Clinical Study of Inhaled GB002 for the Treatment of WHO Group 1 Pulmonary Arterial Hypertension (PAH)
- Conditions
- Pulmonary Arterial Hypertension (PAH)MedDRA version: 20.0Level: LLTClassification code 10077739Term: Pulmonary arterial hypertension WHO functional class ISystem Organ Class: 100000004855Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2019-002669-37-FR
- Lead Sponsor
- GB002, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 80
1. Adult female subjects aged 18 to 80 years, inclusive, or adult male subjects aged 50 to 80 years, inclusive, at the time of signing the ICF prior to initiation of any study specific activities/procedures.
2. A current diagnosis of symptomatic PAH classified by one of the following:
a. Idiopathic PAH (IPAH) or heritable pulmonary arterial hypertension (HPAH).
b. PAH associated with one of the following connective tissue diseases (CTDs):
- Systemic sclerosis,
- Mixed CTD or overlap syndrome,
- Systemic lupus erythematosus.
c. PAH associated with anorexigen or methamphetamine use.
d. Congenital heart disease with simple systemic to pulmonary shunt at least 1 year after surgical repair.
3. 6MWD = 150 meters and = 550 meters at screening. The lower of 2 consecutive distances should be within 15% of the higher distance.
4. WHO FC II or III symptomatology.
5. Treatment with standard of care PAH background therapies. Medications should remain stable for the past 4 weeks prior to consent and throughout screening period.
Exception: As needed (PRN) diuretics for intermittent weight gain and/or edema are allowed and will be considered a stable dose for this study.
6. Documentation of cardiac catheterization within the screening period consistent with the diagnosis of PAH and meeting all following criteria, to be confirmed by a central hemodynamic core laboratory:
a. mPAP = 25 mmHg (at rest);
b. 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;
c. PVR = 400 dyne•s/cm5.
7. Pulmonary function tests (PFTs) and diffusing capacity of the lungs for carbon monoxide (DLCO) at screening with following criteria met:
a. Forced expiratory volume in 1 second (FEV1) =60% (predicted);
b. DLCO =40% predicted except for subjects with PAH associated with systemic sclerosis (SSc-APAH) where DLCO =30% is required.
If the subject uses continuous oxygen therapy, they must be able to complete PFTs without oxygen. Subjects who are unable to complete PFTs without oxygen therapy are not eligible for the study.
Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
8. Women of childbearing potential must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin[hCG]) at screening and a negative urine pregnancy test on Day 1 before first administration of IP. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required and results must be negative.
9. Women of nonchildbearing potential: Evidence of post-menopausal status. Women will be considered post-menopausal if ave been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
- Women <50 years of age would be considered post-menopausal if have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
- Women =50 years of age would be considered post-menopausal if have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation
The subject must be excluded from participating in the study if he/she meets any of the following:
Medical Conditions
1. 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. If not available previously, then test should be performed during the screening period.
2. 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.
3. Systolic blood pressure < 90 mm Hg during screening and baseline visits.
Other Exclusion Criteria
4. WHO Pulmonary Hypertension Group 2–5.
5. HIV- associated PAH.
6. History of left-sided heart disease and/or clinically significant cardiac disease, including but not limited to any of the following:
a. 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);
b. Mechanical cardiac valve requiring anticoagulation;
c. Pericardial constriction or pericardial effusion with tamponade physiology;
d. Restrictive cardiomyopathy;
e. Left ventricular ejection fraction (LVEF) = 50% by ECHO within 12 weeks prior to screening;
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.
f. Documented symptomatic coronary disease (i.e., angina or previous myocardial infarction, percutaneous coronary intervention or coronary artery bypass graft), previous or planned coronary artery bypass surgery).
7. Untreated obstructive sleep apnea.
8. History of atrial septostomy within 180 days prior to screening.
9. Pulmonary venous occlusive disease (PVOD).
10. Moderate-to-severe hepatic impairment classified as Child-Pugh Class B or C at screening.
11. History of malignancy within 5 years prior to screening, with the exception of localized non-metastatic basal cell carcinoma of the skin and in-situ carcinoma of the cervix.
12. History of a potentially life-threatening cardiac arrhythmia with an ongoing risk.
13. Active and/or uncontrolled bacterial, viral, or fungal infections which require systemic therapy.
14. 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).
15. Any musculoskeletal disease or any other disease that limits evaluation of 6MWT.
16 Pregnant or nursing or intends to become pregnant during the duration of the study.
Diagnostic Assessments
17 Body weight < 40 kg at screening.
18. Chronic renal insufficiency as defined by an estimated glomerular filtration rate (eGFR) = 30 mL/min via CKD-epi at screening or requires dialytic therapy or hemofiltration.
19. Hemoglobin (Hgb) concentration < 8.5 g/dL at screening.
20. Evidence of active human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C, or tuberculosis (TB) infections.
Prior Therapy
21. Inhaled prostanoids; these drugs must be withdrawn prior to or at screening.
22. Use of anticoagulants (ie, coumadin or novel oral anticoagulants [NOAC]) at randomization; if on coumadin or a NOAC, these drugs can be withdrawn, if cl
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method