A Study of TAK-007 in Adults With Refractory Lupus Nephritis (LN)

Phase 1

Not yet recruiting

• Conditions: Refractory Lupus Nephritis
• Interventions: Biological: TAK-007; Drug: Chemotherapy Agents

• Registration Number: NCT06377228
• Lead Sponsor: Takeda

Brief Summary

The main aim of the study is to learn how well adults with refractory lupus nephritis (LN) tolerate TAK-007 and to check for side effects (adverse events).

Other aims are to learn how effective treatment with TAK-007 is in adults with refractory LN, what effects TAK-007 has on the human body, and whether participants will produce antibodies against TAK-007.

Detailed Description

The drug being tested in this study is called TAK-007. TAK-007 is being tested to treat people with refractory LN. This study will look at the safety and tolerability of TAK-007.

The study will enroll approximately 20 patients. Participants will receive a single dose of TAK-007, which is an anti-CD19 chimeric antigen receptor natural killer cell (CD19 CAR-NK) therapy.

Participants will be treated with 3 days of intravenous (IV) lymphodepleting chemotherapy (LDC) and then after a gap of at least 2 days, a single IV dose of TAK-007 on Day 1.

This multi-center trial will be conducted in the United States. The overall time to participate in this study is approximately 24 months.

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Study First Submitted: 2024-04-17
• Study First Submitted QC: 2024-04-17
• Study First Posted: 2024-04-22
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-28
• Last Update Posted: 2024-12-03
• Study Start: 2025-05-16
• Primary Completion: 2029-04-23
• Study Completion: 2029-04-23

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. The participant must have a diagnosis of SLE fulfilling European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria.
2. The participant must have a histologically proven glomerulonephritis [proliferative LN class III or IV, with or without the presence of class V, according to 2018 International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria].
3. The participant must be positive for ANA at screening or by documented medical history, and at least one of the following autoantibodies at screening: anti-dsDNA or anti-Smith (Sm) antibody.
4. The participant has had an inadequate response, defined as failure to improve within 12 weeks, based on investigator discretion, to at least 2 standard-of-care treatments for SLE (including glucocorticoids and immunosuppressive agents) OR at least 1 biologic treatment for SLE.
5. The participant has a SLEDAI-2K total score ≥6.
6. The participant must have adequate bone marrow function.
7. The participant must have adequate renal, hepatic, cardiac, and pulmonary function.

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Exclusion Criteria

1. The participant has a history of drug-induced SLE.

2. The participant has a current diagnosis of active or unstable neuropsychiatric lupus (e.g., cerebritis, cerebrovascular accident, and seizures). However, participants with mononeuritis multiplex or polyneuropathy can be included in the study.

3. The participant has a history of catastrophic antiphospholipid syndrome or saddle embolism (antiphospholipid syndrome adequately controlled by anticoagulant therapy for at least 3 months is acceptable).

4. Viral diseases:

   1. The participant is positive for hepatitis C virus (HCV) antibody and has a positive confirmatory test result for HCV ribonucleic acid [RNA] (nucleic acid test or polymerase chain reaction [PCR]).
   2. The participant is positive for hepatitis B surface antigen, hepatitis B virus (HBV) deoxyribonucleic acid (DNA), or hepatitis B core antibody.
   3. The participant has a history of human immunodeficiency virus (HIV) infection or has positive serology for HIV.

5. The participant has a history of significant chronic or recurrent bacterial disease, including but not limited to chronic pyelonephritis or cystitis, chronic bronchitis/pneumonitis, osteomyelitis, chronic skin ulcerations/infections or fungal infections, or latent tuberculosis infection.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TAK-007- 800 × 10^6 CD19-CAR+ Viable NK Cells	TAK-007	Participants will receive IV LDC, for 3 days in conditioning phase (Days -5, -4, and -3), followed by a single dose of IV 800 × 10\^6 TAK-007 on Day 1.
TAK-007- 800 × 10^6 CD19-CAR+ Viable NK Cells	Chemotherapy Agents	Participants will receive IV LDC, for 3 days in conditioning phase (Days -5, -4, and -3), followed by a single dose of IV 800 × 10\^6 TAK-007 on Day 1.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	From first dose of lymphodepleting chemotherapy up to end of study (EOS) [up to Month 24]	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. TEAEs are defined as any AE that begins on or after the start date of LDC.
Number of Participants With Dose Limiting Toxicities (DLTs)	Up to Day 30	DLTs are defined as any event throughout the study meeting the protocol-defined criteria that occur by Day 30 after administration of TAK-007 infusion on Day 1.

Secondary Outcome Measures

Name	Time	Method
Tmax: Time to Reach the Cmax for TAK-007	Predose and at multiple time points post-dose up to Month 24
Percentage of Participants Achieving a Reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Relative to Baseline	Baseline through Month 24	The SLEDAI-2K is a measure of global disease activity in systemic lupus erythematosus (SLE). It consists of 24 weighted clinical and laboratory variables. The scores of the descriptors range from 1 to 8, and the total possible score for all 24 descriptors is 105, with higher scores representing increased disease activity.
Percentage of Participants With Replication Competent Retrovirus (RCR) in Blood	Up to Month 24
Change From Baseline in CD19+ B Cell Counts	Baseline up to Month 24
Duration of CRR	Up to Month 24	CRR is defined as the fulfilment of following criteria: Ratio of urinary protein to creatinine of \<0.5; eGFR that was no worse than 10 % below the pre-flare value or ≥60 mL per minute per 1.73 m\^2; No use of rescue therapy.
Change From Baseline in Complement (C3, C4) Levels	Baseline up to Month 24
Tlast: Time of Last Measurable Concentration Above the Lower Limit of Quantitation for TAK-007	Predose and at multiple time points post-dose up to Month 24
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-007	Predose and at multiple time points post-dose up to Month 24
Percentage of Participants Achieving Complete Renal Response (CRR)	Up to Month 24	CRR is defined as the fulfilment of following criteria: Ratio of urinary protein to creatinine of less than (\<)0.5; Estimated glomerular filtration rate (eGFR) that was no worse than 10 percent (%) below the pre-flare value or greater than or equal to (≥)60 milliliters (mL) per minute per 1.73 meter\^2 (m\^2); No use of rescue therapy.
Percentage of Participants Achieving Lupus Low Disease Activity State (LLDAS)	Up to Month 24	The LLDAS is defined as: SLEDAI-2K less than or equal to (≤)4, with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, fever) and no hemolytic anemia or gastrointestinal activity; no new lupus disease activity compared with the previous assessment; a Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI physician global assessment (scale 0-3) ≤1; a current prednisolone (or equivalent) dose ≤7.5 milligrams (mg) daily; and well-tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents.
Duration of LLDAS	Up to Month 24	The LLDAS is defined as: SLEDAI-2K ≤4, with no activity in major organ systems (renal, CNS, cardiopulmonary, vasculitis, fever) and no hemolytic anemia or gastrointestinal activity; no new lupus disease activity compared with the previous assessment; a SELENA-SLEDAI physician global assessment (scale 0-3) ≤1; a current prednisolone (or equivalent) dose ≤7.5 mg daily; and well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents.
Time to DORIS Remission	Up to Month 24	DORIS remission is defined as achieving a SLEDAI-2K = 0 and a PGA \<0.5, irrespective of serology, with permitted use of antimalarials, low-dose glucocorticoids (prednisolone ≤5 mg/day), and/or stable immunosuppressives and biologics.
Duration of DORIS Remission	Up to Month 24	DORIS remission is defined as achieving a SLEDAI-2K = 0 and a PGA \<0.5, irrespective of serology, with permitted use of antimalarials, low-dose glucocorticoids (prednisolone ≤5 mg/day), and/or stable immunosuppressives and biologics.
Percentage of Participants With Antidrug Antibodies Categorized as Anti-Human Leukocyte Antigen (HLA) and Anti- Chimeric Antigen Receptor (CAR)	Up to Month 24
Cmax: Maximum Observed Plasma Concentration for TAK-007	Predose and at multiple time points post-dose up to Month 24
Duration of B Cell Depletion	Baseline up to Month 24
Change From Baseline in Plasma Cytokine Levels	Baseline up to Month 3
Change From Baseline in Physician's Global Assessment (PGA) Score	Baseline up to Month 24	The PGA is a visual analogue score that reflects a clinician's judgement of overall systemic lupus erythematosus activity. The PGA score ranges from 0 (none) to 3 (severe). Higher score indicates more severe disease activity.
Time to LLDAS	Up to Month 24	The LLDAS is defined as: SLEDAI-2K ≤4, with no activity in major organ systems (renal, CNS, cardiopulmonary, vasculitis, fever) and no hemolytic anemia or gastrointestinal activity; no new lupus disease activity compared with the previous assessment; a SELENA-SLEDAI physician global assessment (scale 0-3) ≤1; a current prednisolone (or equivalent) dose ≤7.5 mg daily; and well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents.
Change From Baseline in Creatinine Levels	Baseline up to Month 24
Time to CRR	Up to Month 24	CRR is defined as the fulfilment of following criteria: Ratio of urinary protein to creatinine of \<0.5; eGFR that was no worse than 10 % below the pre-flare value or ≥60 mL per minute per 1.73 m\^2; No use of rescue therapy.
Change From Baseline in Anti-Double Stranded Deoxyribonucleic Acid (dsDNA) Levels	Baseline up to Month 24
Change From Baseline in Antinuclear Antibody (ANA) Levels	Baseline up to Month 24
Change From Baseline in Proteinuria Levels	Baseline up to Month 24
Change From Baseline in eGFR	Baseline up to Month 24
Percentage of Participants Meeting the Definition of Remission in SLE (DORIS) Criteria	Up to Month 24	DORIS remission is defined as achieving a SLEDAI-2K = 0 and a PGA \<0.5, irrespective of serology, with permitted use of antimalarials, low-dose glucocorticoids (prednisolone ≤5 mg/day), and/or stable immunosuppressives and biologics.