Systemic Lupus Erythematosus
Conditions
Keywords
Systemic Lupus Erythematosus, DS-7011a
Brief summary
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.
Detailed description
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.
Interventions
DRUGDS-7011a
20 mg/kg intravenous dose to be administered every 4 weeks at baseline (Day 1), Day 29, and Day 57
DRUGPlacebo
Saline intravenous solution administered every 4 weeks at baseline (Day 1), Day 29, and Day 57
Sponsors
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female participants must be of 18 years or more with definite SLE for at least 6 months prior to Screening, defined according to the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE, including documented history of positivity for antinuclear antibody (titer ≥1:80). * Body mass index (BMI) ≥18 kg/m\^2 and body weight ≥45 kg. * Presence of active CLE (acute, subacute, and chronic cutaneous lupus), with active skin involvement and a CLASI-A score of 4 or higher at the time of screening and randomization as recognized by 2 adjudicators, ie, the investigator in the periphery at the site and a centrally located arbiter contracted ad hoc (in case of disagreement between these 2 adjudicators, a third adjudicator, also centrally located and contracted ad hoc, will solve the disagreement and provide a final decision), despite adequate use of conventional therapies (either topical corticosteroids or antimalarial agents used for at least 12 weeks prior to Screening) or because of the requirement to discontinue these therapies due to side effects or poor tolerability. * Participants must be willing to have skin tape harvests collected from the affected skin area (skin tape stripping done on the target lesion). * Participants must agree not to participate in any other investigational study during the study Treatment Period and for 3 months after the last dose of study drug. * Participants must give written informed consent to participation in the study prior to Screening. * Participants must be vaccinated against COVID-19
Exclusion criteria
* Active lupus nephritis (LN) on induction therapy, or induction therapy completed within 12 weeks prior to Screening (stable maintenance therapy with mycophenolate or azathioprine allowed). * Active neuropsychiatric SLE, including, but not limited to, the following: seizure, new or worsening impaired level of consciousness, psychosis, delirium or confusional state, aseptic meningitis, ascending or transverse myelitis, chorea, cerebellar ataxia, mononeuritis multiplex, or demyelinating syndromes. * Primary diagnosis of autoimmune or rheumatic disease other than SLE (secondary Sjögren's syndrome or autoimmune thyroiditis are not exclusionary) or drug-induced lupus. * History of chronic, recurrent (3 or more of the same type of infection in 1 year) or recent serious infection, including viral infections, as determined by the investigator, or requiring anti-infective treatment within 12 weeks prior to Screening. * History of severe herpes infection or signs of herpes or varicella zoster viral infection within 12 weeks prior to Screening. * Positive COVID-19 molecular test at Screening or symptoms suggestive of SARS-CoV-2 infection or close contact with an individual with SARS-CoV-2 infection within 2 weeks prior to randomization. * History of malignant disease within the 2 years before Screening or ongoing at the time of Screening, except basal cell carcinomas and squamous cell carcinomas of the skin, or completely excised carcinoma in situ of the cervix * Chronic kidney disease with significant proteinuria (ie, \>2 g/24 h or urine protein to creatinine ratio \>200 mg/g) or decreased renal function (estimated glomerular filtration rate \[eGFR\] \<30 mL/min). * New York Heart Association class III or IV congestive heart failure. * Concomitant disease or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the participant in this study. * History or positive test result for human immunodeficiency virus at Screening. * Active hepatitis B virus (HBV) infection determined at Screening as positive test result for hepatitis B surface antigen. * Active hepatitis C virus (HCV) infection determined at Screening as HCV ribonucleic acid (RNA) above the limit of detection in subjects with positive HCV antibody titer. * History of, or ongoing, active tuberculosis (TB) or untreated latent TB infection (LTBI) at Screening. Participants with documented previously completed appropriate LTBI treatment and without evidence of re-exposure will not be required to be tested. * Any other significant condition that according to the investigator's judgment would prevent compliance with study protocol and full study participation. * Participants must not be participating in another investigational study or have participated in an investigational study within the past 30 days prior to randomization (Day 1). * History of or current inflammatory skin disease other than SLE that in the opinion of the investigator could interfere with the inflammatory skin assessments and confound the disease activity assessments. * History of any non-SLE disease that had required treatment with oral or parenteral corticosteroids for more than a total of 2 weeks within the last 24 weeks prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events Following Administration With DS-7011a in Participants With Systemic Lupus Erythematosus | Post first dose up to Week 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameter Area Under the Concentration Curve Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus | 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 | Area under plasma concentration-time curve up to Day 28 was assessed by non-linear mixed-effect modeling. |
| Pharmacokinetic Parameter Maximum Concentration Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus | Day 1 (first dose), Day 29 (second dose), and Day 57 (third dose) end of infusion | Maximum concentration was assessed by non-linear mixed-effect modeling. |
| Pharmacokinetic Parameter Minimum Concentration Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus | Day 1 (first dose), Day 29 (second dose), and Day 57 (third dose) end of infusion | Minimum concentration was assessed by non-linear mixed-effect modeling. |
| Change From Baseline in Cutaneous Lupus Area and Severity Index Activity Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus | Baseline (Day 1) up to Week 16 | 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. |
| Change From Baseline in Cutaneous Lupus Activity Investigator Global Assessment Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus | Baseline (Day 1) up to Week 16 | 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. |
| Change From Baseline in SLE Disease Activity Index 2000 Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus | Baseline (Day 1) up to Week 16 | 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. |
| Change From Baseline in Clinician's Global Impression of Change Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus | Baseline (Day 1) up to Week 16 | 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". |
| Change From Baseline in Patient's Global Impression of Change Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus | Baseline (Day 1) up to Week 16 | 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". |
| Change From Baseline in Autoantibodies, Anti-Nuclear, Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus | Baseline (Day 1) up to Week 16 | Autoantibodies, including antinuclear, were assessed. |
| Change From Baseline in Autoantibodies, Anti-dsDNA, Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus | Baseline (Day 1) up to Week 16 | Autoantibodies, including anti-dsDNA, were assessed. |
| Change From Baseline in Autoantibodies, Anti-Smith and Anti-Ribonucleoprotein, Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus | Baseline (Day 1) up to Week 16 | Autoantibodies, including anti-Smith \[Sm\], and antiribonucleoprotein \[RNP\] antibodies, were assessed. |
| Change From Baseline in Complement Factors Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus | Baseline (Day 1) up to Week 16 | Complement factors, such as C3 and C4, will be assessed. |
Countries
China, Japan, North Macedonia, United States
Contacts
STUDY_DIRECTORGlobal Clinical Leader
Daiichi Sankyo
Participant flow
Recruitment details
A total of 26 patients were enrolled and randomized to treatment at 14 study sites in China, Japan, Macedonia, and United States of America.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 49.7 years STANDARD_DEVIATION 13.05 |
| Age, Customized 18-64 years | 22 Participants |
| Age, Customized 65-74 years | 3 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants |
| Race/Ethnicity, Customized White | 0 Participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 6 |
| other Total, other adverse events | 11 / 19 | 4 / 6 |
| serious Total, serious adverse events | 0 / 19 | 1 / 6 |
Outcome results
None listed