Clinical trial NCT00709722: Safety and Efficacy on Deoxyspergualin (NKT-01) in Patients With Lupus Nephritis
Official title: Safety and Efficacy Study on Deoxyspergualin (NKT-01) in Patients With Uncontrolled Lupus Nephritis Receiving Oral Corticosteroids and Prior Treatment of Standard Immunosuppressive Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lupus Nephritis
Keywords: Lupus nephritis
Deoxyspergualin
Immunosuppression
Lead sponsor: Nippon Kayaku Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2008-07-03
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of the open multi-center study is to determine an efficient and safe dose and dosing schedule of NKT-01 in induction of response in treatment of lupus nephritis.

Detailed description: The purpose of this phase I/II study ia to establish that dose of NKT-01 which leads to complete response during a minimum of 6 cycles of treatment without causing WHO grade 3 leukopenia (WBC \< 2x10\^9/L). The patients suffered from uncontrolled lupus nephritis (LN) and took OCS (\<= 1.0 mf/kf/day, a maximum dose of 80 mg/day) in addition to NKT-01. Therefore the aim of the open multi-center study is to determine an efficient and safe dose and dosing schedule of NKT-01 in induction of response in treatment of lupus nephritis.

Eligibility criteria: Inclusion Criteria:

* Males and females aged 18-70 years.
* A diagnosis of SLE according to the ACR criteria (at least 4/11 criteria).
* Sufficient signs to diagnose active SLE nephritis.
* Serum creatinine concentration of \<= 5.0 mg/dL.
* Leucocyte counts \>= 4000/uL.
* Receiving OCS (\<= 1.0 mg/kg/day; a maximum dose of 80 mg/day).
* Prior treatment with cyclophosphamide, azathioprine, cyclosporin A, or any other immunosuppressive drugs.

Exclusion Criteria:

* Chronic infection of HIV, Hepatitis B, Hepatitis C.
* Acute infection including fungal, viral, bacterial or protozoal diseases.
* Liver toxicity (WHO CTC class 2 and higher). No adequate liver function (total bilirubin \> 25 umol/L = 1.4 mg/dL unless explained otherwise (e.g. inherited, hemolysis), SGOT \> 2.5 x N, SGPT \> 2.5 x N).
* Pregnant or lactating women
* Female patients of child bearing age without safe method of contraception.
* Anemia (hemoglobin \< 8.0 g/dL), leucopenia (leucocytes \< 4000/uL unless attributable to SLE: leucocytes \< 2000/uL), thrombocytopenia (platelets \< 50000/uL).
* Neutrophils below 1000/uL.
* Hypogammaglobulinemia below 400 mg/dL of serum IgG.
* Any other condition that in the eyes of the investigator might have rendered the patient unsuitable for participation in the study. This especially includes major and active SLE organ involvement other than the kidney. Patients with SLE involvement of the central nervous system are not allowed to be included into the study.
* History of malignancy.
* Current participation in another trial or lass than 6 months since participation in a similar trial.

Primary outcomes:
measure: Complete and Partial Response Rate
timeFrame: Screening, Day 14 of Cycles 4, 6 and 9, up to 27 weeks
Secondary outcomes:
measure: SELENA-SLEDAI Score
timeFrame: Screening, the last day of Cycles 4, 6 and 9, up to 27 weeks
measure: Treatment Days With Corticosteroids of <= 7.5 mg/Day
timeFrame: 1st and 9th Cycle
Other outcomes:
Locations:
city: Prague
country: Czech Republic
facility: General Faculty Hospital
city: Berlin
country: Germany
facility: Universitatsklinikum Charite
city: Frankfurt
country: Germany
facility: Universitat Frankfurt
city: Heidelberg
country: Germany
facility: University of Heidelberg
city: Mannheim
country: Germany
facility: University Hospital Mannheim, Heidelberg University
city: Regensburg
country: Germany
facility: University of Regensburg
Study officials:
affiliation: Heidelberg University
name: Hanns-Martin Lorenz, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lorenz HM, Schmitt WH, Tesar V, Muller-Ladner U, Tarner I, Hauser IA, Hiepe F, Alexander T, Woehling H, Nemoto K, Heinzel PA. Treatment of active lupus nephritis with the novel immunosuppressant 15-deoxyspergualin: an open-label dose escalation study. Arthritis Res Ther. 2011 Mar 1;13(2):R36. doi: 10.1186/ar3268.