Lupus Nephritis
Conditions
Keywords
Lupus nephritis, Deoxyspergualin, Immunosuppression
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.
Interventions
DRUGNKT-01
SC, 0.5 mg/kg/day, consecutive 14 days administrations, 1 week rest, 9 cycles.
Sponsors
Nippon Kayaku Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Czechia, Germany
Participant flow
Recruitment details
The study was conducted at 6 sites in Germany and Czech Republic from 2003 to 2007
Participants by arm
| Arm | Count |
|---|---|
| Deoxyspergualin SC, 0.5 mg/kg/day, consecutive 14 days administrations, 1 week rest, 9 cycles | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Deoxyspergualin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Age, Continuous | 31.3 Years |
| Gender Female | 17 Participants |
| Gender Male | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 21 / 21 |
| serious Total, serious adverse events | 8 / 21 |
Outcome results
Primary
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.
Time frame: Screening, Day 14 of Cycles 4, 6 and 9, up to 27 weeks
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Deoxyspergualin | Complete and Partial Response Rate | 55 Percentage of participants |
Secondary
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.
Time frame: Screening, the last day of Cycles 4, 6 and 9, up to 27 weeks
Population: ITT population
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Deoxyspergualin | SELENA-SLEDAI Score | Screening | 16.9 Score on a scale |
| Deoxyspergualin | SELENA-SLEDAI Score | The last day of Cycle 4 | 12.9 Score on a scale |
| Deoxyspergualin | SELENA-SLEDAI Score | The last day of Cycle 6 | 13.7 Score on a scale |
| Deoxyspergualin | SELENA-SLEDAI Score | The last day of Cycle 9 | 11.7 Score on a scale |
Secondary
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.
Time frame: 1st and 9th Cycle
Population: ITT population
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Deoxyspergualin | Treatment Days With Corticosteroids of <= 7.5 mg/Day | 1st Cycle | 2.8 Days |
| Deoxyspergualin | Treatment Days With Corticosteroids of <= 7.5 mg/Day | 9th Cyvle | 18 Days |