Before any drug is approved for human use by the FDA, and other regulatory agencies around the world, it must be proven to be both safe and effective.
A clinical trial (or study) involves research using human volunteers (also called participants or patients) that is intended to add to medical knowledge. In a clinical trial, participants receive specific interventions, most commonly drugs, according to the research plan or protocol created by the investigators. Clinical trials may compare a new medical approach to a standard one that is already available, to a placebo that contains no active ingredients, or to no intervention. Some clinical trials compare interventions that are already available to each other. When a new product or approach is being studied, it is not usually known whether it will be helpful, harmful, or no different than available alternatives (including no intervention). The investigators determine the safety and efficacy of the intervention by measuring certain outcomes in the participants.
Every clinical trial follows an action plan or protocol. It describes in detail how the research will be conducted, including, who can participate, the length of the study, details about tests and medications, and what information will be collected.
All patients will go through an “informed consent” process, in which researchers provide potential and enrolled participants with information about a clinical study. This information helps people decide whether they want to enroll or continue to participate in the study. The informed consent process is intended to protect participants and should provide enough information for a person to understand the risks of, potential benefits of, and alternatives to the study.
What a clinical trial offers
A clinical trial that is well planned and well conducted offers participants the chance to:
- Try investigational treatments that are being studied in research (investigational drugs)
- Receive regular, careful medical attention from a team of healthcare professionals
- Be part of research that may result in advances in the understanding of a disease or approval of an investigational treatment
Who can be part of a clinical trial?
The clinical trial protocol, developed by the researchers and other highly trained medical professionals, provides a list of characteristics to determine who can and cannot participate in a clinical trial. Examples of these characteristics, sometimes called eligibility criteria or inclusion/exclusion criteria, include items like age, what other medications someone might be taking, having high (or low) levels on various laboratory tests, and a number of other considerations that enable the researchers to make sure that they are testing the new drugs in the most appropriate patient populations.
The screening process is an important step to determine who can be selected to be part of a clinical trial. During this process, there are typically a number of tests and interviews to find out if the person is truly eligible for the clinical trial. The doctor or researcher in charge of the study (the principal investigator) usually does the screening, although some tests may be performed by other members of the staff, or even at separate locations.
The reason there are so many requirements is to ensure that the testing is performed as uniformly as possible. Selection can be very specific, based on the trial design. Unfortunately, that means that not everyone who applies for a clinical trial will be selected. People may not be selected if they do not meet all the eligibility criteria or if researchers already have enough people to complete the study. This does not mean that their contribution and willingness to participate is unimportant. Quite the contrary, being open to the possibility of participation is critical for successful completion of these investigations and bringing new medicines to patients.
Phases of Clinical Trials
In Phase 1 trials the new drug is usually tested in a small group of healthy volunteers. The main goal is to evaluate how safe the new drug is in humans. Researchers gather data to learn about how the human body metabolizes the drug, to identify common side effects and to determine a tolerated dose range.
In Phase 2 trials the drug is tested in patients with the condition being studied. The goal is to further evaluate the safety and efficacy of the drug, and to determine the best dose and regimen for Phase 3 trials.
After a Phase 2 trial has shown that an investigational drug could be effective and safe in limited number of patients, Phase 3 trials test the drug in a larger group of patients. Hundreds or even thousands of participants may be recruited from several different places. When the disease studied is rare, like Familial Chylomicronemia Syndrome (FCS ), the drug development process may involve a single Phase 2/Phase 3 study due to the rarity of the disease and limited number of patients.
The goal of Phase 3 trials is to confirm the preliminary evidence that the drug may be safe and effective. The large number of participants enable researchers to assess how common and how serious any side effects are, to gather more extensive information on the extent to which the drug benefits patients and to determine dose and regimen schedules.
The data gathered from Phase 3 trials can then be used to apply for marketing approval from the licensing authorities. If the application is successful, these data are then used as the basis for the official drug information or label.
After the licensing authorities have approved the marketing of a new drug, post-marketing trials, called Phase 4 trials, are conducted. The goal is continued safety and efficacy monitoring when the drug is used more widely, in order to identify long-term risks and benefits and to identify any rare side effects.
Ionis Pharmaceuticals’ mission is to develop safe and effective RNA-targeting drugs for both rare and more prevalent diseases and providing those drugs to the broadest group of patients as quickly as possible. We do this by conducting clinical trials in which we collect safety and efficacy data about our experimental drugs with the goal of submitting those data to regulatory authorities, like the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), so that these experimental drugs can be approved for use by patients.
At this time, participation in one of our clinical trials is generally the most appropriate way to access our experimental drugs. However, in very rare circumstances, Ionis Pharmaceuticals is able to make an experimental drug that we are developing available for patients outside of a traditional clinical trial under an expanded access protocol, sometimes referred to as a treatment protocol. This is a program where patients may receive the experimental drug as long as they meet certain criteria and are informed about the risks of participation. Ionis Pharmaceuticals is not currently considering individual requests for expanded access that are outside of a company-run expanded access protocol (listed below).
In deciding whether to establish an expanded access protocol, Ionis will evaluate whether:
- there is substantial scientific evidence to support both the safety and the efficacy of an experimental drug for the proposed use, typically after positive Phase 3 data is available;
- it has been established that expanded access will not interfere with the conduct of clinical trials or other aspects of development that could impact marketing approval;
- there is adequate supply of the experimental drug; and
- the experimental drug can be administered, and it is logistically feasible to make it available, outside of the clinical trial setting.
The existence of an expanded access protocol does not guarantee any individual patient access to any specific experimental drug and, at this time, participation in one of our clinical trials is generally the most appropriate way to access our investigational drugs. If you have questions about an Ionis-sponsored clinical trial or our expanded access protocol, please speak with your physician or contact a study site listed on ClinicalTrials.gov.