Trial Outcomes & Findings for 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) (NCT NCT03724916)

Last Updated: 2024-03-29

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

23 participants

Primary outcome timeframe

From the study start to end of the study (up to Week 36)

Results posted on

2024-03-29

Participant Flow

Participants took part in the study at 13 investigative sites in United States from 26 November 2018 to 04 November 2021.

Participants with moderate to severe systemic lupus erythematosus (SLE) were sequentially enrolled to receive TAK-079 45 mg, TAK-079 90 mg, TAK-079 135 mg or TAK-079-matching placebo in a 3:1 ratio in this study.

Participant milestones

Participant milestones
Measure	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 was pooled across all the dose levels.	TAK-079 45mg 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.	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.	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.
Overall Study STARTED	6	6	6	5
Overall Study Safety Analysis Set	5	6	6	5
Overall Study Pharmacokinetic (PK) Analysis Set	0	6	6	5
Overall Study Pharmacodynamic (PD) Analysis Set	5	6	6	5
Overall Study Immunogenicity Analysis Set	5	6	5	5
Overall Study COMPLETED	5	5	5	3
Overall Study NOT COMPLETED	1	1	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	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 was pooled across all the dose levels.	TAK-079 45mg 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.	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.	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.
Overall Study Withdrawal by Subject	0	1	1	2
Overall Study Randomized but not Treated	1	0	0	0

Baseline Characteristics

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)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pooled Placebo n=5 Participants 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 was pooled across all the dose levels.	TAK-079 45mg n=6 Participants 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.	TAK-079 90 mg n=6 Participants 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.	TAK-079 135 mg n=5 Participants 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.	Total n=22 Participants Total of all reporting groups
Age, Continuous	36.4 years STANDARD_DEVIATION 6.58 • n=5 Participants	51.0 years STANDARD_DEVIATION 22.01 • n=7 Participants	46.7 years STANDARD_DEVIATION 6.53 • n=5 Participants	49.6 years STANDARD_DEVIATION 13.50 • n=4 Participants	46.2 years STANDARD_DEVIATION 14.17 • n=21 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	4 Participants n=4 Participants	20 Participants n=21 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	4 Participants n=4 Participants	18 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	9 Participants n=21 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	1 Participants n=4 Participants	10 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: From the study start to end of the study (up to Week 36)

Population: Safety analysis set included all participants who were enrolled and received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=5 Participants 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 was pooled across all the dose levels.	TAK-079 45mg n=6 Participants 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.	TAK-079 90 mg n=6 Participants 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.	TAK-079 135 mg n=5 Participants 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.
Number of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) TEAEs	3 Participants	4 Participants	6 Participants	2 Participants
Number of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) SAEs	0 Participants	1 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: From the study start up to end of the study (up to Week 36)

Population: Safety analysis set included all participants who were enrolled and received at least 1 dose of study drug.

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.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=5 Participants 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 was pooled across all the dose levels.	TAK-079 45mg n=6 Participants 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.	TAK-079 90 mg n=6 Participants 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.	TAK-079 135 mg n=5 Participants 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.
Number of Participants With Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs)	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From the study start up to end of the study (up to Week 36)

Population: Safety analysis set consisted of all participants who were enrolled and received at least 1 dose of study drug.

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.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=5 Participants 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 was pooled across all the dose levels.	TAK-079 45mg n=6 Participants 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.	TAK-079 90 mg n=6 Participants 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.	TAK-079 135 mg n=5 Participants 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.
Percentage of Participants With ≥ 1 Adverse Event (AE) Leading to Treatment Discontinuation	0 Participants	0 Participants	0 Participants	1 Participants

SECONDARY outcome

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

Population: Pharmacokinetics analysis set consisted of all participants who received study drug and had at least 1 measurable serum concentration. Number analyzed is the number of participants available for analysis at the given time point.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=6 Participants 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 was pooled across all the dose levels.	TAK-079 45mg n=6 Participants 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.	TAK-079 90 mg n=5 Participants 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.	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.
Cmax: Maximum Observed Plasma Concentration for TAK-079 Day 1	57.5 nanograms per millilitre (ng/mL) Standard Deviation 71.7	660.0 nanograms per millilitre (ng/mL) Standard Deviation 1050	6130 nanograms per millilitre (ng/mL) Standard Deviation 5170	—
Cmax: Maximum Observed Plasma Concentration for TAK-079 Day 22	95.4 nanograms per millilitre (ng/mL) Standard Deviation 187	1570 nanograms per millilitre (ng/mL) Standard Deviation 2930	6330 nanograms per millilitre (ng/mL) Standard Deviation 9450	—
Cmax: Maximum Observed Plasma Concentration for TAK-079 Day 43	10.6 nanograms per millilitre (ng/mL) Standard Deviation 17.5	1440 nanograms per millilitre (ng/mL) Standard Deviation 2550	559 nanograms per millilitre (ng/mL) Standard Deviation 714	—
Cmax: Maximum Observed Plasma Concentration for TAK-079 Day 64	16.4 nanograms per millilitre (ng/mL) Standard Deviation 17.4	568 nanograms per millilitre (ng/mL) Standard Deviation 841	3100 nanograms per millilitre (ng/mL) Standard Deviation 3900	—

SECONDARY outcome

Population: As pre-specified in SAP, data for AUClast was not evaluated due to sparse PK sampling.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Day 85 (End of Treatment [EOT])

Population: PD analysis set included all participants who received study drug and had at least 1 postdose PD measurement. Overall number analyzed are the number of participants who had baseline and post-baseline data for change.

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.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=4 Participants 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 was pooled across all the dose levels.	TAK-079 45mg n=6 Participants 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.	TAK-079 90 mg n=4 Participants 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.	TAK-079 135 mg n=4 Participants 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.
Number of Participants With Change From Baseline In Immune Cell Subsets Participants who had change in Plasma cell concentration	4 Participants	6 Participants	4 Participants	4 Participants
Number of Participants With Change From Baseline In Immune Cell Subsets Participants who had change in Plasmablasts concentration	4 Participants	6 Participants	4 Participants	4 Participants
Number of Participants With Change From Baseline In Immune Cell Subsets Participants who had change in NK cells concentration	4 Participants	6 Participants	4 Participants	4 Participants
Number of Participants With Change From Baseline In Immune Cell Subsets Participants who had change in B cells concentration	4 Participants	6 Participants	4 Participants	4 Participants
Number of Participants With Change From Baseline In Immune Cell Subsets Participants who had change in T cells concentration	4 Participants	6 Participants	4 Participants	4 Participants
Number of Participants With Change From Baseline In Immune Cell Subsets Participants who had change in Monocytes concentration	4 Participants	6 Participants	4 Participants	4 Participants
Number of Participants With Change From Baseline In Immune Cell Subsets Participants who had change in Lymphocytes concentration	4 Participants	6 Participants	4 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 85 (EOT)

Population: Pharmacokinetics analysis set consisted of all participants who received study drug and had at least 1 measurable serum concentration. Overall number analyzed are the number of participants who had baseline and post-baseline data.

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.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=4 Participants 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 was pooled across all the dose levels.	TAK-079 45mg n=6 Participants 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.	TAK-079 90 mg n=4 Participants 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.	TAK-079 135 mg n=4 Participants 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.
Number of Participants With Change From Baseline in Immune Cell Subsets Determined Based on Receptor Occupancy Participants who had change in receptor occupancy: Plasma Cells	4 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Change From Baseline in Immune Cell Subsets Determined Based on Receptor Occupancy Participants who had change in receptor occupancy: Plasmablasts	4 Participants	5 Participants	4 Participants	4 Participants
Number of Participants With Change From Baseline in Immune Cell Subsets Determined Based on Receptor Occupancy Participants who had change in receptor occupancy: CD38+NK cells	4 Participants	5 Participants	4 Participants	4 Participants
Number of Participants With Change From Baseline in Immune Cell Subsets Determined Based on Receptor Occupancy Participants who had change in receptor occupancy: CD38+B cells	4 Participants	5 Participants	4 Participants	4 Participants
Number of Participants With Change From Baseline in Immune Cell Subsets Determined Based on Receptor Occupancy Participants who had change in receptor occupancy: CD38+T cells	4 Participants	5 Participants	4 Participants	4 Participants
Number of Participants With Change From Baseline in Immune Cell Subsets Determined Based on Receptor Occupancy Participants who had change in receptor occupancy: CD38+Monocytes	4 Participants	5 Participants	4 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 85

Population: Since no participants had potential symptoms of cytokine release syndrome (CRS) or developed a CRS while on study, the assessment for cytokines was never performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Day 85 (EOT)

Population: Immunogenicity set consisted of all participants who received study drug and had a baseline and at least 1 postbaseline immunogenicity sample assessment.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=5 Participants 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 was pooled across all the dose levels.	TAK-079 45mg n=6 Participants 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.	TAK-079 90 mg n=5 Participants 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.	TAK-079 135 mg n=5 Participants 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.
Number of Participants With Positive Anti-drug Antibodies Baseline	3 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Positive Anti-drug Antibodies EOT	3 Participants	2 Participants	0 Participants	2 Participants

Adverse Events

Pooled Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

TAK-079 45mg

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

TAK-079 90 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

TAK-079 135 mg

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pooled Placebo n=5 participants at risk 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 was pooled across all the dose levels.	TAK-079 45mg n=6 participants at risk 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.	TAK-079 90 mg n=6 participants at risk 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.	TAK-079 135 mg n=5 participants at risk 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.
Cardiac disorders Palpitations	0.00% 0/5 • From the study start up to end of the study (up to Week 36) Safety analysis set included all subjects who were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • From the study start up to end of the study (up to Week 36) Safety analysis set included all subjects who were enrolled and received at least 1 dose of study drug.	0.00% 0/6 • From the study start up to end of the study (up to Week 36) Safety analysis set included all subjects who were enrolled and received at least 1 dose of study drug.	0.00% 0/5 • From the study start up to end of the study (up to Week 36) Safety analysis set included all subjects who were enrolled and received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/5 • From the study start up to end of the study (up to Week 36) Safety analysis set included all subjects who were enrolled and received at least 1 dose of study drug.	0.00% 0/6 • From the study start up to end of the study (up to Week 36) Safety analysis set included all subjects who were enrolled and received at least 1 dose of study drug.	0.00% 0/6 • From the study start up to end of the study (up to Week 36) Safety analysis set included all subjects who were enrolled and received at least 1 dose of study drug.	20.0% 1/5 • From the study start up to end of the study (up to Week 36) Safety analysis set included all subjects who were enrolled and received at least 1 dose of study drug.

Other adverse events

Additional Information

Contact

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor reserves the right to review results publications prior to public release and can delay such publications for a period greater than 60 days but no more than 120 days from the date that the publication is submitted to the Sponsor for review. Sponsor can require changes to the publication to protect Sponsor's intellectual property rights and/or confidential information and reserves the right to limit publication timing and scope of data published based on the number of study locations.
Publication restrictions are in place

Restriction type: OTHER