What to Expect in the Trial Process

Where are the Platform Trial sites located, and how can I tell if they are enrolling?
We are partnering with many research centers across the USA to bring you this innovative ALS trial. All participating research centers are listed on the HEALEY ALS Platform Trial site map. Sites that are actively enrolling participants are listed in bold in the space below the site map.

I am interested in participating in the Platform Trial. Where do I start?
Contacting a local Platform Trial research center/(s) to express interest is the first step towards participation. To find a Platform Trial research center near you, please view the site map. Participation in the trial will involve about seven in-person visits over a period of six months, so we encourage participants to select a site that is geographically convenient.

On the site map page, click the name of the contact person listed for your preferred site to send them an email expressing your interest in participating in the trial.

If you would like help connecting with a local Platform Trial research team, please contact the Patient Navigator at HEALEYALSPlatform@mgh.harvard.edu or 833-425-8257 (HALT ALS)

What information will I need to provide when contacting a site?
When contacting a site to express interest in trial participation, it is helpful to provide the following information:

• Where you live (town/state if resident of USA)
• Where you currently receive clinical care for ALS
• Month and year of weakness onset due to ALS
• Predicted % value of your most recent Vital Capacity measurement (forced or slow) and date of test
• If you are able to safely swallow pills and liquids
• Your contact information and preferred method of communication

Who do I contact if I am not sure which site to select, or I do not see a geographically convenient site listed?
A Patient Navigator is available to help you identify a site. Platform Trial research centers are being activated on a rolling basis, so if you do not see an active site that is geographically accessible to you, please contact the Patient Navigator for additional information or check our site map for updates.

Will I be automatically enrolled in the trial when I express my interest in participating?
No, but expressing interest is a great first step! After you express interest in participating, the research team at your site of interest will begin a Pre-Screening Process to assess whether you might be eligible to enroll in the Platform Trial. The research team will review your medical records, which may need to be faxed if you are not an established patient at that center. If it seems like you might meet the criteria for participation, the team will proceed with scheduling a pre-screening phone call. The pre-screen serves as an opportunity to review the eligibility criteria for the trial in more depth. If the pre-screen is successful, the research team might then offer a Master Protocol Screening visit, which is an in-person visit. The Master Protocol Screening visit is the final step to determine whether someone is eligible to participate in the Platform Trial, and it is at this visit that patients can decide to enroll in the trial if they are eligible.

Once I express interest in participating in the trial, how long will it be before I hear back from somebody?
You should expect to receive a response, either by phone or email, directly from your site/(s) of interest within 5 business days of contacting them. A member of the research team will schedule a time that is convenient for you to discuss the inclusion and exclusion criteria for the trial. This discussion usually takes 30-45 minutes. If you do not receive clinical care at your site of interest, the research team may first require an in-person evaluation or request certain medical records prior to scheduling a pre-screening phone call.

Some items that you should be prepared to discuss during the pre-screening process include:

• Any medical records requested by the site beforehand
• List of current medications / supplements and dosages
• Any significant medical history (other than ALS)
• Any questions you may have about the trial

What if I am not contacted by the site after expressing interest?

If you do not receive a response from the site within the expected timeframe of 5 business days, please contact the Patient Navigator for assistance.

Phone: 833-425-8257 (HALT ALS)

Email: HEALEYALSPlatform@mgh.harvard.edu

When will I know if I have passed the Pre-Screening Process, and will be offered the option to proceed with the Master Protocol Screening Visit?

This process is site specific. At the completion of the Pre-Screening visit or phone call, the Research Coordinator or Research Nurse will advise you of next steps, which may include further review of medical records by the team to determine your eligibility to proceed to the Master Protocol Screening Visit, and if applicable, will assist you in setting up that appointment.

What happens at the Master Protocol Screening Visit?
Various members of the trial team may participate in your Master Protocol Screening Visit, including the Site Investigator. This visit must be in-person at the research site. During the visit, the Master Protocol Informed Consent Form is reviewed in entirety, and after all of your questions about the trial have been answered, it is signed by both you and the Site Investigator. The following things may be assessed during this visit: vital signs, vital capacity (breathing test), neurological exam, ALSFRS-R and other questionnaires, review of current medications and supplements, and discussion of any updates on your health or one-time health events since prior communication.

At what point do I need to commit to participation in the trial?

It is important to remember that your participation in research is completely voluntary. The first step toward making a commitment to participate in the Platform Trial occurs at the start of your Master Protocol Screening Visit, when you and the Site Investigator sign the Informed Consent Form. This important step happens after the Site Investigator reviews the Informed Consent Form in its entirety with you, and answers all of your questions about the trial. The Informed Consent Form identifies all aspects of the trial, including things such as time commitments, procedures and tests to be done, data to be collected, and contact information.  Once the Informed Consent Form has been discussed and signed, you will receive a copy of the signed consent form and proceed through the rest of the enrollment process.

When will I be assigned to a regimen?
After reviewing outcome measures from your Master Protocol Screening Visit, if you are determined by the Site Investigator at the site to be eligible to participate in the trial, you will be assigned to a regimen. A member of the team will reach out to you soon after your screening visit to inform you of your eligibility and regimen assignment if applicable.

What if I commit to participating in the trial and then later change my mind?

While we hope that you will complete the six-month placebo-controlled portion of the trial to allow for the appropriate level of data to be collected to advance ALS science, your participation is voluntary, and you may revoke your commitment at any time without repercussion.

How are participants assigned into regimens?
Regimen assignment is done randomly via a computer program and is based on the actively enrolling regimens (investigational products) at the site at which you completed your screening visit.

When will I know which regimen I have been assigned to?
You will be informed of your regimen after the Master Protocol Screening Visit, once your eligibility has been determined. Within the Regimen, you will be randomized again, with a 3:1 ratio of active drug to placebo assignments (each patient has a 75% chance of receiving the study drug). Because the HEALEY ALS Platform Trial is a double-blinded study, neither you, nor the study staff, will know if you are receiving the active drug or placebo throughout the duration of the 6-month placebo-controlled portion of the study.

Do any of the regimens show more potential for efficacy than others?

All regimens have equal potential for efficacy. All of the investigational products have been selected by an expert committee of ALS researchers and scientists based on scientific rationale.

What happens if a regimen is already fully enrolled?

Each regimen will enroll 160 participants. Once that goal has been met for a particular regimen, it closes to enrollment. Because the Platform Trial is a “perpetual trial”, new regimens continue to be added, with the goal of having multiple potential therapies enrolling at any given time.

For a list and description of current and future regimens included in the trial, click here.

What happens at a regimen protocol screening visit?

During the regimen protocol screening visit, you will learn about the investigational product for the regimen you have been assigned, and you will be administered the first dose of study drug or placebo. The following things may be assessed during this visit: vital signs, vital capacity (breathing test), neurological exam, ALSFRS-R and other questionnaires, review of current medications and supplements, and discussion of any updates on your health or one-time health events since prior communication.

If I am ineligible for the regimen I was assigned to, am I able to join a different regimen?

At the regimen protocol screening visit, if you are determined to be ineligible for the regimen you were initially assigned to, you will be assigned to a different regimen during the same visit.

How quickly after being accepted into the regimen will I start my trial visits?

The timeline for beginning your regimen is dependent on the regimen you are assigned to.  For regimen A, if you require the necessary vaccination, your baseline visit would occur at least 14 days after your regimen A screening visit (a meningitis vaccination is required for all Regimen A participants, because the investigational drug being studies acts on the immune system). For regimens B, C, and D, the screening and baseline visits can be combined. Once it is determined that you are eligible for the specific regimen, the baseline visit procedures can occur directly after the screening visit (on the same day).

What is Open Label Extension (OLE)?

Open Label Extension is a program that allows research participants access to the “actual” investigational product being tested in the placebo-controlled portion of the trial. Upon completion of the placebo-controlled portion of the Platform Trial, you will be offered the opportunity to receive the investigational product of the regimen you participated in during the trial. For example, if you participated in regimen B for the six-month trial, as outlined in the Protocol and Informed Consent Form, upon completion, you are eligible to receive that regimen study drug for a specified amount of time. There are no placebos in the OLE period of the study – all participants will be receiving active study drug.

Will all research participants on all regimens be offered Open Label Extension, or will I need to qualify?
Upon completing your six-month commitment to the placebo-controlled portion of the study, you will be eligible for the Open Label Extension Program for your assigned regimen. Participation may require that additional safety qualifications be met, based on the regimen.

Can I participate in Open Label Extension for a regimen other than the one I was randomized in to?

As OLE is considered an extension of the regimen study you will have already participated in, it is not possible to move to another regimen during OLE.

Can I participate in Open Label Extension at a different research site than I began the trial at if one closer to me opens?

OLE is considered an extension of the regimen study you will have already participated in. Your participation in the OLE program must continue under the same study team as your participation in the initial six-month period of the placebo-controlled portion of the study.

How long does Open Label Extension last?

The duration of OLE offered may vary by regimen; however, it will generally last for several months to one year, dependent on study results for that particular regimen. You may choose to discontinue the OLE program at any time.

How long do I have to decide whether I want to participate in the Open Label Extension program or not?

During your Week 16 study visit of the placebo-controlled portion of the trial, you and the Site Investigator will review the Open Label Extension Informed Consent Form. You must decide by the end of your Week 24 visit if you choose to participate in the program.

If I choose not to participate in the Open Label Extension program, can I join another regimen in the placebo-controlled trial?

Yes, you may decide to start the enrollment process again and be assigned to another regimen in the trial. Please keep in mind that the same initial eligibility criteria will apply.

If I join another regimen in the trial, is there a chance that I will be put into the placebo group?

Under the current design of the HEALEY ALS Platform trial, participants are randomly allocated in a 3:1 ratio to active drug or placebo each time they are assigned within a regimen. With a 3:1 allocation ratio, there is a 1 in 4 (25%) chance of being randomized to placebo for any given regimen. If a participant completes one regimen and is re-randomized within a second regimen, the chance of receiving placebo both times is 1 in 16 (6.25%).

What is the best way to decide if I should try OLE or re-randomize?

This can be a very difficult decision to make. It is best to discuss with your ALS clinical provider, as they can talk through your options with you.

When will the trial results be communicated?

Aggregate (pooled) efficacy data will be reviewed after the final participant in the regimen study completes the six-month placebo-controlled portion of the trial, and the database has been locked for changes by the regulatory authorities. The data review period generally takes a few weeks to a few months before results can be understood and communicated.

To ensure the safety of all research participants, safety data is checked throughout the trial. However, efficacy data cannot be assessed during the trial without adversely impacting the ability to potentially receive FDA approval should the experimental therapy be shown to be effective.

Will I know if I was on placebo or active drug?

You will not know if you were on a placebo or study drug during the placebo-controlled portion of the trial until the study has completed. The study is deemed “complete” when all participants have completed the placebo-controlled portion of the trial, aggregated data has been assessed, and trial results have been publicly announced. Should you choose to participate in the Open Label Extension Program (OLE), you will receive the actual investigational product. There is no placebo in OLE!

If a regimen is found to be successful, will the FDA require additional phases/trials?

This is dependent on the statistical significance found in the data. The HEALEY ALS Platform Trial has been implemented in a way that, should one of the experimental drugs be found to be statistically impactful, the drug could potentially be approved by the FDA with no further trials required.