CRPS Patients Needed for Clinical Study

By Pat Anson, Editor

About 80,000 Americans each year are diagnosed with Complex Regional Pain Syndrome (CRPS), a poorly understood condition caused by injury or trauma that leads to throbbing and burning pain that never goes away. It often takes years and multiple doctors before a patient is diagnosed with CRPS – and by then the pain has often migrated to other parts of the body and has become chronic.

That’s the dilemma now faced by Axsome Therapeutics (NASDAQ: AXSM), a biopharmaceutical research company that hopes to win FDA approval for an experimental, non-opioid drug that would be the first medication of any kind approved for treating CRPS --- also known as Reflex Sympathetic Dystrophy (RSD).

Axsome is conducting a Phase 3 clinical study of the drug --- called AXS-02 --- in the United States, Canada, the United Kingdom and Australia.

The challenge? Although Axsome only needs about 190 patients for the CREATE-1 study, it’s having trouble finding enough eligible patients. They’re looking for patients who suffered their initial injury in the last year and who were diagnosed with CRPS in the last six months.

“We’re trying to find patients very early in the stages of CRPS,” says Randall Kaye, MD, chief medical officer of Axsome.  

It typically takes a year or more for a patient to get a CRSP diagnosis because its early symptoms are not all that different from acute pain caused by surgery, a broken bone or some other type of trauma. It takes an experienced doctor to recognize the early signs.

“These are patients who continue to have pain that just doesn’t quite follow the routine course. Even after about a week or two, something is different. The pain is too much or the quality of the pain is just different. They describe a burning sensation or there’s exquisite sensitivity to temperature,” says Kaye. “What happens to these patients is that they continue to see a variety of physicians before they’re given that label of CRPS.”

a CRPS PATIENT 6 MONTHS AFTER leg fracture

a CRPS PATIENT 6 MONTHS AFTER leg fracture

“I wish it was easy to diagnose Complex Regional Pain Syndrome,” says Barby Ingle, president of the International Pain Foundation (iPain), who was diagnosed with RSD/CRPS two years after a car accident that injured her shoulder. “I went from having RSD in my face and shoulder. It then spread to my right arm and hand, then my entire right side. By the time I was properly diagnosed I had full body including organ involvement.”

“I have personally spoken to thousands of patients who have been diagnosed with RSD/CRPS. Out of all of them, two were diagnosed within the first 3 months, most took over a year. For me, I saw 43 providers before receiving a proper diagnosis. Most pain providers were not educated and although providers are getting better education now, there are still major delays.”

Opioids and other pain medications only dull the pain of CRPS, but Axsome is hoping that AXS-02 can also treat the underlying condition that causes the disorder.

“I hope so,” says Kaye. “Instead of just relieving pain, we’re getting right at the underlying pathophysiology of the condition.”

AXS-02 is an oral formulation of zoledronic acid, an injectable bisphosphonate that inhibits the production of compounds that cause bone pain. Bisphosphonates have long been used to treat osteoporosis and Kaye believes they might also stop the progression of CRPS.

“It’s pretty straightforward. Patients take one tablet once a week for six weeks and they’re done,” Kaye told Pain News Network. “We don’t think there will be a reoccurrence based on the mechanism of action. But we want to be sure.”

Proving that AXS-02 can do more than just relieve symptoms of CRPS will take time. If it can find enough patients, Axsome hopes to finish the CREATE-1 study in mid-2017. Additional studies may then be needed. If the clinical results are positive, the Food and Drug Administration has granted “fast track” and “orphan drug” designation for AXS-02, which will speed up the application and approval process.

CRPS patients interested in applying for the CREATE-1 study should click here.    

Experimental Painkiller Leaves Six Hospitalized

By Pat Anson, Editor

Six men have been hospitalized in France after being sickened during a clinical trial of an experimental painkiller. One victim has been declared brain-dead and four others are in critical condition.

(Update: The man who was brain-dead has died, according to local media reports.)

The Phase I trial of the drug has been suspended and all 90 participants have been urged to contact a hospital.

According to reports, the experimental drug being developed by the Portuguese company Bial inhibits a brain enzyme that degrades endogenous cannabinoidsthat are produced naturally by the brain to relieve pain.

By degrading the enzyme called FAAH, Bial hopes to develop compounds that increase brain levels of cannabinoids for use as anti-depressants or pain relievers.

French health officials say the unidentified drug “does not contain cannabis or any derivative of cannabis.”

"We were informed that five participants showed severe symptoms. Following the best international medical practices, they were immediately transferred by the company responsible for conducting the clinical trial to observation at the University Hospital of Rennes, being currently under permanent medical supervision," Bial said in a statement.

Phase I trials are usually conducted to prove the safety of a drug, while the effectiveness of a drug is tested in Phase II and III clinical studies.

The men who were hospitalized were all given multiple doses of the drug, starting January 7. Three days later they started developing neurological symptoms. Two people who were given a harmless placebo developed no symptoms.

“It is definitely the product that is responsible,” said Gilles Edan, head of neuroscience at Pontchaillou Hospital in Rennes, where the men are being treated. She said there is no anti-dote to the drug and its effects could be “irreversible.”

The trial in Rennes was being conducted by Biotrial, a firm that conducts early clinical trials in France and Newark, New Jersey. In France, volunteers can earn nearly $5,000 for participating.  

According to the Daily Mail, Biotrial is able to fast-track early patient studies by “combining the favourable regulatory environment in Western Europe with fast and efficient patient recruitment in Eastern Europe.” 

 “Our thoughts go out to the volunteers and their families. We are working hand in hand with the Health Authorities to understand the cause of this accident,” the company said in a statement.

“The trial has been conducted in full compliance with the international regulations and Biotrial’s procedures were followed at every stage throughout the trial, in particular the emergency procedures for the transfer of subjects to the hospital.”