Back to resultsA 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)
Primary Purpose
Systemic Lupus Erythematosus, Lupus Erythematosus, Systemic
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
TAK-079
TAK-079 Placebo
Sponsored by
About this trial
This is an interventional other trial for Systemic Lupus Erythematosus focused on measuring Drug therapy
Eligibility Criteria
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).
Sites / Locations
- Pinnacle Research Group, LLC
- University of Alabama at Birmingham
- University of California San Diego
- ACRC Studies
- University of Colorado Denver
- Clinical Research of West Florida - Clearwater
- CRIA Research
- Millennium Research
- North Georgia Rheumatology Group-Duluth
- Institute of Arthritis Research
- Massachusetts General Hospital
- Beth Israel Deaconess Medical Center
- Northwell Health
- State University of New York Upstate Medical Center (SUNY)
- University of North Carolina at Chapel Hill
- Oklahoma Medical Research Foundation
- Accurate Clinical Research
- Southwest Rheumatology Research, LLC
- Arthritis Northwest Rheumatology
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
TAK-079
Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Number of Participants who Experience at Least one Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
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.
Percentage of Participants With Greater Than or Equal to (>=) 1 Adverse Event (AE) Leading to Treatment Discontinuation
Secondary Outcome Measures
Cmax: Maximum Observed Plasma Concentration for TAK-079
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-079
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.
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.
Change From Baseline in Cytokines Level
Cytokine measurements will be assessed from baseline at different timepoints for placebo and each TAK-079 dose level.
Number of Participants With Positive Anti-drug Antibodies
Full Information
NCT ID
NCT03724916
First Posted
October 18, 2018
Last Updated
November 8, 2021
Sponsor
Millennium Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03724916
Brief Title
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
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
November 26, 2018 (Actual)
Primary Completion Date
November 4, 2021 (Actual)
Study Completion Date
November 4, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Millennium Pharmaceuticals, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Lupus Erythematosus, Lupus Erythematosus, Systemic
Keywords
Drug therapy
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
58 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TAK-079
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
TAK-079
Intervention Description
TAK-079 Subcutaneous injection.
Intervention Type
Drug
Intervention Name(s)
TAK-079 Placebo
Intervention Description
TAK-079 placebo-matching subcutaneous injection.
Primary Outcome Measure Information:
Title
Number of Participants who Experience at Least one Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
Time Frame
Up to Week 36
Title
Number of Participants With Grade 3 or Higher TEAEs
Description
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.
Time Frame
Up to Week 36
Title
Percentage of Participants With Greater Than or Equal to (>=) 1 Adverse Event (AE) Leading to Treatment Discontinuation
Time Frame
Up to Week 36
Secondary Outcome Measure Information:
Title
Cmax: Maximum Observed Plasma Concentration for TAK-079
Time Frame
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
Title
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-079
Time Frame
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
Title
Number of Participants With Change From Baseline In Immune Cell Subsets
Description
Immune cell subsets will include plasma cells, plasma blast (PBs), natural killer (NK) cells, B cells, T cells, monocytes, and total lymphocytes.
Time Frame
Baseline up to Day 85
Title
Number of Participants With Change From Baseline in (Cluster of Differentiation 38) CD38 Expression Level and Receptor Occupancy
Description
CD38 expression and receptor occupancy will be evaluated for plasma cells, PBs, NK cells, B cells, T cells, and monocytes.
Time Frame
Baseline up to Day 85
Title
Change From Baseline in Cytokines Level
Description
Cytokine measurements will be assessed from baseline at different timepoints for placebo and each TAK-079 dose level.
Time Frame
Baseline up to Day 85
Title
Number of Participants With Positive Anti-drug Antibodies
Time Frame
Baseline up to Day 85
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Millennium Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Pinnacle Research Group, LLC
City
Anniston
State/Province
Alabama
ZIP/Postal Code
36207
Country
United States
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
University of California San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
ACRC Studies
City
Poway
State/Province
California
ZIP/Postal Code
92064
Country
United States
Facility Name
University of Colorado Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Clinical Research of West Florida - Clearwater
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33765
Country
United States
Facility Name
CRIA Research
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33309
Country
United States
Facility Name
Millennium Research
City
Ormond Beach
State/Province
Florida
ZIP/Postal Code
32174
Country
United States
Facility Name
North Georgia Rheumatology Group-Duluth
City
Lawrenceville
State/Province
Georgia
ZIP/Postal Code
30046
Country
United States
Facility Name
Institute of Arthritis Research
City
Idaho Falls
State/Province
Idaho
ZIP/Postal Code
83404
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Northwell Health
City
Great Neck
State/Province
New York
ZIP/Postal Code
11021
Country
United States
Facility Name
State University of New York Upstate Medical Center (SUNY)
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Oklahoma Medical Research Foundation
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Accurate Clinical Research
City
Houston
State/Province
Texas
ZIP/Postal Code
77034
Country
United States
Facility Name
Southwest Rheumatology Research, LLC
City
Mesquite
State/Province
Texas
ZIP/Postal Code
75150
Country
United States
Facility Name
Arthritis Northwest Rheumatology
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
IPD Sharing Access Criteria
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
IPD Sharing URL
https://vivli.org/ourmember/takeda/
Learn more about this trial
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)
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