Inhaled GDC-6988 for Obstructive Lung Disease

Recruiting at 5 trial locations

Overseen By Reference Study ID Number: GB45429 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Genentech, Inc.

Disqualifiers: Pregnancy, Acute respiratory infection, Immunodeficiency, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

128 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of an inhaled drug called GDC-6988 for individuals with muco-obstructive lung diseases. Participants will receive different doses of the medication to assess bodily responses and potential improvements in lung issues. Those with stable lung conditions, such as chronic bronchitis or non-cystic fibrosis bronchiectasis (persistent lung infections causing coughing and mucus), for at least 28 days may qualify. Current smokers or individuals with recent lung infections are not eligible. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Do I need to stop my current medications for the trial?

No, you do not need to stop your current medications. Participants must be on a stable treatment regimen for muco-obstructive diseases for at least 28 days before starting the study and must remain on it throughout the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research is investigating the safety and effectiveness of inhaled GDC-6988 for people with lung diseases that cause mucus buildup. Detailed safety information from past studies is not yet available, as this treatment remains in the early testing stages. Researchers are currently assessing the drug's safety for humans by monitoring side effects and evaluating tolerance. Although this treatment is new, ongoing tests indicate that researchers continue to gather crucial safety data. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for obstructive lung disease, like inhalers and corticosteroids, help by reducing inflammation or relaxing the airway muscles. But GDC-6988 stands out with its novel inhaled formulation that targets lung tissue directly. This innovative delivery method allows the drug to work more quickly and potentially with fewer systemic side effects. Researchers are excited because GDC-6988 might offer faster relief and improved lung function, which could be a game-changer for patients struggling with obstructive lung conditions.

What evidence suggests that inhaled GDC-6988 might be an effective treatment for obstructive lung disease?

Research has shown that GDC-6988 is under investigation as a potential treatment for lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease (COPD), which cause mucus to block airways. Participants in this trial will receive varying doses of GDC-6988 to assess its effectiveness. The treatment enhances the activity of a protein called TMEM16A, which aids in clearing mucus from the lungs. This is crucial because sticky mucus can make breathing difficult. Although specific data on its effectiveness in people is not yet available, early studies suggest the drug could help improve breathing by clearing mucus build-up in the lungs. ^{1 2 3 5 6}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Genentech, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with obstructive lung diseases like asthma, COPD, or bronchiectasis. Participants must have a certain level of lung function (FEV1 ≥ 40%), stable disease for at least 28 days, and be able to use the Smart DPI inhaler correctly. Smokers or former smokers with a significant smoking history are eligible if they meet other criteria such as chronic cough and sputum production.

Inclusion Criteria

My lung function test shows at least 40% normal airflow.

I have been on a stable treatment for my lung condition for at least 28 days and am willing to continue it during the study.

I can correctly use the Smart DPI as judged by the investigator.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive inhaled GDC-6988. Cohort 1 receives low dose on Day 1 and high dose on Day 2. Cohort 2 receives high dose for 14 days. Cohorts 3 and 4 receive low dose for 14 days.

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GDC-6988

Trial Overview The trial is testing GDC-6988, an inhaled medication for people with muco-obstructive diseases. It aims to assess the safety and effects of this treatment on patients' conditions.

How Is the Trial Designed?

Group I: GDC-6988 Experimental Treatment 1 Intervention

Participants in cohort 1 will receive low dose GDC-6988 twice a day (BID) on Day 1 followed by high dose BID on Day 2. Participants in cohort 2 will receive low dose followed by high dose GDC-6988 BID for 14 days. Participants in Cohorts 3 and 4 will receive low dose GDC-6988 BID for 14-days.

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

Published Research Related to This Trial

The fixed-dose combination of glycopyrronium bromide and formoterol (GB/FF) administered twice daily significantly improved lung function in COPD patients compared to glycopyrronium monotherapy, with a notable increase in peak FEV1 after 12 weeks of treatment.

Both treatment groups experienced similar rates of adverse events, indicating that GB/FF is safe and well tolerated for patients with moderate-to-severe COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of glycopyrronium/formoterol fixed-dose combination versus glycopyrronium monotherapy in patients with moderate-to-severe COPD. Salvi, S., Jain, MK., Krishnamurthy, S., et al.[2023]

Glycopyrrolate (GLY) delivered via the eFlow closed system nebulizer is effective for maintaining treatment in chronic obstructive pulmonary disease (COPD), showing significant improvements in lung function and patient-reported outcomes based on phase 2 and phase 3 studies.

The eFlow CS nebulizer offers a rapid and efficient delivery of GLY, providing bronchodilation within 30 minutes and lasting for 12 hours, making it a suitable option for patients who may struggle with traditional inhalers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycopyrrolate/eFlow CS: The First Nebulized Long-Acting Muscarinic Antagonist Approved to Treat Chronic Obstructive Pulmonary Disease. Pleasants, RA.[2020]

In a study involving 466 patients with moderate-to-very severe COPD in China, the glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI) significantly improved lung function compared to both its individual components and a placebo, with a notable increase in forced expiratory volume at Week 24.

GFF MDI also enhanced daily symptom scores and reduced the time to clinically important deterioration, while demonstrating a similar safety profile to the monocomponents and placebo, indicating it is a well-tolerated and effective treatment option for COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy And Safety Of Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler (GFF MDI) Formulated Using Co-Suspension Delivery Technology In Chinese Patients With COPD. Chen, R., Zhong, N., Wang, HY., et al.[2021]

The new 2023 GOLD classification for COPD was found to have poor prognostic properties, showing only a weak ability to predict patient survival compared to previous GOLD classifications and the BODE index.

In particular, patients classified in group B and group E of the new GOLD system had a significantly increased risk of death, but overall, the BODE index provided a better assessment of mortality risk in COPD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic Properties of the GOLD 2023 Classification System. Brat, K., Svoboda, M., Zatloukal, J., et al.[2023]

The study evaluated the pharmacokinetics and safety of a fixed-dose combination of glycopyrronium and formoterol (GFF MDI) in healthy Japanese subjects, showing that the addition of formoterol did not significantly change the pharmacokinetic profile of glycopyrronium.

Both GFF MDI and glycopyrronium MDI were well tolerated, indicating a favorable safety profile, which supports further research on GFF MDI for treating COPD in Japanese patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety of a single dose of the novel LAMA/LABA fixed-dose combination of glycopyrronium/formoterol fumarate dihydrate metered dose inhaler, formulated using co-suspension delivery technology, in Japanese healthy subjects. Reisner, C., Miller, J., DePetrillo, P., et al.[2019]

In a study involving 65 patients with moderate-to-severe COPD, glycopyrronium bromide (GB) significantly improved lung function (FEV1) compared to placebo, with higher doses showing greater efficacy.

GB was found to be safe, with all adverse events being mild to moderate in severity and a lower incidence compared to placebo, suggesting that a dose of 25 μg twice daily may be optimal for treating COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bronchodilator efficacy of extrafine glycopyrronium bromide: the Glyco 2 study. Singh, D., Scuri, M., Collarini, S., et al.[2018]

In a study involving 30 subjects with moderate-to-severe COPD, glycopyrronium bromide (GLY) delivered via a nebulizer (eFlow) showed similar bronchodilation effects compared to a dry powder inhaler (DPI), despite lower systemic drug levels from the nebulizer.

Fewer adverse events were reported with the nebulizer (15 events) compared to the DPI (18 events), suggesting that nebulized GLY may be a safer alternative for patients who struggle with conventional inhalers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of systemic absorption and bronchodilator effect of glycopyrronium bromide delivered by nebulizer or a dry powder inhaler in subjects with chronic obstructive pulmonary disease. Leaker, BR., Singh, D., Nicholson, GC., et al.[2020]

The GOLD guidelines for COPD treatment have evolved significantly from 2001 to 2011, increasing from 35 to 54 recommendations, with 28 new recommendations added, reflecting advancements in the understanding of COPD management.

Approximately 45% of the recommendations in the 2011 guidelines were based on high-quality evidence from randomized controlled trials (grade A), indicating a need for further research to strengthen the evidence base for many treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of changes in guidelines for medication management of stable chronic obstructive pulmonary disease. Lin, FJ., Lee, TA., Wong, PS., et al.[2015]

In a study involving 2379 COPD patients, nebulized glycopyrrolate (GLY) demonstrated significant improvements in lung function and patient-reported outcomes, regardless of pre-existing cardiovascular risk factors.

The safety profile of GLY was acceptable, with similar rates of treatment-emergent adverse events across different cardiovascular risk groups, and lower discontinuation rates due to adverse events compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Nebulized Glycopyrrolate/eFlow® Closed System in Patients with Moderate-to-Very-Severe Chronic Obstructive Pulmonary Disease with Pre-Existing Cardiovascular Risk Factors. Ferguson, GT., Tosiello, R., Sanjar, S., et al.[2020]

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]

In a study involving 80 patients with moderate-to-very severe COPD, the fixed-dose combination inhaler GFF MDI showed similar bronchodilation effects whether used with or without the Aerochamber Plus® VHC, indicating flexibility in its use.

Both delivery methods were well tolerated, with comparable safety profiles, suggesting that the VHC can be beneficial for patients who struggle with using a metered dose inhaler correctly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized study of the effects of Aerochamber Plus® Flow-Vu® on the efficacy, pharmacokinetics and safety of glycopyrronium/formoterol fumarate dihydrate metered dose inhaler in patients with chronic obstructive pulmonary disease. Fakih, F., Spangenthal, S., Sigal, B., et al.[2022]

In a study involving 40 patients with moderate to severe emphysema, R667 was administered in multiple doses (0.2, 0.5, or 1 mg) for 14-16 days, showing that its pharmacokinetics were dose-proportional and similar to those observed in healthy volunteers.

R667 was well tolerated by patients, indicating a favorable safety profile for this novel emphysema treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of a novel agent, R667, in patients with emphysema. Chiu, YY., Roth, MD., Kolis, S., et al.[2018]

In a study involving 1532 patients with severe COPD, the inhaled triple therapy (BDP/FF/G) significantly reduced the rate of moderate-to-severe exacerbations compared to the dual bronchodilator (IND/GLY), with a rate ratio of 0.848 in favor of BDP/FF/G.

Both treatments had similar safety profiles, with pneumonia rates being equal (4% in both groups) and only one serious adverse event reported in each treatment group, indicating that BDP/FF/G does not increase the risk of pneumonia compared to IND/GLY.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial. Papi, A., Vestbo, J., Fabbri, L., et al.[2022]

A consensus among 31 Belgian pulmonologists and 10 European COPD experts supports the use of long-acting bronchodilators as the preferred first-choice treatment for chronic obstructive pulmonary disease (COPD) across various GOLD categories.

For patients classified as GOLD D with FEV1<50%, a strong agreement was found for using a combination of long-acting muscarinic antagonist (LAMA) and long-acting β2-agonist (LABA), while inhaled corticosteroids (ICS) are recommended only for those with frequent or severe exacerbations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled treatment of COPD: a Delphi consensus statement. Ninane, V., Corhay, JL., Germonpré, P., et al.[2022]

In a study of less symptomatic COPD patients, over 50% received inhalation therapies that did not align with the GOLD guidelines, indicating a gap between recommended and actual treatment practices.

Among different inhalation therapies, patients using long-acting muscarinic antagonists (LAMA) showed better lung function compared to those on combination therapies, but there were no significant differences in exacerbation rates, hospitalizations, or mortality across the treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of different inhalation therapies on less symptomatic chronic obstructive pulmonary disease patients in a Chinese population: a real-world study. Song, Q., Lin, L., Zhou, A., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06603246

A Study to Test the Safety and Effects of Inhaled GDC-6988 ... This study evaluates the safety, tolerability, and activity of inhaled GDC-6988 in participants with muco-obstructive disease. Official Title. A Phase Ic, Open- ...

2. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/10.1002/psp4.70027

Mechanistic Physiologically Based Pharmacokinetic Modeling ... GDC-6988 is under investigation as a potential treatment of muco-obstructive lung diseases (e.g., cystic fibrosis, chronic obstructive pulmonary ...

3. withpower.com withpower.com/trial/phase-1-pulmonary-disease-chronic-obstructive-9-2024-4fcfb?condition=Chronic+Obstructive+Pulmonary+Disease&overallStatus=Recruiting&hasNoPlacebo=false

Inhaled GDC-6988 for Obstructive Lung Disease The available research does not provide specific data on the effectiveness of Inhaled GDC-6988 for Obstructive Lung Disease. Instead, it discusses other ...

4. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/respiratory-disorder/copd/a-study-to-test-the-safety-and-effects-of-inhaled-gdc-6-20197.html

Clinical trial for Chronic Obstructive Pulmonary Disease ... Study Summary. This study evaluates the safety, tolerability, and activity of inhaled GDC-6988 in patients with muco-obstructive disease.

5. researchgate.net researchgate.net/publication/390411557_Mechanistic_Physiologically_Based_Pharmacokinetic_Modeling_of_Dry_Powder_and_Nebulized_Formulations_of_Orally_Inhaled_TMEM16A_Potentiator_GDC-6988

(PDF) Mechanistic Physiologically Based Pharmacokinetic ... In this study, a mechanistic lung physiologically based pharmacokinetic (PBPK) model was built using a middle‐out approach (i.e., combining elements of bottom‐ ...

6. synapse.patsnap.com synapse.patsnap.com/drug/3b8441fb616b4690bfaa558900dfdae2

RG-6421 - Drug Targets, Indications, Patents A Phase Ic, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, and Activity of Inhaled GDC-6988 in Patients With Muco-Obstructive Disease.