Answer: A platform trial uses a single Master Protocol, or schedule of study visits and study procedures, to test several treatments in different regimens either at the same time or sequentially.

A regimen is a specific course of treatment. Each regimen in the trial will provide the course of treatment for one study drug.

Throughout the trial, the number of regimens that are available at any given time will depend on the number of study drugs that are available for the trial at that time. There will likely be multiple regimens available at the same time.

All participants must first complete the Master Protocol Screening visit. This visit will determine if you are eligible to participate in the trial. If you are eligible to participate in the trial, you will then be randomly assigned to a regimen. You will have an equal chance of being assigned to any of the available regimens. The regimen you are assigned to will determine which study drug you will receive. You will be told which regimen you are assigned to and the name of the study drug.

If you are not eligible for the trial, you will not be assigned to a regimen and your participation will end.

Your participation in the trial is always your choice. You can choose not to participate in the regimen you are assigned to if you do not want to take the study drug. You would not be immediately re-randomized to another regimen, however.

The schedule of study visits, or the number of times and how often you will need to come into the clinic or participate in a phone call, will be the same no matter which regimen you are assigned to.

Most study procedures will also be the same between regimens.

Some regimens may have a small number of additional procedures. Any additional procedures that will take place in a regimen will be explained to you before you sign the consent form to participate in a regimen during the regimen screening visit.

Study drug administration may be different between regimens. For example, one regimen may have a pill that is swallowed whole while in another regimen, the drug in might be injected under the skin.

Yes. Once you are assigned to a regimen, you will complete a second screening visit to determine if you are eligible to continue in that regimen.

If you are eligible for the regimen you will continue to complete the regimen.

If you are not eligible for the regimen you are assigned to, your participation in that regimen will stop. If this happens, you might be able to participate in a different regimen.

Yes. If you are not eligible to participate in a regimen, or you decide to stop participation on your own, you can participate in another regimen.

Prior to being assigned to another regimen, all participants must re-start the trial from the beginning and complete the Master Protocol screening visit again. The length of time between ending participation in one regimen and completing the Master Protocol screening visit again will depend on the reason your participation in the regimen ended.

If you are still eligible for the trial after completing the Master Protocol screening visit again, you may be randomly assigned to another regimen. If you are eligible for the other regimen you are assigned to then you may continue to complete the assessments for that regimen.

Yes, you may be able to start a second regimen if you complete the Master Protocol Screening visit again and you are still eligible for the trial.

An open label extension may be offered to you when you complete the placebo- controlled portion (some participants receive active study drug and some participants receive placebo) of the regimen.

During the open label extension all participants will receive active study drug.

The option to participate in an open label extension, and the duration of the open label extension will be different between regimens.

REFINE-ALS is an observational study for people with ALS that have decided to start IV or oral edaravone and are not participating in an ALS drug clinical trial. We are doing this research study to understand how edaravone works in the body by measuring changes in biomarkers in the blood and urine over time. This may give us insights into ALS, how edaravone is effective, and how we might develop even more therapies in the future.

If you decide to join this research, you will be asked to complete 8 study visits over approximately a 6- month period where the following types of assessments will be performed: blood and urine sample collection, completion of ALS questionnaires, measurement of breathing function.

It is important to note that edaravone will not be covered by the study. You must obtain insurance approval for edaravone prior to beginning study visits.

Yes, visits for REFINE-ALS can now be done in clinic or at home. If you choose the home visit option, you can now complete this study fully from the comfort of home.

If you decide to take part in this study,

• We will ask you to sign a consent form in clinic or remotely before we do any study procedures.
• The following things will happen:
  • Blood and urine samples will be taken
  • You will be required to complete ALS questionnaires
  • The study staff will measure your respiratory (breathing) function and other clinical measurements.
• You may have the option to complete this study in-clinic or remotely. If you choose the remote option, study visit may be conducted by video telemedicine or by telephone. A home health agency will come to your home to collect blood and urine sample, test vital signs,breathing, etc.

This study will take approximately 24 weeks to complete, during which we will ask you to make 8 study visits (at home or in-clinic). This does not include the time needed for insurance approval for Radicava® (edaravone).

There will be 8 study visits over the course of 6 cycles of edaravone treatment. These visits can be done in the clinic or at home.

• Visit 1 (Screening/Baseline Visit)
• Visit 2 – before start edaravone treatment (before Cycle 1 treatment)  Cycle 1 Visit 3- On Drug
• Cycle 1 Visit 4- Off drug
• Cycle 3 Visit 5- On Drug
• Cycle 3 Visit 6- Off drug
• Cycle 6 Visit 7- On Drug
• Cycle 6 Visit 8- Off drug

The study coordinator will work with you to schedule visits during the appropriate timeframes

If you decide to utilize the home visit option, each REFINE-ALS study visit will have 2 distinct parts: a telephone/video visit with the site team and a home visit by a Symphony homecare nurse.

Prior to a home visit, the Symphony nurse will call you to schedule the visit. During the visit, the symphony nurse will collect your blood and urine, vital signs, Slow Vital Capacity(measurement of breathing function) and questionnaires. The visit will last approximately 2 hours. The nurse may request a clean surface to process samples and access to a sink to wash their hands.