IHCE “The Elephant Man –- Clinical Trial” Case No: 3
Today was the day! Ms. Pritchard, the senior clinical research nurse practitioner, on the team was proud, she had spent months recruiting subjects for the phase I clinical trial of TeGenero’s Theralizumab TGN1412 CD28, superagonist monoclonal antibody (mAb).
The trial was a double- blind, randomized, placebo-controlled study, with two of the eight subjects receiving a placebo, and six receiving TGN1412. All White healthy men, no health complaints; aged 19 to 34 (median 29.5). Ms. Pritchard did all of the informed consents, each taking about 15 minutes. Most of the men were just concerned
about their compensation; she downplayed any risks as being minimal. Dr. Thomas Hunig, the PI for the project was anxious as well. He knew that activation of CD4+ effector memory T-cells by TGN1412 could cause a life–threatening “cytokine storm” in the subjects.
Even TeGenero was aware of the risk, but Dr. Hunig felt benefits outweighed the risks. This would be a billion dollar immunotherapeutic drug for the purpose of balancing the immune system. Drs. Ving and Chou, the immuno-pharmacologist and genetic biochemist, heading up the lab team had shepherded the animal studies every step of the way. Each human subject was to receive a supposed sub-clinical dose of 0.1 mg per kg, some 500 times lower than the dose found safe in animals.
While Drs. Ving & Chou had suggested that the human subjects be dosed one at a time and their progress monitored, Dr. Hunig was anxious to publish, report to the board any preliminary findings; the Parexel boards’ earning call was in a week. He wanted to press on. On March 13, 2006 Hans Klaus, age 21, joined seven other test subjects at an independent clinic at Northwick Park Hospital, a 30 bed facility, run by Parexel, a company which conducts drug trials for pharmaceutical companies.
When Hans signed up for a drugs trial, he thought he had found a way to earn some easy money, $2,000 and do his bit for medical science. Like the other men taking part, he filled out an 11-page consent form which detailed the risks of taking part. But he had no inkling of any “potential hazards” or that the test drug could harm his immune system. The group of eight people had initially been split into two groups of four, grouped together in separate rooms. One person in each room was given a placebo.
The remaining six were given TGN1412. “I was injected at about 8 AM” says Klaus. “We all had a catheter fitted to our arm and an electronic syringe. They came around, plugged in the syringe and pressed go. All six receiving 1/500th of the highest dose used in previous experiments with cynomolgus macaques over a 10 minute infusion time. Klaus had steadily begun to feel unwell. “I began to feel excruciating pain in my back and head, said Klaus. “I felt my head swelling up like an elephant’s – I thought my eyeballs were going to pop out.” “People around me started feeling cold. Everyone was starting to shake like they were freezing, having difficulty breathing,” Klaus reported.
The two placebo subjects had already been released and went home shortly afterwards, before everyone started getting sick. Klaus said “I remember vomiting into a biohazard bag. But the worrying point for me was when one guy, they drew the curtains around him, then these guys with gowns came up, like from an operating theatre. “They went behind the curtain, then went away and came back with all this equipment – life-support stuff.” “Soon another patient was announced to be in ‘cardiac arrest’ that’s when they separated us and took all the remaining subjects to separate rooms,“ Klaus began to panic. TGN1412 had a catastrophic effect on the six men’s bodies.
Headaches and chills rapidly gave way to vomiting, severe pain and shortness of breath. Swollen tissue, plummeting blood pressure and multiple organ failure followed. Klaus said he really was terrified, “what was he to do, what went wrong?” He felt awful, but the researchers weren’t telling him anything. “Around midnight I was taken to intensive care in another facility.” Klaus said he remembers the nurses saying that he was going into organ failure, he needed to go onto hemodialysis immediately to remove toxins from his blood and he was being given massive doses of steroids
as they prepared to place him on a ventilator. Klaus asked them to call his mother, they advised him to say his good-byes. He asked the medical team …. ”am I going to die?”
You are a research ethics team asked to provide a preliminary review of this case and offer recommendations.
