Clinical trial NCT06642961: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Phase II Trail Evaluating the Efficacy and Safety of GR1802 Injection in Patients with Moderate to Severe Asthma
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Phase II Trail Evaluating the Efficacy and Safety of GR1802 Injection in Patients with Moderate to Severe Asthma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Asthma
Lead sponsor: Genrix (Shanghai) Biopharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-10-15
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi-center, randomized, double blind, placebo-controlled study to evaluate the efficacy and safety of GR1802 injection in comparison to placebo in patients with atopic dermatitis. Patients will receive GR1802 injection or Placebo every 2 Weeks.


Eligibility criteria: Inclusion Criteria:

1. Age ≥18 and ≤70 years old, male or female.
2. The subject meet the diagnostic criteria of GINA 2021 requiring a diagnosis of asthma for at least 12 months and fulfilled one of the following criteria:

(1) The subject has received medium-to-high dose ICS combined with at least one control drug, such as LABA, LTRA, theophylline, for at least 3 months before baseline visit, and maintained stable treatment regimen and dosage for at least 1 month before baseline visit; (2) The subject have been on a 3rd controlled drug for at least 3 consecutive months and on a stable dose for ≥1 month prior to baseline visit; (3) The subject must have been on maintenance therapy with ≤10mg/day prednisone or equivalent dose of OCS continuously for at least 3 months and have been receiving therapy at a stable dose for ≥1 month prior to the baseline visit.

3. 35%≤ Pre-bronchodilator FEV1 measured ≤ 80% of the normal predicted value at screening and baseline visits.

4. Asthma Control Questionnaire-5 (ACQ-5) score ≥1.5 at screening and baseline visits.

5. A positive bronchodilation test (≥12% increase in the FEV1 post-bronchodilator and an absolute FEV1 increase of ≥200 mL) within 12 months before screening.

6. Subjects must have experienced at least one severe asthma exacerbation event within 12 months before screening, denfined as: systemic use of glucocorticoids for ≥3 days (at least twice the dose of current use); and/or an emergency visit due to asthma symptoms resulting in hospitalisation, and/or asthma requiring additional systemic glucocorticoid intervention therapy.

7. Willingness to follow the requirements of the study protocol and willingness of the patient or his/her legal representative to sign a written informed consent.

Exclusion Criteria:

1. Chronic obstructive pulmonary disease (COPD) or other lung disease that may impair lung function, as judged by the investigator.
2. Have experienced a severe asthma exacerbation event within 1 month before baseline visit.
3. Lung disease other than asthma with clinically significant impact on efficacy or safety evaluation confirmed by clinical or imaging evidence （e.g., chest X-ray, CT, MRI）within 12 months before baseline visit.
4. Evidence of active tuberculosis infection at screening.
5. Current smokers or former smokers who quit smoking less than 6 months.
6. Former smokers with a smoking history of more than 10 pack-years.
7. Subjects who have history of drug or alcohol abuse (alcohol abuse defined as consumption of more than 28 units of alcohol per week :1 unit = 285 ml of beer or 25 ml of spirits ≥40% alcohol by volume or 1 glass of wine) within 2 years before baseline visit.
8. Long-term reversal of daily sleep patterns (e.g., long-term night shift workers).
9. Subjects who need to be treated with non-selective β1-adrenergic receptor blockers for any reason, or who are on selective β1-blockers but have unstable doses in the 1 month prior to the baseline visit.
10. Underwent an IgE antibody within 130 days prior to the baseline visit, or received prior treatment with an IL-4R antibody (e.g., dupilumab); and those who have received other biologics within 5 half-lives (half-life known) or 6 months (half-life unknown).
11. Treatment with herbs and pCms with asthma-alleviating effects within 4 weeks prior to the baseline visit (except topical herbs).
12. Underwent immunoglobulin (IVIG) therapy, allergen-specific immunotherapy (SIT) within 3 months prior to the baseline visit or plan to be treated with the therapy during the trial.
13. Underwent bronchial thermoplasty within 3years before baseline visit or plan to be treated with the therapy during the trial.
14. Comorbidities requiring ICS (e.g. TB) or LABA (e.g. severe heart disease, insulin-dependent diabetes mellitus, uncontrolled hypertension, hyperthyroidism, etc.) resulting in compromised treatment of the comorbidities.
15. Prolonged QTc interval or ventricular tachycardia requiring pharmacological treatment.
16. Pregnant or lactating women.
17. Positive hepatitis B surface antigen (except for HBVDNA test below 500 IU/ml) and hepatitis B core antibody (except for HBVDNA test below 500 IU/ml) at screening; positive HCV antibody, HIV antibody, and TP-Ab (except for those who are RPR or TRUST negative).
18. Those with existing or suspected acute or chronic infections in the 4 weeks prior to the baseline visit and who have received antibacterial, antiviral, antifungal, antiparasitic or antiprotozoal therapy.
19. Received live or attenuated vaccine within 12 weeks before baseline visit or planned to receive live or attenuated vaccine during the study period.
20. History of vital organ transplantation (e.g. heart, lung, kidney, liver) or haematopoietic stem cell/bone marrow transplantation.
21. Patients with active autoimmune diseases, or autoimmune diseases being treated with immunosuppressive drugs (e.g. inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis, psoriasis, Hashimoto's thyroiditis, Graves' disease).
22. History of severe herpes virus infections, e.g., herpes encephalitis, disseminated herpes.
23. Malignancy within 5 yearsbefore baseline visit (except squamous carcinoma in situ, basal cell carcinoma and cervical carcinoma in situ of the skin, which have been completely treated without any sign of recurrence).
24. Poorly controlled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg. Note: Determined by 2 consecutive elevated readings. If the initial blood pressure reading exceeds this limit, the blood pressure may be re-measured after the subject has rested for ≥10 minutes. If the repeated measurement is below the limit, the second value is acceptable).
25. The following laboratory test abnormalities were present at screening:

    Haemoglobin \<10.0 g/dL (100.0 g/L) (men) or \<9.0 g/dL (90.0 g/L) (women); white blood cell count \<3.0×109/L; neutrophil count \<1.5 x 109 /L; platelet count \<100 x 109 /L; alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ) \> 1.5 times upper limit of normal (ULN); serum creatinine \> 1.0 times ULN; total bilirubin \> 1.5 times ULN; alkaline phosphatase \> 1.5 times ULN.
26. Females and/or males of childbearing potential and their partners who refuse to: use highly effective (female subjects and their partners)/effective (male subjects and their partners) contraception, have a childbearing, egg donation programme (females), or a sperm donation programme (males), from the time of signing the Informed Consent Form until 6 months after the end of the last dose;
27. Participation in another clinical trial treatment within 12 weeks prior to the baseline visit.
28. The investigator considers that there are any conditionswhich are inappropriate to participate in this study.

Primary outcomes:
measure: Change from baseline in pre-bronchodilator FEV1 (forced expiratory volume in 1 second) at 12 weeks.
timeFrame: 12weeks
Secondary outcomes:
measure: Change from baseline in pre-bronchodilator FEV1 at 24 weeks.
timeFrame: 24weeks
measure: Percent change from baseline in pre-bronchodilator FEV1 at 12 and 24 weeks.
timeFrame: 12weeks and 24weeks
measure: Annualized rate of subjects experiencing severe asthma exacerbations.
timeFrame: 24weeks and 32weeks
measure: Time to the first onset of the severe asthma exacerbation event.
timeFrame: 32weeks
measure: Annualized rate of subjects experiencing the event of loss of asthma control (LOAC).
timeFrame: 24weeks and 32weeks
measure: Time to the onset of the first event of LOAC.
timeFrame: 32weeks
measure: Change from baseline in other lung function measures.
timeFrame: 24weeks
measure: Changes from baseline in the Asthma Control Questionnaire-5 (ACQ-5)score and ACQ-7 score at each evaluation time point.
timeFrame: 2、4、8、12、16、20、24、28 、32weeks
measure: Change from baseline in the Asthma Quality of Life Questionnaire (AQLQ) score at 12weeks and 24 weeks.
timeFrame: 12weeks and 24weeks
measure: Total daily use of asthma reliever
timeFrame: 24weeks
measure: Safety evaluation indicators
timeFrame: 32weeks
measure: Concentration of GR1802 at each evaluation time point.
timeFrame: Baseline up to week 32
measure: Anti-drug antibodies (ADAs) and neutralizing antibodies (Nabs).
timeFrame: Baseline up to week 32
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
Study officials:
References: