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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion 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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06587828
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	TScan Therapeutics, Inc.
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Autoimmune Diseases, Ulcerative Colitis, Multiple Sclerosis, Scleroderma, Ankylosing Spondylitis, Celiac Disease, Non-radiographic Axial Spondyloarthritis (nr-axSpA), Crohn&#39;s Disease, Birdshot Chorioretinitis

Arms & Interventions

Arms

: Inflammatory Bowel Diseases- Crohn's Disease and Ulcerative Colitis

Group A: IBD-Treatment Naïve Crohn's: Patients that are scheduled to have an endoscopic procedure to confirm a suspected diagnosis of Crohn's disease and are not currently on any Crohn's directed treatment. Group B: IBD-On-Treatment Crohn's: Patients with an established diagnosis of Crohn's disease and are only on treatments that are allowed under this protocol (see Inclusion and Exclusion criteria) and consent to have extra biopsies obtained from inflamed and normal colon for research purposes during a planned endoscopy for their standard clinical care. Group C: IBD-Ulcerative Colitis: Patients with established or suspected diagnosis of ulcerative colitis who may be on treatments that are allowed under this protocol (see Inclusion and Exclusion criteria). Interventions: Companion blood samples with colonoscopy and biopsies for participants with Crohn's Disease or Ulcerative Colitis

: Celiac Disease: Small intestine endoscopic biopsies obtained during endoscopy

Group A Celiac Disease: Excess small intestine biopsies obtained during endoscopy from patients with celiac disease or from patients who are suspected to have celiac disease. A companion blood sample will be drawn on or around the same day. Group B Celiac Disease: Patients who are suspected to have celiac disease or are known to have celiac disease and who undergo a research endoscopy of the small intestine to obtain biopsy samples from the small intestine. A companion blood sample will be drawn on or around the same day. Interventions: Companion blood samples with upper endoscopy and biopsies.

: Ankylosing spondylitis or non-radiographic axial spondyloarthritis (nr-axSpA) (HLA-B27 positive)

Group A ankylosing spondylitis- arthrocentesis: HLA-B27 positive patients with known or suspected ankylosing spondylitis or nr-axSpA with inflammatory joint involvement who consent to arthrocentesis done for research purposes. A blood sample drawn on or around the same day of the procedure is also required. A minimum of 2 mL and up to 10 mL of joint aspiration fluid is required. Group B ankylosing spondylitis- surgery: HLA-B27 positive patients with known or suspected ankylosing spondylitis or nr-axSpA planned for surgery for their standard clinical care who consent to have excess materials from their resected joint tissues used for research purposes. Bone, joint or biologic materials from the surgical resection is acceptable. A blood sample drawn on or around the same day of the procedure is also required. Interventions: Companion blood samples with arthrocentesis

: Multiple Sclerosis. Excess CSF collected during lumbar puncture

A. Multiple Sclerosis Group A: Extra CSF from standard clinical procedure in patients diagnosed with multiple sclerosis and have a planned lumbar puncture for standard clinical care where extra CSF may be obtained for standard of care. A blood sample drawn on or around the same day is required. CSF in excess of clinical laboratory requirements will be used for study purposes. 2 mL to 10 mL of CSF is required. Up to 20 patients will be recruited into research procedure group. B. Multiple Sclerosis Group B: Research CSF collection - Patients will have CSF collected during a lumbar puncture that is not required for standard clinical care and will also have a companion blood sample collected. The patient will consent to a research lumbar puncture and will be enrolled into the research CSF collection cohort. 2 mL to 10 mL of CSF is required. Up to 10 patients will be recruited into this group. Interventions: Companion blood samples with lumbar puncture

: Scleroderma. Skin tissue biopsy

A. Scleroderma Group A: Excess Tissue - Excess skin tissue obtained during a planned skin tissue biopsy and with a companion blood sample. A minimum sample of a a single 3 mm punch biopsy is required and up to 3 punch biopsies will be allowed. Up to 10 patients will be recruited into this group. B. Scleroderma Group B: Research Skin Biopsy - Patients that agree to a research skin tissue biopsy, not otherwise clinically indicated and obtained at any one point in time, and with a companion blood sample. For skin biopsies, a minimum sample of a single 3 mm punch biopsy is required and up to 3 punch biopsies will be allowed. Up to 10 patients will be recruited into this group. Interventions: Companion blood samples with skin biopsy

: Systemic Sclerosis with pulmonary involvement

Patients would consent to have excess materials from their bronchoscopy, bronchoalveolar lavage fluid or thoracoscopy done for standard of care purposes. Patients should not undergo these procedures unless required for standard clinical care. There is no minimum tissue requirement for this cohort. Up to 10 patients will be recruited into this group. Interventions: Companion blood samples with biopsy

: Other Autoimmune Disease such as psoriasis, vitiligo, type 1 diabetes and others

A. Other Autoimmune Group A: Excess Biologic Material - Excess material sourced from a part of the body exhibiting clinical symptoms of autoimmune disease +/- nearby normal biologic materials, and with a companion blood sample. While there is no minimum tissue requirement for this cohort, tissue requirements from other autoimmune diseases described above may be used to guide tissue collection sample amounts. B. Other Autoimmune Group B: Research Biologic Material - Research skin tissue biopsy, other tissue biopsy or biologic materials collected from an affected part of the body +/- normal healthy biologic materials, and with a companion blood sample. In the instance of a skin biopsy, a minimum of a single 3 mm punch biopsies, and up to three, 3 mm punch biopsies, will be obtained.

: Evolving autoimmune disease

Serial sampling of excess materials, with companion blood samples, can be obtained at intervals consistent with excess materials collected for clinical care.

: Previously cryopreserved, dissociated tissue obtained from a biobank or tissue repository

These samples will have been collected from patients with autoimmune diseases, at any one time point after diagnosis and with a companion blood sample.

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.

Contact a Trial Team

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Arizona Arthritis & Rheumatology, PLLC, Phoenix, Arizona

Status

Recruiting

Address

Arizona Arthritis & Rheumatology, PLLC

Phoenix, Arizona, 85032

Site Contact

Hani Rashid, DO

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