Phase 1 trial of CAR T-cell therapy likely to open soon to SSc patients

Safety study testing ADI-001 in adults with various autoimmune diseases
by Margarida Maia, PhD | March 18, 2025

Adicet Bio expects adults with systemic sclerosis (SSc) soon to start enrolling in its ongoing Phase 1 clinical trial of ADI-001, an experimental CAR T-cell therapy that the company is developing for a number of autoimmune diseases.

The company had expected sites to open to SSc patients before the end of last year, and now anticipates recruitment to be underway by the close of June. The open-label Phase 1 clinical trial (NCT06375993) currently is continuing to enroll adults with lupus nephritis, a common complication of the autoimmune disease lupus.

Depending on the speed with which people with SSc are enrolled, preliminary data on treated patients might be available toward the close of 2025.

ADI-001 targets B-cells, aiming to prevent damaging immune system attacks
ADI-001 recently received fast track status in the U.S. for treating adults with SSc, which works to speed the development and review of therapies for serious diseases with an unmet need.

This designation “highlights the significant unmet need for innovative, off-the-shelf therapies to treat autoimmune diseases,” Chen Schor, president and CEO of Adicet Bio, said in a company press release reporting on last year’s financial results and recent progress.

Systemic sclerosis, also called systemic scleroderma, is a multisystem autoimmune disease marked by the accumulation of scar tissue in the skin and organs that can include the heart, kidneys, lungs, and digestive tract.

Autoimmune diseases like SSc occur when the immune system produces antibodies that mistakenly react against healthy tissues in the body, guiding a damaging immune attack. Antibodies, including self-reactive ones, are produced by immune B-cells.

ADI-001 involves collecting a patient’s immune T-cells and modifying them in the lab before returning them via an infusion. T-cells are modified such that they produce a chimeric antigen receptor, or CAR, that binds to CD20, a protein found on the surface of B-cells.

Most of the T-cells present in ADI-001 are of a subtype called gamma delta T-cells, which naturally target various tissues, according to the company. Once CAR T-cells bind to CD20, they are activated to destroy B-cells, as reported in early clinical data from people with B-cell cancers, another indication for which the therapy is being developed.
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By killing B-cells, ADI-001 is expected to reduce the production of self-reactive antibodies, easing symptoms in people with autoimmune diseases.

Trial goals include treatment safety, changes in self-reactive antibody levels
Adults, ages 18 to 80, living with diffuse or limited SSc for up to six years will be invited to enter the Phase 1 trial, which expects to enroll up to 180 people across its various conditions. Diffuse SSc typically causes thickened skin over larger areas of the body and can affect multiple internal organs. It’s usually more severe than limited SSc, the disease’s other subtype.

After screening, participants will be given a chemotherapy mix of fludarabine and cyclophosphamide to deplete their T-cells and make room for the modified ones, which are infused into the bloodstream as a single dose. Chemotherapy also allows CAR T-cells to expand better.

Initially, the study will test single increasing doses of ADI-001 to find the safest dose level. Once a dose is considered safe, more patients will be treated at that dose level to confirm its safety profile. These data are needed to establish a recommended dose for future Phase 2 clinical testing.

The trial’s main goal is to assess ADI-001’s safety and tolerability over 28 days, the window for dose-limiting toxicity, with checks continuing up to two years. Secondary goals include looking at ADI-001’s pharmacodynamics or effects in the body, and on the levels of self-reactive antibodies. Changes in disease activity scores also will be evaluated.

In addition to SSc and lupus nephritis patients, the trial will include people with ANCA-associated vasculitis, idiopathic inflammatory myopathy, and stiff-person syndrome.
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“We are continuing to enroll [lupus nephritis] patients in our ongoing Phase 1 trial in autoimmune diseases and look forward to sharing preliminary clinical data in the first half of 2025 and additional data in the second half of 2025,” Schor said.