Ensayos clínicos

Inclusion Criteria:

All subjects must meet all of the following inclusion criteria:

• Age ≥ 18 and ≤ 70 at the time of signing the informed consent.
• Body mass index (BMI) < 35 kg/m^2 , inclusive.
• Diagnosis of adult-onset RA as defined by the 2010 ACR/EULAR classification criteria for RA.
• Moderate-to-severe active disease defined by DAS28 ≥ 3.2 (calculated using CRP).
• Must have at least 1 joint that can be used for synovial biopsy.
• Confirmed presence of inflammatory cells and SBT777101 scFv-reactive citrullinated proteins in synovial tissue at screening as evaluated by hematoxylin and eosin (H&E) and immunohistochemistry (IHC) staining, respectively.
• Clinical and/or ultrasound evidence of synovitis.
• Have had an inadequate response to or were unable to tolerate prior treatment with available therapies, including at least 3 prior b/tsDMARDs with differing mechanisms of action:
  • An inadequate response is determined by the treating physician and may be based on RA that is difficult to treat and continued disease activity as measured by ≥ 4/28 tender and ≥ 4/28 swollen joints , DAS28 ≥ 3.2, inability to taper corticosteroids to 7.5 mg or lower, or other appropriate measures, (Nagy et al., 2020), generally after 3 months of therapy on the recommended therapeutic dose (Frankel et al., 2021);
  • Prior b/tsDMARDs include approved therapies that target TNF (e.g., adalimumab, golimumab, etanercept, infliximab), IL-6 (e.g., tocilizumab, sarilumab), IL-1 (e.g., anakinra), T cells (eg, abatacept), CD20 (eg, rituximab), or JAK (eg, baricitinib, filgotinib, tofacitinib).
• Doses of medications for RA (or related biosimilars) including methotrexate, hydroxychloroquine, adalimumab, golimumab, infliximab, certolizumab, etanercept, anakinra, tocilizumab, sarilumab, or long-acting analgesics (eg, extended release) must be stable for 30 days prior to the screening visit. For subjects on rituximab, doses must be stable for at least 90 days prior to the screening visit.
• Women of childbearing potential must agree to use 2 methods of contraceptive for at least 1 year post SBT777101 administration. One method must be considered a highly effective method of contraception, while the second method may be a barrier method.
• Women of childbearing potential must have a negative urine pregnancy test before the administration of study drug performed on the day of study drug administration.
• Males who are sexually active with women of childbearing potential must agree to use one method of contraception for 1 year post SBT777101 administration.
• Male subjects must refrain from donating sperm for 1 year post SBT777101 administration.
• Subjects receiving estrogen replacement therapy must agree to discontinue use at least 1 week or 5 half-lives prior to study treatment.
• Ability to comply with all the requirements of the study, in the Investigator’s opinion.
• Adequate vascular access, in the opinion of the Investigator, for apheresis procedure.
• Willing to undergo repeat synovial biopsies to obtain tissue and synovial fluid collections during the study.
• Willing to comply with study specific safety monitoring requirements.
• Willing and able to provide signed informed consent.

Exclusion Criteria:

• Major surgery (including joint surgery) within 12 weeks prior to screening or planned within 12 months after dosing.
• History of or current inflammatory joint disease other than RA or other autoimmune or inflammatory disease that may confound clinical assessments or increase subject risk in the study.
• Current or previous (within the past 2 years) evidence of serious uncontrolled concomitant cardiovascular, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus) or gastrointestinal disease.
• Active current infection or history of recurrent bacterial, viral, fungal, mycobacterial or other infections, including but not limited to tuberculosis and atypical mycobacterial disease, hepatitis B and C, and herpes zoster ( > 2 episodes within the previous 12 months).
• Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics/anti-infectives within 2 weeks prior to screening.
• Active tuberculosis requiring treatment within 3 years prior to screening.
• Latent tuberculosis diagnosed during screening that has not been appropriately treated.
• Primary or secondary immunodeficiency (history of or currently active), including a history of HIV positivity.
• Prior diagnosis with diverticulitis requiring antibiotic treatment.
• Any known significantly increased risk of hypercoagulability or personal or family history of thromboembolic disease.
• Females who are pregnant or breastfeeding or planning to become pregnant within 12 months from start on study.
• History of malignancy within 5 years from the time of screening (including squamous cell carcinoma of the skin or cervix or carcinoma-in-situ), except adequately treated basal cell carcinoma.
• History of epilepsy or other seizure disorder, stroke, dementia or other central nervous system disorder.
• Known history of drug or alcohol abuse within 1 year of screening.
• Any medical or psychological condition that in the judgment of the Principal Investigator would interfere with the conduct of the study or may confound the interpretation of the study results.
• Any out‑of‑range electrocardiogram (ECG) parameter(s) or abnormal finding(s) considered clinically significant by the Investigator including if the QTc calculated using Fridericia’s formula (QTcF) is:
  • > 450 ms in males or > 470 ms in females.
• Prior treatment with cell or gene therapy.
• Treatment with an investigational agent within 30 days or 5 half-lives, whichever is longer prior to screening.
• Treatment with intra-articular glucocorticoids within 90 days of the screening visit.
• Treatment with leflunomide (without chelation) within 8 weeks of the screening visit:
• Subjects previously on leflunomide may continue on the medication during the screening period if chelation with cholestyramine or activated charcoal is planned for leflunomide washout prior to apheresis.
• Treatment withor guardianship.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 12/21/23. Questions regarding updates should be directed to the study team contact.