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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Safety and Efficacy Study on Deoxyspergualin (NKT-01) in Patients With Uncontrolled Lupus Nephritis Receiving Oral Corticosteroids and Prior Treatment of Standard Immunosuppressive Therapy

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: NKT-01


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>NKT-01 | Drug: NKT-01<br>* SC, 0.5 mg/kg/day, consecutive 14 days administrations, 1 week rest, 9 cycles.<br>* Other names: Deoxyspergualin, gusperimus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete and Partial Response Rate | 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. | Screening, Day 14 of Cycles 4, 6 and 9, up to 27 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SELENA-SLEDAI Score | 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. | Screening, the last day of Cycles 4, 6 and 9, up to 27 weeks | 
| Treatment Days With Corticosteroids of <= 7.5 mg/Day | 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. | 1st and 9th Cycle | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lupus nephritis, Deoxyspergualin, Immunosuppression