Tocilizumab Clinical Trials

What Is Tocilizumab?

Tocilizumab is an FDA-approved medication for rheumatoid arthritis (RA). It is also known by the brand name Actemra. This drug is a humanized monoclonal antibody that targets the interleukin-6 (IL-6) receptor. IL-6 is a signaling protein (cytokine) that plays a key role in inflammation and immune responses in the body. By blocking the IL-6 receptor, tocilizumab helps to reduce inflammation and modulate the immune system.

While approved for rheumatoid arthritis, tocilizumab is also being investigated in clinical trials for a wide range of other conditions. These include other autoimmune and inflammatory disorders, various cancers, and infectious diseases such as COVID-19.

Uses and Conditions Under Study

Tocilizumab is being studied across a broad spectrum of conditions, primarily focusing on its role in modulating the immune system and reducing inflammation:

• Autoimmune and Inflammatory Conditions: Tocilizumab is extensively studied for conditions where the immune system mistakenly attacks the body's own tissues. It is approved for Rheumatoid Arthritis, with 149 trials investigating its use. Other conditions include Juvenile Idiopathic Arthritis (15 trials), Giant Cell Arteritis (14 trials), and Polymyalgia Rheumatica, which are all characterized by chronic inflammation. It is also being explored for rare autoimmune conditions like Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD), which affect the central nervous system. Schnitzler's Syndrome, an autoinflammatory disease causing chronic urticaria and monoclonal gammopathy, is also under investigation.
• Infectious Diseases: Due to its anti-inflammatory properties, tocilizumab has been investigated for severe immune responses in infections. There are 31 trials related to COVID-19 and COVID-19 Pneumonia, where it aims to mitigate the uncontrolled immune response (cytokine storm) that can lead to lung damage and severe illness.
• Cancers: Tocilizumab is being studied in several types of cancer, often in combination with other therapies. There are 11 trials for Multiple Myeloma and 6 trials for Lymphoma. It is also being investigated for Richter's Transformation (a complication of chronic lymphocytic leukemia), Adamantinomatous Craniopharyngioma (a pediatric brain tumor), and Hepatocellular Carcinoma (HCC). In these contexts, it may help manage inflammation or immune-related side effects of cancer treatments.
• Transplant and Other Conditions: Tocilizumab is also being explored for use in kidney transplant patients to prevent organ rejection and in conditions like Graft-versus-host disease (GvHD). Additionally, its potential role in managing inflammation in conditions such as schizophrenia and Thyroid Associated Ophthalmopathy (TAO) is under investigation.

Dosing

Tocilizumab has been studied in various dosage forms and administration routes, including subcutaneous (SC) injection and intravenous (IV) infusion. The specific dose and frequency depend on the condition being treated and the patient's weight.

Commonly studied adult doses include:

• 162 mg administered as a single subcutaneous injection, sometimes weekly or every two to three weeks.
• 4 mg/kg or 8 mg/kg given as an intravenous infusion, typically every four weeks.
• Some trials have explored doses like 280 mg, 40 mg, 120 mg, or 400 mg.

For pediatric patients or those weighing less than 30 kg, weight-based dosing is often used. For example, doses of 10 mg/kg/day or 8 mg/kg have been studied, with administration sometimes divided into multiple daily doses (e.g., every 6 hours) or as a single infusion. The maximum daily dose in some investigational settings has been 400 mg/day. Tocilizumab has also been studied as a prefilled syringe for subcutaneous administration.

Side Effects

The most common side effect reported in clinical trials for Tocilizumab was upper respiratory tract infection. In studies involving over 4,000 patients, 15.8% of patients taking Tocilizumab experienced an upper respiratory tract infection, compared to 11.9% on placebo. Other common side effects, presented in order of frequency, include:

• Nasopharyngitis (common cold symptoms): 11.7% of patients on Tocilizumab experienced this, compared to 11.0% on placebo.
• Increased alanine aminotransferase (a liver enzyme): 8.7% on Tocilizumab versus 6.5% on placebo.
• Urinary tract infection: 8.5% on Tocilizumab versus 5.0% on placebo.
• Bronchitis: 8.1% on Tocilizumab versus 4.0% on placebo.
• Sinusitis: 7.9% on Tocilizumab versus 3.5% on placebo.
• Hypertension (high blood pressure): 7.5% on Tocilizumab versus 5.0% on placebo.

Headache was reported by 8.2% of patients on Tocilizumab compared to 7.7% on placebo, and diarrhea by 7.3% on Tocilizumab compared to 6.0% on placebo.

Clinical Trial Results

Rheumatoid Arthritis (RA)

In a study (NCT00106535) of patients with moderate to severe active RA, Tocilizumab combined with methotrexate showed significant improvements in disease activity and joint damage prevention over 104 weeks compared to placebo plus methotrexate.

• At 52 weeks, 55.8% of patients receiving 8 mg/kg of Tocilizumab achieved an ACR20 response (a 20% improvement in RA symptoms), compared to 24.7% on placebo. For a 50% improvement (ACR50), 36.4% on 8 mg/kg Tocilizumab responded versus 10.2% on placebo.
• Tocilizumab also slowed the progression of joint damage. At 52 weeks, the Modified Total Sharp-Genant Score, which measures joint erosion and narrowing, increased by 0.29 units in the 8 mg/kg Tocilizumab group, compared to an increase of 1.13 units in the placebo group.
• Patients on Tocilizumab experienced faster relief, with a median time to ACR20 response of 57 days for both Tocilizumab doses, compared to 116 days for placebo.

Another study (NCT00531817) further supported these findings. At 24 weeks, patients treated with 8 mg/kg of Tocilizumab plus DMARDs experienced a mean reduction of 2.63 units in their DAS28 score, indicating a greater decrease in disease activity compared to a 0.97 unit reduction in the placebo plus DMARDs group. Additionally, 30.1% of patients on Tocilizumab achieved an ACR50 response at 24 weeks, versus 11.2% on placebo.

However, a study (NCT00535782) investigating the effect of Tocilizumab on markers of atherogenic risk in RA patients showed mixed results. At 24 weeks, patients on Tocilizumab plus methotrexate had a slight increase of 0.01 meters/second in aortic pulse wave velocity (a measure of arterial stiffness), while the placebo group showed a decrease of 0.20 meters/second. Small low-density lipoprotein (sLDL) particle numbers also showed a slight increase of 39.03 nmol/L in the Tocilizumab group compared to 32.41 nmol/L in the placebo group.

In a long-term extension study (NCT00720798), patients who continued Tocilizumab treatment for up to 264 weeks (over 5 years) maintained significant improvements. The average DAS28 score decreased by 2.82 units from baseline. At 264 weeks, 41.2% of patients maintained an ACR20 response, and 59.5% reported a clinically relevant improvement in fatigue scores.

Systemic Juvenile Idiopathic Arthritis (sJIA)

In a study (NCT00642460) for active sJIA, Tocilizumab demonstrated substantial improvements in children. At 12 weeks, 85.3% of patients on Tocilizumab achieved a JIA ACR30 response (a 30% improvement in sJIA symptoms), compared to 24.3% on placebo. Furthermore, 85.4% of patients with fever at baseline were free of fever at Week 12 with Tocilizumab, versus 20.8% on placebo.

Tocilizumab also allowed for significant corticosteroid reduction. At 12 weeks, 24.3% of Tocilizumab-treated patients reduced their concomitant corticosteroid dose, compared to 3.2% on placebo. In the long-term extension of this study, 60% of participants were able to discontinue oral corticosteroids by Week 104.

Currently Recruiting Trials

Researchers are actively studying Tocilizumab, an interleukin-6 receptor inhibitor, across a wide range of conditions. These ongoing clinical trials aim to understand its safety and effectiveness for various diseases, offering potential new treatment options for patients.

• A Phase 3 study, NCT07509645, is investigating the efficacy and safety of Tocilizumab when combined with endovascular treatment for patients experiencing acute posterior circulation large vessel occlusion stroke. This randomized, double-blind, placebo-controlled trial plans to enroll 348 participants.
• For adults with Major Depressive Disorder and signs of peripheral immune activation, a Phase 2 study (NCT07493317) is assessing the feasibility and safety of subcutaneous Tocilizumab. This trial aims to recruit 60 adults.
• A Phase 1 study, NCT06863480, is evaluating the safety of Tocilizumab-aazg (TYENNE) in patients with a burst brain aneurysm, also exploring its potential to prevent strokes. This study is enrolling 30 participants.
• In pediatric and adolescent patients with active systemic juvenile idiopathic arthritis, a Phase 3 study (NCT05609630) is comparing oral Upadacitinib with subcutaneous/intravenous Tocilizumab. This trial seeks to enroll 90 participants.
• Patients with well-controlled Giant Cell Arteritis who have received at least 12 months of high-dose Tocilizumab are invited to join a Phase 2 study (NCT07108387). This trial will assess the efficacy and safety of either continuing Tocilizumab with step-down dosing or withdrawing the medication, involving 78 patients.
• A Phase 3 trial, NCT06297096, is examining the efficacy and safety of combining Nintedanib and Tocilizumab for patients with systemic sclerosis and interstitial lung disease. This study will compare the combination therapy to standard treatment over 56 weeks, with an enrollment target of 86 participants.
• For patients undergoing lung transplantation, a Phase 2 study (NCT06033196) is randomizing 350 primary lung transplant recipients to receive either Tocilizumab or a placebo in addition to standard immunosuppression.

Where to Participate

Clinical trials involving Tocilizumab are globally accessible, with study sites spanning a wide geographic area. Currently, there are 240 sites across 104 cities in 39 states actively recruiting participants. The eligibility criteria for these studies are broad, welcoming individuals aged 0 to 100 years, of all genders. Many trials also include options for healthy volunteers and children, depending on the specific research question. Top recruiting locations in the United States include:

• New York, New York (14 sites)
• Boston, Massachusetts (11 sites)
• Chicago, Illinois (9 sites)
• Houston, Texas (9 sites)
• Nashville, Tennessee (7 sites)
• Philadelphia, Pennsylvania (7 sites)
• Columbus, Ohio (7 sites)
• Aurora, Colorado (6 sites)
• Atlanta, Georgia (6 sites)
• Pittsburgh, Pennsylvania (6 sites)

Development Timeline

The journey of Tocilizumab in clinical research began on March 28, 2005, with initial investigations into conditions like IBS-C and hyperphosphatemia. Since then, the research pipeline has expanded significantly, with the latest trial projected to conclude in 2026. To date, a total of 466 trials have been conducted or are ongoing, involving over 282,041 participants across various phases of development. The primary driver of this extensive research has been Hoffmann-La Roche, sponsoring 167 trials, alongside other key institutions and pharmaceutical companies.

Development has progressed through all phases, with 130 Phase 3 trials demonstrating a strong commitment to late-stage efficacy and safety evaluations. The scope of conditions studied has broadened dramatically, moving from initial gastrointestinal and metabolic indications to a wide array of inflammatory and autoimmune diseases such as Juvenile Idiopathic Arthritis, Giant Cell Arteritis, and Systemic Sclerosis. Tocilizumab has also been explored in various cancers, including Multiple Myeloma and Lymphoma, and notably played a role in the global response to the COVID-19 pandemic, with studies investigating its use in COVID-19 pneumonia and related cytokine release syndrome. This extensive research history reflects a continuous effort to explore the therapeutic potential of Tocilizumab across diverse medical needs.