Tanimilast Add-On Therapy for Chronic Obstructive Pulmonary Disease

(PILASTER Trial)

Recruiting at 453 trial locations

Overseen By Chiesi Clinical Trial info

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Chiesi Farmaceutici S.p.A.

Must be taking: Maintenance triple therapy

Must not be taking: Roflumilast

Disqualifiers: Asthma, Cancer, Depression, Cardiovascular, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

3435 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to evaluate the efficacy and safety of two doses of CHF6001 (Tanimilast), as add-on to maintenance triple therapy in the target patient population.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires participants to have been on regular maintenance triple therapy for at least 12 months before joining. This suggests you should continue your current COPD medications.

How does the drug Tanimilast differ from other treatments for COPD?

Tanimilast is unique because it is an inhaled phosphodiesterase-4 inhibitor, which targets inflammation in the lungs, unlike many other COPD treatments that focus on bronchodilation (widening of the airways). This mechanism may offer additional benefits in reducing lung inflammation for COPD patients. ^{1 2 3 4 5}

Research Team

Klaus F. Rabe, Prof.

Principal Investigator

LungenClinic Grosshansdorf GmbH Wöhrendamm 80 22927 Großhansdorf GERMANY

Eligibility Criteria

This trial is for adults over 40 with COPD and chronic bronchitis who are current or ex-smokers. They must have had a moderate to severe flare-up in the past year, be on triple therapy for at least 3 months, and not have emphysema, asthma, significant neurological diseases, recent roflumilast treatment, serious lab abnormalities, α-1 antitrypsin deficiency-related COPD, major heart issues or liver impairment.

Inclusion Criteria

I have smoked at least 10 pack-years.

I am 40 or older with COPD and chronic bronchitis.

Your CAT score is 10 or higher.

Exclusion Criteria

I have not had a severe COPD flare-up in the last 4 weeks.

I have not taken Roflumilast in the last 6 months.

I have COPD, emphysema, or a combination of lung conditions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CHF6001 (Tanimilast) or placebo as an add-on to maintenance triple therapy

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CHF6001 DPI (Tanimilast)

Trial Overview The study tests two doses of CHF6001 (Tanimilast) added to standard triple therapy against a placebo. It aims to see if Tanimilast can improve symptoms in people with COPD and chronic bronchitis over one year.

Participant Groups

Group I: CHF6001 3200µg Experimental Treatment 1 Intervention

Group II: CHF6001 1600µg Experimental Treatment 1 Intervention

Group III: CHF6001 Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Chiesi Farmaceutici S.p.A.

Lead Sponsor

Trials

206

Recruited

315,000+

Founded

1935

Headquarters

Parma, Italy

Known For

Respiratory diseases

Top Products

NEXThaler, Trimbow, Curosurf, Holoclar

Findings from Research

In a study involving 26 participants, the combination of CHF 5993 (a triple therapy for COPD and asthma) and cimetidine showed small but statistically significant increases in the plasma levels of glycopyrronium bromide (GB), indicating that cimetidine slightly enhances the drug's absorption without causing major changes in its elimination.

The study found no clinically relevant drug-drug interactions between CHF 5993 and cimetidine, as there were few adverse events reported and no serious adverse events, suggesting that the combination is safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Two-Period Open-Label, Single-Dose Crossover Study in Healthy Volunteers to Evaluate the Drug-Drug Interaction Between Cimetidine and Inhaled Extrafine CHF 5993. Mariotti, F., Ciurlia, G., Spaccapelo, L., et al.[2018]

In a Phase IIa study involving 61 patients with COPD, CHF6001, an inhaled phosphodiesterase-4 inhibitor, demonstrated significant anti-inflammatory effects, particularly reducing key inflammatory markers in sputum and blood compared to placebo.

Specifically, CHF6001 at a dose of 800 μg significantly decreased macrophage counts and various inflammatory mediators, including TNFα, indicating its potential to enhance treatment outcomes for patients already on triple inhaled therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the inhaled PDE4 inhibitor CHF6001 on biomarkers of inflammation in COPD. Singh, D., Beeh, KM., Colgan, B., et al.[2022]

In a study of 1130 patients with chronic obstructive pulmonary disease (COPD), the novel inhaled phosphodiesterase-4 inhibitor CHF6001 did not show significant improvements in lung function (pre-dose FEV1) compared to placebo after 12 weeks, indicating limited efficacy in this primary outcome.

However, CHF6001 was well tolerated with no significant safety concerns, and post-hoc analyses suggested that patients with chronic bronchitis, especially those with higher eosinophil counts, may benefit more from the treatment, showing significant reductions in exacerbation rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of CHF6001, a novel inhaled PDE4 inhibitor in COPD: the PIONEER study. Singh, D., Emirova, A., Francisco, C., et al.[2022]

The fixed-dose combination of glycopyrrolate and formoterol (GFF MDI) significantly improved lung function in patients with moderate-to-very severe COPD after 7 days of treatment, outperforming monocomponent inhalers and placebo.

Both doses of GFF MDI (72/9.6 μg and 36/9.6 μg) were well tolerated, indicating a favorable safety profile for this combination therapy in managing COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, seven-day study to assess the efficacy and safety of a glycopyrrolate/formoterol fumarate fixed-dose combination metered dose inhaler using novel Co-Suspension™ Delivery Technology in patients with moderate-to-very severe chronic obstructive pulmonary disease. Reisner, C., Fabbri, LM., Kerwin, EM., et al.[2022]

In a study involving 150 Japanese patients with moderate-to-very severe COPD, the fixed-dose combination of glycopyrrolate/formoterol fumarate (GFF MDI) significantly improved lung function compared to both its individual components and placebo, with a notable increase in forced expiratory volume (FEV1).

The GFF MDI also showed positive trends in patient-reported outcomes related to dyspnea and quality of life, while treatment-related adverse events were low, occurring in 4.5% or fewer patients, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of glycopyrrolate/formoterol fumarate metered dose inhaler delivered using co-suspension delivery technology in Japanese patients with moderate-to-very severe chronic obstructive pulmonary disease. Gon, Y., Nishi, K., Sato, K., et al.[2022]

References

1. France pubmed.ncbi.nlm.nih.gov

A Two-Period Open-Label, Single-Dose Crossover Study in Healthy Volunteers to Evaluate the Drug-Drug Interaction Between Cimetidine and Inhaled Extrafine CHF 5993. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Effect of the inhaled PDE4 inhibitor CHF6001 on biomarkers of inflammation in COPD. [2022]

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

Efficacy and safety of CHF6001, a novel inhaled PDE4 inhibitor in COPD: the PIONEER study. [2022]

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

A randomized, seven-day study to assess the efficacy and safety of a glycopyrrolate/formoterol fumarate fixed-dose combination metered dose inhaler using novel Co-Suspension™ Delivery Technology in patients with moderate-to-very severe chronic obstructive pulmonary disease. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of glycopyrrolate/formoterol fumarate metered dose inhaler delivered using co-suspension delivery technology in Japanese patients with moderate-to-very severe chronic obstructive pulmonary disease. [2022]