nasal corticosteroid or in combination of one anti-histamine recommended by Guidelines.
- •Having any nasal symptom last for at least 2 days or any nasal and eye symptom last for at least one day, and ≥TNSS score of 1
- •Subjects (including partners) have no pregnancy and sperm, egg donation plan and voluntarily take one or more non-pharmaceutical measures for contraception, such as complete abstinence, intrauterine ring, partner ligation at period from drug administration to 6 months after the last study drug administration
- •voluntary participation in this trial and signing the informed consent form
排除标准
- •History of hypersensitivity to any content of the study drugs or its excipients..
- •Subjects with non-allergic rhinitis combined, such as drug rhinitis, vasomotor rhinitis, Nonallergic rhinitis with eosinophilia syndrome, acute and chronic sinusitis, rhinitis sicca anterior, atrophic rhinitis, obvious deviation of nasal septum
- •Subjects with perennial allergic rhinitis ( except for seasonal allergic rhinitis combined with perennial allergic rhinitis, which get attacks seasonally )
- •Subjects who have undergone nasal surgery or sinus surgery within 1 year before screening
- •Subjects who suffer from glaucoma, cataracts, herpes simplex keratitis, infectious conjunctivitis or currently and other eye infections ( Except for allergic conjunctivitis )
- •Subjects with active facial or systemic fungal, bacterial, viral or parasitic infection, and oral candida infection, who still require ongoing treatment
- •With clinically significant uncontrolled systemic disease (unstable ischemic heart disease, NYHA class III/IV left ventricular failure, arrhythmias, uncontrolled hypertension, cerebrovascular disease, neurodegenerative disease, other neurological disorders, uncontrolled hypothyroidism or hyperthyroidism and other autoimmune disorders, hypokalemia, hyperadrenergic status, diagnosed as a malignancy in the past, except for basal cell carcinoma or squamous cell skin cancer ) ; History of myocardial infarction (MI) within 1 year prior to the screening
- •In screening period: a) WBC < 2.5×10^9/L, b)AST or ALT > 2.0×ULN or TBIL > 1.5×ULN, c) Cr > 1.5×ULN
- •Subjects who have been treated by Omalizumab or other similar drugs within 6 months prior to the screening
- •Subjects who have taken systemic glucocorticoids within 4 weeks prior to the screening
- •Subjects who have taken intranasal glucocorticoids, mast cell membrane stabilizers, tricyclic antidepressants, leukotriene receptor antagonists, antihistamines within 1 week prior to the screening
- •Subjects who have taken traditional Chinese medicine for allergic rhinitis within 7 days prior to the screening
- •Subjects who have received allergen immunotherapy within half of year prior to the screening (in treatment), or who have received allergen immunotherapy within 3 years prior to the screening ( completed treatment )
- •During the study period, in addition to standard treatment concomitant drugs and salvage therapy drugs specified in the protocol. Subjects are prohibited from taking medications such as anticholinergics (oral and intranasal anticholinergics, including ipratropium nasal sprays), glucocorticoids, leukotriene receptor antagonists, antihistamines, mast cell membrane stabilizers, decongestants, nasal saline flushing, tricyclic antidepressants, antiallergic Chinese herbal medicines, immunosuppressants, immunomodulators and immunotherapy
- •Subjects with serious organic diseases such as heart, lung, liver, kidney
- •Subjects with poor compliance, such as poor medication compliance, inability to fill in diary cards correctly, and use of prohibited medications
- •Who combined with nerve and mental illness that could not or unwilling to follow the study, and with disabilities as prescribed by law (blind, deaf, mute, mentally disabled, mentally disabled, etc.)
- •Who plan to travel to other regions in which there is no allergic pollen during the study period for more than two consecutive days or three accumulated days
- •Pregnant or lactating women and women who plan pregnancy
- •Participated in other clinical studies within 3 months prior to the start of the study
- •Any condition that the investigator or primary physician believes may not be appropriate for participating the study
研究组 & 干预措施
LP-003 dose 1
Eligible patients randomized to this arm received LP-003 subcutaneously for 8 weeks
干预措施: LP-003 dose 1 (Biological)
LP-003 dose 2
Eligible patients randomized to this arm received LP-003 subcutaneously for 8 weeks
干预措施: LP-003 dose 2 (Biological)
Placebo
Eligible patients randomized to this arm received placebo subcutaneously for 8 weeks
干预措施: Placebo (Biological)
结局指标
主要结局
Mean nasal symptom score
时间窗: peak pollen period(estimated average 4 weeks)
Nasal symptoms (itchy, sneezing, rhinorrhea and nasal congestion) were recorded by the patient everyday in their e-Diary, on a scale of 0 (none) to 3 (intense/severe). Nasal symptom score (0-12 point) consisted of score for severity of itchy (0-3 point), sneezing (0-3 point), rhinorrhea (0-3 point) and nasal congestion (0-3 point). Peak pollen period was defined as the period between the first and last three consecutive days with ≥300 total pollen/1000 mm2 each day.
次要结局
- Daily ocular symptom medication score(pollen period(estimated average 10 weeks))
- Daily nasal symptom medication score(pollen period(estimated average 10 weeks))