Refractory Lupus NephritisPhase 1NCT06377228
A Study of TAK-007 in Adults With Refractory Lupus Nephritis (LN) or Refractory Systemic Sclerosis (SSc)
A Phase 1 study testing TAK-007 and Chemotherapy Agents in people with Refractory Lupus Nephritis and Refractory Systemic Sclerosis, run by Takeda at 1 site in United States.
Trial summary
The main aim of the trial is to learn how well adults with refractory lupus nephritis (LN) or refractory systemic sclerosis (SSc) tolerate TAK-007 and to check for side effects (adverse events). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Refractory Lupus Nephritis, Refractory Systemic Sclerosis
- What is being tested?
- TAK-007 and Chemotherapy Agents
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jun 2025to 2 Sep 2030
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The participant must have a diagnosis of SLE fulfilling European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria.
- 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).
- 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.
- 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.
- The participant has a SLEDAI-2K total score ≥6.
- The participant must have a diagnosis of SSc fulfilling EULAR/ACR 2013 classification criteria.
Show all 25Show fewer
- The participant must have an early disease: 5 years or less of disease duration since first non-Raynaud's sign or symptom.
- The participant must have evidence for presence of Interstitial Lung Disease (ILD) on HRCT imaging.
- The participant must have active disease.
- Positive for ANA (by immunofluorescent assay [IFA] with a titer ≥1:80) at screening or by documented medical history.
- Lack of response or insufficient response (based on investigator discretion), to adequate doses of at least one of the following treatments used for at least 4 months: cyclophosphamide, methotrexate, mycophenolate (MMF)/mycophenolic acid, nintedanib, rituximab, or tocilizumab. Intolerance is not considered an insufficient response.
- The participant must have adequate bone marrow function.
- The participant must have adequate renal, hepatic, cardiac, and pulmonary function.
- The participant is willing and able to understand and fully comply with trial procedures and requirements in the opinion of the investigator.
- The participant has provided informed consent and any required privacy authorization before the initiation of any trial procedures.
- The participant must be aged 18 to 75 years (inclusive) at the time of consent.
- Participants with female reproductive anatomy must be:
- postmenopausal for at least 1 year before the screening visit, OR
- surgically sterile for at least 6 weeks, OR
- if the participant is of childbearing potential, must:
- Agree to practice 1 highly effective method of contraception and 1 additional effective (barrier) method at the same time, from the time of signing the informed consent through at least 24 months following TAK-007 administration OR ii. Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant (periodic abstinence [for example, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception). Female and male condoms should not be used together AND iii. Agree not to donate an egg or eggs (ova) or breastfeed a baby during the trial and until at least 24 months following TAK-007 administration.
- Participants with male reproductive anatomy, even if surgically sterilized (that is, status post vasectomy), must:
- Agree to practice effective barrier contraception from the time of signing the informed consent through at least 6 months following TAK-007 administration, or
- Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant (periodic abstinence [for example, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception), and
- Agree not to donate sperm during the trial and at least 6 months following TAK-007 administration.
Who cannot join
- The participant has a history of drug-induced SLE.
- 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.
- 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).
- The participant has a history or current diagnosis of other autoimmune diseases or current inflammatory joint or skin disease other than SLE that, in the opinion of the investigator and per sponsor assessment, could interfere with the inflammatory arthritis or skin assessments and confound the disease activity assessments.
- The participant has ppFVC ≤45% or DLCO ≤40% or requiring supplemental oxygen at screening.
- The participant has pulmonary arterial hypertension requiring active treatment.
Show all 24Show fewer
- The participant has anti-centromere antibody.
- The participant has a history of severe scleroderma renal crisis OR scleroderma renal crisis within 6 months prior to Day 1.
- The participant has obstructive pulmonary disease (pre-bronchodilator forced expiratory volume in 1 second (FEV1)/FVC <0.7)
- The participant has significant emphysema on screening HRCT, based on qualitative investigator assessment (extent of emphysema exceeds extent of ILD).
- The participant has a history or current diagnosis of other systemic autoimmune diseases or current inflammatory joint or skin disease other than SSc that, in the opinion of the investigator and per sponsor assessment, could interfere with the trial assessments and confound the disease activity assessments.
- The participant has actively bleeding gastric antral vascular ectasia
- The participant has severe SSc-related lower gastrointestinal involvement requiring nutrition via percutaneous endoscopic gastrostomy/percutaneous endoscopic jejunostomy (PEG/PEJ) tube or parental nutrition.
- The participant has any clinically significant medical condition, evidence of an unstable clinical condition (for example, cardiovascular, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, or immunologic), or vital signs/physical/laboratory/electrocardiogram (ECG) abnormality that would, in the opinion of the investigator and per sponsor assessment, put the participant at undue risk or interfere with interpretation of trial results.
- The participant has a history of active infection (for example, coronavirus disease 2019 [COVID-19], influenza) or febrile illness within 7 days before enrollment.
- Viral diseases:
- 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]).
- The participant is positive for hepatitis B surface antigen, hepatitis B virus (HBV) deoxyribonucleic acid (DNA), or hepatitis B core antibody.
- The participant has a history of human immunodeficiency virus (HIV) infection or has positive serology for HIV.
- 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.
- The participant has a known or suspected allergy to TAK-007, or any of its components, or to cyclophosphamide or fludarabine.
- The participant is unable to comply with the restrictions and prohibited treatments and/or discontinuation requirements.
- The participant has given greater than 500 mL of blood or plasma within 30 days of screening (during a clinical trial or at a blood bank donation) or plans to donate blood during the course of the trial.
- The participant is compulsorily detained for treatment of either a psychiatric or physical (for example, infectious disease) illness.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas Health Science Center
Houston, Texas, 77030
About this study
Official title: A Phase 1b, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of TAK-007, an Allogeneic Anti-CD19 Chimeric Antigen Receptor Natural Killer Cell (CD19 CAR-NK) Therapy, in Adult Subjects With Refractory Lupus Nephritis or Refractory Systemic Sclerosis
The main aim of the trial is to learn how well adults with refractory lupus nephritis (LN) or refractory systemic sclerosis (SSc) 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 or refractory SSc, what effects TAK-007 has on the human body, and whether participants will produce antibodies against TAK-007.
Read the detailed description
The drug being tested in this trial is called TAK-007. TAK-007 is being tested to treat people with refractory LN or refractory SSc. This trial will look at the safety and tolerability of TAK-007.
The trial will enroll approximately 26 participants. Participants will receive a single dose or multiple doses of TAK-007, which is an anti-CD19 chimeric antigen receptor natural killer cell (CD19 CAR-NK) therapy.
Participants with refractory LN 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. For participants with refractory SSc the trial has 2 parts. In Part 1, participants with refractory SSc will be treated with 3 days of IV LDC and then after a gap of at least 2 days, a single IV dose (Part 1a - single dose) or three IV doses (Part 1b - multiple doses) of TAK-007. Based on the data of Part 1, Part 2 (expansion) may be initiated in participants with refractory SSc to further evaluate the impact of LDC followed by single dose or multiple doses of TAK-007.
This multi-center trial will be conducted in the United States. The overall time to participate in this study is approximately 24 months.
- Being tested
- TAK-007, Chemotherapy Agents
- Keywords
- Drug Therapy
- Medical subject headings
- Lupus Nephritis, Scleroderma, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAK-007Biological
TAK-007 IV infusion.
Chemotherapy AgentsDrug
Fludarabine and cyclophosphamide IV infusion.
| Study group | Role | What they receive |
|---|---|---|
| LN Cohort: Single Dose TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells | Experimental | Participants with LN 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 with a potential to explore an alternate dose level if deemed appropriate. Receives: Biological: TAK-007; Drug: Chemotherapy Agents |
| SSc Cohort: Part 1a: Single Dose TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells | Experimental | Participants with SSc 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. Receives: Biological: TAK-007; Drug: Chemotherapy Agents |
| SSc Cohort: Part 1b: Multiple Dose TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells | Experimental | Participants with SSc will receive IV LDC, for 3 days in conditioning phase (Days -5, -4, and -3), followed by multiple doses of IV 800 × 10^6 TAK-007 on Days 1, 8, and 15. Receives: Biological: TAK-007; Drug: Chemotherapy Agents |
| SSc Cohort: Part 2 (Dose Expansion): TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells | Experimental | Based on the data of Part 1, Part 2 may be initiated for participants with SSc to receive IV LDC, for 3 days in conditioning phase (Days -5, -4, and -3), followed by either single dose of IV 800 × 10^6 TAK-007 on Day 1 or multiple doses of IV 800 × 10^6 TAK-007 on Days 1, 8, and 15. Receives: Biological: TAK-007; Drug: Chemotherapy Agents |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
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.
Measured: From first dose of LDC up to end of study (EOS) [up to Month 24]
Number of Participants With Dose Limiting Toxicities (DLTs)
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.
Measured: Up to Day 30
Secondary outcomes (34)
Cmax: Maximum Observed Plasma Concentration for TAK-007
Measured: Pre-dose and at multiple time points post-dose up to Month 24
Tmax: Time to Reach the Cmax for TAK-007
Measured: Pre-dose and at multiple time points post-dose up to Month 24
Tlast: Time of Last Measurable Concentration Above the Lower Limit of Quantitation for TAK-007
Measured: Pre-dose 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
Measured: Pre-dose and at multiple time points post-dose up to Month 24
Change From Baseline in CD19+ B Cell Counts
Measured: Baseline up to Month 24
Change From Baseline in Plasma Cytokine Levels
Measured: Baseline up to Month 3
Change From Baseline in Clinician's Global Assessment (CGA) Score
The CGA score is a visual analogue score that reflects a clinician's judgement of overall systemic lupus erythematosus (SLE) activity. The CGA score ranges from 0 (none) to 3 (severe). Higher score indicates more severe disease activity.
Measured: Baseline up to Month 24
Percentage of Participants With Antidrug Antibodies Categorized as Anti-Human Leukocyte Antigen (HLA) and Anti- Chimeric Antigen Receptor (CAR)
Measured: Up to Month 24
Percentage of Participants With Replication Competent Retrovirus (RCR) in Blood
Measured: Up to Month 24
Percentage of Participants With Refractory LN Achieving a Reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Relative to Baseline
The SLEDAI-2K is a measure of global disease activity in systemic lupus erythematosus. 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.
Measured: Baseline through Month 24
Percentage of Participants With Refractory LN Achieving Complete Renal Response (CRR)
CRR is defined as the fulfilment of following criteria: Ratio of urinary protein to creatinine of less than (<)0.5 mg/mg; ; 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.
Measured: Up to Month 24
Time to CRR in Participants With Refractory LN
CRR is defined as the fulfilment of following criteria: ratio of urinary protein to creatinine of <0.5 mg/mg; 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.
Measured: Up to Month 24
Duration of CRR in Participants With Refractory LN
CRR is defined as the fulfilment of following criteria: ratio of urinary protein to creatinine of <0.5 mg/mg; 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.
Measured: Up to Month 24
Percentage of Participants With Refractory LN Achieving Lupus Low Disease Activity State (LLDAS)
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.
Measured: Up to Month 24
Time to LLDAS in Participants With Refractory LN
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.
Measured: Up to Month 24
Duration of LLDAS in Participants With Refractory LN
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.
Measured: Up to Month 24
Percentage of Participants With Refractory LN Meeting the Definition of Remission in Systemic Lupus Erythematosus (DORIS) Criteria
DORIS remission is defined as achieving a SLEDAI-2K = 0 and a physician's global assessment score (PGA) <0.5, irrespective of serology, with permitted use of antimalarials, low-dose glucocorticoids (prednisolone ≤5 mg/day), and/or stable immunosuppressives and biologics.
Measured: Up to Month 24
Time to DORIS Remission in Participants With Refractory LN
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.
Measured: Up to Month 24
Duration of DORIS Remission in Participants With Refractory LN
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.
Measured: Up to Month 24
Change From Baseline in Anti-Double Stranded Deoxyribonucleic Acid (Anti-dsDNA) Levels in Participants With Refractory LN
Measured: Baseline up to Month 24
Change From Baseline in Antinuclear Antibody (ANA) Levels in Participants With Refractory LN
Measured: Baseline up to Month 24
Change From Baseline in Proteinuria Levels in Participants With Refractory LN
Measured: Baseline up to Month 24
Change From Baseline in Serum Creatinine Levels in Participants With Refractory LN
Measured: Baseline up to Month 24
Change From Baseline in eGFR in Participants With Refractory LN
Measured: Baseline up to Month 24
Change From Baseline in Complement (C3, C4) Levels in Participants With Refractory LN
Measured: Baseline up to Month 24
Change From Baseline in Forced Vital Capacity (FVC) in Participants With Refractory SSc
FVC (measured in mL) is defined as the maximal volume of air exhaled with maximally forced expiratory effort from a position of maximal inspiration.
Measured: Baseline up to Month 24
Change From Baseline in Percentage (%) Predicted Forced Vital Capacity (ppFVC) in Participants With Refractory SSc
Measured: Baseline up to Month 24
Percentage of Refractory SSc Participants With no Worsening of Pulmonary Function
Worsening of pulmonary function is defined as a decline from baseline in ppFVC greater than (>)3% predicted.
Measured: Up to Month 24
Change From Baseline in Adjusted Carbon Monoxide Diffusing Capacity (DLCO) % Predicted in Participants With Refractory SSc
Measured: Baseline up to Month 24
Change From Baseline in Modified Rodnan Skin Score (mRSS) in Participants With Refractory SSc
mRSS is a measure to assess skin thickness through skin palpation. The score is based on a scale of 0 to 3 which examines 17 body areas where 0 indicates no thickening of skin and 3 indicates severe thickening. Total mRSS ranges from 0 (best possible outcome) to 51 (worst possible outcome).
Measured: Baseline up to Month 24
Change From Baseline in Patient Global Assessment (PtGA) in Participants With Refractory SSc
PtGA assesses participant's perception regarding the severity of their disease activity. The PtGA is a visual analog scale (VAS) measuring 100 millimeters (mm) in length. The participant marks on the line the value they feel best reflects their current overall SSc activity. The PtGA VAS is anchored with 0 on the left and 10 on the right, where 10 is maximal activity. Lower scores denote improvement.
Measured: Baseline up to Month 24
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) in Participants With Refractory SSc
HAQ-DI is a patient-reported questionnaire which consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants will assess their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task will be summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three=very severe, high-dependency disability.
Measured: Baseline up to Month 24
Percentage of Participants Achieving Revised Composite Response Index in Systemic Sclerosis (R-CRISS) Response
R-CRISS is used to categorize participants as responders or non-responders based on improvement or worsening in applicable components.
Measured: Up to Month 24
Change From Baseline in Quantitative Interstitial Lung Disease Score in the Whole Lung (QILD-WL) on High-Resolution Computed Tomography (HRCT) Scan of the Thorax in Participants With Refractory SSc
Measured: Baseline up to Month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2024
- Study start13 Jun 2025 (estimated)
- Primary completion2 Sep 2030 (estimated)
- Study completion2 Sep 2030 (estimated)
Why it stopped: Business decision (no safety concerns)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory Lupus NephritisStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06377228
- Sponsor's protocol ID
- TAK-007-1001
- Status last verified
- Apr 2025
- First submitted
- 17 Apr 2024
- Last updated
- 6 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of TAK-007, an Allogeneic Anti-CD19 Chimeric Antigen Receptor Natural Killer Cell (CD19 CAR-NK) Therapy, in Adult Subjects With Refractory Lupus Nephritis or Refractory Systemic Sclerosis
- ClinicalTrials.gov ID
- NCT06377228
- Acronym / sponsor ID
- TAK-007-1001
- Keywords
- Drug Therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Business decision (no safety concerns)
- Enrolment
- 0 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- 13 Jun 2025 (estimated)
- Primary completion
- 2 Sep 2030 (estimated)
- Study completion
- 2 Sep 2030 (estimated)
- First posted
- 22 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main aim of the trial is to learn how well adults with refractory lupus nephritis (LN) or refractory systemic sclerosis (SSc) 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 or refractory SSc, 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 trial is called TAK-007. TAK-007 is being tested to treat people with refractory LN or refractory SSc. This trial will look at the safety and tolerability of TAK-007.
The trial will enroll approximately 26 participants. Participants will receive a single dose or multiple doses of TAK-007, which is an anti-CD19 chimeric antigen receptor natural killer cell (CD19 CAR-NK) therapy.
Participants with refractory LN 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. For participants with refractory SSc the trial has 2 parts. In Part 1, participants with refractory SSc will be treated with 3 days of IV LDC and then after a gap of at least 2 days, a single IV dose (Part 1a - single dose) or three IV doses (Part 1b - multiple doses) of TAK-007. Based on the data of Part 1, Part 2 (expansion) may be initiated in participants with refractory SSc to further evaluate the impact of LDC followed by single dose or multiple doses of TAK-007.
This multi-center trial will be conducted in the United States. The overall time to participate in this study is approximately 24 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| LN Cohort: Single Dose TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells | Experimental | Biological: TAK-007, Drug: Chemotherapy AgentsParticipants with LN 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 with a potential to explore an alternate dose level if deemed appropriate. |
| SSc Cohort: Part 1a: Single Dose TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells | Experimental | Biological: TAK-007, Drug: Chemotherapy AgentsParticipants with SSc 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. |
| SSc Cohort: Part 1b: Multiple Dose TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells | Experimental | Biological: TAK-007, Drug: Chemotherapy AgentsParticipants with SSc will receive IV LDC, for 3 days in conditioning phase (Days -5, -4, and -3), followed by multiple doses of IV 800 × 10^6 TAK-007 on Days 1, 8, and 15. |
| SSc Cohort: Part 2 (Dose Expansion): TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells | Experimental | Biological: TAK-007, Drug: Chemotherapy AgentsBased on the data of Part 1, Part 2 may be initiated for participants with SSc to receive IV LDC, for 3 days in conditioning phase (Days -5, -4, and -3), followed by either single dose of IV 800 × 10^6 TAK-007 on Day 1 or multiple doses of IV 800 × 10^6 TAK-007 on Days 1, 8, and 15. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- The participant must have a diagnosis of SLE fulfilling European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria.
- 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).
- 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.
- 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.
- The participant has a SLEDAI-2K total score ≥6.
Key exclusion criteria (24 listed)
- The participant has a history of drug-induced SLE.
- 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.
- 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).
- The participant has a history or current diagnosis of other autoimmune diseases or current inflammatory joint or skin disease other than SLE that, in the opinion of the investigator and per sponsor assessment, could interfere with the inflammatory arthritis or skin assessments and confound the disease activity assessments.
- The participant has ppFVC ≤45% or DLCO ≤40% or requiring supplemental oxygen at screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TAK-007TAK-007 IV infusion. | Biological | LN Cohort: Single Dose TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells, SSc Cohort: Part 1a: Single Dose TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells, SSc Cohort: Part 1b: Multiple Dose TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells, SSc Cohort: Part 2 (Dose Expansion): TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells |
| Chemotherapy AgentsFludarabine and cyclophosphamide IV infusion. | Drug | LN Cohort: Single Dose TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells, SSc Cohort: Part 1a: Single Dose TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells, SSc Cohort: Part 1b: Multiple Dose TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells, SSc Cohort: Part 2 (Dose Expansion): TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells |
Primary outcome
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: From first dose of LDC 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)
Time frame: 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.
34 secondary outcomes
Cmax: Maximum Observed Plasma Concentration for TAK-007
Time frame: Pre-dose and at multiple time points post-dose up to Month 24
Tmax: Time to Reach the Cmax for TAK-007
Time frame: Pre-dose and at multiple time points post-dose up to Month 24
Tlast: Time of Last Measurable Concentration Above the Lower Limit of Quantitation for TAK-007
Time frame: Pre-dose 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
Time frame: Pre-dose and at multiple time points post-dose up to Month 24
Change From Baseline in CD19+ B Cell Counts
Time frame: Baseline up to Month 24
Change From Baseline in Plasma Cytokine Levels
Time frame: Baseline up to Month 3
Change From Baseline in Clinician's Global Assessment (CGA) Score
Time frame: Baseline up to Month 24
Percentage of Participants With Antidrug Antibodies Categorized as Anti-Human Leukocyte Antigen (HLA) and Anti- Chimeric Antigen Receptor (CAR)
Time frame: Up to Month 24
Percentage of Participants With Replication Competent Retrovirus (RCR) in Blood
Time frame: Up to Month 24
Percentage of Participants With Refractory LN Achieving a Reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Relative to Baseline
Time frame: Baseline through Month 24
Percentage of Participants With Refractory LN Achieving Complete Renal Response (CRR)
Time frame: Up to Month 24
Time to CRR in Participants With Refractory LN
Time frame: Up to Month 24
Duration of CRR in Participants With Refractory LN
Time frame: Up to Month 24
Percentage of Participants With Refractory LN Achieving Lupus Low Disease Activity State (LLDAS)
Time frame: Up to Month 24
Time to LLDAS in Participants With Refractory LN
Time frame: Up to Month 24
Duration of LLDAS in Participants With Refractory LN
Time frame: Up to Month 24
Percentage of Participants With Refractory LN Meeting the Definition of Remission in Systemic Lupus Erythematosus (DORIS) Criteria
Time frame: Up to Month 24
Time to DORIS Remission in Participants With Refractory LN
Time frame: Up to Month 24
Duration of DORIS Remission in Participants With Refractory LN
Time frame: Up to Month 24
Change From Baseline in Anti-Double Stranded Deoxyribonucleic Acid (Anti-dsDNA) Levels in Participants With Refractory LN
Time frame: Baseline up to Month 24
Change From Baseline in Antinuclear Antibody (ANA) Levels in Participants With Refractory LN
Time frame: Baseline up to Month 24
Change From Baseline in Proteinuria Levels in Participants With Refractory LN
Time frame: Baseline up to Month 24
Change From Baseline in Serum Creatinine Levels in Participants With Refractory LN
Time frame: Baseline up to Month 24
Change From Baseline in eGFR in Participants With Refractory LN
Time frame: Baseline up to Month 24
Change From Baseline in Complement (C3, C4) Levels in Participants With Refractory LN
Time frame: Baseline up to Month 24
Change From Baseline in Forced Vital Capacity (FVC) in Participants With Refractory SSc
Time frame: Baseline up to Month 24
Change From Baseline in Percentage (%) Predicted Forced Vital Capacity (ppFVC) in Participants With Refractory SSc
Time frame: Baseline up to Month 24
Percentage of Refractory SSc Participants With no Worsening of Pulmonary Function
Time frame: Up to Month 24
Change From Baseline in Adjusted Carbon Monoxide Diffusing Capacity (DLCO) % Predicted in Participants With Refractory SSc
Time frame: Baseline up to Month 24
Change From Baseline in Modified Rodnan Skin Score (mRSS) in Participants With Refractory SSc
Time frame: Baseline up to Month 24
Change From Baseline in Patient Global Assessment (PtGA) in Participants With Refractory SSc
Time frame: Baseline up to Month 24
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) in Participants With Refractory SSc
Time frame: Baseline up to Month 24
Percentage of Participants Achieving Revised Composite Response Index in Systemic Sclerosis (R-CRISS) Response
Time frame: Up to Month 24
Change From Baseline in Quantitative Interstitial Lung Disease Score in the Whole Lung (QILD-WL) on High-Resolution Computed Tomography (HRCT) Scan of the Thorax in Participants With Refractory SSc
Time frame: Baseline up to Month 24
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2025.
- Individual participant dataSharing planned: Yes. 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.
Related trials for Refractory Lupus Nephritis
RecruitingPhase 2
Obe-cel in Severe, Refractory Systemic Lupus Erythematosus (SLE) With Active Lupus Nephritis (LN)
Lupus Nephritis
Not yet recruitingPhase 1/2
CD19-Directed CAR-T Cell Therapy in Refractory Systemic Lupus Erythematosus
Lupus Erythematosus, Systemic
RecruitingPhase 1
A Safety and Efficacy Study Evaluating CTX112 in Adult Subjects With Refractory Autoimmune Disease
SLE (Systemic Lupus), Lupus Erythematosus, Systemic
RecruitingPhase 1
A Clinical Study of YTS109 Cells for the Treatment of R/R Autoimmune Diseases
Systemic Lupus Erythematosus (SLE), Lupus Nephritis (LN)
RecruitingPhase 1
A Clinical Study of YTS109 Cell for R/R Autoimmune Diseases
Systemic Lupus Erythematosus (SLE), Lupus Nephritis (LN)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TAK-007 and Chemotherapy Agents in people with Refractory Lupus Nephritis and Refractory Systemic Sclerosis, run by Takeda at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 6 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (time frame: From first dose of LDC up to end of study (EOS) [up to Month 24]). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2025.