Tanimilast Add-On Therapy for COPD

(PILLAR Trial)

Recruiting at 402 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: Triple therapy

Must not be taking: Roflumilast

Disqualifiers: Asthma, Emphysema, Cancer, 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

3980 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy and the 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 continue their regular maintenance triple therapy for COPD.

Is Tanimilast (also known as Roflumilast) safe for humans?

Roflumilast, a treatment for COPD, is generally well tolerated in humans, with common side effects including diarrhea and weight loss. It is not linked to an increased risk of respiratory disease or infection and may reduce the risk of heart-related issues, though it can increase the risk of psychiatric side effects. ^{1 2 3 4 5}

How does Tanimilast add-on therapy for COPD differ from other treatments?

Tanimilast add-on therapy for COPD is unique because it involves the use of a novel inhalable formulation that targets lung macrophages, potentially enhancing the delivery and effectiveness of the treatment. This approach may offer a more targeted and efficient way to manage COPD compared to traditional treatments. ^{6 7 8 9 10}

Research Team

Fernando J. MARTINEZ, Prof.

Principal Investigator

Weill Cornell Medical College, New York Presbyterian Hospital, 1305 York avenue box 96 NY 10021 USA

Eligibility Criteria

This trial is for adults over 40 with COPD and chronic bronchitis who are current or former heavy smokers. They must have had at least one moderate to severe flare-up in the past year, be on stable triple therapy for COPD, and have a certain level of lung function reduction. People with neurological diseases, active cancer, recent Roflumilast use, other respiratory disorders besides COPD, significant liver issues or cardiovascular conditions can't join.

Inclusion Criteria

I had at least one severe COPD flare-up in the last year.

My lung function is severely reduced, below half of what's expected.

I am 40 or older with COPD and chronic bronchitis.

Exclusion Criteria

I haven't had a severe COPD flare-up in the last 4 weeks.

I currently have or previously had lung cancer.

I have a neurological condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CHF6001 (Tanimilast) or comparator treatments as 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
• Roflumilast

Trial Overview The study tests two doses of CHF6001 (Tanimilast) added to standard triple therapy against a placebo and an existing medication called Roflumilast (Daliresp). It aims to see if Tanimilast is effective and safe over a period of 52 weeks in improving symptoms for those with COPD and chronic bronchitis.

Participant Groups

Group I: CHF6001 3200µg Experimental Treatment 1 Intervention

Group II: CHF6001 1600µg Experimental Treatment 1 Intervention

Group III: Roflumilast Active Control 1 Intervention

Group IV: 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

Roflumilast is an effective treatment for patients with moderate to severe chronic obstructive pulmonary disease (COPD), improving lung function and reducing the risk of exacerbations, especially in those with chronic bronchitis.

While generally well tolerated, the most common side effect is diarrhea, and although there is a risk of psychiatric issues and weight loss, roflumilast does not increase the risk of respiratory infections and may lower cardiovascular risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Roflumilast: A Review in COPD. Garnock-Jones, KP.[2022]

Roflumilast, a phosphodiesterase-4 inhibitor, has shown potential as an effective anti-inflammatory treatment for asthma and COPD, based on various studies including animal and human trials.

The drug has a favorable safety profile with no documented drug interactions, making it a promising option for patients, although further research is necessary to confirm its role in therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential role of roflumilast: the new phosphodiesterase-4 inhibitor. Karish, SB., Gagnon, JM.[2022]

Roflumilast, an oral PDE-4 inhibitor, has been shown to significantly reduce COPD exacerbations and improve lung function in nearly 4500 patients across six clinical trials, particularly benefiting those with severe COPD and chronic bronchitis.

While generally safe, common side effects include diarrhea, nausea, and headache, with potential risks of weight loss and psychiatric events, highlighting the need for careful patient selection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Roflumilast in the management of chronic obstructive pulmonary disease. Lipari, M., Benipal, H., Kale-Pradhan, P.[2019]

Roflumilast is an effective oral treatment for moderate to severe COPD, improving lung function and reducing exacerbation rates, especially when used alongside long-acting bronchodilators.

The treatment is generally well-tolerated, with mild to moderate side effects like nausea, diarrhea, and weight loss, which are mostly self-limiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PDE4-inhibitors: a novel, targeted therapy for obstructive airways disease. Diamant, Z., Spina, D.[2014]

Roflumilast, a phosphodiesterase-4 inhibitor, significantly improved lung function in COPD patients, with an increase in forced expiratory volume (FEV1) of 36-88 mL compared to placebo, based on data from 6 clinical trials.

While roflumilast reduced exacerbation rates in some patients with chronic cough and a history of exacerbations, it also had common adverse effects, leading to discontinuation in 9% to 16% of patients, including gastrointestinal issues and headaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Roflumilast: a phosphodiesterase-4 inhibitor for the treatment of severe chronic obstructive pulmonary disease. Pinner, NA., Hamilton, LA., Hughes, A.[2022]

In a study of 242 HIV-1-infected patients with mild to moderate renal impairment, switching to a once-daily regimen of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) showed no significant change in kidney function after 48 weeks, indicating its safety for this population.

Patients experienced significant improvements in proteinuria and bone mineral density, with 92% maintaining viral suppression, demonstrating the efficacy of E/C/F/TAF without the need for dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Patients With Renal Impairment: 48-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study. Pozniak, A., Arribas, JR., Gathe, J., et al.[2021]

Novel lipid-polymer hybrid nanoparticles (LPHNPs) were developed to effectively deliver Roflumilast for treating chronic obstructive pulmonary disease (COPD), showing good compatibility with human lung cells and targeted uptake by lung macrophages.

These nanoparticles are designed to slowly release the drug and have mucus-penetrating properties, making them suitable for inhalable formulations, which could enhance the delivery and efficacy of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhalable Formulation Based on Lipid-Polymer Hybrid Nanoparticles for the Macrophage Targeted Delivery of Roflumilast. Craparo, EF., Cabibbo, M., Scialabba, C., et al.[2022]

Switching from the E/C/F/TDF regimen to E/C/F/TAF resulted in a significant reduction of tenofovir concentrations in cerebrospinal fluid (CSF), while maintaining stable levels of elvitegravir, indicating effective antiviral activity in the central nervous system.

The study found no virologic failure or significant changes in neurocognitive performance after 24 weeks, suggesting that the E/C/F/TAF regimen is safe and well-tolerated in treatment-experienced adults living with HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switching to Tenofovir Alafenamide in Elvitegravir-Based Regimens: Pharmacokinetics and Antiviral Activity in Cerebrospinal Fluid. Ma, Q., Ocque, AJ., Morse, GD., et al.[2021]

Tenofovir disoproxil fumarate (tenofovir DF) is an effective once-daily oral medication for treating HIV, significantly reducing viral load in both treatment-experienced and treatment-naive patients.

The drug is generally well tolerated and supports sustained suppression of viral replication, making it a convenient option in combination with other antiretroviral agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenofovir disoproxil fumarate: a review of its use in the management of HIV infection. Lyseng-Williamson, KA., Reynolds, NA., Plosker, GL.[2018]

In a study involving 45 patients with HIV, those on boosted Tenofovir alafenamide (TAF) showed similar urine tenofovir (TFV) concentrations to those on unboosted TAF, indicating that the dose adjustments for boosted TAF do not affect drug levels significantly.

These findings suggest that a single point-of-care urine immunoassay for TAF can be used for monitoring adherence in patients regardless of whether they are on boosted or unboosted TAF, simplifying adherence assessments in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief Report: No Difference in Urine Tenofovir Levels in Patients Living With HIV on Unboosted Versus Dose-Adjusted Boosted Tenofovir Alafenamide. Johnson, KA., Okochi, H., Glidden, DV., et al.[2023]

References

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

Roflumilast: A Review in COPD. [2022]

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

The potential role of roflumilast: the new phosphodiesterase-4 inhibitor. [2022]

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

Roflumilast in the management of chronic obstructive pulmonary disease. [2019]

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

PDE4-inhibitors: a novel, targeted therapy for obstructive airways disease. [2014]

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

Roflumilast: a phosphodiesterase-4 inhibitor for the treatment of severe chronic obstructive pulmonary disease. [2022]

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

Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Patients With Renal Impairment: 48-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study. [2021]

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

Inhalable Formulation Based on Lipid-Polymer Hybrid Nanoparticles for the Macrophage Targeted Delivery of Roflumilast. [2022]

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

Switching to Tenofovir Alafenamide in Elvitegravir-Based Regimens: Pharmacokinetics and Antiviral Activity in Cerebrospinal Fluid. [2021]

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

Tenofovir disoproxil fumarate: a review of its use in the management of HIV infection. [2018]

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

Brief Report: No Difference in Urine Tenofovir Levels in Patients Living With HIV on Unboosted Versus Dose-Adjusted Boosted Tenofovir Alafenamide. [2023]