A Biospecimen Collection Study to Identify the Targets of Disease-Reactive T Cells in Patients With Autoimmune Disease

Overview

The most clinically meaningful way to discover new targets of T cells in autoimmune diseases is to study the tissues of patients with active autoimmune disease mediated organ inflammation. These tissues contain both cytotoxic and helper T cells that are driving their disease, and these T cells are being guided by TCRs that recognize tissue-specific targets. By collecting tissue when a patient has active inflammation, it is possible to determine which T cells are activated and undergoing clonal expansion in the patient's diseased organ. TScan has developed a genome-wide, high-throughput technology to determine the natural, physiological target of any TCR (Kula, 2019). The goal of this study is to isolate T cells from inflamed tissues and matched blood samples and/or matched normal tissues (for patients with inflammatory bowel diseases). T cell clones that are expanded in diseased tissues relative to blood or normal tissues will be selected and the targets of their TCRs will be defined using TScan's genome-wide, high-throughput target ID technology. The goal of this study is to discover a collection of peptide targets, along with their associated TCRs to be developed as new tolerogenic therapies for patients with autoimmune diseases.

Interventions

• Procedure Companion blood samples with procedure
  Participants in all cohorts will have a companion blood sample obtained on or around the time of the procedure intended to obtain tissue or fluid.

Primary outcome measures

• Identify peptide targets together with their associated TCRs in patients with autoimmune diseases under study. [Time frame: 3 Years]

Eligibility criteria

Cohort Legend: Cohort 1: Inflammatory Bowel Diseases - Crohn's Disease or Ulcerative Colitis, Cohort 2: Celiac Disease, Cohort 3: Ankylosing spondylitis or non-radiographic axial spondyloarthritis (nr-axSpA), Cohort 4: Multiple Sclerosis, Cohort 5: Scleroderma, Cohort 6: Systemic Sclerosis with pulmonary involvement, Cohort 7: Other Autoimmune Disease, Cohort 8: Apparent Evolving Autoimmune Disease, Cohort 9: Frozen Cryopreserved

Inclusion criteria

• Study cohorts 1,2,3,4,5,6,7,8.9: Known or suspected diagnosis, with subsequent diagnostic confirmation, of one of the following cohorts associated with the following autoimmune diseases:
• Inflammatory Bowel Diseases - Crohn's Disease or ulcerative colitis
• Celiac disease
• Ankylosing spondylitis or Non radiographic axial spondyloarthritis (nr-axSpA)
• Multiple sclerosis
• Scleroderma
• Systemic sclerosis with pulmonary involvement
• Other autoimmune disease (as agreed between Investigator and Sponsor)
• Apparent evolving autoimmune disease
• Frozen cryopreserved
• Age equal or greater than 18 years at time of informed consent.
• Ability to understand and willingness to sign an informed consent document when informed consent is required by an ethical review board.
• On disease-modifying treatments that are not known to be directly T cell toxic.

Such treatments are allowed and include:

• Non-steroidal anti-inflammatory drugs including aspirin, ibuprofen, acetaminophen, celecoxib, indomethacin, diclofenac, etodolac, naproxen, meloxicam, sulindac, nabumetone amongst others.
• Tumor necrosis factor alpha (TNF-alpha) antagonists including infliximab (Remicade), adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi) and biosimilar drugs with the same generic name.
• Interleukin-12/23 antagonists including ustekinumab (Stelara) and risankizumab-rzaa (Skyrizi)
• Alpha-4-integrin antagonists including vedolizumab (Entyvio), natalizumab (Tysabri)
• Interleukin-17 inhibitors including secukinumab (Cosentyx), ixekizumab (Taltz)
• Recombinant interferon beta
• CD20 antagonists including rituximab (Rituxan), ocrelizumab (Ocrevus), ofatumumab (Kesimpta)
• Oral fumarates including dimethyl fumarate (Tecfidera), diroximel fumarate (Vumerity), monomethyl fumarate (Bafiertam)
• Oral sphingosine 1-phosphate receptor (S1PR) modulators including fingolimod (Gilenya), siponimod (Mayzent), ozanimod (Zeposia), ponesimod (Ponvory)
• Oral glatiramer acetate (copolymer 1; Copaxone)
• Patient is an appropriate candidate for a procedure to obtain a biopsy, tissue samples or biologic materials during a clinically indicated procedure where it is expected that excess materials could be used for research OR
• In the opinion of the clinical investigator, a patient is an appropriate, low-risk candidate for a research only procedure to obtain a biopsy, tissue samples or biologic materials.

Exclusion criteria

• On treatment with drugs that are known to be T cell toxic and cannot be held for at least 4 weeks or longer. The following treatments are not allowed except in designated cohorts when approved by Sponsor:
• Glucocorticoids including prednisone, methylprednisolone (Solu-medrol), budesonide (Entocort), hydrocortisone (Solu-cortef), dexamethasone (Decadron), betamethasone (Betaject)
• Sulfasalazine (Azulfidine)
• Aminosalicylates including mesalamine/ mesalazine (Asacol, Pentasa).
• Thiopurines including azathioprine (Imuran) and 6-mercaptopurine (Purixan)
• Systemic JAK inhibitors including tofacitinib (Xeljanz), abrocitinib (Cibinqo), baricitinib (Olumiant), upadacitinib (Rinvoq)
• CD52 inhibitors including alemtuzumab (Campath)
• Methotrexate
• Cladribine
• Teriflunomide (Aubagio)
• Concurrent disease or condition that would make the patient inappropriate for study participation, or any serious medical or psychiatric disorder that would interfere with the subject's safety.
• Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
• Patients receiving research biopsy procedures will not have a history of serious or life-threatening allergic reaction to local anesthetics (i.e., lidocaine, xylocaine), if local anesthetic is required for the procedure or to medications used for sedation during a procedure.
• Pregnant or nursing women are excluded because there may be unanticipated adverse events and increased risk to both mother and fetus in the setting of local anesthetic or study procedures.
• Any other medical or psychiatric condition, which in the opinion of the patient's treating clinician, would make participation in this protocol unreasonably hazardous for the patient.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Case-only

Study locations

United States · 12 centers

• Knowledge Research Center — Orange
• Cura Clinical Research — Sherman Oaks
• Arnold Arthritis & Rheumatology — Skokie
• University of Kentucky Research Foundation — Lexington
• Massachusetts Eye Research and Surgery Institution (MERSI) — Waltham
• Susquehanna Research Group — Harrisburg
• Nexus Research — Cranston
• Nexus Research — Cranston
• … and 4 more centers

Identifiers

NCT: NCT06587828 · 200-05

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗