Purpose of the ATLAS Study.

The ATLAS Study is assessing the safety and potential effectiveness of an investigational drug that may delay the onset of signs or symptoms of ALS and/or slow the decline in function once signs or symptoms appear. We’re conducting this study to learn about the safety and potential efficacy of the investigational drug in people who carry certain SOD1 gene variants prior to onset of signs or symptoms of ALS.

Who may qualify.

Eligible participants must:

  • Not have any signs or symptoms of ALS
  • Have a certain superoxide dismutase 1 (SOD1) gene variant that has high/complete penetrance and is associated with a rapidly progressive disease
    • Penetrance is the probability of individuals carrying a particular variant actually developing disease
  • Be 18 years of age or older

There are additional eligibility requirements that the study doctor can explain to you.

If you decide to take part in the study, all study-related treatments and assessments will be provided to you at no cost. Compensation for time and travel may be available. Participation is voluntary, and you will be able to leave the study at any point without penalty. We would just ask that you contact the study team, and they may ask you to visit the study center for one final visit with assessments.

What important medical question will this study ask?

The ATLAS Study is part of a larger clinical research effort to evaluate the safety, dosing, and potential efficacy of an investigational drug in people who have a SOD1 gene variant. This study will evaluate whether initiating an investigational drug early (before signs or symptoms of ALS) will delay the onset of signs or symptoms of ALS and/or slow the decline in function once signs or symptoms appear.

The investigational drug (BIIB067) is designed to target the SOD1 gene and potentially reduce the level of SOD1 protein in people with ALS associated with a SOD1 gene variant.

What should I expect?

In order to enroll in the study, you will need to provide your informed consent to participate by signing the informed consent form (ICF), which details the study procedures and your responsibilities as a participant.

You will then need to attend the screening visit(s) for initial tests and assessments to see if you are eligible to participate. After all necessary tests and assessments have been completed, and if you are eligible to participate, you may choose to enter the study.

How long will study participation last?

The maximum study duration is approximately six years and six months.

Study participation.

What will happen during the study?

Screening period.

During this period, the study team will perform tests and procedures to make sure the study is a good match for you. To participate in this study, you must undergo genetic testing to see if you have one of the SOD1 gene variants being studied. You will receive both pre-test and post-test genetic counseling sessions, and you may request additional genetic counseling as needed throughout the study at no cost. As a reminder, even if you have a SOD1 gene variant being studied, you may never develop any signs or symptoms of ALS.

This study comprises four segments: Parts A, B, C, and D. 

Part A.

If you test positive for one of the SOD1 gene variants being studied and pass other screening tests, you will be eligible to enter Part A of the study. During this part, you will not receive any study treatment, but your health status and neurofilament (NF) level will be closely monitored. The study team will evaluate your blood samples monthly for an NF level that is above the threshold. You and the study doctor will know when the NF level is above the threshold to consider eligibility for the next part of the study. Part A may last up to approximately four years and three months.

What is neurofilament (NF)?

Neurofilament is a protein made by the body that is found in neurons. This study will use NF as a biomarker. Biomarkers are measurable substances in the body that can change as a result of disease or treatments. Examples of biomarkers include vital signs like pulse and blood pressure, changes detected on imaging tests, and laboratory tests like protein level measurements. Testing for biomarkers can sometimes help diagnose a certain disease, determine or predict the severity of the disease, or evaluate how well and safely a medicine may work in treating the disease.1,2

Individuals with one of the SOD1 variants being studied and with elevated NF levels may be more likely to develop signs or symptoms of ALS in the short term, but it is not certain they will. NF levels will be closely monitored as part of ATLAS Study participation. However, the exact NF level will not be disclosed to the participant or the study doctor.

Part B.

If your NF level increases above the pre-determined threshold during your participation in Part A, the study doctor will evaluate the cause of the increase in NF. If the study doctor determines that the NF increase is not attributable to an alternative cause, you may choose to be screened for eligibility for potential participation in Part B. During this part of the study, you will be assigned to receive either the investigational drug or a placebo. You will be assigned randomly by a computer, and you will have an equal chance of receiving the investigational drug or placebo. Neither you nor the study team will know whether you received the placebo or the investigational drug.

The investigational drug or placebo is delivered intrathecally, which means that it is given to you by a procedure called a lumbar puncture. Before the investigational drug or placebo is given, a trained clinician will perform a lumbar puncture (LP). During the LP, the clinician will insert a needle into the fluid-filled space below the end of your spinal cord through your lower back. The clinician will take a sample of your cerebrospinal fluid and then inject the investigational drug or placebo.

A placebo is a substance that looks like the investigational drug but contains no actual ingredients. Placebos help us make sure that any changes seen during the study are due to the investigational drug alone and not another reason. Participants are assigned their participant group at random (by chance), and neither they nor the study team is told which group they have been placed into until after the study is finished.

Part C.

If you show signs or symptoms of ALS during Part B of the study and your study doctor and a group of independent reviewers confirm these signs or symptoms, you may choose to be screened for eligibility for potential participation in Part C of the study. During this part, you will receive the investigational drug. The total length of participation in Parts B and C of the study is up to approximately two years.

Part D.

If you start to show signs or symptoms of ALS during your participation in Part A or during screening for Part B, and your study doctor and a group of independent reviewers confirm these signs or symptoms, you may choose to be screened for eligibility for potential participation in Part D of the study. Part D is another blinded treatment period. During this part, you will be randomly assigned to receive the investigational drug or a placebo. However, unlike Part B, for every three participants, two will receive the investigational drug and one will receive placebo. The total length of participation in Part D is up to approximately two years.

Can I leave the study if I change my mind?

Participation in any clinical research study is completely voluntary, and participants may choose to leave the study at any time for any reason. If you would like to leave the study, you should discuss this with your study doctor, who will give you information about how to do this safely.

Early termination/end of study visit.

If you stop the study early for any reason, you will have an end of study visit. This will occur about four weeks after the last dose of your assigned study treatment or four weeks after your last visit in Part A. An end of study visit will also be done if you complete treatment in Parts B, C, or D of the study. This visit may be completed at home or at the study center.

If you discontinue Part A, you will not be eligible to participate in Parts B, C, or D. Similarly, if you discontinue study treatment in Part B, you will not be eligible to participate in Part C.

How will participants’ health be monitored?

Because safety is our highest priority, you will have up to 34 visits at the study center and up to 58 home visits. These visits will take place approximately every 28 days (depending on which part and period of the study you are in), and the study team will conduct several assessments to monitor your condition.

  • Study assessments will vary from visit to visit, but may include:
    • Blood sample collection
    • Urine sample collection
    • Health questionnaires
    • Vital sign measurements
    • Electrocardiogram (ECG)
    • Lumbar puncture
    • Reporting signs or symptoms of ALS
    • Neurological exam
    • Physical exam

Are there any potential risks?

It’s important to remember that, as with any investigational drug, you can never be sure of the outcome. Your health may improve, it may stay the same, or it may get worse. This could happen even if you are assigned to the placebo group.

Not all side effects of this investigational drug (BIIB067) are known, and there may be side effects that are unpredictable. In a previous study with the investigational drug, BIIB067, the most common side effects experienced by patients were: headache, procedural pain, post-lumbar puncture syndrome, and falls. It’s important that you tell the study team if you experience anything unusual during your time in the study. The effects of the investigational drug when combined with other medicines or substances, such as alcohol, are not fully known. A combination of medicines and alcohol or other substances might result in serious or even life-threatening reactions. Therefore, while you are in the study, you should always discuss the use of any medicine (over-the-counter, prescription, herbal, or recreational drug), or substances such as alcohol, with your doctor before taking the investigational drug. Further details regarding risks and potential side effects are provided to you in the informed consent form. You can always talk to your study doctor about any concerns you have at any point during the study.

Some of these assessments may be uncomfortable or may carry certain risks, but the study team will explain each assessment to you in detail if you decide to take part.

References.

  1. ALS Association (n.d.). Biomarkers. www.als.org/research/research-we-fund/scientific-focus-areas/biomarkers.
  2. U.S. Food & Drug Administration (2017, March 3). What are biomarkers and why are they important? transcript. www.fda.gov/drugs/biomarker-qualification-program/what-are-biomarkers-and-why-are-they-important-transcript.