Rupatifen Fumarate Capsules in Patients With Seasonal Allergic Rhinitis

A Randomized, Double-blind, Positive-control and Placebo-controlled Phase Ⅲ Clinical Study to Evaluate the Efficacy and Safety in Rupatifen Fumarate Capsules for the Seasonal Allergic Rhinitis Patients

This Phase Ⅲ randomized, double-blind, active- and placebo-controlled trial aims to assess the efficacy and safety of Rupatifen Fumarate Capsules for seasonal allergic rhinitis. Eligible participants will be randomized to Rupatifen Fumarate Capsules, Rupatadine Fumarate Tablets (active comparator), or matching placebo. All treatments are administered once daily at a consistent time with a 24 ± 2-hour interval between doses for 2 consecutive weeks.

Inclusion Criteria:

• Aged from 18 to 65 years inclusive, no restriction on gender.
• Clinical diagnosis shall comply with Chinese Guidelines for the Diagnosis and Treatment of Allergic Rhinitis (Revised 2022) issued by Rhinology Group, Chinese Society of Otorhinolaryngology Head and Neck Surgery, Chinese Medical Association; documented medical history of seasonal allergic rhinitis ≥2 years (subject's self-reported history is acceptable). Prior to randomization, subjects shall test positive for one or more locally prevalent seasonal allergens (e.g., tree pollen, grass pollen). Any of the following allergen testing results are recognized: skin prick test (SPT), intradermal test or serum specific immunoglobulin E (sIgE). Specific immunoglobulin E (sIgE) results obtained within 1 year prior to randomization demonstrating positivity to relevant seasonal allergens are acceptable. Clinical manifestations shall meet the following: a) Symptoms: ≥2 of paroxysmal sneezing, rhinorrhea, nasal pruritus and nasal congestion; total daily symptom duration ≥1 hour, with possible accompanying ocular manifestations including lacrimation, ocular pruritus and conjunctival hyperemia. b) Signs: typical pale and edematous nasal mucosa with watery nasal discharge. c) Allergic symptoms manifest seasonally in spring and/or autumn, and subjects are in an active symptomatic episode at screening.
• At screening, reflective Total Nasal Symptom Score (rTNSS) ≥6 points, nasal congestion subscore ≥2 points, and at least one subscore ≥2 points among rhinorrhea, nasal pruritus and sneezing.
• Subjects are willing to provide written informed consent and comply with study procedures, including proper completion of subject diary cards; capable of adhering to scheduled study medication, laboratory examinations and other trial-related assessments.
• Subjects satisfying all criteria below after the 1-week run-in phase are eligible to proceed to the treatment observation period: 1)The reflective Total Nasal Symptom Score (rTNSS) ≥6 points prior to study drug administration on Day -7 (first day of run-in) and prior to the first dose in treatment period; nasal congestion subscore ≥2 points plus ≥2 points in at least one of rhinorrhea, nasal pruritus or sneezing. The mean baseline reflective Total Nasal Symptom Score (rTNSS) ≥6 points, calculated as the average of seven reflective Total Nasal Symptom Score (rTNSS) assessments: morning and evening of Day -3, Day -2, Day -1 plus morning of Day 1; 2) Diary completion rate during run-in period ≥80%; 3) Total number of recorded reflective Total Nasal Symptom Score (rTNSS) and instantaneous Total Nasal Symptom Score (iTNSS) scores in run-in period ≥12 times, with no missing values for the seven baseline assessments; 4) Run-in study drug administration frequency ≥6 times; 5) No rescue medication administered throughout the run-in period.

Exclusion Criteria:

• (Medical inquiry) Patients with asthma requiring long-term treatment (subjects with occasional asthmatic symptoms such as dyspnea or exercise-induced asthma who require no medication during the trial may be enrolled).
• Subjects with infectious conjunctivitis or other ocular infections (allergic conjunctivitis excluded).
• Subjects with concomitant nasal diseases or conditions at screening (e.g., acute/chronic sinusitis, nasal polyps, deviated nasal septum, rhinitis medicamentosa, cerebrospinal fluid rhinorrhea, status within 1 year post nasal surgery, etc.) that may interfere with efficacy assessment as judged by the investigator (self-reported history is acceptable).
• (Medical inquiry) Active respiratory tract infection occurring within 14 days prior to screening or throughout the run-in period, including but not limited to bronchitis, pneumonia, upper respiratory tract infection or sinus infection.
• (Medical inquiry) Subjects receiving sinus surgery within 3 months before screening or with incompletely healed nasal trauma.
• (Medical inquiry) Severe pulmonary disease or impaired pulmonary function such as chronic obstructive pulmonary disease (COPD).
• (Medical inquiry) Subjects with cardiac disorders requiring treatment; male subjects with QT interval corrected by Fridericia's formula (QTcF) greater than 470 ms, female subjects with QT interval corrected by Fridericia's formula (QTcF) greater than 480 ms, uncorrectable hypokalemia, progressive arrhythmias including bradycardia or acute myocardial ischemia who are deemed ineligible for enrollment per investigator's judgment.
• (Medical inquiry) Subjects receiving allergen immunotherapy within 6 months prior to screening.
• Subjects with severe hepatic or renal disorders, or abnormal hepatic and renal laboratory results: alanine aminotransferase (ALT) / aspartate aminotransferase (AST) greater than or equal to 2 times the upper limit of normal (ULN), or creatinine (Cr) greater than 1.2 times the upper limit of normal (ULN).
• (Medical inquiry) Inadequate washout of prohibited medications prior to screening; specified washout periods for common medicines are listed below: Intranasal or systemic decongestants, anticholinergics, intranasal antihistamines: 3 days; Systemic antihistamines (cetirizine, fexofenadine, loratadine, desloratadine etc.): 10 days; Mast cell stabilizers, tricyclic antidepressants, anti-allergic herbal medicines, leukotriene receptor antagonists: 2 weeks; Systemic glucocorticoids: 4 weeks; potent topical or intranasal glucocorticoids: 2 weeks; anti-immunoglobulin E (Anti-IgE) therapy, interleukin-4 (IL-4R) inhibitors (dupilumab, tezepelumab etc.): 3 months or 5 elimination half-lives, whichever is longer; allergen immunotherapy: 6 months. For other unlisted drugs relevant to allergic rhinitis treatment in this trial: washout of no less than 5 elimination half-lives or 3 days prior to run-in period initiation, whichever is longer.
• (Medical inquiry) Subjects unable to discontinue concomitant medications that may interfere with efficacy evaluation throughout the trial, including but not limited to tricyclic antidepressants, systemic/potent topical/intranasal glucocorticoids, decongestants (except rescue medication), antihistamines, leukotriene receptor antagonists, mast cell stabilizers (cromolyn sodium, nedocromil sodium, lodoxamide tromethamine, pemirolast potassium, tranilast etc.), central nervous system depressants, anti-immunoglobulin E (anti-IgE) agents (omalizumab), anticholinergics and anti-allergic herbal medicines, regular nasal irrigation.
• (Medical inquiry) Subjects who have received moderate or potent Cytochrome P450 3A4 (CYP3A4) inhibitors or other Cytochrome P450 3A4 (CYP3A4) isoenzyme inhibitors within 2 weeks before screening or cannot discontinue such agents during the trial (examples: ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin, conivaptan, lopinavir, voriconazole, erythromycin, fluconazole, cobicistat-containing formulations etc.).
• (Medical inquiry) Subjects planning to travel to areas outside endemic pollen regions during the run-in period, or planning out-of-town travel for consecutive greater than or equal to 2 days or cumulative greater than or equal to 3 days during the trial.
• (Medical inquiry) Subjects engaged in precision operations including vehicle driving, machinery operation or high-altitude work.
• (Medical inquiry) Subjects with documented alcohol addiction within the past 5 years (alcoholism defined as weekly intake greater than 14 alcohol units; 1 unit is approximately equal to 360 mL beer / 45 mL 40% alcohol by volume (ABV) distilled spirits / 150 mL wine), drug abuse or tobacco addiction (daily cigarette consumption greater than 10 cigarettes), or unable to abstain from alcohol throughout the trial.
• Subjects with known hypersensitivity to investigational medicinal product or its excipients.
• Pregnant or lactating females; female subjects or male subjects (or their female partners) planning pregnancy during the entire trial and within 3 months after trial completion.
• (Medical inquiry) Subjects participating in another clinical trial with investigational product within 3 months prior to screening.
• Subjects with any condition deemed by the investigator to impair ability to provide informed consent or comply with study protocol, or whose trial participation would compromise trial outcomes or personal safety.