Ensayos clínicos

Inclusion Criteria:

• Adult female subjects aged 18 to 75 years, inclusive, or adult male subjects aged 50 to 75 years, inclusive, at the time of signing the ICF prior to initiation of any study-specific activities/procedures.
• A current diagnosis of symptomatic PAH classified by one of the following:
  • Idiopathic PAH (IPAH) or heritable pulmonary arterial hypertension (HPAH);
  • PAH associated with connective tissue diseases (CTD-APAHs):
    • Systemic sclerosis;
    • Mixed CTD or overlap syndrome;
    • Systemic lupus erythematosus.
  • Other CTD established by ACR/EULAR guidelines;
  • PAH associated with anorexigen or methamphetamine use;
  • Congenital heart disease with simple systemic to pulmonary shunt at least 1 year after surgical repair.
• 6MWD ≥ 150 meters and ≤ 550 meters at screening.
• WHO FC II or III symptomatology.
• Treatment with standard of care PAH background therapies.
• Documentation of cardiac catheterization within the screening period that is consistent with the diagnosis of PAH and meeting all the following criteria, to be confirmed by a central hemodynamic core laboratory:
  • Mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg (at rest);
  • Pulmonary capillary wedge pressure ≤ 15 mmHg, or mean left atrial pressure (mLAP) or left ventricular-end diastolic pressure (LVEDP) ≤ 15 mmHg in the absence of left atrial obstruction;
  • PVR ≥ 400 dyne•s/cm^5.
• Pulmonary function tests (PFTs) at screening with the following criteria met:
  • Forced expiratory volume in 1 second (FEV1) divided by the forced vital capacity (FVC) ≥ 760% (predicted);
  • Total lung capacity (TLC) or FVC ≥ 70% predicted.

Exclusion Criteria:

• Evidence of chronic thromboembolic disease or acute pulmonary embolism as assessed by ventilation-perfusion (V/Q) scan, computed tomography (CT)-angiogram, or pulmonary angiogram prior to screening.
• Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure > 160 mm Hg or sitting diastolic blood pressure > 100 mm Hg during screening visit after a period of rest.
• Systolic blood pressure < 90 mm Hg during screening and baseline visits.
• WHO Pulmonary Hypertension Group 2-5.
• Human immunodeficiency virus (HIV)-associated PAH.
• History of left-sided heart disease and/or clinically significant cardiac disease, including but not limited to any of the following:
  • Aortic or mitral valve disease (stenosis or regurgitation) defined as greater than mild aortic insufficiency, mild aortic stenosis (AS), mild mitral stenosis (MS), moderate mitral regurgitation (MR);
  • Mechanical cardiac valve requiring anticoagulation;
  • Pericardial constriction or pericardial effusion with tamponade physiology;
  • Restrictive cardiomyopathy;
  • Left ventricular ejection fraction (LVEF) ≤ 50% by echocardiography (ECHO) within 6 weeks prior to screening; if  ECHO from the prior 6 weeks is not available, the screening ECHO results may be used to establish this criterion.
  • Note: If ECHO images are not adequate to provide an accurate estimate of LVEF then a multigated acquisition (MUGA) or cardiac magnetic resonance imaging (cMRI) scan or single photon emission computed tomography (SPECT) imaging can be used to obtain an accurate LVEF.
  • Left Atrial Area greater than 29cm2 by ECHO within 6 weeks prior to screening; if historical ECHO from the prior 6 weeks is not available, screening ECHO results may be used to establish this criterion. g. Documented uncontrolled symptomatic coronary disease (ie, unstable angina or percutaneous coronary intervention or coronary artery bypass graft within 12 months prior to screening, or planned coronary intervention or coronary artery bypass surgery).
• Untreated obstructive sleep apnea.
• History of atrial septostomy within 180 days prior to screening.
• Pulmonary venous occlusive disease (PVOD).
• Subjects with a history of portopulmonary hypertension or portal hypertension due to cirrhosis classified as Child-Pugh Class A or higher; or baseline ALT or AST > 2 x ULN or Total Bilirubin ≥ 2 X ULN.
• History of malignancy within 5 years prior to screening, with the exception of localized nonmetastatic basal cell carcinoma of the skin and in-situ carcinoma of the cervix.
• History of a potentially life-threatening cardiac arrhythmia with an ongoing risk.
• Uncontrolled bacterial, viral, or fungal infections which require systemic therapy.
• Severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or IP administration (eg, history of intracranial hemorrhage), or absolute neutrophil count (ANC) < 1 x 10^9 /L or platelet count < 50 x10^ 9 /L.
• Any musculoskeletal disease or any other disease that limits evaluation of 6MWT.
• Pregnant or nursing or intends to become pregnant during the duration of the study.
• Body weight < 40 kg at screening.
• Chronic renal insufficiency as defined by an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73m^2 via CKD-epi (Levey, 2009) at screening or requires dialytic therapy or hemofiltration.
• Hemoglobin (Hgb) concentration < 8.5 g/dL at screening.
• Evidence of active human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C, or tuberculosis (TB) infections.
• Inhaled prostanoids; these drugs may be withdrawn ≥ 4 weeks prior to screening, if clinically indicated.
• Use of oral anticoagulants (i.e., coumadin warfarin or novel oral anticoagulants [NOAC]) at randomization; if on coumadin warfarin or a NOAC, these drugs can be withdrawn, if clinically appropriate, during the screening period, and subjects should have normal coagulation parameters prior to the randomization for examples of prohibited anticoagulants).
• Requirement of intravenous (IV) inotropes (i.e., levosimendan, dopamine, dobutamine, milrinone, norepinephrine) other than an IV prostanoid within 4 weeks of screening. Prior/Concurrent Clinical Study Experience.
• Prior participation in GB002 studies and/or prior treatment with GB002.
• Currently participating in or has participated in a study of an investigational agent or has used an investigational device for the treatment of PAH within 4 weeks prior to screening.
  • Note: Subjects who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks or at least 5 half-lives (whichever is greater) after the last dose of the previous investigational agent.
• Current use of inhaled tobacco and/or inhaled marijuana.
• Current alcohol use disorder as defined by DSM-5 and/or a positive test for drugs of abuse (amphetamines, methamphetamines, cocaine, phencyclidine [PCP]). Retest may be performed for potential false positive results. Subjects with a history of methamphetamine abuse must be abstinent for a minimum of 1 year prior to screening, in the opinion of the investigator.as documented by at least two negative urine or serology tests during the 12 months prior to screening. Certain drugs may be allowed IF prescribed by medical personnel and is under medical supervision for documented medical conditions (ie, opioids for pain, benzodiazepines for anxiety). Ingestible or topical marijuana is allowed, per local restrictions and regulations.
• Subjects with a history of severe milk protein allergy. In addition, subjects with known intolerance or hypersensitivity to lactose who, in the opinion of the investigator, may experience severe symptoms following the ingestion of lactose. 
• QTcF of > 480 msec recorded on a screening or baseline ECG or receiving concurrent treatment with medications that prolong QT interval. 
• Have any other condition or reason that, in the opinion of the Investigator or Medical Monitor, would prohibit the subject from participating in the study.

Eligibility last updated 1/25/22. Questions regarding updates should be directed to the study team contact.