The Study of GR1802 in Patients with Chronic Rhinosinusitis with Nasal Polyps

A Randomized, Double Blind, Placebo-Controlled Phase II Study to Evaluate the Efficacy, Safety of GR1802 Injection in Patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)

This is a multi-center, randomized, double blind, placebo-controlled study to evaluate the efficacy, safety, PK, PD and immumogenicity of GR1802 injection in comparison to placebo in addition to a background treatment of mometasone furcate nasal spray (MFNS) in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). Patients will receive GR1802 injection or Placebo every 2 Weeks.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Rhinosinusitis with Nasal Polyps
• Intervention / Treatment: Biological: GR1802 injection; Biological: placebo

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled phase II clinical trial evaluating the preliminary efficacy and safety of GR1802 injection in patients with chronic rhinosinusitis with nasal polyps.

The study consists of a Screening/run-in Period (up to 4 weeks), a Randomized, Double Blind Treatment Period (16 weeks) and a Safety Follow-up Period (8 weeks).

70 subjects will be randomized 1:1 into the 300 mg first dose doubling Q2W group and the placebo Q2W group. Throughout the dosing period, all subjects continued treatment with standard therapy at a stable dose.

Patient-reported outcome including Nasal congestion score will be collected using patient diary. Central reading will be implemented to Nasal endoscopic nasal polyp score (NPS) and nasal polyp biopsy tissue analysis to eosinophil counts & percentage.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Beijing Tongren Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Bilateral CRSwNP with prior treatment with systemic corticosteroids (SCS), and/or contraindicate to or intolerance to SCS, and/or with prior surgery to nasal polyps
2. Bilateral NPS of ≥5 with a minimum score of 2 in each nasal cavity at screening and at baseline.
3. Ongoing symptoms of nasal congestion/obstruction(NCS score of 2 or 3 at screening and at baseline).
4. Recorded use of intranasal corticosteroids for at least 4 weeks before screening

Exclusion Criteria:

1. Insufficient washout time for drugs that have an impact on the evaluation of efficacy and safety。
2. Concurrent disease that may interfere with the evaluation of safety and efficacy in subjects, or affect the risk- benefit evaluation of subjects. eg. specific ongoing nasal diseases, severe asthma, active infection, Severe cardiovascular disease, Severe laboratory test abnormalities.
3. Other.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: GR1802; GR1802 injection 300mg every two weeks for 16-week treatment	Biological: GR1802 injection; 150mg/1ml. 2 ml every two weeks Route of administration: Subcutaneous
Placebo Comparator: Placebo Comparator: Placebo; Placebo every two weeks for 16-week treatment	Biological: placebo; 0mg/1ml. 2 ml every two weeks Route of administration: Subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline at Week 16 in Nasal Congestion/Obstruction Symptom(NCS) Severity Score	Change from baseline in the NCS score. NCS score (0-3), higher score means worse nasal symptom.	at Week 16
Change From Baseline at Week 16 in Nasal Polyp Score	NPS score ranges from 0-8. (sum of 0-4 for each nasal passage scores), higher score means a worse outcome.	at Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to the first response of NPS	Time to the first response of NPS (defined as bilateral endoscopic NPS improved ≥1).	Baseline up to Week 24
University of Pennsylvania Smell Identification Test (UPSIT)	Change from baseline in UPSIT. UPSIT score (0-40). Higher score means better sense of smell.	at Week 16
Safety parameters	Incidence of treatment-emergent adverse events (TEAEs), of treatment-emergent serious AEs (TESAEs), etc.	Baseline up to Week 24
Lund-Mackay score	Change from baseline in the Lund-Mackay score on CT scan. The range of LM score is 0-24. Higher score means worse rhinosinusitis.	at Week 16
Bilateral endoscopic NPS	Change from baseline in the bilateral endoscopic NPS at Week 4, 8, 12, 24.	at Week 4, 8, 12, 24
Nasal Congestion/Obstruction Symptom score(NCS)	Change from baseline in NCS at Week 4, 8, 12, 24.	at Week 4, 8, 12, 24
Total Nasal Symptom Score(TNSS) score	Change from baseline in TNSS score. TNSS score (0-9). Higher score means worse nasal symptom.	at Week 16
Visual Analogue Scale (VAS) for Rhinosinusitis	Change from baseline in VAS score. VAS score (0-10). Higher score means worse nasal symptom.	at Week 16
Proportion of subjects receiving rescue therapy for nasal polyps	Rescue therapy includes Systemic Corticosteroids and endoscopic surgery	Baseline up to Week 24
Pharmacokinetics(PK)	Plasma concentration of GR1802 injection. PK parameter including trough concentration and exposure（CL/F, Vz/F etc.）	Baseline up to Week 24
Pharmacodynamics(PD)	Change from baseline in serum biomarker level (Periostin, TARC, total IgE and eosinophil level) and biomarkers in nasal secretions and nasal exfoliated cells。	at Week 16
Anti-drug antibodies(ADA)	Incidence of ADA	Baseline up to Week 24

Collaborators and Investigators

• Sponsor: Genrix (Shanghai) Biopharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2023
• Primary Completion (Estimated): October 30, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: May 16, 2023
• First Submitted That Met QC Criteria: May 16, 2023
• First Posted (Actual): May 24, 2023

Study Record Updates

• Last Update Posted (Actual): September 25, 2024
• Last Update Submitted That Met QC Criteria: September 23, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Pathological Conditions, Anatomical; Paranasal Sinus Diseases; Nose Diseases; Rhinitis; Sinusitis; Nasal Polyps; Polyps; Rhinosinusitis
• Other Study ID Numbers: GR1802-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No