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)

Systemic Lupus Erythematosus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03724916
• Other study ID #: TAK-079-2001
• Secondary ID: U1111-1220-2497
• Status: Completed
• Phase: Phase 1
• Start date: November 26, 2018
• Est. completion date: November 4, 2021

Study information

• Verified date: October 2023
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: November 4, 2021
• Est. primary completion date: November 4, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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).

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Drug:
• TAK-079
TAK-079 subcutaneous injection.
• TAK-079 Placebo
TAK-079 placebo-matching subcutaneous injection.

Locations

Country	Name	City	State
United States	Pinnacle Research Group, LLC	Anniston	Alabama
United States	University of Colorado Denver	Aurora	Colorado
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Clinical Research of West Florida - Clearwater	Clearwater	Florida
United States	CRIA Research	Fort Lauderdale	Florida
United States	Northwell Health	Great Neck	New York
United States	Accurate Clinical Research	Houston	Texas
United States	Institute of Arthritis Research	Idaho Falls	Idaho
United States	University of California San Diego	La Jolla	California
United States	North Georgia Rheumatology Group-Duluth	Lawrenceville	Georgia
United States	Southwest Rheumatology Research, LLC	Mesquite	Texas
United States	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma
United States	Millennium Research	Ormond Beach	Florida
United States	ACRC Studies	Poway	California
United States	Arthritis Northwest Rheumatology	Spokane	Washington
United States	State University of New York Upstate Medical Center (SUNY)	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)	An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an AE with an onset that occurs after receiving study drug. An SAE is an adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	From the study start to end of the study (up to Week 36)
Primary	Number of Participants With Grade 3 or Higher Treatment Emergent Adverse Events (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.	From the study start up to end of the study (up to Week 36)
Primary	Percentage of Participants With = 1 Adverse Event (AE) Leading to Treatment Discontinuation	An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug.	From the study start up to end of the study (up to Week 36)
Secondary	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
Secondary	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.
Secondary	Number of Participants With Change From Baseline In Immune Cell Subsets	Immune cell subsets included plasma cells, plasma blast (PBs), natural killer (NK) cells, B cells, T cells, monocytes, and total lymphocytes. The concentration of each plasma subset cell type is measured at baseline and post-baseline timepoints and the number of participants who had change in the concentration of each plasma subset cells from baseline were evaluated and reported in this outcome measure.	Baseline up to Day 85 (End of Treatment [EOT])
Secondary	Number of Participants With Change From Baseline in Immune Cell Subsets Determined Based on Receptor Occupancy	Receptor occupancy was evaluated for plasma cells, PBs, NK cells, B cells, T cells, and monocytes. The concentration of cells expressing CD38+ and those not expressing the same is correlated and used to determine receptor occupancy. The receptor occupancy of these cells was determined at baseline and post-baseline timepoints. The number of participants who had change in the receptor occupancy of these cells from baseline were evaluated and reported in this outcome measure.	Baseline up to Day 85 (EOT)
Secondary	Change From Baseline in Cytokines Level		Baseline up to Day 85
Secondary	Number of Participants With Positive Anti-drug Antibodies		Baseline up to Day 85 (EOT)