Osteoarthritis is the most common form of arthritis, affecting one in ten adults. There are currently many clinical trials for osteoarthritis of the knee. The following is a brief report of some of the latest clinical trials and most recent drugs being tested for treatment of pain associated with knee osteoarthritis.
Osteoarthritis of the knee is a condition in which there is wear and tear of the cartilage of the knee and, consequently, less cushioning in the joint. Because of this, the bones rub more closely together, resulting in pain, swelling and stiffness of the joint. The most common risk factors for osteoarthritis include: age, weight, heredity, and repetitive stress injuries.
Treatments for osteoarthritis consist of combinations of exercise, lifestyle modification, and analgesic drugs. Joint replacement surgery is also an option in advanced, debilitating stages of the disease. Although there is no cure for osteoarthritis, continued research is allowing patients to better manage the disease and associated pain, thereby improving quality of life. Summarized in this article are four of the latest drugs in clinical development for knee osteoarthritis.
A Phase 2 trial is currently underway for the oral vascular adhesion protein-1 antagonist, PRX167700. This study, assessing the safety, tolerability, and pharmacokinetics of the drug and evaluating its anti-inflammatory effects in patients with osteoarthritis of the knee, is being conducted in the UK by Proximagen.
This new anti-inflammatory drug is thought to work through regulation of immune cell migration from the blood to the sites of inflammation, thereby modulating the inflammatory process, and reducing the symptoms of inflammation. An advantage of this mechanism of action is that it has the potential to prevent any further damage to the affected area by reducing the movement of the damaging cells to the site of inflammation.
To date, PRX167700 has been effective in models of rheumatoid arthritis, multiple sclerosis, and inflammatory pain.
http://www.reuters.com/article/2012/02/29/idUS62628+29-Feb-2012+RNS20120229 Last Accessed: Dec 12, 2013.
Clinicaltrials.gov “An Exploratory Study of PRX167700 in Patients with Knee Osteoarthritis” Available from: http://clinicaltrials.gov/ct2/show/NCT01945346?term=NCT01945346&rank=1 Last Accessed: Dec 12, 2013.
SYNERA® is a prescription patch that is currently used to prevent pain associated with needle-related medical procedures. The patch is applied to the skin and numbs the area due to the medicinal ingredients: lidocaine and tetracaine. In addition, the patch contains a heating pod that warms the area to allow greater penetration of the medicine.
Currently SYNERA® is being assessed in a Phase 2 trial at Northwestern University, Chicago, Illinois, for its pain-relieving effects in exercise induced knee pain in patients with osteoarthritis of the knee. The premise is that several topical non-steroidal anti-inflammatory drugs have been shown to reduce pain in knee osteoarthritis, suggesting that SYNERA® may be a useful and effective approach to treatment.
http://www.synera.com Last Accessed: Dec 13, 2013.
http://www.nuvoresearch.com/ Last Accessed: Dec 13, 2013.
Clinicaltrials.gov “Efficacy and Safety of Synera in Osteoarthritis Pain” Available from: http://clinicaltrials.gov/ct2/show/NCT01654302?term=NCT01654302&rank=1 Last Accessed: Dec 13, 2013.
Cebranopadol is an oral small molecule analgesic, currently in Phase II clinical trials across Europe and the USA, for the treatment of pain associated with knee osteoarthritis. It was discovered by scientists in Germany, at the pharmaceutical company Grünenthal, and is currently in development internationally by Grünenthal and its partner, Forest Laboratories Inc., based in the USA. Current trials will assess the safety, tolerability, and effectiveness of Cebranopadol in reducing pain in patients with moderate to severe painful osteoarthritis.
Cebranopadol works by activation of both the ORL-1 receptor and the mu opioid receptor. This differs from currently available medications such as morphine and oxycodone, which only activate the mu opioid receptor. Because of this dual activation, the compound may have an additive effect on pain reduction and less side-effects associated with treatment.
http://www.grunenthal.net/grt-oceanic/265600020.jsp Last Accessed: December 11, 2013.
http://www.frx.com/assets/pdf/FRX_Corporate_Fact_Sheet.pdf Last Accessed: December 11, 2013.
http://www.biotechnologyevents.com/node/4160 Last Accessed: December 11, 2013.
Clinicaltrials.gov “Safety and Efficacy Study of GRT6005 in Patients with Osteoarthritis Knee Pain.” Available from http://clinicaltrials.gov/ct2/show/NCT01709214?term=GRT6005&rank=3 Last Accessed: December 11, 2013.
Clinicaltrials.gov “Assessment of GRT6005 in Painful Osteoarthritis of the Knee.” Available from: http://clinicaltrials.gov/ct2/show/NCT01357837?term=GRT6005&rank=1 Last Accessed: December 11, 2013.
AF-219 is a small molecule P2X3 antagonist currently under investigation by Afferent Pharmaceuticals of San Mateo, California, USA. P2X3 is an ion channel located in neurons that are a part of the pain sensing system in the body. AF-219 blocks activation of these neurons containing the P2X3 receptors. Due to the selective expression of P2X3, there is less of a chance that AF-219 will have other adverse effects in the brain, gastrointestinal, or cardiovascular tissues. This gives AF-219 an advantage over currently available therapies that have dose-limiting side-effects.
Scientific studies have implicated P2X3 receptor-mediated activation in several pain states including: inflammatory, visceral, neuropathic pain, migraine, and cancer pain. However, Afferent Pharmaceuticals are currently conducting proof of concept studies in patients to confirm these scientific findings and determine their clinical relevance. AF-210 is currently in Phase 2 studies in 34 locations across the United States for assessment of efficacy, safety, and tolerability in patients with moderate to severe pain associated with knee osteoarthritis.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265711/ Last Accessed: Dec 13, 2013.
Clinicaltrials.gov “A Four-Week Multicenter Study Evaluating the Safety and Efficacy of AF-219 in Subjects with Osteoarthritis of the Knee” Available from: http://clinicaltrials.gov/ct2/show/study/NCT01554579?term=NCT+01554579&rank=1#locn Last Accessed: Dec 13, 2013.
Written by Deborah Tallarigo, PhD