Efficacy and Safety of Artesunate Plus Standard of Care in Active Lupus Nephritis (AURORA)

A Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Artesunate Plus Standard of Care in Active Lupus Nephritis: Pilot Study

This is a multi-center, randomized, double-blind, placebo-controlled study. Study subjects are class III, IV, V, III+V, IV+V lupus nephritis patients, according to ISN/RPS 2003 classification of LN, with active lesion needing corticosteroid in combination with immunosuppressant therapy.

Subjects who meet the eligibility criteria during screening will be randomized to 1 of 3 treatment groups in a 1:1:1 ratio: 25mg bid artesunate, 50mg bid artesunate or placebo plus standard of care (prednisone plus mycophenolate mofetil ［MMF］) for 6 month.

Study Overview

• Status: Recruiting
• Conditions: Lupus Nephritis
• Intervention / Treatment: Drug: Artesunate; Other: placebo

Detailed Description

Lupus nephritis (LN) can be observed in up to 70% of SLE patients and is often associated with a poor long-term prognosis. Artesunate, one analogues of antimalarial agent artemisinin, have immunomodulatory properties that might be useful for treating autoimmune diseases including SLE. it is still lack of solid evidence from RCT to evaluate efficacy and safety of artesunate plus standard of care in active LN. Regarding no data could be referred to decide the sample size and optimal dosage, we designed this pilot study. The result and experience of pilot study will answer these questions, and guarantee the multicenter RCT to be conducted successfully.

This is a multi-center, randomized, double-blind, placebo-controlled study. Study subjects are class III, IV, V, III+V, IV+V lupus nephritis patients, according to ISN/RPS 2003 classification of LN, with active lesion needing corticosteroid in combination with immunosuppressant therapy.

Subjects who meet the eligibility criteria during screening will be randomized to 1 of 3 treatment groups in a 1:1:1 ratio: 25mg bid artesunate, 50mg bid artesunate or placebo plus standard of care (prednisone plus mycophenolate mofetil ［MMF］) for 6 month.

All the subjects were asked to visit the hospital for weekly follow-up for four weeks, then monthly thereafter.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Xueqing Yu, MD, Phd; Phone Number: 13802793488; Email: yuxq@mail.sysu.edu.cn
• Study Contact Backup: Name: Wei Chen, MD, Phd; Phone Number: 13924150966; Email: vvchen66@qq.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • The 1st Affiliated Hospital, Sun Yet-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1, Subjects of either sex, 14-65 years of age, 2, Diagnosis of SLE according to the ACR criteria (1997), 3, Renal biopsy within 6 months prior to randomization with a histological diagnosis (ISN/RPS 2003 classification of LN) class III, IV, V, III+V and IV+V [excluding Class III(C), IV-S(C), and IV-G(C)], 4, Class IV or IV+V LN: proteinuria ≥1g/24hr (or Urinary protein: creatinine ratio≥ 1.0) or Scr>1.3mg/dl, with active urinary sediment [> 5 RBCs/hpf or> 5 WBCs/hpf (or within the reference range of the laboratory) in absence of menses and genitourinary tract infection, or presence of cellular casts (RBC or WBC casts)], 5, Class III, III+V or V LN: proteinuria ≥2g/24hr (or Urinary protein: creatinine ratio ≥ 2.0) or Scr>1.3mg/dl, 6, Provision of written informed consent by subject or guardian.

Exclusion Criteria:

1. eGFR<30ml/min/1.73m2,
2. Subjects who have previously failed both MMF (or other forms of mycophenolate) induction therapies,
3. Subjects who received an induction therapy with CTX or MMF within 3 months prior to the planned initiation of the current induction for the study,
4. Have severe active central nervous system (CNS) lupus (including seizures, psychosis, organic brain syndrome, cerebrovascular accident [CVA], cerebritis, or CNS vasculitis) requiring therapeutic intervention within 60 days of baseline (Day 0),
5. Have acute or chronic infection requiring management based on the investigator's opinion,
6. Pregnant, nursing or under unreliable contraceptive method,
7. Subjects who have been on continuous dialysis starting >2 weeks before randomization into the induction phase and/or continuous dialysis with an anticipated duration >8 weeks,
8. Have a history of kidney transplant or a plan of kidney transplant,
9. Known hypersensitivity or contraindication to any drug products or any component of these drug products they plan to receive (e.g. Artesunate, CTX, MMF, AZA, corticosteroids),
10. Have severe acute or chronic diseases (e.g. cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological or infectious diseases) which, in the opinion of the principal investigator, could confound the results of the study or put the subject at under risk,
11. Have a history of malignant neoplasm within the last 5 years, except for adequately treated carcinoma in situ of the uterine cervix,
12. Recruited by other trial and/or use study agent within 4 weeks.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: low dose Art; 25mg bid Artesunate and standard of care was given to patients	Drug: Artesunate; Artesunate was produced by pharmaceutical factory for research specifically; Other Names: Art
Experimental: high dose Art; 50mg bid Artesunate and standard of care was given to patients	Drug: Artesunate; Artesunate was produced by pharmaceutical factory for research specifically; Other Names: Art
Placebo Comparator: placebo; Placebo and standard of care was given to patients	Other: placebo; placebo was produced by pharmaceutical factory for research specifically

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Remission	Complete remission: Proteinuria < 0.3g/ 24hr, no active urinary sediment, normal albumin, stable Scr (within 15% fluctuation).; Partial remission: Proteinuria between 0.3 and 2.9g /24hr and a decrease in value of at least 50% of base value, albumin≥30g/L, stable Scr (within 15% fluctuation).	6 month

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: The First Affiliated Hospital of Nanchang University; Tongji Hospital; First Affiliated Hospital of Fujian Medical University; The Third Xiangya Hospital of Central South University; Shenzhen Second People's Hospital; General Hospital of Ningxia Medical University; The First People's Hospital of Yunnan

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2019
• Primary Completion (Anticipated): September 30, 2022
• Study Completion (Anticipated): September 30, 2022

Study Registration Dates

• First Submitted: July 8, 2017
• First Submitted That Met QC Criteria: July 8, 2017
• First Posted (Actual): July 12, 2017

Study Record Updates

• Last Update Posted (Actual): September 23, 2021
• Last Update Submitted That Met QC Criteria: September 21, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: artesunate
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Connective Tissue Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Nephritis; Lupus Nephritis; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Anthelmintics; Schistosomicides; Antiplatyhelmintic Agents; Artesunate
• Other Study ID Numbers: AURORA (Other Identifier: Mayo Clinic)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No