Spinal Muscular AtrophyPhase 3ENDEARNCT02193074
A Study to Assess the Efficacy and Safety of Nusinersen (ISIS 396443) in Infants With Spinal Muscular Atrophy
A Phase 3 study testing nusinersen in people with Spinal Muscular Atrophy, run by Biogen at 31 sites in 13 countries.
Trial summary
The primary objective of the study is to examine the clinical efficacy of nusinersen (ISIS 396443) administered intrathecally (IT) to participants with infantile-onset with infantile-onset spinal muscular atrophy (SMA). Read more about this study
- Who is it for?
- Ages Up to 210 days
- Conditions the study is for
- Spinal Muscular Atrophy
- What is being tested?
- nusinersen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 122 participants
- Where
- 31 sitesin 13 countries
- Study dates
- 19 Aug 2014to 21 Nov 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 210 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Be born (gestational age) between 37 and 42 weeks
- Be medically diagnosed with spinal muscular atrophy (SMA)
- Have Survival Motor Neuron2 (SMN2) Copy number = 2
- Body weight equal to or greater than 3rd percentile for age using appropriate country-specific guidelines
- Be able to follow all study procedures
- Reside within approximately 9 hours ground-travel distance from a participating study center, for the duration of the study
Who cannot join
- Hypoxemia (oxygen [O2] saturation awake less than 96% or O2 saturation asleep less than 96%, without ventilation support) during screening evaluation
- Clinically significant abnormalities in hematology or clinical chemistry parameters or Electrocardiogram (ECG), as assessed by the Site Investigator, at the Screening visit that would render the participant unsuitable for participation in the study
- Participant's parent or legal guardian is not willing to meet standard of care guidelines (including vaccinations and respiratory syncytial virus prophylaxis if available), nor provide nutritional and respiratory support throughout the study
- NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
31 sites in 13 countries.
31 sites in 13 countries
United States12 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
Boston Children's Hospital
Boston, Massachusetts, 02115
Ann and Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
UT Southwestern Medical Center/Children's Medical Center Dallas
Dallas, Texas, 75235
Duke Children's Hospital
Durham, North Carolina, 27710
UCLA Medical Center
Los Angeles, California, 90095
Columbia University Medical Center
New York, New York, 10032
Nemours Children's Hospital
Orlando, Florida, 32827
Children's Hospital of Philadelphia - Neurology
Philadelphia, Pennsylvania, 19104
Doernbecher Children's Hospital
Portland, Oregon, 97239
Primary Children's Medical Center (University of Utah)
Salt Lake City, Utah, 84112
Washington University School of Medicine
St Louis, Missouri, 63110
Australia2 sites
Royal Children's Hospital, Children's Neuroscience Centre
Parkville, Victoria, 3052
Sydney Children's Hospital
Sydney, New South Wales, 2031
Canada2 sites
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
British Columbia Children's Hospital/UBC
Vancouver, British Columbia, V6H 3N1
Germany2 sites
Universitatsklinikum Essen
Essen, 45147
Universtatsklinikum Freiburg, Zentrum fur Kinder-und Jugendmedizin , Abteilung Neuropadiatrie und Muskelerkrankungen
Freiburg im Breisgau, 79106
Italy2 sites
Istituto Giannina Gaslini, Centro Traslazionale di Miologia e Patologie Neurodegenerative
Genova, 16148
Pediatric Neurology Unit, Catholic University
Rome, 00153
Japan2 sites
Hyogo College of Medicine
Nishinomiya, Hyōgo, 663-8131
Tokyo Women's Medical University
Tokyo, 162-8666
Spain2 sites
Hospital Universitario Vall d'Hebron
Barcelona, 08035
Hospital Universitario La Paz, Pediatric Neurology Department
Madrid, 28046
United Kingdom2 sites
UCL Institute of Child Health/Great Ormond Street
London, WC1N 1EH
MRC Centre for Neuromuscular Diseases at Newcastle, Institute of Genetic Medicine Newcastle University
Newcastle, NE1 3BZ
Belgium1 site
Hôpital Universitaire des Enfants Reine FABIOLA (HUDERF)
Brussels, 15 - 1020
Sweden1 site
University of Gothenburg, The Queen Silvia Children's Hospital
Gothenburg
About this study
Official title: A Phase 3, Randomized, Double-Blind, Sham-Procedure Controlled Study to Assess the Clinical Efficacy and Safety of ISIS 396443 Administered Intrathecally in Patients With Infantile-onset Spinal Muscular Atrophy
The primary objective of the study is to examine the clinical efficacy of nusinersen (ISIS 396443) administered intrathecally (IT) to participants with infantile-onset with infantile-onset spinal muscular atrophy (SMA). The secondary objective of the study is to examine the safety and tolerability of nusinersen administered intrathecally to participants with infantile-onset SMA.
Read the detailed description
This study was conducted and the protocol was registered by Ionis Pharmaceuticals, Inc..
In August 2016, sponsorship of the trial was transferred to Biogen.
- Conditions
- Spinal Muscular Atrophy
- Being tested
- nusinersen, Sham procedure
- Keywords
- Spinal Muscular Atrophy, SMA, SMN, SMNRx, ISIS-SMNRx, ISIS-SMN Rx, ISIS 396443, IONIS-SMNRx, IONIS-SMN Rx, Spinraza, ENDEAR
- Medical subject headings
- Muscular Atrophy, Spinal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nusinersenDrug
Also called ISIS 396443, BIIB058, Spinraza, IONIS-SMN Rx
Administered by intrathecal (IT) injection as specified in the treatment arm.
Sham procedureProcedure or surgery
Small needle prick on the lower back at the location where the IT injection is normally made
| Study group | Role | What they receive |
|---|---|---|
| nusinersen | Experimental | Not described Receives: Drug: nusinersen |
| Sham procedure | Sham comparator | Not described Receives: Procedure: Sham procedure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Motor Milestones Responders
The definition of a motor milestones responder was based on improvement in the motor milestones categories in Section 2 of the Hammersmith Infant Neurological Examination (HINE), with the exclusion of voluntary grasp, as follows:
(i) subject demonstrates ≥ 2-point increase in the motor milestones category of ability to kick or achievement of maximal score on that category (touching toes), or a 1-point increase in the motor milestones category of head control, rolling, sitting, crawling, standing, or walking, and (ii) among the motor milestone categories, with the exclusion of voluntary grasp, there are more categories where there is improvement as defined in (i) than worsening. (For the category of ability to kick, worsening is defined as ≥ 2-point decrease or decrease to the lowest possible score of no kicking. For the other categories, worsening is defined as ≥ 1-point decrease.) The lowest possible score for the HINE is 0 (zero), and the highest possible score for the HINE is 28.
Measured: assessed at the later of the Day 183, Day 302, or Day 394 study visits
Time to Death or Permanent Ventilation
Estimated proportion of participants who died or required permanent ventilation by a given study day, based on the Kaplan-Meier product-limit method. Time to death or permanent ventilation was defined as either tracheostomy or ≥ 16 hours ventilation/day continuously for > 21 days in the absence of an acute reversible event. This endpoint was adjudicated by a blinded, independent group of experienced clinicians, the Event Adjudication Committee (EAC), based on review of clinical study data and supporting information. Results are based on all available data.
Measured: Day 91, Day 182, Day 273, Day 364, Day 394
Secondary outcomes (12)
Percentage of Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) Responders
A participants was considered a CHOP-INTEND responder if the change from baseline in CHOP-INTEND total score is ≥ 4 points based on assessment at the later of the Day 183, Day 302, or Day 394 study visits. CHOP-INTEND tests includes 16 items structured to move from easiest to hardest with the grading including gravity eliminated (lower scores) to antigravity movements (higher scores). Total scores range from 0 to 64, with higher scores indicating better movement functioning. Results are based on all available data.
Measured: assessed at Baseline and the later of the Day 183, Day 302, or Day 394 study visits
Summary of Time to Death
Estimated proportion of participants who died by given duration thresholds, based on the Kaplan-Meier product-limit method.
Measured: Day 91, Day 182, Day 273, Day 364, Day 394
Percentage of Participants Not Requiring Permanent Ventilation
Measured: Up to Day 394
Percentage of Compound Muscular Action Potential (CMAP) Responders
CMAP is an electrophysiological technique that can be used to determine the approximate number of motor neurons in a muscle or group of muscles. A participant was defined as a CMAP responder if the CMAP amplitude at the peroneal nerve was increasing to or maintained at ≥ 1 mV (comparing to the baseline) based on assessment at the later of the Day 183, Day 302, or Day 394 study visits. Results are based on all available data.
Measured: assessed at the later of the Day 183, Day 302, or Day 394 study visits
Time to Death or Permanent Ventilation in the Subgroup of Participants Below the Study Median Disease Duration
Estimated proportion of participants who died or required permanent ventilation (EAC-adjudicated events) among participants below the study median disease duration (13.1 weeks), by given duration thresholds, based on the Kaplan-Meier product-limit method.
Measured: Day 91, Day 182, Day 273, Day 364, Day 394
Time to Death or Permanent Ventilation in the Subgroup of Participants Above the Study Median Disease Duration
Estimated proportion of participants who died or required permanent ventilation (EAC-adjudicated events) among participants above the study median disease duration (13.1 weeks), by given duration thresholds, based on the Kaplan-Meier product-limit method.
Measured: Day 91, Day 182, Day 273, Day 364, Day 394
Number of Participants Experiencing Adverse Events (AEs), Serious AEs (SAEs) and Discontinuations Due to AEs
AE: any unfavorable and unintended sign, symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE is considered related to the investigational drug product. SAE: any AE that in the view of either the Investigator or Sponsor, meets any of the following criteria: results in death; is life threatening: that is, poses an immediate risk of death at the time of the event; requires in-patient hospitalization or prolongation of existing hospitalization; results in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly or birth defect in the offspring of the participant (whether male or female); is an important medical event in the opinion of the Investigator or Sponsor.
Measured: Screening through Day 394 (± 7 days) or early termination
Number of Participants With AEs Corresponding to Changes in Hematology Values
Measured: up to Day 394 (± 7 days) or early termination
Number of Participants With AEs Corresponding to Changes in Blood Chemistry Values
Measured: up to Day 394 (± 7 days) or early termination
Number of Participants Meeting Selected Vital Sign Criteria Post-Baseline
Measured: up to Day 394 (± 7 days) or early termination
Summary of Shifts in 12-lead Electrocardiogram (ECG) Results
Shift to 'abnormal, not clinically significant' includes 'unknown' or 'normal' to 'abnormal, not clinically significant'. Shift to 'abnormal, clinically significant' includes 'unknown' or 'normal' to 'abnormal, clinically significant'.
Measured: up to Day 394 (± 7 days) or early termination
Number of Participants With Clinically Significant Changes From Baseline in Urinalysis Values
Measured: up to Day 394 (± 7 days) or early termination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2014 (estimated)
- Study start19 Aug 2014
- Primary completion21 Nov 2016
- Study completion21 Nov 2016
Why it stopped: After a positive interim analysis, the decision was made to terminate the study early to allow for participants to enroll into an open label study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Spinal Muscular AtrophyStudies of the same condition, open and under way.
- More trials run by BiogenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 122 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Biogen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02193074
- Sponsor's protocol ID
- ISIS 396443-CS3B
- Other IDs
- 2013-004422-29
- Acronym
- ENDEAR
- Status last verified
- Feb 2021
- First submitted
- 14 Jul 2014
- Last updated
- 17 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Expanded access
- Available
Publications
Kokaliaris C, Evans R, Hawkins N, Mahajan A, Scott DA, Sutherland CS, Nam J, Sajeev G. Long-Term Comparative Efficacy and Safety of Risdiplam and Nusinersen in Children with Type 1 Spinal Muscular Atrophy. Adv Ther. 2024 Jun;41(6):2414-2434. doi: 10.1007/s12325-024-02845-6. Epub 2024 May 5.
PubMed 38705943Darras BT, Farrar MA, Mercuri E, Finkel RS, Foster R, Hughes SG, Bhan I, Farwell W, Gheuens S. An Integrated Safety Analysis of Infants and Children with Symptomatic Spinal Muscular Atrophy (SMA) Treated with Nusinersen in Seven Clinical Trials. CNS Drugs. 2019 Sep;33(9):919-932. doi: 10.1007/s40263-019-00656-w.
PubMed 31420846Dabbous O, Maru B, Jansen JP, Lorenzi M, Cloutier M, Guerin A, Pivneva I, Wu EQ, Arjunji R, Feltner D, Sproule DM. Survival, Motor Function, and Motor Milestones: Comparison of AVXS-101 Relative to Nusinersen for the Treatment of Infants with Spinal Muscular Atrophy Type 1. Adv Ther. 2019 May;36(5):1164-1176. doi: 10.1007/s12325-019-00923-8. Epub 2019 Mar 16.
PubMed 30879249Finkel RS, Mercuri E, Darras BT, Connolly AM, Kuntz NL, Kirschner J, Chiriboga CA, Saito K, Servais L, Tizzano E, Topaloglu H, Tulinius M, Montes J, Glanzman AM, Bishop K, Zhong ZJ, Gheuens S, Bennett CF, Schneider E, Farwell W, De Vivo DC; ENDEAR Study Group. Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy. N Engl J Med. 2017 Nov 2;377(18):1723-1732. doi: 10.1056/NEJMoa1702752.
PubMed 29091570Finkel RS, Chiriboga CA, Vajsar J, Day JW, Montes J, De Vivo DC, Yamashita M, Rigo F, Hung G, Schneider E, Norris DA, Xia S, Bennett CF, Bishop KM. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2016 Dec 17;388(10063):3017-3026. doi: 10.1016/S0140-6736(16)31408-8. Epub 2016 Dec 7.
PubMed 27939059
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Double-Blind, Sham-Procedure Controlled Study to Assess the Clinical Efficacy and Safety of ISIS 396443 Administered Intrathecally in Patients With Infantile-onset Spinal Muscular Atrophy
- ClinicalTrials.gov ID
- NCT02193074
- Acronym / sponsor ID
- ENDEAR / ISIS 396443-CS3B
- Conditions
- Spinal Muscular Atrophy
- Keywords
- Spinal Muscular Atrophy, SMA, SMN, SMNRx, ISIS-SMNRx, ISIS-SMN Rx, ISIS 396443, IONIS-SMNRx
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: After a positive interim analysis, the decision was made to terminate the study early to allow for participants to enroll into an open label study
- Enrolment
- 122 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Study start
- 19 Aug 2014 (actual)
- Primary completion
- 21 Nov 2016 (actual)
- Study completion
- 21 Nov 2016 (actual)
- First posted
- 17 Jul 2014 (estimated)
- Results
- Posted 28 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of the study is to examine the clinical efficacy of nusinersen (ISIS 396443) administered intrathecally (IT) to participants with infantile-onset with infantile-onset spinal muscular atrophy (SMA). The secondary objective of the study is to examine the safety and tolerability of nusinersen administered intrathecally to participants with infantile-onset SMA.
Detailed description
This study was conducted and the protocol was registered by Ionis Pharmaceuticals, Inc..
In August 2016, sponsorship of the trial was transferred to Biogen.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| nusinersen | Experimental | Drug: nusinersen |
| Sham procedure | Sham comparator | Procedure: Sham procedure |
Who may qualify
- Ages
- Up to 210 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Be born (gestational age) between 37 and 42 weeks
- Be medically diagnosed with spinal muscular atrophy (SMA)
- Have Survival Motor Neuron2 (SMN2) Copy number = 2
- Body weight equal to or greater than 3rd percentile for age using appropriate country-specific guidelines
- Be able to follow all study procedures
Key exclusion criteria (4 listed)
- Hypoxemia (oxygen [O2] saturation awake less than 96% or O2 saturation asleep less than 96%, without ventilation support) during screening evaluation
- Clinically significant abnormalities in hematology or clinical chemistry parameters or Electrocardiogram (ECG), as assessed by the Site Investigator, at the Screening visit that would render the participant unsuitable for participation in the study
- Participant's parent or legal guardian is not willing to meet standard of care guidelines (including vaccinations and respiratory syncytial virus prophylaxis if available), nor provide nutritional and respiratory support throughout the study
- NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| nusinersenAlso: ISIS 396443, BIIB058, Spinraza, IONIS-SMN RxAdministered by intrathecal (IT) injection as specified in the treatment arm. | Drug | nusinersen |
| Sham procedureSmall needle prick on the lower back at the location where the IT injection is normally made | Procedure or surgery | Sham procedure |
Primary outcome
Percentage of Motor Milestones Responders
Time frame: assessed at the later of the Day 183, Day 302, or Day 394 study visits
The definition of a motor milestones responder was based on improvement in the motor milestones categories in Section 2 of the Hammersmith Infant Neurological Examination (HINE), with the exclusion of voluntary grasp, as follows: (i) subject demonstrates ≥ 2-point increase in the motor milestones category of ability to kick or achievement of maximal score on that category (touching toes), or a 1-point increase in the motor milestones category of head control, rolling, sitting, crawling, standing, or walking, and (ii) among the motor milestone categories, with the exclusion of voluntary grasp, there are more categories where there is improvement as defined in (i) than worsening. (For the category of ability to kick, worsening is defined as ≥ 2-point decrease or decrease to the lowest possible score of no kicking. For the other categories, worsening is defined as ≥ 1-point decrease.) The lowest possible score for the HINE is 0 (zero), and the highest possible score for the HINE is 28.
Time to Death or Permanent Ventilation
Time frame: Day 91, Day 182, Day 273, Day 364, Day 394
Estimated proportion of participants who died or required permanent ventilation by a given study day, based on the Kaplan-Meier product-limit method. Time to death or permanent ventilation was defined as either tracheostomy or ≥ 16 hours ventilation/day continuously for > 21 days in the absence of an acute reversible event. This endpoint was adjudicated by a blinded, independent group of experienced clinicians, the Event Adjudication Committee (EAC), based on review of clinical study data and supporting information. Results are based on all available data.
12 secondary outcomes
Percentage of Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) Responders
Time frame: assessed at Baseline and the later of the Day 183, Day 302, or Day 394 study visits
Summary of Time to Death
Time frame: Day 91, Day 182, Day 273, Day 364, Day 394
Percentage of Participants Not Requiring Permanent Ventilation
Time frame: Up to Day 394
Percentage of Compound Muscular Action Potential (CMAP) Responders
Time frame: assessed at the later of the Day 183, Day 302, or Day 394 study visits
Time to Death or Permanent Ventilation in the Subgroup of Participants Below the Study Median Disease Duration
Time frame: Day 91, Day 182, Day 273, Day 364, Day 394
Time to Death or Permanent Ventilation in the Subgroup of Participants Above the Study Median Disease Duration
Time frame: Day 91, Day 182, Day 273, Day 364, Day 394
Number of Participants Experiencing Adverse Events (AEs), Serious AEs (SAEs) and Discontinuations Due to AEs
Time frame: Screening through Day 394 (± 7 days) or early termination
Number of Participants With AEs Corresponding to Changes in Hematology Values
Time frame: up to Day 394 (± 7 days) or early termination
Number of Participants With AEs Corresponding to Changes in Blood Chemistry Values
Time frame: up to Day 394 (± 7 days) or early termination
Number of Participants Meeting Selected Vital Sign Criteria Post-Baseline
Time frame: up to Day 394 (± 7 days) or early termination
Summary of Shifts in 12-lead Electrocardiogram (ECG) Results
Time frame: up to Day 394 (± 7 days) or early termination
Number of Participants With Clinically Significant Changes From Baseline in Urinalysis Values
Time frame: up to Day 394 (± 7 days) or early termination
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38705943Kokaliaris C, Evans R, Hawkins N, Mahajan A, Scott DA, Sutherland CS, Nam J, Sajeev G. Long-Term Comparative Efficacy and Safety of Risdiplam and Nusinersen in Children with Type 1 Spinal Muscular Atrophy. Adv Ther. 2024 Jun;41(6):2414-2434. doi: 10.1007/s12325-024-02845-6. Epub 2024 May 5.
- Derived from this study: PubMed 31420846Darras BT, Farrar MA, Mercuri E, Finkel RS, Foster R, Hughes SG, Bhan I, Farwell W, Gheuens S. An Integrated Safety Analysis of Infants and Children with Symptomatic Spinal Muscular Atrophy (SMA) Treated with Nusinersen in Seven Clinical Trials. CNS Drugs. 2019 Sep;33(9):919-932. doi: 10.1007/s40263-019-00656-w.
- Derived from this study: PubMed 30879249Dabbous O, Maru B, Jansen JP, Lorenzi M, Cloutier M, Guerin A, Pivneva I, Wu EQ, Arjunji R, Feltner D, Sproule DM. Survival, Motor Function, and Motor Milestones: Comparison of AVXS-101 Relative to Nusinersen for the Treatment of Infants with Spinal Muscular Atrophy Type 1. Adv Ther. 2019 May;36(5):1164-1176. doi: 10.1007/s12325-019-00923-8. Epub 2019 Mar 16.
- Derived from this study: PubMed 29091570Finkel RS, Mercuri E, Darras BT, Connolly AM, Kuntz NL, Kirschner J, Chiriboga CA, Saito K, Servais L, Tizzano E, Topaloglu H, Tulinius M, Montes J, Glanzman AM, Bishop K, Zhong ZJ, Gheuens S, Bennett CF, Schneider E, Farwell W, De Vivo DC; ENDEAR Study Group. Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy. N Engl J Med. 2017 Nov 2;377(18):1723-1732. doi: 10.1056/NEJMoa1702752.
- Derived from this study: PubMed 27939059Finkel RS, Chiriboga CA, Vajsar J, Day JW, Montes J, De Vivo DC, Yamashita M, Rigo F, Hung G, Schneider E, Norris DA, Xia S, Bennett CF, Bishop KM. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2016 Dec 17;388(10063):3017-3026. doi: 10.1016/S0140-6736(16)31408-8. Epub 2016 Dec 7.
- Cure SMALink provided by the sponsor.
- Muscular Dystrophy AssociationLink provided by the sponsor.
- National Organization for Rare DiseasesLink provided by the sponsor.
- Clinical Study Report (CSR) Synopsis - a results summaryLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Biogen
31 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing nusinersen in people with Spinal Muscular Atrophy, run by Biogen at 31 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 31 sites in United States, Australia, Canada, Germany, Italy and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Motor Milestones Responders (time frame: assessed at the later of the Day 183, Day 302, or Day 394 study visits). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02193074, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2021.