Inhaled Treprostinil for Pulmonary Arterial Hypertension

Not currently recruiting at 24 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Liquidia Technologies, Inc.

Disqualifiers: Pregnancy, Lung transplant, others

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

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: 2.5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the long-term safety of a new inhaled treatment called LIQ861 (inhaled treprostinil) for individuals with pulmonary arterial hypertension, a condition that causes high blood pressure in the lungs and makes breathing difficult. Participants will use a special inhaler to take LIQ861 at varying strengths up to four times a day. This trial is ideal for those who have previously used LIQ861 in a study and wish to continue their treatment. Participants should not have discontinued the previous study due to side effects or plan to become pregnant during the trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of this treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that LIQ861 Inhaled Treprostinil is likely to be safe for humans?

Research has shown that LIQ861, an inhaled medication, is generally well-tolerated by people with pulmonary arterial hypertension (PAH). One study found that this treatment was safe for patients over a two-week period, meeting the safety standards set by the U.S. FDA. LIQ861 is designed to deliver the medicine deep into the lungs, potentially allowing for higher doses compared to other inhaled treatments.

Other studies have also found that LIQ861 is a safe option for treating PAH. It uses a dry powder inhaler to deliver the medication, which has proven to be both safe and easy to tolerate.

Overall, the evidence suggests that LIQ861 is a promising treatment with a good safety profile for those with PAH. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike traditional treatments for pulmonary arterial hypertension (PAH), which often involve oral or intravenous medication, LIQ861 is inhaled directly into the lungs using a dry powder inhalation device. This unique delivery method allows the medication to target the lungs more directly, potentially improving effectiveness while reducing systemic side effects. Additionally, LIQ861 offers flexible dosing, allowing for titration to meet individual patient needs under medical supervision. Researchers are excited because this approach could offer a more convenient and potentially more effective treatment option for PAH patients.

What evidence suggests that LIQ861 inhaled treprostinil might be an effective treatment for pulmonary arterial hypertension?

Research has shown that inhaled treprostinil can aid people with pulmonary arterial hypertension (PAH) by improving their exercise capacity. One study found that adding inhaled treprostinil to current treatments enhanced patients' functional ability. Another study demonstrated its benefits for exercise in individuals with certain lung diseases. In this trial, participants will receive the inhaled version, LIQ861, which offers easier use compared to other forms. Overall, these findings suggest that LIQ861 can effectively enhance the quality of life for PAH patients. ^{2 6 7 8 9}

Who Is on the Research Team?

Nicholas S Hill, MD

Principal Investigator

Tufts Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with pulmonary arterial hypertension who have previously participated in LIQ861 studies. They must understand the study, follow its procedures, and agree to use contraception if there's a risk of pregnancy. Participants should have completed prior LIQ861 study requirements or reached an endpoint.

Inclusion Criteria

Evidence of a personally signed and dated informed consent document exists indicating that the patient has been informed of all pertinent aspects of the study prior to initiation of any study-related procedures

Patient is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Patient has fulfilled all entry criteria at the time of enrollment in original study with LIQ861

Exclusion Criteria

Patient prematurely discontinued LIQ861 due to a drug-related AE/SAE or tolerability issue in the original LIQ861 study in which they were enrolled, or patient did not complete protocol defined study procedures at an end of study visit (not Early Termination visit) in their original LIQ861 study

Patient withdrew consent during participation in another LIQ861 study

Any reason exists that, in the opinion of the Investigator or Medical Monitor, precludes the patient from participating in the study, e.g., any previous or intercurrent medical condition that may increase the risk associated with study participation or that would confound study analysis or impair study participation or cooperation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive LIQ861 inhaled treprostinil using a dry powder inhaler, with doses titrated under clinical supervision

2.5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive LIQ861 to evaluate long-term safety

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• LIQ861 Inhaled Treprostinil

Trial Overview The focus of this extension study is on the long-term safety of inhaling a drug called Treprostinil (LIQ861) as a dry powder for treating pulmonary arterial hypertension. It continues from previous LIQ861 trials.

How Is the Trial Designed?

Group I: LIQ861 Inhaled Treprostinil Experimental Treatment 1 Intervention

LIQ861 inhaled treprostinil at capsule strengths of 25 μg, 50 μg, 75 μg and 100 μg. LIQ861 will be administered using the RS00 Model 8 dry powder inhalation (DPI) device (Plastiape S.p.A.; Osnago, Italy) at dose levels of 25 μg capsule strength to 200 μg capsule strength treprostinil four times a day (QID) in individual patients. Titrating to dose levels beyond 200 μg capsule strength QID, under clinical investigator supervision, requires review and approval from the Medical Monitor.

Who Is Running the Clinical Trial?

Liquidia Technologies, Inc.

Lead Sponsor

Trials

7

Recruited

500+

Nuventra, Inc.

Collaborator

Trials

2

Recruited

210+

Nuventra, Inc.

Industry Sponsor

Trials

5

Recruited

340+

Published Research Related to This Trial

Nebulised ensifentrine showed a clear dose-response relationship in improving lung function (FEV1) in asthma patients, outperforming placebo and demonstrating effectiveness comparable to salbutamol, a standard asthma treatment.

All doses of ensifentrine were well tolerated with no significant adverse effects on heart rate or potassium levels, unlike salbutamol, which caused dose-related reductions in potassium and increased heart rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a first-in-class inhaled PDE3/4 inhibitor (ensifentrine) vs salbutamol in asthma. Bjermer, L., Abbott-Banner, K., Newman, K.[2020]

LIQ861, a dry-powder formulation of treprostinil, shows comparable bioavailability to the nebulized Tyvaso® inhalation solution, with exposure parameters indicating similar effectiveness in delivering the medication to patients with pulmonary arterial hypertension (PAH).

Both LIQ861 and Tyvaso® were well tolerated by participants, suggesting that LIQ861 offers a safe and convenient alternative for PAH patients, allowing for effective treatment in just 1 to 2 breaths.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative bioavailability of inhaled treprostinil administered as LIQ861 and Tyvaso® in healthy subjects. Roscigno, RF., Vaughn, T., Parsley, E., et al.[2021]

The study found that the vibrating mesh nebulizer is an effective alternative to the Tyvaso Inhalation System for delivering inhaled treprostinil, with similar fine particle fractions and often greater inhaled mass across various age models (neonatal, pediatric, and adult).

In particular, using the vibrating mesh nebulizer with high-frequency oscillatory ventilation in neonatal and pediatric models resulted in higher delivery of treprostinil, which could lead to higher than expected dosages for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled Treprostinil Drug Delivery During Mechanical Ventilation and Spontaneous Breathing Using Two Different Nebulizers. Parker, DK., Shen, S., Zheng, J., et al.[2018]

The combination of oral sildenafil and inhaled treprostinil was found to be safe and well tolerated in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), showing no relevant side effects during the study.

This combination therapy resulted in significant improvements in pulmonary vascular resistance and mean pulmonary arterial pressure, indicating a strong potential for effective long-term treatment of these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute effects of the combination of sildenafil and inhaled treprostinil on haemodynamics and gas exchange in pulmonary hypertension. Voswinckel, R., Reichenberger, F., Enke, B., et al.[2022]

The study established a reliable in vitro method for delivering treprostinil, a treatment for pulmonary arterial hypertension, through a ventilator circuit, achieving a controlled dose of 54 μg in just 29 seconds.

The method demonstrated that the AeroTech II nebulizer could effectively deliver aerosolized treprostinil with consistent dosing across various breathing patterns, highlighting the importance of precise nebulization conditions for optimal drug delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro delivery of aerosolized treprostinil via modern mechanical ventilation. Patel, RB., Smaldone, GC., Cuccia, AD., et al.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7682229/

Pharmacokinetics and tolerability of LIQ861, a novel dry ... A dry-powder inhaled formulation of treprostinil (LIQ861) produced using PRINT® technology offers a substantial advantage over current nebulized therapy.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2008470

Inhaled Treprostinil in Pulmonary Hypertension Due to ... In patients with pulmonary hypertension due to interstitial lung disease, inhaled treprostinil improved exercise capacity from baseline.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00147199

Study Details | NCT00147199 | Clinical Investigation Into ... This is a double-blind placebo-controlled clinical investigation into the efficacy and tolerability of inhaled treprostinil in patients with severe pulmonary ...

4. jhltonline.org jhltonline.org/article/S1053-2498%2811%2901121-1/fulltext

Long-term effects of inhaled treprostinil in patients with ... Inhaled treprostinil improved functional capacity as add-on therapy in the short-term management of patients with pulmonary arterial hypertension (PAH). This ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0735109710007795

Addition of Inhaled Treprostinil to Oral Therapy for ... This study assessed the efficacy and safety of inhaled treprostinil in pulmonary arterial hypertension (PAH) patients receiving therapy with either bosentan or ...

6. liquidia.com liquidia.com/news-releases/news-release-details/liquidia-technologies-reports-positive-interim-liq861-safety

Press release LIQ861 was well-tolerated in PAH patients at two-weeks of treatment, the safety endpoint requested by U.S. FDA; NDA submission targeted for ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03399604

Study Details | NCT03399604 | Investigation of the Safety ... The study will evaluate the long term safety and tolerability of LIQ861 in PAH patients transitioning from stable doses of inhaled treprostinil therapy, or who ...

8. liquidia.com liquidia.com/static-files/e352a7e5-3283-402e-b922-db460e190f91

Safety and Tolerability of LIQ861 in Pulmonary Arterial ... LIQ861 dry powder formulation of treprostinil provides a safe and tolerable treatment for patients with PAH. LIQ861 Dry-Powder. Formulation. RS00 Model 8. Dry- ...

9. mayo.edu mayo.edu/research/clinical-trials/cls-20477328

A Study to Evaluate the Long-term Safety and Tolerability ... The primary purpose of this study is to evaluate the long-term safety and tolerability of LIQ861, a dry powder formulation of treprostinil, in patients with ...