Safety and Efficacy Study of PA9159 Nasal Spray for the Treatment of Seasonal Allergic Rhinitis

NCT ID: NCT05234580

Last Updated: 2023-02-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 204 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-15
• Study Completion Date: 2022-12-25

Brief Summary

PA9159 is a highly potent novel corticosteroid. The purpose of this study is to evaluate the safety, efficacy and characteristics of population pharmacokinetics of multiple dosing of PA9159 Nasal Spray in patients with seasonal allergic rhinitis.

Detailed Description

This is a multicenter, randomized, double-blind, parallel, placebo-controlled clinical trial. Subjects of 200 with seasonal allergic rhinitis are planned to be included in this study. With a ratio of 1: 1: 1: 1 to be randomized allocated to receive PA9159 Nasal Spray of 10 μg, 20 μg, and 40 μg, or placebo, with 50 subjects in each group. The duration of this study is approximately 12 months, including screening, baseline, treatment observation, and follow-up.

Conditions

Allergic Rhinitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

PA9159 10 μg

Fifty subjects will be randomly assigned to receive 10 μg of PA9159 Nasal Spray for 14 days. Subjects will be administered two vials of drug (spray bottle A and spray bottle B) once daily in the morning, one spray each in the left and right nostril, in the order of first spray A and then spray B. Spray Bottle A: 5 μg/spray; Spray Bottle B: 0 μg/spray.

Group Type: EXPERIMENTAL

PA9159 nasal spray solution, 10 μg once daily for 14 days

Intervention Type: DRUG

PA9159 of 10 μg is delivered intranasally through a metered-dose mechanical spray pump, once daily in the morning for 14 days.

PA9159 20 μg

Fifty subjects will be randomly assigned to receive 20 μg of PA9159 Nasal Spray for 14 days. Subjects will be administered two vials of drug (spray bottle A and spray bottle B) once daily in the morning, one spray each in the left and right nostril, in the order of first spray A and then spray B. Spray Bottle A: 0 μg/spray; Spray Bottle B: 10 μg/spray.

Group Type: EXPERIMENTAL

PA9159 nasal spray solution, 20 μg once daily for 14 days

Intervention Type: DRUG

PA9159 of 20 μg is delivered intranasally through a metered-dose mechanical spray pump, once daily in the morning for 14 days.

PA9159 40 μg

Fifty subjects will be randomly assigned to receive 40 μg of PA9159 Nasal Spray for 14 days. Subjects will be administered two vials of drug (spray bottle A and spray bottle B) once daily in the morning, one spray each in the left and right nostril, in the order of first spray A and then spray B. Spray Bottle A: 10 μg/spray; Spray Bottle B: 10 μg/spray.

Group Type: EXPERIMENTAL

PA9159 nasal spray solution, 40 μg once daily for 14 days

Intervention Type: DRUG

PA9159 of 40 μg is delivered intranasally through a metered-dose mechanical spray pump, once daily in the morning for 14 days.

Placebo

Fifty subjects will be randomly assigned to receive placebo Nasal Spray without active of PA9159 for 14 days. Subjects will be administered two vials of drug (spray bottle A and spray bottle B) once daily in the morning, one spray each in the left and right nostril, in the order of first spray A and then spray B. Spray Bottle A: 0 μg/spray; Spray Bottle B: 0 μg/spray.

Group Type: PLACEBO_COMPARATOR

Placebo nasal spray solution without PA9159, once daily for 14 days

Intervention Type: DRUG

Placebo nasal spray solution is delivered intranasally through a metered-dose mechanical spray pump, once daily in the morning for 14 days.

Interventions

PA9159 nasal spray solution, 10 μg once daily for 14 days

PA9159 of 10 μg is delivered intranasally through a metered-dose mechanical spray pump, once daily in the morning for 14 days.

Intervention Type: DRUG

PA9159 nasal spray solution, 20 μg once daily for 14 days

PA9159 of 20 μg is delivered intranasally through a metered-dose mechanical spray pump, once daily in the morning for 14 days.

Intervention Type: DRUG

PA9159 nasal spray solution, 40 μg once daily for 14 days

PA9159 of 40 μg is delivered intranasally through a metered-dose mechanical spray pump, once daily in the morning for 14 days.

Intervention Type: DRUG

Placebo nasal spray solution without PA9159, once daily for 14 days

Placebo nasal spray solution is delivered intranasally through a metered-dose mechanical spray pump, once daily in the morning for 14 days.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age ≥ 12 years, male or female;
• Clinical diagnosis is based on the Chinese Guidelines for the Diagnosis and Treatment of Allergic Rhinitis (2018 Edition) issued by the Rhinology Group of the Otorhinolaryngology Head and Neck Surgery Branch of the Chinese Medical Association, with a clear history of Seasonal Allergic Rhinitis (SAR) ≥ 1 year (written or verbal confirmation), and positive test for one or more allergens before randomization. Recognize the results of any one of the skin prick test (SPT), intradermal test, and serum specific IgE test; Clinical manifestations may include:

1. Symptoms: 2 or more symptoms such as sneezing, runny nose, itchy nose and nasal congestion, lasting or accumulating for more than 1 h each day, may be accompanied by ocular symptoms such as itching, lacrimation, and red eyes;

2. Signs: pallor and edema of the nasal mucosa and watery nasal secretions;

3. Allergic symptoms are characterized by seasonal onset in spring and/or fall, and at the time of this enrollment, it is during the onset of symptoms.

• Reflective Total Nasal Symptom Score (rTNSS) ≥ 6 points, nasal congestion ≥ 2 points, and one of the three symptoms of sneezing, runny nose and itchy nose ≥ 2 points, all these three conditions are met simultaneously at the time of screening, baseline and the first dosing during treatment; The mean rTNSS at baseline was the mean of a total of 8 scores on evening of D-4, morning and evening of D-3, D-2 and D-1, and the morning of D1;
• Capable of demonstrating the correct use of nasal spray techniques after training at screening;
• Capable of performing respiratory exercise as required at the time of intranasal administration after training at screening;
• Is willing to sign the informed consent form (ICF), comply with the study procedures, including the correct use of the nasal spray device, and understand and accurately record the patient diary card; Ability to understand and receive treatment, laboratory tests, and other study procedures as planned.

Exclusion Criteria

• Previous intolerance to intranasal administration;
• Patients with asthma requiring long-term treatment (patients with occasional acute asthma, or mild, exercise-induced asthma requiring no medication or only beta-agonist treatment during the study may be included);
• Active or inactive tuberculosis infection, untreated local or systemic fungal, bacterial, viral, or parasitic infection;
• Presence of glaucoma, cataract, ocular herpes simplex, infectious conjunctivitis, or other ocular infections (except allergic conjunctivitis);
• Any nasal mucosal erosion, septal ulceration, or nasal septal perforation at screening or prior to the first dose on D1;Presence of other nasal disorders that may affect intranasal drug deposition as judged by the investigator, such as acute or chronic sinusitis, drug-induced rhinitis, nasal polyps, or nasal septal deviation;
• History with sinus surgery within 3 months or nasal trauma that have not completely healed;
• Respiratory tract infections treated with antibiotics within 4 weeks prior to screening;
• Patients with severe lung diseases, such as COPD (chronic obstructive pulmonary disease), etc.;
• Patients with unstable heart disease with drug-control;
• Patients who have received desensitization therapy within 6 months prior to screening;
• Severe liver and kidney disease, or abnormal liver and kidney function tests (ALT, AST ≥ 2 times the upper limit of normal, or Cr > 1.2 times the upper limit of normal);
• Use of short-lasting prescriptions and OTC antihistamines within 3 days prior to screening; Use of nasal glucocorticoids within four weeks; Inhalation, oral, intramuscular/intravascular injection, topical hormones (except hydrocortisone cream containing ≤ 1%) within 8 weeks prior to screening; Use of nasal or ophthalmic cromoglycic acid within 14 days prior to screening; Use of long-lasting antihistamines such as loratadine, desloratadine, fexofenadine, or cetirizine within 10 days prior to screening; Oral or nasal decongestants, nasal anticholinergics, or oral antileukotrienes within 72 h prior to screening; Use of Omalizumab subcutaneously within 5 months prior to screening; Use of anti-allergic Chinese herbal medicines within 14 days prior to screening.
• Planned use of the following medications or/and treatments during the study: a. Strong CYP3A4 inhibitors, such as ketoconazole, clarithromycin, etc.; b. Chronic or intermittent use of inhaled, oral, intramuscular, intravenous, and/or potent topical corticosteroids; c. Antihistamines (except salvage medications required during the trial); d. Leukotriene modulators; e. Mast cell membrane stabilizers (including cromoglycate sodium, nidolate sodium, tetrazolone, nedocromil sodium, pemirolast potassium, and tranilast, etc.); f. Decongestants; g. Anticholinergics; h. Immunotherapeutic agents; i. Anti-allergic Chinese herbal medicine;
• Planned to travel outside the local area for 2 consecutive days (48 h) or a total of more than 3 days during the trial;
• Alcohol addicts in the previous 1 year (alcoholism defined as: greater than 14 units of alcohol per week;1 unit of alcohol ≈ 360 mL of beer or 45 mL of spirits or 150 mL of wine containing 40% alcohol), drug abusers, drug addicts, or smoking addicts (average of more than 10 cigarettes per day);
• Allergic to the investigational drug and its excipients;
• Pregnant or lactating women, and male subjects (or their partners) or female subjects who have a pregnancy plan throughout the trial and for 3 months after the end of the study;
• Participated in other drug clinical trials within 3 months prior to screening, and used the study drug;
• Based on the judgment of the investigator, the subject may have an impact on compliance with any aspect of the protocol (including visit plan and completion of diary cards or questionnaires) due to physical, educational level, or geographic location;
• Based on the opinion of the investigator, there are any circumstances that may affect the subject's informed consent or compliance with the protocol, or that the subject's participation in the trial may affect the results of the study or their own safety.

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Anhui Palo Alto Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Luo Zhang, phD

Role: PRINCIPAL_INVESTIGATOR

Beijing Tongren Hospital

Locations

The First Affiliated Hospital of Bengbu Medical College

Bengbu, Anhui, China

The Second Hospital of Anhui Medical University

Hefei, Anhui, China

Beijing Shijitan Hospital

Beijing, Beijing Municipality, China

Beijing TongRen Hospital

Beijing, Beijing Municipality, China

Dongfang Hospital Beijing University of Chinese Medicine

Beijing, Beijing Municipality, China

Renmin Hospital of Wuhan University

Wuhan, Hubei, China

Northern Jiangsu People's Hospital

Yangzhou, Jiangsu, China

The Affiliated Hospital of Changchun University of Chinese Medicine

Changchun, Jilin, China

Tonghua Central Hospital

Tonghua, Jilin, China

Yanbian University Hospital(Yanbian Hospital)

Yanji, Jilin, China

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, China

Yantai Yuhuangding Hospital

Yantai, Shandong, China

Zibo Central Hospital

Zibo, Shandong, China

First Hospital of Shanxi Medical University

Taiyuan, Shanxi, China

Second Hospital of Shanxi Medical University

Taiyuan, Shanxi, China

Tianjin People's Hospital

Tianjin, Tianjin Municipality, China

Zhejiang Provincial People's Hospital

Hangzhou, Zhejiang, China

Countries

China

Other Identifiers

PA9159-201

Identifier Type: -

Identifier Source: org_study_id