Canakinumab Clinical Trials

What Is Canakinumab?

Canakinumab is an FDA-approved medication for familial Mediterranean fever, systemic onset juvenile idiopathic arthritis, TNF-receptor associated periodic fever syndrome, and cryopyrin-associated periodic syndromes (CAPS), which include Familial Cold Autoinflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS), and Neonatal Onset Multisystem Inflammatory Disease (NOMID).

Canakinumab is a high-affinity human monoclonal antibody that targets and blocks interleukin-1 beta (IL-1β). IL-1β is a protein in the body that plays a key role in inflammation. By binding to and neutralizing IL-1β, canakinumab helps to reduce inflammation in various IL-1β driven inflammatory diseases.

Beyond its approved uses, canakinumab is also being investigated in clinical trials for conditions such as rheumatoid arthritis, non-small cell lung cancer, acute gout, myelodysplastic syndromes, Schnitzler syndrome, gouty arthritis, and type 2 diabetes mellitus.

Uses and Conditions Under Study

Canakinumab is being studied across a broad range of conditions, with a total of 85 trials involving 21,677 participants. Many of these investigations focus on inflammatory and autoimmune disorders due to canakinumab's mechanism of action in blocking IL-1β.

• Inflammatory and Autoinflammatory Diseases: Canakinumab is approved for and continues to be studied in conditions like Systemic Juvenile Idiopathic Arthritis (5 trials), Hereditary Periodic Fevers (2 trials), Schnitzler Syndrome (2 trials), and Neonatal Onset Multisystem Inflammatory Disease (2 trials). These are diseases characterized by uncontrolled inflammation, where IL-1β is believed to play a central role in driving symptoms like fever, rash, and joint pain. Rheumatoid Arthritis (4 trials), another chronic inflammatory condition affecting joints, is also under investigation.

• Gout and Gouty Arthritis: Acute Gout (3 trials) and Gouty Arthritis (2 trials) are painful inflammatory conditions caused by the buildup of uric acid crystals in the joints. IL-1β is known to be a key mediator of the inflammatory response in gout flares, suggesting canakinumab could help reduce pain and swelling.

• Cancers: Canakinumab is being explored in Non-small Cell Lung Cancer (4 trials) and Myelodysplastic Syndromes (3 trials). Inflammation can contribute to cancer development and progression, and targeting IL-1β may offer a new therapeutic approach in these malignancies.

• Metabolic Conditions: Diabetes Mellitus, Type 2 (2 trials) is also under study. Chronic low-grade inflammation, often involving IL-1β, is implicated in the development and progression of type 2 diabetes, making canakinumab a potential treatment option to improve metabolic control.

Dosing

Canakinumab has been studied in various dosage forms and administration routes, primarily as an injection. It is available as a solution for subcutaneous injection, often provided in pre-filled syringes. A lyophilizate (powder for reconstitution) has also been studied, indicating flexibility in preparation.

The recommended standard dose of canakinumab is often 150 mg administered subcutaneously. However, investigational doses vary significantly depending on the condition and patient population:

• Adult Dosing: For certain conditions, doses of 150 mg, 250 mg, or 300 mg have been administered subcutaneously. Some regimens involve injections every 28 days, every 4 weeks (q4wk), or every 2 weeks (q2wk). Higher doses, such as an initial 600 mg intravenous (IV) dose followed by 300 mg q2wk, have also been explored.

• Pediatric Dosing: In young children and for conditions like PFAPA flares or in Kawasaki patients, doses are often weight-based, such as 4 mg/kg. Specific cohort studies have investigated lower fixed doses like 2 mg or 4 mg.

• Investigational Doses and Regimens: A wide range of doses from 5 mg, 10 mg, 15 mg, 25 mg, 50 mg, 90 mg, 100 mg, and 200 mg have been studied. These include different frequencies and combinations, such as 150 mg every 3 months, or various doses of canakinumab combined with other medications like metformin, chemotherapy, or other immunotherapies.

Side Effects

In clinical trials, patients taking Canakinumab experienced certain side effects more often than those taking a placebo. These side effects were reported across multiple trials involving a total of up to 3072 patients in the Canakinumab treatment arms.

• Anemia occurred in 14.1% of patients on Canakinumab, compared to 12.0% on placebo.
• Asthenia (lack of energy or physical weakness) was reported by 11.9% of patients taking Canakinumab, versus 9.0% on placebo.
• Cough affected 11.3% of patients on Canakinumab, compared to 10.9% on placebo.
• Arthralgia (joint pain) was experienced by 10.9% of patients on Canakinumab, versus 10.3% on placebo.
• Constipation occurred in 10.6% of patients on Canakinumab, compared to 8.5% on placebo.
• Fatigue was reported by 10.2% of patients taking Canakinumab, versus 8.3% on placebo.
• Diarrhea affected 9.3% of patients on Canakinumab, compared to 8.7% on placebo.
• Upper respiratory tract infection occurred in 7.7% of patients on Canakinumab, versus 5.8% on placebo.
• Nasopharyngitis (common cold) was reported by 6.9% of patients on Canakinumab, compared to 4.1% on placebo.

Some side effects were reported less frequently in patients taking Canakinumab than in those on placebo. For example, pyrexia (fever) occurred in 10.4% of Canakinumab patients compared to 11.1% on placebo, nausea in 10.2% versus 10.5%, and headache in 7.7% versus 8.7%.

Clinical Trial Results

Rheumatoid Arthritis (RA)

In a study (NCT00424346) evaluating Canakinumab in patients with active rheumatoid arthritis, various doses were tested against a placebo. At Week 12, patients receiving Canakinumab 150 mg every four weeks showed an American College of Rheumatology (ACR) 20 response rate ranging from 23.2% to 50.0%, compared to 14.3% to 28.6% for those on placebo. Canakinumab also led to greater reductions in disease activity. For instance, the Disease Activity Score (DAS28) decreased by 0.8 to 1.5 scores with Canakinumab 150 mg every four weeks, compared to a decrease of 0.5 to 0.9 scores with placebo. High-sensitive C-Reactive Protein (hsCRP) levels, a marker of inflammation, were reduced by 3.5 to 8.0 mg/L with Canakinumab 150 mg every four weeks, while placebo resulted in smaller reductions of 0.7 to 1.7 mg/L or no change.

Another study (NCT00487825) investigated Canakinumab combined with methotrexate in early rheumatoid arthritis. At 26 weeks, 17.3% to 46.2% of participants on Canakinumab plus methotrexate achieved a good European League Against Rheumatism (EULAR) response, compared to 11.5% to 42.3% on methotrexate alone. For ACR50 response, 10 to 24 participants on combination therapy achieved this, compared to 5 to 11 participants on methotrexate alone.

Long-term data from a study (NCT00554606) of Canakinumab in rheumatoid arthritis patients showed sustained responses. Participants achieved ACR20 response rates ranging from 41.7% to 61.4%, ACR50 response rates from 23.5% to 38.8%, and ACR70 response rates from 11.3% to 26.5%.

Chronic Obstructive Pulmonary Disease (COPD)

A study (NCT00581945) in patients with COPD evaluated the effect of Canakinumab on lung function. There was no clear improvement in key lung function measures. For example, the mean change from baseline in Forced Expiratory Volume in 1 second (FEV1) ranged from -0.027 to -0.044 Liters with Canakinumab, compared to -0.006 to -0.033 Liters with placebo.

Type 2 Diabetes

In a study (NCT00605475) of patients with type 2 diabetes, Canakinumab was investigated for its effects on metabolic markers. Canakinumab infusions (across various doses) led to a mean reduction in HbA1c (a measure of average blood sugar) ranging from 0.04% to 0.59%. In comparison, placebo-treated patients showed a range from a 0.12% reduction to a 0.32% increase. Plasma glucose levels, as measured by the Area Under the Curve (AUC) during an oral glucose tolerance test, also showed mean reductions ranging from 0.5 to 4.7 mmol*h/L with Canakinumab, compared to 0.9 to 2.8 mmol*h/L with placebo. Additionally, mean plasma fructosamine levels were reduced by 2.2 to 16.6 µmol/L with Canakinumab (10 mg/kg dose), compared to 0.7 to 13.9 µmol/L with placebo.

Currently Recruiting Trials

Where to Participate

• New York, New York (2 sites)
• Houston, Texas (2 sites)
• Boston, Massachusetts (1 site)
• Columbus, Ohio (1 site)
• Dallas, Texas (1 site)
• Miami, Florida (1 site)
• Nashville, Tennessee (1 site)

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