Clinical trial NCT03214731: Efficacy and Safety of Artesunate Plus Standard of Care in Active Lupus Nephritis
Official title: A Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Artesunate Plus Standard of Care in Active Lupus Nephritis: Pilot Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Lupus Nephritis
Keywords: artesunate
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: The First People's Hospital of Yunnan
name: The First Affiliated Hospital of Nanchang University
name: General Hospital of Ningxia Medical University
name: First Affiliated Hospital of Fujian Medical University
name: Shenzhen Second People's Hospital
name: The Third Xiangya Hospital of Central South University
name: Tongji Hospital
First posted: 2017-07-12
Enrollment: 90
Sex: ALL
Minimum age (years): 14
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Remission
timeFrame: 6 month
Secondary outcomes:
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The 1st Affiliated Hospital, Sun Yet-sen University
state: Guangdong
Study officials:
References: