Efficacy and Safety of Mepolizumab in Adults With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP)/ Eosinophilic Chronic Rhinosinusitis (ECRS) (MERIT)

JRCT ID: jRCT2031200306

Registered date:20/01/2021

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Chronic rhinosinusitis with nasal polyps/Eosinophilic chronic rhinosinusitis
• Date of first enrollment: 08/02/2021
• Target sample size: 160
• Countries of recruitment: China,Japan,Russia,Japan
• Study type: Interventional

Intervention(s)

Participants will receive one dose of 100 mg mepolizumab SC or placebo SC on top of SoC every 4 weeks during the 52-week treatment period.
Drug: Mepolizumab
Mepolizumab will be available as a clear to opalescent, colorless solution for SC injection in a single-use, safety syringe at a unit dose strength of 100 mg/milliliters (mL).
Drug: Placebo
Placebo will be available as a clear to opalescent, colorless sterile solution for SC injection in a single-use, safety syringe

Outcome(s)

Primary Outcome

1.Change from Baseline in total endoscopic NP score at Week 52 (scores on a scale)
2.Change from Baseline in mean nasal obstruction visual analogue scale (VAS) score (scores on a scale)

Secondary Outcome

1.Change from Baseline in sino-nasal outcome test (SNOT)-22 total score at Week 52 (scores on a scale)
2.Change from Baseline in mean overall VAS symptom score (scores on a scale)
3.Change from Baseline in the mean composite VAS score [combining VAS scores for nasal obstruction, nasal discharge, mucus in the throat and loss of smell] (scores on a scale)
4.Change from Baseline in Lund Mackay (LMK) computed tomography (CT) score at Week 52 (scores on a scale)
5.Change from Baseline in mean individual VAS symptom score for loss of smell (scores on a scale)
6.Time to first nasal surgery or course of systemic corticosteroids (CS) for CRSwNP/ECRS up to Week 52

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. 18 years of age and older inclusive, at the time of signing the informed consent.
2. Body weight greater than or equal to 40kg.
3. Male or female participants (with appropriate contraceptive methods) to be eligible for entry into the study.
4. A documented blood eosinophil count of over 2% in the 12 months prior to Visit 0 OR through a blood sample taken between Visit 0 and Visit 1. ALL participants must meet blood eosinophil count of over 2% by Visit 1.
Participants with peripheral blood eosinophil count over 2% to 5% must also have comorbid bronchial asthma, aspirin intolerance, or nonsteroidal anti-inflammatory drug intolerance at Visit 1 assessment in order to return for Visit 2.
5. 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
6. 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
7. Participants with severe NP symptoms defined as a nasal obstruction VAS symptom score of >5
8. Presence of symptoms of CRS as described by at least two different symptoms for at least 12 weeks prior to Visit 1.
9. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this study protocol.

Exclude criteria

- As a result of medical interview, physical examination, or screening investigation the physician responsible considers the participant unfit for the study. (e.g. symptomatic herpes zoster within 3 months prior to screening, evidence of tuberculosis [TB] active or latent).
- Cystic fibrosis
- Eosinophilic granulomatosis with polyangiitis (also known as Churg Strauss syndrome), Young's, Kartagener's or dyskinetic ciliary syndromes.
- Antrochoanal polyps.
- Severe nasal septal deviation preventing full assesment of nasal polyps in both nostrils.
- Acute sinusitis or upper respiratory tract infection (URTI) at screening or in 2 weeks prior to screening.
- Ongoing rhinitis medicamentosa (rebound or chemical induced rhinitis).
- Participants who have had an asthma exacerbation requiring admission to hospital within 4 weeks of screening.
- 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.
- Participants where NP surgery is contraindicated in the opinion of the Investigator.
- Participants with a known medical history of Human Immunodeficiency Virus (HIV) infection.
- Participants with a known, pre-existing parasitic infestation within 6 months prior to Visit 1.
- Participants who are currently receiving or have received within 3 months (or 5 half-lives - whatever is the longest) prior to first mepolizumab dose, chemotherapy, radiotherapy or investigational medications/therapies.
- Participants with a history of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline (GSK) Medical Monitor, contraindicates their participation. Aspirin sensitive participants are acceptable.
- Participants with a history of allergic reaction to anti-IL-5 or other monoclonal antibody therapy.
- Participants that have taken part in previous mepolizumab clinical studies.
- Participants currently using intranasal corticosteroids (INCS) and inhaled corticosteroids exhalation through nose (ICS/ETN) for the management of their ECRS who are not willing to maintain using this method of administration throughout the study.
- Use of systemic corticosteroids (including oral corticosteroids) or corticosteroid nasal solution (intranasal corticosteroid is excepted) within 4 weeks prior to screening or planned use of such medications during the double-blind period.
- INCS and/or inhaled corticosteroids exhalation through nose (ICS/ETN) dose changes within 1 month prior to Visit 1 (if applicable).
- Treatments with biological or immunosuppressive treatment (other than Xolair) treatment within 5 terminal phase half-lives of Visit 1.
- Omalizumab (Xolair) treatment in the 130 days prior to Visit 1.
- Commencement or change of dose of leukotriene antagonist treatment less than 30 days prior to Visit 1.
- Commencement or change of dose of allergen immunotherapy within the previous 3 months.
- Women who are pregnant or lactating or are planning on becoming pregnant during the study.
- Any participant who is considered unlikely to survive the duration of the study period or has any rapidly progressing disease or immediate life-threatening illness (e.g. cancer). In addition, any participant who has any other condition (e.g. neurological condition) that is likely to affect respiratory function should not be included in the study.
- Participants who have known, pre-existing, clinically significant endocrine, autoimmune, cardiovascular, metabolic, neurological, renal, gastrointestinal, hepatic, hematological or any other system abnormalities that are uncontrolled with standard treatment.
- Participants with symptoms suggestive of active Coronavirus Disease-2019 (COVID-19) infection (that is fever, cough etc) are excluded.
- Participants with known COVID-19 positive contacts within the past 14 days should be excluded for at least 14 days since the exposure and the participant remains symptom free.
- A known immunodeficiency (e.g. HIV), other than that explained by the use of corticosteroids taken as therapy.
- A current malignancy or previous history of cancer in remission for less than 12 months prior to screening.
- Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment).
- Alanine aminotransferase (ALT) >2 times Upper limit of normal (ULN).
- Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
- Participants with a QT interval, from the electrocardiogram (ECG) conducted at Screening Visit 1, corrected with Fridericia's formula (QTcF) >450 milliseconds (msec) (or QTcF >480msec in participants with bundle branch block).
- Known or suspected history of alcohol or drug abuse within 2 years prior to Screening (Visit 1) that in the opinion of the investigator would prevent the participant from completing the study procedures.
- Is an investigator, sub-investigator, and study coordinator, employee of a participating investigator or study site, or immediate family member of the aforementioned that is involved in this study.
- In the opinion of the investigator, any participant who is unable to read and/or would not be able to complete a questionnaire.

Related Information

• Primary Sponsor: Sugiyama Yutaro
• Secondary ID(s): NCT04607005