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)

• ClinicalTrials.gov Identifier: NCT03724916
• Recruitment Status: Completed
• First Posted: October 30, 2018
• Results First Posted: March 29, 2024
• Last Update Posted: March 29, 2024
• Sponsor: Millennium Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Takeda ( Millennium Pharmaceuticals, Inc. )

Tracking Information

• First Submitted Date: October 18, 2018
• First Posted Date: October 30, 2018
• Results First Submitted Date: November 3, 2022
• Results First Posted Date: March 29, 2024
• Last Update Posted Date: March 29, 2024
• Actual Study Start Date: November 26, 2018
• Actual Primary Completion Date: November 4, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 7, 2023)

• Number of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) [ Time Frame: From the study start to end of the study (up to Week 36) ]
  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.
• Number of Participants With Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs) [ Time Frame: From the study start up to end of the study (up to Week 36) ]
  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 ≥ 1 Adverse Event (AE) Leading to Treatment Discontinuation [ Time Frame: From the study start up to end of the study (up to Week 36) ]
  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.

Original Primary Outcome Measures (submitted: October 29, 2018)

• Number of Participants who Experience at Least one Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) [ Time Frame: Up to Week 36 ]
• Number of Participants With Grade 3 or Higher TEAEs [ Time Frame: Up to Week 36 ]
  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 [ Time Frame: Up to Week 36 ]

Current Secondary Outcome Measures (submitted: October 7, 2023)

• 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 ]
• 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. ]
• Number of Participants With Change From Baseline In Immune Cell Subsets [ Time Frame: Baseline up to Day 85 (End of Treatment [EOT]) ]
  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.
• Number of Participants With Change From Baseline in Immune Cell Subsets Determined Based on Receptor Occupancy [ Time Frame: Baseline up to Day 85 (EOT) ]
  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.
• Change From Baseline in Cytokines Level [ Time Frame: Baseline up to Day 85 ]
• Number of Participants With Positive Anti-drug Antibodies [ Time Frame: Baseline up to Day 85 (EOT) ]

Original Secondary Outcome Measures (submitted: October 29, 2018)

• 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 ]
• 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 ]
• Number of Participants With Change From Baseline In Immune Cell Subsets [ Time Frame: Baseline up to Day 85 ]
  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 [ Time Frame: Baseline up to Day 85 ]
  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 [ Time Frame: Baseline up to Day 85 ]
  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 [ Time Frame: Baseline up to Day 85 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Other

Condition

• Systemic Lupus Erythematosus
• Lupus Erythematosus, Systemic

Intervention

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

Study Arms

• Placebo Comparator: Pooled Placebo
  TAK-079 placebo-matching injection, subcutaneously, once every 3 weeks in combination with principal investigator-directed background therapy for SLE for up to 12 weeks. Placebo data will be pooled across all the dose levels.
  Intervention: Drug: TAK-079 Placebo
• Experimental: TAK-079 45 mg
  TAK-079 45 mg injection subcutaneously, once every 3 weeks in combination with principal investigator-directed background therapy for SLE for up to 12 weeks.
  Intervention: Drug: TAK-079
• Experimental: TAK-079 90 mg
  TAK-079 90 mg injection subcutaneously, once every 3 weeks in combination with principal investigator-directed background therapy for SLE for up to 12 weeks.
  Intervention: Drug: TAK-079
• Experimental: TAK-079 135 mg
  TAK-079 135 mg injection subcutaneously, once every 3 weeks in combination with principal investigator-directed background therapy for SLE for up to 12 weeks.
  Intervention: Drug: TAK-079

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 7, 2023): 23
• Original Estimated Enrollment (submitted: October 29, 2018): 24
• Actual Study Completion Date: November 4, 2021
• Actual Primary Completion Date: November 4, 2021 (Final data collection date for primary outcome measure)

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03724916
• Other Study ID Numbers: TAK-079-2001; U1111-1220-2497 ( Other Identifier: World Health Organization )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• 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.
• URL: https://vivli.org/ourmember/takeda/

• Current Responsible Party: Takeda ( Millennium Pharmaceuticals, Inc. )
• Original Responsible Party: Same as current
• Current Study Sponsor: Millennium Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Millennium Pharmaceuticals, Inc.

• PRS Account: Takeda
• Verification Date: October 2023