Systemic lupus erythematosus (SLE) is a systemic chronic autoimmune disease characterized by autoantibody production, inflammation, and tissue damage in multiple organs. Standard of care therapies used to treat SLE are only partially effective and have a wide range of toxicities. There is a need for more effective and safer therapies for patients with SLE.
This Phase 1b/2 study will initially explore the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and efficacy of DS-7011a in patients with SLE. DS-7011a is an anti-Toll-like receptor 7 (TLR7) antagonistic monoclonal antibody developed for the treatment of SLE.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
26
Pinnacle Research Group LLC
Anniston, Alabama, United States
Number of Participants With Treatment-emergent Adverse Events Following Administration With DS-7011a in Participants With Systemic Lupus Erythematosus
TEAEs are defined as new AEs that occur after the first dose of study drug or as AEs that were present prior to the dose of study drug but which worsened in severity after the start of study drug.
Time frame: Post first dose up to Week 24
Pharmacokinetic Parameter Area Under the Concentration Curve Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus
Area under plasma concentration-time curve up to Day 28 was assessed by non-linear mixed-effect modeling.
Time frame: AUC assessed up to 28 days after each dose on Day 1 (first dose), Day 29 (second dose), and Day 57 (third dose) end of infusion
Pharmacokinetic Parameter Maximum Concentration Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus
Maximum concentration was assessed by non-linear mixed-effect modeling.
Time frame: Day 1 (first dose), Day 29 (second dose), and Day 57 (third dose) end of infusion
Pharmacokinetic Parameter Minimum Concentration Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus
Minimum concentration was assessed by non-linear mixed-effect modeling.
Time frame: Day 1 (first dose), Day 29 (second dose), and Day 57 (third dose) end of infusion
Change From Baseline in Cutaneous Lupus Area and Severity Index Activity Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus
Measurement scores for each area are assigned based on the most severe lesion within the area of interest. CLASI-A scores of 0 to 9, 10 to 20, and 21 to 70 represent disease severity of mild, moderate, and severe, respectively. The change from baseline is being reported with greater negative index activity scores indicating clinical improvement.
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Time frame: Baseline (Day 1) up to Week 16
Change From Baseline in Cutaneous Lupus Activity Investigator Global Assessment Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus
Cutaneous Lupus Activity Investigator's Global Assessment (CLA-IGA) is a five-point score that defines the level of disease severity based on overall lesion characteristics where 0 is "clear" and "4" is severe. The change from baseline is being reported with greater negative scores indicating clinical improvement.
Time frame: Baseline (Day 1) up to Week 16
Change From Baseline in SLE Disease Activity Index 2000 Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus
Each symptom presented is assigned between 1 and up to 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms). The change from baseline is being reported with greater negative activity scores indicating clinical improvement.
Time frame: Baseline (Day 1) up to Week 16
Change From Baseline in Clinician's Global Impression of Change Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus
CGI-C is a brief rating scale that reflects the clinician's evaluation on the changes in systemic lupus erythematosus disease severity rated at each visit based on the clinician's judgment as "Very Much Worse", "Much Worse", "Minimally Worse", "No Change", "Minimally Improved", "Much Improved", "Very Much Improved".
Time frame: Baseline (Day 1) up to Week 16
Change From Baseline in Patient's Global Impression of Change Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus
PGI-C is a self-rated scale that ask respondents to describe the retrospective change in their lupus skin symptoms at a given time point based on a 7-point scale as "Very Much Worse", "Much Worse", "Minimally Worse", "No Change", "Minimally Improved", "Much Improved", "Very Much Improved".
Time frame: Baseline (Day 1) up to Week 16
Change From Baseline in Autoantibodies, Anti-Nuclear, Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus
Autoantibodies, including antinuclear, were assessed.
Time frame: Baseline (Day 1) up to Week 16
Change From Baseline in Autoantibodies, Anti-dsDNA, Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus
Autoantibodies, including anti-dsDNA, were assessed.
Time frame: Baseline (Day 1) up to Week 16
Change From Baseline in Autoantibodies, Anti-Smith and Anti-Ribonucleoprotein, Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus
Autoantibodies, including anti-Smith \[Sm\], and antiribonucleoprotein \[RNP\] antibodies, were assessed.
Time frame: Baseline (Day 1) up to Week 16
Change From Baseline in Complement Factors Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus
Complement factors, such as C3 and C4, will be assessed.
Time frame: Baseline (Day 1) up to Week 16