A Study of LY2127399 in Participants With Systemic Lupus Erythematosus

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Subcutaneous LY2127399 in Patients With Systemic Lupus Erythematosus (SLE)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01205438

Enrollment

1124

Registered

2010-09-20

Start date

2011-01-31

Completion date

2015-03-31

Last updated

2018-07-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Autoimmune Disease, Connective Tissue Disease, Systemic Lupus Erythematosus

Keywords

SLE, Systemic Lupus Erythematosis, Lupus, autoimmune disease, LY2127399, Immune System Disease

Brief summary

The purpose of this SLE study is to evaluate the efficacy, safety and tolerability of two different doses of LY2127399 administered in addition to standard of care therapy in participants with active SLE.

Interventions

DRUGLY2127399

120mg administered via subcutaneous injection for 52 weeks. 240 mg loading dose will be administered as the first dose of study drug

DRUGPlacebo every 2 weeks

Administered via subcutaneous injection for 52 weeks. A matching loading dose will also be administered at the first dose.

DRUGPlacebo every 4 weeks

Administered via subcutaneous injection for 52 weeks.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Clinical diagnosis of SLE as defined by American College of Rheumatology (ACR) criteria * Have positive antinuclear antibodies (ANA) * Agree not to become pregnant throughout the course of the trial * Have a screening SELENA-SLEDAI score ≥6. (The participant must be actively exhibiting all the symptoms scored on the screening SELENA-SLEDAI on the day of screening.)

Exclusion criteria

* Have active severe Lupus kidney disease * Have active Central Nervous System or peripheral neurologic disease * Have received intravenous immunoglobulin (IVIg) within 180 days of randomization * Have active or recent infection within 30 days of screening * Have had a serious infection within 90 days of randomization * Have evidence or test positive for Hepatitis B * Have Hepatitis C * Are human immunodeficiency virus (HIV) positive * Have evidence of active or latent tuberculosis (TB) * Presence of significant laboratory abnormalities at screening * Have had a malignancy in the past 5 years, except for cervical carcinoma in-situ or basal cell or squamous epithelial skin cell that were completely resected with no reoccurrence in the 3 yrs prior to randomization * Have received greater than 40 mgs of prednisone or equivalent in the past 30 days * Have changed your dose of antimalarial drug in the past 30 days * Have changed your dose of immunosuppressive drug in the past 90 days * Have previously received rituximab

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Achieving an SLE Responder Index Response at Week 52	52 weeks	Percentage of participants with a ≥ 5 point reduction from baseline in SELENA SLEDAI score, and no worsening (increase of \< 0.30 points from baseline) in PGA, and no new BILAG A organ domain score or 2 new BILAG B organ domain scores compared with baseline. SELENA SLEDAI is calculated from 24 individual descriptors across 9 organ systems; 0 indicates inactive disease and the maximum theoretical score is 105; scores \> 20 are rare. PGA is a visual analog scale scored from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe). BILAG uses a single score for each of the 9 organ domains; range is from severe (A) to no disease (E). Participants who were unable to comply with allowed concomitant medications requirements were considered non-responders, as were participants who dropped out or were missing Week 52 data.

Secondary

Measure	Time frame	Description
Change From Baseline to 52 Weeks in Anti-double Stranded Deoxyribonucleic Acid (Anti-dsDNA) Level	Baseline, 52 weeks	Anti-double stranded deoxyribonucleic acid (anti-dsDNA) is a lab analyte used to assist in the diagnosis of SLE.
Change From Baseline to 52 Week Endpoint in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI2K) Score	Baseline, 52 weeks	SLE Disease Activity Index 2000 (SLEDAI-2K) score is a weighted, cumulative index of lupus disease activity. SLEDAI-2K is calculated from 24 individual descriptors across 9 organ systems; 0 indicates inactive disease and the maximum theoretical score is 105.
Time to First Severe SLE Flare (SFI)	Baseline through 52 weeks	The SFI uses the SELENA-SLEDAI disease activity index score, disease activity scenarios, treatment changes, and PGA to define mild/moderate and severe flares. The index takes into account the absolute change in total scores, new or worsening symptoms, and increases in corticosteroid use or hospitalization due to the disease activity. Time to first severe SLE flare (SFI) (in days) is calculated as: (Start date of first severe SLE flare (SFI) - Date of randomization + 1).
Change From Baseline to 52 Week Endpoint in Physician's Global Assessment (PGA)	Baseline, 52 weeks	PGA is a single-item clinician rated assessment of the participant's current level of disease activity measured on a continuous 100-millimeter (mm) visual analytic scale with benchmarks of 0, 1, 2, and 3 from left to right corresponding to no, mild, moderate, and severe SLE disease activity. Scores are presented from 0 to 100. No worsening defined as increase of ≤ 0.30 points from Baseline.
Change From Baseline to 52 Week Endpoint Lupus Quality of Life (LupusQOL) Domain Scores	Baseline, 52 weeks	The LupusQoL is a disease-specific, 34-item, self-report questionnaire designed to measure the health-related quality of life (HRQoL) of participants with SLE within 8 domains.Responses are based on a 5-point Likert scale where 0 (all of the time) to 4 (never). A LupusQoL score for each domain is reported on a 0 to 100 scale, with greater values indicating better HRQoL.
Percentage of Participants With No Worsening in Physician Global Assessment (PGA) Score at 52 Weeks	52 weeks	Physician's Global Assessment (PGA) is a single-item clinician rated assessment of the participant's current level of disease activity measured on a continuous 100-mm visual analytic scale with benchmarks of 0, 1, 2, and 3 from left to right corresponding to no, mild, moderate, and severe SLE disease activity. Scores are presented from 0 to 100.No worsening defined as increase of ≤ 0.30 points from Baseline.
Percentage of Participants Able to Decrease Dose of Prednisone or Equivalent With No Increase in Disease Activity at Week 52	52 weeks	A participant achieves corticosteroid sparing effects (quiescent disease) if they have met the following criteria during Weeks 24 through 52; able to decrease their dose of prednisone or equivalent to 7.5 mg/day or less, have quiescent disease (BILAG C score or better in all nine systems), and no BILAG A or B flares in the previous three months, without an increase in either antimalarials or immunosuppressants on or prior to the visit.
Time to First New British Isles Lupus Assessment Group (BILAG A) or 2 New BILAG B SLE Flares	Baseline through 52 weeks	The British Isles Lupus Assessment Group (BILAG) instrument assesses global disease activity across 9 organ system domains. BILAG flare is assessed for each of the 9 organ domains using BILAG2004 index flare rules; A is a severe flare and B is a moderate flare. Time to first BILAG A or two BILAG B flares (in days) is calculated as: (Start date of first BILAG A or two BILAG B flares - Date of randomization + 1). The two BILAG B flares must occur in different domains at the same visit.
Percentage of Participants With an Increase in Corticosteroids Dose at 52 Weeks	52 weeks	An increase in corticosteroids at a visit was defined as a change from baseline greater than 2.5 mg/day in dose or prednisone or equivalent using average daily dose of corticosteroids taken since the previous scheduled visit.
Change From Baseline to 52 Weeks Endpoint in SELENA-SLEDAI Disease Activity Score	Baseline, 52 weeks	Safety of Estrogens in Lupus Erythematosus National Assessment - SLE Disease Activity Index (SELENA-SLEDAI) score is a weighted, cumulative index of lupus disease activity. SELENA-SLEDAI is calculated from 24 individual descriptors across 9 organ systems; 0 indicates inactive disease and the maximum theoretical score is 105.
Number of Participants With No New BILAG A and No More Than One New BILAG B Disease Activity Scores Compared to Baseline	Baseline through 52 weeks	The British Isles Lupus Assessment Group (BILAG) instrument assesses global disease activity across 9 organ system domains. BILAG flare is assessed for each of the 9 organ domains using BILAG2004 index flare rules; A is a severe flare and B is a moderate flare.
Percentage of Participants Achieving a Response as Measured by Modified SRI With No BILAG A or No More Than 1 BILAG B Organ Domain Flares at 52 Weeks	52 weeks	Percentage of participants with a ≥ 5 point reduction from baseline in SELENA SLEDAI score, and no worsening (increase of \< 0.30 points from baseline) in PGA, and no new BILAG A or no more than 1 new BILAG B organ domain flare compared with baseline. (Primary outcome modified to use BILAG flare instead of BILAG disease score) SELENA SLEDAI is calculated from 24 individual descriptors across 9 organ systems; 0 indicates inactive disease and the maximum theoretical score is 105. PGA is a visual analog scale scored from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe). BILAG flare is assessed for each of the 9 organ domains; A is a severe flare and B is a moderate flare. Participants who were unable to comply with allowed concomitant medications requirements were considered non-responders, as were participants who dropped out or were missing Week 52 data.
Change From Baseline to 52 Week Endpoint in Brief Fatigue Inventory (BFI) Scores	Baseline, 52 weeks	A participants-reported scale that measures the severity of fatigue based on the worst fatigue experienced during the past 24-hours. The severity scores ranged from 0 (no fatigue) to 10 (fatigue as severe as you can imagine).

Countries

Australia, Brazil, Canada, Ecuador, France, Hungary, India, Israel, Latvia, Malaysia, Mexico, New Zealand, Romania, Russia, Serbia, South Africa, Spain, Taiwan, Tunisia, United Kingdom, United States

Participant flow

Participants by arm

Arm	Count
LY2127399 Every 2 Weeks 120mg LY2127399 administered via subcutaneous injection for 52 weeks. 240 mg loading dose will be administered as the first dose of study drug.	372
LY2127399 Every 4 Weeks During the Treatment Period, for blinding purposes, participants will alternate injections of LY2127399 and injections of placebo every 2 weeks. 120mg LY2127399 administered via subcutaneous injection for 52 weeks. 240 mg loading dose will be administered as the first dose of study drug Placebo every 4 weeks: Administered via subcutaneous injection for 52 weeks.	376
Placebo Placebo every 2 weeks: Administered via subcutaneous injection for 52 weeks. A matching loading dose will also be administered at the first dose.	376
Total	1,124

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	19	17	24
Overall Study	Death	1	1	3
Overall Study	Entry Criteria Not Met	16	15	13
Overall Study	Lack of Efficacy	14	11	14
Overall Study	Lost to Follow-up	6	7	8
Overall Study	Physician Decision	0	3	2
Overall Study	Protocol Violation	2	7	4
Overall Study	Sponsor Decision	0	1	1
Overall Study	Withdrawal by Subject	19	25	19

Baseline characteristics

Characteristic	LY2127399 Every 2 Weeks	Total	Placebo	LY2127399 Every 4 Weeks
Age, Continuous	42.3 years STANDARD_DEVIATION 12.41	41.8 years STANDARD_DEVIATION 12.4	41.9 years STANDARD_DEVIATION 12.08	41.2 years STANDARD_DEVIATION 12.73
Anti-dsDNA Antibody Level	116.8 International Unit / Milliliter (IU/mL) STANDARD_DEVIATION 118.17	113.1 International Unit / Milliliter (IU/mL) STANDARD_DEVIATION 116.03	112.0 International Unit / Milliliter (IU/mL) STANDARD_DEVIATION 116.6	110.6 International Unit / Milliliter (IU/mL) STANDARD_DEVIATION 113.51
At Least One BILAG A or Two BILAG B Disease Activity Scores	230 Participants	657 Participants	209 Participants	218 Participants
Brief Fatigue Inventory (BFI) Score	5.8 units on a scale STANDARD_DEVIATION 2.57	5.6 units on a scale STANDARD_DEVIATION 2.73	5.6 units on a scale STANDARD_DEVIATION 2.81	5.6 units on a scale STANDARD_DEVIATION 2.81
Ethnicity (NIH/OMB) Hispanic or Latino	110 Participants	301 Participants	99 Participants	92 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	229 Participants	697 Participants	235 Participants	233 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	33 Participants	126 Participants	42 Participants	51 Participants
Lupus Quality of Life (LupusQOL) Domain Scores Body Image	61.1 units on a scale STANDARD_DEVIATION 28.99	62.1 units on a scale STANDARD_DEVIATION 28.61	61.9 units on a scale STANDARD_DEVIATION 29.2	63.2 units on a scale STANDARD_DEVIATION 27.67
Lupus Quality of Life (LupusQOL) Domain Scores Burden to Others	52.8 units on a scale STANDARD_DEVIATION 30.7	51.3 units on a scale STANDARD_DEVIATION 31.15	49.3 units on a scale STANDARD_DEVIATION 32.39	51.9 units on a scale STANDARD_DEVIATION 30.31
Lupus Quality of Life (LupusQOL) Domain Scores Emotional Health	65.7 units on a scale STANDARD_DEVIATION 25.19	65.7 units on a scale STANDARD_DEVIATION 25.14	64.6 units on a scale STANDARD_DEVIATION 26.22	66.7 units on a scale STANDARD_DEVIATION 23.99
Lupus Quality of Life (LupusQOL) Domain Scores Fatigue	56.0 units on a scale STANDARD_DEVIATION 26.39	54.6 units on a scale STANDARD_DEVIATION 26.36	53.4 units on a scale STANDARD_DEVIATION 27.14	54.4 units on a scale STANDARD_DEVIATION 25.54
Lupus Quality of Life (LupusQOL) Domain Scores Intimate Relationships	56.2 units on a scale STANDARD_DEVIATION 33.92	58.8 units on a scale STANDARD_DEVIATION 33.36	56.8 units on a scale STANDARD_DEVIATION 34.21	63.3 units on a scale STANDARD_DEVIATION 31.53
Lupus Quality of Life (LupusQOL) Domain Scores Pain	56.1 units on a scale STANDARD_DEVIATION 28.4	55.5 units on a scale STANDARD_DEVIATION 27.95	53.6 units on a scale STANDARD_DEVIATION 28.62	56.9 units on a scale STANDARD_DEVIATION 26.75
Lupus Quality of Life (LupusQOL) Domain Scores Physical Health	59.2 units on a scale STANDARD_DEVIATION 24.98	58.4 units on a scale STANDARD_DEVIATION 25.43	56.9 units on a scale STANDARD_DEVIATION 26.17	59.1 units on a scale STANDARD_DEVIATION 25.13
Lupus Quality of Life (LupusQOL) Domain Scores Planning	61.2 units on a scale STANDARD_DEVIATION 30.37	60.8 units on a scale STANDARD_DEVIATION 30.01	59.0 units on a scale STANDARD_DEVIATION 30.92	62.1 units on a scale STANDARD_DEVIATION 28.69
Physician's Global Assessment (PGA) Score	47.2 units on a scale STANDARD_DEVIATION 15.45	46.3 units on a scale STANDARD_DEVIATION 15.9	44.9 units on a scale STANDARD_DEVIATION 16.57	46.8 units on a scale STANDARD_DEVIATION 15.6
Race (NIH/OMB) American Indian or Alaska Native	31 Participants	94 Participants	30 Participants	33 Participants
Race (NIH/OMB) Asian	38 Participants	112 Participants	40 Participants	34 Participants
Race (NIH/OMB) Black or African American	43 Participants	140 Participants	51 Participants	46 Participants
Race (NIH/OMB) More than one race	14 Participants	34 Participants	6 Participants	14 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants	3 Participants	0 Participants	2 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	245 Participants	741 Participants	249 Participants	247 Participants
Region of Enrollment Australia	9 Participants	19 Participants	3 Participants	7 Participants
Region of Enrollment Brazil	23 Participants	70 Participants	22 Participants	25 Participants
Region of Enrollment Canada	3 Participants	8 Participants	2 Participants	3 Participants
Region of Enrollment Ecuador	20 Participants	49 Participants	12 Participants	17 Participants
Region of Enrollment France	2 Participants	4 Participants	1 Participants	1 Participants
Region of Enrollment Hungary	18 Participants	53 Participants	18 Participants	17 Participants
Region of Enrollment India	11 Participants	40 Participants	16 Participants	13 Participants
Region of Enrollment Israel	9 Participants	28 Participants	12 Participants	7 Participants
Region of Enrollment Latvia	3 Participants	9 Participants	2 Participants	4 Participants
Region of Enrollment Malaysia	2 Participants	7 Participants	4 Participants	1 Participants
Region of Enrollment Mexico	19 Participants	64 Participants	23 Participants	22 Participants
Region of Enrollment New Zealand	3 Participants	8 Participants	1 Participants	4 Participants
Region of Enrollment Romania	9 Participants	30 Participants	13 Participants	8 Participants
Region of Enrollment Russia	12 Participants	43 Participants	12 Participants	19 Participants
Region of Enrollment Serbia	19 Participants	76 Participants	32 Participants	25 Participants
Region of Enrollment South Africa	14 Participants	38 Participants	7 Participants	17 Participants
Region of Enrollment Spain	9 Participants	30 Participants	9 Participants	12 Participants
Region of Enrollment Taiwan	20 Participants	50 Participants	16 Participants	14 Participants
Region of Enrollment Tunisia	21 Participants	61 Participants	20 Participants	20 Participants
Region of Enrollment United Kingdom	3 Participants	9 Participants	3 Participants	3 Participants
Region of Enrollment United States	143 Participants	428 Participants	148 Participants	137 Participants
Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA-SLEDAI) Score	10.4 units on a scale STANDARD_DEVIATION 4.07	10.2 units on a scale STANDARD_DEVIATION 3.86	9.8 units on a scale STANDARD_DEVIATION 3.28	10.4 units on a scale STANDARD_DEVIATION 4.17
Sex: Female, Male Female	342 Participants	1037 Participants	349 Participants	346 Participants
Sex: Female, Male Male	30 Participants	87 Participants	27 Participants	30 Participants
Time of Onset of Lupus	8.36 years STANDARD_DEVIATION 8.5	8.01 years STANDARD_DEVIATION 7.748	7.74 years STANDARD_DEVIATION 7.078	7.94 years STANDARD_DEVIATION 7.615

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	249 / 371	239 / 374	246 / 376	16 / 72	15 / 78	13 / 66
serious Total, serious adverse events	46 / 371	59 / 374	70 / 376	8 / 72	12 / 78	14 / 66

Outcome results

Primary

Percentage of Participants Achieving an SLE Responder Index Response at Week 52

Percentage of participants with a ≥ 5 point reduction from baseline in SELENA SLEDAI score, and no worsening (increase of \< 0.30 points from baseline) in PGA, and no new BILAG A organ domain score or 2 new BILAG B organ domain scores compared with baseline. SELENA SLEDAI is calculated from 24 individual descriptors across 9 organ systems; 0 indicates inactive disease and the maximum theoretical score is 105; scores \> 20 are rare. PGA is a visual analog scale scored from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe). BILAG uses a single score for each of the 9 organ domains; range is from severe (A) to no disease (E). Participants who were unable to comply with allowed concomitant medications requirements were considered non-responders, as were participants who dropped out or were missing Week 52 data.

Time frame: 52 weeks

Population: Intention to treat (ITT), all randomized participants who received at least one dose of study drug.Non-responder imputation (NRI) included.

Arm	Measure	Value (NUMBER)
LY2127399 Every 2 Weeks	Percentage of Participants Achieving an SLE Responder Index Response at Week 52	38.5 percentage of participants
LY2127399 Every 4 Weeks	Percentage of Participants Achieving an SLE Responder Index Response at Week 52	34.8 percentage of participants
Placebo	Percentage of Participants Achieving an SLE Responder Index Response at Week 52	27.7 percentage of participants

Secondary

Change From Baseline to 52 Week Endpoint in Brief Fatigue Inventory (BFI) Scores

A participants-reported scale that measures the severity of fatigue based on the worst fatigue experienced during the past 24-hours. The severity scores ranged from 0 (no fatigue) to 10 (fatigue as severe as you can imagine).