A Phase Ib Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Preliminary Efficacy of RC1416 Injection in Patients With Moderate to Severe Asthma
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Nanjing RegeneCore Biotech Co., Ltd.
- Enrollment
- 40
- Locations
- 18
- Primary Endpoint
- AE
Overview
Brief Summary
This is a Phase Ib study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and preliminary efficacy of RC1416 injection in patients with moderate to severe asthma.
Detailed Description
This study is a randomized, double-blind, placebo-controlled, ascending dose Phase Ib clinical study. RC1416 is a bispecific antibodies .It is being developed by Nanjing RegeneCore Biotech Co., Ltd. as a potential therapy for asthma. A total 40 patients with moderate to severe asthma will be enrolled in 4 groups to access the safety, tolerability, PK, PD, immunogenicity and preliminary efficacy of RC1416 injection.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •The subject fully understands the purpose, nature, methods and potential adverse events of the trial and voluntarily signs the informed consent form (ICF);
- •Male or female patients aged ≥18 and ≤75 years at the time of ICF signing;
- •The subject has been diagnosed with asthma for at least one year;
- •The subject has been treated with medium to high-dose inhaled corticosteroids (ICS) (e.g.,fluticasone propionate ≥ 250 μg daily or equivalent ICS dose) in combination with at least one additional controller medication \[such as long-acting β2 receptor agonists (LABA), long-acting anticholinergic drugs (LAMA), leukotriene receptor antagonists (LTRA), or sustained-release theophylline\] for ≥ 3 months prior to ICF signing, with a stable dosing for ≥ 1 month before randomization;
- •ACQ-6 score \> 1.5 or ACT score \< 20 ;
- •Pre-bronchodilator FEV1 ≤ 80% of predicted value at screening;
- •Positive objective tests for variable airflow obstruction within one year before randomization or during the screening period (including bronchodilation test, bronchial provocation test or peak expiratory flow variability, etc.).
- •The subject agrees to take effective contraceptive measures (as specified in the protocol) from the time of ICF signing until 6 months post-treatment.
Exclusion Criteria
- •Based on the investigator's judgment,Clinically diagnosed with chronic obstructive pulmonary disease (COPD) or other lung diseases that may significantly impair lung function (such as atelectasis, pulmonary fibrosis, bronchopulmonary dysplasia, bronchiectasis, emphysema, etc.) ;
- •Subjects who had required at least one systemic glucocorticoid treatment due to asthma exacerbation or other reasons, or who had been hospitalized or treated emergency department due to asthma exacerbation within one month before administration;
- •Subjects with a history of near-fatal asthma requiring endotracheal intubation and mechanical ventilation;
- •Subjects who are Excessive dependence on short-acting β-agonists (SABA) (\>10-12 puffs per day) , especially use more than one vial of salbutamol (or equivalent) per month;
- •Subjects who used non-selective β-blockers within 1 month before screening until randomization;
- •Subjects with pulmonary or other infection and oral or intravenous antibiotics or antifungal or antiviral drugs within one month before administration; Subjects have need local antibiotic or antiviral treatment within 7 days before screening;Subjects with a history of recurrent infections (≥3 times per year) and underlying diseases that predispose to infection; Subjects with a history of disseminated herpes simplex infection or recurrent (\>1 time) or disseminated herpes zoster; Subjects with a history of opportunistic infections;
- •Subjects who underwent major surgery within 6 months prior to screening or planned major surgery during the trial.
- •Subjects who have suffered form malignancy within 5 years,except:
- •Subjects with cervical carcinoma in situ that has been completely resected and has no evidence of recurrence or metastasis for at least 3 years;
- •Subjects with basal cell or squamous cell carcinoma that have been completely resected and have no recurrence for at least 3 years;
Arms & Interventions
RC1416
Intervention: RC1416 (Drug)
Placebo
Intervention: RC1416 Placebo (Drug)
Outcomes
Primary Outcomes
AE
Time Frame: up to 141 days
incidence ,severity and relation to investigational drugs of Adverse Events according to CTCAE V5.0
SAE
Time Frame: up to 141 days
incidence ,severity and relation to investigational drugs of Adverse Events according to CTCAE V5.0
Vital Signs
Time Frame: up to 141 days
number of praticipants with clinically notable Vital Signs according to CTCAE V5.0
Laboratory Tests
Time Frame: up to 141 days
number of praticipants with clinically Laboratory Tests Values according to CTCAE V5.0
ECG
Time Frame: up to 141 days
number of praticipants with clinically notable Electrocardiogram(ECG) Values according to CTCAE V5.0
Injection Site Reaction
Time Frame: up to 85 days
number of praticipants with clinically notable Injection Site Reaction according to CTCAE V5.0
Secondary Outcomes
- t1/2(up to 141 days)
- MRT(up to 141 days)
- λz(up to 141 days)
- CL/F(up to 141 days)
- Cmax(up to 141 days)
- AUC0-t(up to 141 days)
- AUC0-inf(up to 141 days)
- Anti-Drug antibody (ADA)(up to 141 days)
- Tmax(up to 141 days)
- Vz/F(up to 141 days)
- Change from baseline in fractional exhaled nitric oxide (FeNO)(up to 141 days)
- Change from baseline in total IgE (immunoglobulin E), human thymus and activation-regulated chemokine (TARC)(up to 141 days)
- Change from baseline in blood eosinophil (EOS) count, free or bound IL-5 and total IL-5, and free IL-4 and IL-13 levels(up to 141 days)