Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
Register:
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EUCTR |
Last refreshed on:
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5 January 2021 |
Main ID: |
EUCTR2019-002663-10-GB |
Date of registration:
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01/09/2020 |
Prospective Registration:
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Yes |
Primary sponsor: |
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Public title:
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Study of Nusinersen (BIIB058) in Participants With Spinal Muscular
Atrophy
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Scientific title:
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Escalating Dose and Randomized, Controlled Study of Nusinersen
(BIIB058) in Participants With Spinal Muscular Atrophy - Study of Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy |
Date of first enrolment:
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17/12/2020 |
Target sample size:
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152 |
Recruitment status: |
Authorised-recruitment may be ongoing or finished |
URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-002663-10 |
Study type:
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Interventional clinical trial of medicinal product |
Study design:
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Controlled: yes
Randomised: yes
Open: no
Single blind: no
Double blind: no
Parallel group: no
Cross over: no
Other: yes
Other trial design description: Sequential Assignment: Part A - Open Label. Part B - Double Blind. Part C - Open Label
If controlled, specify comparator, Other Medicinial Product: no
Placebo: no
Other: yes
Other specify the comparator: Part B only - commercial Spinraza
Number of treatment arms in the trial: 4
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): yes
Therapeutic confirmatory - (Phase III): yes
Therapeutic use (Phase IV): no
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Countries of recruitment
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Argentina
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Australia
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Brazil
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Canada
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Chile
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Colombia
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Estonia
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Germany
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Greece
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Hungary
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Ireland
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Israel
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Italy
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Korea, Republic of
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Latvia
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Lebanon
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Mexico
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Poland
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Russian Federation
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Saudi Arabia
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Spain
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Taiwan
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Turkey
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United Kingdom
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United States
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Contacts
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Name:
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Medical Director
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Address:
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Innovation House, 70 Norden Road
SL6 4AY
Maidenhead
United Kingdom |
Telephone:
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Email:
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clinicaltrials@biogen.com |
Affiliation:
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Biogen Idec Research Limited |
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Name:
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Medical Director
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Address:
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Innovation House, 70 Norden Road
SL6 4AY
Maidenhead
United Kingdom |
Telephone:
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Email:
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clinicaltrials@biogen.com |
Affiliation:
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Biogen Idec Research Limited |
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Key inclusion & exclusion criteria
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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 = 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: - Participants = 18 years of age at Screening must be ambulatory - Currently on nusinersen treatment at the time of Screening, with the first dose being at least 1 year prior to Screening Are the trial subjects under 18? yes Number of subjects for this age range: 140 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
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 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 (SMN2)- splicing modifier or gene therapy; or prior antisense oligonucleotide treatment, or cell transplantation Part B: - 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 - 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 (SMN2)- splicing modifier or gene therapy; or prior antisense oligonucleotide treatment, or cell transplantation Part C: - Concurrent or previous participation and/or administration of nusinersen in another clinical study NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
Age minimum:
Age maximum:
Gender:
Female: yes Male: yes
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Health Condition(s) or Problem(s) studied
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Muscular Atrophy, Spinal MedDRA version: 20.1
Level: PT
Classification code 10041582
Term: Spinal muscular atrophy
System Organ Class: 10010331 - Congenital, familial and genetic disorders
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Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
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Intervention(s)
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Trade Name: Spinraza Product Name: Spinraza Pharmaceutical Form: Solution for injection INN or Proposed INN: Nusinersen CAS Number: 125894-36-9 Current Sponsor code: ISIS 396443 (BIIB058) Other descriptive name: NUSINERSEN SODIUM Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 2.4-
Product Name: Nursinersen Product Code: ISIS 396443, BIIB058 Pharmaceutical Form: Solution for injection INN or Proposed INN: Nursinersen CAS Number: 125894-36-9 Current Sponsor code: ISIS 396443 (BIIB058) Other descriptive name: NUSINERSEN SODIUM Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 12.0-
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Primary Outcome(s)
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Secondary Objective: 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).
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Main Objective: The primary objectives of this study are to examine the safety and tolerability of nusinersen administered intrathecally at higher doses to participants with spinal muscular atrophy (SMA) (Parts A and C); to examine the clinical efficacy of nusinersen administered intrathecally at higher doses to participants with SMA, as measured by change in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) total score (Part B).
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Timepoint(s) of evaluation of this end point: Part B Infantile-onset SMA: 1) Baseline up to Day 183 Part A and C: 2) Screening up to Day 389 3) Screening up to Day 302 4) Screening up to Day 302 5) Screening up to Day 302 6) Baseline up to Day 302 Part C Infantile-onset SMA: 7) Baseline up to Day 302 8) Baseline up to Day 302 9) Baseline up to Day 302 Part A and C Later-onset SMA: 10) Baseline up to Day 302 Part A and C: 11) Baseline up to Day 302 12) Baseline up to Day 302 Part C: 13) Baseline up to Day 302 Part A and C: 14) Baseline up to Day 269 15) Baseline up to Day 269 16) Baseline up to Day 269 17) Baseline up to Day 302 18) Baseline up to Day 302 19) Baseline up to Day 302 20) Baseline up to Day 302
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Primary end point(s): Part B Infantile-onset SMA: 1) Change from Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Total Score Part A and C: 2) Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) 3) Number of Participants with Clinically Significant Shifts from Baseline in Clinical Laboratory Parameters 4) Number of Participants with Clinically Significant Shifts from Baseline in Electrocardiograms (ECGs) 5) Number of Participants with Clinically Significant Shifts from Baseline in Vital Signs 6) Change from Baseline in Body Length/Height Part C Infantile-onset SMA: 7) Change from Baseline in Head Circumference 8) Change from Baseline in Chest Circumference 9) Change from Baseline in Arm Circumference Part A and C Later-onset SMA: 10) Change from Baseline in Ulnar Length Part A and C: 11) Ratio of Weight for Age 12) Ratio of Weight for Length Part C: 13) Ratio of Head-to-chest Circumference Part A and C: 14) Change from Baseline in Activated Partial Thromboplastin Time (aPTT) 15) Change from Baseline in Prothrombin Time (PT) 16) Change from Baseline in International Normalized Ratio (INR) 17) Change in Urine Total Protein 18) Change from Baseline in Neurological Examination Outcomes 19) Percentage of Participants with a Postbaseline Platelet Count Below the Lower Limit of Normal on at least 2 Consecutive Measurements 20) 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
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Secondary Outcome(s)
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Secondary end point(s): Part B Infantile-onset SMA: 1) Percentage of Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestone Responders Part B Infantile-onset SMA: 2) Change from Baseline in HINE Section 2 Motor Milestones Total Score 3) Time to Permanent Ventilation 4) Time to Death (Overall Survival) Part A and B Later-onset SMA: 5) Change from Baseline in Hammersmith Functional Motor Scale – Expanded (HFMSE) Score Part A, B and C Later-onset SMA 6) Change from Baseline in Revised Upper Limb Module (RULM) Score Part A and B Later-onset SMA 7) Number of New WHO Motor Milestones Responders 8) Change from Baseline in Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) 9) Change from Baseline in Pediatric Quality of Life Inventory™ (PedsQL) Part B: 10) Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) 11) Number of Participants with Clinically Significant Shifts from Baseline in Clinical Laboratory Parameters 12) Number of Participants with Clinically Significant Shifts from Baseline in Electrocardiograms (ECGs) 13) Number of Participants with Clinically Significant Shifts from Baseline in Vital Signs 14) Change from Baseline in body length/height Part B Infantile-onset SMA: 15) Change from Baseline in Head Circumference 16) Change from Baseline in Chest Circumference 17) Change from Baseline in Arm Circumference Part B Later-onset SMA: 18) Change from baseline in Ulnar Length Part B: 19) Ratio of Weight for Age 20) Ratio of Weight for Length 21) Ratio of Head-to-chest Circumference 22) Change from Baseline in aPTT 23) Change from Baseline in PT 24) Change from Baseline in INR 25) Change in Urine Total Protein 26) Change from Baseline in Neurological Examination Outcomes 27) Percentage of Participants with a Postbaseline Platelet Count Below the Lower Limit of Normal on at least 2 Consecutive Measurements 28) Percentage of Participants with a Postbaseline QTcF of > 500 millisecond (msec) and an Increase from Baseline to Any Postbaseline Timepoint in QTcF of > 60 msec Part A, B and C: 29) Number of Hospitalizations 30) Duration of Hospitalizations 31) Clinical Global Impression of Change (CGIC) 32) Number of Participants with Serious Respiratory Events Part B Infantile-onset SMA: 33) Percentage of Time on Ventilation Parts A, B and C: 34) Ventilator Use Part B Infantile-onset SMA: 35) Change from Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale Part C : 36) Change from Baseline in HFMSE Score 37) Number of New WHO Motor Milestone Responders 38) Change from Baseline in ACEND 39) Change from Baseline in PedsQL 40) Change from Baseline in CHOP INTEND Total Score 41) Change from Baseline in HINE Section 2 Motor Milestones Total Score Parts A and B Later-onset SMA: 42) Change from Baseline in the PASA Scale
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Timepoint(s) of evaluation of this end point: 1) Day 302 2) Baseline up to Day 302 3) Screening up to Day 302 4) Screening up to Day 399 5) to 9) - Baseline up to Day 302 10) Screening to day 399 11) Screening to Day 302 12) Day 1 up to Day 302 13) Screening up to Day 302 14) Baseline up to Day 302 15) to 17) Baseline up to Day 302 18) Baseline up to Day 302 19) to 21) Baseline up to Day 302 22) to 24) Baseline up to Day 279 25) Baseline to Day 302 26) to 28) Baseline up to Day 302 29) and 30) Day 1 to Day 279 31) Day 302 32) Screening up to Day 399 33) Screening up to Day 302 34) Screening up to Day 302 35) Baseline up to Day 302 36) to 41) Baseline to up Day 302 42) Baseline up to Day 302
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Secondary ID(s)
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NCT04089566
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110011
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2019-002663-10-LV
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232SM203
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Source(s) of Monetary Support
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Biogen Idec Research Limited
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Ethics review
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Status: Approved
Approval date: 17/12/2020
Contact:
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Results
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Results available:
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Date Posted:
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Date Completed:
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URL:
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