Proof of Concept Study of IMMUNOadsorption Therapy in Patients With Idiopathic Pulmonary Arterial Hypertension

Study Overview
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Brief Summary
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This clinical investigation is a medical device trial to examine the safety and efficacy of TheraSorb® Ig flex adsorber treatment (as an add-on to conventional treatment) used exclusively with the LIFE 18® apheresis system for extracorporeal application for IA therapy (5 treatments) performed over 5 to 8 consecutive days in patients with Idiopathic Pulmonary Arterial Hypertension and WHO functional classification III.

Official Title
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A Clinical Proof of Concept Study of IMMUNOadsorption Therapy in Patients With Idiopathic Pulmonary Arterial Hypertension

Conditions
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Idiopathic Pulmonary Arterial Hypertension

Intervention / Treatment
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* Device: TheraSorb® - Ig flex


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to understand and willing to sign the Informed Consent Form age > 18 and < 80 years at time of informed consent Idiopathic pulmonary arterial hypertension diagnosed by right heart catheter WHO functional classification III Application of conventional IPAH therapy, which has been stable for the prior 8 weeks Able to perform a 6-minute-walk test (MWT) Negative pregnancy test (β-HCG) at the start of the trial and appropriate contraception throughout the trial for women with child-bearing potential. Exclusion Criteria: Pregnancy and/or lactation PAH of any cause other than permitted in the inclusion criteria, e.g. concomitantly to portal hypertension, complex congenital heart disease, reversed shunt, HIV infection, suspected pulmonary veno-occlusive disease Contraindication for right heart catheterization Any change in disease-targeted therapy within 8 weeks prior to inclusion Walking impairment due to causes other than IPAH that would preclude performance of a 6MWT Any patient who has received any investigational medication within 8 weeks prior to the start of this trial or who is scheduled to receive another investigational drug during the course of the trial between visits V1 and V9 Known intolerance to immunoadsorption in general or to one of the excipients (e.g. sheep antibodies or agarose) or other supporting agents Hemoglobin concentration of < 75% below the lower limit of normal Systolic blood pressure < 85 mmHg Lack of compliance or other similar reason that, in the judgment of the Investigator, precludes satisfactory participation in the trial Concurrent severe or uncontrolled medical disease (i.e. uncontrolled diabetes, congestive heart failure, myocardial infarction within 6 months prior to the study, unstable and uncontrolled hypertension, chronic renal disease, or active uncontrolled generalized viral, bacterial and/ or mycotic infection) which by assessment of the treating Investigator could compromise patients safety or participation in the study Drug or alcohol abuse within the last 5 years Hypercoagulability Known severe immunodeficiency (e.g. AIDS) Severe lung disease: FEV1/FVC < 50%, total capacity < 60% of normal value Indications that prohibit transient anticoagulation using Heparin and/or ACD-A-solutions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immunoadsorption<br>Patients are treated with the TheraSorb® Ig flex adsorber used exclusively with the LIFE 18® apheresis system for extracorporeal application for IA therapy (5 treatments) performed over 5 to 8 consecutive days | Device: TheraSorb® - Ig flex<br>* TheraSorb® Treatment with one TheraSorb® Ig flex adsorber pair, used exclusively with the LIFE 18® apheresis system for extracorporeal application for IA therapy. 5 treatments performed over 5 to 8 consecutive days.<br>* Other names: Immunoadsorption;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary endpoint is the change of pulmonary vascular resistance (PVR) at rest before immunoadsorption compared to 3 months after immunoadsorption therapy determined by right heart catheterization (RHC). |  | Baseline, 3 months after therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| all-cause mortality | The patients will be followed for the duration of the study participation, an expected average of 6 months. |  6months | 
| occurrence and number of Adverse Events | The patients will be followed for the duration of the study participation, an expected average of 6 months. |  6 months | 
| Six-minute walk test (6MWT) |  | Measurements at baseline,  1 week,  1 month,  3 months and  6 months after start of therapy | 
| Quality of life questionnaires | SF-36 EQ-5D™ | Measurements at baseline, and after  1 month,  3 months,  6 months | 
| WHO functional classification | WHO functional classification of pulmonary hypertension (according to the Evian Symposium,1998, modified New York Heart Association (NYHA) Classification | Measurements at baseline,  1 week,  1 month,  3 months and  6 months after start of therapy | 
| Analysis of Hemodynamics by right heart catheterization: RAP, PAPm, CO, CI, SvO2; sPAP | (Right atrial pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac output, cardiac index, venous oxygen saturation, systolic pulmonary arterial pressure.) | Measurements at baseline, after  3 months | 
| Reduction of IgG |  | Measurements at baseline, during each treatment visit,  1 week,  1 month and  3 months after start of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Hypertension, Pulmonary Arterial Hypertension, TheraSorb, immunoadsorption