AD17002 Treating Poorly Controlled, Moderate to Severe Eosinophilic Asthma

Eosinophilic Asthma Clinical Trial

Official title:

A Single-blind (Patient-blind), Randomized, Placebo-controlled, Intranasal Administration Study on Mechanisms and Potential Efficacy of AD17002 in Subjects With Poorly Controlled, Moderate to Severe Eosinophilic Asthma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05985694
• Other study ID #: ADV_Asthma_17002-1
• Status: Recruiting
• Phase: Phase 2
• Start date: November 27, 2023
• Est. completion date: September 27, 2024

Study information

• Verified date: July 2023
• Source: Advagene Biopharma Co. Ltd.
• Contact: Mingi Chang, Ph.D.
• Phone: +886-2-7970073
• Email: mingi.chang[@]advagene.com.tw
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This clinical trial aims to investigate patients with poorly controlled, moderate to severe eosinophilic asthma. The main questions it aims to answer are

1. Could the LTh(αK) intranasal treatment improve the clinical condition of these patients?

2. Could patients self-administrate LTh(αK) via the intranasal route?

3. Is the LTh(αK) at multiple doses safe for asthmatic patients?

4. Participants will be asked to self-administrate two doses per week for a total of 6 weeks (11 doses). A diary on LTh(αK) usage, adverse events, and reliever medication will be recorded.

Description:

Eosinophilic asthma is recognized as a sub-phenotype of asthma based on the pattern of inflammatory cellular infiltration in the airway. Eosinophilic asthma can be associated with increased asthma severity, atopy, late-onset disease, and steroid refractoriness. Induced sputum cell count is the standard for identifying eosinophilic inflammation in asthma and fractional exhaled nitric oxide (FeNO) and serum periostin are emerging as potential surrogates.

The Type I and III interferons (IFNs) can negatively regulate the allergic reaction, and their production from mucosal epithelium is reported to be lower in patients with asthma. The investigational intranasal pharmaceutical product named AD17002 contains a detoxified Escherichia coli heat-labile enterotoxin, LTh(αK). Studies have shown that AD17002 enhanced the production of Type I and III IFNs from mucosal epithelial cells. Studies also supported that AD17002 attenuates allergic reactions.

The safety and tolerability of LTh(αK) have been demonstrated in several clinical trials as an intranasal adjuvant for influenza vaccine (NCT03293732 and NCT03784885) or an intranasal immunomodulator for respiratory hypersensitivity (NCT04088721) and viral infection (NCT05069610 and NCT05541510).

This study is conducted to determine the potential efficacy and mechanism of LTh(αK) as an immunomodulator in attenuating the severity of clinical manifestations in patients with unstable, moderate to severe eosinophilic asthma. Patients with clinical history and ongoing eosinophilic asthma will be randomly assigned to either AD17002 (10 μg or 20 μg) or placebo, per 3-4 days, in a 1:1 ratio, in a single-blinded (patient-blinded) fashion. The nasal administration will be self-administrated by participants. Progression and improvement in asthmatic symptoms will be recorded. All study subjects will sign ethics committee-approved informed consent forms before participating in any trial-related activities. Subjects who participate in this trial of AD17002 will provide information about the dosing, efficacy, and safety of the new indication that will guide its future clinical use.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: September 27, 2024
• Est. primary completion date: June 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Subject 20-80 years of age on the day of signing informed consent

2. Subject who is not a current smoker with poorly controlled, moderate to severe eosinophilic asthma based on GINA 2022 criteria.

3. The subject is diagnosed with asthma.

4. Subjects who have the post-bronchodilator reversibility of Forced expiratory volume 1 (FEV1) of = 12% and = 200 mL in response to a SABA at the screening visit or documented in the medical chart within 3 months of the screening visit.

5. Subjects who have =3% eosinophil counts in the induced sputum within 7 days of Visit 1.

6. Subjects with ACT scores = 19 under regular low to moderate-dose inhaled corticosteroids (ICS) and/or a combination with inhaled long-acting beta 2 agonists for at least 3 months before the Screening Visit.

7. Have a negative serum pregnancy test at the screening, and randomization visits (female subjects of childbearing potential). A female subject who is of reproductive potential agrees to remain abstinent or use (or have their partner use) an acceptable method of birth control within the projected duration of the trial. Acceptable birth control methods are intrauterine devices, hormonal contraception, diaphragm with spermicide, contraceptive sponge, condoms, and vasectomy, as per local regulations or guidelines.

8. A female subject who is not of reproductive potential is eligible without requiring the use of contraception. A female subject who is not of reproductive potential is defined as one who has either

9. Reached natural menopause (defined as 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone levels in the postmenopausal range as determined by the laboratory, or 12 months of spontaneous amenorrhea),

10. Six weeks postsurgical documented total hysterectomy and/or bilateral salpingo-oophorectomy, or

11. Bilateral tubal ligation.

12. Subject or the subject's legal representative understands the trial procedures, alternative treatments available, and risks involved with the trial, and voluntarily agrees to participate by giving written informed consent.

13. Provide written informed consent for the trial and be willing to adhere to dose and visit schedules.

Exclusion Criteria:

1. Subjects with serious underlying chronic illness or severe systemic disease, including SLE, malignant diseases, uremia and heart failure, or abnormal liver function.

2. Subjects without a recent respiratory tract infection within 3 weeks before the study.

3. Subjects without a recent COVID-19 infection within 1 month before study.

4. Subjects with clinically important lung disease, including but not limited to COPD (Chronic Obstructive Pulmonary Disease), chronic respiratory infection, lung cancer, etc.

5. Arrhythmia, myocardial infarction, or stroke in the last 3 months.

6. Active COVID-19 disease (SARS-CoV-2 Lateral flow tests (LFA)-positive) at Screening.

7. A clinical history of persistent allergic asthma or rhinitis caused by an allergen to which the subject is regularly exposed and sensitized.

8. A clinical history of active chronic sinusitis (> 3 months).

9. Any clinically relevant chronic disease (>=3 months duration) (e.g. cystic fibrosis, malignancy, renal or hepatic insufficiency).

10. Subject with a documented history of Bell's palsy.

11. The subject has any nasal condition that could confound the efficacy or safety assessments.

12. Immunosuppressive treatment (ATC code L04 or L01) within 3 months before the screening visit (except the specified concomitant medications for allergy and asthma symptoms).

13. Has unstable or severe asthma, as judged by the clinical Investigator, or a subject who has experienced a life-threatening asthma attack or an occurrence of any clinical deterioration of asthma that resulted in emergency treatment, hospitalization due to asthma, or treatment with systemic corticosteroids (but allowing SABA) at any time within the last 3 months before Screening Visit.

14. Has asthma requiring high-dose oral corticosteroid (OCS) within the last 3 months before Screening Visit.

15. Has a history of anaphylaxis with cardiorespiratory symptoms with prior immunotherapy, unknown cause, or inhalant allergen.

16. Is pregnant or expecting to conceive within the projected duration of the trial.

17. Is nursing at randomization and within the projected duration of the trial?

18. Has had previous exposure to the study drug or Flu Vaccine AD07030.

19. The subject is receiving ongoing treatment with any specific immunotherapy at the time of the Screening Visit.

20. Has a known history of allergy, hypersensitivity, or intolerance to investigational medicinal products, rescue medications, or self-injectable epinephrine.

Related Conditions & MeSH terms

• Asthma
• Eosinophilic Asthma
• Pulmonary Eosinophilia

Intervention

Drug:
• AD17002
The investigational intranasal pharmaceutical product named AD17002 contains a detoxified Escherichia coli heat-labile enterotoxin, LTh(aK). Dosing days: 1, 4, 8, 11, 15, 18, 22, 25, 29, 32.
• Placebo
Formulation buffer. Dosing days: 1, 4, 8, 11, 15, 18, 22, 25, 29, 32.

Locations

Country	Name	City	State
Taiwan	Taipei Medical University Hospital	Taipei

Sponsors (2)

Lead Sponsor	Collaborator
Advagene Biopharma Co. Ltd.	Taipei Medical University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	FEV1 improvement	Lung function tests with spirometry	Day 1 to Day 78
Secondary	Change to the use of Short-Acting Beta Agonists (SABA)	The number of use of rescue Short-Acting Beta Agonists	Day 1 to Day 78
Secondary	Fractional exhaled nitric oxide (FeNO) change	Change to the FeNO levels	Day 1 to Day 78
Secondary	Sputum eosinophil change	Change to the induced sputum eosinophils' count	Day 1 to Day 78
Secondary	Asthma Control Test (ACT) scores improvement	Change to the ACT scores. A maximum score of 25 points indicates complete asthma control. A score between 20 and 25 represents well controlled asthma, while a score of 19 or below represents not well controlled asthma, and a score less than 16 indicates very poorly controlled asthma.	Day 1 to Day 78
Secondary	Corticosteroid used to control asthma	Numbers of corticosteroid used, inhaled or oral	Day 1 to Day 78
Secondary	Immunological biomarkers of sputum	Changes in the concentration of sputum IL-4, -5, -13, IFN-a, eosinophil peroxidase (EPO), eosinophil cationic protein (ECP) from the baseline	Day 1 to Day 78
Secondary	Immunological biomarkers of serum	Change of concentration from baseline of induced serum IL-4, -5, -13	Day 1 to Day 78
Secondary	Peripheral eosinophil count	Change of cell numbers from baseline of peripheral eosinophil count	Day 1 to Day 78
Secondary	Adverse events_clinical visit	Clinical visit and check up by physicians	Day 1 to Day 36 and Day 78
Secondary	Adverse events-Diary	Patient self report adverse events via diary	Day 1 to Day 78