Astegolimab for Chronic Obstructive Pulmonary Disease

Recruiting at 227 trial locations

Overseen By Reference Study ID Number: GB43311 www.roche.com/about_roche/roche_worldwide.htm

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Genentech, Inc.

Must be taking: ICS, LABA, LAMA

Must not be taking: Oral corticosteroids

Disqualifiers: Asthma, Pulmonary disease, Cardiac disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 12 weeks

1440 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medication called astegolimab along with usual COPD treatments. It targets people with COPD who smoke or used to smoke and often have flare-ups. The medication aims to reduce lung inflammation, helping to prevent these flare-ups and improve breathing.

Will I have to stop taking my current medications?

The trial requires you to stay on your current COPD maintenance therapy without changes before and during the study. 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 chronic obstructive pulmonary disease (COPD)?

Astegolimab, which targets the ST2 receptor involved in inflammation, has shown potential in reducing exacerbations in COPD, similar to how other monoclonal antibodies like mepolizumab have been effective in certain COPD patients with specific inflammatory profiles. ^{1 2 3 4 5}

Is Astegolimab safe for humans?

Astegolimab has been tested in patients with severe asthma and showed typical behavior for a monoclonal antibody-based drug, with no unexpected safety concerns. The highest dose tested performed close to the maximum effect, suggesting it is generally safe at the tested doses. ^{1 2 5 6 7}

How is the drug astegolimab different from other treatments for COPD?

Astegolimab is unique because it targets the ST2 receptor, blocking interleukin-33 signaling, which is involved in airway inflammation in COPD. This mechanism is different from other treatments like mepolizumab, which targets interleukin-5 for eosinophilic inflammation. ^{1 2 3 5 8}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with COPD who smoke or used to smoke, have had frequent flare-ups, and are on stable lung medication. They must not have other significant lung diseases, recent respiratory infections or hospitalizations, unstable heart conditions, or be starting new pulmonary treatments.

Inclusion Criteria

I've had 2 or more severe health flare-ups in the last year.

I often feel short of breath when moving around.

I have been on a stable COPD treatment plan for at least 4 weeks.

Exclusion Criteria

I am enrolled or planning to enroll in a lung rehab program.

I have been on oxygen therapy using more than 4 liters per minute for a long time.

I have had a lung transplant.

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 in combination with standard COPD maintenance therapy

12 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Astegolimab
• Placebo

Trial Overview The study tests Astegolimab's effectiveness and safety in combination with standard COPD care versus a placebo. It aims to see if this treatment can help reduce the number of severe breathing problems (exacerbations) in people with COPD.

Participant Groups

Group I: Astegolimab Q4W Experimental Treatment 1 Intervention

Participants will receive alternating SC astegolimab and placebo Q2W, thus receiving astegolimab every 4 weeks (Q4W).

Group II: Astegolimab Q2W Experimental Treatment 1 Intervention

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

Group III: Placebo Placebo Group 1 Intervention

Participants will receive SC placebo Q2W.

Who Is Running the Clinical Trial?

Genentech, Inc.

Lead Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

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]

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 two phase 3 trials involving patients with chronic obstructive pulmonary disease (COPD) and an eosinophilic phenotype, mepolizumab (100 mg) significantly reduced the annual rate of moderate or severe exacerbations compared to placebo, particularly in patients with higher blood eosinophil counts.

The safety profile of mepolizumab was comparable to that of placebo, indicating that it is a safe treatment option for reducing exacerbations in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mepolizumab for Eosinophilic Chronic Obstructive Pulmonary Disease. Pavord, ID., Chanez, P., Criner, GJ., et al.[2022]

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]

Astegolimab, a monoclonal antibody targeting the ST2 receptor, was evaluated in a phase 2b study involving 368 patients with uncontrolled severe asthma, showing typical pharmacokinetic behavior for monoclonal antibodies.

The study found that the highest tested dose of 490 mg every 4 weeks approached maximum efficacy, indicating that increasing the dose further may not yield additional benefits in reducing asthma exacerbations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics and Exposure-Response Relationships of Astegolimab in Patients With Severe Asthma. Kotani, N., Dolton, M., Svensson, RJ., et al.[2022]

Tezepelumab, a monoclonal antibody for severe asthma, showed an acceptable safety profile in a phase 1 study with 24 healthy Japanese men, with no serious adverse events reported and no participants developing antibodies against the drug.

The pharmacokinetics of tezepelumab demonstrated linear absorption and a long half-life of approximately 24 days, indicating it is well-tolerated and may provide sustained therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Subcutaneous Tezepelumab in Healthy Japanese Men. Sakamoto, K., Matsuki, S., Irie, S., et al.[2022]

Tezepelumab, a monoclonal antibody approved for severe uncontrolled asthma, significantly improved forced expiratory volume (FEV1) by 0.15 L and reduced asthma exacerbation rates by 0.60 per year compared to placebo, based on a meta-analysis of six trials with 2667 patients.

The treatment was found to have an acceptable safety profile, with no higher incidence of adverse drug reactions compared to placebo, indicating it is a safe option for patients with severe asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tezepelumab for Patients with Severe Uncontrolled Asthma: A Systematic Review and Meta-Analysis. Zoumot, Z., Al Busaidi, N., Tashkandi, W., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

Mepolizumab for Eosinophilic Chronic Obstructive Pulmonary Disease. [2022]

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

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

5. England pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics and Exposure-Response Relationships of Astegolimab in Patients With Severe Asthma. [2022]

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

A Phase 1, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Subcutaneous Tezepelumab in Healthy Japanese Men. [2022]

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

Tezepelumab for Patients with Severe Uncontrolled Asthma: A Systematic Review and Meta-Analysis. [2022]

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

No genetic associations with mepolizumab efficacy in COPD with peripheral blood eosinophilia. [2020]