Anti-CD20 Antibodies for Treatment of SLE-PAH

NCT05828147 | Recruiting Phase 4

• 1 other identifier: CSTAR-K2761
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Systemic Lupus Erythematosus; Pulmonary Arterial Hypertension

Keywords

anti-CD20 antibodies; Systemic Lupus Erythematosus; Pulmonary Arterial Hypertension; multi-omics

Outcome Measures

Primary Outcomes (1)

• pulmonary vascular resistance (PVR)

  PVR as assessed by right heart catheterization, the gold standard method to assess cardiopulmonary haemodynamics. Standardized Fick-based pulmonary vascular resistance (PVRf, in Woods Units) are calculated as follows: PVR = TPG / CO, where TPG = Transpulmonary Gradient (mmHg), CO = Cardiac Output (L/min)

  0-24 weeks

Secondary Outcomes (8)

• 6MWD

  0-24 weeks

• Right atrium Pressure (RAP)

  0-24 weeks

• Cardiac Index (CI)

  0-24 weeks

• Clinical worsening

  0-24 weeks

• BNP/NT proBNP

  0-24 weeks

Study Arms (1)

Rituximab group

EXPERIMENTAL

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.

Drug: Rituximab

Interventions

Rituximab DRUG

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.

Also known as: Hanlikang

Rituximab group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Subject has provided written informed consent.
• \. Subject must be between the ages of 18 and 65, inclusive at the time of recruitment
• \. Clinical diagnosis of systemic lupus erythematosus. Diagnosis of SLE-PAH within the past 5 years, with a mean pulmonary arterial pressure (mPAP) of ≥ 25 mmHg, PAWP ≤15mmHg, mean PVR of \> 3 Wood units at entry.
• \. WHO Functional Class II, III, or IV.
• \. Subjects must have been treated with background medical therapy for PAH (prostanoid, endothelin receptor antagonist, PDE-5 inhibitor, and/or guanylate cyclase stimulators) for a minimum of 8 weeks and have been on stable dose(s) of those medical therapy(ies) for at least 4 weeks prior to randomization with no expectation of change for 24 weeks after randomization.

You may not qualify if:

• \. Treatment with immunocompromising biologic agents (including, but not limited to TNF inhibitors, anakinra, abatacept, and tocilizumab) within 4 weeks prior to treatment initiation or treatment with infliximab within 8 weeks prior to treatment initiation.
• \. SLE combined with important organ damage endangers life:
• Neuropsychiatric lupus with high risk such as status epilepticus;
• Refractory thrombocytopenic purpura has a clear bleeding tendency;
• Pulmonary alveolar hemorrhage leads to respiratory failure;
• \. Uncontrolled infection;
• \. Severe organ dysfunction:
• Patients with moderate or severe liver function impairment (Child-Pugh grade B and C);
• Patients with left ventricular dysfunction (left ventricular ejection fraction\<45%);
• \. Other diseases are limited to completing a 6-minute walking test: angina pectoris, vascular, musculoskeletal lesions, etc
• \. Abnormal laboratory test: platelet\<100 × 109/L, or hemoglobin\<9 g/dL, or white blood cell count\<3 × 109/L, or alanine aminotransferase (ALT)/aspartate aminotransferase (AST) greater than 1.5 times the upper limit of normal value, or total bilirubin and blood lipids greater than 2 times the upper limit of normal value
• \. Persistent hypotension, i.e. systolic blood pressure (SBP)\<90 mmHg
• \. PAH caused by any reason other than SLE: other rheumatic diseases (such as SSc, rheumatoid arthritis, dermatomyositis, etc.); Portal hypertension, hereditary hemorrhagic telangiectasia, etc; Congenital heart disease; Suspicious drugs and poisons;
• \. Chronic hypoxic disease related pulmonary hypertension: moderate or severe obstructive pulmonary disease: FEV1\<55%; Moderate or severe restrictive pulmonary disease: TLC\<60%;
• \. Chronic thromboembolic pulmonary hypertension: Pulmonary ventilation/perfusion imaging indicates moderate to high suspicion of pulmonary thromboembolism;

Sponsors & Collaborators

• Chinese SLE Treatment And Research Group: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

Related Publications (7)

• Kiriakidou M, Ching CL. Systemic Lupus Erythematosus. Ann Intern Med. 2020 Jun 2;172(11):ITC81-ITC96. doi: 10.7326/AITC202006020.

  PMID: 32479157 BACKGROUND

• Li M, Zhang W, Leng X, Li Z, Ye Z, Li C, Li X, Zhu P, Wang Z, Zheng Y, Li X, Zhang M, Zhang F, Zhao Y, Zeng X; CSTAR co-authors. Chinese SLE Treatment and Research group (CSTAR) registry: I. Major clinical characteristics of Chinese patients with systemic lupus erythematosus. Lupus. 2013 Oct;22(11):1192-9. doi: 10.1177/0961203313499086. Epub 2013 Aug 20.

  PMID: 23963101 BACKGROUND

• Qian J, Li M, Zhang X, Wang Q, Zhao J, Tian Z, Wei W, Zuo X, Zhang M, Zhu P, Ye S, Zhang W, Zheng Y, Qi W, Li Y, Zhang Z, Ding F, Gu J, Liu Y, Wang Y, Zeng X; following investigators were collaborators in the CSTAR-PAH study:. Long-term prognosis of patients with systemic lupus erythematosus-associated pulmonary arterial hypertension: CSTAR-PAH cohort study. Eur Respir J. 2019 Feb 14;53(2):1800081. doi: 10.1183/13993003.00081-2018. Print 2019 Feb.

  PMID: 30635295 BACKGROUND

• Gomez Mendez LM, Cascino MD, Garg J, Katsumoto TR, Brakeman P, Dall'Era M, Looney RJ, Rovin B, Dragone L, Brunetta P. Peripheral Blood B Cell Depletion after Rituximab and Complete Response in Lupus Nephritis. Clin J Am Soc Nephrol. 2018 Oct 8;13(10):1502-1509. doi: 10.2215/CJN.01070118. Epub 2018 Aug 8.

  PMID: 30089664 BACKGROUND

• Dorfmuller P, Perros F, Balabanian K, Humbert M. Inflammation in pulmonary arterial hypertension. Eur Respir J. 2003 Aug;22(2):358-63. doi: 10.1183/09031936.03.00038903.

  PMID: 12952274 BACKGROUND

• Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, Carlsen J, Coats AJS, Escribano-Subias P, Ferrari P, Ferreira DS, Ghofrani HA, Giannakoulas G, Kiely DG, Mayer E, Meszaros G, Nagavci B, Olsson KM, Pepke-Zaba J, Quint JK, Radegran G, Simonneau G, Sitbon O, Tonia T, Toshner M, Vachiery JL, Vonk Noordegraaf A, Delcroix M, Rosenkranz S; ESC/ERS Scientific Document Group. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2023 Jan 6;61(1):2200879. doi: 10.1183/13993003.00879-2022. Print 2023 Jan. No abstract available.

  PMID: 36028254 RESULT

• Zamanian RT, Badesch D, Chung L, Domsic RT, Medsger T, Pinckney A, Keyes-Elstein L, D'Aveta C, Spychala M, White RJ, Hassoun PM, Torres F, Sweatt AJ, Molitor JA, Khanna D, Maecker H, Welch B, Goldmuntz E, Nicolls MR. Safety and Efficacy of B-Cell Depletion with Rituximab for the Treatment of Systemic Sclerosis-associated Pulmonary Arterial Hypertension: A Multicenter, Double-Blind, Randomized, Placebo-controlled Trial. Am J Respir Crit Care Med. 2021 Jul 15;204(2):209-221. doi: 10.1164/rccm.202009-3481OC.

  PMID: 33651671 RESULT

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Pulmonary Arterial Hypertension

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Mengtao Li, Prof

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mengtao Li, Prof

CONTACT

86-10-69159958; mengtao.li@cstar.org.cn

Yufang Ding, MD

CONTACT

86-10-69159958; 54dingyufang@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: single-arm, all patients will receive anti-CD20 antibodies.

Study Record Dates

• First Submitted: March 28, 2023
• First Posted: April 25, 2023
• Study Start: May 25, 2023
• Primary Completion: March 1, 2025
• Study Completion: March 1, 2026
• Last Updated: February 7, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 2025.12-2027.12
• Access Criteria: open access

Locations

CN (1)