Clinical Study of Inhaled GB002 for the Treatment of WHO Group 1 Pulmonary Arterial Hypertension (PAH)
- Conditions
- Pulmonary Arterial Hypertension (PAH)Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]MedDRA version: 20.0Level: LLTClassification code 10077739Term: Pulmonary arterial hypertension WHO functional class ISystem Organ Class: 100000004855
- Registration Number
- EUCTR2019-002669-37-AT
- 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 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.
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 connective tissue diseases (CTD-APAH):
- Systemic sclerosis,
- Mixed CTD or overlap syndrome,
- Systemic lupus erythematosus.
-Other CTD established by ACR/EULAR guidelines
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 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 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 following criteria, to be confirmed by the central hemodynamic core laboratory:
a. mPAP = 25 mmHg (at rest), AND
b. PVR = 400 dyne·s/cm5, AND
c. PCWP or LVEDP =12 mm Hg if PVR =400 to <500 dyne·sec/cm5 OR
d. PCWP or LVEDP =15 mmHg if PVR =500 dyne·sec/cm5
7. Pulmonary function tests (PFTs) at screening with following criteria met:
a. Forced expiratory volume in 1 second (FEV1) divided by the forced vital capacity (FVC) =70%
b. Total lung capacity (TLC) or FVC = 70% predicted
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 they have 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, bilateral salpingectomy, tubal ligation, 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-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical s
1.Evidence of chronic thromboembolic disease or acute pulmonary embolism as assessed by V/Q scan, 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 BP>160 mm Hg or sitting diastolic blood pressure>100 mm Hg during screening visit after a period of rest
3.Systolic BP<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 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
f. Left Atrial Area greater than 29cm2 by ECHO within 6 weeks prior to screening; if 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)
7. Untreated severe obstructive sleep apnea.
8. History of atrial septostomy within 180 days prior to screening.
9. Pulmonary venous occlusive disease (PVOD).
10. 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.
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. 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), or absolute neutrophil count (ANC) < 1x109/L or platelet count < 50x109/L.
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.
17.Body weight < 40 kg at screening.
18.Chronic renal insufficiency as defined by an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73m2 via CKD-epi (Levey, 2009) 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.
21.Inhaled prostanoids; these drugs may be withdrawn = 4 weeks prior to screening, if clinically indicated.
22.Use of oral anticoagulants (i.e.warfarin or novel oral anticoagulants [NOAC]) at randomizat
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