Clinical trial NCT06587828: A Biospecimen Collection Study to Identify the Targets of Disease-Reactive T Cells in Patients with Autoimmune Disease
Official title: A Biospecimen Collection Study to Identify the Targets of Disease-Reactive T Cells in Patients with Autoimmune Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Autoimmune Diseases
Ulcerative Colitis
Multiple Sclerosis
Scleroderma
Ankylosing Spondylitis
Celiac Disease
Non-radiographic Axial Spondyloarthritis (nr-axSpA)
Crohn&amp;#39;s Disease
Birdshot Chorioretinitis
Keywords: Autoimmune Diseases
Multiple Sclerosis
Systemic Sclerosis
Ankylosing Spondylitis
Scleroderma
Inflammatory Bowel Disease
Crohn&amp;#39;s Disease
Non-radiographic axial spondyloarthritis (nr-axSpA)
Birdshot Chorioretinitis
Lead sponsor: TScan Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2024-09-19
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with a known or suspected autoimmune disease will be enrolled into the study. Additionally, patients who have an apparent evolving autoimmune disease may be eligible.

Patients with autoimmune disease who had excess materials cryopreserved in a manner that is expected to yield sufficient T cells for this research study, and where biologic samples were ethically obtained, will be utilized for this study.

Both men and women and members of all races and ethnic groups are eligible for this protocol. It is expected that the mix of patients entering this study will reflect the demographics of the clinic population seen in hospitals and associated clinics in the region from which the biologic materials are collected.

Brief summary: 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.


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.

Primary outcomes:
measure: Identify peptide targets together with their associated TCRs in patients with autoimmune diseases under study.
timeFrame: 3 Years
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Arthritis & Rheumatology, PLLC
state: Arizona
city: Murrieta
country: United States
facility: Inland Empire Gastroenterology
state: California
city: Orange
country: United States
facility: Knowledge Research Center
state: California
city: Sherman Oaks
country: United States
facility: Cura Clinical Research
state: California
city: Port Charlotte
country: United States
facility: Neurostudies, LLC
state: Florida
city: Muncie
country: United States
facility: Rheumatology of Central Indiana
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky Research Foundation
state: Kentucky
city: Rochester
country: United States
facility: Gastroenterology Group of Rochester
state: New York
city: Mentor
country: United States
facility: Great Lakes Gastroenterology Research, LLC
state: Ohio
city: Oklahoma City
country: United States
facility: Digestive Disease Specialists, Inc
state: Oklahoma
city: Harrisburg
country: United States
facility: Susquehanna Research Group
state: Pennsylvania
city: Cranston
country: United States
facility: Nexus Research
state: Rhode Island
city: Cranston
country: United States
facility: Nexus Research
state: Rhode Island
city: Cranston
country: United States
facility: Nexus Research
state: Rhode Island
city: Cranston
country: United States
facility: Nexus Research
state: Rhode Island
city: Cranston
country: United States
facility: Nexus Research
state: Rhode Island
city: Providence
country: United States
facility: University Gastroenterology
state: Rhode Island
city: Summerville
country: United States
facility: Palmetto Gastroenterology Clinical Research, LLC
state: South Carolina
city: Union City
country: United States
facility: Advanced Gastroenterology
state: Tennessee
city: Bellaire
country: United States
facility: Novel Research
state: Texas
city: Chesterfield
country: United States
facility: GI Research Partners, LLC
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
References: