A Study to Evaluate the Efficacy and Safety of Astegolimab in Patients with Chronic Obstructive Pulmonary Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

14 Jul 2023 → 9 Jul 2025

Decision date (initial)

2023-07-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Others, Pharmacokinetic

To evaluate the efficacy of astegolimab compared with placebo
on the basis of annualized rate of moderate and severe COPD exacerbations over the 52-week treatment period

Secondary objectives 8

1. To evaluate the efficacy of astegolimab compared with placebo on the basis of time to first moderate or severe COPD exacerbation during the 52-week treatment period
2. To evaluate the efficacy of astegolimab compared with placebo on the basis of 1] absolute change from baseline in health-related quality of life (HRQoL) at Week 52, as assessed through the Saint George’s Respiratory Questionnaire-COPD (SGRQ-C) total score, 2] post-bronchodilator forced expiratory volume in 1 second (FEV1)(liters) and 3] Evaluating Respiratory Symptoms in COPD (E-RS:COPD) total score at Week 52
3. To evaluate the efficacy of astegolimab compared with placebo on the basis of proportion of participants with improvement in HRQoL, defined as a decrease from baseline of >= 4 points in SGRQ-C total score, at Week 52
4. To evaluate the efficacy of astegolimab compared with placebo on the basis of annualized rate of severe COPD exacerbations over the 52-week treatment period
5. To evaluate the safety of astegolimab compared with placebo
6. To characterize the astegolimab PK profile
7. To evaluate the immune response to astegolimab
8. To evaluate the efficacy of astegolimab compared with placebo on the basis of annualized rate of moderate and severe COPD exacerbations over the 52-week treatment period.

Conditions and MedDRA coding

Chronic Obstructive Pulmonary Disease (COPD)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Documented COPD diagnosis for >= 12 months prior to Visit 1
2. History of frequent exacerbations, defined as having had 2 or more moderate or severe COPD exacerbations within 12 months prior to Visit 1
3. Post-bronchodilatir FEV1 >= 20% and < 80% of predicted and FEV1/ forced vital capacity (FVC) < 0.70 at Visit 1 or Visit 2
4. mMRC score >= 2 at screening
5. Current tobacco smoker or former smoker (having stopped smoking for at least 6 months prior to Visit 1) with a history of smoking >= 10 pack-years (e.g., 20 cigarettes/day for 10 years)
6. On optimized COPD maintenance therapy of inhaled corticosteroid (ICS) plus long-acting beta-agonist (LABA), long-acting muscarinic antagonist (LAMA) plus LABA, or ICS plus LAMA plus LABA for >= 12 months prior to Visit 1

Exclusion criteria 6

1. History of clinically significant pulmonary disease other than COPD
2. History of long-term treatment with oxygen at > 4.0 liters/minute. While breathing supplemental oxygen, the participant should demonstrate an oxyhemoglobin saturation of >= 89%
3. Lung volume reduction surgery or procedure within 12 months prior to Visit 1
4. Any other serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant’s safe participation in and completion of the study
5. Unstable cardiac disease, myocardial infarction, or New York Heart Association Class III or IV heart failure within 12 months prior to screening
6. Pregnant or breastfeeding, or intention of becoming pregnant during the study or within 12 weeks after the final dose of astegolimab

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Annualized rate of moderate and severe COPD exacerbations over the 52-week treatment period

Secondary endpoints 12

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 >= 4 points in SGRQ-C total score, at Week 52
6. Annualized rate of severe COPD exacerbations over the 52-week treatment period
7. Incidence and severity of all treatment-emergent adverse events (TEAE), including Serious Adverse Events (SAEs), adverse events of special interests (AESIs), and TEAEs leading to death or discontinuation
8. Change from baseline in selected vital signs
9. Change from baseline in selected clinical laboratory test results and electrocardiograms (ECGs)
10. Serum concentration of astegolimab at specified timepoints
11. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study
12. Annualized rate of moderate and severe COPD exacerbations over the 52-week treatment period

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel Town

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information Support Line-TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information Support Line-TISL

Third parties 7

Locations

16 EU/EEA countries · 128 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 446 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

45 submissions — initial application plus substantial / non-substantial modifications