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Ryan Wilson had to have part of his feet and his fingers amputated after the trial. Photo Channel 4.

The Infamous ‘Elephant Man’ Drugs Trial 

A catastrophic clinical test that left six volunteers fighting for life in intensive care became notorious as the “Elephant Man” drug trial because of the horrific side effects they endured

 On the morning of Monday 13 March 2006, six out of eight healthy male volunteers in a clinical trial received the first dose of a drug never before given to humans, in an independent commercially-run clinical trials unit within the grounds of Northwick Park Hospital. After a drug is confirmed as safe and efficacious in preclinical studies, it is tested in healthy human volunteers for first in man trials.

This was planned and expected to be completely routine. However, all six men had a life-threatening reaction requiring an emergency response by the NHS, which not only had a lasting impact on them but also brought about changes in how higher-risk clinical trials are run and regulated in the UK, EU, and beyond.

Saving the lives of those volunteers once they were transferred to NHS care required a huge, coordinated effort from the intensive care unit team, senior colleagues from other specialties, and many other clinical and operational staff across Northwick Park Hospital, with support from neighbouring critical care units and assistance from other agencies including the London Ambulance Service and the Metropolitan Police.

A comment from a distressed partner caught live on camera became the infamous ‘Elephant Man’ label. In truth, it was not a specific symptom or effect of the drug, or some kind of explosive growth of the head. Critically ill people develop leaky blood vessels and shock, and the large volume of fluid we give them in the first few hours causes temporary swelling – most noticeable in the face. It gets better as they recover, but can look understandably upsetting to their friends and family.

Researchers hoped TGN1412 would significantly improve cancer treatment. Photo BBC

The Potential wonder cure TGN1412 left the men writhing in agony and projectile vomiting before their immune systems crashed and they suffered multiple organ failure.

Each developed high fever and early signs of shock within a few hours; and then, after briefly rallying with initial treatment on the trials unit, progressed to life-threatening illness, some more quickly and devastatingly than others.

By late Monday night, fourteen hours after they all received the drug, the worst affected volunteer was in advanced multi-organ failure, his condition deteriorating so rapidly that it took two hours for the duty intensive care consultant and team to stabilise and transfer him on full life support to the intensive care unit (ICU) at Northwick Park Hospital.
Doing so took up the last empty bed on ICU, and it was already clear that the five other young, previously healthy men who had received the trial drug were also visibly deteriorating. Some were becoming sicker faster than others, but they were all developing multiple organ failure and all needed to be in intensive care.

Bringing six people who needed immediate treatment at the same time into a fully-occupied ICU would seriously challenge any intensive care unit in any health system in the world – as many of them have since told us. Splitting the volunteers among several other hospitals would have put them at risk, not least in trying to co-ordinate their treatment in the days ahead in an already complex situation.

The reaction fitted the recognised label of a ‘cytokine storm’, an unintended dramatic release of inflammatory biological signals in response to an attempted treatment drug, causing a chain reaction in the immune system.

Ryan had to spend four months in hospital after suffering heart, liver and kidney failure (Photo: BBC)

More than 11 years ago, six young men were left writhing in agony with their organs failing after agreeing to take part in a routine drugs trial in London.

The group were part of a team of eight who were each offered £2,000 for a three-day trial that would potentially help revolutionise cancer treatment.

The men, who had been selected to be aged between 19 and 34, had been told the worst symptoms would be a headache, nausea and, in rare cases, hives.

However, soon after receiving the drug, six were left vomiting and screaming in agony – with one having to have body parts amputated.

TGN1412 was the trial name for a type of monoclonal antibody therapy manufactured by German firm TeGenero. It was meant to manipulate the body’s immune system to treat leukaemia and auto-immune diseases such as arthritis. Researchers had high hopes for it after macaque monkeys injected with it showed no problems. The next step was to test it on human guinea pigs in a so-called Phase 1 trial. As the TGN1412 drugs trial spiralled into one of Britain’s most infamous medical emergencies, shocked medics battled to save the young men.

Raste Khan, who had a placebo, said it was like a horror film watching the other men fall violently ill. Photo BBC

The disastrous ‘Elephant Man Drug Trial’ caused shockwaves in the medical and pharmaceutical community. TGN1412, a novel monoclonal antibody drug developed by TeGenero, a German biotech company, was intended for the treatment of autoimmune diseases and leukaemia.  The Phase I trial (first-in-human testing) was conducted by Paraxel at an independent clinical trials unit at the Northwick Park. Clinical and animal testing, including on non-human primates, had already been completed and reported not to indicate any safety issues.

TGN1412 was administered to the six men by intravenous infusion over the course of 3 to 6 minutes. Each patient received the experimental drug in quick succession. Within 60 minutes, the first participants suffered severe headaches, muscle pain, nausea, vomiting, diarrhoea, severe fever, restlessness, rash and rigors. After four hours, the volunteers developed hypotension, tachycardia and onset of respiratory failure.

By the following day all of the recipients had been admitted to the ITU at Northwick Park. Their symptoms progressed to multi-organ failure. It was later established that the TGN1412 doses had caused a “cytokine storm” in the volunteers; an extreme and near fatal immune response. The participants were hospitalised for periods of three to six weeks. The long-term effects on their immune systems remain unknown, though on discharge some were warned they may suffer an increased risk of cancers and auto-immune diseases.

Eight volunteers took part in the Elephant Man drugs trial at Northwick Park Hospital (reconstruction) Photo BBC.

The dramatic events left the human guinea pigs fighting for their lives in a private unit at Northwick Park Hospital in north-west London run by Parexel, a US company.
Throughout the Phase 1 trial, a number of the men suffered from swelling – with their heads inflating like balloons.

One victim’s girlfriend later said he looked like “the Elephant Man” which led to the TGN1412 legal proceedings’ nickname, ‘the Elephant Man drug trial’ – although the swelling was likely caused by the treatment for the reaction, which included administering large quantities of fluid and steroids.

The drug, which had been successfully tried out on monkeys, had never been tested on humans, making it a ‘first in man’ trial. It was later found that while macaques and humans are incredibly close from a DNA perspective, the cells that the drug targeted differ slightly between the species.

The incident quickly transformed into one of Britain’s most infamous medical emergencies. Ryan Wilson spent four months in hospital and had his toes and parts of his feet and fingers amputated after battling the symptoms of pneumonia, septicaemia and dry gangrene. In an interview with the Guardian in 2007, Wilson said he is still haunted by the words of his father, who told him the night before the trial: “Don’t do it. Your body is a temple.”

Fortunately, doctors were able to save the lives of all of the young men – and a few weeks later, five of the men were able to leave the hospital, however, the drug had attacked their tissue and left them with wasted muscles. One, David Oakley, said it had left him feeling like ‘an 80-year-old’. Ryan Wilson, the sixth and youngest participant aged 21, spent the next four months being treated for heart, liver and kidney failure. Sections of his feet were amputated and his fingertips also fell off. It was later revealed that two of the participants were given a placebo and did not suffer the effects.

New Zealander David Oakley’s head swelled up so much he was dubbed the Elephant Man. Photo BBC

David Oakley was the first to receive the drug and at 3.30am he was so gravely ill that his fiancée Katrina was told to come to the hospital, where she prepared for the worst.

She said: “I don’t think anything could prepare you for what you saw when you first went in.

“His cheeks were very swollen, so much that his eyes looked more like slits. His face was just round like a ball and his stomach was huge. It was pretty scary to see somebody you love so disfigured.”

In 2008, David was the only victim to develop early signs of lymphoma, a form of cancer. The signs were picked up in the regular checks he has to have as a result of the trial. He says: ‘We have tests every six months so that when something happens they can catch it quickly. ‘They are looking for markers that could be early indicators of cancer, arthritis, lupus, MS; a variety of immune deficiency diseases. ‘There was a time that I was showing a marker for lymphoma.

‘Luckily at the next test it came back negative. Recently another marker suggested arthritis.’ David has been told that he now lives under the constant threat of developing lymphoma.

‘We’re deemed high-risk. They thought these risks would reduce over time.

‘Originally they had thought that after five to ten years the risk should be reduced to that of a normal person but now they’re saying that the risk could potentially be for a lot longer – potentially lifelong.

‘At least we know,’ he says. Naturally good-natured and optimistic, David tries to take each hurdle in his stride but there is no denying that every day can be a struggle. He explains: ‘My short-term memory is shot. Being in intensive care was the most extreme time. ‘They had got me a little portable TV and the Commonwealth Games was on. ‘I would watch a race and then an hour-and-a-half later they would repeat it and I had no idea who had won.

‘Now I write lists for everything, otherwise I couldn’t get through the day.

‘I put everything into the diary on my mobile phone, from paying a bill to picking someone up from the airport to what I need to decorate the spare room.

‘If it’s not on my phone, I don’t know about it.

‘About a year ago, they gave me a lumbar puncture to find out what was wrong with my memory.’It was terrible, absolutely terrible. The headache it gave me was so bad that I was practically throwing up with the pain.

‘They think that some of the drug crossed from the blood stream into my brain.

‘They’re not sure if that’s it or if it will ever improve. There are lots of don’t knows. ‘I still get tired very quickly, particularly when I have to concentrate.

‘I can do some work around the house but if I tried to go for a run I got breathless very quickly and my joints would hurt. That is just how it is now.

‘So there won’t be any more running but I can do a little bit of walking.

‘I used to love trekking. In New Zealand we’d just take the back packs and head off for six or seven days into the middle of nowhere.

‘Now, we do English trekking – just a gentle walk from one pub to another.

Rob Oldfield, who also took part in the trial, says he was rushed to intensive care at around midnight (Photo: BBC)

Rob Oldfield vividly remembers the events of 2006:

“I went into the trial partly for the money, and also to do something for the good of people. I thought it could have been a massive break-through in medical science. I don’t really remember the risks being spoken about; we were given a ten page information document which we didn’t really have time to read. Everything was played down a lot. I had no idea it altered the immune system.

“Not long after I was injected I started to feel very cold. I remember being sick into a biohazard bag, and all of us being very ill. I was taken to ITU. The steroids masked the pain somewhat. I didn’t really realise how bad things were – my Mother received a call from medical staff the same night. It was as if they were saying “this is your goodbye – this person could die”. My immune system crashed and my liver, kidneys and lungs were failing. Fluid seeped into my lungs.”

“Thankfully, after three weeks treatment, I survived.”

All of the men had their lives saved but some suffered amputations or months of health issues (Picture: BBC)

When Rob Oldfield signed up for a drugs trial at Northwick Park Hospital in 2006, he thought he had found a way to earn some easy money, and do his bit for medical science. On the morning of 13 March, 2006 Oldfield joined seven other test subjects at an independent clinic at Northwick Park Hospital.

The German company that developed the drug hoped it would revolutionise treatment of leukaemia and rheumatoid arthritis.

But within minutes of having the drug administered, all of the test subjects began feeling unwell.

“I was injected at about 8 am,” says Oldfield. “Around midnight I was taken to intensive care.”

The group of eight people had initially been split into two groups of four, who were put in separate rooms. One person in each room was given a placebo. The remaining six were given TGN1412.

“They administered to everybody in the other room,” recalls Oldfield, who was subject number seven, “then they came into our room.”

“We all had a catheter fitted to our arm and an electronic syringe. They came around, plugged in the syringe and pressed go.

“People started feeling cold. Everyone was starting to look a bit under the weather, freezing cold, a bit of the shivers. I thought ‘it’ll be OK, I’ll probably be a placebo’.”

Oldfield had no such luck. Subject number eight was given the placebo and went home shortly afterwards.

“They activated the needle – injected me – then I began to feel cold,” recalls Oldfield. “The nurses didn’t know what was going on really. They were faffing around looking for blankets to keep us warm.

“I remember being sick into a biohazard bag, and all of us being very ill. 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.”

Oldfield had signed up to the trial for a fee of £2,000. He had spent two months in the US training as a screen actor and returned to the UK with some debts he wanted to clear.

“A friend of mine had told me about medical trials before I’d gone. I thought I may as well take advantage of it. Plus I thought I could be a kind of ambassador 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 that the “potential hazards” could have resulted in him needing life-support.

“I didn’t know it was dangerous. I had no idea it altered the immune system.”

Swollen tissue, plummeting blood pressure and multiple organ failures followed. One by one, all six were transferred to intensive care.

“I remember quite vividly being pushed through those corridors that hospitals have, and when they go outside and it’s like a glass enclosure.

“I remember the cool air hitting me and feeling faint because of the temperature change.”

Oldfield ended up in an area where people recover after surgery. Intensive care was short of room.

“There were six of us in this triage space, and that’s where they started putting machines on us – haemo-filtration, cleaning your blood.”

Despite the drama, it took Oldfield some time to grasp the danger he was in.

He was given steroids, which masked his symptoms, and for a time he thought the adverse reaction to TGN1412 was within expectations – it was a trial after all, and the medical staff treating him were not being explicit about his situation.

“They were just saying we need to put this in the top of your leg, put a big tube into the neck, just to give drugs – it wasn’t like ‘you are seriously ill’.”

At about 02:00, some 18 hours after Oldfield was injected, medical staff called his mother and told her she should come to the hospital.

For two weeks, Oldfield’s blood was filtered 24 hours a day, he recalls. His immune system had crashed, and his liver, kidneys and lungs were failing. Fluid seeped into his lungs and he had to breathe air through a mask, while a direct line pumped vital drugs into his heart.

Thankfully, like all of the men injected with TGN1412 that day, Oldfield survived. After three weeks in the hospital, including seven days in intensive care, he emerged alive.

His short-term memory was impaired – for months afterwards he would forget conversations and appointments – and his immune system made extremely weak. Doctors advised him not to use public transport, and avoid other places where he might be exposed to viruses.

But he was, relatively speaking, fortunate.

Programme Name: The Drug Trial: Emergency At The Hospital Katrina Oakley was called to the hospital at 3.30am. Photographer: Raw TV/BBC

Clinical trials (and the safe drugs that hopefully emerge) benefit humanity; without them, numerous life-saving medicines would not exist. Yet when things go wrong the human cost can be very high- individuals suffer life-changing physical and psychological injuries.

Rob recalls:
“For around a year afterwards I had a short term memory loss. I struggled to remember everyday things. We were told to stay away from public transport, choose our food carefully, that sort of thing – because our immune systems might not be able to cope. It really affected my everyday life. Ten years on, I still get mouth ulcers more than I used to. I don’t know what the long term effects on my immune system will be.
Now, I feel quite cynical about clinical trials. I had thought it was a good thing – being an ambassador for science – but because of trial, I feel like I was just equipment within a system, not a human being. It is hard to see that the corporations are interested in anything other than money.
The compensation helped me to rebuild my life. I hired a personal trainer who helped me to build my strength back up. It felt like a real fight against TeGenero to get it though; surely adequate compensation should be by right? ”
Thankfully, despite Northwick Park, there appears to be no reduction in interest in early stage clinical trials: the MHRA reports that the number of UK clinical trial authorisation applications has, since May 2004, remained stable at 900 – 1,000 per year.
It is for this reason that the fight for safe clinical trials, and adequate compensation, continues.

The long-term effects of the trial on the volunteers remain unknown. One man has since had a cancer diagnosis (which may or may not be connected) while another believes that his auto-immune system has been permanently damaged. Ironically, the drug has probably left the six at greater risk of contracting the very diseases it was designed to help cure.

In the immediate aftermath of TGN1412/ Northwick Park drug trial, there was much discussion within the scientific, medical and regulatory community about what went wrong and the steps which could be taken to prevent a similar disaster in the future. The apparent unpredictability of the adverse events associated with the trial raised significant alarms.
The Medicines and Healthcare Regulatory Agency (MHRA) regulates clinical trials in the UK. In an interim report, of 5 April 2006, they identified the likely cause of the adverse reaction in the TGN1412 trial an “..unpredicted biological action of the drug in humans”. The ‘unpredictability’ raised serious concerns. Shortly after, the UK Secretary of State for Health established an “Expert Scientific Group” (ESG), to “review what could be learned from the TGN1412 trial”, and consider future recommendations for Phase I trials.

The worst-affected of the men lost fingers and toes, and all the men were subsequently told they would be likely to develop cancers or autoimmune diseases as a result of exposure to the drug.

Some of the men later described how the drug had made them feel like their brains were on fire and that their eyeballs would pop out.

Parexel said it had followed all of the recommended regulatory, clinical and medical guidelines and that such cases were extremely rare. But a report into the trial said the company was not clear about what was a safe dose to start testing on humans was and found that it should have tested the drug on one person at a time.

The investigators tasked with discovering what went wrong said: “This was treated as a crime scene. Something could have been tampered with, sabotaged, poisoned and that these folk might have been the victims of such foul play.”

Parexel, the company which ran the clinic where the drug trial was carried out, was found to have acted within its protocols in an interim review by the Medicines and Healthcare products Regulatory Agency.

A final report, however, stated the trial had not properly considered the safe dosage of the drug for humans.

It is understood that some volunteers have received confidential compensation payments, but still suffer from weakened immune systems and other side effects, and will never know the true legacy of the drug which so nearly cost them their lives.

The report made a number of recommendations, including the Medicines and Health Products Regulatory Agency – which had approved Parexel’s trial – ensuring that committees considered pre-clinical data to decide whether the first dose of the drug to be tested on a human was the right dose.

Although this was not an NHS trial, the real story is that the volunteers survived precisely because the trial did take place in the grounds of a large acute hospital which was able to mount a rescue without delay, and what was learned has gone toward making all such higher-risk trials safer regardless of who is running them.

Credit should go to the volunteers, who not only showed remarkable grace and courage at the height of their illness during what was clearly a frightening time, but who have also, without exception, always been very generous and clear from the outset that they wanted their experience and information shared where it could do the most good in advancing science, and especially to make clinical trials safer for others.

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BBC – The Drug Trial: Emergency At The Hospital – Media Centre

‘I nearly died in a medical drug trial’ – BBC News

Elephant man drug trial – Medical Dictionary – The Free Dictionary

Ten years after the ‘Elephant Man’ drug trial – Leigh Day

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The troubled history of clinical drug trials | The Independent

Drug trial victim is like Elephant Man, says girlfriend – Telegraph

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Drug trial ‘Elephant Man’ to lose fingers and toes • The Register

TGN1412: From Discovery to Disaster – NCBI – NIH

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