Evaluate the Efficacy and Safety of FB704A in Adult With Severe Asthma
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Approximately 40 subjects who meet the criteria for study entry are planned to be enrolled to the study. Eligible subjects will be randomized to receive placebo or FB704A in a 1:1 ratio. There are 20 subjects participate in each arm.
Eligibility will be checked in patients with severe asthma during the 4-week screening period. Potential candidates should provide signed informed consent forms before starting the screening activities. The subjects will receive four dose of 4 mg/kg FB704A or placebo. The study drug will be administered as a 1-hour IV infusion.
Patients may administer albuterol as rescue medications as needed throughout the study.
Subjects will have site visits after receiving study drug for efficacy, safety, PK, and biomarker evaluation (see Study Flow Chart). Subjects who prematurely withdraw from the study will have an end of study (EOS) visit within 7 days.
Relative change in pre-bronchodilator FEV 1 , post-bronchodilator FEV 1, exhaled NO and asthma symptom s will be evaluated during the study.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: FB704A placebo placebo |
Biological: FB704A placebo
lacebo
|
| Experimental: FB704A Anti-IL6 antibody |
Biological: FB704A
Anti-IL-6 antibody
|
Outcome Measures
Primary Outcome Measures
- Proportion of the number of Adverse Event reported during the treatment period [week 8]
AE
Secondary Outcome Measures
- Change from baseline in blood neutrophil counts [week 4, 8, 12, 16, and 20]
neutrophil counts
- Change from baseline in sputum neutrophil counts [week 8]
neutrophil counts
- ACT score [week 4, 8, 12, and 20]
The ACT Score > 19 means well controlled.
- Change from baseline in Asthma control test (ACT) [week 4, 8, 12, and 20]
The ACT Score > 19 means well controlled.
- Percentage of patients achieving decrease in score by greater than or equal to 0.5 points on the ACQ 5 (with a minimal importance difference improvement) [week 4, 8, 12, and 20]
The Asthma symptom score and 5 item Asthma Control Questionnaire (ACQ 5) will be applied to evaluate the condition of asthma control. Subjects will perform the test.
- Change from baseline in ACQ-5 [week 4, 8, 12, and 20]
The Asthma symptom score and 5 item Asthma Control Questionnaire (ACQ 5) will be applied to evaluate the condition of asthma control. Subjects will perform the test.
- Change from baseline in AQLQ [week 4, 8, 12, and 20]
Standardized Asthma Quality of Life Questionnaire (AQLQ) will be applied to evaluate the asthma specific quality of life.
- Change from baseline in pre-bronchodilator FEV1 , post-bronchodilator FEV1, exhaled NO and asthma symptoms [week 8 and 20]
Forced expiratory volume in 1 second (FEV1) is the volume exhaled during the first second of a forced expiratory maneuver started from the level of total lung capacity. Spirometry testing must be performed in the morning between 6 11 am according to the schedule of study procedures. After the first screening spirometry completed, the
- Proportion of the number of AE reporting (incidence of adverse event) [during the study (8 weeks treatment period and 12 weeks follow up]
AE
Other Outcome Measures
- Change in IL-6 [during the study (8 weeks treatment period and 12 weeks follow up]
IL-6
Eligibility Criteria
Criteria
Inclusion Criteria:
-
18 to 70 years of age, either sex, any race.
-
Diagnosed as severe asthma based on 2020GINA guideline.
-
An ACT score is <20.
-
Induced sputum neutrophil count 50% of total sputum cells at Screening.
-
Documented diagnosis of severe asthma (within past 5 years), and have at least one of the following: 12% and 200 mL improvement in Forced Expiratory Volume in 1 second (FEV1) post bro nchodilator, and/or airway hyperresponsiveness (eg, positive methacholine challenge <8 mg/mL).
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Nonsmoker or previous smoker with cumulative smoking history less than 10 pack years (pack year = 2 0 cigarettes smoked daily for 1 year). Previous smokers may no t 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.
-
Must not have had an 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.
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Must be willing to give written informed consent to participate in the study
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Must be capable of complying with the dosing regimen, adhere to the visit schedule, and participate in all treatment procedures, including sputum induction.
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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 re cord 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:
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Chronic Obstructive Pulmonary Disease (COPD)/other relevant lung disease (other than asthma)
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4 weeks prior to/or Screening: upper/lower respiratory tract infection
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Screening: Inadequate amount or difficulty producing sputum
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Screening: Sputum neut rophil count over 10 million/mL
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Screening: peripheral blood neutrophil (PBN) count <3000/µL
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Post bronchodilator FEV1 <1L
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Clinically significant chronic infectious disease(s) (eg, Human Immunodeficiency Virus [HIV], hepatitis B or C)
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Allergy/sensitivity to study drug/excipients
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Breast feeding, pregnant/intends to become pregnant during study
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Requiring mechanical ventilation for respiratory eve nt within 6 months of Screening
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Medical condition(s) (eg, hema tologic, cardiovascular, renal, hepatic, neurologic, or metabolic) or medication that may interfere with effect of study medication
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Within 30 days of Screening: any other investigational drug
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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
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Active infection, including opportunistic infections, requiring systemic therapy within the past 2 weeks
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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)
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History of diverticulitis, diverticulosis requiring antibiotic treatment, or other symptomatic lower gastrointestinal (GI) conditions that might predispose to perforations
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Immunization with a live/attenuated vaccine within 4 weeks prior to treatment
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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)
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Liver enzymes: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 3x upper limit of normal
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Serum bilirubin > 2x upper limit of normal
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Low platelet count (<100,000/mm3)
-
Dyslipidemia
-
Participation in any other clinical study
-
Part of the staff personnel involved with the study
-
Family member of investigational study staff
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | China Medical University Hospital | Taichung city | Taiwan | ||
| 2 | Ministry of Health and Welfare Shuang-Ho Hospital | Taipei | Taiwan | ||
| 3 | Taipei Medical University Hospital | Taipei | Taiwan | ||
| 4 | Taipei Municipal Wanfang Hospital | Taipei | Taiwan | ||
| 5 | Taipei Veterans General Hospital | Taipei | Taiwan |
Sponsors and Collaborators
- Oneness Biotech Co., Ltd.
Investigators
- Principal Investigator: NienYi Chen, PhD, Oneness Biotech
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- FB704ACLIS-02