Clinical trial NCT05018299: Evaluate the Efficacy and Safety of FB704A in Adult With Severe Asthma
Official title: A Randomized, Placebo Controlled, Double Blind Phase IIa Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Clinical Activity of Multiple Intravenous Doses of FB704A in Adults With Severe Asthma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Severe Asthma
Keywords: Asthma
Lead sponsor: Oneness Biotech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-08-24
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 Short-acting beta agonists (SABAs), such as 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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of the number of Adverse Event reported during the treatment period
timeFrame: Day 57
Secondary outcomes:
measure: Change from baseline in blood neutrophil counts
timeFrame: Day 36, 57, 85, 113, and 141
measure: Change from baseline in sputum neutrophil counts
timeFrame: Day 57
measure: ACT score
timeFrame: Day 36, 57, 85, and 141
measure: Change from baseline in Asthma control test (ACT)
timeFrame: Day 36, 57, 85, and 141
measure: 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)
timeFrame: week 4, 8, 12, and 20
measure: Change from baseline in ACQ-5
timeFrame: Day 36, 57, 85, and 141
measure: Change from baseline in AQLQ
timeFrame: Day 36, 57, 85, and 141
measure: Change from baseline in pre-bronchodilator FEV1 , post-bronchodilator FEV1, exhaled NO and asthma symptoms
timeFrame: Day 57 and 141
measure: Proportion of the number of AE reporting (incidence of adverse event)
timeFrame: 12 weeks follow up
Other outcomes:
measure: Change in IL-6
timeFrame: during the study (8 weeks treatment period and 12 weeks follow up
Locations:
city: Hsinchu
country: Taiwan
facility: NTUH Hsin-Chu Branch
city: Taichung city
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: Ministry of Health and Welfare Shuang-Ho Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University Hospital
city: Taipei
country: Taiwan
facility: Taipei Municipal Wanfang Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Oneness Biotech
name: NienYi Chen, PhD
role: PRINCIPAL_INVESTIGATOR
References: