Tanimilast Add-On Therapy for COPD

(PILLAR Trial)

Recruiting at 531 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

3973 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well a new drug, Tanimilast, works when added to the usual COPD treatment. COPD (chronic obstructive pulmonary disease) makes breathing difficult, and the trial aims to determine if Tanimilast can improve symptoms and ensure safety. Participants will receive either Tanimilast, Roflumilast (a medication used to reduce lung inflammation), or a placebo (a pill with no active medicine) for comparison. Suitable candidates have COPD with chronic bronchitis and have experienced at least one significant COPD flare-up in the past year. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Tanimilast (CHF6001) is generally well-tolerated in clinical studies, with no unexpected or concerning side effects observed. Tanimilast primarily targets the lungs, reducing its presence in the rest of the body. This design minimizes common side effects associated with its drug class, PDE4 inhibitors, which can sometimes cause issues like nausea.

Long-term studies on Roflumilast have shown it does not increase the risk of death over five years in people with COPD (Chronic Obstructive Pulmonary Disease). It improves quality of life by reducing lung inflammation and other symptoms. While generally safe, some individuals might experience mild side effects like weight loss or stomach upset.

Both treatments are under evaluation to determine their effectiveness when added to existing COPD therapies. So far, safety data from past studies is promising for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CHF6001 as a potential add-on therapy for COPD because it offers a novel mechanism of action compared to current treatments like bronchodilators and corticosteroids. Unlike these standard options, CHF6001 works by inhibiting the enzyme PDE4, which helps reduce inflammation in the lungs, a key issue in COPD. This targeted approach could lead to better control of symptoms and potentially fewer side effects, making it a promising alternative for those who don't respond well to existing therapies. Additionally, the study explores different dosages, which might help in finding the optimal balance between efficacy and safety.

What evidence suggests that this trial's treatments could be effective for COPD?

This trial will compare Tanimilast and Roflumilast as add-on therapies for COPD. Studies have shown that Tanimilast, which participants in this trial may receive, effectively treats COPD by reducing lung inflammation. It functions as an inhaled medication that calms lung inflammation. Research using animal models and lab tests with human cells has confirmed its ability to reduce inflammation.

Roflumilast, another treatment option in this trial, has been shown in studies to reduce flare-ups and improve lung function in people with COPD. It also lowers the frequency of symptom worsening, enhancing the quality of life for patients. Both treatments target inflammation, a major issue in COPD. ^{3 4 6 7 8}

Who Is on the Research Team?

Fernando J. MARTINEZ, Prof.

Principal Investigator

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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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, 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8977061/

Effectiveness of Roflumilast in Treating Chronic Obstructive ... Another study stated that roflumilast helps avoid COPD exacerbation and improves the quality of life [6]. This study was conducted to establish ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12511809/

Effects of Roflumilast on Exacerbations and Lung Function ... At 1-year follow-up, the roflumilast group exhibited a significantly higher rate of moderate exacerbations (69.2% vs. 31.3%, p=0.007) and greater frequency (2.0 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00297102

Study Details | NCT00297102 | Effect of Roflumilast on ... The aim of the study is to investigate the effect of roflumilast on exacerbation rate and pulmonary function in patients with chronic obstructive pulmonary ...

4. atsjournals.org atsjournals.org/doi/full/10.1164/rccm.200610-1563oc

Effect of 1-Year Treatment with Roflumilast in Severe ... In severe, stable COPD, PDE4 inhibition with roflumilast produced a modest but significant improvement in lung function without changing the exacerbation rate ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0954611113003831

Pooled subpopulation analyses of the effects of roflumilast ... Roflumilast reduced exacerbation rates and improved lung function in patients with COPD who received concomitant LABA, regardless of prior ICS use.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39185393/

Long-Term Safety of Roflumilast in Patients with Chronic ... There was no observed increase in 5-year mortality risk with the use of roflumilast in Sweden or Norway. A small increase in 5-year ...

7. chestpulmonary.org chestpulmonary.org/article/S2949-7892(25)00077-7/fulltext

Lung Function and Safety Outcomes in Patients With ... It is important to note that roflumilast is indicated to reduce the risk of COPD exacerbations in a limited population of patients with severe ...

8. journals.lww.com journals.lww.com/md-journal/fulltext/2018/02160/effect_and_safety_of_roflumilast_for_chronic.24.aspx

Effect and safety of roflumilast for chronic obstructive... This trial aimed to evaluate the efficacy and safety of roflumilast for treating Chinese patients with chronic obstructive pulmonary disease (COPD).