Etanercept for the Treatment of Lupus Nephritis

• ClinicalTrials.gov Identifier: NCT00447265
• Recruitment Status: Terminated
• First Posted: March 14, 2007
• Results First Posted: December 19, 2011
• Last Update Posted: February 12, 2013
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Care Provider); Primary Purpose: Treatment
• Condition: Lupus Nephritis
• Interventions: Drug: Etanercept; Drug: Lupus Treatment- Standard of Care; Drug: Placebo
• Enrollment: 1

Participant Flow

Recruitment Details	Participant recruitment occurred at 6 sites. All sites were affiliated with a university and utilized a lupus clinic and outside referrals for recruitment. The first site (UCSF) was activated on 1 Feb 2008. The remaining 5 sites (Feinstein, Rochester, Colorado, Duke, and UAB) were activated over the next year.
Pre-assignment Details	The participant signed an informed consent before study screening procedures commenced to assess eligibility criteria (lupus diagnosis with active nephritis, positive ANA, presence of dsDNA antibodies, and stable medication regimens of either mycophenolate mofetil (MMF, CellCept®, Myfortic®) or azathioprine at the screening visit.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description	Participants (or their caretaker) would administer 50 mg etanercept subcutaneous injections once weekly for 24 weeks. They would continue receiving their usual treatment with corticosteroids and either mycophenolate mofetil or azathioprine.	Participants (or their caretaker) would administer 50 mg placebo subcutaneous injections once weekly for 24 weeks. They would continue receiving their usual treatment with corticosteroids and either mycophenolate mofetil or azathioprine.
Period Title: Overall Study
Started	1	0
Completed	0 [1]	0
Not Completed	1	0
Reason Not Completed
Physician Decision	1	0
[1] The participant completed treatment and discontinued follow-up at week 39 after randomization

Baseline Characteristics

Arm/Group Title		Etanercept
Arm/Group Description		Participant self-administered 50 mg etanercept subcutaneous injections once weekly for 24 weeks. She continued receiving her usual treatment with corticosteroids and mycophenolate mofetil.
Overall Number of Baseline Participants		1
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	1 100.0%
	>=65 years	0 0.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants
	Female	1 100.0%
	Male	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	1 participants
		1
Day 0 GFR (mL/min per 1.73m^2) [1]; Mean (Full Range); Unit of measure: mL/min/1.73m^2
	Number Analyzed	1 participants
		96.9; (96.9 to 96.9)
		[1] Measure Description: Glomerular filtration rate (GFR) is calculated based on the "Modification of Diet in Renal Disease" equation (Levy, AS, Coresh J, Galk E et al, National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med, 139(2): 137-47, 2003)
Day 0 random urine protein; Mean (Full Range); Unit of measure: mg/dL
	Number Analyzed	1 participants
		141; (141 to 141)
SLEDAI total score [1]; Mean (Full Range); Unit of measure: Score
	Number Analyzed	1 participants
		22; (22 to 22)
		[1] Measure Description: The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) is a concise measure of lupus disease activity with excellent test-retest reliability and high responsiveness to clinically important changes in the disease. The total score is derived from ratings on 24 conditions plus the Physician's Global Assessment; 0 indicates inactive disease and the maximum theoretical score is 105 with higher scores representing increased disease activity.

Outcome Measures

1. Primary Outcome

Title	Number of Adverse Events (AEs)Grade 3 or Higher Experienced by Participant During Treatment Phase of Study
Description	Number of adverse events (AEs) or serious adverse events (SAEs) Grade 3 or higher experienced by participant over the duration of the treatment period. [1] [1] This study graded the severity of AEs experienced by the study participant according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0.
Time Frame	24 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etanercept
Arm/Group Description:	Etanercept plus standard of care
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: Events
	0

2. Secondary Outcome

Title	Number of Participant Adverse Events (AEs) From Baseline to Early Study Withdrawal Visit
Description	Number of participant AEs during the trial. This study graded the severity of AEs experienced by the study participant according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0.
Time Frame	39 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etanercept
Arm/Group Description:	Etanercept plus standard of care
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: Events
	3

3. Secondary Outcome

Title	Percent of Participants Who Achieved a Renal Response at Week 24
Description	Percent of study participants who achieved a renal response at 24 weeks.[1] [1]A renal response is defined as: 1) 50% reduction in proteinuria compared to baseline as measured by urinary protein: creatinine ratio; and 2) stable or improving renal function as defined by the Glomerular filtration rate (GFR) calculated based on the "Modification of Diet in Renal Disease" equation (Levy, AS, Coresh J, Galk E et al, National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med, 139(2): 137-47, 2003)
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etanercept
Arm/Group Description:	Etanercept plus standard of care
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: Percent of Participants
	100

4. Secondary Outcome

Title	Time to Participant's Renal Response
Description	Time to when participant achieved a renal response[1] [1]A renal response is defined as: 1) 50% reduction in proteinuria compared to baseline as measured by urinary protein: creatinine ratio; and 2) stable or improving renal function as defined by the Glomerular filtration rate (GFR) calculated based on the "Modification of Diet in Renal Disease" equation (Levy, AS, Coresh J, Galk E et al, National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med, 139(2): 137-47, 2003)
Time Frame	First 24 Weeks of Study Period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etanercept
Arm/Group Description:	Etanercept plus standard of care
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: Weeks
	24

5. Secondary Outcome

Title	Participant Systematic Lupus Erythematosus Disease Activity Index (SLEDAI) Score at Baseline and at Early Study Withdrawal Visit
Description	Reported here is the baseline and week 39 Systematic Lupus Erythematosus Disease Activity Index (SLEDAI) scores. The SLEDAI is a concise measure of lupus disease activity with excellent test-retest reliability and high responsiveness to clinically important changes in the disease. The total score is derived from ratings on 24 conditions plus the Physician's Global Assessment; 0 indicates inactive disease and the maximum theoretical score is 105, with higher scores representing increased disease activity.
Time Frame	Baseline, Week 39 (Early Study Withdrawal Visit)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etanercept
Arm/Group Description:	Etanercept plus standard of care
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: Points on a scale
Baseline SLEDAI Score	22
Week 39 SLEDAI score	8

6. Secondary Outcome

Title	Number of Participants With a C to B Score Change From Baseline to Week 24 in the British Isles Lupus Assessment Group (BILAG) Mucocutaneous Score
Description	Reported here is the number of participants with a change in their BILAG Mucocutaneous Score from C (at baseline) to B (at week 24). A single alphabetic score (A through E) is used to denote disease severity. The BILAG score is a converted numerical score (A=9, B=3, C=1, D=0, E=0). A maximum mucocutaneous score of 9 signifies higher disease activity and a score of 0 is indicative of inactive systematic lupus erythematosus (SLE) in the specified organ system.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etanercept
Arm/Group Description:	Etanercept plus standard of care
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: Participants
	1

7. Secondary Outcome

Title	Number of Participants With a B to D Change From Baseline to Week 24 in the British Isles Lupus Assessment Group (BILAG) Musculoskeletal Score
Description	Reported here is the number of participants with a change in their BILAG Musculoskeletal Score from B (at baseline) to D (at week 24). A single alphabetic score (A through E) is used to denote disease severity. The BILAG score is a converted numerical score (A=9, B=3, C=1, D=0, E=0).A maximum musculoskeletal score of 9 signifies higher disease activity and a score of 0 is indicative of inactive systematic lupus erythematosus (SLE) in the specified organ system.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etanercept
Arm/Group Description:	Etanercept plus standard of care
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: Participants
	1

8. Secondary Outcome

Title	Number of Participants With an A to B Score Change From Baseline to Week 24 in the British Isles Lupus Assessment Group (BILAG) Renal Score
Description	Reported here is the number of participants with a change in their BILAG Renal Score from A (at baseline) to B (at week 24). A single alphabetic score (A through E) is used to denote disease severity. The BILAG score is a converted numerical score (A=9, B=3, C=1, D=0, E=0).A maximum renal score of 9 signifies higher disease activity and a score of 0 is indicative of inactive systematic lupus erythematosus (SLE) in the specified organ system
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etanercept
Arm/Group Description:	Etanercept plus standard of care
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: Participants
	1

9. Secondary Outcome

Title	Participant Medical Outcome Study Short-Form 36 (SF-36) Physical Component Score at Baseline and Week 24
Description	Reported here is the participant baseline and week 24 SF-36 Physical Component scores. The SF-36 measures 8 domains: physical functioning, role limitations due to physical health, body pain, social functioning, mental health, role limitations due to emotional problems, vitality, and general health perceptions[1]. The Physical Component scores of the SF-36 range from 0 to 100; 0 equals worst health state. Higher numbers reported here indicate more improvement in condition from baseline. [1]Ref: Ware JE, Sherbourne CD. The MOS36-item short-form health survey Med Care. 1992; 30:473-483.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etanercept
Arm/Group Description:	Etanercept plus standard of care
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: Score on a scale
Baseline SF-36 Physical Component Score	44.4
Week 24 SF-36 Physical Component Score	42.3

10. Secondary Outcome

Title	Participant Medical Outcome Study Short Form 36 (SF-36) Mental Component Score at Baseline and Week 24
Description	Reported here are the participant SF-36 Mental Component scores at baseline and week 24. The SF-36 measures 8 domains: physical functioning, role limitations due to physical health, bodily pain, social functioning, mental health, role limitations due to emotional problems, vitality, and general health perceptions.[1] The Mental Component score of the SF-36 ranges from 0 to 100; 0 equals worst health state. Higher numbers reported here indicate more improvement in condition from baseline. [1]Ref: Ware JE, Sherbourne CD. The MOS36-item short-form health survey. Med Care. 1992; 30:473-483
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etanercept
Arm/Group Description:	Etanercept plus standard of care
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: Score on a scale
Baseline SF-36 Mental Component Score	31.4
Week 24 SF-36 Mental Component Score	52.3

Adverse Events

Time Frame	Baseline to 39 weeks
Adverse Event Reporting Description	This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0
Arm/Group Title	Etanercept
Arm/Group Description	Participant received self-administered 50 mg etanercept subcutaneous injections once weekly for 24 weeks while continuing to receive her usual lupus treatment of corticosteroids and mycophenolate mofetil.
All-Cause Mortality
	Etanercept
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Etanercept
	Affected / at Risk (%)	# Events
Total	0/1 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Etanercept
	Affected / at Risk (%)	# Events
Total	1/1 (100.00%)
Infections and infestations
Otitis media †	1/1 (100.00%)	1
Injury, poisoning and procedural complications
Muscle Strain †	1/1 (100.00%)	1
Skin and subcutaneous tissue disorders
Rash †	1/1 (100.00%)	1
† Indicates events were collected by systematic assessment

Limitations and Caveats

The study terminated early with 1 subject enrolled. Based on safety info from other trials, the protocol chairs decided possible risks to patients outweighed the potential benefits. Analysis of groups is not possible. Study objectives cannot be met.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Associate Director for Clinical Research
• Organization: DAIT/NIAID
• Phone: 301-594-7669
• EMail: DAITClinicalTrialsGov@niaid.nih.gov

Publications:

Aringer M, Graninger WB, Steiner G, Smolen JS. Safety and efficacy of tumor necrosis factor alpha blockade in systemic lupus erythematosus: an open-label study. Arthritis Rheum. 2004 Oct;50(10):3161-9. doi: 10.1002/art.20576.

De Rycke L, Baeten D, Kruithof E, Van den Bosch F, Veys EM, De Keyser F. The effect of TNFalpha blockade on the antinuclear antibody profile in patients with chronic arthritis: biological and clinical implications. Lupus. 2005;14(12):931-7. doi: 10.1191/0961203305lu2240rr.

Mor A, Bingham CO 3rd, Barisoni L, Lydon E, Belmont HM. Proliferative lupus nephritis and leukocytoclastic vasculitis during treatment with etanercept. J Rheumatol. 2005 Apr;32(4):740-3. Erratum In: J Rheumatol. 2014 Nov;41(11):2336. Bingham, Clifton 3rd [corrected to Bingham, Clifton O 3rd].

Scheinfeld N. A comprehensive review and evaluation of the side effects of the tumor necrosis factor alpha blockers etanercept, infliximab and adalimumab. J Dermatolog Treat. 2004 Sep;15(5):280-94. doi: 10.1080/09546630410017275.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00447265
• Other Study ID Numbers: DAIT ALN01
• First Submitted: March 12, 2007
• First Posted: March 14, 2007
• Results First Submitted: October 7, 2011
• Results First Posted: December 19, 2011
• Last Update Posted: February 12, 2013