CTRI/2023/10/059272 [Registered on: 30/10/2023] Trial Registered Prospectively
Last Modified On:
27/01/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Other
Public Title of Study
A Study to Evaluate Astegolimab in Participants With Chronic Obstructive Pulmonary Disease
Scientific Title of Study
A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Evaluate The Efficacy And Safety Of Astegolimab In Patients With Chronic Obstructive Pulmonary Disease
Trial Acronym
Nil
Secondary IDs if Any
Secondary ID
Identifier
GB44332_Protocol Ver 2.0 dated 09Nov2022
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
Country Head - 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 MAHARASHTRA 400099 India
Phone
02266022900
Fax
912266022999
Email
rashmi.chitgupi@ppd.com
Details of Contact Person Public Query
Name
Rashmi Chitgupi
Designation
Country Head - 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 MAHARASHTRA 400099 India
Phone
02266022900
Fax
912266022999
Email
rashmi.chitgupi@ppd.com
Source of Monetary or Material Support
F. Hoffmann-La Roche Ltd
Grenzacherstrasse 124
4070 Basel, Switzerland
Primary Sponsor
Name
F. Hoffmann-La Roche Ltd Grenzacherstrasse 124 4070 Basel, Switzerland
Address
Grenzacherstrasse 124
4070 Basel, Switzerland
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
Argentina Australia Austria Belgium Brazil Bulgaria Canada Chile China Czech Republic Democratic People's Republic of Korea Denmark Egypt France Germany Greece Hong Kong Hungary India Israel Italy Japan Kenya Latvia Mexico Netherlands New Zealand Philippines Poland Romania South Africa Spain Sweden Switzerland Taiwan Thailand Turkey United Kingdom United States of America Viet Nam
Clinical Trial Unit MRU (Multidisciplinary Research Unit
Basement ESIC Medical college & Hospital, NH3, NIT, Faridabad-121001, Haryana, India
Faridabad HARYANA
7027076007
drmksen@yahoo.com
Dr Vivek Gupta
Criti Care Hospital & Research Institute
4th
Floor, Dhanshree Complex, Near Hotel
Hardeo, Sitabuldi, Nagpur, Maharashtra, India-
440012 Nagpur MAHARASHTRA
9373115548
vivekurvashi@yahoo.co.in
Dr Anand K Patel
GMERS Medical college & Hospital, Gotri
Department of Respiratory Medicine, 2nd Floor, Hospital Building,Old TB Hospital Campus,Gotri Road Vadodara GUJARAT
0989771079
dranandkpatel@gmail.com
Dr Kirankumar Chandubhai Rami
GMERS Medical College and Civil Hospital, Sola
104-TB & Chest Department,A Block,OPD Buidling, Nr Gujarat high court, Sola gram road Ahmadabad GUJARAT
97232228665
drkiranrami117@gmail.com
Dr Naveed Shah
Government Chest Disease Hospital
Department of Pulmonary Medicine(GMC), Dalgate Road, 190001, India Srinagar JAMMU & KASHMIR
9419016438
naveednazirshah@yahoo.com
Dr Rojith K B
Government Medical College
Department of General Medicine, Kozhikode, Kerala-673008 Kozhikode KERALA
91-495-2350216
drrojithkbalakrishnan@gmail.com
Dr K Sunil Naik
Government Medical College and Government General Hospital
Department of Medicine, Srikakulam-532001, Andhra Pradesh, India.
Srikakulam ANDHRA PRADESH
9440828299
drsunilnaikggh@gmail.com
Dr Jotideb Mukhopadhyay
Institute of Post Graduate Medical Education and Research and SSKM Hospital
Department of Medicine, 4th Floor, 244, A.J.C Bose Road, 700020, India. Kolkata WEST BENGAL
9433770356
drjotideb60@gmail.com
Dr Piyush Arora
Jawahar Lal Nehru Medical College
Clinical Research Department Jawahar Lal Nehru Medical College Kala Bagh 305001 Ajmer RAJASTHAN
9887088122
Doctor.piyusharora@gmail.com
Dr Mohammad Shameem
Jawaharlal Nehru Medical College
Department of Tuberculosis and Chest Disease,
Jawaharlal Nehru Medical College, Aligarh MuslimUniversity, Aligarh, Uttar Pradesh 202002, India.
Aligarh UTTAR PRADESH
9412731835
mshameen@myamc.ac.in
Dr Deepali Kamdar
Jaydeep Hospital
Near St. Xavier Loyola School, Opposite Kamnath mahadev, Near Darpan Six road, Navarangpura,380013, India Ahmadabad GUJARAT
9825038282
drdjkamdar_27@yahoo.com
Dr Ram S Kaulgud
Karnataka Institute of Medical Sciences
Vidya nagar, Hubballi 580022, Karnataka, India Dharwad KARNATAKA
08362373348
ramkaulgud@gmail.com
Dr Ajay Kumar Verma
King George Medical University
Department of Respiratory Medicine, 226003, India Lucknow UTTAR PRADESH
9919788862
drajay21@gmail.com
Dr Himanshu Pophale
Kothrud Hospital
Opp. Hill View Park, (Metro Car Depot),
Paud Road, Kothrud,
Pune, Maharashtra 411038, India.
Pune MAHARASHTRA
9503939461
himanshupophale@yahoo.co.in
Dr Manish Jain
Maharaja Agrasen Superspeciality Hospital
Central Spine, Agrasen Aspatal Marg, Sector - 7, Vidhyadhar Nagar- 302039, India Jaipur RAJASTHAN
8233099078
doctormanishjain2@gmail.com
Dr Nitesh Shah
Marengo CIMS hospital Pvt Ltd.
Plot no 67/1,Opp.Panchamrut bunglows,
Nr.shuakan Mall,Off.Science City Road, Sola,
Ahmedabad – 380060, India
Ahmadabad GUJARAT
07927712771
nitesh00@rediffmail.com
Dr Nainesh Patel
Meditrina Institute of Medical Sciences
278 Central Bazar Rd, Ramdaspeth, 440012, India Nagpur MAHARASHTRA
8806132539
pdrnainesh@gmail.com
Dr Sandeep Kumar Gupta
MV Hospital and Research Centre
314/30 Mirza Mandi Chowk, - 226003, India Lucknow UTTAR PRADESH
Aakash Healthcare Super Specialty Hospital Institutional Ethics Committee
Approved
Apollo Specialty Hospital Kanpur Ethics Committee
Approved
Criticare Hospital and Research Institute Ethics Committee
Approved
Ethics Committee Of Care Institute Of Medical Science
Approved
Ethics Committee S M S Medical College and attached Hospitals
Approved
IEC, Maharaja Agrasen Hospital
Approved
IEC,Jawahar Lal Nehru Medical College
Approved
Institute of Post Graduate Medical Education & Research, Research Oversight Committee
Submittted/Under Review
Institutional Ethics Committe -Yashoda Academy of Medical Education and Research
Submittted/Under Review
Institutional Ethics Committee for ESIC Faridabad
Approved
Institutional Ethics Committee for M. V. Hospital and Research Centre
Approved
Institutional Ethics Committee GMERS Medical College , Sola
Approved
Institutional Ethics Committee Jawaharlal Nehru Medical College and Hospital
Approved
Institutional Ethics Committee Karnataka institute of medical sciences
Approved
Institutional Ethics committee, GMC
Submittted/Under Review
Institutional Ethics Committee, GMC, Kozhikode
Submittted/Under Review
Institutional Ethics Committee, Government Medical College & Government General Hospital
Approved
Institutional Ethics Committee, KGMU
Submittted/Under Review
Institutional Ethics committee- Neelima Hospitals
Approved
Intitution Human Ethics committeeGMERS Medical College and Hospital,Gotri
Approved
Kaizen Ethics Committee
Approved
Meditrina Institute Ethics Committee
Approved
Royal Pune Independent Ethics Committee
Approved
Shree Hospital Ethics Committee
Approved
Sir Ganga Ram Hospital Ethics Committee
Submittted/Under Review
Sushruta Hospitals Ethics Committee
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
Astegolimab (RO7187807)
Astegolimab and placebo will be supplied by the Sponsor as a sterile liquid in 2.25 mL pre-filled
syringes with a needle safety device, providing 238 mg/1.7 mL of astegolimab or placebo
Each dose of study drug (astegolimab or placebo) will be administered as 2 SC injections (for a
total of 3.4 mL), with each injection administered on a different side of the abdomen (i.e., right or
left).
The treatment regimens for each arm are as follows:
• Astegolimab 476 mg SC every 2 weeks (Q2W)
• Astegolimab 476 mg SC every 4 weeks (Q4W)
To ensure that all study participants undergo the same visit schedule, participants
randomized to the Q4W dosing arm will alternate between injections of astegolimab and
placebo Q2W (beginning with astegolimab on Day 1), thus receiving astegolimab Q4W.
• Placebo SC Q2W
The Study has a 52-week Treatment period.
Comparator Agent
N/A
N/A
Inclusion Criteria
Age From
40.00 Year(s)
Age To
80.00 Year(s)
Gender
Both
Details
Potential participants are eligible to be included in the study only if all of the following
criteria apply:
- Able and willing to provide written informed consent and to comply with the
study protocol
- Age 40-80 years at Visit 1
- Documented COPD diagnosis for more than or equal to 12 months prior to Visit 1
- History of frequent exacerbations, defined as having had 2 or more moderate or
severe COPD exacerbations within 12 months prior to Visit 1
- A moderate COPD exacerbation is defined as new or increased COPD symptoms (e.g., dyspnea, sputum volume, and sputum purulence) that lead totreatment with systemic corticosteroids (oral, IV, or intramuscular [IM]) and/or antibiotics.
-Prior use of antibiotics alone does not qualify as a moderate exacerbation,
unless the use was specifically for the treatment of worsening symptoms of COPD.
-A severe COPD exacerbation is defined as new or increased COPD symptoms that lead to hospitalization (duration more than 24 hours) or lead to death.
- Post-bronchodilator FEV1 more than or equal to 20% and less than 80% of predicted at Visit 1 or Visit 2
- Post-bronchodilator FEV1/FVC less than 0.70 at Visit 1 or Visit 2
- mMRC score more than or equal to 2 at screening
- Current tobacco smoker (see definition in Section 8.2.2) or former smoker (having
stopped smoking for at least 6 months prior to Visit 1) with a history of smoking more than or equal to 10 pack-years (e.g., 20 cigarettes/day for 10 years)
- At Visit 1, participants who meet the protocol definition of current smoker will receive smoking cessation counseling (see Section 8.2.2)
- On optimized COPD maintenance therapy as defined below for more than or equal to 12 months prior to
Visit 1.
– Inhaled corticosteroid (ICS) plus long-acting beta-agonist (LABA)
– Long-acting muscarinic antagonist (LAMA) plus LABA
– ICS plus LAMA plus LABA
Participants must be stable on current medications and doses for at least 4 weeks
prior to Visit 1.
Initiation of new COPD therapy, including a methylxanthine preparation,
maintenance macrolide therapy, and/or phosphodiesterase 4 (PDE4) inhibitor is not
permitted within 4 weeks prior to Visit 1.
- Chest X-ray or computed tomography (CT) scan within 6 months prior to Visit 1 or
chest X-ray during the screening period (prior to Visit 2) that confirms the absence
of clinically significant lung disease besides COPD
Demonstrated ability to use and comply with electronic diary (eDiary) requirements,
defined as completion of all questions on at least 5 of 7 days prior to Visit 2
Participants unable to demonstrate compliance with the eDiary during the
screening period will be screen failed. Participants will have the opportunity to
demonstrate eDiary compliance if re-screened (see Section 8.3.3.3).
- For female participants of childbearing potential: agreement to remain abstinent
(refrain from heterosexual intercourse) or use contraception, as defined below:
Female participants must remain abstinent or use contraceptive methods with a
failure rate of less than 1% per year during the treatment period and for 12 weeks after
the final dose of astegolimab.
A female participant is considered to be of childbearing potential if she is
postmenarchal, has not reached a postmenopausal state (more than or equal to 12 continuous
months of amenorrhea with no identified cause other than menopause), and is
not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes,
and/or uterus) or another cause as determined by the investigator
(e.g., Müllerian agenesis). Per this definition, a female participant with a tubal
ligation is considered to be of childbearing potential. The definition of
childbearing potential may be adapted for alignment with local guidelines
or regulations.
Examples of contraceptive methods with a failure rate of less than 1% per year include
bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit
ovulation, hormone-releasing intrauterine devices, and copper intrauterine
devices.
The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and the preferred and usual lifestyle of the individual.
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation
methods) and withdrawal are not adequate methods of contraception.
If required per local guidelines or regulations, locally recognized adequate
methods of contraception and information about the reliability of abstinence will
be described in the local Informed Consent Form.
For male participants: agreement to remain abstinent (refrain from heterosexual
intercourse) or use a condom, and agree to refrain from donating sperm, as
defined below:
With a female partner of childbearing potential or pregnant female partner, male
participants must remain abstinent or use a condom during the treatment period
and for 12 weeks after the final dose of astegolimab to avoid exposing the
embryo. Male participants must refrain from donating sperm during this
same period.
The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and the preferred and usual lifestyle of the individual.
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation
methods) and withdrawal are not adequate methods of preventing drug
exposure. If required per local guidelines or regulations, information about the
reliability of abstinence will be described in the local Informed Consent Form.
For participants enrolled in the extended China enrollment phase at China’s sites:
must be current residents of mainland China, Hong Kong, or Taiwan, and of
Chinese ancestry.
ExclusionCriteria
Details
• Current documented diagnosis of asthma
• History of clinically significant pulmonary disease other than COPD
• Diagnosis of 1-antitrypsin deficiency
• History of long-term treatment with oxygen at > 4.0 liters/minute
• Lung volume reduction surgery or procedure within 12 months prior to screening
• Individuals participating in, or scheduled for, an intensive COPD rehabilitation program (participants who are in the maintenance phase of a rehabilitation program are eligible)
• History of lung transplant
• Any infection that resulted in hospital admission for ≥ 24 hours and/or treatment with oral, IV, or IM antibiotics within 4 weeks prior to or during screening
• Upper or lower respiratory tract infection within 4 weeks prior to or during screening
• Treatment with oral, IV, or IM corticosteroids within 4 weeks prior to initiation of study drug
• Initiation of or change in non-biologic immunomodulatory or immunosuppressive therapy within 3 months prior to screening
• Unstable cardiac disease, myocardial infarction, or New York Heart Association Class III or IV heart failure within 12 months prior to screening
Method of Generating Random Sequence
Stratified randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Annualized rate of moderate & severe COPD exacerbations over the 52 week
treatment period
A moderate COPD exacerbation is defined as new or increased COPD symptoms
(e.g. dyspnea, sputum volume, & sputum purulence) that lead to treatment
(duration more than or equal to 3 days) with systemic corticosteroids (oral, IV, or IM) at a dose of
more than 10 mg/day prednisolone equivalent and/or antibiotics.
A severe COPD exacerbation is defined as new or increased COPD symptoms that
lead to hospitalization (duration more than 24 hours) or lead to death.
52 week treatment period.
Secondary Outcome
Outcome
TimePoints
1. Time to first moderate or severe COPD exacerbation during the 52 week treatment
period
2. Absolute change from baseline in HRQoL at Week 52, as assessed through the
SGRQ C total score
3. Absolute change from baseline in post-bronchodilator FEV1 (liters) at Week 52
4. Absolute change from baseline in E RS COPD total score at Week 52
5. Proportion of participants with improvement in HRQoL, defined as a decrease from
baseline of more than or equal to 4 points in SGRQ C total score, at Week 52
6. Annualized rate of severe COPD exacerbations over the 52 week treatment period
1. During the 52 week Treatment period
2. Week 52
3. Week 52
4. Week 52
5. Week 52
6. Over the 52 week treatment period
Target Sample Size
Total Sample Size="1290" Sample Size from India="80" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 3
Date of First Enrollment (India)
20/11/2023
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
09/01/2023
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="1" Months="3" Days="0"
Recruitment Status of Trial (Global)
Open to Recruitment
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a Phase III, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of astegolimab in combination with standard of care (SOC) compared with placebo in combination with SOC, in participants with COPD who are former or current smokers and have a history of frequent exacerbations. Approximately 1290 participants with COPD are expected to be enrolled globally.
Following a screening period of at least 7 days and to up to 4 weeks, participants will be randomized in a 1:1:1 ratio to 1 of 3 treatment arms to receive blinded treatment with either astegolimab or placebo. Randomization will be stratified by smoking status at screening (former smoker vs. current smoker) and region. The first dose of study drug (astegolimab or placebo) will be administered on Day 1; treatment
will continue through Week 50, followed by a 12-week safety follow-up period.