Ignite Creation Date:
2024-05-06 @ 6:54 PM
Last Modification Date:
2024-10-26 @ 2:57 PM
Study NCT ID:
NCT05828147
Status:
RECRUITING
Last Update Posted:
2024-02-07
First Post:
2023-03-28
Brief Title:
Anti-CD20 Antibodies for Treatment of SLE-PAH
Sponsor:
Chinese SLE Treatment And Research Group
Organization:
Chinese SLE Treatment And Research Group
Study Overview
Official Title:
Efficacy and Mechanism of Anti-CD20 Antibodies in Systemic Lupus Erythematosus Associated Pulmonary Arterial Hypertension Based on Multi Omics Studies
Status:
RECRUITING
Status Verified Date:
2024-02
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:
This is a prospective single-arm single-center explorative clinical trial to evaluate the effect of Rituximab on disease progression in subjects with SLE-PAH receiving concurrent stable-dose standard medical therapy The study will focus on assessment of clinical response and safety measures longitudinally In addition the biomarker of treatment efficacy with Rituximab and pathogenic autoantibody response in this disease will be investigated
Detailed Description:
This is a prospective single-arm single-center explorative clinical trial to evaluate the effect of Rituximab on disease progression in subjects with SLE-PAH receiving concurrent stable-dose standard medical therapy with a prostanoid endothelin receptor antagonist phosphodiesterase 5 PDE-5 inhibitor andor guanylate cyclase stimulators
Objective The study will focus on assessment of clinical response and safety measures longitudinallyThe primary objective of this study is to explore the safety and efficacy of Rituximab in patients with SLE-PAH In addition the biomarker of treatment efficacy with Rituximab and pathogenic autoantibody response in this disease will be investigated
Study population Subjects with SLE-PAH with mean pulmonary artery pressure 25mmHg pulmonary artery wedge pressure 15mmHg and pulmonary vascular resistance 3WU as measured by right heart catheterization will be enrolled The diagnosis of SLE-PAH should be confirmed by a rheumatologist experienced in the diagnosis and treatment of systemic lupus erythematosus in conjunction with a cardiologist specializing in management of PAH Both specialists will be part of the study team at each site
Treatment Rituximab will be administered as two IV infusions of 1000 mg each given two weeks apart at Day 0 and Week 2 All subjects will receive 40 mg of prednisone orally the night before and morning of each infusion with diphenhydramine and acetaminophen orally thirty to sixty minutes prior to each infusion of rituximab Subjects will remain on their baseline standard medical regimen
Fifty eligible subjects will be accrued Each potential study subject will provide written informed consent prior to screening procedures All inclusion and exclusion criteria must be met at time of recruitment prior to receipt of the first dose of rituximab Day 0 Treatment Initiation
Clinical assessments and sample collection will occur regularly through Week 24 with telephone follow-up conducted intermittently The peripheral proteome bulk-RNA sequencing whole exome sequencing cytokine profile and TB cell subsets will be assessed in 0 and Week 24 During this study AEs and SAEs will be assessed providing the subject has not withdrawn consent to capture any infectious event Grade 3 using the National Cancer Institute-Common Terminology Criteria for Adverse Events NCI-CTCAE No additional study-related data will be collected
The primary efficacy endpoint is the change in pulmonary vascular resistance PVR from baseline to 24 weeks after treatment initiation Hemodynamic measures will be assessed at baseline and Week 24 contributing to the understanding of the relationship between PVR and clinical endpoints Time to clinical worsening will be assessed as a secondary outcome measure through Week 24 contributing to the understanding of the relationship between PVR and clinical endpoints Initiation of new therapy due to disease worsening prior to Week 24 will prompt an endpoint visit and right heart catheterization prior to initiation of the new therapy The mechanistic study objective is to identify biomarkers which correlate with treatment response as measured by exercise capacity 6MWD and PVR right heart catheterization Proteomics whole exome sequencing cytokine profileTB cell subsets and bulk-RNA sequencing will be measured before and after rituximab treatment The other mechanistic objective is to determine if the biomarkers anti-U1 RNP anti-cardiolipin and other autoantibodies and quantitative immunoglobulin levels including IgG subclasses correlate with treatment response as measured by PVR right heart catheterization
The total duration of the study is anticipated to be approximately 3 years
Objective The study will focus on assessment of clinical response and safety measures longitudinallyThe primary objective of this study is to explore the safety and efficacy of Rituximab in patients with SLE-PAH In addition the biomarker of treatment efficacy with Rituximab and pathogenic autoantibody response in this disease will be investigated
Study population Subjects with SLE-PAH with mean pulmonary artery pressure 25mmHg pulmonary artery wedge pressure 15mmHg and pulmonary vascular resistance 3WU as measured by right heart catheterization will be enrolled The diagnosis of SLE-PAH should be confirmed by a rheumatologist experienced in the diagnosis and treatment of systemic lupus erythematosus in conjunction with a cardiologist specializing in management of PAH Both specialists will be part of the study team at each site
Treatment Rituximab will be administered as two IV infusions of 1000 mg each given two weeks apart at Day 0 and Week 2 All subjects will receive 40 mg of prednisone orally the night before and morning of each infusion with diphenhydramine and acetaminophen orally thirty to sixty minutes prior to each infusion of rituximab Subjects will remain on their baseline standard medical regimen
Fifty eligible subjects will be accrued Each potential study subject will provide written informed consent prior to screening procedures All inclusion and exclusion criteria must be met at time of recruitment prior to receipt of the first dose of rituximab Day 0 Treatment Initiation
Clinical assessments and sample collection will occur regularly through Week 24 with telephone follow-up conducted intermittently The peripheral proteome bulk-RNA sequencing whole exome sequencing cytokine profile and TB cell subsets will be assessed in 0 and Week 24 During this study AEs and SAEs will be assessed providing the subject has not withdrawn consent to capture any infectious event Grade 3 using the National Cancer Institute-Common Terminology Criteria for Adverse Events NCI-CTCAE No additional study-related data will be collected
The primary efficacy endpoint is the change in pulmonary vascular resistance PVR from baseline to 24 weeks after treatment initiation Hemodynamic measures will be assessed at baseline and Week 24 contributing to the understanding of the relationship between PVR and clinical endpoints Time to clinical worsening will be assessed as a secondary outcome measure through Week 24 contributing to the understanding of the relationship between PVR and clinical endpoints Initiation of new therapy due to disease worsening prior to Week 24 will prompt an endpoint visit and right heart catheterization prior to initiation of the new therapy The mechanistic study objective is to identify biomarkers which correlate with treatment response as measured by exercise capacity 6MWD and PVR right heart catheterization Proteomics whole exome sequencing cytokine profileTB cell subsets and bulk-RNA sequencing will be measured before and after rituximab treatment The other mechanistic objective is to determine if the biomarkers anti-U1 RNP anti-cardiolipin and other autoantibodies and quantitative immunoglobulin levels including IgG subclasses correlate with treatment response as measured by PVR right heart catheterization
The total duration of the study is anticipated to be approximately 3 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None