Last doses of study drug and study visits occurred in November 2019. Safety follow-up visits will occur within 4-12 weeks after your last dose of study drug.
End of Trial and Open-Label Extension (OLE) Frequently Asked Questions
These FAQs are current as of 02/07/2020. Some questions may now be out of date. Please refer to the latest press release for updated information.
When do the solanezumab (“sola”) and gantenerumab (“gant”) blinded drug arms in the DIAN-TU trial officially end?
When will the DIAN-TU announce the results of the current trial drug arms of solanezumab and gantenerumab; and where can I look for the results?
Results of the current trial are planned to be announced by the end of March 2020 and a communication will be sent to your current study doctor at your DIAN-TU site. A press release will be posted on the DIAN website and will be sent out to DIAN Expanded Registry (DIAN EXR) participants.
What does a “positive” readout of the drug(s) mean?
The level of success will be 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 is pre-specified (documented prior to study results or data analysis) in a detailed statistical plan that is 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 will consider the other (secondary) outcome measures, which are the additional measures (tests) that are done during the trial. The amount of the drug’s effect, and any other information that we have from the 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 benefit we see, and how much the drug actually helps, can influence the decisions about continuing with the Open Label Extension.
What does “Open Label Extension or OLE” mean?
Open Label Extension, or OLE, may begin after the randomized (blinded) portion of the trial is completed and if one or both drugs are found to have the potential for benefit. Eligible trial participants will 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 importantly, it offers the opportunity for participants who were previously on placebo to take the active drug. OLE enables the trial to continue to measure the drug’s effectiveness, how long that effect may last, and if the effect will be sustained (continued).
When will I find out whether I was on active drug or placebo during my participation in the trial?
If there is an Open Label Extension (OLE), you may request to find out whether or not you were on placebo or active drug at the end of the OLE period. If there is not an OLE, you may ask for this information when notified that there will not be an OLE. If neither arm demonstrates the potential for benefit, and you wish to maintain your genetic blinding, you will need to receive genetic counseling and testing before being informed of active or placebo status, since information on receiving an active drug would be unblinding to your genetic status.
Why do I have to wait to learn whether I was on active drug or placebo?
It is possible that additional information will be needed during the OLE that will help to determine the true benefit of the drug(s). 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.
What happens if I am participating in the gantenerumab arm and only solanezumab shows benefit; or I am in the solanezumab arm and only gantenerumab shows benefit?
If only one of the drugs shows the potential for benefit, then participants who are in the other drug arm will have the opportunity to enroll in the open label extension for the drug that showed potential for benefit. If both drugs show the desired benefit or potential for benefit, you would continue in the drug arm you were assigned to during the trial.
Who will participate in a possible Open Label Extension?
Individuals who participated in the blinded period of the trial may be eligible to continue in the Open Label Extension. Participants must know that they are positive for the Alzheimer’s disease-causing mutation, and the study doctor must confirm it is safe for each participant to receive active drug. You cannot join OLE if you did not participate in either the gantenerumab or solanezumab blinded drug arms.
Will I have to find out my genetic mutation status in order to enroll in OLE, and why?
Yes, since placebo will not be offered, only participants who know they are positive for the genetic mutation, and therefore have potential to benefit from the treatment, will be able to enroll into OLE to receive the active drug. Once a drug is shown to be beneficial, or have the potential for benefit, only the active drug should be administered because there is no benefit for participants to continue with study procedures and receive placebo.
If I do not want to learn my genetic status, can I still enroll in the next drug arm(s)?
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. This will depend on the final study design and whether there is a placebo-only arm of the study.
When will Open Label Extension begin?
Open Label Extension could start as soon as the second quarter of 2020 (April-June 2020).
Why may I have to wait for 6 months after my last study dose to start in the OLE (also knowns as a ‘wash-out’ period)?
If the drug arm you were assigned to during the trial does not show potential for benefit but the other drug does, you will have to wait for six (6) months after your last dose of blinded study drug to start the other drug. This is known as a washout period, which is necessary to allow your current study drug to be normally cleared from the body before starting the new drug. This will be required even if you were on placebo because you will not know whether you were on placebo or active medication during the trial.
How long would the effects of either solanezumab or gantenerumab stay in my system? Will any potential benefits continue once I stop dosing, or will the benefits stop as soon as I stop receiving the drug?
Both of these drugs (known as an antibody) remain in the body for five to six months after last drug administration. This is why having a wash-out of 6 months is necessary. Because of this, you may continue to experience potential benefit for months after you stop receiving doses. Changes in Alzheimer disease are generally slow, often measured in years, so we expect changes in your disease will not be large from going a few months without receiving drug.
Will I visit my current study site for OLE and still have a study nurse come to my home for drug administration?
Yes, you will have an annual site visit and monthly home health nurse visits to administer the drug and cognitive testing at certain visits.
Will my study partner still need to participate in annual visits during OLE?
Yes, a study partner will still be needed during OLE to complete assessments about your memory and thinking. This will help us continue to study the drug’s effect.
What tests are performed in OLE?
You will have cognitive testing every 6 months. Depending on which drug is included in OLE, there may be additional safety measurements including safety MRIs during drug escalation/titration (dose increase). At the annual visits, it is possible you will have a lumbar puncture, PET scans (PIB-PET, FDG PET, and AV-1451 tau PET), MRI, bloodwork, and clinical and cognitive testing; however, the exact tests will not be determined until the study team has reviewed the results of the placebo-controlled phase of the study.
Why do I have to do dose titration (slow dose increase) again?
Dose titration is the process of slowly increasing your dose of drug to minimize any potential side effects. Because you will not know whether you were on active drug or placebo in the blinded period, all participants will need to dose titrate/escalate and start at the lower dose and increase to the highest dose.
How long will I receive the active drug in OLE?
The OLE period is expected to last up to approximately two years, or if/when the active drug is approved and becomes available to clinical doctors to prescribe to their patients. If the OLE period is opened, it does not guarantee that the drug will be approved. There is always the potential that the drug may not be approved and the OLE period would be stopped/closed.
What happens if there is no Open Label Extension?
If there is no Open Label Extension, you may be eligible to enroll into the Cognitive Run-In (CRI) period of the trial which will then begin randomizing new tau-based drug(s) and placebo in 2020 or 2021.
How do I arrange for genetic counseling and testing?
Contact the DIAN Expanded Registry (DIAN EXR) at firstname.lastname@example.org to request genetic counseling and testing. You may also contact your site coordinator to make the request, and the DIAN EXR will work with the coordinator to provide you the necessary steps.