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Register:	ClinicalTrials.gov
Last refreshed on:	29 April 2024
Main ID:	NCT04089566
Date of registration:	11/09/2019
Prospective Registration:	Yes
Primary sponsor:	Biogen
Public title:	Study of Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy DEVOTE
Scientific title:	Escalating Dose and Randomized, Controlled Study of Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy
Date of first enrolment:	March 26, 2020
Target sample size:	145
Recruitment status:	Active, not recruiting
URL:	https://clinicaltrials.gov/ct2/show/NCT04089566
Study type:	Interventional
Study design:	Allocation: Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: Double (Participant, Care Provider).
Phase:	Phase 3

Countries of recruitment
Australia	Brazil	Canada	Chile	China	Colombia	Estonia	France
Germany	Greece	Hungary	Ireland	Israel	Italy	Japan	Korea, Republic of
Latvia	Lebanon	Mexico	Netherlands	Poland	Russian Federation	Saudi Arabia	Spain
Taiwan	Turkey	United Kingdom	United States

Contacts

Name:	Medical Director
Address:
Telephone:
Email:
Affiliation:	Biogen

Key inclusion & exclusion criteria

Key Inclusion Criteria:

Part A, B and C:

- Genetic documentation of 5q SMA (homozygous gene deletion, mutation, or compound
heterozygote)

Part A:

- Onset of clinical signs and symptoms consistent with SMA at > 6 months (> 180 days) of
age (i.e., later-onset SMA)

- Age 2 to = 15 years, inclusive, at the time of informed consent

Part B:

- Participants with SMA symptom onset = 6 months (= 180 days) of age (infantile onset)
should have age > 1 week to = 7 months (= 210 days) at the time of informed consent

- Participants with SMA symptom onset > 6 months (> 180 days) of age (later onset):

- Age 2 to < 10 years at the time of informed consent

- Can sit independently but has never had the ability to walk independently

- HFMSE score = 10 and = 54 at Screening

Part C:

- Currently on nusinersen treatment at the time of Screening, with the first dose being at
least 1 year prior to Screening

Part C Cohort 1:

- Participants of any age (individuals =18 years of age at Screening must be ambulatory)

Part C Cohort 2:

- Participants =18 years of age at Screening (can be ambulatory or nonambulatory)

- HFMSE total score =4 points at Screening

- RULM entry item A score =3 points at Screening

Key Exclusion Criteria:

Part A, B and C:

- Presence of an untreated or inadequately treated active infection requiring systemic
antiviral or antimicrobial therapy at any time during the Screening period

- Presence of an implanted shunt for the drainage of cerebrospinal fluid (CSF) or of an
implanted central nervous system (CNS) catheter

- Hospitalization for surgery, pulmonary event, or nutritional support within 2 months
prior to Screening or planned within 12 months after the participant's first dose

Part A:

- Respiratory insufficiency, defined by the medical necessity for invasive or
noninvasive ventilation for > 6 hours during a 24-hour period, at Screening

- Medical necessity for a gastric feeding tube

- Treatment with an investigational drug given for the treatment of SMA, biological
agent, or device within 30 days or 5 half-lives of the agent, whichever is longer,
prior to Screening or anytime during the study; any prior or current treatment with
any survival motor neuron-2 gene (SMN2)-splicing modifier or gene therapy; or prior
antisense oligonucleotide treatment, or cell transplantation

Part B:

- Treatment with an investigational drug including but not limited to the treatment of
SMA, biological agent, or device within 30 days or 5 half-lives of the agent,
whichever is longer, prior to Screening or anytime during the study; any prior or
current treatment with any SMN2-splicing modifier or gene therapy; or prior antisense
oligonucleotide treatment, or cell transplantation

- Participants with SMA symptom onset > 6 months (> 180 days) of age (later onset):

- Respiratory insufficiency, defined by the medical necessity for invasive or
noninvasive ventilation for > 6 hours during a 24-hour period, at Screening

- Medical necessity for a gastric feeding tube

- Participants with SMA symptom onset = 6 months (= 180 days) of age (infantile onset):
Signs or symptoms of SMA present at birth or within the first week after birth

Part C:

- Concurrent or previous participation and/or administration of nusinersen in another
clinical study

- Concomitant or previous administration of any SMN2-splicing modifier (excluding
nusinersen) or gene therapy, either in a clinical study or as part of medical care.

- Concurrent or previous participation in any interventional investigational study for
any other drug or device within 30 days or 5 half-lives of the agent, whichever is
longer, prior to Screening

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Age minimum: 7 Days
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Muscular Atrophy, Spinal

Intervention(s)

Drug: Nusinersen

Primary Outcome(s)

Part A and C: Change from Baseline in Neurological Examination Outcomes [Time Frame: Baseline up to Day 302]

Part A and C: Ratio of Weight for Age [Time Frame: Baseline up to Day 302]

Part C: Ratio of Head-to-chest Circumference [Time Frame: Baseline up to Day 302]

Part A and C: Change from Baseline in Activated Partial Thromboplastin Time (aPTT) [Time Frame: Baseline up to Day 269]

Part A and C: Change in Urine Total Protein [Time Frame: Baseline up to Day 302]

Part A and C: Number of Participants with Clinically Significant Shifts from Baseline in Vital Signs [Time Frame: Screening up to Day 302]

Part A and C: Percentage of Participants with a Postbaseline Platelet Count Below the Lower Limit of Normal on at least 2 Consecutive Measurements [Time Frame: Baseline up to Day 302]

Part A and C: Change from Baseline in Body Length/Height [Time Frame: Baseline up to Day 302]

Part A and C Later-onset SMA: Change from Baseline in Ulnar Length [Time Frame: Baseline up to Day 302]

Part A and C: Change from Baseline in International Normalized Ratio (INR) [Time Frame: Baseline up to Day 269]

Part A and C: Number of Participants with Clinically Significant Shifts from Baseline in Clinical Laboratory Parameters [Time Frame: Screening up to Day 302]

Part B Infantile-onset SMA: Change from Baseline in CHOP-INTEND Total Score [Time Frame: Baseline up to Day 183]

Part A and C: Change from Baseline in Prothrombin Time (PT) [Time Frame: Baseline up to Day 269]

Part A and C: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time Frame: Screening up to Day 389]

Part A and C: Number of Participants with Clinically Significant Shifts from Baseline in Electrocardiograms (ECGs) [Time Frame: Screening up to Day 302]

Part A and C: Ratio of Weight for Length [Time Frame: Baseline up to Day 302]

Part C Infantile-onset SMA: Change from Baseline in Head Circumference [Time Frame: Baseline up to Day 302]

Part A and C: Percentage of Participants with a Postbaseline Corrected QT Interval Using Fridericia's Formula (QTcF) of > 500 millisecond (msec) and an Increase from Baseline to Any Postbaseline Timepoint in QTcF of > 60 msec [Time Frame: Baseline up to Day 302]

Part C Infantile-onset SMA: Change from Baseline in Arm Circumference [Time Frame: Baseline up to Day 302]

Part C Infantile-onset SMA: Change from Baseline in Chest Circumference [Time Frame: Baseline up to Day 302]

Secondary Outcome(s)

Part A and B Later-onset SMA: Change from Baseline in Revised Upper Limb Module (RULM) Score [Time Frame: Baseline up to Day 302]

Part A and B Later-onset SMA: Total Number of New WHO Motor Milestones [Time Frame: Baseline up to Day 302]

Part C: Change from Baseline in HINE Section 2 Motor Milestones Total Score [Time Frame: Baseline up to Day 302]

Part A and B Later-onset SMA: Change from Baseline in Pediatric Quality of Life Inventory™ (PedsQL) [Time Frame: Baseline up to Day 302]

Part A, B and C: Clinical Global Impression of Change (CGIC) [Time Frame: Day 302]

Part A, B and C: Number of Hospitalizations [Time Frame: Day 1 to Day 302]

Part B Infantile-onset SMA: Change from Baseline in Chest Circumference [Time Frame: Baseline up to Day 302]

Part B Infantile-onset SMA: Change from Baseline in Head Circumference [Time Frame: Baseline up to Day 302]

Part B: Change from Baseline in aPTT [Time Frame: Baseline up to Day 279]

Part B: Percentage of Participants with a Postbaseline Platelet Count Below the Lower Limit of Normal on at least 2 Consecutive Measurements [Time Frame: Baseline up to Day 302]

Part B Infantile-onset SMA: Change from Baseline in HINE Section 2 Motor Milestones Total Score [Time Frame: Baseline up to Day 302]

Part B Infantile-onset SMA: Percentage of Time on Ventilation [Time Frame: Screening up to Day 302]

Part B: Change from Baseline in Body Length/Height [Time Frame: Baseline up to Day 302]

Part A and B Later-onset SMA: Change from Baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) Score [Time Frame: Baseline up to Day 302]

Part B: Change from Baseline in PT [Time Frame: Baseline up to Day 279]

Part B: Number of Participants with AEs and SAEs [Time Frame: Screening up to Day 399]

Part B: Change from Baseline in INR [Time Frame: Baseline up to Day 279]

Part B: Number of Participants with Clinically Significant Shifts from Baseline in ECGs [Time Frame: Day 1 up to Day 302]

Part B: Ratio of Head-to-chest Circumference [Time Frame: Baseline up to Day 302]

Part C: Change from Baseline in ACEND [Time Frame: Baseline up to Day 302]

Part B Infantile-onset SMA: Percentage of Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestone Responders [Time Frame: Day 302]

Parts A and B: Change from Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale [Time Frame: Baseline up to Day 302]

Part A and B Later-onset SMA: Change from Baseline in Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) [Time Frame: Baseline up to Day 302]

Part C: Total Number of New WHO Motor Milestones [Time Frame: Baseline up to Day 302]

Part A, B and C: Number of Participants with Serious Respiratory Events [Time Frame: Screening up to Day 399]

Part B Infantile-onset SMA: Change from Baseline in Arm Circumference [Time Frame: Baseline up to Day 302]

Part B: Number of Participants with Clinically Significant Shifts from Baseline in Clinical Laboratory Parameters [Time Frame: Screening up to Day 302]

Part B Infantile-onset SMA: Time to Death or Permanent Ventilation [Time Frame: Screening up to Day 302]

Part B: Change from Baseline in Neurological Examination Outcomes [Time Frame: Baseline up to Day 302]

Part B: Percentage of Participants with a Postbaseline QTcF of > 500 msec and an Increase from Baseline to Any Postbaseline Timepoint in QTcF of > 60 msec [Time Frame: Baseline up to Day 302]

Part B: Ratio of Weight for Length [Time Frame: Baseline up to Day 302]

Part C: Change from Baseline in RULM Score [Time Frame: Baseline up to Day 302]

Part A, B and C: Duration of Hospitalizations [Time Frame: Day 1 to Day 302]

Part B Infantile-onset SMA: Time to Death (Overall Survival) [Time Frame: Screening up to Day 399]

Part B Later-onset SMA: Change from Baseline in Ulnar Length [Time Frame: Baseline up to Day 302]

Part B: Change in Urine Total Protein [Time Frame: Baseline up to Day 302]

Part C: Change from Baseline in CHOP-INTEND Total Score [Time Frame: Baseline to up Day 302]

Part B: Number of Participants with Clinically Significant Shifts from Baseline in Vital Signs [Time Frame: Screening up to Day 302]

Part B: Ratio of Weight for Age [Time Frame: Baseline up to Day 302]

Part C: Change from Baseline in HFMSE Score [Time Frame: Baseline up to Day 302]

Part C: Change from Baseline in PedsQL™ [Time Frame: Baseline up to Day 302]

Parts A, B and C: Ventilator Use [Time Frame: Screening up to Day 302]

Secondary ID(s)

232SM203

2019-002663-10

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Ethics review

Results

Results available:
Date Posted:
Date Completed:
URL:

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