Hypertension,Pulmonary Clinical Trial
— SAPPHIREOfficial title:
A Multicentre, Late Phase Clinical Trial to Establish the Efficacy and Safety of Repeat Dosing of Autologous Endothelial Progenitor Cells (EPCs) Transfected With Human Endothelial NO-synthase (eNOS) in Patients With Pulmonary Arterial Hypertension (PAH) on Top of Conventional Treatments
| Verified date | January 2024 |
| Source | Northern Therapeutics |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The SAPPHIRE clinical trial seeks to establish the efficacy and safety of repeated monthly dosing of autologous EPCs transfected with human eNOS (heNOS) in patients with symptomatic severe PAH on available PAH-targeted medical therapy.
| Status | Active, not recruiting |
| Enrollment | 12 |
| Est. completion date | December 2033 |
| Est. primary completion date | November 1, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 80 Years |
| Eligibility | Inclusion Criteria: - Age = 18 years, = 80 years - Established diagnosis of PAH due to the following: - Idiopathic or heritable PAH; - Scleroderma associated PAH (limited or diffuse); - Drugs (anorexigens) or toxins; - Congenital heart defects (atrial septal defects, ventricular septal defects, and patent ductus arteriosus) repaired = 1 years - WHO functional class II, III, or IV on appropriate stable therapy for PAH for at least 3 months prior to the screening period and up until randomization, apart from modification of anticoagulant or diuretic dosages, or small adjustments in prostaglandin dose that are considered by the Investigator to be consistent with stable parenteral therapy. - Able to walk unassisted (oxygen use allowed). Aids for carrying oxygen (such as a wheel chair or walker) are permitted provided they are not also required as mobility aids. - An average 6-Minute Walk Distance (6MWD) of = 125 meters and = 440 meters on two consecutive tests during the Screening period - Previous diagnostic right heart cardiac catheterization (RHC) at the time of PAH diagnosis with findings consistent with PAH: specifically, mean pulmonary arterial pressure (mPAP) = 25 mmHg (at rest); pulmonary vascular resistance (PVR) = 3 WU; pulmonary capillary wedge pressure (PCWP) (or left ventricular end diastolic pressure) =12 mmHg if PVR = 3 to < 5 WU, or pulmonary capillary wedge pressure (PCWP) (or left ventricular end diastolic pressure) = 15 mmHg if PVR = 5 WU. If repeat testing has occurred since initial diagnosis, the most recent results should be used. - Echocardiography performed within 12 months prior to the Screening Period confirming a left atrial volume index (LAVI) of = 34 ml/m2 and the absence of any clinically significant left heart disease including evidence of more than mild left-sided valvular heart disease, systolic or diastolic left ventricular dysfunction - Ventilation and perfusion (VQ) nuclear scan performed as part of the initial workup to establish the diagnosis of PAH showing absence (i.e. low probability) of pulmonary embolism. If repeat testing has occurred since initial diagnosis, the most recent results should be used. In the absence of a VQ scan to establish eligibility, a CT angiogram that has been reviewed by a radiologist with expertise in the work up for pulmonary endarterectomy and deemed negative for chronic thromboembolic disease may be used instead. - Pulmonary function tests conducted within 2 years prior to the Screening Period to confirm: total lung capacity (TLC) = 65% the predicted value; and forced expiratory volume at one second (FEV1) of = 65% the predicted value - Must have a resting arterial oxygen saturation (SaO2) =88% with or without supplemental oxygen as measured by pulse oximetry at the Screening Visit - Must not be enrolled in an exercise training program for pulmonary rehabilitation within 3 months prior to the Screening Visit and must agree not to enroll in an exercise training program for pulmonary rehabilitation during the Screening Period and the first 6 months of the study. Participants enrolled in an exercise program for pulmonary rehabilitation 3 months prior to screening may enter the study if they agree to maintain their current level of rehabilitation for the first 6 months of the study - Women of child-bearing potential (defined as less than 1 year post-menopausal and not surgically sterile) must be practicing abstinence or using two highly effective methods of contraception (defined as a method of birth control that results in a low failure rate, i.e., less than 1% per year, such as approved hormonal contraceptives, barrier methods [such as a condom or diaphragm] used with a spermicide, or an intrauterine device). Subjects must have a negative ß-hCG pregnancy test during the Screening period and negative urine pregnancy test results at all other study visits - Must be willing and able to comply with study requirements and restrictions. Exclusion Criteria: - Pregnant or lactating - PAH related to any condition not covered under inclusion criteria, including but not limited to pulmonary venous hypertension, pulmonary veno-occlusive disease, pulmonary capillary hemangiomatosis, or chronic thromboembolic pulmonary hypertension - Evidence of more than mild interstitial lung disease on Chest CT within the last 5 years (last 3 years for patients with scleroderma associated PAH) - Treatment with an investigational drug, device or therapy within 3 months prior to the screening period or is scheduled to receive an investigational drug, device or therapy during the course of the study - Any musculoskeletal disease or any other disease that would significantly limit ambulation - Unrepaired or recently repaired (< 1 year) congenital systemic-to-pulmonary shunt other than patent foramen ovale - Patients having three or more of the following four AMBITION study HFpEF risk factors will be excluded: - BMI = 30 kg/m2, - History of essential hypertension, - Diabetes mellitus (any type) - Historical evidence of significant coronary artery disease (CAD) by ANY ONE of the following: - History of MI - History of PCI - Prior coronary angiography evidence of CAD (>50% stenosis in =1 vessel) - Previous positive Stress Test - Previous CABG - Stable angina - Creatinine clearance <30 ml/min (using the Cockroft-Gault formula) or requires hemodialysis - Inability to undergo the apheresis procedure due to poor venous access or laboratory tests that are not within acceptable ranges (not including INR for patients on Coumadin) - Childs-Pugh class C liver cirrhosis - Previous atrial septostomy - Any other clinically significant illness or abnormal laboratory values (measured during the screening period) that, in the opinion of the Investigator, might put the subject at risk of harm during the study or might adversely affect the interpretation of the study data - Anticipated survival less than 1 year due to concomitant disease - History of cancer in the past 5 years (except for low grade and fully resolved non-melanoma skin cancer) - Results during screening consistent with current infection with HIV, Hepatitis B(HBV) or C(HCV), human T-cell lymphotropic virus (HTLV- I/II) or syphilis - Systemic arterial systolic blood pressure < 85 mm Hg - Known allergy to gentamicin or amphotericin - Patients who have participated in any gene therapy study or an angiogenic growth factor protein study - Patients unable to provide informed consent and comply with the visit schedule. |
| Country | Name | City | State |
|---|---|---|---|
| Canada | Peter Lougheed Center, University of Calgary | Calgary | Alberta |
| Canada | London Health Sciences Center | London | Ontario |
| Canada | University of Ottawa Heart Institute | Ottawa | Ontario |
| Canada | Toronto General Hospital | Toronto | Ontario |
| Lead Sponsor | Collaborator |
|---|---|
| Northern Therapeutics | Ottawa Hospital Research Institute |
Canada,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Change in 6 Minute Walk Distance (6MWD) from Baseline | Comparison of change from baseline after delivery of 4 doses of study product (Arms 2 and 3 versus Arm 1) | 6 months | |
| Secondary | Change in 6 Minute Walk Distance (6MWD) from Baseline | Comparison of change from baseline after delivery of 4 versus 8 doses of study product (Arms 1 versus Arm 3) | 12 months | |
| Secondary | Change in 6 Minute Walk Distance (6MWD) from Baseline | Comparison of change from baseline to assess durability of any measured improvement (Arm 2 only) | 3 and 9 months | |
| Secondary | Change in Pulmonary Vascular Resistance from Baseline | Comparison of change from baseline after 4 doses of study product (Arms 2 and 3 versus Arm 1) | 6 months | |
| Secondary | Change in Pulmonary Vascular Resistance from Baseline | Comparison of change from baseline after delivery of 4 versus 8 doses of study product (Arm 1 versus Arm 3) | 12 months | |
| Secondary | Change in Pulmonary Vascular Resistance from Baseline | Comparison of change from baseline to assess durability of any measured improvement (Arm 2 only) | 3 and 9 months | |
| Secondary | Number of Deaths or Clinical Worsening of Pulmonary Arterial Hypertension | Comparision of number measured from baseline (Arms 2 and 3 versus Arm 1). Clinical worsening will be defined by any of the following: all-cause mortality, hospitalization due to worsening cardiopulmonary status attributable to progression of disease, decrease in 6MWD by = 15%, worsening of WHO functional class | 6 months | |
| Secondary | Number of Deaths or Clinical Worsening of Pulmonary Arterial Hypertension | Comparison of number measured from baseline after delivery of 4 versus 8 doses of study product (Arm 1 versus Arm 3). Clinical worsening will be defined by any of the following: all-cause mortality, hospitalization due to worsening cardiopulmonary status attributable to progression of disease, decrease in 6MWD by = 15%, worsening of WHO functional class | 12 months | |
| Secondary | Change in Echocardiography Right Ventricular (RV) Function Measures from Baseline | Comparison of change from baseline after 4 doses of study product (Arms 2 and 3 versus Arm 1) | 6 months | |
| Secondary | Change in Echocardiography Right Ventricular (RV) Function Measures from Baseline | Comparison of change from baseline after delivery of 4 versus 8 doses of study product (Arm 1 versus Arm 3) | 12 months | |
| Secondary | Change in Magnetic Resonance Imaging Right Ventricular (RV) Function Measures from Baseline | Comparison of change from baseline after delivery of 4 doses of study product (Arms 2 and 3 versus Arm 1) | 6 months | |
| Secondary | Change in Magnetic Resonance Imaging Right Ventricular (RV) Function Measures from Baseline | Comparison of change from baseline after delivery of 4 versus 8 doses of study product (Arm 1 versus Arm 3) | 12 months | |
| Secondary | Change in Quality of Life Measures from Baseline | Comparison of change from baseline measured by SF-36 Survey after delivery of 4 doses of study product (Arms 2 and 3 versus Arm 1) | 6 months | |
| Secondary | Change in Quality of Life Measures from Baseline | Comparison in change from baseline measured by SF-36 Survey after delivery of 4 versus 8 doses of study product (Arm 1 versus Arm 3) | 12 months |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT02267200 -
The Screening and Analysis of Plasma Biomarkers in Irreversible PAH-CHD
|
N/A |