Mosliciguat for Pulmonary Hypertension

(PHocus Trial)

Recruiting at 17 trial locations

Overseen By Pulmovant

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Pulmovant, Inc.

Must not be taking: Mosliciguat, sGC stimulators

Disqualifiers: PH Group 1, 2, 4, 5, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new inhaled treatment called mosliciguat to determine its safety and effectiveness for people with pulmonary hypertension (high blood pressure in the lungs) linked to interstitial lung disease (a lung condition that causes scarring). Participants will be randomly assigned to receive either mosliciguat or a placebo for 24 weeks. Afterwards, everyone may have the opportunity to receive mosliciguat. This trial suits individuals diagnosed with interstitial lung disease who have confirmed pulmonary hypertension and can walk at least 100 meters. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant medical advancements.

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

The trial information does not specify if you need to stop taking your current medications. However, if you are on investigational or experimental therapy, you must stop it at least 42 days before joining the trial.

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

Research has shown that mosliciguat, the treatment under study for pulmonary hypertension, has undergone testing in earlier studies. These studies examined its safety and tolerability. In past trials, daily inhalation of mosliciguat showed no signs of serious systemic side effects, indicating that the treatment is generally well-tolerated. The current trial is in Phase 2, suggesting that earlier tests demonstrated sufficient safety to expand testing to more participants. While more information is needed to fully understand its safety, the results so far appear promising. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pulmonary hypertension?

Unlike the standard treatments for pulmonary hypertension, which typically include vasodilators like sildenafil or endothelin receptor antagonists such as bosentan, mosliciguat offers a new approach by targeting the nitric oxide-soluble guanylate cyclase (sGC) pathway. This novel mechanism aims to enhance blood flow and reduce pressure in the lungs more effectively. Additionally, mosliciguat is administered via inhalation, potentially offering a more direct and rapid impact on the lungs compared to oral medications. Researchers are excited because this could lead to improved outcomes and quality of life for patients with pulmonary hypertension.

What evidence suggests that mosliciguat might be an effective treatment for pulmonary hypertension?

Research shows that mosliciguat might help people with pulmonary hypertension by improving blood flow in the lungs. In this trial, participants will receive either inhaled mosliciguat or a matched placebo daily for 24 weeks. Studies have found that inhaled mosliciguat remains in the body longer than other forms, potentially enhancing its effectiveness for lung treatment. It targets a specific area to help lower blood pressure in the lungs. Although more research is needed, early results suggest it could be a promising option for those with pulmonary hypertension related to interstitial lung disease. ^{1 3 4 6 7}

Who Is on the Research Team?

Ubaldo Martin, MD

Principal Investigator

Pulmovant, Inc.

Are You a Good Fit for This Trial?

This trial is for people with a condition where high blood pressure in the lungs is caused by scarring or inflammation of lung tissue (PH-ILD). Participants should have this specific type of lung and heart issue but not be dealing with other major health problems that could interfere with the study.

Inclusion Criteria

Participants willing and able to provide informed consent

I can walk 100 meters or more without stopping.

I have a lung condition diagnosed by a CT scan with less than 70% normal lung function.

Exclusion Criteria

I have had a bad reaction or no improvement with mosliciguat or similar medications.

My lung condition hasn't worsened in the last 28 days.

I need more than 10 liters per minute of oxygen at rest.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive inhaled mosliciguat or placebo daily for 24 weeks in a double-blind, placebo-controlled period

24 weeks

Extension

All participants who complete the 24-week double-blind period may continue to receive mosliciguat in the extension period

Beyond 24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mosliciguat

Trial Overview The study tests mosliciguat, a new treatment delivered through an inhaler, against a placebo (a substance with no active drug) to see if it's safe and effective for PH-ILD. People will be randomly assigned to either get mosliciguat or the placebo without knowing which one they receive.

How Is the Trial Designed?

Group I: Extension Experimental Treatment 2 Interventions

After Week 24, all participants may receive mosliciguat through an Extension period

Group II: Mosliciguat Active Control 2 Interventions

Participants will be randomized to receive inhaled mosliciguat or placebo daily for 24 weeks

Group III: Matched Placebo Placebo Group 2 Interventions

Participants will be randomized to receive inhaled mosliciguat or placebo daily for 24 weeks

Who Is Running the Clinical Trial?

Pulmovant, Inc.

Lead Sponsor

Trials

1

Recruited

120+

Published Research Related to This Trial

In a study of 39 patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) treated with riociguat for 3 to 12 months, significant reductions in right ventricular size and improvements in right heart function were observed, indicating the drug's efficacy.

Long-term riociguat treatment led to measurable improvements in right ventricular area, right atrial area, and functional capacity (6-minute walking distance), suggesting it effectively alleviates symptoms and enhances heart function in patients with these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Change of right heart size and function by long-term therapy with riociguat in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Marra, AM., Egenlauf, B., Ehlken, N., et al.[2017]

In a study of 27 patients with pulmonary hypertension, treatment with riociguat significantly improved right ventricular (RV) contractile function, as measured by echocardiographic studies.

The improvement in RV strain was observed even after accounting for changes in RV afterload, indicating that riociguat effectively enhances heart function in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Riociguat, a soluble guanylate cyclase stimulator, ameliorates right ventricular contraction in pulmonary arterial hypertension. Murata, M., Kawakami, T., Kataoka, M., et al.[2020]

Riociguat, a first-in-class drug that activates soluble guanylate cyclase, has been shown to significantly improve exercise capacity in patients with pulmonary hypertension, as evidenced by the CHEST-1 and PATENT-1 phase-3 clinical trials involving 16 weeks of therapy.

The drug demonstrated a modest safety profile, with hypotension being the most common adverse effect, and has received regulatory approval for treating pulmonary arterial hypertension and inoperable chronic thromboembolic pulmonary hypertension, offering new hope for patients with this serious condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Riociguat: Something new in pulmonary hypertension therapeutics? Shanmugam, E., Jena, A., George, M.[2020]

Riociguat (Adempas) is an innovative medication specifically designed to treat pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), conditions that cause high blood pressure in the lungs.

Clinical studies have demonstrated that riociguat effectively improves exercise capacity and overall functional status in patients with these types of pulmonary hypertension, making it a valuable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Riociguat (adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Khaybullina, D., Patel, A., Zerilli, T.[2020]

In a double-blind placebo-controlled trial involving 16 patients with sarcoidosis-associated pulmonary hypertension, riociguat significantly delayed clinical worsening compared to placebo, with no patients on riociguat meeting the worsening criteria versus five on placebo.

Riociguat also improved exercise capacity, as shown by a median increase of 42.7 meters in the 6-minute walk distance (6MWD) compared to a decrease of 55.9 meters in the placebo group, indicating its efficacy without significant adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Riociguat for Sarcoidosis-Associated Pulmonary Hypertension: Results of a 1-Year Double-Blind, Placebo-Controlled Trial. Baughman, RP., Shlobin, OA., Gupta, R., et al.[2023]

In the 12-week PATENT-1 study, riociguat significantly improved the 6-minute walking distance and WHO functional class in patients with pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD), with these benefits lasting for up to 2 years.

The safety profile of riociguat in PAH-CTD patients was comparable to that of the overall study population, and the 2-year survival rate for these patients was 93%, similar to those with idiopathic PAH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Riociguat for the treatment of pulmonary arterial hypertension associated with connective tissue disease: results from PATENT-1 and PATENT-2. Humbert, M., Coghlan, JG., Ghofrani, HA., et al.[2022]

In pivotal phase III trials, riociguat significantly improved the 6-minute walking distance (6MWD) in Chinese patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), with increases of +46 m in PATENT-1 and +102 m in CHEST-1.

Riociguat was well tolerated and also led to improvements in secondary endpoints such as pulmonary vascular resistance (PVR) and WHO functional class, indicating its efficacy and safety in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Riociguat for the treatment of pulmonary hypertension: Chinese subgroup analyses and comparison. Wang, C., Jing, ZC., Huang, YG., et al.[2020]

In a study of 71 patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) treated with riociguat for 3 to 12 months, significant reductions in right atrial and right ventricular size were observed after 12 months, indicating improved heart function.

Long-term riociguat treatment also led to an increase in right ventricular function measures, such as TAPSE and fractional area change, suggesting that riociguat is effective in improving right heart function in patients with PAH and CTEPH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Right ventricular size and function under riociguat in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (the RIVER study). Marra, AM., Halank, M., Benjamin, N., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40402373/

Results from Randomized Phase I Studies in Healthy Men The results show that mosliciguat remains in the body for longer when given as an inhalation than when given orally or intravenously.

2. respiratory-research.biomedcentral.com respiratory-research.biomedcentral.com/articles/10.1186/s12931-022-02189-1

Inhaled mosliciguat (BAY 1237592): targeting pulmonary ... Inhaled mosliciguat may overcome treatment limitations in patients with pulmonary hypertension by improving pulmonary circulation and airway resistance.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03754660

This Study Tests the Safety of Inhaled BAY1237592, How ... This Study Tests the Safety of Inhaled BAY1237592, How the Drug is Tolerated and How it Effects Patients With High Blood Pressure in the Arteries of the Lungs ...

4. link.springer.com link.springer.com/article/10.1007/s40262-025-01503-6

Results from Randomized Phase I Studies in Healthy Men Mosliciguat (BAY 1237592), which is currently under development for the treatment of PH, is the first sGC activator specifically designed for ...

5. clinicaltrials.bayer.com clinicaltrials.bayer.com/study/17293

Hypertension, Pulmonary | Study 17293 This study tests the safety of inhaled BAY1237592, how the drug is tolerated and how it effects patients with high blood pressure in the arteries of the lungs.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9526466/

Inhaled mosliciguat (BAY 1237592): targeting pulmonary ... Here we describe a new inhaled soluble guanylate cyclase activator to target apo-soluble guanylate cyclase and outline its therapeutic potential.

7. biospace.com biospace.com/press-releases/pulmovant-announces-publication-of-pharmacokinetics-and-lung-deposition-data-for-inhaled-mosliciguat-in-clinical-pharmacokinetics

Pulmovant Announces Publication of Pharmacokinetics ... Three Phase 1 studies support once-daily inhaled administration of mosliciguat with no evidence of serious systemic side effects.