Overview

This is a randomized, placebo controlled and double blind study to evaluate the safety, tolerability, pharmacokinetics, and clinical activity of FB704A in adult patients with severe asthma. The study comprised a 4-week screening period, a 8-week treatment period and a 12-week follow-up period.

Eligibility

Inclusion Criteria:

1.18 to ≦75 years of age, either sex, any race.

2.Diagnosed as severe asthma based on 2020 GINA guideline.

3.An ACT score is <20.

4.Induced sputum neutrophil count ≧50% of total sputum cells during Screening.

        5.Documented diagnosis of severe asthma (within past 5 years), and have at least one of the
        following:≧12% and/or 200 mL improvement in Forced Expiratory Volume in 1 second (FEV1)
        post-bronchodilator, and/or airway hyperresponsiveness (eg, positive methacholine challenge
        <8 mg/mL).
        6.Nonsmoker or previous smoker with cumulative smoking history less than 10 pack-years
        (pack-year = 20 cigarettes smoked daily for 1 year). Previous smokers may not have smoked
        within 1 year prior to Screening. A smoker is defined as a subject who has taken inhaled
        nicotine containing products (e.g. cigarette, cigar, pipe), including e-cigarettes prior to
        screening.
        7.Must not have had a severe asthma exacerbation of asthma for 4 weeks prior to Screening
        and must be on a stable medication regimen for asthma at least 4 weeks prior to Screening.
        A Severe asthma exacerbation is defined as a deterioration of asthma leading to treatment
        for 3 days or more with systemic glucocorticoids or hospitalization or an emergency
        department visit leading to treatment with systemic glucocorticoids.
        8.Must be willing to give written informed consent to participate in the study.
        9.Must be capable of complying with the dosing regimen, adhere to the visit schedule, and
        participate in all treatment procedures, including sputum induction.
        10.Female subject of childbearing potential must have a negative serum pregnancy test at
        Screening and must be using a medically acceptable, highly effective, adequate form of
        birth control (ie, failure rate <1% per year when used consistently and correctly) prior to
        Screening and agree to continue using it while in the study (Screening and Treatment
        Periods). Medically acceptable, highly effective forms of birth control are hormonal
        implants, oral contraceptives, medically acceptable prescribed intrauterine devices (IUDs),
        and monogamous relationship with a male partner who has had a vasectomy. Female subject who
        is not of childbearing potential must have a medical record of being surgically sterile
        (eg, hysterectomy, tubal ligation), or be at least 1 year postmenopausal. Absence of menses
        for at least 1 year will indicate that a female is postmenopausal. A female subject should
        be encouraged to continue using a highly effective method of birth control for 30 days
        following the end of treatment.
        Male subject must agree to use an adequate form of contraception for the duration of the
        study and agree to have sexual relations only with women who use a highly effective birth
        control method.
        Exclusion Criteria:
        1.Chronic Obstructive Pulmonary Disease (COPD)/other relevant lung disease (other than
        asthma)
        2.4 weeks prior to/or Screening: upper/lower respiratory tract infection
        3.Screening: Inadequate amount or difficulty producing sputum
        4.Screening: Sputum neutrophil count over 10 million/mL
        5.Screening: peripheral blood neutrophil (PBN) count <3000/µL
        6.Clinically significant chronic infectious disease(s) (eg, Human Immunodeficiency Virus
        [HIV], hepatitis B or C)
        7.Allergy/sensitivity to study drug/excipients
        8.Breast-feeding, pregnant/intends to become pregnant during study
        9.Requiring mechanical ventilation for respiratory event within 6 months of Screening
        10.Medical condition(s) (eg, hematologic, cardiovascular, renal, hepatic, neurologic, or
        metabolic) or medication that may interfere with effect of study medication
        11.Within 30 days of Screening: any other investigational drug
        12.Known history of active tuberculosis (TB) or evidence of tuberculosis infection as
        defined by a positive purified protein derivative (PPD) skin test and/or interferon-gamma
        release assay. The interferon-gamma release assay should be repeated in case of an
        indeterminate result
        13.Active infection, including opportunistic infections, requiring systemic therapy within
        the past 2 weeks
        14.A deep space infection within the past 2 years (including, but not limited to
        meningitis, epiglottitis, endocarditis, septic arthritis, fasciitis, abdominal or pleural
        abscess, or osteomyelitis)
        15.History of diverticulitis, diverticulosis requiring antibiotic treatment, or other
        symptomatic lower gastrointestinal (GI) conditions that might predispose to perforations
        16.Immunization with a live/attenuated vaccine within 4 weeks prior to treatment
        17.Evidence of active malignant disease, malignancies diagnosed within the previous 5 years
        (including hematological malignancies and solid tumors, except basal and squamous cell
        carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and
        cured)
        18.Liver enzymes: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 3x
        upper limit of normal
        19.Serum bilirubin > 2x upper limit of normal
        20.Low platelet count (<100,000/mm3)
        21.Dyslipidemia
        22.Participation in any other clinical study
        23.Part of the staff personnel involved with the study
        24.Family member of investigational study staff