AlloNK

Summary

Rheumatoid arthritis (RA) is a chronic condition in which the body’s immune system mistakenly attacks the lining of healthy joints. RA is one of the most common autoimmune diseases, affecting nearly 1.3 million people in the U.S. RA leads to pain, redness, swelling, and stiffness—particularly in the hands, wrists, or feet. Numerous selfcare practices, conventional medications (for example, glucocorticoids, methotrexate), and biologics (such as monoclonal antibodies [like rituximab]) are available that decrease symptoms and help prevent permanent joint damage due to RA.

However, as many as 21% of cases of RA still do not respond well to available therapies (refractory RA). New agents and treatment combinations for refractory RA are urgently needed. One novel strategy involves using the immune cells known as natural killer (NK) cells. NK cells are part of the body’s first line of defense. Their job is to destroy potential threats, including infected, cancerous, or other abnormal cells. Pairing targeted NK cells with a monoclonal antibody may eliminate the faulty B cells that attack normal joint linings and cause RA symptoms.

The AlloNK study investigates whether NK cells from healthy donors (alloNK cells) can be used with rituximab to decrease the abnormal B cells that cause RA. Each treatment cycle of the study includes 5 infusion days and a maximum of 27 clinic visits. Because these infusions do not require hospitalization, participants receive them in an outpatient setting. Treatment cycle 1 will take place over 4 weeks. Depending on test results at 24 weeks, treatment cycle 2 may or may not be needed. Follow-up visits occur every 3 – 4 months, beginning soon after the last treatment and continuing for about 2 years.

To be included in AlloNK, participants must be / have

• Diagnosis of RA according to standard clinical guidelines
• Prior treatment with a biologic disease-modifying anti-rheumatic drug for at least 12 weeks but deemed treatment refractory by the treating physician
• Positive for rheumatoid factor (RF) or anti citrullinated protein antibody (ACPA)
• High-sensitivity C-reactive protein (hs-CRP) > 3 mg/L or erythrocyte sedimentation rate (ESR) > 28 mm/h
• Minimum of 6 swollen joint counts (SJC) and 6 tender joint counts (TJC), according to joint assessment

To be included in AlloNK, participants must not be / have

• Cyclophosphamide within 28 days before treatment day 1
• Prednisone > 10 mg within 48 hours before treatment day 1
• Prior treatment with any B-cell depleting therapy (e.g., rituximab, obinutuzumab) within 6 months of the start of the planned lymphodepletion regimen

Keywords
AB-101; Autoimmune disease; Refractory rheumatoid arthritis; Rheumatoid arthritis