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Antisense Oligonucleotide

High-Dose Nusinersen for Spinal Muscular Atrophy (ASCEND Trial)

Phase 3

Recruiting

Research Sponsored by Biogen

Eligibility Criteria Checklist

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

Must have

RULM entry item A score ≥3

RULM total score ≥5 and ≤30 at Screening

Must not have

Any major illness within 1 month before the screening examination or within 1 week prior to Screening and up to first dose administration

History of bacterial meningitis, viral encephalitis, or hydrocephalus

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to day 1695

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing a new drug for spinal muscular atrophy and its effects on motor function. The safety and tolerability of the drug will also be monitored.

Who is the study for?

This trial is for individuals aged 15-50 with a confirmed genetic diagnosis of spinal muscular atrophy (SMA), weighing over 20 kg, and able to perform certain functional assessments. Participants must have been previously treated with risdiplam but are willing to stop it and start high-dose nusinersen treatment. They should not be able to walk independently for 15 feet, not have severe illnesses or conditions that could affect the study, nor be pregnant or breastfeeding.

What is being tested?

The trial is testing whether a higher dose of nusinersen can improve motor function in patients who have SMA and were previously treated with risdiplam. It will also assess the safety and tolerability of this increased dosage regimen.

What are the potential side effects?

While specific side effects for high-dose nusinersen are being studied, common ones may include back pain from injections, respiratory infections due to weakened muscles, headache, constipation or nausea. Serious side effects might involve kidney damage or bleeding complications.

Eligibility Criteria

Inclusion Criteria

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

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My upper limb mobility score is 3 or higher.

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My RULM score is between 5 and 30.

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I am willing to stop taking risdiplam.

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I have been taking risdiplam as prescribed or through a special program.

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I have been treated with risdiplam for at least 6 months and have not used nusinersen.

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My SMA symptoms started after I was 6 months old.

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I weigh more than 20 kilograms.

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I have a confirmed genetic form of SMA due to SMN1 gene changes.

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I stopped taking nusinersen over 16 months ago and have been on risdiplam for more than 12 months.

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I cannot walk 15 feet on my own without help.

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I am between 15 and 50 years old.

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I am ready and can start treatment with HD nusinersen.

Exclusion Criteria

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

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I haven't had a major illness in the month before my screening or in the week leading up to my first dose.

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I have had bacterial meningitis, viral encephalitis, or hydrocephalus.

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I am not pregnant, breastfeeding, nor planning to become pregnant during the study.

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I have an active infection that needs treatment with antibiotics or antivirals.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to day 1695

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to day 1695

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to day 1695 for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Change in Total Revised Upper Limb Module (RULM) Score

Secondary study objectives

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Side effects data

From 2017 Phase 3 trial • 126 Patients • NCT02292537

45%

Upper respiratory tract infection

36%

Pyrexia

36%

Nasopharyngitis

21%

Cough

19%

Gastroenteritis

17%

Rhinorrhoea

17%

Joint contracture

14%

Pneumonia

12%

Vomiting

12%

Ear infection

10%

Constipation

10%

Bronchitis

10%

Gastroenteritis viral

10%

Otitis media

10%

Arthralgia

Diarrhoea

Pharyngitis streptococcal

Pain in extremity

Scoliosis

Headache

Faecaloma

Influenza

Dehydration

Respiratory distress

Conjunctivitis

Upper respiratory tract congestion

Pneumonia adenoviral

Respiratory syncytial virus infection

Respiratory failure

Pneumonia parainfluenzae viral

100%

80%

60%

40%

20%

Study treatment Arm

Sham Procedure

Nusinersen

Awards & Highlights

No Placebo-Only Group

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

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Higher Dose NusinersenExperimental Treatment1 Intervention

All participants in the core study period, previously treated with risdiplam (nusinersen-naive participants and nusinersen-experienced participants), will receive HD nusinersen, administered as 2 loading doses of 50 milligrams (mg) each, approximately 2 weeks apart, followed by maintenance doses of 28 mg approximately every 4 months. Following the core study period, participants may be given the opportunity to receive maintenance doses of 28 mg nusinersen administered approximately every 4 months up to 2 years during the optional long-term extension (LTE) period.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Nusinersen

2014

Completed Phase 3

~340

0 / 16Eligibility criteria met