Autoimmune DiseasesPhase 1NCT06208280
F01 in the Treatment of Autoimmune Diseases
A Phase 1 study testing After preconditioning with Fludarabine and Cyclophosphamide, F01 will be evaluated. in people with Autoimmune Diseases, run by RenJi Hospital at 1 site in China.
Trial summary
This is a multicenter, open lable clinical study to evaluate the safety and tolerability of F01 in autoimmune diseases. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Autoimmune Diseases
- What is being tested?
- After preconditioning with Fludarabine and Cyclophosphamide, F01 will be evaluated.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 9 Jan 2024to Dec 2025
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must meet all of the following inclusion criteria to be enrolled in the study:
- Age ≥18 and ≤65 years old, gender unlimited.
- Special criteria for different indications:
- 2.1 Patients with moderately to severely active SLE need to meet the following criteria：
- Diagnosis of systemic lupus erythematosus (SLE) according to the European League Against Rheumatology/American College of Rheumatology (EULAR/ACR) SLE classification criteria (Aringer et al 2019) at least 6 months prior to screening.
- Positive antinuclear antibody, and/or anti-double-stranded DNA antibody at screening.
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- Moderate to severe activity is defined as: SLEDAI 2000 score ≥ 8 points at screening Disease remains active after at least 2 months of use of standard SLE treatment regimen prior to screening.
- Standard regimens for SLE include glucocorticoids and/or antimalarials, combined immunosuppressants/immunomodulators (including but not limited to azathioprine, mycophenolate mofetil, leflunomide, iratimod, methotrexate, cyclophosphamide, mycophenolate mofetil, cyclosporine, tacrolimus, etc.), and/or biologic agents (including but not limited to rituximab, belimumab, telitacicept, etc.).
- 2.2 Patients with relapsed or refractory AAV should meet the following criteria：
- Clinical diagnosis of granulomatosis with polyangitis (GPA) and microscopic polyangiitis (MPA) as defined by the 2012 Chapel Hill Consensus Conference (CHCC); At least one major item, or at least three other items, in Birmingham Vasculitis Activity Score (BVAS) version 3; Positive anti-protease-3 (PR3-ANCA) or antimyeloperoxidase (MPO-ANCA) at screening;
- Relapsed/refractory is defined as:
- Subjects with relapsed AAV: At least 1 disease recurrence (defined as the presence of at least one important item on the BVAS assessment, or at least 3 other items) after at least 3 months of treatment with glucocorticoids in combination with immunosuppressants (cyclophosphamide, rituximab, azathioprine, methotrexate, mycophenolate mofetil, etc.) (BVAS score 0 and glucocorticoid dose ≤ 7.5 mg/day prednisone or other equivalent glucocorticoid drugs) or 1-2 new items in two consecutive assessments), and disease recurrence occurred within 12 weeks prior to screening; Subjects with refractory AAV: Glucocorticoids combined with immunosuppressants (cyclophosphamide, rituximab, azathioprine, methotrexate, mycophenolate mofetil, etc.) for at least 3 months have not been effective (BVAS score of 0 and glucocorticoid dose ≤ 7.5 mg/day prednisone or other equivalent glucocorticoid drugs); 2.3 Patients with moderately to severely active IIM need to meet the following criteria： According to the 2017 EULAR/ACR classification criteria, the probability of diagnosing IIM is ≥55%, and it is classified as dermatomyositis (DM), polymyositis (PM), or immune-mediated necrotizing myopathy (IMNM) based on age at first onset, skin and muscle strength performance, laboratory tests, and muscle biopsy features;
- Disease activity/severity meets the following criteria:
- MMT-8 score ≤141 out of 150;
- At least 2 of the other CSMs exceptions are met:
- Patient-assessed overall activity (based on visual analogue scale (VAS) score≥2 points (range 0-10 points); Physician-assessed overall disease activity VAS score ≥2 points (range 0-10 points); Extramuscular global mobility VAS score ≥2 points (range 0-10 points); Health Assessment Questionnaire (HAQ) score ≥0.25 (range 0-3). At least 1 muscle enzyme level > 1.5 times ULN. - Prior intolerance or inadequate response to treatment with glucocorticoids and at least one other immunosuppressant or modulator, requiring that: Treatment with glucocorticoids and at least 2 immunosuppressants (azathioprine, methotrexate, mycophenolate mofetil, etc.) at known effective doses for at least 3 months; 2.4 Subjects with relapsed/refractory active diffuse cutaneous systemic sclerosis (dcSSc) need to meet the following criteria：
- Diagnosed systemic sclerosis according to the 2013 American College of Rheumatology/European Federation of Rheumatological Societies (ACR/EULAR) classification criteria for systemic sclerosis (SSc);
- Consistent with diffuse cutaneous manifestations according to the criteria defined by LeRoy et al. 1988, i.e., extensive skin fibrosis with skin involvement of the elbow and/or proximal knee; Co-ordination of interstitial lung diseases (ILD) at screening with 45% predicted ≤ forced vital capacity (FVC) ≤ 70% predicted, or 40% predicted ≤ diffusing capacity of the lungs for carbon monoxide (DLCO) ≤ 70% predicted Relapsed/refractory is defined as relapse after failure to respond to conventional therapy or remission of disease.
- Conventional treatment refers to the use of glucocorticoids, cyclophosphamide and at least one immunosuppressive/modulating drug for 6 months ≥, including azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, rituximab, belimumab, telitacicept, etc.
- Activity is defined as having at least one of the following: Evidence of skin progression at screening, i.e., a ≥10% increase in mRSS score in the last 6 months;
- Evidence of activity in any of the following interstitial lung diseases (ILD) at screening:
- Newly diagnosed ILD within the last 6 months; 10% reduction in FVC or 5% reduction in FVC with a 15% decrease in diffusing capacity of the lungs for carbon monoxide (DLCO) in participants with prior ILD in the last 6 months.
- The expected survival is greater than 6 months.
- Adequate bone marrow, liver, kidney, lung, cardiac, and coagulation function, defined as:
- Bone marrow function without blood transfusion and growth factor use within 7 days before routine blood: hemoglobin (Hb) ≥ 80 g/L, neutrophil count (ANC) ≥ 1.5×109/L, platelet count (PLT) ≥ 50×109/L;
- Renal function: creatinine clearance (CCr) ≥ 50 ml/min without hydration assistance, serum creatinine ≤ 1.5 times the upper limit of normal;
- Liver function: serum ALT and AST ≤ 2.5 times the upper limit of normal, total bilirubin ≤ 1.5 times the upper limit of normal;
- Lung function: Under indoor ventilation conditions, the blood oxygen saturation in the non-oxygen state is ≥ 92%; There was no clinically significant pleural effusion;
- Cardiac function: Left ventricular ejection fraction ≥ 40%; Echocardiography confirmed no clinically significant pericardial effusion., No clinically significant abnormalities were found in the ECG;
- During the screening period, the serum pregnancy test results of fertile female subjects must be negative (women who have been surgically sterilized or have been menopausal for at least 2 years are considered not fertile). Fertile female subjects and male subjects must use highly effective contraceptive methods throughout the clinical study period and within 1 year after the last study treatment; At the same time, a commitment should be made not to donate eggs (egg cells, oocytes)/sperm for assisted reproduction within 1 year after the last study treatment.
- Voluntarily participate in clinical trials and sign informed consent.
Who cannot join
- Subjects who meet any of the following exclusion criteria will not be admitted to this clinical study:
- Severe pulmonary disease in the past 1 year, such as moderate to severe pulmonary hypertension (echocardiographic mean pulmonary artery pressure > 60 mmHg), requiring oxygen storage mask oxygen therapy or non-invasive or invasive ventilator to assist breathing at screening Primary central nervous system lymphoma; SLE subjects need to exclude subjects who have had lupus crisis in the past 3 months, active central nervous system lupus, severe hemolytic anemia, severe thrombocytopenic purpura, severe neutropenia, severe myocardial damage, severe lupus pneumonia or pulmonary hemorrhage, severe lupus hepatitis, severe vasculitis;
- Combined with severe kidney disease, including severe lupus nephritis, severe nephrotic syndrome, etc. Severe is defined as:
- Have received any of the following treatments within the specified time: Previous kidney transplantation; Dialysis or plasmapheresis within 3 months prior to screening; Pulse glucocorticoid therapy (defined as a dose ≥ 500 mg/d prednisone or equivalent dose of other glucocorticoids) within 1 month prior to screening;
- Need to receive either of the following treatments during the study: Need to use protocol prohibited medications; Need for dialysis or plasmapheresis; Kidney transplantation is required or planned.
- History of severe cardiovascular disease, including but not limited to: symptomatic chronic heart failure requiring intervention, acute myocardial infarction in the past 6 months, unstable angina, history of severe arrhythmia, stroke; or New York Heart Association (NYHA) grade III~IV; History of other autoimmune diseases other than those for the target indication, including eosinophilic granulomatosis with polyangitis (EGPA), Henoch-Schoenlein purpura, rheumatoid arthritis, cryoglobulinemia vasculitis, inclusion body myositis (IBM), Anti-glomerular basement membrane disease, Behcet's disease or Takayasu's arteritis, etc; Family history of non-IIM myopathies such as drug-induced; myopathies, human immunodeficiency virus-associated myopathies, thyroid diseases, and myopathies; Patients with a history of malignancy, including tumor-related polymyositis/dermatomyositis. Patients who have been surgically resected and cured for non-melanoma skin cancer, carcinoma in situ of the cervix, localized prostate cancer, low-stage bladder cancer, ductal carcinoma in situ, or patients who have recovered without evidence of recurrence in the past two years and do not require treatment; Patients with known allergies, hypersensitivity, intolerance, or contraindications to F01 or any ingredient of drugs that may be used in the study (including fludarabine, cyclophosphamide, tocilizumab), or patients who have had a severe allergic reaction in the past;
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- Patients who have received the following treatments within the prescribed time frame prior tolymphodepletion pretreatment:
- Received autologous/allogeneic hematopoietic stem cell transplantation or CAR-T and other cell therapy; Pulse glucocorticoid therapy within 2 months (defined as a dose of ≥500 mg/day prednisone or equivalent dose of other glucocorticoids); Have been treated with biologics such as belimumab or telitacicept within 1 month; Received major surgery, received live vaccine or received other clinical study treatment within 1 month; Presence of uncontrolled active infection requiring treatment with systemic antibiotics, antiviral, or antifungal drugs within 14 days, except for prophylactic therapy.
- prednisone or equivalent glucocorticoids should be reduced to ≤20 mg/day at least 7 days before lymphodepletion Concomitant active hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus infection (HIV), or syphilis infection.
- Risk of active tuberculosis at screening, regardless of completion of adequate treatment: presence of signs or symptoms of active tuberculosis (such as fever, cough, night sweats, and weight loss) as judged by the investigator at screening; Chest imaging (e.g., chest x-ray, chest CT scan) documented at screening or at any time within 6 months prior to screening showing active tuberculosis; Evidence of latent tuberculosis infection, such as a positive γ-interferon release test, at screening; Use of drug combinations/combination therapies prohibited by the protocol during screening; Any situations that the investigator believes the patients are not suitable for the study.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Department of Rheumatology, Ren Ji Hospital South Campus, School of Medicine, Shanghai JiaoTong University
Shanghai, Shanghai Municipality, 200001
Qiong Fu, MD, 86-13585603288, Fuqiong5@163.com
Chunmei Wu, MD, 86-15800605296, wuchunmei_1988@163.com
About this study
Official title: An Exploratory Clinical Study to Evaluate the Safety and Tolerability of F01 in the Treatment of Autoimmune Diseases
This is a multicenter, open lable clinical study to evaluate the safety and tolerability of F01 in autoimmune diseases.
Read the detailed description
Approximately up to 20 participants with autoimmune diseases (including moderate-to-severe active systemic lupus erythematosus, relapse or refractory antineutrophil cytoplasmic antibody associated vasculitis,refractory idiopathic inflammatory myopathies and relapsed/refractory active diffuse cutaneous systemic sclerosis) are planned to enroll. This study is divided into two stages: dose escalation and dose extension.
- Conditions
- Autoimmune Diseases
- Being tested
- After preconditioning with Fludarabine and Cyclophosphamide, F01 will be evaluated.
- Keywords
- NK, Autoimmune Diseases
- Medical subject headings
- Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
After preconditioning with Fludarabine and Cyclophosphamide, F01 will be evaluated.Drug
Drug: After preconditioning with Fludarabine and Cyclophosphamide, F01 will be evaluated.
Biological: 0.5-3×10^9 CAR+NK Cells, Treatment follows a lymphodepletion Drug: Fludarabine: 25-30 mg/m^2 (D-5~D-3) Drug: Cyclophosphamide: 250-300 mg/ m^2 (D-5~D-3)
| Study group | Role | What they receive |
|---|---|---|
| Assigned Interventions | Experimental | Not described Receives: Drug: After preconditioning with Fludarabine and Cyclophosphamide, F01 will be evaluated. |
What is being measured
The primary outcome is the main question the study is designed to answer.
The proportion of subjects with AEs and SAEs
The incidence and severity of all adverse events, serious adverse events, and abnormal laboratory test results
Measured: Up to 12 weeks
The proportion of subjects with DLT
Incidence of DLT
Measured: Up to 4 weeks
Secondary outcomes (2)
Efficacy of F01 cells in autoimmune diseases
Proportion of SLE subjects with CR, LLDAS, and SRI-4 response(including SELENA-SLEDAI ≥4-Point improvement, BILAG 2004 with No new A domain score AND no more than 1 new B domain scores, PGA score increase less than 0.3 point from baseline)
Measured: 24 weeks after infusion
Cellular kinetics
CAR transgene levels by quantitative polymerase chain reaction (qPCR) in peripheral blood
Measured: 96 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2024
- Study start9 Jan 2024 (estimated)
- Primary completionJan 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autoimmune DiseasesStudies of the same condition, open and under way.
- More trials run by RenJi HospitalThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- RenJi Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai Simnova Biotechnology Co.,Ltd.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06208280
- Sponsor's protocol ID
- SNC 103-CD19CAR NK-103
- Status last verified
- Jan 2024
- First submitted
- 5 Jan 2024
- Last updated
- 17 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Clinical Study to Evaluate the Safety and Tolerability of F01 in the Treatment of Autoimmune Diseases
- ClinicalTrials.gov ID
- NCT06208280
- Acronym / sponsor ID
- SNC 103-CD19CAR NK-103
- Conditions
- Autoimmune Diseases
- Keywords
- NK, Autoimmune Diseases
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- RenJi HospitalUniversity, hospital or other
- Collaborators
- Shanghai Simnova Biotechnology Co.,Ltd.
- Study start
- 9 Jan 2024 (estimated)
- Primary completion
- Jan 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 17 Jan 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.
This is a multicenter, open lable clinical study to evaluate the safety and tolerability of F01 in autoimmune diseases.
Detailed description
Approximately up to 20 participants with autoimmune diseases (including moderate-to-severe active systemic lupus erythematosus, relapse or refractory antineutrophil cytoplasmic antibody associated vasculitis,refractory idiopathic inflammatory myopathies and relapsed/refractory active diffuse cutaneous systemic sclerosis) are planned to enroll. This study is divided into two stages: dose escalation and dose extension.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Assigned Interventions | Experimental | Drug: After preconditioning with Fludarabine and Cyclophosphamide, F01 will be evaluated. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- Participants must meet all of the following inclusion criteria to be enrolled in the study:
- Age ≥18 and ≤65 years old, gender unlimited.
- 2.1 Patients with moderately to severely active SLE need to meet the following criteria：
- Diagnosis of systemic lupus erythematosus (SLE) according to the European League Against Rheumatology/American College of Rheumatology (EULAR/ACR) SLE classification criteria (Aringer et al 2019) at least 6 months prior to screening.
- Positive antinuclear antibody, and/or anti-double-stranded DNA antibody at screening.
Key exclusion criteria (10 listed)
- Subjects who meet any of the following exclusion criteria will not be admitted to this clinical study:
- Severe pulmonary disease in the past 1 year, such as moderate to severe pulmonary hypertension (echocardiographic mean pulmonary artery pressure > 60 mmHg), requiring oxygen storage mask oxygen therapy or non-invasive or invasive ventilator to assist breathing at screening Primary central nervous system lymphoma; SLE subjects need to exclude subjects who have had lupus crisis in the past 3 months, active central nervous system lupus, severe hemolytic anemia, severe thrombocytopenic purpura, severe neutropenia, severe myocardial damage, severe lupus pneumonia or pulmonary hemorrhage, severe lupus hepatitis, severe vasculitis;
- Combined with severe kidney disease, including severe lupus nephritis, severe nephrotic syndrome, etc. Severe is defined as:
- Have received any of the following treatments within the specified time: Previous kidney transplantation; Dialysis or plasmapheresis within 3 months prior to screening; Pulse glucocorticoid therapy (defined as a dose ≥ 500 mg/d prednisone or equivalent dose of other glucocorticoids) within 1 month prior to screening;
- Need to receive either of the following treatments during the study: Need to use protocol prohibited medications; Need for dialysis or plasmapheresis; Kidney transplantation is required or planned.
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 |
|---|---|---|
| After preconditioning with Fludarabine and Cyclophosphamide, F01 will be evaluated.Drug: After preconditioning with Fludarabine and Cyclophosphamide, F01 will be evaluated. Biological: 0.5-3×10^9 CAR+NK Cells, Treatment follows a lymphodepletion Drug: Fludarabine: 25-30 mg/m^2 (D-5~D-3) Drug: Cyclophosphamide: 250-300 mg/ m^2 (D-5~D-3) | Drug | Assigned Interventions |
Primary outcome
The proportion of subjects with AEs and SAEs
Time frame: Up to 12 weeks
The incidence and severity of all adverse events, serious adverse events, and abnormal laboratory test results
The proportion of subjects with DLT
Time frame: Up to 4 weeks
Incidence of DLT
2 secondary outcomes
Efficacy of F01 cells in autoimmune diseases
Time frame: 24 weeks after infusion
Cellular kinetics
Time frame: 96 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2024.
- Individual participant dataSharing planned: No
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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.
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 After preconditioning with Fludarabine and Cyclophosphamide, F01 will be evaluated. in people with Autoimmune Diseases, run by RenJi Hospital at 1 site in China.
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 31 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 17 Jan 2024. 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 China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Qiong Fu, Ph.D (86-13585603288, Fuqiong5@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The proportion of subjects with AEs and SAEs (time frame: Up to 12 weeks). 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 17 Jan 2024.