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
Conditions
Sponsors
Biogen Idec Research Limited
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 - Dosing with onasemnogene abeparvovec-xioi (Zolgensma) within 6 months prior to Screening 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 prior to Screening or anytime during the study; prior treatment with risdiplam or branaplam; or any history of gene therapy, prior antisense oligonucleotide treatment, or cell transplantation Part B: - 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 prior to Screening or anytime during the study; prior treatment with risdiplam or branaplam; or any history of gene therapy, prior antisense oligonucleotide treatment, or cell transplantation Part C: - Concurrent participation and/or administration of nusinersen in another clinical study NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 CHOP INTEND total score (Part B).;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, to examine the pharmacokinetic(s) PK of nusinersen [cerebrospinal fluid (CSF) and plasma] after intrathecal administration of nusinersen given 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).;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 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part B Infantile-onset SMA: 1) Percentage of Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestone Responders Part B and C Infantile-onset SMA: 2) Change from Baseline in HINE Section 2 Motor Milestones Total Score Part B Infantile-onset SMA: 3) Time to Permanent Ventilation 4) Time to Death (Overall Survival) Part A, B and C Later-onset SMA: 5) Change from Baseline in Hammersmith Functional Motor Scale – Expanded (HFMSE) Score 6) Change from Baseline in Revised Upper Limb Module (RULM) Score 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 fro | — |
Countries
Argentina, Australia, Brazil, Canada, Chile, Colombia, Estonia, France, Germany, Greece, Hungary, Ireland, Italy, Korea, Republic of, Latvia, Lebanon, Mexico, Netherlands, Poland, Russian Federation, Saudi Arabia, Spain, United Kingdom, United States
Contacts
Public ContactMedical Director
Biogen Idec Research Limited
Outcome results
None listed