A Study to Evaluate the Effectiveness and Safety of Risdiplam Administered as an Early Intervention in Pediatric Patients with Spinal Muscular Atrophy (SMA) After Gene Therapy

1. Why is the HINALEA 1 clinical trial needed?

Currently there are reported cases of risdiplam being started after SMA gene therapy, yet there is no standard way this is done; some doctors add risdiplam early after gene therapy and some start risdiplam later when the patient may not be responding well.

This trial is studying the effects, good or bad, of risdiplam given early after gene therapy to see if it may provide benefit and is safe. Risdiplam is approved for the treatment of SMA in pediatric and adult patients.

2. How does the HINALEA 1 clinical trial work?

This clinical trial is recruiting children under 2 years old with a health condition called Spinal Muscular Atrophy (SMA) and have received gene therapy. If a child takes part in this clinical trial, they will be given risdiplam orally, daily for 2.5 years. The clinical trial doctor will see them every 12 weeks (approximately 3 months). These visits will include checks to see how the participant responds to the treatment and any side effects they may have. Parents/guardians can choose to withdraw the child from trial treatment and leave the clinical trial at any time.

3. What are the main endpoints of the HINALEA 1 clinical trial?

The main clinical trial endpoint (the main result that is measured in the trial to see if the medicine has worked) is the change in the Gross Motor Score (motor function) in a measurement called Bayley Scales of Infant and Toddler Development, Third Edition, or BSID-III, from baseline to week 72.

The other clinical trial endpoints assessed at 72 weeks and over time after the child starts risdiplam treatment include changes in swallowing function, how the child is growing, changes in motor development, changes in respiratory function and safety of the study treatment.

4. Who can take part in this HINALEA 1 clinical trial?

To be able to take part in this clinical trial, the child must be < 2 years of age at the time of consent, have a confirmed diagnosis of SMA with two SMN2 gene copies and received gene therapy for SMA (no less than 13 weeks, but not more than 30 weeks at the time of enrollment). The child must not have experienced clinically significant decline in function from the time when gene therapy was given.

The child will not be able to take part in this trial if they had joined another investigational study before or during enrollment, if they have unresolved laboratory abnormalities (as per gene therapy prescribing information) and if they are receiving or previously received SMN2-targeting antisense oligonucleotide or anti-myostatin either in a clinical study or as part of medical care.

5. What treatment will participants be given in this HINALEA 1 clinical trial?

All children who join this clinical trial will be given risdiplam. This is an open-label trial, which means everyone involved, including the parents/guardians and the clinical trial doctor, will know the clinical trial treatment the child has been given. There is no placebo or “sugar pill” group.

6. Are there any risks or benefits in taking part in this HINALEA 1 clinical trial?

The safety or effectiveness of risdiplam given as an early intervention after gene therapy is not fully known at the time of the trial. Most trials involve some risks to the participant. However, it may not be greater than the risks related to routine medical care or the natural progression of the Spinal Muscular Atrophy (SMA). The study doctor will explain to the parents or guardians the potential risks and benefits of the child taking part in the clinical trial, as well as any additional procedures, tests, or assessments they will be asked to undergo. The parents or guardians will additionally be given an informed consent document that will provide details to help them decide whether to volunteer the child for this study. The parents or guardians of the child should discuss these with members of the research team and with their usual health care provider. Anyone interested in enrolling their child in a clinical trial should know as much as possible about the trial and feel comfortable asking the research team any questions about the trial.

Risks associated with the clinical trial
The child may have side effects from the study drug or procedures used in this clinical trial. Side effects can be mild to severe, even life-threatening, and vary from person to person. The child will be closely monitored during the clinical trial; safety assessments will be performed regularly.

Risdiplam (Evrysdi)
The study doctor will explain to parents or guardians about the known side effects of risdiplam, and possible side effects based on human and laboratory studies or knowledge of similar drugs. Risdiplam is a liquid given by mouth (orally) or by feeding tube daily at home.

Potential benefits associated with the clinical trial
The child’s health may or may not improve from participation in the clinical trial, but the information that is collected may help other people with similar medical conditions in the future.