Evaluate the Efficacy and Safety of FB704A in Adult With Severe Asthma

Prior treatment

• 2.4 weeks prior to/or Screening: upper/lower respiratory tract infection
• 11.Within 30 days of Screening: any other investigational drug
• 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)

Other illness

• 1.Chronic Obstructive Pulmonary Disease (COPD)/other relevant lung disease (other than asthma)
• 6.Clinically significant chronic infectious disease(s) (eg, Human Immunodeficiency Virus \[HIV\], hepatitis B or C)
• 7.Allergy/sensitivity to study drug/excipients
• 10.Medical condition(s) (eg, hematologic, cardiovascular, renal, hepatic, neurologic, or metabolic) or medication that may interfere with effect of study medication
• 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

Lab values

• 4.Screening: Sputum neutrophil count over 10 million/mL
• 5.Screening: peripheral blood neutrophil (PBN) count \<2000/µL
• 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)

Other

• 3.Screening: Inadequate amount or difficulty producing sputum
• 8.Breast-feeding, pregnant/intends to become pregnant during study
• 9.Requiring mechanical ventilation for respiratory event within 6 months of Screening
• 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.

• 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. Additionally, subjects must have at least one of the following: a) ≧12% and/or 200 mL improvement in Forced Expiratory Volume in 1 second (FEV1) post-bronchodilator, OR b) airway hyperresponsiveness (e.g., positive methacholine challenge \<8 mg/mL), OR c) within the past 24 months, airway variability with a ≧12% and 200 mL change in FEV1 between clinic visits outside of respiratory infections, documented prior to Visit 1, OR d) within the past 24 months, average daily PEF variability \> 10% over a 2-week period, documented prior to Visit 1.
• 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.