Trial Outcomes & Findings for Safety and Efficacy on Deoxyspergualin (NKT-01) in Patients With Lupus Nephritis (NCT NCT00709722)

NCT ID: NCT00709722

Last Updated: 2017-01-10

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 21 participants
• Primary outcome timeframe: Screening, Day 14 of Cycles 4, 6 and 9, up to 27 weeks
• Results posted on: 2017-01-10

Participant Flow

The study was conducted at 6 sites in Germany and Czech Republic from 2003 to 2007

Participant milestones

Measure	Deoxyspergualin SC, 0.5 mg/kg/day, consecutive 14 days administrations, 1 week rest, 9 cycles
Overall Study STARTED	21
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Deoxyspergualin SC, 0.5 mg/kg/day, consecutive 14 days administrations, 1 week rest, 9 cycles
Overall Study Adverse Event	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Deoxyspergualin n=20 Participants SC, 0.5 mg/kg/day, consecutive 14 days administrations, 1 week rest, 9 cycles
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	20 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	31.3 Years n=5 Participants
Gender Female	17 Participants n=5 Participants
Gender Male	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Screening, Day 14 of Cycles 4, 6 and 9, up to 27 weeks

Population: ITT population

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.

Outcome measures

Measure	Deoxyspergualin n=20 Participants SC, 0.5 mg/kg/day, consecutive 14 days administrations, 1 week rest, 9 cycles
Complete and Partial Response Rate	55 Percentage of participants

SECONDARY outcome

Timeframe: Screening, the last day of Cycles 4, 6 and 9, up to 27 weeks

Population: ITT population

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.

Outcome measures

Measure	Deoxyspergualin n=20 Participants SC, 0.5 mg/kg/day, consecutive 14 days administrations, 1 week rest, 9 cycles
SELENA-SLEDAI Score Screening	16.9 Score on a scale Interval 12.0 to 32.0
SELENA-SLEDAI Score The last day of Cycle 4	12.9 Score on a scale Interval 4.0 to 21.0
SELENA-SLEDAI Score The last day of Cycle 6	13.7 Score on a scale Interval 4.0 to 22.0
SELENA-SLEDAI Score The last day of Cycle 9	11.7 Score on a scale Interval 6.0 to 21.0

SECONDARY outcome

Timeframe: 1st and 9th Cycle

Population: ITT population

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.

Outcome measures

Measure	Deoxyspergualin n=20 Participants SC, 0.5 mg/kg/day, consecutive 14 days administrations, 1 week rest, 9 cycles
Treatment Days With Corticosteroids of <= 7.5 mg/Day 1st Cycle	2.8 Days Interval 0.0 to 21.0
Treatment Days With Corticosteroids of <= 7.5 mg/Day 9th Cyvle	18 Days Interval 7.0 to 21.0

Adverse Events

Deoxyspergualin

Serious events: 8 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Measure	Deoxyspergualin n=21 participants at risk SC, 0.5 mg/kg/day, consecutive 14 days administrations, 1 week rest, 9 cycles
Blood and lymphatic system disorders Cyclophosphamide induced leucopenia	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Blood and lymphatic system disorders Leucopenia	4.8% 1/21 • Number of events 2 • Throughout study period, up to 27 weeks
Cardiac disorders Angina pectris	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
General disorders Fever	4.8% 1/21 • Number of events 2 • Throughout study period, up to 27 weeks
Infections and infestations Herpes zoster	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Infections and infestations Oral candidiasis	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Infections and infestations Parodontitis, tooth infection, fever	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Infections and infestations Pneumonia	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Investigations Increase in serum creatinine (renal failure)	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Musculoskeletal and connective tissue disorders Myalgia	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Nervous system disorders Headache	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Renal and urinary disorders Increased lupus activity with increased proteinuria and pain	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Renal and urinary disorders Lupus flare (arthritis, myalgia, skin rash)	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Renal and urinary disorders Renal failure (Severe proteinuria)	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Surgical and medical procedures Excision of an uterine myoma	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Surgical and medical procedures Hospitalization for a second cyclophosphamide pulse	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks

Other adverse events

Measure	Deoxyspergualin n=21 participants at risk SC, 0.5 mg/kg/day, consecutive 14 days administrations, 1 week rest, 9 cycles
Infections and infestations Urinary tract infection	28.6% 6/21 • Number of events 12 • Throughout study period, up to 27 weeks
Infections and infestations Oral candidiasis	28.6% 6/21 • Number of events 7 • Throughout study period, up to 27 weeks
Infections and infestations Vaginal candidiasis	19.0% 4/21 • Number of events 5 • Throughout study period, up to 27 weeks
Infections and infestations Nasopharyngitis	19.0% 4/21 • Number of events 5 • Throughout study period, up to 27 weeks
Infections and infestations Respiratory tract infection	14.3% 3/21 • Number of events 4 • Throughout study period, up to 27 weeks
Infections and infestations Bronchitis	9.5% 2/21 • Number of events 4 • Throughout study period, up to 27 weeks
Infections and infestations Pneumonia	14.3% 3/21 • Number of events 3 • Throughout study period, up to 27 weeks
Infections and infestations Herpes simplex	9.5% 2/21 • Number of events 3 • Throughout study period, up to 27 weeks
Infections and infestations Herpes zoster	9.5% 2/21 • Number of events 3 • Throughout study period, up to 27 weeks
Infections and infestations Dental caries	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Infections and infestations Fungal skin infection	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Infections and infestations Gasteroenteritis	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Infections and infestations Infected insect bite	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Infections and infestations Labyrinthitis	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Infections and infestations Onychomycosis	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Infections and infestations Otitis media	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Infections and infestations Pharyngitis	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Infections and infestations Rhinitis	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Infections and infestations Sialoadentitis	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Infections and infestations Tinea infection	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Infections and infestations Tonsillitis	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks
Infections and infestations Tooth infection	4.8% 1/21 • Number of events 1 • Throughout study period, up to 27 weeks

Additional Information

Pharmaceuticals Group

Nippon Kayaku Co., Ltd.

Phone: +81-3-6731-5200

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place