Pulmonary Arterial Hypertension
Conditions
Keywords
CS1, Pulmonary Arterial Hypertension, PAH, Sodium Valproate, Valproic Acid, Pulmonary Vascular Resistance, 6-Minute Walk Distance
Brief summary
This Phase 2 study (EPIMODE) will evaluate the efficacy and safety of CS1 compared with placebo when added to standard-of-care therapy in participants with pulmonary arterial hypertension. Participants completing Treatment Period 1 (Week 36) will be re-randomized to continue or switch study treatment for Treatment Period 2 through Week 52.
Interventions
DRUGCS1
160 mg delayed release capsules taken orally once daily in the evening
DRUGPlacebo
Matching placebo capsules taken orally once daily in the evening
Sponsors
Cereno Scientific AB
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 80 years * WHO Group 1 pulmonary arterial hypertension * WHO Functional Class II or III * REVEAL Lite 2 score ≥6 * Receiving stable standard-of-care PAH therapy for at least 90 days prior to screening * Hemodynamic confirmation of PAH by right heart catheterization * 6-minute walk distance ≥150 m and \<550 m
Exclusion criteria
* Pulmonary hypertension WHO Group 2, 3, 4, or 5 * Significant left-sided heart disease * Recent major cardiovascular or cerebrovascular event * Prior heart or heart-lung transplantation or active lung transplant listing * Significant renal or hepatic dysfunction * Current use of prohibited medications that cannot be discontinued * Pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in pulmonary vascular resistance (PVR) | Baseline to Week 36 | Pulmonary vascular resistance calculated from right heart catheterization measurements using the Thermodilution or Fick method for determination of cardiac output. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in 6-minute walk distance (6MWD) | Baseline to Week 36 | — |
| Change from baseline in Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL) Lite 2 score | Baseline to Week 36 | — |
| Change from baseline in REVEAL Risk Score (RRS) 2.0 | Baseline to Week 36 | — |
| Change from baseline in tricuspid annular plane systolic excursion (TAPSE) | Baseline to Week 36 | — |
| Change from baseline in right ventricular (RV) strain | Baseline to Week 36 | — |
| Change from baseline in World Health Organization (WHO) Functional Class | Baseline to Week 36 | WHO Functional Class ranges from Class I to Class IV, with lower class indicating better functional status. |
| Percentage of participants with improvement in WHO Functional Class | Week 36 | WHO Functional Class ranges from Class I to Class IV, with lower class indicating better functional status. |
| Change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) or B-type natriuretic peptide (BNP) | Baseline to Week 36 | — |
| Change from baseline in mean pulmonary arterial pressure (mPAP) | Baseline to Week 36 | — |
| Change from baseline in cardiac output (CO) | Baseline to Week 36 | — |
| Percentage of participants with clinical worsening of pulmonary arterial hypertension (PAH) | Week 36 | Clinical worsening as defined in the study protocol. |
| Time to first clinical worsening event | Baseline through Week 36 | Clinical worsening as defined in the study protocol. |
| Change from baseline in PAH-SYMPACT (Pulmonary Arterial Hypertension Symptoms and Impact Questionnaire) domain scores | Baseline to Week 36 | Domain scores assess symptoms and impacts of PAH; higher scores indicate greater symptom burden and disease impact. |
| Change in 6MWD from Week 36 | Week 36 to Week 52 | — |
| Change in TAPSE from Week 36 | Week 36 to Week 52 | — |
| Change in RV strain from Week 36 | Week 36 to Week 52 | — |
| Change in NT-proBNP or BNP from Week 36 | Week 36 to Week 52 | — |
| Change in WHO Functional Class from Week 36 | Week 36 to Week 52 | WHO Functional Class ranges from Class I to Class IV, with lower class indicating better functional status. |
| Change in REVEAL Lite 2 score from Week 36 | Week 36 to Week 52 | — |
| Incidence of treatment-emergent adverse events (TEAEs) | Up to Week 56 | — |
| Incidence of serious adverse events (SAEs) | Up to Week 56 | — |
Outcome results
None listed