Pulmonary Arterial Hypertension (PAH) MedDRA version: 21.1 Level: PT Classification code 10037400 Term: Pulmonary hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
Altavant Sciences GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients are eligible to be included in the study only if all the following criteria are met: 1. Male and female patients must be at least 18 years of age at the time of signing the informed consent. a. Male patients and female partners of childbearing potential must agree to use contraception as detailed in a Section 5.4.1 to the protocol starting 4 weeks prior to the first dose of IP, during the treatment period, and for at least 100 days after the last dose of IP. Male patients must refrain from donating sperm during this period. b. Female patients of childbearing potential must agree to use contraception as detailed in Section 5.4.1 starting at Screening, during the treatment period, and for at least 4 weeks after the last dose of IP. 2. Body mass index (BMI) = 18 kg/m2 and = 38 kg/m2 3. Patients with symptomatic PAH belonging to one of the following 2018 Clinical Group 1 sub types: a. Idiopathic PAH b. Heritable PAH c. Drug or toxin induced d. PAH associated with: 1. Connective tissue disease 2. Congenital systemic to pulmonary shunt (atrial septal defect, ventricular septal defect, patent ductus arteriosus) repaired at least one year prior to Screening 3. Human immunodeficiency virus (HIV) infection - if diagnosed with HIV, must have stable disease status defined as follows: a. stable treatment with HIV medications for at least 8 weeks prior to Screening b. no active opportunistic infection during the Screening Period c. no hospitalizations due to HIV for at least 4 weeks prior to Screening 4. WHO FC II or III 5. Confirmed diagnosis of PAH and meet all the following hemodynamic criteria by means of a screening RHC completed prior to randomization: a. mPAP of = 20 mmHg b. PVR = 400 dyne•sec/cm5 c. Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) of = 12 mmHg if PVR = 400 and < 500 dyne•sec/cm5, or PCWP/LVEDP = 15 mmHg if PVR = 500 dyne•sec/cm5 d. 6MWD of 100 to 550 meters at Screening 6. Currently on a stable treatment regimen with one or more treatments approved for PAH. Stable therapy is defined as receiving the same medication(s) for = 12 weeks prior to the screening RHC and at a stable dose level for each for = 8 weeks prior to the screening RHC. Any instances where doses of a medication have been missed prior to RHC must be discussed with the Medical Monitor prior to performing the RHC. 7. Meet all of the following criteria determined by pulmonary function tests completed no more than 24 weeks prior to Screening (performed with or without bronchodilation): a. Forced expiratory volume in one second (FEV1) = 60% of predicted normal, and b. FEV1:FVC ratio = 0.70, and c. Total lung capacity (TLC) = 70% of predicted normal (high resolution computed tomography [HRCT] required for TLC = 60% and < 70%) 8. If participating in an exercise program for pulmonary rehabilitation, the program must have been initiated = 12 weeks prior to Screening, and patient must agree to maintain the current level of rehabilitation for the first 24 weeks of receiving IP. If not participating in an exercise training program for pulmonary rehabilitation, patient must agree not to enroll in an exercise training program for pulmonary rehabilitation during the Screening Period and the first 24 weeks of receiving IP. 9. Willing and able to give written informed consent and to comply with the requirements of the study for its duration Are the trial subjects under 18? no Number of subjects for this age range:
Exclusion criteria
Exclusion criteria: Patients are excluded from the study if any of the following criteria are met: 1. Women of childbearing potential who are pregnant, planning to become pregnant, or lactating or female/male patients unwilling to use effective contraception as defined in Section 5.4.1 Medical Conditions 2. WHO pulmonary hypertension (PH) Group 1 PAH associated with portal hypertension or schistosomiasis; PH due to left heart disease (WHO PH Group 2), lung diseases and/or hypoxia (WHO PH Group 3), chronic thromboembolic PH (WHO PH Group 4), or PH with unclear multifactorial mechanisms (WHO PH Group 5) 3. PAH associated with significant venous or capillary involvement (PCWP > 15 mmHg), pulmonary capillary hemangiomatosis, portal hypertension, or unrepaired congenital heart defects (CHD) 4. Three or more of the following risk factors for left ventricular disease: a. BMI > 30 kg/m2 b. Diagnosis of essential hypertension that is actively treated c. Diabetes mellitus d. History of significant coronary artery disease (e.g., chronic stable angina, history of coronary intervention within the last 3 months, or a stenosis > 70% at coronary angiography) e. Atrial fibrillation f. Left atrial volume index > 41 mL/m2 5. Known genetic hypertrophic cardiomyopathy 6. Known cardiac sarcoidosis or amyloidosis 7. The patient has a history of, or currently has, a constrictive cardiomyopathy. 8. Known history of any left ventricular ejection fraction (LVEF) Grade 3) 10. Severe arthritis, musculoskeletal problems, or morbid obesity that, in the opinion of the Investigator, is the cause of the patient’s functional limitation and would affect the patient’s ability to perform or complete the 6MWT. 11. Planned major surgery within the next 3 months, including lung transplantation, major abdominal or major intestinal surgery 12. End stage renal disease defined as receiving peritoneal dialysis, hemodialysis, or status after renal transplantation, or severe liver disease defined as Child Pugh Class C, with or without cirrhosis 13. Known congenital LQTS or known family history of LQTS 14. Depression that is currently rated as severe (defined as a score of = 16 on the QIDS C and/or [HADS] Depression and/or Anxiety score = 15), recent suicidal behavior (either preparatory acts/behavior, aborted attempt, interrupted attempt, or actual attempt in the past 3 months per the Screening C SSRS), or active suicidal ideation with intent to act (defined as C SSRS category score of 4 or 5 in the past month) 15. Uncontrolled arterial hypertension (SBP > 180 mmHg and/or Diastolic Blood Pressure [DBP] > 110 mmHg), or hypotension (SBP < 90 mmHg and/or DBP < 50 mmHg) 16. Clinically significant electrolyte abnormality (e.g., hypokalemia, hypomagnesemia, or hypocalcemia) in the judgement of the Investigator 17. Current or prior history within the last 5 years of neoplasm (except for treated basal cell or squamous small cell carcinoma of the skin with no evidence of recurrence) 18. Any concurrent clinically significant medical condi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of rodatristat ethyl on the percent change from baseline of pulmonary vascular resistance (PVR), as measured by right heart catheterization (RHC) in patients with PAH.;Secondary Objective: • To evaluate the effect of rodatristat ethyl from baseline to Week 24 on: o Cardiopulmonary Hemodynamics o Time to Clinical Worsening (TTCW) o Death from any cause o WHO FC o 6MWD o N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) o Echocardiographic measures of right atrial size & RV function (tricuspid annular plane systolic excursion [TAPSE], tricuspid annular systolic velocity, and RV fractional area change) o Pulmonary Arterial Hypertension-Symptoms and Impact Questionnaire (PAH-SYMPACT) o Register to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2 score • To assess safety & tolerability of rodatristat ethyl in patients with PAH • To assess the PK of rodatristat ethyl • To assess the effect of rodatristat ethyl on plasma and urinary 5-HIAA;Primary end point(s): Percent change from baseline to 24 weeks of pulmonary vascular resistance (PVR) between an active arm and the placebo arm.;Timepoint(s) of evaluation of this end point: Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change from baseline in cardiac index, mPAP, mRAP, SvO2 at rest and PAC • Change from baseline in TTCW • Death from any cause • Change from baseline in WHO FC • Change from baseline in 6MWD • Change from baseline in NT proBNP • Change from baseline in right atrial size & RV function (TAPSE, tricuspid annular systolic velocity, & RV fractional area change) • Change from baseline in PAH SYMPACT • Change from baseline in REVEAL Lite 2.0 Score • Safety parameters including AEs, vital signs, laboratory values, and electrocardiogram (ECG) assessments • Population PK parameters of rodatristat ethyl and active metabolite rodatristat • Change from baseline in 5 hydroxyindoleacetic acid (5 HIAA; plasma and spot urine concentration) ;Timepoint(s) of evaluation of this end point: Week 24 | — |
Countries
Austria, Belgium, Bosnia and Herzegovina, Bulgaria, Canada, Czechia, Czech Republic, France, Germany, Italy, Latvia, Poland, Russian Federation, Serbia, Spain, Ukraine, United Kingdom, United States
Contacts
Public ContactInformation Desk
Altavant Sciences GmbH
Outcome results
None listed