Clinical Study on the Efficacy and Safety of SHR-4597 Inhalant in Adult Patients With Asthma

Официальное название

To Evaluate the Efficacy and Safety of SHR-4597 Inhalants in Adults With Asthma: a Multicenter, Randomized, Open-label, Positive-controlled Phase II Clinical Study

Обзор

To evaluate the efficacy and safety of SHR-4597 inhalants in adults with asthma: a multicenter, randomized, open-label, positive-controlled Phase II clinical study

Вмешательства

• Препарат SHR4597
  SHR4597
• Препарат Budesonide inhalant
  Budesonide inhalant

Первичные конечные точки

• Changes in FEV1 (Pre-BD) from baseline [Срок оценки: 6 weeks]

Вторичные конечные точки (7)

• Changes in FEV1 before bronchodilator (Pre-BD) administration compared with baseline at week 42 [Срок оценки: at week 42]
• Changes in forced vital capacity (FVC) before bronchodilator (Pre-BD) use compared with baseline at week 42 [Срок оценки: at week 42]
• Changes in peak expiratory flow (PEF) before bronchodilator (Pre-BD) use compared with baseline at week 42 [Срок оценки: at week 42]
• Changes in exhaled nitric oxide (FeNO) from baseline at 42 weeks [Срок оценки: at 42 weeks]
• Changes in Asthma Control Questionnaire (ACQ-6) scores from baseline at 42 weeks [Срок оценки: at 42 weeks]
• Change in mean number of nightly awakenings from baseline over 42 weeks [Срок оценки: 42 weeks]
• Changes in ACT questionnaire scores from baseline at 42 weeks [Срок оценки: at 42 weeks]

Критерии участия

Критерии включения

• Age ≥18 years old and ≤75 years old, gender is not limited;
• Body mass index (BMI) ≥18 and ≤30 kg/m2 during screening period;
• Medical history and objective evidence consistent with current guidelines supporting an asthma diagnosis within the 12 months prior to randomization;
• Did not receive inhaled corticosteroids (ICS) and/or combined with other asthma control medications within 2 weeks prior to randomization;
• FEV1 during the screening period and before bronchodilator inhalation at baseline accounted for ≥40% and < 80% of the estimated value;
• Screening and baseline visit, Asthma Control Questionnaire-6 (ACQ-6) score ≥1.5;
• FeNO values at screening period and baseline ≥25 ppb;
• Patients with asthma who were treated for the first time or who had previously taken irregular medication were selected; Among them, the definition of irregular past use was: patients did not regularly use asthma control drugs within the first 3 months of enrollment, and the average weekly use compliance was < 50%.
• A fertile female subject or a male subject whose partner is a fertile female must agree not to have a family plan and to voluntarily use highly effective contraception (including the partner) from the time of signing the informed consent until 1 month after the last study drug administration, and refrain from sperm/egg donation;
• Voluntarily sign informed consent to participate in this study.
• The subjects were unable to complete the questionnaires due to their limited educational level, or neither the subjects themselves nor their families could fill in the subject log card.
• The researchers determined that there were other circumstances that were not suitable for participation in this study.

Критерии исключения

• Combined diseases or conditions

• Clinically significant pulmonary diseases, including but not limited to active pulmonary tuberculosis, bronchiectasis, atelectasis, idiopathic pulmonary fibrosis, bronchopulmonary aspergillosis, and chronic obstructive pulmonary disease (COPD);

• Malignant tumors diagnosed within 5 years prior to randomization (except those with a low risk of metastasis and death, such as well-treated basal cell carcinoma of the skin or carcinoma in situ of the cervix);

• Combined with poorly controlled hypertension (systolic blood pressure ≥180mmHg, and/or diastolic blood pressure ≥110mmHg during the screening period) or uncontrolled severe cardiovascular and cerebrovascular diseases; ④ Known immunodeficiency;

• A history of infection requiring clinical intervention within 4 weeks prior to randomization, including but not limited to respiratory infection;

⑥ Known presence of parasitic infection within 6 months prior to randomization;

⑦ Blood donation or significant blood loss (≥400ml), or transfusion of blood products or immunoglobulin within 4 weeks prior to randomization;

⑧ A history of life-threatening acute asthma attacks (including admission to the intensive care unit and/or the need for invasive ventilator support \[intubation/tracheotomy\]);

⑨ History of acute asthma attack in the 4 weeks prior to randomization.

• Combination of medication or treatment

• Receiving non-selective beta-blockers (e.g., propranolol) within 1 week prior to screening;

• Live attenuated vaccine or recombinant vaccine with viral vector were received within 4 weeks before randomization;

• Receiving allergen immunotherapy 8 weeks before randomization;

• Within 12 weeks before randomization or within 5 half-lives of the drug (refer to the drug instructions, whichever is older; For those with unknown half-lives, the first 12 weeks of randomization will be the use of systemic immunosuppressants (except for systemic glucocorticoids for asthma treatment, and systemic glucocorticoids for other conditions <3 days) or immunomodulators, or biologics or Th2 cytokine inhibitors, Including but not limited to methotrexate, cyclosporine, interferon-alpha, anti-IL-5 monoclonal antibody,anti-TSLP monoclonal antibody, anti-IGE monoclonal antibody, mesulast, etc.

• Receiving a single dose of long-acting β2 agonist within 4 weeks prior to screening; ⑥4 weeks before randomization, inhaled corticosteroids (>500 micrograms of beclomethasone dipropionate per day \[BDP\] or equivalent dose);

⑦4 weeks before randomization, systemic glucocorticoid therapy;

• Received bronchial thermoplasty or bronchial cryoablation within 1 year before randomization; ⑨There is a surgical plan during the study, or other treatment that the investigator believes may affect the evaluation of the subject;
• Laboratory examination

①Significant abnormalities during screening or baseline laboratory tests:

• White blood cell (WBC) < 3.0×109/L;
• Blood eosinophils >1500cells/μL (1.5×109/L)
• Hemoglobin (Hb) ≤90 g/L;
• Alanine aminotransferase (ALT) > 3×ULN (upper limit of normal);
• Aspartate aminotransferase (AST) > 3×ULN;
• Total bilirubin (TBIL) > 1.5×ULN;
• Prothrombin time (PT) > ULN+3s;
• Creatinine (Cr) > 1.5×ULN;
• Co-active hepatitis B (peripheral blood hepatitis B virus deoxyribonucleic acid (HBV DNA) ≥1×103 IU\[or copy\] / mL), or hepatitis C antibody positive, or human immunodeficiency virus (HIV) positive, or treponema pallidum antibody positive.

• Prolonged ECG QTc interval (>450ms) or other clinically significant abnormal results that may pose significant safety risks to subjects during the screening period;
• General situation

• Smoking or smoking cessation less than 6 months during the screening period, or previous smoking ≥10 pack years (pack years = number of years of smoking × number of packs per day); ②A history of drug use, alcohol abuse (average weekly consumption of ≥14 units of alcohol: 1 unit = 285 mL for beer, 25 mL for spirits, or 100 ml for wine) or drug abuse in the year prior to screening;

• Have participated in other clinical studies and used investigational drugs containing active ingredients within 30 days prior to screening, or have been within 5 half-lives of investigational drugs at the time of screening (whichever is older);

• Subjects who are pregnant (screening or baseline blood pregnancy test positive) or who plan to become pregnant while breastfeeding or during the study; ⑥Other reasons deemed unsuitable for study participation by the researcher.
• Excessive alcohol consumption and drug abuse were prohibited throughout the study period (the definition of excessive alcohol consumption is the same as exclusion criterion IV.2).

• Smoking (including e-cigarettes) was prohibited throughout the study period.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• West China Hospital, Sichuan University — Чэнду

Идентификаторы

NCT: NCT06940700 · SHR-4597-201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗