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 Participants With Systemic Lupus Erythematosus (SLE)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01196091

Enrollment

1164

Registered

2010-09-08

Start date

2010-12-31

Completion date

2015-06-30

Last updated

2018-06-12

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

Lupus, SLE, Systemic Lupus Erythematosis, 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 participants with active SLE.

Interventions

DRUGLY2127399

120 mg administered via subcutaneous (SC) 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 of corticosteroids, NSAIDs, antimalarials, or immunosuppressants will also be administered at the first dose

DRUGPlacebo every 4 weeks

Administered via subcutaneous injection for 52 weeks.

DRUGStandard of Care

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 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).
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 patient'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 is defined as increase of ≥0.3 points.
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).
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 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. Only participants receiving a prednisone or equivalent dose of more than 7.5 mg/day at baseline are included.
Change From Baseline to 52 Week Endpoint in PGA	Baseline, 52 weeks	Physician's Global Assessment (PGA) is a single-item clinician rated assessment of the patient'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 range from 0, being worst possible to 100 being very active or best possible.
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.
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. Patients 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.
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 BILAG2004 index is a validated global disease activity index designed on the basis of the physician's ITT, focusing on changes in disease manifestations (new, improved, worsening, etc) occurring in the last 4 weeks compared with the previous 4 weeks. The instrument assesses 97 clinical signs, symptoms, and laboratory parameters across 9 organ system domains: constitutional, mucocutaneous, neuropsychiatric, musculoskeletal, cardiorespiratory, gastrointestinal, opthalmic, renal and hematology.
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.

Countries

Argentina, Austria, Belarus, Bulgaria, Canada, Chile, Colombia, Croatia, Egypt, Germany, Guatemala, Italy, Japan, North Macedonia, Peru, Philippines, Poland, Puerto Rico, Singapore, South Korea, Thailand, Ukraine, United States

Participant flow

Pre-assignment details

Intent to Treat population (ITT) is all randomized participants who received at least 1 dose of study drug, excluding two sites' participants due to good clinical practice (GCP) issues.

Participants by arm

Arm	Count
LY2127399 Every 2 Weeks LY2127399: 120 mg administered via subcutaneous injection for 52 weeks. 240 mg loading dose will be administered as the first dose of study drug.	381
LY2127399 Every 4 Wks During the Treatment Period, for blinding purposes, patients will alternate injections of LY2127399 and injections of placebo every 2 weeks. LY2127399: 120 mg 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.	378
Placebo Placebo every 2 weeks: Administered via subcutaneous injection for 52 weeks. A matching loading dose will also be administered at the first dose	379
Total	1,138

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	22	27	26
Overall Study	Death	3	2	2
Overall Study	Entry Criteria Not Met	11	11	10
Overall Study	Excluded Site	5	11	8
Overall Study	Lack of Efficacy	15	12	17
Overall Study	Lost to Follow-up	5	5	6
Overall Study	Parent/Caregiver Decision	0	0	1
Overall Study	Physician Decision	3	3	4
Overall Study	Protocol Violation	1	3	3
Overall Study	Randomized, No Study Drug Received	1	0	1
Overall Study	Sponsor Decision	6	5	4
Overall Study	Withdrawal by Subject	16	19	22

Baseline characteristics

Characteristic	LY2127399 Every 2 Weeks	Total	Placebo	LY2127399 Every 4 Wks
Age, Continuous	39.8 years STANDARD_DEVIATION 12.51	39.7 years STANDARD_DEVIATION 11.82	39.1 years STANDARD_DEVIATION 11.69	40.2 years STANDARD_DEVIATION 11.21
Anti-dsDNA Antibody Level	107.2 International Units/Milliliter (IU/mL) STANDARD_DEVIATION 113.5	108.2 International Units/Milliliter (IU/mL) STANDARD_DEVIATION 112.41	107.1 International Units/Milliliter (IU/mL) STANDARD_DEVIATION 112.4	110.4 International Units/Milliliter (IU/mL) STANDARD_DEVIATION 111.58
At Least One BILAG A or Two BILAG B Disease Activity Scores No	21 Participants	90 Participants	31 Participants	38 Participants
At Least One BILAG A or Two BILAG B Disease Activity Scores Yes	360 Participants	1047 Participants	347 Participants	340 Participants
Brief Fatigue Inventory (BFI) Score (Worst Level of Fatigue in the Last 24 Hours)	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	119 Participants	357 Participants	122 Participants	116 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	233 Participants	687 Participants	229 Participants	225 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	29 Participants	94 Participants	28 Participants	37 Participants
Lupus Quality of Life (lupus QOL) Domain Score 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 (lupus QOL) Domain Score 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 (lupus QOL) Domain Score 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 (lupus QOL) Domain Score 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 (lupus QOL) Domain Score 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 (lupus QOL) Domain Score 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 (lupus QOL) Domain Score 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 (lupus QOL) Domain Score 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	46.3 millimeters (mm) STANDARD_DEVIATION 15.7	46.5 millimeters (mm) STANDARD_DEVIATION 16	47.1 millimeters (mm) STANDARD_DEVIATION 16.1	46.1 millimeters (mm) STANDARD_DEVIATION 16.2
Race (NIH/OMB) American Indian or Alaska Native	65 Participants	187 Participants	67 Participants	55 Participants
Race (NIH/OMB) Asian	68 Participants	195 Participants	66 Participants	61 Participants
Race (NIH/OMB) Black or African American	40 Participants	120 Participants	39 Participants	41 Participants
Race (NIH/OMB) More than one race	4 Participants	8 Participants	2 Participants	2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	204 Participants	627 Participants	205 Participants	218 Participants
Region of Enrollment Argentina	20 Participants	66 Participants	22 Participants	24 Participants
Region of Enrollment Austria	3 Participants	7 Participants	1 Participants	3 Participants
Region of Enrollment Belarus	4 Participants	12 Participants	2 Participants	6 Participants
Region of Enrollment Bulgaria	8 Participants	31 Participants	12 Participants	11 Participants
Region of Enrollment Canada	2 Participants	4 Participants	2 Participants	0 Participants
Region of Enrollment Chile	8 Participants	13 Participants	5 Participants	0 Participants
Region of Enrollment Colombia	16 Participants	44 Participants	18 Participants	10 Participants
Region of Enrollment Croatia	1 Participants	2 Participants	0 Participants	1 Participants
Region of Enrollment Egypt	19 Participants	59 Participants	21 Participants	19 Participants
Region of Enrollment Germany	12 Participants	24 Participants	7 Participants	5 Participants
Region of Enrollment Guatemala	13 Participants	43 Participants	13 Participants	17 Participants
Region of Enrollment Italy	1 Participants	10 Participants	2 Participants	7 Participants
Region of Enrollment Japan	15 Participants	45 Participants	15 Participants	15 Participants
Region of Enrollment Macedonia	3 Participants	12 Participants	3 Participants	6 Participants
Region of Enrollment Peru	32 Participants	99 Participants	34 Participants	33 Participants
Region of Enrollment Philippines	26 Participants	62 Participants	22 Participants	14 Participants
Region of Enrollment Poland	19 Participants	54 Participants	19 Participants	16 Participants
Region of Enrollment Puerto Rico	3 Participants	21 Participants	11 Participants	7 Participants
Region of Enrollment Singapore	0 Participants	2 Participants	0 Participants	2 Participants
Region of Enrollment South Korea	11 Participants	43 Participants	14 Participants	18 Participants
Region of Enrollment Thailand	14 Participants	34 Participants	11 Participants	9 Participants
Region of Enrollment Ukraine	23 Participants	74 Participants	29 Participants	22 Participants
Region of Enrollment United States	128 Participants	377 Participants	116 Participants	133 Participants
Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA-SLEDAI) Score	10.2 units on a scale STANDARD_DEVIATION 3.5	10.4 units on a scale STANDARD_DEVIATION 3.7	10.7 units on a scale STANDARD_DEVIATION 3.9	10.4 units on a scale STANDARD_DEVIATION 3.6
Sex: Female, Male Female	354 Participants	1066 Participants	360 Participants	352 Participants
Sex: Female, Male Male	27 Participants	72 Participants	19 Participants	26 Participants
Time of Onset of Lupus	7.5 years STANDARD_DEVIATION 7.4	7.3 years STANDARD_DEVIATION 7.4	6.4 years STANDARD_DEVIATION 6.8	8.1 years STANDARD_DEVIATION 7.9

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	250 / 386	243 / 389	246 / 387	13 / 103	11 / 105	13 / 128
serious Total, serious adverse events	42 / 386	56 / 389	50 / 387	14 / 103	16 / 105	23 / 128

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: Intent to Treat population (ITT) all randomized participants who received at least 1 dose of study drug and evaluable SLE scores, excluding two sites' participants due to good clinical practice (GCP) issues.

Arm	Measure	Value (NUMBER)
LY2127399 Every 2 Weeks	Percentage of Participants Achieving an SLE Responder Index Response at Week 52	31.8 percentage of participants
LY2127399 Every 4 Wks	Percentage of Participants Achieving an SLE Responder Index Response at Week 52	35.2 percentage of participants
Placebo	Percentage of Participants Achieving an SLE Responder Index Response at Week 52	29.3 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).