Clinical trial explores biologic treatment for CVID lung condition

A potentially life-threatening lung condition associated with common variable immunodeficiency (CVID) is the focus of a clinical trial to determine if a biologic medication already approved for other uses will benefit patients.

Sponsored by the Cincinnati Children’s Hospital Medical Center, the trial is enrolling CVID patients with granulomatous lymphocytic interstitial lung disease (GLILD), a non-infectious lung condition. Granulomas, or small masses of white blood cells, form in the lungs of patients with GLILD, causing long-term lung damage and impaired respiratory function. Between 10-20% of patients with CVID develop GLILD, which reduces life expectancy in adults by more than 50% after diagnosis.

GlILD is an autoimmune complication. Autoimmunity occurs when the patient’s own cells attack the body. In the case of GLILD, overactive T cells cause inflammation and granulomas, leading to lung damage and, in some cases, enlarged spleen and lymph nodes.

Researchers are exploring whether a drug called abatacept will reduce granulomas in the lungs caused by GLILD. Abatacept works by reducing the overactivation of T cells. Abatacept is a biologic medicine derived from two human proteins and is administered through infusion either subcutaneously or intravenously.

Known by the trade name Orencia, it is already approved for use in patients with rheumatoid arthritis to relieve swelling, pain, and stiffness caused by overactive T cells in that condition. Providers prescribe abatacept for GLILD, but it’s considered an “off-label” use by the Food and Drug Administration (FDA), meaning it’s an approved drug used for an unapproved purpose.

Standard of care therapy for CVID patients with GLILD is lacking. The first line of defense is immunoglobulin (Ig) replacement therapy to prevent GLILD and infections. However, for reasons unknown, some CVID patients develop GLILD even while on Ig therapy. Providers typically start treatment with steroids, but that treatment can be ineffective. Other treatments include various biologic medicines designed to reduce inflammation. Bone marrow transplant (BMT) is another treatment option but has risks such as graft versus host disease.

Frequently, patients don’t have symptoms when GLILD starts, so screening CVID patients with periodic CT scans is recommended. If patients do present with symptoms, it might be cough or shortness of breath.

The Cincinnati Children’s Hospital Medical Center clinical trial for abatacept is a multi-site phase 2 study enrolling 38 patients at the Cincinnati Children’s Hospital Medical Center, the University of California, San Francisco, the Mayo Clinic in Rochester, Minn., and Duke University Health System in Durham, N.C.

The study accepts children age 4 and above and adults. Patients must be on Ig replacement therapy for at least six months, have GLILD diagnosed by lung biopsy, and persisting or worsening disease as shown on CT scan. Some study participants will receive the abatacept and others a placebo during the 26-week study.

The study's primary goal is to achieve a 30% or greater reduction in granulomas in a volume of lung tissue after six months. Researchers also aim to improve lung function and quality of life and reduce steroid use while avoiding new infections.

If approved, abatacept would be administered regularly as a therapeutic instead of a one-time treatment.

Join IDF on Thursday, Oct. 19 at 7 p.m. ET for an IDF webinar, "PI & Lung Health," featuring Patricia Lugar, MD, MS, who will explore how primary immunodeficiency impacts overall lung health. She also will provide an update on the ongoing clinical trial studying abatacept for the treatment of CVID with interstitial lung disease. Lugar will highlight the study's goals and how interested parties may participate. Registration is required.