A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in Subjects with Pulmonary Arterial Hypertension (ADVANCE OUTCOMES)
American Journal of Respiratory and Critical Care Medicine
; 205(1), 2022.
Article
in English
| EMBASE | ID: covidwho-1927795
ABSTRACT
RATIONALE Pulmonary arterial hypertension (PAH) is a rare, progressive disease leading to right ventricular failure and premature death. The functional limitation and survival of patients with PAH remains unsatisfactory. Ralinepag, an orally available, potent, and selective, nonprostanoid, prostacyclin receptor agonist, is a new chemical entity in development to treat PAH. METHODS:
The ADVANCE OUTCOMES (NCT03626688) study is a randomized, double-blind, placebocontrolled, event-driven study evaluating the efficacy and safety of ralinepag in subjects with PAH. In this event-driven, Phase 3 study, approximately 700 subjects with PAH treated with standard of care are randomly assigned (11) to receive ralinepag or placebo. Dosing is individualized and titrated based on tolerability and clinical response. The primary objective is to assess the effect of ralinepag on the time to first adjudicated clinical worsening event;a composite endpoint including death, hospitalization due to worsening of PAH, initiation of inhaled or infused prostacyclins, disease progression, or unsatisfactory long-term response. Additional secondary assessments during the study include changes from Baseline to Week 28 in N-terminal pro-brain natriuretic peptide (NT-proBNP), 6-minute walk distance (6MWD), WHO/New York Heart Association (NYHA) Functional Class, and health-related quality of life measures. Exploratory assessments will evaluate biomarkers and pharmacogenetics. Subject safety is evaluated by capturing adverse events, hospitalizations, clinical laboratory, and ECG parameters. Subjects who experience a clinical worsening event or are participating at study closure are eligible to enter an open-label extension study (ROR-PH-303 [NCT03683186]). Long-term survival will be followed for all subjects until study closure.RESULTS:
Enrollment is ongoing at approximately 200 sites in 33 countries following implementation of risk mitigation steps related to the Covid-19 pandemic. Enrollment will continue until 228 adjudicated clinical worsening events have occurred. The interim assessment includes 281 subjects randomized in 29 different countries;97% of participants have completed 28 weeks of treatment. The majority of subjects were female (79.4%) with a median age of 48.0 years, were receiving dual background therapy (82.9%), and were classified as Functional Class II (59.3%). Overall, 48 clinical worsening events have been reported at the time of the interim assessment. Of these, 34 subjects elected to continue treatment in the open-label extension study. An independent Data Monitoring Committee reviewed safety data after 50, 100, and 250 subjects were randomized and recommended study continuation without modification.CONCLUSIONS:
ADVANCE OUTCOMES will assess whether ralinepag can improve function, delay disease progression, and prolong survival in subjects with PAH.
amino terminal pro brain natriuretic peptide; biological marker; endogenous compound; placebo; prostacyclin; ralinepag; adult; clinical laboratory; clinical trial; comparative effectiveness; conference abstract; controlled study; coronavirus disease 2019; double blind procedure; drug dose titration; drug efficacy; drug safety; drug therapy; drug tolerability; electrocardiogram; electrocardiography; female; health care quality; hospitalization; human; long term survival; major clinical study; middle aged; multicenter study; New York Heart Association class; outcome assessment; pandemic; pharmacogenetics; phase 3 clinical trial; professional standard; pulmonary hypertension; quality of life; randomized controlled trial; six minute walk test
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Type of study:
Experimental Studies
/
Randomized controlled trials
Language:
English
Journal:
American Journal of Respiratory and Critical Care Medicine
Year:
2022
Document Type:
Article
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