Safety and Efficacy on Deoxyspergualin (NKT-01) in Patients With Lupus Nephritis

Phase 1

Completed

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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
1	NKT-01	NKT-01

Primary Outcome Measures

Name	Time	Method
Complete and Partial Response Rate	Screening, Day 14 of Cycles 4, 6 and 9, up to 27 weeks	A four-point scale was defined: complete response (CR), partial response (PR), stable disease (SD) or treatment failure (TF). The response criteria were defined prior to the start of the study: for a CR, PR or SD prednisone had to be decreased to \<= 7.5 mg/day, a higher dosage was automatically classified as TF. The presence of urinary erythrocyte or granular casts excluded CR. As the baseline activity of every patient is different, it was necessary to define baseline proteinuria (g/24 h) or kidney function (estimated glomerular filtration rate) as the reference value for the definition of response for every patient individually. The baseline was defined as the renal function and proteinuria level before the onset of the recent LN flare which qualified the patient for the study. Response was determined as the ratio of the proteinuria or kidney function at cycle 4, 6 or 9 to the baseline values of the individual patient.

Secondary Outcome Measures

Name	Time	Method
SELENA-SLEDAI Score	Screening, the last day of Cycles 4, 6 and 9, up to 27 weeks	The "Safety of Estrogen in Lupus Erythematosus National Assessment - systemic lupus erythematosus disease activity index' (SELENA-SLEDAI) document the current activity of SLE/LN. It contains 24 items (descriptors), which are differently weighed. The score has a total range of 0 - 105. As a maximum 105 score points can be reached meaning the worst disease activity.
Treatment Days With Corticosteroids of <= 7.5 mg/Day	1st and 9th Cycle	Entry to the study was permitted for patients with doses of oral corticosteroids (OCS) of \<= 1.0 mg/kg/day (maximum dose 80 mg/day). OCS dosage was maintained, decreased or increased according to the response to DSG. The number of days on which the OCS dose was \<= 7.5 mg/day was counted in each cycle.

Locations (6): Universitat Frankfurt
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Frankfurt, Germany
University of Regensburg
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Regensburg, Germany
University Hospital Mannheim, Heidelberg University
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Mannheim, Germany
Universitatsklinikum Charite
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Berlin, Germany
General Faculty Hospital
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Prague, Czech Republic
University of Heidelberg
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Heidelberg, Germany