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What is a phase one clinical trial? A phase one clinical trial is really the first assessment of a new drug in in humans. Phase one trials generally include a smaller amount of patients, generally 15 to 25 patients. They're done in a brief period of time, usually between 6 and 12 months. The goal of a phase one trial is to assess safety primarily. What we try to gain from a phase one trial is identification of what's called an MTD or maximum tolerated dose or a recommended phase two dose.
A phase one trial's purpose is typically in new drug development, trying to understand what the right dose and schedule is for a new drug. So the express purpose of the trial is really about understanding the safety and optimal schedule of the drug. While our goal for any study for a myeloma patient is to help, the stated purpose of the study is to really understand the toxicities of the drug and best schedule. Phase one is typically used for safety of a drug. Not been used in people before, a very limited use in people before. So in phase one, you're typically looking at low dose and you're ramping it up and seeing pretty much where your maximum level is to where you start having some safety concerns. In other words, you're finding your dose for future trials. You don't even typically look much at response rates, you're just looking to see if it's safe to give people.
Phase one can have as little as three people in each cohort. Three people taking five milligrams, three people then take 10 milligrams, etc. But the overall phase one will often have many more than that, and it really depends, but it can be a variable number of patients.
What is dose escalating? One of the very common study designs for a phase one trial is what's called a three plus three study design, and in in that particular study design, what you're looking at is a drug. You're starting off at low doses, making sure it's safe, and then you're increasing the doses as tolerability is confirmed.
What is phase two of a clinical trial? So phase two trials is a trial that is looking at both safety and efficacy. So it's a continuation of development of a drug, and the phase two trial continues to give us safety data. We're starting to get a real signal about the efficacy of a drug, so these trials generally take a bit longer to conduct. They include more patients. The goal of these phase two trials is really to identify a therapeutic dose regimen to take into the further phases of trials. And a phase two studies purpose is to understand what is the efficacy or what is the benefit of the medication. In myeloma, we ask the question, what is the response rate to this medication? What is the likelihood that this medication, whether given alone or a combination, is beneficial to an individual patient? At the whole time continuing to monitor what the potential side effects of that medication are. So then when the drug looks safe, they go to phase two, which is where you have your set dose, say 50 milligrams, and you give it to X number of people. And as opposed to doing three at a time, you already know your dose. So you might do a hundred people, and what you're really looking for there is what's the response. Are people responding to it? Does it work at all? And you're still looking at safety, of course.
Does a phase two trial have one arm or two arms? In general, phase two trials are single arm trials. There are examples of a randomized phase two trials, however, for the most part, a phase two trial will be single armed.
What is a phase three trial? Are there a lot of people in a phase three trial? So phase three trial is a trial that's used to confirm safety and efficacy. In general, these are multi-center randomized controlled trials. What we are trying to do is identify the regimen that's going to be used potentially for say FDA approval. There's generally, as far as the number of patients that we see on phase three trials, we're talking hundreds, and in general, these trials take anywhere from a couple of years to many years to conduct.
A phase three study is done after a phase one and two. Phase one looks at the toxicity and schedule. Phase two says, yes, this regiment, this drug or this combination of drugs is effective. Now the question is, is it more effective or safer than the standard therapy? And there's different ways to do a phase three trial, but in a large part, a phase three trial is a randomized study, and the randomization is between a standard approach of therapy versus a new therapy. And typically in myeloma, the way it's done, it's the standard approach of therapy plus an additional agent. And in these are randomized trials where there's a coin flip of which arm of the treatment do you get. This the individual, you can get the standard treatment, or do they get the new treatment? And we do the randomization because we don't know that that newer therapy is truly better, is true, not only more efficacious, but more efficacious and safe. And so in a phase three study, the minimum that a myeloma patient would get would be the standard of care, and then it would be compared against the standard care plus a drug. There are some myeloma studies where the patient gets the standard of care plus a placebo, but in that placebo group, that patient's still getting the standard of care, still getting the treatment they would get if they weren't on a study. And then that standard of care again is compared to the new treatment, whether it's a new drug or a new combination.
In terms of the numbers of patients who are on these different phases of study, phase one studies differ, is typically a relatively small study, anywhere between 10 and 30 patients. The typical phase two study is probably closer to the 30 to 100 range, 30 to 80 patients. And when we do a phase three study where we're really, we're trying to change the standard of care, we're now looking at several hundred patients to to to do a phase three study. So anywhere between one to two hundred patients per treatment arm, or that is two to four hundred patients total, to to 400 to 500 patients per arm. In a myeloma study, if it looks like it's promising at the end of a phase two, then you typically move to phase three where you prove that it's better than what your standard is. And then in phase three, you'll typically then use that phase two's dose, and you'll have in myeloma often a few hundred patients. Half of them will get whatever the standard of care is, and then half of them will get your new treatment, and you'll follow that for years, and you'll see if your new treatment is better, safer. And that's how they get FDA approval.
There's also phase four, which is well, a lot of people call those observational trials where you might be looking at a quiz, or you might be looking back at your data and seeing people, how did people tolerate certain treatments, not really a controlled trial, but kind of looking at data. Or you might have patients giving you updates and how they're doing, called they can also be called registry trials. So you're not actually getting any specific drug for that, people are just observing how things are going and looking at treatment patterns that that may impact further trials.
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