A Study of TAK-007 in Adults With Refractory Lupus Nephritis (LN) or Refractory Systemic Sclerosis (SSc)

NCT06377228 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: TAK-007-1001
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Refractory Lupus Nephritis; Refractory Systemic Sclerosis

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Up to Day 30

Secondary Outcomes (34)

• Cmax: Maximum Observed Plasma Concentration for TAK-007

  Pre-dose and at multiple time points post-dose up to Month 24

• Tmax: Time to Reach the Cmax for TAK-007

  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

  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

  Pre-dose and at multiple time points post-dose up to Month 24

• Change From Baseline in CD19+ B Cell Counts

  Baseline up to Month 24

Study Arms (4)

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.

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.

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.

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.

Biological: TAK-007; Drug: Chemotherapy Agents

Interventions

TAK-007 BIOLOGICAL

TAK-007 IV infusion.

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 Agents DRUG

Fludarabine and cyclophosphamide IV infusion.

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

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

University of Texas Health Science Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Lupus Nephritis; Scleroderma, Systemic

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin Diseases

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2024
• First Posted: April 22, 2024
• Study Start: June 13, 2025
• Primary Completion (Estimated): September 2, 2030
• Study Completion (Estimated): September 2, 2030
• Last Updated: April 6, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

US (1)