CTRI/2022/12/047957 [Registered on: 07/12/2022] Trial Registered Prospectively
Last Modified On:
24/08/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Other
Public Title of Study
A clinical trial to investigate the effect of mepolizumab on severe COPD patients who are suffering from frequent exacerbations (or COPD attacks) and raised blood eosinophils
Scientific Title of Study
A multi-center, randomized, double-blind, parallel-group, placebo-controlled study of mepolizumab 100 mg SC as add-on treatment in participants with COPD experiencing frequent exacerbations and characterized by eosinophil levels (Study 208657)
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
208657_Protocol Amendment 6-STD 06-DEC-2021
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
Details of Contact Person Scientific Query
Name
Rashmi Chitgupi
Designation
Director - Clinical Management
Affiliation
PPD Pharmaceutical Development India Private Limited
Address
PPD Pharmaceutical Development India Private Limited, 101, A Wing, Fulcrum, Hiranandani Business Park, Sahar Road, Andheri East, Mumbai Mumbai (Suburban) MAHARASHTRA 400099 India
Phone
912266022900
Fax
912266022999
Email
rashmi.chitgupi@ppd.com
Details of Contact Person Public Query
Name
Rashmi Chitgupi
Designation
Director - Clinical Management
Affiliation
PPD Pharmaceutical Development India Private Limited
Address
PPD Pharmaceutical Development India Private Limited, 101, A Wing, Fulcrum, Hiranandani Business Park, Sahar Road, Andheri East, Mumbai Mumbai (Suburban) MAHARASHTRA 400099 India
Phone
912266022900
Fax
912266022999
Email
rashmi.chitgupi@ppd.com
Source of Monetary or Material Support
GlaxoSmithKline Research & Development Limited 980 Great West Road Brentford Middlesex, TW8 9GS UK
Primary Sponsor
Name
GlaxoSmithKline Research & Development Limited
Address
980 Great West Road Brentford Middlesex, TW8 9GS UK
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
Hungary Argentina Australia Austria Belgium Brazil Canada China Denmark France Germany Greece India Ireland Israel Italy Mexico Netherlands New Zealand Poland Republic of Korea Spain Sweden United Kingdom United States of America
Apollo Spectra Hospital Apollo Speciality Hospital
Pvt Ltd 14 138 Chunni
Ganj Kanpur Uttar Pradesh
208002 Kanpur Nagar UTTAR PRADESH
9889888181
skkatiyar_in@yahoo.com
Dr Boyilla Nagaraju
Aster Prime Hospital
Aster Prime Hospital
Opp Passport Seva Kendra
Ameerpet Hyderabad- 500038,
Telangana, India Hyderabad TELANGANA
9848883444
nagaraj.boyilla@gmail.com
Dr Amit Patel
Care Institute of Medical Sciences
CIMS hospital Pvt Ltd, Plot No 67/1, Opp.Panchamrut Bunglows, Near Shukan Mall, Off.Science City Road, Ahmedabad-380060, Gujarat, India Ahmadabad GUJARAT
9824310250
amit.patel@cimshospital.org
Dr Vivek Gupta
Criticare Hospital and Research Institute
Criticare Hospital and
Research Institute 4th Floor
Dhanshree Complex Near
Hotel Hardeo Sitabuldi Nagpur
Maharashtra 440010 Nagpur MAHARASHTRA
9373115548
vivekurvashi@yahoo.co.in
Dr Sandeep Nayar
Dr B L Kapur Memorial Hospital
Dr B L Kapur Memorial Hospital, Pusa Road, New Delhi-110005, India New Delhi DELHI
9810006781
Sandeep.Nayar@blkhospital.com
Dr Rajesh Swarnakar
Getwell Hospital and Research Institute
Getwell Hospital & Research Institute,
20/1, Dr. Khare Marg, Dhantoli,
Nagpur, Maharashtra - 440012 Nagpur MAHARASHTRA
9822225130
pidrswarnakar@gmail.com
Dr Zuber Ahmad
Jawaharlal Nehru Medical College
Department of T B and
Respiratory disease
J N Medical College
Aligarh Muslim
University Aligarh
Uttar Pradesh 202002 Aligarh UTTAR PRADESH
9412175925
zrin_amu@yahoo.com
Dr Deepali Kamdar
Jaydeep Hospital
Jaydeep Hospital , Near St Xaviers Loyola school, Opp. Kamnath Mahadev , Nr Darpan Six Road , Naranpura , Ahmedabad – 380013, Gujrat, India Ahmadabad GUJARAT
9825038282
drdjkamdar_27@yahoo.com
Dr Sandeep Kumar Gupta
M V Hospital and Research Center
M V Hospital and Research Center
314/30 Mirza Mandi Chowk,
Lucknow-226003 Uttar Pradesh
Lucknow UTTAR PRADESH
Meenakshi Mission Hospital and Research Centre
Department of Pulmonology and Sleep Medicine
Lake Area Melur Road Madurai 625107 Madurai TAMIL NADU
0452-4263054
gvk.tbrd@gmail.com
Dr Akash Balki
Shree Hospital Ethics Committee
Shree Hospital
The Chairman Shree Hospital Ethics Committee
3rd Floor 799 Omnagar Opp Tajshree Building
Mirchi Bazaar Sakkardara Chowk Umred Road
Nagpur Maharashtra 440009 Nagpur MAHARASHTRA
9890812215
akashbalki49@gmail.com
Dr Amit Dhamija
Sir Ganga Ram Hospital
Sir Ganga Ram Hospital
SGRM Marg Rajinder Nagar
New Delhi Delhi - 110060 New Delhi DELHI
09811684520
dhamijaamit09@gmail.com
Dr Venkata Nagarjuna Maturu
Yashoda hospital Hyderabad
Department of Pulmonology
Room No 208 2nd Floor,
Yashoda Hospital, Hitech City,
Cyber Towers to JNTU Road,
Hyderabad - 500084,
Telangana State, India Hyderabad TELANGANA
Institutional Ethics committee for MV Hospital and Research centre
Approved
Institutional Ethics Committee Aster Prime Hospital
Approved
Institutional Ethics Committee Jawaharlal Nehru Medical College
Approved
Kaizen Ethics Committee
Approved
Meenakshi Mission Hospital & Research Centre
Approved
Shree Hospital Ethics Committee
Approved
Sir Ganga Ram Hospital Ethics Committee
Approved
Yashoda Academy of Medical Education and Research
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: J441||Chronic obstructive pulmonary disease with (acute) exacerbation,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Mepolizumab 100 mg SC
120 mg/mL sucrose, 4.16 mg/mL Sodium phosphate dibasic heptahydrate, 0.95 mg/mL Citric
Acid Monohydrate, 0.2 mg/mL polysorbate 80, 0.019 mg/mL EDTA Disodium Dihydrate.
Mepolizumab is a sterile liquid formulation. It will be administered as a SC injection (100 mg/mL) delivered once every 4 weeks using a pre-filled safety syringe.
Comparator Agent
Placebo
120 mg/mL sucrose, 4.16 mg/mL Sodium phosphate dibasic heptahydrate, 0.95 mg/mL Citric Acid Monohydrate, 0.2 mg/mL polysorbate 80, 0.019 mg/mL EDTA Disodium Dihydrate. This dose not contain active drug
Inclusion Criteria
Age From
40.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1. Participant must be at least 40 years of age at Screening Visit 1.
2. Participants with a peripheral blood eosinophil count of more than or equal to 300 cells per microliter (μL) from the hematology sample collected at Screening Visit 0 AND a documented historical blood eosinophil count of more than or equal to 150 cells per μL in the 12 months prior to Screening Visit 0 that meets the following: It must have been measured between 12 months and 1 month prior to Screening Visit 0, and it must not have been measured within 14 days of a COPD exacerbation. Participants with no documented historical blood eosinophil count of more than or equal to 150 cells per µL must meet this threshold at the Screening Visit 1 assessment.
3. Participants with a clinically documented history of COPD for at least 1 year in accordance with the definition by the American Thoracic Society or European Respiratory Society.
4. Participants must present with a measured pre- and post-salbutamol Forced expiratory volume in one second (FEV1)/Forced vital capacity (FVC) ratio of <0.70 at Screening Visit 1 to confirm the diagnosis of COPD and with a measured post-salbutamol FEV1 less than 20% and less than or equals to 80% of predicted normal values calculated using NHANES III reference equations at Screening Visit 1.
5. Participants must have a well-documented history (for example, medical record verification) in the 12 months prior to Screening Visit 1 of two or more moderate COPD exacerbations that were treated with systemic corticosteroids (intramuscular [IM], intravenous, or oral) with or without antibiotics or at least one severe COPD exacerbation requiring hospitalization.
6. Participants must have a well-documented requirement for optimized standard of care background therapy that includes inhaled corticosteroids (ICS) plus 2 additional COPD medications (ICS-based triple therapy) for the 12 months prior to Screening Visit 1 and meets the following criteria: immediately prior to Screening Visit 1, minimum of 3 months of use of an 1) inhaled corticosteroid at a dose less than or equals to 500 microgram (mcg) per day fluticasone propionate dose equivalent plus 2) Long acting beta2-agonist (LABA) and 3) Long acting muscarinic antagonist (LAMA) unless documentation of safety or intolerance issues related to LABA or LAMA. For participants who are not continually maintained on ICS plus LABA plus LAMA for the entire 12 months prior to Visit 1 use of the following is allowed (but not in the 3 months immediately prior to Visit 1); inhaled corticosteroid at a dose more than or equal to 500 mcg per day fluticasone propionate dose equivalent plus inhaled LABA or inhaled LAMA and Phosphodiesterase-4-inhibitors, methylxanthines, or scheduled daily use of short acting beta2-agonist (SABA) and/or short acting muscarinic antagonist (SAMA).
7. Current or former cigarette smokers with a history of cigarette smoking of more than or equal to 10 pack-years at Screening (Visit 1) calculated as (number of pack years equal to [number of cigarettes per day/20] multiplied by number of years smoked [For example, 20 cigarettes per day for 10 years or 10 cigarettes per day for 20 years]).
8. Contraceptive use for female participant should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
9. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: She is not a woman of childbearing potential (WOCBP) or she is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of more than 1%, during the intervention period and for at least 16 weeks after the last dose of study intervention. The principal investigator (PI) should evaluate the effectiveness of the contraceptive method in relation to the first dose of study intervention.
10. A WOCBP must have a negative highly sensitive pregnancy urine test within 24 hours before the first dose of study intervention. If a urine test cannot be confirmed as negative (For example, 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.
11. Participants capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
12. Participants must meet following randomization inclusion criteria at Visit 2 to be randomized and commence the study intervention period: a) Participants that do not have documented historical blood eosinophil count of more than or equal to 150 cells/μL prior to Screening Visit must meet this threshold based on the Screening Visit 1 assessment, b) Participants must have eosinophil count of more than 300 cells/μL from the hematology sample collected at Screening Visit 0, c) Compliance with completion of the e-diary defined as completion of all questions on 5 or more days out of the 7 days immediately preceding Visit 2.
ExclusionCriteria
Details
1. Participants with a past history or concurrent diagnosis of asthma are excluded regardless of whether they have active or inactive disease.
2. The Investigator must judge that COPD is the primary diagnosis accounting for the clinical manifestations of the lung disease. Participants with alpha1-antitrypsin deficiency as the underlying cause of COPD are excluded. Also, excluded are participants with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases.
3. Participants with pneumonia, COPD exacerbation, or lower respiratory tract infection within the 4 weeks prior to Screening Visit 1.
4. Participants with lung volume reduction surgery within the 12 months prior to Screening Visit 1.5. Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Screening Visit 1. Participants who are in the maintenance phase of a pulmonary rehabilitation program are not excluded.
5. Participants receiving treatment with oxygen more than 2 liter (L) per minute at rest over 24 hours. For participants receiving oxygen treatment, participants should demonstrate an oxyhemoglobin saturation greater than or equal to 89percent while breathing supplemental oxygen.
6. Participants with a QT interval, from the electrocardiogram (ECG) conducted at Screening Visit 1, corrected with Fridericias formula (QTcF) more than 450 millisecond (msec) (or QTcF more than 480 msec in participants with bundle branch block). Fridericias formula must be used to determine eligibility and discontinuation for an individual participant. Participants are excluded if an abnormal ECG finding from the 12 lead ECG conducted at Screening Visit 1 is considered to be clinically significant and would impact the participants participation during the study, based on the evaluation of the Investigator.
7. Participants with any of the following would be excluded- myocardial infarction or unstable angina in the 6 months prior to Screening Visit 1, unstable or life threatening cardiac arrhythmia requiring intervention in the 3 months prior to Screening Visit 1, New York Heart Association (NYHA) Class IV Heart failure.
8. Participants with (historical or) current evidence of clinically significant, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled. Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the participant at risk through participation, or which could affect the efficacy or safety analysis if the disease or condition exacerbated during the study.
9. Participants with other conditions that could lead to elevated eosinophils such as Hypereosinophilic syndromes including Eosinophilic Granulomatosis with Polyangiitis (EGPA), also known as Churg-Strauss Syndrome, or Eosinophilic Esophagitis.
10. Participants with a known, pre-existing parasitic infestation within 6 months prior to Screening Visit 1.
11. A current malignancy or previous history of cancer in remission for less than 12 months prior to Screening Visit 1 (participants that had localized carcinoma of the skin or cervix which was resected for cure will not be excluded).
12. Participants with a known immunodeficiency (For example, human immunodeficiency virus), other than that explained by the use of corticosteroids taken for COPD.
13. Participants with cirrhosis or current unstable liver disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice. Stable non-cirrhotic chronic liver disease (including Gilberts syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C e.g., presence of hepatitis B surface antigen (HbsAg) or positive hepatitis C antibody test result) is acceptable if the participant otherwise meets entry criteria.
14. Participants who have received interventional product in previous mepolizumab studies are excluded.
15. Participants who have received any monoclonal antibody within 5 half-lives of Screening Visit 1.
16. Participants who have received an investigational drug within 30 days of Visit 1, or within 5 drug half-lives of the investigational drug, whichever is longer (this also includes investigational formulations of a marketed product).
17. Participants who have received short term use of oral corticosteroids within 30 days of Visit 1.
18. Participants with a known allergy or sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates participation in the study or intolerance to another monoclonal antibody or biologic including history of anaphylaxis to another biologic.
19. Participants at risk of non-compliance, or unable to comply with the study procedures. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits.
20. Participants with conditions that will limit the validity of informed consent to participate in the study, for example, uncontrolled psychiatric disease or intellectual deficiency.
21. Participants with a known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1.
22. Participant is an Investigator, sub-Investigator, study coordinator, employee of a participating Investigator or study site, or immediate family member of the aforementioned that is involved in this study.
23. Participants with a current active COVID19 infection, either laboratory confirmed or according to the investigators medical judgement and who are known to be in contact with active COVID-19 positive individuals within the past 14 days. Participant will not be randomized if they meet any of the following randomization exclusion criteria at Visit 2 a) Participants who have pneumonia, exacerbation, lower respiratory infection during the Run-in period. b) Evidence of clinically significant abnormality in the hematological or biochemical screen at Visit 1, as judged by the Investigator. c) Participants who meet the following based on results from sample taken at Screening Visit 1 Alanine aminotransferase (ALT) more than 2x upper limit of normal (ULN), bilirubin more than 1.5 x ULN (isolated bilirubin more than 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35percent), cirrhosis or current unstable liver or biliary disease per Investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice. d) Participants who are pregnant or breastfeeding. Participants should not be randomized if they plan to become pregnant during the time of study participation. e) Participants that had an active COVID-19 infection during the Run-in period, either laboratory confirmed or according to the investigators medical judgment or known to be in contact with active COVID-19 positive individuals within the past 14 days. f) Participants with a QT interval, from the ECG conducted at Visit 2, corrected with Fridericias formula (QTcF) more than 450 msec (or QTcF more than 480 msec in participants with bundle branch block).
Method of Generating Random Sequence
Other
Method of Concealment
Other
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
To evaluate the efficacy of mepolizumab 100 mg subcutaneous (SC) compared to placebo, given every 4 weeks in liquid formulation by safety syringe (SS) to COPD participants at high risk of exacerbations despite the use of optimized COPD maintenance therapy.
Annualized rate of moderate/severe exacerbations.
Up to Week 104
Secondary Outcome
Outcome
TimePoints
To evaluate mepolizumab 100 mg SC compared to placebo given every 4 weeks in liquid formulation by SS on additional efficacy assessments, health related quality of life (HRQoL), health care utilization, and symptoms
Time to first moderate/severe exacerbation. Up to Week 104
Proportion of CAT responders(CAT score from Baseline), at Week 52
Proportion of SGRQ total score responders, at Week 52
Proportion of E-RS- COPD responders, at Week 52
Annualized rate of exacerbations requiring ED visit and or hospitalization, Up to Week 104
Target Sample Size
Total Sample Size="800" Sample Size from India="45" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a multi-center, randomized, placebo-controlled,
double-blind, parallel group study designed to confirm the benefits of
mepolizumab treatment on moderate or severe exacerbations in chronic
obstructive pulmonary disease (COPD) participants given as an add on to their
optimized maintenance COPD therapy. The maximum duration of participant
participation is approximately 109 weeks, consisting of 2 screening visits (up
to 3 weeks), a run-in period (up to 2 weeks), and an intervention period of at
least 52 weeks and up to 104 weeks. 800 participants will be randomized in a
1:1 ratio to receive mepolizumab 100 milligrams (mg) or placebo every 4 weeks
for at least 13 doses (52 weeks treatment period) up to a maximum of 26 doses
(104 weeks treatment period). The number of randomized participants may
increase up to approximately 1400.