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A Study of LY2127399 in Participants With Systemic Lupus Erythematosus

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ClinicalTrials.gov Identifier: NCT01205438
Recruitment Status : Completed
First Posted : September 20, 2010
Results First Posted : June 19, 2018
Last Update Posted : July 17, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

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.

Condition or disease Intervention/treatment Phase
Systemic Lupus Erythematosus Connective Tissue Disease Autoimmune Disease Drug: LY2127399 Drug: Placebo every 2 weeks Drug: Placebo every 4 weeks Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1124 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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)
Study Start Date : January 2011
Actual Primary Completion Date : August 2014
Actual Study Completion Date : March 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lupus

Arm Intervention/treatment
Experimental: LY2127399 every 2 weeks Drug: LY2127399
120mg administered via subcutaneous injection for 52 weeks. 240 mg loading dose will be administered as the first dose of study drug

Experimental: LY2127399 every 4 weeks
During the Treatment Period, for blinding purposes, participants will alternate injections of LY2127399 and injections of placebo every 2 weeks.
Drug: LY2127399
120mg administered via subcutaneous injection for 52 weeks. 240 mg loading dose will be administered as the first dose of study drug

Drug: Placebo every 4 weeks
Administered via subcutaneous injection for 52 weeks.

Placebo Comparator: Placebo Drug: Placebo every 2 weeks
Administered via subcutaneous injection for 52 weeks. A matching loading dose will also be administered at the first dose.




Primary Outcome Measures :
  1. Percentage of Participants Achieving an SLE Responder Index Response at Week 52 [ Time Frame: 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 Outcome Measures :
  1. Percentage of Participants Able to Decrease Dose of Prednisone or Equivalent With No Increase in Disease Activity at Week 52 [ Time Frame: 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.

  2. Change From Baseline to 52 Weeks in Anti-double Stranded Deoxyribonucleic Acid (Anti-dsDNA) Level [ Time Frame: Baseline, 52 weeks ]
    Anti-double stranded deoxyribonucleic acid (anti-dsDNA) is a lab analyte used to assist in the diagnosis of SLE.

  3. Change From Baseline to 52 Week Endpoint in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI2K) Score [ Time Frame: 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.

  4. Time to First Severe SLE Flare (SFI) [ Time Frame: 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).


  5. Change From Baseline to 52 Week Endpoint in Physician's Global Assessment (PGA) [ Time Frame: 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.

  6. Change From Baseline to 52 Week Endpoint Lupus Quality of Life (LupusQOL) Domain Scores [ Time Frame: 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.

  7. Percentage of Participants With No Worsening in Physician Global Assessment (PGA) Score at 52 Weeks [ Time Frame: 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.

  8. Change From Baseline to 52 Week Endpoint in Brief Fatigue Inventory (BFI) Scores [ Time Frame: 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).

  9. Time to First New British Isles Lupus Assessment Group (BILAG A) or 2 New BILAG B SLE Flares [ Time Frame: 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.


  10. Percentage of Participants With an Increase in Corticosteroids Dose at 52 Weeks [ Time Frame: 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.

  11. Change From Baseline to 52 Weeks Endpoint in SELENA-SLEDAI Disease Activity Score [ Time Frame: 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.

  12. Number of Participants With No New BILAG A and No More Than One New BILAG B Disease Activity Scores Compared to Baseline [ Time Frame: 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.

  13. 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 [ Time Frame: 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.




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01205438


  Show 185 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9AM - 5PM Eastern time (UTC/GMT -5 hours, EST) Eli Lilly and Company

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01205438     History of Changes
Other Study ID Numbers: 13653
H9B-MC-BCDT ( Other Identifier: Eli Lilly and Company )
First Posted: September 20, 2010    Key Record Dates
Results First Posted: June 19, 2018
Last Update Posted: July 17, 2018
Last Verified: June 2018

Keywords provided by Eli Lilly and Company:
SLE
Systemic Lupus Erythematosis
Lupus
autoimmune disease
LY2127399
Immune System Disease

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs