A Study to Evaluate the Safety, Pharmacokinetics (PK), and Pharmacodynamics (PD) of TAK-079 in Combination With Standard Background Therapy in Participants With Moderate to Severe Systemic Lupus Erythematosus (SLE)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of TAK-079 in comparison with matching placebo, administered once every 3 weeks over a 12-week dosing period in participants with active SLE who are receiving stable background therapy for SLE.

Detailed Description
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TAK-079 is being tested in a study population with moderate to severe SLE. This study will evaluate the safety and biologic activity of TAK-079 or matching placebo in combination with stable SLE background therapy. The study will enroll approximately 24 participants across 3 sequentially enrolling cohorts. Each cohort will enroll 8 participants, where 6 participants will be assigned to TAK-079 injection, and 2 participants will be assigned to Placebo. Participants will receive TAK-079 or matching placebo in combination with principal investigator directed background therapy for SLE. This multi-center trial will be conducted in the United States. Participants will make multiple visits to the clinic, and will be followed up for the safety assessment for the additional 12 weeks up to Week 24 after receiving their last dose of study drug. Based on the clinical assessments, participants may complete or may advance to long-term safety follow up period for an additional 12-week safety monitoring period up to Week 36.

Official Title
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A Phase 1b Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of TAK-079 in Combination With Standard Background Therapy in Patients With Moderate to Severe Systemic Lupus Erythematosus

Conditions
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Systemic Lupus Erythematosus, Lupus Erythematosus, Systemic

Intervention / Treatment
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* Drug: TAK-079
* Drug: TAK-079 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant been diagnosed with SLE as defined by either the 2012 Systemic Lupus International Collaborating Clinics or the American College of Rheumatology diagnostic criteria. The participant has a systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score greater than or equal to (>=) 6. The participant is positive for anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies and/or anti-extractable nuclear antigens (ENA) antibodies. Exclusion Criteria: The participant had an opportunistic infection less than or equal to (<=)12 weeks before initial study dosing or is currently undergoing treatment for a chronic opportunistic infection, such as tuberculosis (TB), pneumocystis pneumonia, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria. The participant currently has, or recently had, an acute or chronic infection requiring one or more of the following interventions: Hospitalization <=30 days before the screening visit. - Administered parenteral (IV or intramuscular) antibacterial, antiviral, antifungal, or antiparasitic agents <=30 days before the screening visit. The participant has drug-induced SLE or any other rheumatologic or autoimmune disease (excluding secondary Sjögren syndrome or mixed connective tissue disease).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAK-079<br>TAK-079 injection, subcutaneously, once every 3 weeks for up to 12 weeks in combination with principal investigator-directed background therapy for SLE. Dose escalation of TAK-079 dose will be based on PK, safety and tolerability data. | Drug: TAK-079<br>* TAK-079 Subcutaneous injection.<br>|
| Placebo Comparator: Placebo<br>TAK-079 placebo-matching injection, subcutaneously, once every 3 weeks for up to 12 weeks in combination with principal investigator-directed background therapy for SLE. | Drug: TAK-079 Placebo<br>* TAK-079 placebo-matching subcutaneous injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants who Experience at Least one Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) |  | Up to Week 36 | 
| Number of Participants With Grade 3 or Higher TEAEs | The severity of TEAEs will be graded using National cancer institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 definitions of Grade 1 through Grade 5. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. | Up to Week 36 | 
| Percentage of Participants With Greater Than or Equal to (>=) 1 Adverse Event (AE) Leading to Treatment Discontinuation |  | Up to Week 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax: Maximum Observed Plasma Concentration for TAK-079 |  | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose; Day 22 pre-dose and at multiple time points (up to 108 hours) post-dose; Days 43 and 64 pre-dose and at multiple time points (up to 5 hours) post-dose | 
| AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-079 |  | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose; Day 22 pre-dose and at multiple time points (up to 108 hours) post-dose; Days 43 and 64 pre-dose and at multiple time points (up to 5 hours) post-dose | 
| Number of Participants With Change From Baseline In Immune Cell Subsets | Immune cell subsets will include plasma cells, plasma blast (PBs), natural killer (NK) cells, B cells, T cells, monocytes, and total lymphocytes. | Baseline up to Day 85 | 
| Number of Participants With Change From Baseline in (Cluster of Differentiation 38) CD38 Expression Level and Receptor Occupancy | CD38 expression and receptor occupancy will be evaluated for plasma cells, PBs, NK cells, B cells, T cells, and monocytes. | Baseline up to Day 85 | 
| Change From Baseline in Cytokines Level | Cytokine measurements will be assessed from baseline at different timepoints for placebo and each TAK-079 dose level. | Baseline up to Day 85 | 
| Number of Participants With Positive Anti-drug Antibodies |  | Baseline up to Day 85 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug therapy