The ASCEND Study
is evaluating a
potential treatment option for SMA.
If you or your child has been diagnosed with spinal muscular atrophy (SMA), the ASCEND Study may interest you. This clinical research study is investigating how safe and how well an investigational higher dose of nusinersen may work in participants with SMA who were previously treated with risdiplam.
The purpose of the ASCEND Study is to evaluate the safety and efficacy of an investigational higher dose of nusinersen for participants with SMA who were previously treated with risdiplam. This higher dose of nusinersen is not currently approved for SMA and is considered an investigational medication.
About the study drug.
Nusinersen is an antisense oligonucleotide, a man-made molecule with highly modified structures similar to DNA and RNA, that is designed to bind to pieces of RNA and makes them work in a specific way. For people with SMA, nusinersen may help increase the production of the survival motor neuron (SMN) protein, the protein that is needed by motor neurons to function but people with SMA cannot make enough of.
While taking nusinersen, it is possible that side effects may occur. Some of these are known to us already and will be discussed with you before you agree to take part in the trial. We encourage all participants to report any changes in their health to the study team.
Study participation.
The total length of participation is about two and a half years and consists of a Screening Period, a Core Study Period, and an End of Core Study Period Visit. After completing the End of Core Study Period Visit, participants may be given the opportunity to continue in an optional Long-Term Extension (LTE). For participants enrolling in both the Core Study Period and the LTE, the total study duration will be approximately four and a half years.
Screening Period.
During this period, the study team will perform tests and procedures to make sure the study is a good match for you or your child. You or your child will also undergo genetic testing, as well as talk about your or your child’s medical history with the study team. This period will last approximately three weeks.
Core Study Period.
During this period, you or your child will receive the study drug given through a lumbar puncture (LP), which will be performed by a trained clinician. During this procedure, the doctor will put a thin needle into the fluid-filled space below the end of the spinal cord through the lower back. The doctor will take a sample of the cerebrospinal fluid and inject the study drug. You or your child must stay very still during the entire procedure. The first two doses will be received approximately two weeks apart. After that, the doses will be every four months for two years. The first two visits, Day 1 and Day 15, will include a 24-hour stay at the study site. During all of the visits, the study team will check your or your child’s vital signs; collect urine and blood samples; perform an electrocardiogram (ECG); assess motor function; conduct a physical and neurological exam; and ask questions about quality of life and ventilator use, if applicable. See below for more information about the study assessments.
End of Core Study Period Visit.
Four months after the final Core Study visit, there will be an End of Core Study Period Visit for participants not continuing in the optional LTE to check your or your child’s health. During this visit, the study team will conduct a final check of your or your child’s vital signs; collect urine and blood samples; perform an ECG; assess motor function; perform a physical and neurological exam; and ask questions about quality of life and ventilator use, if applicable.
Long-Term Extension Period.
After completing the End of Core Study Period Visit, participants may be given the opportunity to continue study drug treatment in a Long-Term Extension (LTE). For participants transitioning to the LTE, the End of Core Study Period Visit will also serve as the first dosing visit of the LTE. The LTE will comprise of approximately two years of continued treatment. During all of the visits, the study team will check your or your child’s vital signs; collect urine and blood samples; perform an ECG, conduct a physical and neurological exam; and ask questions about ventilator use, if applicable.
End of LTE Visit.
Four months after the final LTE visit, there will be an End of LTE Visit to check your or your child’s health. During this visit, the study team will conduct a final check of your or your child’s vital signs; collect urine and blood samples; perform an ECG; conduct a physical and neurological exam; and ask questions about ventilator use, if applicable.
Because safety is so important, participants will have up to 11 visits total through the Core Study Period. The first two visits in the Core Study Period are two weeks apart. After that, visits will take place about every four months, and the study team will conduct several assessments to monitor your or your child’s condition. Additionally, those who participate in the optional LTE will have up to seven additional visits. These visits will follow the same dosing schedule via lumbar puncture every four months for an additional two years, and the study doctor will continue to review your or your child’s overall health.
Study assessments will vary from visit to visit, but may include:
Lumbar puncture
Vital sign measurements
Physical exam
Neurological exam
ECG
Urine sample collection
Blood sample collection
Compound muscle action potential (CMAP) test
Motor function test
Health questionnaires
Pulmonary function tests
Ventilator-use diary
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.
Find a participating site.
To learn more, and to see if you or your child may qualify, contact the participating site nearest you.
SMA is a rare genetic disease that affects the nerves in the spinal cord, causing severe muscle weakness, loss of movement, and difficulty breathing. It is an autosomal-recessive genetic disorder, which means that generally both parents must carry a mutated survival motor neuron 1 (SMN1) gene for their baby to inherit SMA. Because each parent typically has only one mutated SMN1 gene, the parents do not have SMA. They are considered “carriers.” SMA affects approximately one out of every 11,000 babies in the US.
While there are now treatment options, there is still no cure for SMA, and unmet medical needs remain. Researchers conducting the ASCEND Study are examining a medication known as nusinersen to determine its safety and effectiveness at a higher dose in individuals previously treated with risdiplam.
*curesma.org/about-sma/
Understanding the genes behind SMA.
Genetic testing.
In the general population, a test for SMA can detect about 95% of carriers.
The American College of Obstetricians and Gynecologists (ACOG) recommends that all women who are thinking about becoming pregnant, or who are already pregnant, should undergo a carrier screening for SMA and other genetic conditions. If the woman is a carrier, her partner can then be tested.
In addition, individuals with a family history of SMA are often encouraged to have carrier screening. Deciding whether to undergo genetic testing is highly personal, and we strongly recommend discussing it with a physician or genetic counselor.
What you should know about
clinical research studies.
What is a clinical research study?
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 or have your child leave the study, you should discuss this with the study doctor, who will give you information about how to do this safely.
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 or your child is eligible to participate. After all necessary tests and assessments have been completed, and if you or your child is eligible to participate, you may choose to enter the study.
How long will study participation last?
The maximum duration of the Core Study Period is approximately two and a half years. For participants enrolling in both the Core Study Period and the LTE, the total study duration will be approximately four and a half years.
Are there any potential risks?
It’s important to remember that, as with any study drug, you can never be sure of the outcome. A participant’s health may improve, it may stay the same, or it may get worse.
Details regarding risks and potential side effects are provided to you in the informed consent form. You can always talk to the study doctor about any concerns you have at any point during the study.
No personal identifying information of individuals referred to the study or individuals participating in the study will be shared outside the study team and regulatory agencies.
A clinical research study is a scientific investigation designed to answer important questions about a study drug, such as:
Is it safe?
Does it work?
Which dose works best?
What are the side effects?
All study drugs must be tested in clinical research studies before they are approved and available to be prescribed by doctors.
People take part in clinical studies for a number of reasons. For example, they may:
Have run out of approved or alternative treatment options
Want to help others like them or add to our knowledge of their disease or condition
Be interested in the close monitoring they receive when in a clinical research study
Even before a study starts, safety is a high priority. Every study must be reviewed and monitored by either an institutional review board (IRB) or an independent ethics committee (IEC). These groups, which are made up of both scientists and nonscientists, review the study’s plan to make sure that:
The rights of participants will be protected
There are no unnecessary risks involved
The study answers important unanswered medical questions
Lumbar puncture
Vital sign measurements
Physical exam
Neurological exam
ECG
Urine sample collection
Blood sample collection
Compound muscle action potential (CMAP) test
Motor function test
Health questionnaires
Pulmonary function tests
Ventilator-use diary