A Trial of SHR-1703 in Asthma

• Status: Not yet recruiting
• Trial end date: 2022-09-09
• Target enrollment: 0
• Participant gender: All

Summary

SHR-1703 is a monoclonal antibody under development for severe asthma. This study is the first study in patients with asthma. The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics ，pharmacodynamics and immunogenic characteristics of multiple subcutaneous injections of SHR-1703 in asthmatic patients.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Criteria

Inclusion Criteria:

1. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

2. Able to read, comprehend and write at a sufficient level to complete study materials.

3. Aged 18 to 65 years (inclusive).

4. Body weight equal or more than 40.0 kg.

5. Diagnosis of asthma ≥1 year history

6. Use of standard asthma medications, including asthma maintenance medications and/or emergency relief medications as needed, during the first 4 weeks of screening. If asthmatic maintenance medications are used, use should be stable and the condition is stable. The asthma maintenance therapy class includes one or more of the inhaled glucocorticoids (ICS), the inhaled long-acting β2 receptor agonist (LABA), and the inhaled long-acting cholinergic receptor antagonist (LAMA). Emergency relievers are limited to short-acting beta-2 receptor agonists (SABA) or short-acting cholinergic receptor antagonists (SAMA) inhaled on demand.

7. Serum eosinophil count at screening and baseline ≥0.15/L;

8. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin were less than the upper limit of normal range (ULN) during screening;

9. During the screening period, the FEV1/ estimated value of lung function test before bronchodilators was ≥45% (the examination time was between 6:00 a.m. and 12:00 a.m.), and the short-acting bronchodilators were stopped for at least 4 hours before the examination;

10. Screening period (and baseline period, if applicable) : Subjects are assessed by the investigator through history, physical examination, and supplementary examinations to be free of any disease that would significantly affect the study or pose additional health risks, and are expected to be in stable health status during the study period without medical intervention. If a subject has an abnormality reported on the test, they will only be enrolled if the investigator assesses that the abnormality does not interfere with the study and does not pose an additional health risk. For abnormal laboratory tests with clinical significance, if there are clear and reasonable reasons, retest can be conducted within one week, and the retest results can be used to determine whether the subjects meet the conditions.

11. Subjects (including partners) had no family planning and were voluntarily using effective contraceptives during the study period and during the last visit (see appendix for specific contraceptives).

Exclusion Criteria:

1. People who are allergic to IL-5 antibody drugs and their excipients or to other biological agents;

2. Patients with diseases other than asthma that cause elevated blood eosinophils, including but not limited to eosinophilic syndrome, eosinophilic granulomatosis with polyangiitis (EGPA), eosinophilic esophagitis, etc.;

3. Has a history of clinically significant lung diseases other than asthma, including pneumonia, tuberculosis, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis or has been diagnosed with emphysema or chronic bronchitis or lung cancer;

4. ≥1 clinically significant acute asthma exacerbation occurred 4 weeks before or during the screening period (clinically significant acute asthma exacerbation was defined as requiring systemic glucocorticosteroid treatment for ≥3 days and/or worsening of asthma requiring emergency department visit or hospitalization);

5. An acute exacerbation of life-threatening asthma occurred within 5 years prior to screening. Acute episodes of life-threatening asthma are defined as seizures requiring intubation and/or hypercapnia, respiratory arrest, or hypoxic seizures;

6. Bacterial or viral infections of the upper or lower respiratory tract, sinuses, or middle ear occurring 4 weeks before or during the screening period that result in changes in asthma management or are considered likely to change by the investigator and are expected to affect subjects' asthma status or their ability to participate in the study;

7. Previous cancer history with current malignant tumor or remission period less than 5 years before screening;

8. Patients with any diseases of the liver and biliary system, except Gilbert syndrome or asymptomatic gallstones;

9. Any clinically relevant cardiovascular, gastrointestinal tract, kidney, metabolism, hematology, nervous system, bones, muscles and joints, spirit, eye disease or infectious diseases or immune deficiency disorders, or combined with any other disease, need medical intervention or researchers (after consultation with bidders medical department) that will be harmful to subjects to participate in this study;

10. Hepatitis B virus surface antigen (HBsAg), human immunodeficiency virus antibody (HIV-Ab), serological examination of syphilis, hepatitis C virus antibody (HCV-Ab) positive at screening;

11. Screening the clinical trial participants who had participated in any drug or medical device within the previous 3 months. The clinical trial participants were defined as: those who had signed the informed consent of the clinical trial and used the experimental drug (including placebo) or experimental medical device; Or is still in the follow-up period of a clinical study or within 5 half-lives of the investigational drug (whichever is the longer) before screening;

12. Screening for patients who received any monoclonal antibody for inflammatory disease within the first 6 months, including but not limited to anti-IgE /IL-5R/IL-5/IL-4R/TSLP antibody drugs, or who used drugs with less than 5 half-lives (whichever is the longer);

13. Regular topical or systematic use of glucocorticoids in the 12 months prior to screening for diseases other than asthma;

14. Use of any drug (including prescription drugs, over-the-counter drugs, Chinese herbal medicines and dietary supplements, except conventional vitamins) or use of the drug for less than 5 half-lives (whichever is the longer) within 1 month prior to use of the study drug; Prescription drugs include but are not limited to: Penicillin and cephalosporin, sulfa, tetracycline, granulocyte macrophage colony stimulating factor (gm-csf), interleukin 2 (IL 2) and ranitidine non-steroidal anti-inflammatory drugs, ureide within, allopurinol, b, L - tryptophan, willow nitrogen sulfonyl pyridine, carbamazepine, hydrochlorothiazide, ring spore, nevirapine, clozapine, o o n peace made pp azole, etc .

15. Screening patients who had severe trauma or had undergone surgery within the preceding 6 months, or who planned to undergo surgery during the study period;

16. Screened patients who had donated blood within 1 month prior to the screening, or had severe blood loss (total blood volume ≥400 mL), or had received blood transfusion within 2 months;

17. Those who have received live (attenuated) vaccine within 1 month before screening or who plan to receive live (attenuated) vaccine during the course of screening;

18. Parasite infection/infection was suspected within 6 months prior to screening;

19. Women who are pregnant or lactating (pregnancy is defined as the period from conception to termination of pregnancy) and have a positive blood test for human chorionic gonadotropin (HCG);

20. Smokers who smoked in the 6 months before screening and in the screening period, or who had quit smoking for more than 6 months at the time of screening had smoked ≥10 packs per year (packet year = number of years of smoking × number of packs per day). Alcohol consumption in the first 3 months of screening (more than 15 g of alcohol per day for women and more than 25 g for men (5 g of alcohol is equivalent to 150 mL beer, 50 mL wine or about 17 mL light alcohol) more than twice per week). A history of substance abuse;

21. Visits smoke screen, drug screen and alcohol breath test positive during screening period;

22. Researchers and related staff of the research center or others directly involved in the implementation of the program；

23. Investigator believes that there are any conditions that may prevent subjects from completing the study or pose significant risks to subjects or other factors (such as weakness) that may reduce the likelihood of enrolment.