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

NCT04607005 | Completed Phase 3 Results

• 1 other identifier: 209692
• Study Type: interventional
• Target: 169
• Locations: 3 countries
• Sites: 61

Brief Summary

This is a randomized, double blind, placebo controlled, parallel group phase III study designed to assess the clinical efficacy and safety of 100 milligrams (mg) subcutaneous (SC) mepolizumab treatment in adults with CRSwNP/ECRS for the purpose of registration in Japan and China. Approximately 160 participants will be randomized in a 1:1 ratio to receive either 100 mg SC mepolizumab or placebo SC. The study will include a 4-week run-in period followed by randomization to a 52-week treatment period, where participants will be administered 4-weekly doses of mepolizumab or placebo via a pre-filled safety syringe device (SSD) injection.

Conditions

Nasal Polyps

Keywords

Chronic rhinosinusitis; Eosinophilic chronic rhinosinusitis; Mepolizumab

Outcome Measures

Primary Outcomes (4)

• Mean Change From Baseline in Total Endoscopic Nasal Polyps (NP) Score at Week 52 - ITT Population Excluding Medipharma Managed Sites

  Total endoscopic nasal polyp score is collected at clinical visits. Independent reviewers, blinded to treatment, reviewed image recordings of nasal endoscopies to determine total endoscopic NP score based on NP size. The right and left nostrils were scored from 0 to 4 (0 = No polyps; 1 = Small polyps in the middle meatus not reaching below the inferior border of the middle concha; 2 = Polyps reaching below the lower border of the middle turbinate; 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle concha; and 4 = Large polyps causing complete obstruction/congestion of the inferior meatus). The total score is the sum of the right and left nostril scores and ranges from 0 to 8 (calculated by summing the scores \[0 to 4\] in each nostril), higher scores indicate worse status. Baseline was defined as Day 1 value. Change from Baseline = Post-baseline value minus Baseline value.

  Baseline (Day 1) up to week 52

• Mean Change From Baseline in Total Endoscopic NP Score at Week 52 - Intent-to-Treat (ITT) Population

  Total endoscopic nasal polyp score is collected at clinical visits. The assessments were performed by central video image recordings of nasal endoscopy (NE). The right and left nostrils were scored from 0 to 4 (0 = No polyps; 1 = Small polyps in the middle meatus not reaching below the inferior border of the middle concha; 2 = Polyps reaching below the lower border of the middle turbinate; 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle concha; and 4 = Large polyps causing complete obstruction/congestion of the inferior meatus). The total score is the sum of the right and left nostril scores and ranges from 0 to 8 (calculated by summing the scores \[0 to 4\] in each nostril), "0" score represents better status while "8" represents worse status. Baseline was defined as last value prior to first dose (Day 1). Change from Baseline = Post-baseline value minus Baseline value.

  Baseline (Day 1) up to Week 52

• Mean Change From Baseline in Mean Nasal Obstruction Visual Analogue Scale (VAS) Score During the 4 Weeks Prior to Week 52 - ITT Population Excluding Medipharma Managed Sites

  Participants rated individual (nasal obstruction, nasal discharge, mucus in the throat, loss of smell, facial pain) and overall symptoms on a visual analog scale (VAS) using an electronic diary (eDiary). Captured scores ranged between 0 (none) and 100 (as bad as you can imagine), final scores derived from the electronically captured scores by dividing by 10. The final nasal obstruction VAS score ranged between 0 (none) and 10 (worst), with higher scores indicating greater disease severity. The average of daily scores in 4-weekly intervals were calculated and data is presented for Weeks 49-52. Baseline was defined as the average score from the 7 days of eDiary data collected prior to Day 1. Change from Baseline = Post-baseline value minus Baseline value.

  Baseline (Day 1) up to 4 weeks prior to week 52

• Mean Change From Baseline in Mean Nasal Obstruction VAS Score During the 4 Weeks Prior to Week 52 - ITT Population

  Participants rated individual (nasal obstruction, nasal discharge, mucus in the throat, loss of smell, facial pain) and overall symptoms on a visual analog scale (VAS) using an electronic diary (eDiary). Captured scores ranged between 0 (none) and 100 (as bad as you can imagine), final scores derived from the electronically captured scores dividing by 10. The final nasal obstruction VAS score ranged between 0 and 10, with higher scores indicating greater disease severity. The average of daily scores in 4-weekly intervals were calculated and data is presented for Weeks 49-52. Baseline was defined as the average score from the 7 days of eDiary data collected prior to Day 1. Change from Baseline = Post-baseline value minus Baseline value.

  Baseline (Day 1) up to 4 weeks prior to week 52

Secondary Outcomes (12)

• Mean Change From Baseline in Mean Overall VAS Symptom Score During the 4 Weeks Prior to Week 52 - ITT Population Excluding Medipharma Managed Sites

  Baseline (Day 1) up to 4 weeks prior to week 52

• Mean Change From Baseline in Mean Overall VAS Symptom Score During the 4 Weeks Prior to Week 52 - ITT Population

  Baseline (Day 1) up to 4 weeks prior to week 52

• Mean Change From Baseline in Lund Mackay (LMK) Computed Tomography (CT) Score at Week 52 - ITT Population Excluding Medipharma Managed Sites

  Baseline (Day 1) and Week 52

• Mean Change From Baseline in LMK CT Score at Week 52 - ITT Population

  Baseline (Day 1) and Week 52

• Mean 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] During the 4 Weeks Prior to Week 52 - ITT Population Excluding Medipharma Managed Sites

  Baseline (Day 1) up to 4 weeks prior to week 52

Study Arms (2)

Participants receiving mepolizumab + Standard of care (SoC)

EXPERIMENTAL

Participants will receive one dose of 100 mg mepolizumab SC on top of SoC every 4 weeks during the 52-week treatment period.

Drug: Mepolizumab; Drug: Standard of care

Participants receiving placebo + SoC

PLACEBO COMPARATOR

Participants will receive one dose of placebo via SC route on top of SoC, every 4 weeks during the 52-week treatment period.

Drug: Placebo; Drug: Standard of care

Interventions

Mepolizumab DRUG

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).

Participants receiving mepolizumab + Standard of care (SoC)

Placebo DRUG

Placebo will be available as a clear to opalescent, colorless sterile solution for SC injection in a single-use, safety syringe

Participants receiving placebo + SoC

Standard of care DRUG

Participants will continue to receive Standard of care as they are used to before entry in the study.

Participants receiving mepolizumab + Standard of care (SoC); Participants receiving placebo + SoC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants of 18 years of age and older inclusive, at the time of signing the informed consent.
• Body weight greater than or equal to 40 kilograms (kg).
• Male or female participants (with appropriate contraceptive methods) to be eligible for entry into the study.
• Female participant is eligible to participate if she is not pregnant or breastfeeding, one of the following conditions applies:
• Is a woman of non- childbearing potential (WONCBP) : or
• Is a woman of child bearing potential (WOCBP) and using a contraceptive method that is highly effective \[with a failure rate of less than (\<)1percent (%) per year\], preferably with low user dependency, during the study intervention period and for at least 105 days after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (for example \[e.g.\] noncompliance, recently initiated) in relationship to the first dose of study intervention.
• A WOCBP must have a negative highly sensitive urine pregnancy test within 24 hours before the first dose of study intervention.
• If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
• 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.
• 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.
• 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.
• Participants with severe NP symptoms defined as a nasal obstruction VAS symptom score of greater than (\>)5.
• Presence of symptoms of CRS as described by at least two 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
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and study protocol.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• BioClinica, Inc.: collaborator
• Signant Health: collaborator

Study Sites (61)

GSK Investigational Site

Dongguan, Guangdong, 523326, China

Location

GSK Investigational Site

Guangzhou, Guangdong, 510000, China

Location

GSK Investigational Site

Zhongshan, Guangdong, 528400, China

Location

GSK Investigational Site

Haikou, Hainan, 570311, China

Location

GSK Investigational Site

Wuhan, Hubei, 430060, China

Location

GSK Investigational Site

Nanjing, Jiangsu, 210029, China

Location

GSK Investigational Site

Qingdao, Shandong, 266061, China

Location

GSK Investigational Site

Zibo, Shandong, 255036, China

Location

GSK Investigational Site

Taiyuan, Shanxi, 300201, China

Location

GSK Investigational Site

Beijing, 100191, China

Location

GSK Investigational Site

Beijing, 100730, China

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GSK Investigational Site

Chengdu, 610041, China

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GSK Investigational Site

Shanghai, 200003, China

Location

GSK Investigational Site

Shanghai, 200030, China

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GSK Investigational Site

Wuhan, 430022, China

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GSK Investigational Site

Xiamen, 361004, China

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GSK Investigational Site

Yantai, 264000, China

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GSK Investigational Site

Aichi, 457-8511, Japan

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GSK Investigational Site

Aichi, 464-8547, Japan

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GSK Investigational Site

Aichi, 471-8513, Japan

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GSK Investigational Site

Chiba, 262-0015, Japan

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GSK Investigational Site

Chiba, 272-0143, Japan

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GSK Investigational Site

Fukui, 910-1193, Japan

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GSK Investigational Site

Fukuoka, 806-8501, Japan

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GSK Investigational Site

Fukuoka, 810-0001, Japan

Location

GSK Investigational Site

Hiroshima, 734-8551, Japan

Location

GSK Investigational Site

Hyōgo, 663-8501, Japan

Location

GSK Investigational Site

Hyōgo, 665-0827, Japan

Location

GSK Investigational Site

Ibaraki, 309-1793, Japan

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GSK Investigational Site

Ishikawa, 920-0293, Japan

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GSK Investigational Site

Kagawa, 763-8502, Japan

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GSK Investigational Site

Kagoshima, 890-0062, Japan

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GSK Investigational Site

Kanagawa, 211-8533, Japan

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GSK Investigational Site

Kanagawa, 232-0024, Japan

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GSK Investigational Site

Kanagawa, 250-8558, Japan

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GSK Investigational Site

Kumamoto, 860-0814, Japan

Location

GSK Investigational Site

Kyoto, 600-8216, Japan

Location

GSK Investigational Site

Kyoto, 602-8026, Japan

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GSK Investigational Site

Mie, 514-8507, Japan

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GSK Investigational Site

Miyagi, 983-8512, Japan

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GSK Investigational Site

Nagano, 395-8505, Japan

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GSK Investigational Site

Niigata, 940-2085, Japan

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GSK Investigational Site

Okayama, 701-0192, Japan

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GSK Investigational Site

Osaka, 565-0871, Japan

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GSK Investigational Site

Osaka, 569-8686, Japan

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GSK Investigational Site

Osaka, 570-8507, Japan

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GSK Investigational Site

Osaka, 583-8588, Japan

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GSK Investigational Site

Tokyo, 113-8655, Japan

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GSK Investigational Site

Tokyo, 141-0001, Japan

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GSK Investigational Site

Tokyo, 142-8666, Japan

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GSK Investigational Site

Tokyo, 143-8541, Japan

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GSK Investigational Site

Tokyo, 153-8515, Japan

Location

GSK Investigational Site

Tokyo, 160-0023, Japan

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GSK Investigational Site

Tokyo, 162-8543, Japan

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GSK Investigational Site

Moscow, 108840, Russia

Location

GSK Investigational Site

Moscow, 119991, Russia

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GSK Investigational Site

Saint Petersburg, 190013, Russia

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GSK Investigational Site

Saint Petersburg, 194356, Russia

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GSK Investigational Site

Saint Petersburg, 196158, Russia

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GSK Investigational Site

Saint Petersburg, 197022, Russia

Location

GSK Investigational Site

Yaroslavl, 150003, Russia

Location

Related Publications (1)

• Fujieda S, Wang C, Yoshikawa M, Asako M, Suzaki I, Bachert C, Han JK, Fuller A, Baylis L, Su L, Sasaki E, Sousa AR, Chan R, Zhang L. Mepolizumab in CRSwNP/ECRS and NP: the phase III randomised MERIT trial in Japan, China, and Russia. Rhinology. 2024 Oct 1;62(5):576-589. doi: 10.4193/Rhin24.156.

  PMID: 39058315 BACKGROUND

MeSH Terms

Conditions

Nasal Polyps

Interventions

mepolizumab; Standard of Care

Condition Hierarchy (Ancestors)

Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Polyps; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The site staff and central study team will be blinded to each participant's eosinophil count (including white blood count differential) and to central overread nasal polyps scores following randomization.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be randomized in a ratio of 1:1 to receive a single SC dose of 100 mg mepolizumab or placebo every 4 weeks during 52-week treatment period.

Study Record Dates

• First Submitted: October 23, 2020
• First Posted: October 28, 2020
• Study Start: April 22, 2021
• Primary Completion: April 12, 2023
• Study Completion: April 12, 2023
• Last Updated: November 25, 2024
• Results First Posted: November 25, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD is made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

Locations

CN (17); JP (37); RU (7)