Clinical trial NCT01015456: The Efficacy of Enteric-coated Mycophenolate Sodium (EC-MPS) (Myfortic) in The Treatment of Relapse or Resistant Proliferative Lupus Nephritis
Official title: The Clinical Efficacy and Economic Evaluation of EC-MPS (Myfortic) in the Treatment of Relapse or Resistant Proliferative Lupus Nephritis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Lupus Nephritis
Keywords: lupus nephritis
mycophenolate sodium
cyclophosphamide
Lead sponsor: Chulalongkorn University
Sponsor class: OTHER
Collaborators: name: Clinical Research Collaborative Network
name: Health Intervention and Technology Assessment Program (HITAP)
First posted: 2009-11-18
Enrollment: 59
Sex: ALL
Minimum age (years): 16
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To investigate the efficacy and safety of enteric-coated mycophenolate sodium (Myfortic) as compared to intravenous cyclophosphamide in the treatment of active nephritis. The primary outcomes are complete and partial renal remission, as assessed by renal function, urinary sediment and proteinuria in patients with International Society of Nephrology/ Renal Pathology Society (ISN/RPS) class III or IV lupus nephritis.

Detailed description: In this study, there are two sub-studies in order to define secondary endpoints.

1. Pharmacokinetics study of Mycophenolic acid
2. Identify biomarkers for therapy-resistant prediction.
3. Identify biomarkers for predicting a loss of kidney function.

Eligibility criteria: Inclusion Criteria:

* age 16 years of above at the time of screening
* ability and willingness to provide written informed consent (or to obtain consent from parent guardian where applicable) and to comply with the schedule of protocol requirements
* Diagnosis of SLE according to ACR criteria. At least 4 criteria must have been present for the diagnosis of SLE. The 4 criteria do not have to be present at the time of screening
* Active lupus nephritis defined as follows: Biopsy proven (within 16 weeks prior to screening) ISN Class III or IV (A or A/C) not include III(C) IV(C) and VI (\>90% chronic irreversible scarring)
* Relapse or resistant to (3 consecutive doses) IVCY
* Resistant lupus or Relapse lupus nephritis defined as follows:

  * Increase in serum creatinine \>/= 0.3 mg/dl or
  * Increase in proteinuria \> 1.5 g/day (which must have improved by ≥ 50% in the preceding 3 months)
* Life-time cumulative dose of IVCY \> 6 grams
* Female patients of childbearing potential must have a negative serum pregnancy

Exclusion Criteria:

Relates to SLE

* Diagnosis of rapid progressive glomerulonephritis (RPGN): doubling serum creatinine and/or crescentic glomeruli ≥ 30%
* Severe renal impairment as defined by calculated creatinine clearance or MDRD-GFR \< 30 ml/min(except creatinine clearance or MDRD-GFR \> 50 ml/min in the 12 weeks prior to screening)
* History of serious disease or complication in any organ system that not appropriate to treatment immunosuppressive drug groups.
* Severe extra-renal organ involvement

Related to Treatment

* Previous of any Mycophenolate groups in the 6 months prior to screening
* Treatment with any investigational drugs in the 3 months prior to screening

Related to General Health

* Pregnancy or breast feeding mothers.
* Concomitant condition which has required treatment moderate to high dose steroid in the 12 weeks prior to screening.
* Evidence of significant uncontrolled concomitant disease in any organ system not related to SLE.
* History of cancer, including solid tumors, hematological malignancies and carcinoma.
* Evidence of current abuse of drugs or alcohol.

Related to Laboratory Findings

* Neutrophile \< 1,500/mm3, Hb \< 7g/L, Platelet \< 50,000/mm3 (except active SLE)
* Positive HBsAg or anti-HCV or anti-HIV.

Primary outcomes:
measure: Efficacy of enteric-coated Mycophenolate Sodium at 12 months in the treatment of lupus nephritis
timeFrame: 12 months
Secondary outcomes:
measure: The cost-effectiveness of using enteric-coated Mycophenolate Sodium as compared to standard treatment
timeFrame: 12 months
measure: The ratio of patients with declined renal function
timeFrame: 12 months
measure: Time to remission
timeFrame: 12 months
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: Nopparat Rajathani
city: Khon Kaen
country: Thailand
facility: Khon Kaen University
city: Pathumthani
country: Thailand
facility: Thammasart University
Study officials:
affiliation: Chulalongkorn University
name: Yingyos Avihingsanon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Anutrakulchai S, Panaput T, Wongchinsri J, Chaishayanon S, Satirapoj B, Traitanon O, Pima W, Rukrung C, Thinkhamrop B, Avihingsanon Y. A multicentre, randomised controlled study of enteric-coated mycophenolate sodium for the treatment of relapsed or resistant proliferative lupus nephritis: an Asian experience. Lupus Sci Med. 2016 Jan 14;3(1):e000120. doi: 10.1136/lupus-2015-000120. eCollection 2016.