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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Asthma
• Intervention / Treatment: Drug: 610 30mg group; Drug: 610 100mg group; Drug: 610 300mg group; Other: Placebo 30mg group; Other: Placebo 100mg group; Other: Placebo 300mg group

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200080
      • Shanghai General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 β₂ 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 610 30mg group; 610 30 mg administered subcutaneously every 4 weeks	Drug: 610 30mg group; 610 30mg subcutaneous (SC) Q4W，8 times
Experimental: 610 100mg group; 610 100 mg administered subcutaneously every 4 weeks	Drug: 610 100mg group; 610 100mg subcutaneous (SC) Q4W，8 times
Experimental: 610 300mg group; 610 300mg administered subcutaneously every 4 weeks	Drug: 610 300mg group; 610 300mg subcutaneous (SC) Q4W，8 times
Placebo Comparator: Placebo 30mg group; placebo subcutaneous (SC) Q4W，8 times	Other: Placebo 30mg group; placebo subcutaneous (SC) Q4W，8 times
Placebo Comparator: Placebo 100mg group; placebo subcutaneous (SC) Q4W，8 times	Other: Placebo 100mg group; placebo subcutaneous (SC) Q4W，8 times
Placebo Comparator: Placebo 300mg group; placebo subcutaneous (SC) Q4W，8 times	Other: Placebo 300mg group; placebo subcutaneous (SC) Q4W，8 times

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics-Tmax	Time to Cmax of 610	From Day 0 to Day 308
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
Pharmacokinetics-AUC0-inf	Area under the concentration-time curve from time 0 to infinity after 610 subcutaneous	From Day 0 to Day 308
Pharmacokinetics-Cmax	Maximum observed concentration of 610	From Day 0 to Day 308
Pharmacokinetics-CL/F	Apparent clearance of 610	From Day 0 to Day 308
Pharmacokinetics-Vz/F	Apparent volume of distribution during terminal phase of 610	From Day 0 to Day 308
Pharmacokinetics-t1/2	Terminal elimination half-life of 610	From Day 0 to Day 308
Pharmacodynamics-Eosinophils	Absolute eosinophils account and change from baseline in percentage	From Day 0 to Day 308
Anti-drug-antibody	The percentage of subjects with positive ADA titers over time for 610	From Day 0 to Day 308
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd.
• Investigators: Study Director: Qinghong Zhou, MD, Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd.; Principal Investigator: Min Zhang, MD, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine; Principal Investigator: Xin Zhou, MD, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2021
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: October 9, 2022
• First Submitted That Met QC Criteria: October 17, 2022
• First Posted (Actual): October 18, 2022

Study Record Updates

• Last Update Posted (Actual): October 18, 2022
• Last Update Submitted That Met QC Criteria: October 17, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Asthma; Exacerbations; Placebo; Eosinophilic asthma; 610
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Leukocyte Disorders; Eosinophilia; Hypereosinophilic Syndrome; Asthma; Pulmonary Eosinophilia
• Other Study ID Numbers: SSGJ-610-BA-I/II-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No