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

Primary Purpose

Lupus Nephritis

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
NKT-01
Sponsored by
Nippon Kayaku Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lupus Nephritis focused on measuring Lupus nephritis, Deoxyspergualin, Immunosuppression

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • General Faculty Hospital
  • Universitatsklinikum Charite
  • Universitat Frankfurt
  • University of Heidelberg
  • University Hospital Mannheim, Heidelberg University
  • University of Regensburg

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

NKT-01

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
July 2, 2008
Last Updated
November 13, 2016
Sponsor
Nippon Kayaku Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT00709722
Brief Title
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

2. Study Status

Record Verification Date
July 2008
Overall Recruitment Status
Completed
Study Start Date
October 2003 (undefined)
Primary Completion Date
April 2007 (Actual)
Study Completion Date
April 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Nippon Kayaku Co., Ltd.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lupus Nephritis
Keywords
Lupus nephritis, Deoxyspergualin, Immunosuppression

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
NKT-01
Intervention Type
Drug
Intervention Name(s)
NKT-01
Other Intervention Name(s)
Deoxyspergualin, gusperimus
Intervention Description
SC, 0.5 mg/kg/day, consecutive 14 days administrations, 1 week rest, 9 cycles.
Primary Outcome Measure Information:
Title
Complete and Partial Response Rate
Description
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.
Time Frame
Screening, Day 14 of Cycles 4, 6 and 9, up to 27 weeks
Secondary Outcome Measure Information:
Title
SELENA-SLEDAI Score
Description
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.
Time Frame
Screening, the last day of Cycles 4, 6 and 9, up to 27 weeks
Title
Treatment Days With Corticosteroids of <= 7.5 mg/Day
Description
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.
Time Frame
1st and 9th Cycle

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hanns-Martin Lorenz, Professor
Organizational Affiliation
Heidelberg University
Official's Role
Principal Investigator
Facility Information:
Facility Name
General Faculty Hospital
City
Prague
ZIP/Postal Code
12808
Country
Czech Republic
Facility Name
Universitatsklinikum Charite
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Universitat Frankfurt
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
University of Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
University Hospital Mannheim, Heidelberg University
City
Mannheim
ZIP/Postal Code
68135
Country
Germany
Facility Name
University of Regensburg
City
Regensburg
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
21356124
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.
Results Reference
derived

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

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