Breakthrough Gene Therapy for Rheumatoid Arthritis Enters Phase 1 Trial

Arthrogen’s Recruitment for Rheumatoid Arthritis Drug ART-I02

Overview of Arthrogen’s Initiative

Arthrogen, a biopharmaceutical company focused on gene therapy, is currently seeking participants with rheumatoid arthritis to participate in clinical trials for a new medication, ART-I02.

Mrs. Johnson’s Daily Life with Rheumatoid Arthritis

Mrs. Johnson, a 40-year-old mother of three, lives with rheumatoid arthritis. To accommodate her condition, she opts for clothing without buttons, primarily wearing pants with elastic waistbands, thus avoiding zippers. She also relies on electric toothbrushes for dental hygiene, as her condition makes manual brushing challenging. When preparing peanut butter and jelly sandwiches for her children, she loosens the lids to facilitate easier opening the next day. This scenario, while hypothetical in the accompanying image, resonates with many individuals living with rheumatoid arthritis.

The Impact of Rheumatoid Arthritis

Rheumatoid arthritis is a chronic inflammatory condition that affects over 4.6 million Canadians, with a higher prevalence among women. In 2010, Ontario recorded approximately 97,500 cases, and this number is expected to rise. The disease causes symptoms such as swollen, stiff, and painful joints, often accompanied by warmth, redness, deformity, and diminished mobility. Although the precise cause remains unidentified, experts suggest that genetic, environmental, and hormonal factors contribute to its development.

Current Treatment Options

Doctors typically prescribe a range of medications for rheumatoid arthritis, including disease-modifying anti-rheumatic drugs (DMARDs), non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, and corticosteroids. Early intervention with DMARDs is now standard practice, as they can slow disease progression and promote remission. However, newer DMARD therapies may increase the risk of infections due to their immunosuppressive effects.

Aiming for Clinical Remission

Achieving clinical remission, defined as the absence of significant inflammatory activity, remains the primary goal of treatment. Current therapies focus on reducing joint inflammation and pain by targeting cytokines and immune cells involved in joint damage. Recent advances in biologic drug treatments have led to improved outcomes for many patients, though drug-free remission remains uncommon, necessitating ongoing immunosuppressive treatments and posing risks of serious infections.

The Need for Improved Therapies

Approximately 50% of rheumatoid arthritis patients continue to experience symptoms despite treatment. In such cases, doctors often resort to injecting glucocorticoids into inflamed joints, although this approach varies in effectiveness. Amgen, a biopharmaceutical company, acknowledges the demand for additional therapies that offer good tolerability and efficacy. They propose that intra-articular gene therapy may provide localized treatment for patients still experiencing joint inflammation.

Intra-Articular Gene Therapy with ART-I02

Introduction to ART-I02

ART-I02 is an investigational gene therapy developed by Amgen. It aims to express interferon-beta (IFN-β), a protein known to reduce the production of other proteins involved in the progression of rheumatoid arthritis. Preclinical studies have shown promising results with a single injection of IFN-β in animal models.

Phase I Clinical Trial Recruitment

Currently, researchers are recruiting participants for a Phase I clinical trial to assess the safety and tolerability of ART-I02. Sponsored by Amgen and led by Dr. William O. Martin at the University of Calgary, this non-randomized, open-label trial aims to enroll 15 individuals with rheumatoid arthritis affecting their wrists.

Trial Design and Participant Grouping

The study will utilize a dose escalation design, dividing participants into three groups according to the dosage received: the lowest dose, the highest dose, and the maximum tolerated dose based on prior assessments. Initially, three individuals will receive the lowest dose and three the highest, with a minimum two-week interval between patient dosing to monitor safety. A two-week pause will follow the dosing of the first two groups to ensure thorough safety evaluations before enrolling participants in the third group at the maximum tolerated dose. The trial commenced on January 3, 2018, with an expected completion date in January 2020.

References

(1) ART-I02 in Patients With Rheumatoid Arthritis With Inflamed Wrists [Internet]. Clinicaltrials.gov. 2018 [cited 1 May 2018]. Available from: https://clinicaltrials.gov/ct2/show/record/NCT03445715?recrs=a&cntry=CA&draw=6&view=record
(2) Aalbers C, Bevaart L, Loiler S, de Cortie K, Wright J, Mingozzi F et al. Preclinical Potency and Biodistribution Studies of an AAV 5 Vector Expressing Human Interferon-β (ART-I02) for Local Treatment of Patients with Rheumatoid Arthritis. PLOS ONE. 2015;10(6):e0130612.
(3) Rheumatoid Arthritis: Practice Essentials, Background, Pathophysiology [Internet]. Medscape. 2018 [cited 1 May 2018]. Available from: https://emedicine.medscape.com/article/331715-overview#a2
(4) Evans C, Ghivizzani S, Robbins P. Gene Delivery to Joints by Intra-Articular Injection. Human Gene Therapy. 2018;29(1):2-14.
(5) Rheumatoid Arthritis | UCB [Internet]. UCB-Canada. 2018 [cited 1 May 2018]. Available from: https://www.ucb-canada.ca/en/Patients/Conditions/Rheumatoid-Arthritis
(6) Widdifield J, Paterson J, Bernatsky S, Tu K, Tomlinson G, Kuriya B et al. The Epidemiology of Rheumatoid Arthritis in Ontario, Canada. Arthritis & Rheumatology. 2014;66(4):786-793.
(7) Scott D, Wolfe F, Huizinga T. Rheumatoid arthritis. The Lancet. 2010;376(9746):1094-1108.