Clinical Trials
A clinical trial, or interventional study, tests new drugs and treatments for spinal muscular atrophy (SMA) in a controlled setting using protocols, or plans, that will likely provide conclusive results.
Cure SMA’s Approach
The process of conducting clinical trials can be long, complicated, and difficult. On average, only ten percent of drugs in clinical development get approved by the U.S. Food and Drug Administration (FDA). Through the SMA Industry Collaboration, we fund research to ensure that effective, safe treatments for SMA can progress through clinical trials quickly and gain approval from the FDA and international regulators. Our research also ensures these treatments address the unmet needs of the SMA community, and that the community’s priorities and goals are incorporated into the development, review, and approval of therapies.
See below for spinal muscular atrophy (SMA) clinical trials currently recruiting for participants.
The following list contains currently recruiting trials testing new interventional drugs. New potential drugs need to pass through three phases of interventional testing to show that they are safe and effective before receiving approval from the U.S. Food and Drug Administration (FDA).
- Efficacy and Safety of Intrathecal OAV101 (AVXS-101) in Pediatric Patients With Type 2 SMA (STEER)
- Escalating Dose and Randomized, Controlled Study of Spinraza in Participants with SMA (DEVOTE)
- A Study of Nusinersen Among Participants with SMA Who Received Zolgensma (RESPOND)
- Study of Safety and Efficacy of IV Zolgensma in Pediatric Patients with SMA (SMART)
- A Study to Investigate the Safety and Efficacy of RO7204239 in Combination With Risdiplam (RO7034067) in Ambulatory Children With Spinal Muscular Atrophy (MANATEE)
- A Study to Evaluate Higher Dose (HD) Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy Previously Treated With Risdiplam (ASCEND)
- A Phase 3 clinical trial to further evaluate the safety and efficacy of apitegromab in those living with SMA (SAPPHIRE)
- A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants With Spinal Muscular Atrophy (RESILIENT)
Clinical trials often include an extended post-study follow-up period ranging anywhere from months to years to assess the long-term impact of the treatment. Long-term follow-up (LTFU) studies are conducted to address the needs of the scientific community and regulators, and they may help to inform clinical decision making. Some LTFU studies may only be open to participants of prior clinical trials testing that drug. Others may be open to anyone currently taking the drug and meeting certain criteria. Below is a list of LTFU studies for participants with SMA:
- Long-Term Follow-Up Study of Risdiplam in Participants with SMA (WeSMA)
- Long-term Follow-up of Patients With Spinal Muscular Atrophy Treated With OAV101 in Clinical Trials
See additional SMA clinical trials that are recruiting here.
How Clinical Trials Work
The following is a summary of the clinical trial process. For a more detailed description, download our care series booklet, Learning About Clinical Trials.
Clinical Trial Phases
A drug must pass each individual phase of a clinical trial before advancing. The number of participants in each phase can vary. The numbers given below are typical of trials for an orphan disease, such as SMA. For additional information on major drug programs in development, visit the SMA Drug Pipeline.
Phase 1
Tests safety and dosage levels, usually ten to 20 individuals. Sometimes, these volunteers are healthy individuals. However, for an orphan disease like SMA, some or all may be patients with the condition being studied.
Phase 2
Tests a slightly larger group, usually twenty to 40 individuals, all of whom have the condition being studied.
Phase 3
Increases the number of people tested — up to 100-200, including the control or placebo group. A drug that passes these three phases can be approved and marketed to the general public.
Phase 4
Primarily involves ongoing evaluation and monitoring, even after a drug is approved for the general public.
Regulating Clinical Trials
Clinical trials are regulated before they begin and while in progress.
FDA Approval. Clinical trials are usually conducted in multiple cities/states to ensure the most comprehensive, accurate results. The FDA must approve a drug for use in a clinical trial so the drug can be distributed across state lines. To get FDA approval for the trial, clinical trial sponsors submit an Investigational New Drug (IND) application. Once approved, the IND allows them to distribute the drug for the duration of the trial
IRB Review. Clinical trials are approved by an Institutional Review Board (IRB). This independent committee ensures that a trial is conducted ethically, potential benefits justify any risks, and the rights of participants are protected. The IRB reviews the trial as it progresses
Informed Consent. Trial participants must receive all facts about a trial before it starts and sign an informed consent document. Informed consent is not a contract. Participants can still withdraw from the trial
The SMA Industry Collaboration strives to engage the FDA and other regulatory agencies to bring the priorities of the community to the drug development and assessment process. Learn more about the collaboration’s regulatory engagements to date.
Clinical Trial Protocols
Protocols are a study plan for clinical trials and cover important details.
Who Can Participate. These rules, called “inclusion and exclusion criteria,” typically include age, stage, or type of disease, previous treatment history, and other medical conditions
Study Expectations. This includes what procedures, medications, and dosages will be given to each participant, and how often
Timing Details. This involves working with participants on when they must see a study doctor and what tests or measurements the doctor will use to evaluate them
Control Group (if applicable). Participants in the control group will receive a placebo—an inactive pill, liquid, or powder—or the current standard treatment. The other group is given the experimental treatment. Participants are often not told which group they are in, and the researchers may not know either. This “double-blind” format keeps participant or researcher bias from affecting results
Clinical Trials for Combination Therapy
In the SMA community there is increasing interest in understanding the safety and efficacy of combination therapy. The concept of combining treatments stems from the potential to see added or synergistic benefit by addressing multiple aspects of the disease at the same time to improve outcomes. Clinical trials provide an opportunity to explore the safety and efficacy of combination therapy in a controlled setting using testing protocols and inclusion criteria most likely to yield conclusive results. Protocols will often compare outcomes from combined treatments to the use of a single treatment alone.
Learn more about potential benefit and risk considerations of combination therapy.
There are multiple approaches being explored to treat SMA. “SMN dependent” methods increase the amount of survival motor neuron protein (SMN) in the body; this may be achieved by replacing or correcting the faulty SMN1 gene or modulating the low-functioning SMN2 “back-up gene”. A second approach, commonly called “SMN independent,” aims to target other pathways, systems, and processes within the body.
SMN Dependent Therapeutic Strategies
Gene therapy: Replaces the missing SMN1 gene via a viral vector
SMN2 promoter activation: Causes the SMN2 gene to be “on” more, generating more fully functional protein
SMN2 splicing modulation: Redirects splicing of SMN2 to make more full-length transcripts containing exon 7
SMN Independent Therapeutic Strategies
Neuroprotection: Protects against neuronal injury or degradation
Muscle enhancement: Prevents and restores loss of motor function
Neuronal function: Enhances neuronal transmission
Participate
There are many factors you should consider when deciding whether or not to enroll in a clinical trial. It’s important to understand how the process works and what your family should expect before you begin.
Finding a Trial
The FDA website, www.clinicaltrials.gov, is the best way to get more details about a particular trial or to see the progress of trials that are in stages other than recruitment. Other sources include Clinical Trial and Study Opportunities page and Cure SMA Latest News, through which we regularly announce new trials and trial updates. Your healthcare provider may also have information on trials that are recruiting participants.
Information About Trial Participation
There are many things to consider when choosing to participate in a clinical trial. For more detailed information on clinical trial participation, download our care series booklet, Learning About Clinical Trials.
Benefits and Risks
A well-designed and well-executed trial offers many benefits:
Advance knowledge about SMA, contribute to the development of a potential treatment, and help others with SMA in the future
Potentially receive access to an investigational drug
Offer appointments with an SMA study team
Receive trial-related care, monitoring, and assessments
There are also possible risks to consider:
There may be unpleasant, serious, or even life-threatening side effects to experimental drugs
The experimental drug might not be effective
The protocol may require more of your time and attention than a standard course of treatment, including trips to the study site, more drugs, hospital stays, or complex dosage requirements
Often, though not always, you must forgo taking an approved therapy while you are in the clinical trial
Questions to Ask
When deciding to participate, learn as much as possible about the clinical trial, the care expected, the cost, and the team that will be conducting the trial. We recommend you write down a list of questions to ask before meeting with the study doctors. Here are some potential questions you might ask:
What is being studied?
If researchers are studying an investigational drug, why do they believe it may be effective for SMA?
How long will participation last?
How often will I have to visit the hospital or clinic? Will any of these visits require an overnight stay?
Is there a chance of receiving a placebo?
What types of tests and medical procedures will be performed?
What are the possible risks and benefits of participation?
Who will oversee my healthcare while participating?
Will the results of the clinical trial be available to participants?
Who will pay the costs associated with participation?
Will I be reimbursed for other expenses?
Is travel support included?
Is there a planned extension trial?
You should also discuss your decision with your primary physician, family members, and, if needed, a counselor, therapist, or spiritual advisor.
During the Trial
Follow all instructions given by the study team
Tell the principal investigator of any new health-related problems. Even if you don’t consider them to be caused by the clinical trial or the investigational drug, any small change is very important to report
Complete questionnaires about your health status (or your family member’s health status) between visits
Attend all scheduled visits
Tell the principal investigator about any new medications or changes in the doses or frequency of medication
Be mindful about discussing the clinical trial with other participants, including whether you think you or your family member may be receiving a placebo