Ignite Creation Date:
2024-05-05 @ 10:20 PM
Last Modification Date:
2024-10-26 @ 10:17 AM
Study NCT ID:
NCT01086540
Status:
COMPLETED
Last Update Posted:
2023-02-21
First Post:
2010-03-11
Brief Title:
Rituximab for Treatment of Systemic Sclerosis-Associated Pulmonary Arterial Hypertension SSc-PAH
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institute of Allergy and Infectious Diseases NIAID
Study Overview
Official Title:
A Randomized Double-Blind Placebo-Controlled Phase II Multicenter Trial of a Monoclonal Antibody to CD20 Rituximab for the Treatment of Systemic Sclerosis-Associated Pulmonary Arterial Hypertension SSc-PAH
Status:
COMPLETED
Status Verified Date:
2023-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Systemic sclerosis-associated pulmonary arterial hypertension SSc-PAH is a serious life-threatening manifestation of systemic sclerosis SSc an autoimmune disease of the connective tissue characterized by scarring fibrosis and atrophy of the skin joints and tendons skeletal muscles and internal organs and immunological disturbances One-year survival for patients with SSc-PAH ranges from 50-81 There is currently no cure for SSc-PAH and treatment is limited to vasodilator therapy used in all forms of PAH In recent studies immunotherapy was shown to be effective in treating SSc-interstitial lung disease another serious life-threatening manifestation of SSc In addition there are compelling pre-clinical data and anecdotal clinical reports that suggest modulation of the immune system may be an effective strategy for treating SSc-PAH To test this approach this trial will determine if rituximab an immunotherapy has a marked beneficial effect on clinical disease progression with minimal toxicity in patients with SSc-PAH when compared to placebo
Detailed Description:
This prospective double-blind placebo-controlled multi-center randomized trial will evaluate the effect of rituximab on disease progression in subjects with SSc-PAH receiving concurrent stable-dose standard medical therapy with a prostanoid endothelin receptor antagonist andor phosphodiesterase 5 PDE-5 inhibitor The study will focus on assessment of clinical response and safety measures longitudinally In addition the effects of treatment with rituximab on the underlying immune mechanisms associated with B-cell dysregulation and pathogenic autoantibody response in this disease will be investigated 1000 mg of rituximab or placebo will be administered as two IV infusions given two weeks apart Clinical assessments and sample collection will occur at monthly visits through Week 48 If a participant has not recovered B cells by Week 48 B cell studies will be conducted quarterly until reconstitution is documented or for 2 years after initial treatment
This trial will include a sub-study entitled Right Ventricular Response to Rituximab in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension - A Magnetic Resonance Imaging Sub-study RESTORE Sub-study The objective of the RESTORE sub-study is to evaluate the therapeutic effect of rituximab on the right ventricle of patients with SSc-PAH Changes in right ventricular end diastolic volume index RVEDVI and stroke volume SV determined by cardiac MRI will be used as surrogates of right ventricle function and prognosis Enrollment for the RESTORE sub-study will parallel that of main trial Twenty patients from each treatment arm distributed among all participating sites will be recruited for this sub-study Each patient will be studied at baseline ie prior to initiation of study drug and after 24 weeks or at time of discontinuation In addition to the data collection and testing specified in the main trial participants in RESTORE will undergo comprehensive cardiac MRI evaluation All main trial study inclusion and exclusion criteria apply as well as additional exclusion criteria that pertain only to the RESTORE sub-study 1 known hypersensitivity to Gadolinium 2 inability to tolerate or cooperate with MRI 3 morbid obesity and 4 presence of metallic objects or pacemakers
This trial will include a sub-study entitled Right Ventricular Response to Rituximab in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension - A Magnetic Resonance Imaging Sub-study RESTORE Sub-study The objective of the RESTORE sub-study is to evaluate the therapeutic effect of rituximab on the right ventricle of patients with SSc-PAH Changes in right ventricular end diastolic volume index RVEDVI and stroke volume SV determined by cardiac MRI will be used as surrogates of right ventricle function and prognosis Enrollment for the RESTORE sub-study will parallel that of main trial Twenty patients from each treatment arm distributed among all participating sites will be recruited for this sub-study Each patient will be studied at baseline ie prior to initiation of study drug and after 24 weeks or at time of discontinuation In addition to the data collection and testing specified in the main trial participants in RESTORE will undergo comprehensive cardiac MRI evaluation All main trial study inclusion and exclusion criteria apply as well as additional exclusion criteria that pertain only to the RESTORE sub-study 1 known hypersensitivity to Gadolinium 2 inability to tolerate or cooperate with MRI 3 morbid obesity and 4 presence of metallic objects or pacemakers
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None