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A Study of LY3471851 in Adults With Systemic Lupus Erythematosus (SLE)

Phase 2
Completed
Conditions
Systemic Lupus Erythematosus
Interventions
Drug: Placebo
Registration Number
NCT04433585
Lead Sponsor
Nektar Therapeutics
Brief Summary

The reason for this study is to see if the study drug LY3471851 (NKTR-358) is safe and effective in adults with systemic lupus erythematosus (SLE).

Detailed Description

LY3471851 is a potential first-in-class therapeutic that may address an underlying immune system imbalance in people with many autoimmune conditions. It targets the interleukin (IL-2) receptor complex in the body in order to stimulate proliferation of inhibitory immune cells known as regulatory T cells. By activating these cells, LY3471851 may act to bring the immune system back into balance.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
291
Inclusion Criteria
  • Have a clinical diagnosis of SLE at least 24 weeks prior to screening.
  • Have documentation of having met at least 4 of 11 Revised Criteria for Classification of Systemic Lupus Erythematosus according to the 1997 Update of the 1982 American College of Rheumatology (ACR) criteria for classification of SLE prior to randomization.
  • Have a positive antinuclear antibody (ANA) (titer ≥1:80) and/or a positive anti-double-stranded deoxyribonucleic acid (dsDNA), and/or a positive anti-Smith (anti-Sm) as assessed by a central laboratory during screening.
  • Have a total Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≥6 during screening.
  • Have a clinical SLEDAI-2K score ≥4 at randomization.
  • Have active arthritis and/or active rash.
Exclusion Criteria
  • Have severe active lupus nephritis.
  • Have active central nervous system (CNS) lupus.
  • Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute an unacceptable risk when taking investigational product or interfere with the interpretation of data.
  • Have a current or recent clinically serious viral, bacterial, fungal, or parasitic infection.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
LY3471851 Low DoseLY3471851LY3471851 administered SC
LY3471851 High DoseLY3471851LY3471851 administered subcutaneously (SC).
LY3471851 Mid DoseLY3471851LY3471851 administered SC.
PlaceboPlaceboPlacebo administered SC.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants Who Achieved a ≥4 Point Reduction in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2000 (2K) Score at Week 24Week 24

Percentage of Participants who Achieved a ≥4 Point Reduction in SLEDAI-2K Score at Week 24. A SLEDAI-4 response is defined as a ≥4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score from baseline. The SLEDAI-2K score range is from a minimum of 0 to a maximum of 105 (higher scores represent higher disease activity).

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants Who Achieved British Isles Lupus Assessment Group (BILAG) Based Composite Lupus Assessment (BICLA) Response at Week 24.Week 24

Percentage of Participants who Achieve BICLA Response at Week 24. The BILAG-based Composite Lupus Assessment (BICLA) is a composite index used to assess disease activity in SLE. A BICLA response is defined as:

* Reduction of all baseline BILAG-2004 A to B or C or D; and baseline BILAG-2004 B to C or D; and no BILAG-2004 worsening in other organ systems, as defined by ≥1 new BILAG-2004 A or ≥2 new BILAG-2004 B.

* No worsening from baseline in SLEDAI-2K, where worsening is defined as any increase from baseline in SLEDAI-2K.

* No worsening from baseline in participants' lupus disease activity, where worsening is defined by an increase ≥0.30 points on a 3-point PGA visual analogue scale (VAS).

Percentage of Participants Who Achieved Lupus Low Disease Activity State (LLDAS) at Week 24Week 24

Percentage of Participants who Achieved LLDAS at Week 24. A LLDAS response is defined as a low level of disease activity attained without use of low-dose steroids and/or standard-of-care immunosuppressant medications.

Percentage of Participants Who Achieved Systemic Lupus Erythematosus Responder Index 4 (SRI-4) Response at Week 24Week 24

Percentage of Participants who Achieved a SRI-4 Response at Week 24. A SRI-4 response is defined as a decrease in SLEDAI-2K \>= 4 from baseline. No new BILAG A and no more than 1 new BILAG B disease activity score / organ domain (both compared with baseline), and no worsening in PGA (defined as an increase of 0.3 points \[10 mm\] from baseline.

Pharmacokinetics (PK): Trough Concentrations (Ctrough) of LY3471851Week 24

LY3471851 plasma trough concentrations are the concentrations of drug in plasma immediately before the next dose is administered.

Trial Locations

Locations (112)

University of California - San Diego

🇺🇸

La Jolla, California, United States

Desert Medical Advances

🇺🇸

Palm Desert, California, United States

Stanford University Hospital

🇺🇸

Stanford, California, United States

Inland Rheumatology & Osteoporosis Medical Group

🇺🇸

Upland, California, United States

University of Colorado School of Medicine

🇺🇸

Aurora, Colorado, United States

Clinical Research Center of CT/NY

🇺🇸

Danbury, Connecticut, United States

Yale University School of Medicine

🇺🇸

New Haven, Connecticut, United States

Stamford Therapeutics Consortium

🇺🇸

Stamford, Connecticut, United States

University of Miami School of Medicine

🇺🇸

Miami, Florida, United States

New Horizon Research Center

🇺🇸

Miami, Florida, United States

Scroll for more (102 remaining)
University of California - San Diego
🇺🇸La Jolla, California, United States

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