Clinical trial NCT05638802: A Study of DS-7011a in Patients With Systemic Lupus Erythematosus
Official title: A Phase 1b/2, Double-Blind, Placebo-Controlled, Randomized, Parallel-Arm Study to Explore the Safety, Pharmacokinetics, and Proof of Biological Activity of DS-7011a in Patients With Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Systemic Lupus Erythematosus
Keywords: Systemic Lupus Erythematosus
DS-7011a
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2022-12-06
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants with Treatment-emergent Adverse Events Following Administration with DS-7011a in Participants With Systemic Lupus Erythematosus
timeFrame: Screening up to Week 24
Secondary outcomes:
measure: Pharmacokinetic Parameter Area Under the Concentration Curve Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus
timeFrame: Day 1 (at predose and at end of infusion), Day 2 (24 hours after administration), Day 8 (1 week after administration), Days 29 and 57 (at predose and at end of infusion), and Days 85 and 113
measure: Pharmacokinetic Parameter Maximum Concentration Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus
timeFrame: Day 1 (at predose and at end of infusion), Day 2 (24 hours after administration), Day 8 (1 week after administration), Days 29 and 57 (at predose and at end of infusion), and Days 85 and 113
measure: Pharmacokinetic Parameter Minimum Concentration Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus
timeFrame: Day 1 (at predose and at end of infusion), Day 2 (24 hours after administration), Day 8 (1 week after administration), Days 29 and 57 (at predose and at end of infusion), and Days 85 and 113
measure: Change From Baseline in Cutaneous Lupus Area and Severity Index Activity Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus
timeFrame: Screening up to Week 16
measure: Change From Baseline in Cutaneous Lupus Activity Investigator Global Assessment Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus
timeFrame: Screening up to Week 16
measure: Change From Baseline in SLE Disease Activity Index 2000 Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus
timeFrame: Screening up to Week 16
measure: Change From Baseline in Clinician's Global Impression of Change Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus
timeFrame: Screening up to Week 16
measure: Change From Baseline in Patient's Global Impression of Change Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus
timeFrame: Screening up to Week 16
measure: Change From Baseline in Autoantibodies Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus
timeFrame: Screening up to Week 16
measure: Change From Baseline in Complement Factors Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus
timeFrame: Screening up to Week 16
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group LLC
state: Alabama
city: North Little Rock
country: United States
facility: Arkansas Research Trials
state: Arkansas
city: North Miami Beach
country: United States
facility: Office of Tory P. Sullivan, M.D. - North Miami Beach
state: Florida
city: Tamarac
country: United States
facility: West Broward Rheumatology Associates
state: Florida
city: Kansas City
country: United States
facility: The University of Kansas Medical Center
state: Kansas
city: Auburn Hills
country: United States
facility: Oakland Hills Dermatology
state: Michigan
city: Troy
country: United States
facility: Revival Research Institute, LLC
state: Michigan
city: Saint Joseph
country: United States
facility: MediSearch Clinical Trials
state: Missouri
city: Charlotte
country: United States
facility: Joint & Muscle Research Institute
state: North Carolina
city: Minot
country: United States
facility: Trinity Health Center Medical Arts
state: North Dakota
city: Colleyville
country: United States
facility: Precision Comprehensive Clinical Research Solutions
state: Texas
city: Dallas
country: United States
facility: Metroplex Clinical Research Center, LLC
state: Texas
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: