A Dose Ranging Placebo-controlled Double-blind Study to Evaluate the Safety, Pharmacokinetics and Efficacy of 610 in Participants With Severe Eosinophilic Asthma

Asthma Clinical Trial

Official title:

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase Ib Study to Determine the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Recombinant Anti-IL-5 Humanized Monoclonal Antibody Therapy in Adult Subjects With Severe Eosinophilic Asthma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05584306
• Other study ID #: SSGJ-610-BA-I/II-01
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: December 6, 2021
• Est. completion date: September 2023

Study information

• Verified date: October 2022
• Source: Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will assess the safety, tolerability, pharmacokinetics and preliminary efficacy of 610 as an adjunctive therapy in adult subjects with severe eosinophilic asthma.

Description:

This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of 610 in adults with severe eosinophilic asthma. Plan to recruit 24 subjects, and the subjects divided into 3 groups: 610 30mg group，100mg group, 610 300mg group，8 subjects in each dose group, of which 6 received the trial drug and 2 received placebo. The study is divided into screening period of 2 weeks, treatment period of 32 weeks and follow-up period of 12 weeks.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 24
• Est. completion date: September 2023
• Est. primary completion date: September 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosed with asthma for =12 months

• Within 3 months before screening, treatment with medium to high dose inhaled corticosteroid(ICS,inhaled fluticasone at a dosage of at least 500 µg, or equivalent, daily.)and at least one other additional controller medication, such as long-acting ß2 receptor agonist (LABA), leukotriene receptor antagonist (LTRA), theophylline, long-acting Anticholinergic drugs (LAMA), etc. Those medicine must be stable for = 28 days prior to screening and baseline and must continue without dosage changes throughout the study

• In the past 12 months prior to screening, at least one time asthma exacerbations history

• Pre-bronchodilator FEV1 <80% predicted value

• Asthma-related blood eosinophils = 150 cells/µL within 3 months before administration

Exclusion Criteria:

• With clinically important lung diseases other than asthma that may affect safety or efficacy and evaluated by investigator. This includes lung infection, chronic obstructive pulmonary disease, bronchiectasis, hypersensitivity pneumonitis, pulmonary fibrosis, Allergic bronchopulmonary aspergillosis, etc.

• With other conditions that could lead to elevated eosinophils such as hypereosinophilic syndromes, eosinophilic granulomatosis with polyangiitis (EGPA), or eosinophilic esophagitis

• In past 12 months prior to screening,patients has done bronchial thermoplasty or radiotherapy or plan to do it during of the trial

• with severe cardiac disease or uncontrolled or severe cardiac arrhythmia

• poorly controlled systemic disease

• Active infection 7 day before screening

• Parasitic infection within 6 months before screening

• At screening, HBsAg or HCV Ab or HIV Ab or TP Ab positive; HBsAg or HCV Ab positive need to be further tested of HBV DNA titer detection or HCV RNA detection (More than normal value range needs to be excluded)

• Subjects who have received any monoclonal antibody treatment of anti IL-4Ror anti-IL-5/5R

• Vaccination history with live vaccines (including live attenuated vaccines) within 4 weeks before screening, or plan to receive during of the trial

• Participated in any interventional clinical trial and received intervention within 3 months before screening

Related Conditions & MeSH terms

• Asthma
• Pulmonary Eosinophilia

Intervention

Drug:
• 610 30mg group
610 30mg subcutaneous (SC) Q4W,8 times
• 610 100mg group
610 100mg subcutaneous (SC) Q4W,8 times
• 610 300mg group
610 300mg subcutaneous (SC) Q4W,8 times

Other:
• Placebo 30mg group
placebo subcutaneous (SC) Q4W,8 times
• Placebo 100mg group
placebo subcutaneous (SC) Q4W,8 times
• Placebo 300mg group
placebo subcutaneous (SC) Q4W,8 times

Locations

Country	Name	City	State
China	Shanghai General Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events(AEs)	The incidence and severity of AEs, including SAEs, as well as clinical symptoms, and any abnormalities of vital signs, physical examinations#electrocardiogram#laboratory tests and, etc.	From Day 0 to Day 308
Secondary	Pharmacokinetics-Tmax	Time to Cmax of 610	From Day 0 to Day 308
Secondary	Pharmacokinetics-AUC0-last	Area under the concentration-time curve from time 0 to last time point after 610 subcutaneous	From Day 0 to Day 308
Secondary	Pharmacokinetics-AUC0-inf	Area under the concentration-time curve from time 0 to infinity after 610 subcutaneous	From Day 0 to Day 308
Secondary	Pharmacokinetics-Cmax	Maximum observed concentration of 610	From Day 0 to Day 308
Secondary	Pharmacokinetics-CL/F	Apparent clearance of 610	From Day 0 to Day 308
Secondary	Pharmacokinetics-Vz/F	Apparent volume of distribution during terminal phase of 610	From Day 0 to Day 308
Secondary	Pharmacokinetics-t1/2	Terminal elimination half-life of 610	From Day 0 to Day 308
Secondary	Pharmacodynamics-Eosinophils	Absolute eosinophils account and change from baseline in percentage	From Day 0 to Day 308
Secondary	Anti-drug-antibody	The percentage of subjects with positive ADA titers over time for 610	From Day 0 to Day 308
Secondary	Number of asthma exacerbation	Asthma exacerbation are defined as worsening of asthma which required use of systemic corticosteroids (=3 days. For maintenance of systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization and/or emergency department (ED) visits.	From Day 0 to Day 308
Secondary	Changes from baseline in pre-bronchodilator forced expiratory volume in one second (FEV1)	FEV1 is defined as the volume of air expelled from the lungs in 1 second. Pre-bronchodilator FEV1 measurements were taken by spirometry.	From Day 0 to Day 308
Secondary	Percentage change from baseline in pre-bronchodilator forced expiratory volume in one second (FEV1)	Percentage of FEV1 will be measured using spirometry.	From Day 0 to Day 308
Secondary	Time to first asthma exacerbation event	Asthma exacerbation are defined as worsening of asthma which required use of systemic corticosteroids (=3 days. For maintenance of systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization and/or emergency department (ED) visits.	From Day 0 to Day 308
Secondary	Number of asthma exacerbations requiring hospitalization (including intubation and ICU admission) or emergency room visits (not conversion to hospitalization)	Asthma exacerbations that are associated with a hospitalization or an emergency room visit.	From Day 0 to Day 308
Secondary	Number of asthma exacerbations requiring hospitalization (including intubation and ICU admission)	Asthma exacerbations that are associated with a hospitalization.	From Day 0 to Day 308
Secondary	Change from baseline in Asthma Control Questionnaire score	The ACQ has 7 questions- the first 5 items assess the most common asthma symptoms plus 6. short-acting bronchodilator use and 7. FEV1 (pre-bronchodilator use, % and % predicted use). Patients are asked to recall how their asthma has been during the previous week and to respond to the symptom questions on a 7-point scale (0=no impairment, 6= maximum impairment).	From Day 0 to Day 308
Secondary	Change From Baseline in the St. George's Respiratory Questionnaire Total Score	The St. George's Respiratory Questionnaire is an established instrument, comprising 50 questions, evaluating symptoms, activity, and impacts; to measure Quality of Life in participants with diseases of airway obstruction and to elicit the participant's opinion of his/her health.	From Day 0 to Day 308