DIAN-TU-001: FAQs

The level of success was determined by several different factors. There is a measure called the primary outcome, which is the one thing that is used to determine whether the study is positive. The level of effect was pre-specified (documented prior to study results or data analysis) in a detailed statistical plan that was agreed upon, approved, and shared with our partners, including regulatory authorities and others. That is one of the main driving factors for measuring the drug(s)’ success; however, we also considered the other (secondary) outcome measures, which are the additional measures (tests) that were done during the trial. The amount of a drug’s effect, and any other information that we have from a trial, can be used to help determine whether a drug is beneficial or not.

The answer can be complicated and is not always a simple ‘success’ or ‘failure’. There is a lot of information and degrees of success. The size of the effect we see can influence the decisions about continuing with the Open Label Extension. In the case of both solanezumab and gantenerumab, the primary outcome was determined to be negative. However, there were some positive biomarker measures of disease activity and progression in the trial.

Open. Label. Extension, or OLE, is a phase of a study that occurs after the randomized (blinded) portion of the trial is completed if a drug is found to have the potential for benefit. Eligible trial participants take the active form of the drug without placebo. OLE allows active drug to be given to all participants at the same time and to follow them over time. OLE allows more scientific data to be collected and it offers the opportunity for participants who were previously on placebo to take the active drug. OLE enables a trial to continue to measure the drug’s effectiveness, how long that effect may last, and if the effect will be sustained (continued).

Additional information will be needed during the OLE that will help to determine the potential benefit of gantenerumab. Because of this, it is important to keep the OLE period of the trial as close to the original, blinded part of the trial as possible. If participants and site investigators find out who was on active drug or placebo during the blinded period of the trial, it could influence performance on important cognitive tests during the OLE period.

It is possible that you could enroll into the Cognitive Run-In (CRI) period of the DIAN-TU trial, and the next/future drug arm(s), without learning your genetic status.

Contact your DIAN-TU site coordinator to request genetic counseling and disclosure of test results. You may receive genetic counseling remotely via phone and/or video chat (in-person counseling may also be requested, if available) and will not need to have a new blood draw. You will be able to receive results from genetic testing performed when you first enrolled in the trial. This process is only available for those eligible for the gantenerumab exploratory OLE. If you cannot reach your site coordinator, please contact the DIAN Expanded Registry at dianexr@wustl.edu.

Dr. Bateman – The vast majority of mutations which have been discovered today are eligible to be enrolled in both the DIAN-TU trials and the DIAN observational study. The DIAN-TU trials has a limitation that we can only enroll those mutations which have been shown to be pathogenic, and that we have determined by looking at the literature of the scientific results and can even do blood sample draws or experiments to prove that that mutation causes the disease. That’s necessary in order for us to be able to predict who’s going to get the disease and about when they’re going to get it.

There must be a documented autosomal dominant mutation in the family, however, participants may not be required to know or learn their personal genetic mutation status in order to participate in a trial. Each trial will outline the specific requirements regarding mutation status knowledge. If a person knows their mutation status is positive, they may be eligible for a trial. Individuals that know their mutation status is negative, meaning they do not have the mutation that causes AD in their family, are not eligible to participate in a trial.

Dr. Bateman – In order to find out if one has the genetic mutation there’s a genetic test, a simple blood test, that’s sent off to the lab, and after some number of weeks those results come back. Before that’s done, extensive discussion with that person and their family has been had about whether they want to find out, what the implications of finding out, what kinds of insurance might they need before they find out.

No. There are a number of specific enrollment or “eligibility” criteria for a DIAN TU trial that must be met in order to qualify for participation. The DIAN-TU study team, in collaboration with our Pharma partners and the regulatory agencies in participating countries, such as the US Food and Drug Administration (FDA), design these criteria to make ensure the trials are as safe and effective as possible, as well as ensure the results of the trials will provide useful information as to whether the tested treatments impact AD.

Some DIAN-TU trials use placebo; these trials are called placebo-controlled. In order to determine the effectiveness and/or action of the study drug(s), the trials are designed to include a placebo which is an inactive preparation designed to resemble the test drug.

In placebo-controlled trials, a computer system randomly assigns participants to active drug or placebo. The assignment to drug or placebo is double-blinded, which means neither the participant nor any member of the study team will know whether an individual is receiving study medication or placebo. All mutation negative participants are assigned to placebo for safety purposes and so that mutation status is not revealed to participants or study teams.

All participants are given consent forms to review prior to enrolling in a study; the list of potential side effects will be included in the consent form. Participants are encouraged to take as much time as needed to review the consent form. A member of the study team will be available to answer any questions prior to the first study visit. Once enrolled in a study, participants will be followed closely by the study nurse team. There may also be unknown side effects.

No. Even people on placebo may have side effects. A side effect is likely to be mild and may not be different from everyday type discomforts such as headache, fatigue, and nausea. Participants will be encouraged to report all side effects they experience so they can be documented. The study team will do everything possible to keep study team and participants blinded their mutation status, but it is possible that participation in a study could result in learning their mutation status, for example if having a side effect that is associated with the active drug.

Yes. The DIAN-TU has arranged to have visiting nurses available to complete study visits at participant homes and offices. The visiting nurses are available on weekdays, weekends and also during evening hours, if necessary. The study teams will work with participants to schedule study visits to ensure all safety visits are completed as conveniently as possible. Visiting nurses are not site personnel but are contracted through a home health care company.

Participants may be able to remain on many prescription medications and enroll in a trial (this is determined by the specific trial criteria). For more detailed information, contact the DIAN expanded registry and a trial nurse will be able to provide more specific information.

No. You do not have to tell your primary care doctor or any other health professional that you are participating in a trial. It is completely your decision whether or not you choose to share this information with your doctor.

If you would like more information, please see the DIAN Expanded Registry section of this website or visit clinicaltrials.gov The trial currently has many active participating sites around the world.

Dr. Clifford – Lumbar punctures are a really critical part of much of brain research. The brain is very protected from all of the rest of the world. It’s such a vital and delicate organ that it, literally, is walled off by special blood vessels and the bones of the skull. It’s really hard to study the brain but it turns out that it soaks in fluid, it’s almost like a shock absorber fluid that we call the cerebrospinal fluid or CSF, and you can safely sample this sort of cushion around the brain by doing lumbar punctures – putting the needle in the low back and taking a sample of the fluid. That fluid is constantly replenished so when we take a sample, it’s replaced generally in 1/2 an hour to one hour. So, people can give up that fluid and it can be safely sampled. So, this has become a very important way to know what’s going on and it turns out that several of the best biomarkers for the onset of Alzheimer’s disease even long before there are any symptoms changes in these proteins in the spinal fluids. So, we hope to see that the treatment turns the curve of those so that they become more normal rather than getting more and more abnormal as they would if we were not succeeding in treating Alzheimer’s. So, it’s a safe procedure. It’s uncomfortable and we recognize that we wish there were an easier way but at present it’s really a wonderful window into what’s going on in the brain and it’s so important to the studies so we really appreciate the fact that our patients are being extremely brave to put up with doing this and it’s all really to speed the gathering of essential information about how these treatments are working.

Dr. McDade – And now we have the ability to look at one of the other hallmarks of Alzheimer’s pathology in addition to those amyloid plaques, there’s these things called the Tau tangles. So now we have PET scans that can actually look at these Tau tangles, and what’s really important is that the Tau tangles seem to be associated more with symptoms, but the amyloid plaques seem to be one of the earlier hallmarks or one of the earlier signatures of the disease that we can pick up. And so now we’re trying to identify what’s the sequence, what’s the best time to intervene. Is it best to focus on amyloid, which is what we’re doing right now, and how does changing amyloid potentially change Tau or vice versa. So, the PET scans are extremely critical to us and, likewise, we have the ability to look at spinal fluid and, in fact, diagnostically we can use spinal fluid even in the clinic. So in in my dementia clinic, I can obtain spinal fluid and test for the amyloid protein as well as the tau protein. And we already know that there’s changes that happen in the spinal fluid many years before we expect people to have symptoms. So what we’re trying to do right now is to identify within things like the blood, within spinal fluid, through cognitive testing, through scans what’s going to be our most reliable and most effective targets for both diagnosing as well as measuring treatment response. And right now, we’re approaching this in a sense sort of openly without making assumptions or biases which could impact future research and future effective therapies. So it’s really important that our participants really do their best to participate in all aspects of the trial.

You may not enroll in another intervention study while participating in a DIAN-TU clinical trial, as such participation could interfere with trial results. Examples of interventions include medication trials, studies in which your memory is tested regularly, or for which you have multiple PET scans. If you have further questions about potential participation in other studies, please contact your study coordinator.

No, you may not take anti-amyloid or anti-tau medications while enrolled in a DIAN-TU trial. If you previously took these medications, you must wait approximately 6 months before joining a DIAN-TU trial.

Depending on the trial enrollment criteria and how informed your family members are regarding these criteria, it is possible that someone in your family could learn your status by knowing that you are a participant. For instance, in the current DIAN-TU Secondary Prevention Trial (E2814), all participants must be mutation carriers. If family members are aware of this criterion and know that you are enrolled in the study, they will know you are positive for the family mutation.