What side effects are associated with this type of intervention?

The most common treatments for Spinal Muscular Atrophy (SMA) include Risdiplam, Nusinersen, and Onasemnogene abeparvovec. Risdiplam, an SMN2 splicing modifier, can cause side effects such as fever, diarrhea, rash, and upper respiratory tract infections. Nusinersen, administered via intrathecal injection, may lead to side effects like headache, back pain, and post-lumbar puncture syndrome. Onasemnogene abeparvovec, a gene therapy, can cause liver enzyme elevations, vomiting, and thrombocytopenia. Patients should discuss these potential side effects with their healthcare provider to make informed treatment decisions.

What prior FDA approvals exist?

The FDA has approved several treatments for Spinal Muscular Atrophy (SMA). One of the first was Nusinersen (Spinraza), an antisense oligonucleotide that modifies SMN2 splicing to increase the production of functional SMN protein. Another significant approval was for Onasemnogene abeparvovec-xioi (Zolgensma), a gene therapy that delivers a functional copy of the SMN1 gene. Risdiplam (Evrysdi), an oral SMN2 splicing modifier, was also approved and works by increasing the production of the SMN protein through modifying the splicing of SMN2 pre-mRNA. These treatments have provided new therapeutic options for managing SMA.

What other types of research exist?

Promising novel alternatives to Risdiplam for SMA patients include: 1) Onasemnogene abeparvovec (Zolgensma), a gene therapy that delivers a functional copy of the SMN1 gene. 2) Nusinersen (Spinraza), an antisense oligonucleotide that modifies SMN2 splicing to increase SMN protein production. Both therapies have shown significant efficacy in clinical trials and are approved for use in SMA patients.

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SMN2 Splicing Modifier

Risdiplam for Presymptomatic Spinal Muscular Atrophy (Rainbowfish Trial)

Phase 2

Waitlist Available

Research Sponsored by Hoffmann-La Roche

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Males and females aged from birth (1 day) to 6 weeks (42 days) of age at the time of first dose (Day 1); a minimum age of 7 days at first dose is required for the first infant to be enrolled

Genetic diagnosis of 5q-autosomal recessive SMA, including confirmation of homozygous deletion or compound heterozygosity predictive of loss of function of the SMN1 gene

Must not have

Concomitant or previous administration of an SMN2-targeting antisense oligonucleotide, SMN2-splicing modifier, or gene therapy either in a clinical study or as part of medical care

Multiple or fixed contractures and/or hip subluxation or dislocation at birth

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 7 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a medicine called risdiplam, which is taken by mouth. It aims to help infants who have a genetic diagnosis of spinal muscular atrophy (SMA) but are not yet showing symptoms. The medicine works by helping the body make more of a protein that muscles need to stay healthy. The goal is to see if early treatment can prevent or lessen the severity of SMA.

Who is the study for?

This trial is for infants from birth to 6 weeks old with a genetic diagnosis of spinal muscular atrophy (SMA) but no symptoms yet. They must be able to travel safely for study visits, have supportive caregivers, and not require invasive ventilation. Infants should weigh in the normal range for their age and have been born after a full-term pregnancy.

What is being tested?

The trial is testing an oral medication called Risdiplam on infants who are genetically diagnosed with SMA but haven't shown symptoms. The goal is to see if early treatment can prevent or lessen muscle weakness caused by SMA.

What are the potential side effects?

Risdiplam may cause sensitivity reactions, potential blood test abnormalities, and could interact with other medications affecting liver enzymes or those known for retinal toxicity. It's important that neither the infant nor breastfeeding mother takes certain drugs before joining.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My child is between 1 day and 6 weeks old and has not received the first dose before 7 days of age.

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I have a genetic form of spinal muscular atrophy linked to the SMN1 gene.

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My body weight is at or above the 3rd percentile for my age.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have received treatments targeting the SMN2 gene.

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I was born with joint stiffness and/or hip issues.

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I need a machine to help me breathe.

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My oxygen levels drop below 95% when I'm awake, with or without a breathing machine.

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My child was not exposed to drugs harmful to the eyes during pregnancy or breastfeeding.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 7 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 7 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 7 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Percentage of Participants With Two Copies of the Survival Motor Neuron (SMN) 2 Gene (Excluding the Known SMN2 Gene Modifier Mutation c.859G>C) and Baseline Compound Muscle Action Potential (CMAP) >=1.5 Millivolt (mV) Who Are Sitting Without Support

Secondary study objectives

Change From Baseline Score in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Motor Function Scale at Month 12

Change From Baseline in Compound Muscle Action Potential (CMAP) Amplitude

Number and Percentage of Participants Within 3rd Percentile of Normal Range for Head Circumference-for-age

+10 more

Side effects data

From 2023 Phase 2 trial • 231 Patients • NCT02908685

22%

Nasopharyngitis

15%

Upper respiratory tract infection

13%

Vomiting

13%

Pyrexia

10%

Headache

10%

Cough

Diarrhoea

Gastroenteritis

Pneumonia

Respiratory tract infection

Abdominal pain

Bronchitis

Pharyngitis

Rash

Ear pain

Back pain

Nausea

Arthralgia

Influenza

Limb injury

Oropharyngeal pain

Rhinorrhoea

Eczema

Constipation

Influenza like illness

Ear infection

Contusion

Erythema

Urinary tract infection

Sinusitis

Arthropod bite

Gastritis

Decreased appetite

Pain in extremity

Dry skin

Pruritus

Gastrointestinal infection

Ocular hyperaemia

Infective thrombosis

Encephalitis

Brain contusion

Nephrolithiasis

Atelectasis

Neck pain

Amenorrhoea

Dysmenorrhoea

Pneumonia mycoplasmal

Rhinitis

Scarlet fever

Tonsillitis

Dehydration

Device related infection

Herpes zoster

Post procedural infection

Pyelonephritis

Viral upper respiratory tract infection

Partial seizures

Haematuria

Pneumonitis aspiration

Pneumothorax

Dizziness

Nasal congestion

Rhinitis allergic

Tachycardia

Asthma

Epistaxis

Productive cough

Acne

Alopecia

Blister

Dermatitis

Abdominal pain upper

Aphthous ulcer

Asthenia

Seborrhoeic dermatitis

Hypersensitivity

Conjunctivitis

Cystitis

Groin infection

100%

80%

60%

40%

20%

Study treatment Arm

Part 2 OLT: Risdiplam/Risdiplam

Part 2 OLT: Placebo/Risdiplam

Part 2 OLE: Risdiplam

Part 1 Group B: Children (0.25 mg/kg Risdiplam)

Part 1 Group A: Adolescents and Adults (3 mg Risdiplam)

Part 1 Group A: Adolescents and Adults (5 mg Risdiplam)

Part 1 Group B: Children (Placebo-Control Period Pooled)

Part 1 Group A: Adolescents and Adults (Placebo-Control Period Pooled)

Part 1 Group B: Children (0.02 mg/kg Risdiplam)

Part 1 Group B: Children (0.05 mg/kg Risdiplam)

Part 1 Group B: Children (0.15 mg/kg Risdiplam)

Part 1 Group A: OLE

Part 1 Group B: OLE

Part 2 Placebo-Controlled: Risdiplam

Part 2 Placebo-Controlled: Placebo

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Open-label RisdiplamExperimental Treatment1 Intervention

Participants will be enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Risdiplam

2016

Completed Phase 2

~420

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Spinal Muscular Atrophy (SMA), such as Risdiplam, work by modifying the splicing of the SMN2 gene to increase the production of the survival motor neuron (SMN) protein. These treatments promote the inclusion of exon 7 in the SMN2 mRNA, resulting in the production of a more functional SMN protein. This mechanism is vital for SMA patients because higher levels of SMN protein help maintain motor neuron function and slow the progression of the disease, thereby improving quality of life and potentially extending survival.