OncoTrials - мониторинг клинических исследований

Описание

This study evaluates the efficacy and safety of benralizumab as an add-on therapy in uncontrolled eosinophilic asthma participants treated with medium-dose ICS-LABA compared to the conventional treatment step of escalation of inhaled therapy to high-dose ICS-LABA.

Критерии включения

• * Written informed consent
• * Participant must be 12 to 75 years of age
• * Documented history of physician-diagnosed asthma requiring treatment with at least medium-dose ICS (/> 250 μg fluticasone dry powder formulation equivalents total daily dose) and a LABA, for at least 12 months prior to Visit (V) 1.
• * Documented treatment with medium-dose ICS and LABA for at least 3 months prior to Visit 1 with or without additional asthma controllers (excluding oral corticosteroids).
• * Weight of ≥ 35 kg.
• * Pre-Bronchodilator (BD) Forced expiratory volume in 1 second (FEV1) of ≤ 90% predicted
• * Documented at least 2 asthma exacerbations in the 12 months prior to the date of informed consent.
• * ACQ-6 score ≥ 1.5 at Visit 1, plus at least once in the run-in period (from V2 to V3) and at V3.
• * Evidence of asthma as documented by excessive variability in lung function, as defined in the protocol.
• * Peripheral blood eosinophil count of ≥ 150 cells/μL, as defined in the protocol.
• * At least 70% compliance with usual asthma controller ICS-LABA during run-in period (from Visit 2 to Visit 3) based on asthma daily diary.

Критерии исключения

• * Important pulmonary disease other than asthma at the discretion of the investigator, or ever been diagnosed with pulmonary or systemic disease, other than asthma, which are associated with elevated peripheral eosinophil counts.
• * Asthma exacerbation requiring use of Systemic corticosteroids (SCS), or acute upper/lower respiratory infection that requires antibiotics or antiviral medication within 30 days prior to the date informed consent is obtained or during the screening/run-in period
• * Any unstable disorder that in the opinion of the investigator could affect the study according to the study protocol.
• * Clinically significant chronic or ongoing active infections requiring systemic treatment (at investigator`s discretion)
• * Concurrent participation in another clinical study with an IP or a post-authorisation safety study.
• * History of alcohol or drug abuse within 12 months prior to the date informed consent is obtained.
• * Current smokers or former smokers with a smoking history ≥ 10 pack-years. Former smokers must have stopped for at least 6 months prior to Visit 1 to be eligible.

Описание

The purpose of this study is to evaluate the Pharmacodynamic, Efficacy and Safety of SHR-1703 in Asthma Patients with Eosinophil Phenotype

Критерии включения

• 1. At least 12 years of age
• 2. A minimum weight of 40kg
• 3. A medical history of at least 1 year that meets the diagnosis of asthma;
• 4. Current treatment with medium- or high- doses of ICS for at least 6 months and using steadily at least 3 months
• 5. Current treatment with an additional controller medication, besides ICS, for at least 3 months and using steadily at least 1 month
• 6. Absolute count of blood eosinophils suggests eosinophilic asthma
• 7. During the screening period and baseline, pre- BD FEV1% /< 80%
• 8. During the screening period and baseline, ACQ-6 score indicates asthma poor control
• 9. History of severe asthma exacerbation within the past 12 months prior to screening
• 10. Good compliance with eDiary completion
• 11. Take efficient contraceptive measures
• 12. Voluntarily sign the informed consent form to participate in this study

Критерии исключения

• 1. With other condition that could lead to elevated eosinophils
• 2. With Clinically significant pulmonary diseases
• 3. With existing immunodeficiency disease
• 4. With other clinically significant diseases that may affect lung function
• 5. With uncontrolled severe cardiovascular and cerebrovascular diseases
• 6. With uncontrolled hypertension and/or diabetes
• 7. With exacerbation, allergic rhinitis or sinusitis attacks, or clinical significant infection requiring intervention during 4 weeks prior to randomization
• 8. Recent major surgeries or surgical plans during the study period, or treatment measures that investigators believe may affect subject evaluation
• 9. Existing parasitic infections
• 10. Diagnosed as malignant tumor within the first 5 years of randomization
• 11. Significant abnormalities in screening period or baseline laboratory tests
• 12. Screening period or baseline ECG QTc prolongation
• 13. Prohibited drugs using during the pre randomization period
• 14. Participated in other clinical trials within 30 days prior to screening and used research drugs containing active ingredients, or was still within 5 half lives of the research drug at the time of screening
• 15. Smoking or quitting smoking for less than 6 months during screening, or previous smoking history ≥ 10 pack years
• 16. History of drug use, alcoholism, or substance abuse within the past year prior to screening
• 17. Allergic or intolerant to IL-5 monoclonal antibodies or other biological agents
• 18. Pregnant or lactating subjects
• 19. Other reasons why the researcher deemed it unsuitable for conducting this experiment

Описание

Background:

Hypereosinophilic syndrome (HES) is a blood disorder that causes high levels of white blood cells called eosinophils. HES can damage the lungs and airways, intestines, skin, and other organs. The current primary treatment for HES can cause serious side effects. Secondary treatments do not work in all people.

Objective:

To test an approved drug (dupilumab), combined with other drugs, in people with HES.

Eligibility:

People aged 18 years and older who take drugs (mepolizumab, reslizumab, or benralizumab) to treat HES.

Design:

Participants will have up to 6 clinic visits and 7 remote visits in up to 48 weeks.

Participants will be screened. They will have blood and urine tests. They will have a test of their heart function. They will take surveys about how HES affects their daily life. Some participants may have a bone marrow biopsy: A sample of tissue and fluid from inside a bone will be removed with a large needle.

Participants will have other tests specific to their symptoms. For example, those with symptoms affecting their lungs will have breathing tests. Others may have tests that target symptoms in their sinuses, gastrointestinal tract, or skin.

Dupilumab is injected under the skin once every 1 or 2 weeks. Dose and timing will vary among participants. They will be taught how to inject themselves at home between clinic visits. They will take dupilumab plus their current medications for 24 weeks. If the drug is helping them, they will continue taking it for another 24 weeks.

Participants will have a final visit 12 weeks after their last dose.

Критерии включения

• * INCLUSION CRITERIA:
• To be eligible to participate in this study, an individual must meet all the following criteria:
• 1. Age />=18 years
• 2. Documented diagnosis of HES with historic AEC/>1.5x10/^9/L on two occasions, no secondary etiology for the eosinophilia despite careful clinical evaluation, and evidence of end organ damage (histologic evidence of tissue infiltration by eosinophils and/or objective evidence of clinical pathology in any organ system that is temporally associated with eosinophilia and not clearly attributable to another cause)
• 3. Currently receiving treatment with an eosinophil-lowering biologic (mepolizumab, reslizumab, or benralizumab) for a minimum of 24 weeks
• 4. AEC/<0.5x10/^9/L
• 5. Residual symptoms after a minimum of 24 weeks of eosinophil-lowering biologic therapy with at least 1 most bothersome symptom of moderate severity (HES-SI score />=2) consistent with />=1 of the following diagnoses:
• a. asthma, defined as physician-documented asthma requiring medium to high dose inhaled corticosteroids + long-acting beta agonist b. atopic dermatitis, defined as physician-documented chronic or recurrent inflammatory skin disease
• c. CRSwNP, defined as evidence of rhinosinusitis and nasal polyposis on physical examination or imaging
• d. EoE, defined as biopsy-proven esophageal eosinophilia />15 eosinophils/high power field
• 6. For participants who can become pregnant: sexual abstinence or use of highly effective contraception (i.e., partner vasectomy, bilateral tubal ligation, IUD, progestin implants, and other hormonal methods) starting 4 weeks prior to study drug initiation and agreement to use such a method during study participation and for an additional 12 weeks after the end of study drug administration
• 7. Participation in NIH protocol 94-I-0079 (Activation and function of eosinophils in conditions with blood or tissue eosinophilia)
• 8. Ability of subject to understand and the willingness to sign a written informed consent document

Критерии исключения

• An individual who meets any of the following criteria will be excluded from participation in this study:
• 1. Pregnancy or lactation
• 2. Known allergic reaction to dupilumab or any of the excipients in Dupixent(TM)
• 3. Febrile illness within 7 days of enrollment
• 4. Treatment with an investigational drug or other intervention other than mepolizumab, reslizumab, or benralizumab within 12 weeks or 4 half-lives of the investigational agent (whichever is longer).
• 5. Known or suspected acquired or inborn immunodeficiency disorder, including HIV infection
• 6. Known diagnosis of eosinophilic granulomatosis with polyangiitis
• 7. Change in eosinophil-active therapy within the past 6 weeks, including but not limited to topical corticosteroids, leukotriene inhibitors, initiation or change of a food-elimination diet regimen or re-introduction of a previously eliminated food (in patients with gastrointestinal involvement), and proton pump inhibitors (in patients with gastrointestinal involvement)
• 8. Planned or anticipated major surgical procedure during the study
• 9. Active parasitic infection
• 10. History of malignancy within 5 years, excluding completely treated in situ carcinoma of the cervix, or squamous or basal cell carcinoma of the skin
• 11. Any condition that, in the investigator s opinion, places the patient at undue risk by participating in the study
• For patients with eosinophilic gastrointestinal disease only:
• 1. Active infection with Helicobacter pylori
• 2. History of achalasia, Crohn s disease, ulcerative colitis, celiac disease, or prior esophageal surgery
• 3. Any esophageal stricture unable to be passed with a standard, diagnostic, 9 to 10 mm upper endoscope