Trial no.:	PACTR202305580698795	Date of Approval:	18/05/2023
Trial Status:	Registered in accordance with WHO and ICMJE standards

TRIAL DESCRIPTION

Public title

A Study to Evaluate Astegolimab in Participants With Chronic Obstructive Pulmonary Disease

Official scientific title

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

Brief summary describing the background and objectives of the trial

This is a Phase III, randomized, double-blind, placebo-controlled, multicenter study. Approximately 1290 participants with chronic obstructive pulmonary disease (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. This study will evaluate the efficacy and safety of astegolimab compared with placebo in participants with COPD who are former or current smokers and have a history of frequent exacerbations.

Type of trial

RCT

Acronym (If the trial has an acronym then please provide)

ARNASA

Disease(s) or condition(s) being studied

Respiratory

Sub-Disease(s) or condition(s) being studied

Purpose of the trial

Treatment: Drugs

Anticipated trial start date

02/10/2023

Actual trial start date

Anticipated date of last follow up

09/12/2024

Actual Last follow-up date

Anticipated target sample size (number of participants)

1290

Actual target sample size (number of participants)

Recruitment status

Recruiting

Publication URL

Secondary Ids	Issuing authority/Trial register
GB44332	Sponsor

STUDY DESIGN
Intervention assignment	Allocation to intervention	If randomised, describe how the allocation sequence was generated	Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms	Masking	If masking / blinding was used
Parallel: different groups receive different interventions at same time during study	Randomised	Simple randomization using a randomization table created by a computer software program	Allocation was determined by the holder of the sequence who is situated off site	Masking/blinding used	Care giver/Provider,Participants

INTERVENTIONS
Intervention type	Intervention name	Dose	Duration	Intervention description	Group size	Nature of control
Experimental Group	Astegolimab	476 mg	52 weeks	Subcutaneous (SC) every 2 weeks (Q2W)	430
Experimental Group	Astegolimab	476 mg	52 weeks	Alternating subcutaneous (SC) astegolimab and placebo every 2 weeks (Q2W), thus receiving SC astegolimab every 4 weeks (Q4W)	430
Control Group	Placebo Comparator	Matching placebo	52 weeks	Subcutaneous (SC) every 2 weeks (Q2W)	430	Placebo

ELIGIBILITY CRITERIA
List inclusion criteria	List exclusion criteria	Age Category	Minimum age	Maximum age	Gender
Documented COPD diagnosis for ≥ 12 months History of frequent exacerbations, defined as having had 2 or more moderate or severe COPD exacerbations within 12 months prior to screening Post-bronchodilator FEV1 ≥ 20% and < 80% of predicted at screening Post-bronchodilator FEV1/FVC < 0.70 at screening Modified Medical Research Council (dyspnea scale) (mMRC) score ≥ 2 Current tobacco smoker or former smoker with a history of smoking ≥ 10 pack-years On optimized COPD maintenance therapy as defined below for ≥ 12 months prior to screening, and stable on current therapy for at least 4 weeks prior to screening: Inhaled corticosteroid (ICS) plus long-acting beta-agonist (LABA), Long-acting muscarinic antagonist (LAMA) plus LABA, ICS plus LAMA plus LABA Chest X-ray or computed tomography (CT) scan within 6 months prior to screening or chest X-ray during the screening period that confirms the absence of clinically significant lung disease besides COPD	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	80 and over: 80+ Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s)	40 Year(s)	80 Year(s)	Both

ETHICS APPROVAL

Has the study received appropriate ethics committee approval

Date the study will be submitted for approval

Date of approval

Name of the ethics committee

No

31/03/2023

KEMRI Scientific and Ethics Review Unit KEMRI SERU

Ethics Committee Address
Street address	City	Postal code	Country
P.O.Box 54840	Nairobi	00200	Kenya

Has the study received appropriate ethics committee approval

Date the study will be submitted for approval

Date of approval

Name of the ethics committee

No

11/04/2023

MKU Institutional Scientific and Ethics Review Committee

Ethics Committee Address
Street address	City	Postal code	Country
Mount Kenya University, Alumni Plaza, 9th Floor, Room 904	Thika	01000	Kenya

OUTCOMES
Type of outcome	Outcome	Timepoint(s) at which outcome measured
Primary Outcome	Annualized rate of moderate and severe COPD exacerbations over the 52-week treatment period	52 weeks
Secondary Outcome	Time to first moderate or severe COPD exacerbation during the 52-week treatment period	52 weeks
Secondary Outcome	Absolute change from baseline in health-related quality of life (HRQoL) at Week 52 as assessed through the St. George's Respiratory Questionnaire-COPD (SGRQ-C) total score	Week 52
Secondary Outcome	Absolute change from baseline in post-bronchodilator forced expiratory volume (FEV1) at Week 52	Week 52
Secondary Outcome	Absolute change from baseline in the Evaluating Respiratory Symptoms in Chronic Obstructive Pulmonary Disease (E-RS:COPD) total score at Week 52	Week 52
Secondary Outcome	Proportion of participants with improvement in HRQoL at Week 52	Week 52
Secondary Outcome	Annualized rate of severe COPD exacerbations over the 52-week treatment period	52 weeks

RECRUITMENT CENTRES
Name of recruitment centre	Street address	City	Postal code	Country
Kenya Medical Research Institute Centre for Respiratory Disease Research KEMRI CRDR	Kenyatta Hospital complex Off hospital road	Nairobi	00100	Kenya
Clinical Research Health Network	P.O. Box 19	Machakos	90100	Kenya
University of Nairobi Clinical Research Centre	Prof Mungai Road Off Wasawo Drive Off Riverside Drive Chiromo Campus University Of Nairobi P.O. Box 19676	Nairobi	00202	Kenya
KEMRI Mtwapa Clinical Annex	P.O. Box 428-80108, Mtwapa	Kilifi	80108	Kenya
Center for Research In Tropical Medicine and Community Development	P.O Box 6387	Thika	01000	Kenya
KEMRI CRDR Siaya Clinical Research Annex	Siaya County Referral Hospital Grounds	Siaya	40600	Kenya

FUNDING SOURCES
Name of source	Street address	City	Postal code	Country
Hoffmann La Roche	Grenzacherstrasse 124	Basel	4070	Switzerland

SPONSORS
Sponsor level	Name	Street address	City	Postal code	Country	Nature of sponsor
Primary Sponsor	Hoffmann La Roche	Grenzacherstrasse 124	Basel	4070	Switzerland	Commercial Sector/Industry

COLLABORATORS
Name	Street address	City	Postal code	Country
Nadia Walli	7070 Mississauga Road	Mississauga	L5N 5M8	Canada

CONTACT PEOPLE
Role	Name	Email	Phone	Street address
Principal Investigator	Jacqueline Mirera	jacquline.mirera@crean-health.com	+254715867708	Machakos Level 5 Hospital Site P.O. Box 19-90100 Machakos Kenya
City	Postal code	Country	Position/Affiliation
Machakos	90100	Kenya	Principal Investigator
Role	Name	Email	Phone	Street address
Principal Investigator	Jesse Gitaka	jgitaka@mku.ac.ke	+254722425613	P.O. Box 6387, Thika, Kenya
City	Postal code	Country	Position/Affiliation
Thika	00100	Kenya	Principal Investigator
Role	Name	Email	Phone	Street address
Principal Investigator	Teresia Kinyari	tmwendwa@uonbi.ac.ke	+254707028067	Prof Mungai Road Off Wasawo Drive Off Riverside Drive Chiromo Campus University Of Nairobi P.O. Box 19676 00202 Nairobi Kenya
City	Postal code	Country	Position/Affiliation
Nairobi	00202	Kenya	Principal Investigator
Role	Name	Email	Phone	Street address
Principal Investigator	Mary Matilu	inzianimatilu@gmail.com	+254722523370	KEMRI-Mtwapa Clinical Annex P.O. Box 428-80108, Mtwapa
City	Postal code	Country	Position/Affiliation
Kilifi	80108	Kenya	Principal Investigator
Role	Name	Email	Phone	Street address
Principal Investigator	Videlis Nduba	vnduba@gmail.com	+254724522474	Kenyatta Hospital complex Off hospital road
City	Postal code	Country	Position/Affiliation
Nairobi	00100	Kenya	Principal Investigator
Role	Name	Email	Phone	Street address
Public Enquiries	Videlis Ndube	vnduba@gmail.com	+254724522474	Kenyatta Hospital complex Off hospital road
City	Postal code	Country	Position/Affiliation
Nairobi	00100	Kenya	Principal Investigator
Role	Name	Email	Phone	Street address
Scientific Enquiries	Videlis Nduba	vnduba@gmail.com	+254724522474	Kenyatta Hospital complex Off hospital road
City	Postal code	Country	Position/Affiliation
Nairobi	00100	Kenya	Principal Investigator
Role	Name	Email	Phone	Street address
Principal Investigator	Videlis Nduba	vnduba@gmail.com	+254724522474	Siaya County Referral Hospital Grounds
City	Postal code	Country	Position/Affiliation
Siaya	144	Kenya	Principal Investigator

REPORTING
Share IPD	Description	Additional Document Types	Sharing Time Frame	Key Access Criteria
Yes	The Sponsor will comply with the requirements for publication of study results. All of the study data will be labelled with a participant identification (ID) number that is unique to the participants and not related to or derived from information that identifies the participants (such as name or any other personally identifying information).	Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol	2 years	Controlled , third-party
URL	Results Available	Results Summary	Result Posting Date	First Journal Publication Date
https://www.ClinicalTrials.gov	No
Result Upload 1:	Result Upload 2:	Result Upload 3:	Result Upload 4:	Result Upload 5:

Result URL Hyperlinks	Link To Protocol
Result URL Hyperlinks

Changes to trial information

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