Chronic Rhinosinusitis with Nasal Polyps
Conditions
Brief summary
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.
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.
Interventions
BIOLOGICALGR1802 injection
150mg/1ml. 2 ml every two weeks Route of administration: Subcutaneous
BIOLOGICALplacebo
0mg/1ml. 2 ml every two weeks Route of administration: Subcutaneous
Sponsors
Genrix (Shanghai) Biopharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at Week 16 in Nasal Congestion/Obstruction Symptom(NCS) Severity Score | at Week 16 | Change from baseline in the NCS score. NCS score (0-3), higher score means worse nasal symptom. |
| Change From Baseline at Week 16 in Nasal Polyp Score | at Week 16 | NPS score ranges from 0-8. (sum of 0-4 for each nasal passage scores), higher score means a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bilateral endoscopic NPS | at Week 4, 8, 12, 24 | Change from baseline in the bilateral endoscopic NPS at Week 4, 8, 12, 24. |
| Nasal Congestion/Obstruction Symptom score(NCS) | at Week 4, 8, 12, 24 | Change from baseline in NCS at Week 4, 8, 12, 24. |
| University of Pennsylvania Smell Identification Test (UPSIT) | at Week 16 | Change from baseline in UPSIT. UPSIT score (0-40). Higher score means better sense of smell. |
| Total Nasal Symptom Score(TNSS) score | at Week 16 | Change from baseline in TNSS score. TNSS score (0-9). Higher score means worse nasal symptom. |
| Visual Analogue Scale (VAS) for Rhinosinusitis | at Week 16 | Change from baseline in VAS score. VAS score (0-10). Higher score means worse nasal symptom. |
| Time to the first response of NPS | Baseline up to Week 24 | Time to the first response of NPS (defined as bilateral endoscopic NPS improved ≥1). |
| Pharmacokinetics(PK) | Baseline up to Week 24 | Plasma concentration of GR1802 injection. PK parameter including trough concentration and exposure（CL/F, Vz/F etc.） |
| Pharmacodynamics(PD) | at Week 16 | Change from baseline in serum biomarker level (Periostin, TARC, total IgE and eosinophil level) and biomarkers in nasal secretions and nasal exfoliated cells。 |
| Anti-drug antibodies(ADA) | Baseline up to Week 24 | Incidence of ADA |
| Safety parameters | Baseline up to Week 24 | Incidence of treatment-emergent adverse events (TEAEs), of treatment-emergent serious AEs (TESAEs), etc. |
| Proportion of subjects receiving rescue therapy for nasal polyps | Baseline up to Week 24 | Rescue therapy includes Systemic Corticosteroids and endoscopic surgery |
| Lund-Mackay score | at Week 16 | Change from baseline in the Lund-Mackay score on CT scan. The range of LM score is 0-24. Higher score means worse rhinosinusitis. |
Countries
China
Outcome results
None listed