A clinical research study tests the safety and effectiveness of an investigational medicine in children or adults who agree to participate. Every medicine goes through the clinical research process before it is approved by regulators who then allow doctors to prescribe it outside of a research study. Study participants therefore play a very important role in advancing medicine for both present and future generations.

An investigational medicine has not been approved by the U.S. Food and Drug Administration (FDA) or other health authorities but has permission to be given to study participants for clinical research.

Maralixibat is a grape-flavored liquid taken by mouth. It is an investigational medicine being studied in several rare liver diseases, including biliary atresia. Over 1,600 people have received maralixibat, including more than 120 children with liver disease. Maralixibat has been studied in children with other conditions where bile does not drain effectively from the liver, such as Alagille syndrome (ALGS) and Progressive Familial Intrahepatic Cholestasis (PFIC). Maralixibat has been approved by the U.S. Food and Drug Administration (FDA) to treat cholestatic pruritus (itch) in patients aged 1 and older with Alagille syndrome.

Maralixibat reduces the level of bile acids circulating in the body by helping remove them during digestion. This results in more bile acids being in the feces (poop), a normal route for bile acids to leave the body and lower levels of bile acids circulating in the body.

A placebo is similar in appearance to the study medicine but does not contain any active ingredients. In this study, all packaged study medicine components will be identical to avoid participants or study doctors knowing what each participant is receiving. The study analysis will compare the safety and effectiveness between maralixibat and placebo.

The study team will give the first dose of the study medicine to your child. They will also show you how to do this at home and give you instructions to take with you. The amount of medicine your child will need depends on how much your child weighs. Your study doctor will tell you how much this should be at each visit, but the volume will be less than 1ml (1/4 teaspoon) of liquid per dose. The study medicine should be given once in the morning and once in the evening. You will get dosing dispensers to squirt the study medicine into your child’s mouth.

The study will last approximately two years. For the first 6 months, half of the children will be randomly chosen to receive maralixibat, while the other half will receive a near identical liquid without the medicine in it (placebo). After the first 6 months, all children, including those originally assigned to receive the placebo, will be given maralixibat. This means that all children involved in this study will have the opportunity to receive maralixibat.

There is a chance that your child may experience the side effects associated with the study medicine.

Maralixibat has been studied in more than 1,600 people already, including over 120 children. In previous studies, maralixibat was generally well tolerated with the most common side effects being loose stools (diarrhea) and stomach pain. These symptoms were generally of mild or moderate intensity, were short in duration, and resolved on their own.

Participation in clinical research studies is voluntary and you do not have to join this study. If you decide to not take part in this research, your care will not be affected. If you do decide to take part in this research, then you can withdraw your consent at any time without penalty. During the study you will be asked to follow the instructions in the Informed Consent Form. If you are unable to follow these, your child may not continue the study.

To help protect your child’s health, the study will be supervised by a study doctor and their trained team. You may need to share information on your child’s current and past health during the screening period and at clinic visits.

You will be asked to complete a dosing diary, making note of what time and how much of the study medicine has been given to your child. We also ask a series of other questions such as whether you had to take any time off work because of your child’s biliary atresia. This helps us understand the full impact of the condition not only for the patients, but for their families as well.

If you have a family doctor, it is strongly recommended that you inform them of your interest in this study.

There is no cost to you and your family to participate in this study. Participants will receive reimbursement for any reasonable out-of-pocket costs associated with being part of the EMBARK study, such as travel, parking, and meals. We can also arrange for someone to book and pay for rail and flight tickets if you don’t live close to the study clinic. Certain limitations apply.

At the end of the EMBARK study, your study doctor will talk to you about your child’s future care. For those families who want to continue maralixibat treatment, Mirum will help ensure that opportunities to access this medicine continue to be available as appropriate.

More information on the EMBARK clinical study can be found at: https://clinicaltrials.gov/ct2/show/NCT04524390?term=NCT04524390&draw=2&rank=1