Clinical trial NCT03724916: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Systemic Lupus Erythematosus
Lupus Erythematosus, Systemic
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2018-10-30
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. The participant has a systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score greater than or equal to (\>=) 6.
3. The participant is positive for anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies and/or anti-extractable nuclear antigens (ENA) antibodies.

Exclusion Criteria:

1. 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.
2. 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.
3. The participant has drug-induced SLE or any other rheumatologic or autoimmune disease (excluding secondary Sjögren syndrome or mixed connective tissue disease).

Primary outcomes:
measure: Number of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
timeFrame: From the study start to end of the study (up to Week 36)
measure: Number of Participants With Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs)
timeFrame: From the study start up to end of the study (up to Week 36)
measure: Percentage of Participants With ≥ 1 Adverse Event (AE) Leading to Treatment Discontinuation
timeFrame: From the study start up to end of the study (up to Week 36)
Secondary outcomes:
measure: Cmax: Maximum Observed Plasma Concentration for TAK-079
timeFrame: 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
measure: AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-079
timeFrame: 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.
measure: Number of Participants With Change From Baseline In Immune Cell Subsets
timeFrame: Baseline up to Day 85 (End of Treatment [EOT])
measure: Number of Participants With Change From Baseline in Immune Cell Subsets Determined Based on Receptor Occupancy
timeFrame: Baseline up to Day 85 (EOT)
measure: Change From Baseline in Cytokines Level
timeFrame: Baseline up to Day 85
measure: Number of Participants With Positive Anti-drug Antibodies
timeFrame: Baseline up to Day 85 (EOT)
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group, LLC
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Poway
country: United States
facility: ACRC Studies
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Clearwater
country: United States
facility: Clinical Research of West Florida - Clearwater
state: Florida
city: Fort Lauderdale
country: United States
facility: CRIA Research
state: Florida
city: Ormond Beach
country: United States
facility: Millennium Research
state: Florida
city: Lawrenceville
country: United States
facility: North Georgia Rheumatology Group-Duluth
state: Georgia
city: Idaho Falls
country: United States
facility: Institute of Arthritis Research
state: Idaho
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Great Neck
country: United States
facility: Northwell Health
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical Center (SUNY)
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Oklahoma City
country: United States
facility: Oklahoma Medical Research Foundation
state: Oklahoma
city: Houston
country: United States
facility: Accurate Clinical Research
state: Texas
city: Mesquite
country: United States
facility: Southwest Rheumatology Research, LLC
state: Texas
city: Spokane
country: United States
facility: Arthritis Northwest Rheumatology
state: Washington
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: