Mepolizumab Long-term Study to Assess Real World Safety and Effectiveness of Eosinophilic Granulomatosis With Polyangiitis (EGPA) in Japan (MARS)

A Single Arm, Multi-center Study to Assess the Long-term Real-world Safety and Effectiveness of Nucala in EGPA Patients Who Have Already Used Nucala for at Least 96 Weeks in Japan

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as the Churg-Strauss syndrome, is a systemic necrotizing vasculitis that affects small and medium sized blood vessels. NUCALA® (mepolizumab 300 milligrams [mg], subcutaneous administration) was approved in Japan in 2018 for the treatment of EGPA in adult participants. This is a single-arm, multi-center, prospective, non-interventional study that aims to assess long-term (2 to 4 years) real-world safety and effectiveness of NUCALA. Approximately 120 participants who completed the NUCALA Post Marketing Surveillance (PMS) study (National Clinical Trial [NCT]03557060) will be enrolled in the study.

NUCALA is a registered trademark of GlaxoSmithKline (GSK) group of companies.

Study Overview

• Status: Completed
• Conditions: Churg-Strauss Syndrome; Eosinophilic Granulomatosis With Polyangiitis

• Study Type: Observational
• Enrollment (Actual): 118

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan, 489-8642
    • GSK Investigational Site
  • Gunma, Japan, 371-8511
    • GSK Investigational Site
  • Hyogo, Japan, 653-0013
    • GSK Investigational Site
  • Hyogo, Japan, 670-8520
    • GSK Investigational Site
  • Hyogo, Japan, 674-0063
    • GSK Investigational Site
  • Hyogo, Japan, 675-8611
    • GSK Investigational Site
  • Ishikawa, Japan, 920-8530
    • GSK Investigational Site
  • Ishikawa, Japan, 923-8560
    • GSK Investigational Site
  • Kanagawa, Japan, 252-0392
    • GSK Investigational Site
  • Kanagawa, Japan, 216-8511
    • GSK Investigational Site
  • Kanagawa, Japan, 241-0801
    • GSK Investigational Site
  • Kanagawa, Japan, 241-0811
    • GSK Investigational Site
  • Kochi, Japan, 780-8522
    • GSK Investigational Site
  • Mie, Japan, 510-8567
    • GSK Investigational Site
  • Mie, Japan, 511-0061
    • GSK Investigational Site
  • Miyagi, Japan, 980-8574
    • GSK Investigational Site
  • Osaka, Japan, 534-0021
    • GSK Investigational Site
  • Osaka, Japan, 533-0024
    • GSK Investigational Site
  • Saitama, Japan, 350-8550
    • GSK Investigational Site
  • Shiga, Japan, 520-2192
    • GSK Investigational Site
  • Shizuoka, Japan, 430-8525
    • GSK Investigational Site
  • Shizuoka, Japan, 436-8555
    • GSK Investigational Site
  • Tokyo, Japan, 113-8655
    • GSK Investigational Site
  • Tokyo, Japan, 113-8603
    • GSK Investigational Site
  • Tokyo, Japan, 104-8560
    • GSK Investigational Site
  • Tokyo, Japan, 113-8431
    • GSK Investigational Site
  • Tokyo, Japan, 204-8585
    • GSK Investigational Site
  • Tokyo, Japan, 173-8606
    • GSK Investigational Site
  • Tokyo, Japan, 183-8524
    • GSK Investigational Site
  • Tokyo, Japan, 190-0014
    • GSK Investigational Site
  • Tokyo, Japan, 194-0023
    • GSK Investigational Site
  • Tottori, Japan, 680-0833
    • GSK Investigational Site
  • Wakayama, Japan, 640-8558
    • GSK Investigational Site
  • Yamaguchi, Japan, 755-8505
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult participants with EGPA who have already received NUCALA treatment for 96 weeks after its market launch in Japan.

Description

Inclusion Criteria:

• Adult participants with EGPA of >=20 years of age inclusive, at the time of signing the informed consent.
• Participants must have a current clinical diagnosis of EGPA by physician.

• Participants have continuously used NUCALA for at least 96 weeks for the treatment of EGPA as mentioned in the current label in Japan.

  • Participants thus were registered and completed the NUCALA PMS study (special drug use investigation; Protocol Number 208505, NCT03557060) prior to be enrolled in this study.

• Physician's decision to continue treatment with NUCALA for the treatment of EGPA as mentioned in the current label in Japan.
• Prior to commencing any study related activities, participants must be able and willing to provide written informed consent.

Exclusion Criteria:

• Participants who have previously discontinued NUCALA treatment for EGPA for more than 12 weeks.
• Participating in another clinical trial within the past 12 months, in which the participant has been exposed to an investigational or non-investigational pharmaceutical product.
• Participants with any reasons that in physician's opinion would place the participants at risk.
• Participants who are pregnant or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Participants with EGPA who have received NUCALA treatment; Data will be collected of participants who have already received NUCALA for 96 weeks in routine clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interests (AESI)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with study participation, whether or not considered related to study participation. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, and other situations which involve medical or scientific judgment. An AESI may be of scientific and medical concern related to the treatment, monitored, and rapidly communicated by investigator to sponsor. AESIs included Hypersensitivity (including anaphylaxis), Infections and Malignant tumors.	Up to 96 weeks
Number of Participants With Adverse Drug Reactions (ADRs)	An ADR is defined as an AE for which the investigator classifies the possible relationship to study intervention as "Yes". ADRs related to NUCALA were collected.	Up to 96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Clinical Symptoms	Clinical symptoms as assessed by 9 organ-systems (i.e. systemic, skin, mucous membranes/eyes, ears/nose/throat, chest, cardiovascular, abdominal, renal, nervous system [motor and sensory]) relevant to EGPA in systemic vasculitis were assessed. Data were summarized for following categories; none, active, worsening, active + worsening. "None" is defined as absence of clinical symptoms. "Active disease" is defined as follows: The participant has clinical symptoms, or worsening of symptoms is noted as compared to those in the preceding observation period and the status in the preceding observation period was assessed as "None". "Worsening" is defined as follows: The participant has worsening clinical symptoms, or worsening of symptoms is noted as compared to those in the preceding observation period and the status in the preceding observation period was assessed as "Active disease" or "Worsening". Percentage values are rounded off.	At 96 weeks
Percentage of Participants With Eosinophilic Granulomatosis With Polyangiitis (EGPA) Relapse	EGPA relapse is defined as any of the following with worsening EGPA: increased dose of oral corticosteroids (OCS), initiation/increased dose of immuno-suppressive agents or EGPA treatment with hospitalization. Percentage of participants with EGPA relapse were reported. Percentage values are rounded off.	Up to 96 weeks
Annualized Rate of Hospitalization for EGPA-related Events	Annualized rate of hospitalization = (Number of corresponding hospital visits * 365)/ (number of days in the observation period). The annualized rate and associated 95 percent (%) confidence intervals (CIs) were calculated using a negative binomial generalized linear model with logarithm of time as an offset variable, without covariate. Number (estimated event per person year) and 95% CI were reported.	Up to 96 weeks
Annualized Rate of Emergency Room/Unscheduled Visit for EGPA-related Events	Annualized rate of Emergency Room/Unscheduled Visit = (Number of corresponding Emergency Room/Unscheduled Visits * 365)/(number of days in the observation period). The annualized rate and associated 95% CIs were calculated using a negative binomial generalized linear model with logarithm of time as an offset variable, without covariate. Number (estimated event per person year) and 95% CI were reported.	Up to 96 weeks
Average Daily Dose (Prednisolone-equivalent) of Oral Corticosteroid (OCS)	Average daily dose of OCS for each participant was calculated by 12-weekly periods as: Total dosage of OCS (mg) / Total duration of administration of OCS (day). Total duration of administration is defined as: Last date of period minus later date of (first date of each period or start date of OCS) +1.	Week 0, Weeks 9-12, Weeks 21-24, Weeks 33-36, Weeks 45-48, Weeks 57-60, Weeks 69-72, Weeks 81-84, Weeks 93-96
Number of Participants by Dosing Categories Relative to Average Daily OCS (Prednisolone-equivalent)	Number of participants by each category of average daily prednisolone-equivalent of OCS were assessed. The dosing categories included: zero, greater than (>)0 to less than or equal to (<=) 4.0 milligrams per day (mg/day), >4.0 to <=7.5 mg/day, >7.5 mg/day.	Week 0, Weeks 9-12, Weeks 21-24, Weeks 33-36, Weeks 45-48, Weeks 57-60, Weeks 69-72, Weeks 81-84, Weeks 93-96

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2020
• Primary Completion (Actual): April 27, 2023
• Study Completion (Actual): April 27, 2023

Study Registration Dates

• First Submitted: September 11, 2020
• First Submitted That Met QC Criteria: September 11, 2020
• First Posted (Actual): September 16, 2020

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: NUCALA; Eosinophilic granulomatosis with polyangiitis; Real world setting; Long term safety and efficacy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Respiratory Tract Diseases; Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Autoimmune Diseases; Lung Diseases; Vasculitis; Skin Diseases, Vascular; Lung Diseases, Interstitial; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Granuloma; Granulomatosis with Polyangiitis; Churg-Strauss Syndrome; Systemic Vasculitis
• Other Study ID Numbers: 213684

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