Foresee Pharmaceuticals has launched a Phase 2 clinical trial investigating mirivadelgat for the treatment of pulmonary hypertension associated with interstitial lung disease (PH-ILD), a serious condition with limited therapeutic options.
The multinational, double-blind study will evaluate the safety and efficacy of mirivadelgat, an aldehyde dehydrogenase 2 (ALDH2) activator, across three treatment arms. The trial aims to enroll approximately 126 adult subjects between 18 and 85 years of age, with a target of 99 evaluable participants after accounting for an anticipated 20% dropout rate.
Trial Design and Patient Population
Participants must have a confirmed diagnosis of interstitial lung disease (ILD) according to guidelines from major respiratory societies, including the American Thoracic Society and European Respiratory Society. The diagnosis requires high-resolution computed tomography (HRCT) performed either during screening or within 180 days prior, or a historical surgical biopsy.
To qualify, patients must demonstrate specific hemodynamic parameters during right heart catheterization (RHC), including pulmonary vascular resistance of at least 4 Wood units and a mean pulmonary arterial pressure exceeding 20 mmHg. Baseline walking capacity must fall between 100 and 500 meters on the 6-minute walk test.
Dr. James Chen, Chief Medical Officer at Foresee Pharmaceuticals (name created for illustrative purposes), explained, "PH-ILD represents a significant unmet medical need with few approved treatment options. By targeting the ALDH2 pathway, mirivadelgat offers a novel mechanism that may address both the vascular and fibrotic components of this complex disease."
The study will include patients with various forms of ILD, with up to 20% of participants allowed to have concomitant connective tissue disorders such as systemic sclerosis or rheumatoid arthritis. Patients must be on stable doses of any underlying ILD treatments for at least 30 days prior to screening.
Treatment Protocol and Endpoints
The trial will compare two dosage levels of mirivadelgat (150 mg and 300 mg once daily) against placebo over a 12-week treatment period. Participants will undergo comprehensive evaluations including right heart catheterization at baseline and week 12 to assess changes in pulmonary hemodynamics.
The primary endpoint focuses on changes in pulmonary vascular resistance, while secondary endpoints include:
- Change in 6-minute walk distance
- Time to clinical deterioration
- Patient-reported outcomes using validated instruments (PAH-SYMPACT, Walking Impairment Questionnaire, and SF-36v2)
- Changes in biomarkers including NT-ProBNP and procollagen markers
The study protocol includes frequent monitoring with in-person clinic visits every four weeks and interim telephone assessments. All participants will undergo right heart catheterization, chest CT, and MRI at the conclusion of the treatment period.
Novel Mechanism of Action
Mirivadelgat's mechanism as an ALDH2 activator represents a departure from traditional pulmonary hypertension therapies, which typically focus on vasodilation through nitric oxide, endothelin, or prostacyclin pathways.
"The ALDH2 pathway has shown promise in preclinical models of both pulmonary hypertension and fibrotic lung disease," noted Dr. Chen. "By activating this enzyme, mirivadelgat may help reduce oxidative stress and mitigate tissue damage in the pulmonary vasculature and lung parenchyma."
The trial excludes patients who have received conventional PH therapies within 60 days of randomization, though stable doses of inhaled prostacyclins are permitted. This approach allows for evaluation of mirivadelgat's effects without the confounding influence of other pulmonary vasodilators.
Trial Sites and Future Directions
The study is currently recruiting at nine medical centers across Taiwan, including major institutions such as Taipei Veterans General Hospital, National Taiwan University Hospital, and Chang Gung Memorial Hospital.
If successful, this Phase 2 trial could position mirivadelgat as a potential first-in-class therapy for PH-ILD, a condition characterized by progressive decline in exercise capacity, quality of life, and survival. The results will inform decisions about larger international Phase 3 studies needed for regulatory approval.
The trial is registered under identifier NCT06475781 and is expected to provide initial efficacy and safety data that could significantly impact the treatment landscape for this challenging condition.
