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

Palo Alto (17 mi)

Age: Any Age

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: Biogen

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 jurisdictions

Trial Summary

What is the purpose of this trial?The primary objectives of this study are to examine the clinical efficacy of nusinersen administered intrathecally at higher doses to participants with spinal muscular atrophy (SMA), as measured by change in Children's Hospital of Philadelphia-Infant Test of Neuromuscular Disorders (CHOP-INTEND) total score (Part B); to examine the safety and tolerability of nusinersen administered intrathecally at higher doses to participants with SMA (Parts A and C). The secondary objectives of this study are to examine the clinical efficacy of nusinersen administered intrathecally at higher doses to participants with SMA (Parts A, B and C); to examine the effect of nusinersen administered intrathecally at higher doses to participants with SMA (Parts A and C); to examine the safety and tolerability of nusinersen administered intrathecally at higher doses to participants with SMA, to examine the effect of nusinersen administered intrathecally at higher doses compared to the currently approved dose in participants with SMA (Part B).

Eligibility Criteria

This trial is for individuals with spinal muscular atrophy (SMA). Eligible participants include those aged 2-10 years who can sit but not walk, have a specific score on the HFMSE test, and genetic confirmation of SMA. Infants up to 7 months old with symptom onset by 6 months are also eligible. Participants must be currently treated with nusinersen for at least one year prior to screening.

Inclusion Criteria

My condition is confirmed by genetic testing for 5q SMA.

I am 18 or older and can move with or without help, with specific movement scores.

I am between 2 and 9 years old.

I have been on nusinersen treatment for over a year.

I can sit by myself but I've never been able to walk on my own.

Exclusion Criteria

I need a machine to help me breathe for more than 6 hours a day.

I haven't used experimental drugs or treatments for SMA in the last 30 days or longer.

I have an active infection needing treatment with drugs.

I have not used any SMN2-splicing modifiers or gene therapy for my condition, except nusinersen.

I need a feeding tube for my stomach due to medical reasons.

Treatment Details

The study tests higher doses of Nusinersen given through spinal injection in people with SMA. It aims to see if these doses improve muscle function more than the standard dose, using a scale called CHOP-INTEND as a measure for children's motor skills.

4Treatment groups

Experimental Treatment

Active Control

Group I: 50/28 mg Active Treatment GroupExperimental Treatment1 Intervention

Part B: Participants with infantile- or later-onset SMA will receive loading doses of 50 mg of nusinersen intrathecally on Days 1 and 15 followed by maintenance doses of 28 mg on Days 135 and 279. Sham procedure will be administered on Days 29, 64 and 183.

Group II: 28/28 Milligram (mg) Safety GroupExperimental Treatment1 Intervention

Part A: Participants with later-onset SMA will receive loading doses of 28 mg of nusinersen intrathecally on Days 1, 15 and 29 followed by maintenance doses of 28 mg on Days 149 and 269.

Group III: 12/50/28 mg Titration GroupExperimental Treatment1 Intervention

Part C: Participants who have been receiving the approved dose of 12 mg for at least 1 year prior to entry, will receive a single bolus dose of 50 mg of nusinersen intrathecally on Day 1 (4 months after their most recent maintenance dose of 12 mg) followed by maintenance doses of 28 mg on Days 121 and 241.

Group IV: 12/12 mg Active Control GroupActive Control1 Intervention

Part B: Participants with infantile- or later-onset SMA will receive loading doses of 12 mg of nusinersen intrathecally on Days 1, 15, 29, and 64 followed by maintenance doses of 12 mg on Days 183 and 279. Sham procedure will be administered on Day 135.

Nusinersen is already approved in United States, European Union for the following indications:

🇺🇸 Approved in United States as Spinraza for: