Clinical trial NCT06488755: SIM0718 Treatment of Asthma Clinical Study
Official title: A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Phase III Clinical Study Evaluating the Efficacy and Safety of SIM0718 in Adults and Adolescents With Asthma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Asthma; Eosinophilic
Lead sponsor: Simcere Pharmaceutical Co., Ltd
Sponsor class: OTHER
First posted: 2024-07-05
Enrollment: 418
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Phase III clinical study of SIM0718 asthma

Detailed description: A multicenter, randomized, double-blind, parallel-group, placebo-controlled phase III clinical study evaluating the efficacy and safety of SIM0718 in adults and adolescents with asthma

Eligibility criteria: Inclusion Criteria:

* Age 12 to 75 years, weight ≥ 40 kg, diagnosed with asthma for at least 12 months；
* Currently receiving medium- to high-dose inhaled corticosteroids (ICS) in combination with 1 or 2 control medications and have been on a stable dose for at least 28 days prior to randomization；
* Pre-bronchodilator (trough) FEV1 ≤ 80% of predicted normal for adults and ≤90% of predicted normal for adolescents ；
* Positive bronchodilator response within 12 months prior to randomization or during the screening period;
* Asthma Control Questionnaire (ACQ-5) score ≥ 1.5;
* At least one severe asthma exacerbation within 12 months prior to the screening visit and no occurrence within 28 days prior to randomization;
* Based on the investigator judgment, the subject demonstrates acceptable inhaler, peak flow meter, and spirometry techniques;
* Compliance with usual asthma controller use ≥ 80% based on the patient diary in 7 days prior to dosing;
* Voluntarily participate in this clinical study and sign the informed consent form and be able to comply with the clinical visit schedule and study-related procedures;
* Female subjects of childbearing potential who are sexually active with non-sterilized male partners, male subjects, and their female partners of childbearing potential agree to use adequate and effective contraception throughout the study;

Exclusion Criteria:

* Current respiratory disease that may impair lung function as judged by the investigator;
* Diagnosis of helminth parasitic infection within 24 weeks prior to randomization and who have not received or have not responded to standard therapy;
* Within 28 days prior to randomization, with acute or chronic infection; or have a severe viral infection;
* Has a known or suspected history of immunosuppression or frequent, recurrent, or long-term infection;
* History of active tuberculosis; or untreated latent tuberculosis or tuberculosis not receiving standard treatment, unless the investigator judges that the patient has been adequately treated;
* People with hepatitis B, hepatitis C, or HIV infection;
* History of malignancy;
* Major surgery within 8 weeks prior to signing the informed;
* Bronchial thermoplasty within 12 months prior to randomization;
* Treatment of systemic glucocorticoid during 4 weeks prior to signing informed to randomization;
* Previous use or ongoing use of systemic immunosuppressants or biologics for the treatment of autoimmune or inflammatory diseases in 8 weeks or 5 half-lives prior to randomization;
* Within 16 weeks or 5 half-lives prior to randomization, received a biologic agent with the same therapeutic purpose;
* Participated in an interventional clinical trial of any drug or medical device within 3 months or 5 half-lives prior to randomization;
* Poor response to or intolerance to prior anti-IL-4Rα antibody therapy;
* Within 3 months prior to randomization, received specific immunotherapy；
* Receipt of intravenous human immunoglobulin (IVIG) or blood products within 30 days prior to randomization;
* Vaccination with live(attenuated) vaccine within 30 days prior to randomization or plan to receive live (attenuated) vaccine during the study;
* Are using concomitant medications or treatments that are prohibited in the protocol;
* The following laboratory abnormalities occurred during the screening period: eosinophils≥1500 cells/mm3 or 1.5×109/L; Platelets≤80,000 cells/mm3 or 80×109/L; phosphocreatine kinase (CPK) ≥5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) ≥3-fold ULN; aspartate aminotransferase (AST)≥ 3-fold ULN; Bilirubin ≥ 2x ULN;
* History of alcohol abuse or drug abuse within 12 months prior to randomization;
* Current smokers, or those who have been smoking in recent 6 months, or former smokers who have not been smoking for 6 months with a smoking history of ≥10 pack years;
* Allergy to L-histidine, trehalose, or Tween 80, or history of systemic hypersensitivity to any biologic products;
* Females of childbearing potential have a positive pregnancy test result during the screening period; Females planning to become pregnant or breastfeeding;
* Any clinically significant examination abnormality or serious and/or uncontrolled disease that, in the opinion of the investigator, may affect the subject safety, or affect the evaluation of efficacy, or preclude the subject completion of the entire study.

Primary outcomes:
measure: Annualized rate of severe asthma exacerbation events
timeFrame: 52 weeks
Secondary outcomes:
measure: Change from baseline in forced expiratory volume in the first second before bronchodilator use
timeFrame: 12 weeks
measure: Change from baseline in Forced Vital Capacity (FVC)
timeFrame: During the 52-week treatment period
measure: Change from baseline in pre-bronchodilator forced expiratory volume in 1 second
timeFrame: During the 52-week treatment period
measure: Change from baseline in Peak Expiratory Flow (PEF)
timeFrame: During the 52-week treatment period
measure: Time from baseline to the first severe asthma exacerbation event, proportion of subjects with ≥ 1 severe asthma exacerbation
timeFrame: During the 52-week treatment period
measure: Annualized rate of "loss of asthma control" events, time from baseline to "loss of asthma control"event
timeFrame: During the 52-week treatment period
measure: Change from baseline in annualized rate of hospitalization or emergency department visits, utilization of medical resources
timeFrame: During the 52-week treatment period
measure: Change from baseline in ASTHMA CONTROL QUESTIONNAIRE(ACQ-5) score
timeFrame: During the 52-week treatment period
measure: Asthma symptom score
timeFrame: During the 52-week treatment period
measure: Use of rescue medication
timeFrame: During the 52-week treatment period
measure: Number of days of awakenings due to asthma and number of awakenings due to asthma
timeFrame: During the 52-week treatment period
measure: Change from baseline in standardized asthma quality of life questionnaire score ASTHMA QUALITY OF LIFE QUESTIONNAIRES(AQLQ(S))
timeFrame: During the 52-week treatment period
measure: Adverse events
timeFrame: during the 64 week study period
measure: Vital signs
timeFrame: during the 64 week study period
measure: Electrocardiograph (12-ECG)
timeFrame: during the 64 week study period
measure: Laboratory tests
timeFrame: during the 64 week study period
measure: SIM0718 blood concentration
timeFrame: During the 52-week treatment period
measure: Positive rate and titer of anti-drug antibodies, positive rate of neutralizing antibodies
timeFrame: 64 weeks during the study
Other outcomes:
Locations:
city: Beijing
country: China
facility: China Japan Friendship Hospital
state: Beijing
Study officials:
affiliation: Simcere Pharmaceutical Co., Ltd
name: L I hong zhuang
role: STUDY_DIRECTOR
References: