Chronic Rhinosinusitis with Nasal Polyps MedDRA version: 20.1 Level: PT Classification code 10080060 Term: Chronic rhinosinusitis with nasal polyps System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply at screening: AGE 1. 18 years of age and older inclusive, at the time of signing the informed consent. CRSwNP / ECRS DIAGNOSIS 2. Endoscopic bilateral NP score of at least 5 out of a maximum score of 8 (with a minimum score of 2 in each nasal cavity) assessed by the investigator (see Appendix 10) 3.Participants who have had at least one of the following at Visit 1: • previous nasal surgery for the removal of NP;, • have used at least three consecutive days of systemic corticosteroids in the previous 2 years for the treatment of NP;, •medically unsuitable or intolerant to systemic corticosteroid. 4.Participants (except for those in Japan) must be on daily treatment with INCS (including intranasal liquid steroid wash/douching) for at least the 8 weeks immediately prior to screening 5. Participants presenting with severe NP symptoms defined as symptoms of nasal congestion/blockade/obstruction with moderate or severe severity (VRS score of 2 or 3) and loss of smell or rhinorrhoea (runny nose) based on clinical assessment by the investigator. 6.Presence of symptoms of chronic rhinosinusitis as described by at least 2 different symptoms for at least 12 weeks prior to Visit 1, one of which should be either nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior nasal drip), plus • facial pain/pressure and/or •reduction or loss of smell GENDER 7.Male or eligible female participants: Female Participants: • A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: o Is a woman of non-childbearing potential (WONCBP) as defined in Appendix 4 OR o Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: CONCURRENT CONDITIONS/MEDICAL HISTORY 1.As a result of medical interview, physical examination, or screening investigation the physician responsible considers the participant unfit for the study 2.Cystic fibrosis 3.Antrochoanal polyps 4. Nasal cavity tumor (malignt or benign) 5. Fungal rhinosinusitis 6.Severe nasal septal deviation occluding one nostril preventing full assessment of nasal polyps in both nostrils 7.Participants who had a sino-nasal or sinus surgery changing the lateral wall structure of the nose making impossible the evaluation of nasalpolyp score 8.Acute sinusitis or upper respiratory tract infection (URTI) at screening or in 2 weeks prior to screening 9.Ongoing rhinitis medicamentosa (rebound or chemical induced rhinitis) 10.Participants who have had an asthma exacerbation requiring admission to hospital within 4 weeks of Screening 11.Participants who have undergone any intranasal and/or sinus surgery (for example polypectomy, balloon dilatation or nasal stent insertion) within 6 months prior to Visit 1; nasal biopsy prior to Visit 1 for diagnostic purposes only is excepted. 12.Participants where NP surgery is contraindicated in the opinion of the Investigator 13.Eosinophilic Diseases: Participants with other conditions that could lead to elevated eosinophils such as hyper-eosinophilic syndromes including (but not limited to) EGPA (formerly known as Churg-Strauss Syndrome) or Eosinophilic Esophagitis 14.Parasitic infection: Participants with a known, pre-existing parasitic infestation within 6 months prior to Visit 1 15.Immunodeficiency: A known immunodeficiency (e.g. human immunodeficiency virus – HIV), other than that explained by the use of corticosteroids (CSs) taken as therapy for asthma 16.Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to screening(NOTE:Participants that had localised carcinoma of the skin which was resected for cure will not be excluded). 17.Liver Disease: Alanine aminotransferase (ALT) >2x ULN Total bilirubin >1.5x ULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices, persistent jaundice. NOTE: Stable non-cirrhotic chronic liver disease (including Gilbert's syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C) are acceptable if participant otherwise meets entry criteria. 18.Other Concurrent Medical Conditions: Participants who have known,pre-existing, clinically significant cardiac, endocrine, autoimmune,metabolic, neurological, renal, gastrointestinal, hepatic, haematological or any other system abnormalities that are uncontrolled with standard treatment. 19.Vasculitis: Participants with current diagnosis of vasculitis. Participants with high clinical suspicion of vasculitis at screening will be evaluated and current vasculitis must be excluded prior to enrolment. 20.Hypersensitivity: Participants with allergy/intolerance to the excipients of depemokimab in Section 6.1, a monoclonal antibody, or biologic. 21.COVID-19: Participants that, according to the investigator's medical judgment, are likely to have active COVID-19 infection must be excluded. Participants with known COVID-19 positive contac
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of depemokimab 100mg SC + SoC compared to placebo + SoC at Week 52 in participants with a diagnosis of CRSwNP;Secondary Objective: •To evaluate the efficacy of depemokimab 100 mg SC + SoC compared to placebo + SoC at Week 52 in terms of symptom scores for rhinorrhea (runny nose) and loss of smell •To evaluate the efficacy of depemokimab 100 mg SC + SoC compared to placebo + SoC at Week 52 in terms of the Lund Mackay CT score •To evaluate the impact on quality of life of depemokimab 100 mg SC +SoC compared to placebo + SoC at Week 52 in patients with a diagnosis of CRSwNP •To evaluate the impact on asthma control of depemokimab 100 mg SC+ SoC compared placebo + SoC at Week 52 in the sub-group of participants with asthma and a diagnosis of CRSwNP •To evaluate the efficacy of depemokimab 100 mg SC + SoC compared to placebo + SoC prior to Week 26 in participants with a diagnosis of CRSwNP;Primary end point(s): Co-primary endpoints: a) Change from baseline in total endoscopic NP score at Week 52 (centrally read) Change from baseline in mean nasal obstruction score (verbal response scale [VRS]) from Week 49 through to Week 52;Timepoint(s) of evaluation of this end point: Baseline through to Week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change from baseline in mean symptom score for rhinorrhoea (runny nose) (VRS) from Week 49 through to Week 52 •Change from baseline in mean symptom score for loss of smell (VRS) from Week 49 through to Week 52 •Change from baseline in Lund Mackay CT score at Week 52 •Change from baseline in SNOT-22 total score at Week 52 •Change from baseline in Asthma Control Questionnaire (ACQ-5) score at Week 52 in participants with an ACQ-5 score >0.75 at baseline. •Change from baseline in mean nasal obstruction score (VRS) from Week 21 through to Week 24 •Change from baseline in total endoscopic NP score at Week 26;Timepoint(s) of evaluation of this end point: Baseline through to Week 52 | — |
Countries
China, Italy, Japan, Poland, Romania, Spain, Sweden, Turkey, United States
Contacts
Public ContactGSK Clinical Support Help Desk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed