Astegolimab for COPD

(ARNASA Trial)

Recruiting in Palo Alto (17 mi)

+319 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Hoffmann-La Roche

Must be taking: ICS, LABA, LAMA

Must not be taking: Oral corticosteroids

Disqualifiers: Asthma, Pulmonary disease, Heart failure, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This study will evaluate the efficacy and safety of astegolimab compared with placebo in participants with chronic obstructive pulmonary disease (COPD) who are former or current smokers and have a history of frequent exacerbations.

Will I have to stop taking my current medications?

The trial requires that you stay on your current COPD maintenance therapy, which includes inhaled corticosteroids, long-acting beta-agonists, and long-acting muscarinic antagonists, for at least 4 weeks before screening. If you are on other medications, the protocol does not specify if you need to stop them.

What data supports the effectiveness of the drug Astegolimab for treating COPD?

Research suggests that targeting the IL-33/ST2 pathway, which Astegolimab does, may help reduce inflammation in COPD patients. This pathway is linked to disease progression, and similar treatments targeting related pathways have shown benefits in reducing exacerbations in certain COPD patients. ^{1 2 3 4 5}

How is the drug Astegolimab unique for treating COPD?

Astegolimab is unique because it targets the ST2 receptor, which is involved in the immune response, potentially offering a novel approach for treating COPD (chronic obstructive pulmonary disease) compared to traditional therapies that focus on bronchodilation or inflammation control. ^{6 7 8 9 10}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults over 18 with COPD, diagnosed at least a year ago. Participants should be current or former smokers with a significant smoking history and have had multiple COPD flare-ups in the past year. They must be on standard COPD medications but free from other lung conditions like asthma.

Inclusion Criteria

I have had 2 or more severe COPD flare-ups in the last year.

I have smoked at least 10 pack-years.

I was diagnosed with COPD over a year ago.

Exclusion Criteria

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous astegolimab or placebo every 2 or 4 weeks

24 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Astegolimab (Monoclonal Antibodies)
• Placebo (Other)

Trial Overview The study is testing astegolimab against a placebo to see if it's more effective in treating people with chronic obstructive pulmonary disease (COPD) who smoke or used to smoke and often have exacerbations of their condition.

Participant Groups

Group I: Astegolimab SC Q4W Experimental Treatment 1 Intervention

Participants will receive alternating SC astegolimab and placebo Q2W, thus receiving SC astegolimab Q4W.

Group II: Astegolimab SC Q2W Experimental Treatment 1 Intervention

Participants will receive subcutaneous (SC) astegolimab every 2 weeks (Q2W)

Group III: Placebo SC Q2W Placebo Group 1 Intervention

Participants will receive SC placebo Q2W

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Findings from Research

Dupilumab was found to be effective in treating chronic obstructive pulmonary disease (COPD) characterized by type 2 inflammation, as indicated by elevated eosinophil counts.

The study suggests that targeting type 2 inflammation with dupilumab could provide a new therapeutic approach for patients with COPD, potentially improving their respiratory function and overall quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In COPD with type 2 inflammation despite inhaled triple therapy, dupilumab safely reduced exacerbations. Estrada, RA., Maselli, DJ., Anzueto, AR.[2023]

The IL-33/ST2 pathway is significantly involved in the inflammation and alveolar damage seen in COPD, with its expression linked to disease progression, highlighting a potential target for new therapies.

Current research includes the development of antibodies targeting IL-33 and ST2, with ongoing clinical trials exploring their efficacy in treating COPD, which could lead to novel treatment options beyond existing inhaled corticosteroids and bronchodilators.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of IL-33/ST2 in COPD and Its Future as an Antibody Therapy. Riera-Martínez, L., Cànaves-Gómez, L., Iglesias, A., et al.[2023]

In a phase 2a trial involving patients with moderate-to-very severe COPD, astegolimab did not significantly reduce the rate of exacerbations compared to placebo, indicating limited efficacy in preventing acute worsening of the disease.

However, astegolimab was associated with improved health status as measured by the Saint George's Respiratory Questionnaire, suggesting potential benefits in quality of life despite not affecting exacerbation rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Astegolimab, an anti-ST2, in chronic obstructive pulmonary disease (COPD-ST2OP): a phase 2a, placebo-controlled trial. Yousuf, AJ., Mohammed, S., Carr, L., et al.[2023]

Monoclonal antibody (mAB) therapies have a moderate effect on reducing the risk of exacerbations in chronic obstructive pulmonary disease (COPD), but they do not significantly improve lung function (FEV1) or quality of life (SGRQ).

In eosinophilic COPD patients, the IL-5 antagonist mepolizumab was found to reduce exacerbation risk, while benralizumab showed effectiveness in improving both lung function and quality of life, highlighting the potential of targeting IL-5 pathways in specific patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging biological therapies for treating chronic obstructive pulmonary disease: A pairwise and network meta-analysis. Rogliani, P., Matera, MG., Puxeddu, E., et al.[2019]

A subset of patients with chronic obstructive pulmonary disease (COPD) who have elevated blood eosinophils may benefit from biologic treatments like mepolizumab, which targets eosinophilic inflammation.

Mepolizumab, a monoclonal antibody against interleukin-5 (IL-5), has shown potential therapeutic effects in these patients, particularly in those who do not respond adequately to standard inhaled corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mepolizumab in the treatment of eosinophilic chronic obstructive pulmonary disease. Mkorombindo, T., Dransfield, MT.[2020]

In a study involving 668 adults with moderate-to-severe Crohn's disease, those who received maintenance therapy with certolizumab pegol after an initial response were significantly more likely to maintain their response (62% vs. 34% for placebo) and achieve remission (48% vs. 29% for placebo) at 26 weeks.

Certolizumab pegol was effective regardless of concurrent treatments like glucocorticoids or immunosuppressants, but there were some safety concerns, including a 3% incidence of serious infections in the certolizumab group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance therapy with certolizumab pegol for Crohn's disease. Schreiber, S., Khaliq-Kareemi, M., Lawrance, IC., et al.[2022]

Pateclizumab, a humanized monoclonal antibody targeting lymphotoxin α, was found to be well-tolerated in rheumatoid arthritis patients, with no serious adverse events reported during the study involving both single and multiple ascending doses.

In the multiple ascending dose phase, patients receiving 3.0 mg/kg of pateclizumab showed significant clinical improvement, with 75% achieving ACR20 response rates, compared to 57% in the placebo group, indicating its potential efficacy in reducing disease activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and biologic activity of pateclizumab, a novel monoclonal antibody targeting lymphotoxin α: results of a phase I randomized, placebo-controlled trial. Emu, B., Luca, D., Offutt, C., et al.[2023]

In a 24-week study involving 316 Japanese rheumatoid arthritis patients, certolizumab pegol (CZP) combined with methotrexate (MTX) showed significantly higher ACR20 response rates compared to placebo, indicating effective symptom relief.

CZP treatment not only reduced RA symptoms but also significantly inhibited joint damage progression and improved health-related quality of life, with a similar safety profile across all treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of certolizumab pegol plus methotrexate in Japanese rheumatoid arthritis patients with an inadequate response to methotrexate: the J-RAPID randomized, placebo-controlled trial. Yamamoto, K., Takeuchi, T., Yamanaka, H., et al.[2022]

In a study of 662 adults with moderate-to-severe Crohn's disease, certolizumab pegol showed a modest improvement in response rates compared to placebo, with 35% of patients responding at week 6 versus 27% in the placebo group.

While certolizumab pegol was effective in inducing a response, it did not significantly improve remission rates, and there were some safety concerns, including serious adverse events occurring in 10% of patients treated with certolizumab compared to 7% in the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Certolizumab pegol for the treatment of Crohn's disease. Sandborn, WJ., Feagan, BG., Stoinov, S., et al.[2022]

A 39-year-old man developed thrombotic microangiopathy after 6 months of treatment with certolizumab pegol for ankylosing spondylitis, highlighting a potential adverse effect of this medication.

The patient's condition improved significantly with plasma exchange and corticosteroids, suggesting that while certolizumab pegol is effective for treating certain autoimmune diseases, it can also lead to serious complications like thrombotic microangiopathy, which may be immune-mediated or due to dose-dependent toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Induced Thrombotic Microangiopathy with Certolizumab Pegol Baysal, M., Ümit, EG., Sarıtaş, F., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

In COPD with type 2 inflammation despite inhaled triple therapy, dupilumab safely reduced exacerbations. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

The Role of IL-33/ST2 in COPD and Its Future as an Antibody Therapy. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Astegolimab, an anti-ST2, in chronic obstructive pulmonary disease (COPD-ST2OP): a phase 2a, placebo-controlled trial. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Emerging biological therapies for treating chronic obstructive pulmonary disease: A pairwise and network meta-analysis. [2019]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Mepolizumab in the treatment of eosinophilic chronic obstructive pulmonary disease. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Maintenance therapy with certolizumab pegol for Crohn's disease. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and biologic activity of pateclizumab, a novel monoclonal antibody targeting lymphotoxin α: results of a phase I randomized, placebo-controlled trial. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of certolizumab pegol plus methotrexate in Japanese rheumatoid arthritis patients with an inadequate response to methotrexate: the J-RAPID randomized, placebo-controlled trial. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Certolizumab pegol for the treatment of Crohn's disease. [2022]

10. Turkey pubmed.ncbi.nlm.nih.gov

Drug Induced Thrombotic Microangiopathy with Certolizumab Pegol [2019]