MG Clinical Trials: Your Questions Answered

On October 27, 2019, Conquer Myasthenia Gravis hosted its Fall Patient Seminar. Speakers:

Rabia Malik

Rabia Malik, MD, Asst. Professor, Rush University Medical Center

Angela Pontius, Ra Pharmaceuticals, Director, Clinical Operations & Patient Advocacy









Click to see these videos from the seminar. And keep reading below for seminar highlights.

Click here for a list of clinical trials that are currently recruiting individuals who have myasthenia gravis.

Click our sponsor logos to learn more about their developing MG therapies!







About Trials

Q:   What is the biggest challenge running a clinical trial related to a rare disease?

Rabia Malik, MD: Myasthenia is a rare disease. There are few physicians who treat it, and few centers that participate in trials. So getting enough participants is a challenge.

Angela Pontius/Ra Pharma: It’s important for MG patients to participate in the national MG Registry

Q:   What is the greatest reward?

Malik:  The biggest reward is when the trial leads to a new treatment that’s more effective and is able to improve my patients’ quality of life – where they have more days where they feel like themselves and less like an MG patient.

Pontius/Ra Pharma: It’s very satisfying when we’re able to develop new treatments for patients whose options aren’t working for them.

Q: What is the difference between a “clinical trial” and a “basic science study”?

Malik: Clinical studies involve people, while basic science studies are conducted in laboratories.

Q: Clinical trials are referred to as “Phases.” What does that mean?   

Malik: Most clinical trials are done in a series of steps called phases. If a treatment is successful in one phase, it moves on to the next. The studies get progressively larger – with more participants – at each phase.

  • Phase 1: Involves a small number of patients, to determine safety, dosing, and how the treatment affects the body. Is it safe for humans?
  • Phase 2: More patients are enrolled to determine safety, how it affects the body, and initial understanding of effectiveness. How effective is it?
  • Phase 3: Involves a large group of patients to compare new treatment with existing treatment.

Q: What role does the physician play in a clinical trial?

Malik: The physician has to understand the inclusion criteria, to consider who might be a good candidate. We help with recruitment by making patients aware of clinical trials at our institutions.  Before we start a patient in a study there is a screening visit. We’ll review the study protocol, inclusion criteria, the risks and benefits, and informed consent.


Q: What is “informed consent”?

Malik: It’s the process of providing information about the study, along with its risks and benefits, to participants. The information should help you decide whether or not to enroll. When you sign an informed consent form, it means you understand the risks and benefits of the study. It is not a contract. At any point during the study you have the right to change your mind and drop out of the study.



Q: What questions should the patient ask before participating in a trial?  

Malik: As a patient, you should ask:

  • What is being studied? Is it new, or has it been studied before?
  • Why do researchers believe that this intervention would be effective?
  • Has it been tested before?
  • What possible interventions might I receive? A drug, placebo, blood tests, other tests?
  • How will it be determined which interventions I receive – for instance whether I get assigned to receive the drug or a placebo?
  • How often do I have to visit the hospital and clinic?
  • Will I be reimbursed for the extra clinic visits, travel, or other costs?

You can ask as many questions as you like during the trial, too. For more information, you can visit the Office for Human Research Protections website.

Marie-Helene Jouvin, MD, Momenta, Senior Medical Director

Q: What role does pharmaceutical company play in a clinical trial?

Pontius/Ra Pharma: On the pharmaceutical side, there are scientists in the lab developing the drug, people who are writing the protocols and working with regulatory colleagues to ensure we comply with FDA guidelines, and those who work with patient groups like Conquer MG to take into account your perspective. We’re collecting the data for FDA approval to make the drug commercially available.

Marie-Helene Jouvin/Momenta: We work closely with the FDA when we write a protocol, to satisfy their requirements. We also have to think about what’s important to payers – insurance companies – to make sure they’ll cover the drug.


Q:  How do you determine clinical trial sites?  Why don’t some doctors participate?

Pontius/Ra Pharma: We identify key opinion leaders, doctors who are experts in treating MG, and their institutions. We choose locations that have large patient populations, to minimize patient travel. Some doctors don’t participate because they don’t see that many MG patients. Or they may be very busy, and don’t have the bandwidth to work with more than one study.

Malik: Participation takes a lot of time, with email communication and site visits to make sure we’re on task and our documentation is in order. Research is not a money-maker for the institution, so doctors often do the work on their own time.

Jouvin/Momenta: These studies may require staffing with administrators and study coordinators, which prevents some locations from participating. That said, if you have a physician who would be interested, let us know.

Q:  Not all therapies for MG go through the clinical trial process. What is the benefit of having clinical trial results?

Malik: Many MG patients take medications that have not gone through clinical trials specifically for MG, which is called “off label.” We know they work, based on anecdotal information. When a drug goes through a clinical trial we get a lot more information about it, how effective it is, how safe it is. A drug that has been approved by the FDA may be more easily covered by insurance, compared to one that is off label.

Q: What do clinical trials accomplish? What don’t they accomplish?

Pontius/Ra Pharma: When we design a clinical trial, we try to think about all the different tests and assessments we can collect data on. We also have to be aware of the patient and doctor, because for every assessment added, their time and workload increase. We ask essential questions required for study and sometimes we can’t ask everything.

Jouvin/Momenta: We consider eligibility criteria. Sometimes we can’t include all types of MG, so the results will be as clear as possible. The clinical trials need to be limited in duration. But sometimes people will be taking a drug for years. We can’t think of all issues that might arise over the course of years. There are ways to address this, e.g., the FDA will ask the pharmaceutical company to continue monitoring patients for years to ensure a safety issue doesn’t arise. If something does come up, there might be a change in the labeling to identify a new risk that couldn’t be identified during the clinical trial.


The Patient Experience

About Eligibility

Q: How do you decide on eligibility criteria?

Pontius/Ra Pharma: We’re careful about inclusion criteria, so we can move through the FDA approval process more quickly. Sometimes we are asked why a person who already is taking the drug can’t participate. It’s because it could potentially affect the data on how our drug is working. The data we supply to FDA has to be very clear.

Some studies determine eligibility based on which MG-causing autoantibodies a patient has. For example, some studies allow AChR-positive patients versus MuSK patients.

Q: If the study limits eligibility to AChR positive patients or to MuSK patients, what does it mean for study results?

Malik: As a physician I’m hesitant to apply data collected for one group of MG to another subtype of MG. If a drug is successful with one type of MG, it may not be effective with another type. An insurance company will have the same argument.

Q: How sick do you want a participant to be?

Pontius/Ra Pharma: Our zilucoplan study requires you to have an MG ADL score of 6 or higher, and QMG of 12 or higher. Enrolling healthier individuals with lower scores wouldn’t help us evaluate the therapy, to see if it makes a difference in patient health.

Juvain/Momenta: We also consider the risk compared to the benefit. No drug is without side effects. If you’re in remission, it would be more risky to take the drug. We have to show the FDA that the risk of new drug side effects is lower than the benefit it could produce.

The Patient Engages with Doctor and Pharma

Q: How do you typically engage with patients throughout the clinical trial process from pre-trial planning all the way through?

Pontius/Ra Pharma: Before a trial starts, we conduct surveys and host focus groups to discover what frustrates patients about current treatments. As we go into phase 3, we’re getting close to drug launch.  We want to make sure when the end user picks up the medication, it looks like something he or she would be comfortable using. We get patient input at walks and conferences.

Juvain/Momenta: Ten years ago the FDA did not care about the patient voice. This is changing. There is the possibility for patient organizations to go to the FDA and advocate for a specific drug. Now the FDA may require a patient to be on pharma clinical trial team.  We work on the way that you have access to the drug in a timely manner.

Q: Do participants still see their regular doctors? Do they see a different doctor for the trial? Does the trial doctor keep in touch with their regular neurologist?

Malik: A trial would not be part of your regular care. So if you are seeing another neurologist for your regular care, you’d still see that doctor for your regular visits.

Pontius/Ra Pharma:  The trial would likely require you to have extra clinic visits, extra testing (such as blood draws, or an EKG). If you were seeing Dr. Malik for the study and plus another neurologist, they’d definitely be talking with each other.

Q: Does anyone get a placebo or “no treatment”?

Malik: It varies by study. Some studies are set up so some participants are randomly placed in a placebo group.

Jouvin/Momenta:   It’s not possible for a drug company to ask you to stop all your current treatments and go on a placebo. The FDA would not allow that. If you are on a treatment, you could continue current treatment even if you are randomized to the placebo. It would not be ethical to deprive patients of treatments that are working.

Pontius/Ra Pharma: Many companies have an extension period, in which all patients – whether they receive the active drug or placebo during the double blind period (where no one knows who is getting which), can enroll in an a separate study or an extension of the current study using the new drug.

Q: Are any expenses reimbursed for the patient?

Pontius/Ra Pharma: The information would be laid out in the consent form. Usually out of pocket costs like parking and mileage are covered. Because you have to get a meningitis vaccine to participate in Ra Pharma study, cost for this is covered. We would pay the reasonable cost of any out-of-pocket expense that’s study-related.

Jouvin/Momenta: It’s very common practice among companies for these types of expenses to be covered.

Q: What if a participant gets very sick – with MG or with something else?

Pontius/Ra Pharma: If the person is very sick and it appears that it’s due to the drug, then the person would be taken off the drug. In our study if someone is on a placebo, then we have the option of rescue therapy with plasmapheresis or IVIG. Those items are covered by the sponsor.

Malik: In my experience, our patient did need rescue therapy. He was still able to continue with the study drug because we didn’t feel it was the cause of his illness. There are safety nets in place. You might be taken off the study drug, or you still could continue in the trial.

Deciding Whether or Not to Participate

Q: Why do some people choose to participate?

Malik: They are frustrated by the disease and have tried options that didn’t work. They’re hopeful that a new treatment will make a difference.

Q:  What are the pros and cons of participating?

Pontius/Ra Pharma: The biggest pro is that you potentially could receive a drug that works for you. You also have access to a huge team of doctors. On the con side, it’s possible it won’t work for you or you could receive a placebo for the initial study. And it takes time to go to clinic visits. We try to respond to this by requiring fewer clinic visits over time, or by shipping supplies directly to your home.


Q: Are there misconceptions that keep people from participating?

Malik: Some people feel participants are “guinea pigs.” But clinical trials undergo a rigorous review process. These treatments have been studied extensively in the lab before being brought to the clinical stage. There is a lot of brain power behind the design of these trials.

Pontius/Ra Pharma: There is a very rigorous process to get a clinical study approved. We go through the design review with the FDA. They have to think there is enough potential benefit to patients for the study to go forward. Then there is an approval process at each site with an Internal Review Board. The IRBs include scientists, doctors, and lay members.

Also, you’re never stuck in a study. We prefer you stay in, of course, but if you feel you need to pull out at any point, that’s possible.  The consent process doesn’t stop with the initial consent.

Trial Results

Q: What does it mean to have a “successful” trial?

Pontius: The most successful study meets the goals that you predefined with the FDA. But not all clinical trials will make it through every phase. Sometimes you stop at Phase 2 because you find the treatment is not working well enough to proceed.

Malik: Even if a trial doesn’t meet the goals that you established, you still learn why it failed, and a little more about the disease.

Why Now?

Q: After 30 years with no new MG therapies, why are we seeing so much activity now?

Malik: we understand the disease a bit differently now. We recognize there are other players, not just acetylcholine receptors involved in MG. So there’s been an explosion for research. These studies are helping the medical community understand other diseases. And the drugs that are successful for MG, we can extrapolate and explore whether they’ll help with other autoimmune diseases.