Phase 2a trial of natural killer T-cell therapy in IPF starts enrolling

The oral capsule GRI-0621 was developed to suppress iNKT cells' activity

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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A Phase 2a trial is recruiting people with idiopathic pulmonary fibrosis (IPF) to assess the effectiveness of GRI-0621, GRI Bio‘s investigational natural killer T-cell (NKT)-targeted therapy.

The multicenter biomarker study, which was cleared to start by the U.S. Food and Drug Administration, is expected to have early results in the first part of the new year and top-line results later next year.

“The start of enrollment marks another important step forward for GRI as we continue to execute our clinical development plans for our lead program, GRI-0621. We are pleased to meet this significant milestone and remain focused on the successful execution of this Phase 2a study,” Marc Hertz, PhD, CEO of GRI Bio, said in a company press release. “With the progress made to date and the start of patient dosing expected imminently, we are poised for an exciting 2024 and look forward to unlocking the potential of GRI-0621 for the treatment of fibrotic indications, starting with IPF.”

In IPF, scar tissue (fibrosis) accumulates in the lungs due to an unknown cause. leading to symptoms such as shortness of breath and cough.

NKT immune cells are part of the body’s first line of defense against potential threats. Research is implicating the cells in IPF, especially a subset called type 1 invariant NKT (iNKT) cells, which have been reported to initiate a series of cellular processes that drive inflammation and fibrosis in IPF.

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What will Phase 2a trial of GRI-0621 test?

GRI-0621 is a small molecule that’s aimed at suppressing the activity of iNKT cells. It’s delivered as a once daily oral capsule.

The Phase 2a trial will have about 36 IPF patients, who will be randomly assigned to GRI-0621 (4.5 mg) or a placebo in a 2:1 ratio, that is, twice the number of patients will receive GRI-0621. Treatment will last 12 weeks, about three months.

The primary goal is to determine oral GRI-0621’s safety and tolerability, as assessed by whether side effects occur, along with lab tests and the impact on vital signs at the end of treatment.

Secondary measures include changes in blood biomarkers and pharmacodynamics (the effects of a drug on the body). These assessments will be made at six and 12 weeks and compared to the study’s start. The pharmacodynamics will specifically address the efficacy of GRI-0621 in inhibiting iNKT cell activation. The therapy’s pharmacokinetics —  its movement into, through, and out of the body — will be assessed at the end of the study.

An interim analysis will be made when the first 24 participants, including around eight on a placebo, have completed six weeks. An exploratory analysis will focus on changes in lung function after six and 12 weeks of treatment. A substudy of up to 12 patients will also evaluate the number and activity of NKT cells in lung fluid.

According to GRI Bio, data from preclinical models and a Phase 2a trial (NCT02949375) of GRI-0621 in people with chronic fibrotic liver disease showed it eased fibrosis in animals and inhibited iNKT cells in patients.

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