Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02462759
Other study ID # 232SM202
Secondary ID 2014-003657-33
Status Terminated
Phase Phase 2
First received
Last updated
Start date August 19, 2015
Est. completion date September 24, 2018

Study information

Verified date February 2021
Source Biogen
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The primary objective of Part 1 of this study is to assess the safety and tolerability of Nusinersen in participants with SMA who are not eligible to participate in the clinical studies ISIS 396443-CS3B (NCT02193074) or ISIS 396443-CS4 (NCT02292537). The secondary objective of Part 1 of this study is to examine the pharmacokinetics (PK) of Nusinersen in participants with SMA. The primary objective of Part 2 of this study is to assess the long-term safety and tolerability of Nusinersen in participants with SMA who participated in Part 1 and completed their End of Part 1 Evaluation assessments. The secondary objective of Part 2 of this study is to examine the PK of Nusinersen in participants with SMA who participated in Part 1 and completed their End of Part 1 Evaluation assessments.


Description:

Part 2 is an Open Label extension phase.


Recruitment information / eligibility

Status Terminated
Enrollment 21
Est. completion date September 24, 2018
Est. primary completion date September 24, 2018
Accepts healthy volunteers No
Gender All
Age group N/A and older
Eligibility Key Inclusion Criteria: - Genetic documentation of 5q SMA homozygous gene deletion, mutation, or compound heterozygote. - Onset of clinical signs and symptoms consistent with SMA at =6 months of age and have documentation of 3 SMN2 copies OR onset of clinical signs and symptoms consistent with SMA at =6 months of age, >7 months of age (211 days) at screening, and have documentation of 2 SMN2 copies OR onset of clinical signs and symptoms consistent with SMA at >6 months of age, are =18 months of age at screening, and have documentation of 2 or 3 SMN2 copies. - Meets age-appropriate institutional criteria for use of anesthesia/sedation, if use is planned for study procedures. - Medical care, such as routine immunizations meets and is expected to continue to meet guidelines set out in the Consensus Statement for Standard of Care in SMA, in the opinion of the Investigator. - Participants with 2 SMN2 copies must reside within approximately 9 hours' ground-travel distance from a participating study site for the duration of the study. Key Exclusion Criteria: - Meets additional study related criteria. - Any previous exposure to ISIS 396443; previous dosing in this study or previous studies with ISIS 396443. - Signs or symptoms of SMA present at birth or within the first week after birth. - Ventilation for =16 hours per day continuously for >21 days at screening. - Permanent tracheostomy, implanted shunt for CSF drainage, or implanted central nervous system (CNS) catheter at screening. - History of brain or spinal cord disease that would interfere with the LP procedure, CSF circulation, or safety assessments. - Hospitalization for surgery (e.g., scoliosis surgery), pulmonary event, or nutritional support within 2 months prior to screening, or hospitalization for surgery planned during the study. - Clinically significant abnormalities in hematology or clinical chemistry parameters or Electrocardiogram (ECG), as assessed by the Investigator. - Treatment with an investigational drug for SMA (e.g., albuterol/salbutamol, riluzole, carnitine, sodium phenylbutyrate, valproate, hydroxyurea), biological agent, or device within 30 days prior to screening. Any history of gene therapy, prior antisense oligonucleotide (ASO) treatment, or cell transplantation. For Part 2 only: To be eligible to participate in Part 2 of this study, participants must meet the following eligibility criteria at the time of consent to participate in Part 2: Participation in Part 1 and completion of the End of Part 1 Evaluation assessments. Ability of parent(s) or legal guardian(s) to understand the purpose and risks of the study and to provide signed and dated informed consent on the Part 2 informed consent form (ICF) and authorization to use confidential health information in accordance with national and local participant privacy regulations. Able to complete all study procedures, measurements, and visits, and parent or legal guardian/participant has adequately supportive psychosocial circumstances, in the opinion of the Investigator. Participants will be excluded from the Part 2 if they meet the following exclusion criterion at the time of consent into Part 2 of the study: Any significant change in clinical status, including laboratory tests that, in the opinion of the Investigator, would make them unsuitable to participate in Part 2. The Investigator must reassess the subject's medical fitness for participation and consider any diseases that would preclude treatment. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Design


Intervention

Drug:
Nusinersen
Administered by intrathecal injection.
Procedure:
Sham Procedure
Small needle prick on the lower back at the location where the IT injection is normally made.

Locations

Country Name City State
Germany LMU-Campus Innenstadt Muenchen
United States The Johns Hopkins Hospital Baltimore Maryland
United States The University of Texas Southwestern Medical Center Dallas Texas
United States Connecticut Childrens Medical Hartford Connecticut
United States David Geffen School of Medicine at UCLA Los Angeles California
United States Gillette Children's Specialty Healthcare Saint Paul Minnesota
United States Seattle Children's Research Institute Seattle Washington

Sponsors (1)

Lead Sponsor Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A SAE is any untoward medical occurrence that at any dose results in death, life-threatening event, requires inpatient hospitalization, significant disability/incapacity or congenital anomaly. Part 1 and 2: From first dose/sham procedure to end of study (up to 1080 days)
Primary Number of Participants With Change From Baseline in Clinical Laboratory Parameters Clinically significant changes in laboratory parameters were evaluated for assessing the safety of ISIS 396443. Part 1 and 2: From first dose/sham procedure to end of study (up to 1080 days)
Primary Number of Participants With Change From Baseline in Electrocardiograms (ECGs) Clinically significant changes in ECG measurements were evaluated for assessing the safety of ISIS 396443. Part 1: Day 2, 29 and 422; Part 2: Day 1 to 596
Primary Number of Participants With Change From Baseline in Vital Signs Clinically significant changes in vital signs were evaluated for assessing the safety of ISIS 396443. Vital signs that were assessed included resting systolic and diastolic blood pressure, pulse rate, respiratory rate, temperature, pulse oximetry, and transcutaneous carbon dioxide. Part 1: Day 2, 29 and 422; Part 2: Day 1 to 596
Primary Change From Baseline in Head Circumference Participants were analyzed for change in growth parameter of head circumference to evaluate clinical efficacy. WHO Child Growth Standards were used to determine the head circumference percentile. Study days were windowed for integrated analysis and labelled as follows: Days <=1 as Baseline; Days >1 to <= 22 as Day 15;Days >22 to <=47 as Day 29;Days >47 to <= 123 as Day 64;Days >123 to <=242 as Day 183;Days >242 to <=362 as Day 302;Days >362 to <=482 as Day 422;Days >482 to <= 600 as Day 540;Days >600 to <= 719 as Day 659;Days >719 to <= 838 as Day 778;Days >838 to <= 958 as Day 898;Days >958 to <= 1078 as Day 1018;Days >1078 to <= 1198 as Day 1138. Part 2: Baseline, Day 15, 29, 64, 183, 302, 422, 540, 659, 778, 898, 1018 and 1138
Primary Change From Baseline in Chest Circumference Participants were analyzed for change in growth parameter of chest circumference to evaluate clinical efficacy. WHO Child Growth Standards were used to determine the chest circumference percentile. Study days were windowed for integrated analysis and labelled as follows: Days <=1 as Baseline; Days>1 to <= 22 as Day 15;Days >22 to <=47 as Day 29;Days >47 to <= 123 as Day 64;Days >123 to <=242 as Day 183;Days >242 to <=362 as Day 302;Days >362 to <=482 as Day 422;Days >482 to <= 600 as Day 540;Days >600 to <= 719 as Day 659;Days >719 to <= 838 as Day 778;Days >838 to <= 958 as Day 898;Days >958 to <= 1078 as Day 1018;Days >1078 to <= 1198 as Day 1138. Part 2: Baseline, Day 15, 29, 64, 183, 302, 422, 540, 659, 778, 898, 1018 and 1138
Primary Change From Baseline in Arm Circumference Participants were analyzed for change in growth parameter of arm circumference to evaluate clinical efficacy. WHO Child Growth Standards were used to determine the arm circumference percentile. Study days were windowed for integrated analysis and labelled as follows: Days <=1 as Baseline; Days >1 to <= 22 as Day 15;Days >22 to <=47 as Day 29;Days >47 to <= 123 as Day 64;Days >123 to <=242 as Day 183;Days >242 to <=362 as Day 302;Days >362 to <=482 as Day 422;Days >482 to <= 600 as Day 540;Days >600 to <= 719 as Day 659;Days >719 to <= 838 as Day 778;Days >838 to <= 958 as Day 898;Days >958 to <= 1078 as Day 1018;Days >1078 to <= 1198 as Day 1138. Part 2: Baseline, Day 15, 29, 64, 183, 302, 422, 540, 659, 778, 898, 1018 and 1138
Primary Change From Baseline in Weight for Age Participants were analyzed for change in growth parameter of weight for age to evaluate clinical efficacy. WHO Child Growth Standards were used to determine the weight for age percentile. Study days were windowed for integrated analysis and labelled as follows: Days <=1 as Baseline; Days >1 to <= 22 as Day 15;Days >22 to <=47 as Day 29;Days >47 to <= 123 as Day 64;Days >123 to <=242 as Day 183;Days >242 to <=362 as Day 302;Days >362 to <=482 as Day 422;Days >482 to <= 600 as Day 540;Days >600 to <= 719 as Day 659;Days >719 to <= 838 as Day 778;Days >838 to <= 958 as Day 898;Days >958 to <= 1078 as Day 1018;Days >1078 to <= 1198 as Day 1138. Part 2: Baseline, Day 15, 29, 64, 183, 302, 422, 540, 659, 778, 898, 1018 and 1138
Primary Change From Baseline in Weight Participants were analyzed for change in growth parameter of weight to evaluate clinical efficacy. WHO Child Growth Standards were used to determine the weight percentile. Study days were windowed for integrated analysis and labelled as follows: Days <=1 as Baseline; Days >1 to <= 22 as Day 15;Days >22 to <=47 as Day 29;Days >47 to <= 123 as Day 64;Days >123 to <=242 as Day 183;Days >242 to <=362 as Day 302;Days >362 to <=482 as Day 422;Days >482 to <= 600 as Day 540;Days >600 to <= 719 as Day 659;Days >719 to <= 838 as Day 778;Days >838 to <= 958 as Day 898;Days >958 to <= 1078 as Day 1018;Days >1078 to <= 1198 as Day 1138. Part 2: Baseline, Day 15, 29, 64, 183, 302, 422, 540, 659, 778, 898, 1018 and 1138
Primary Change From Baseline in Head to Chest Circumference (HCC) Ratio Participants were analyzed for change in growth parameter of HCC to evaluate clinical efficacy. WHO Child Growth Standards were used to determine the HCC circumference percentile. Study days were windowed for integrated analysis and labelled as follows: Days <=1 as Baseline; Days >1 to <= 22 as Day 15;Days >22 to <=47 as Day 29;Days >47 to <= 123 as Day 64;Days >123 to <=242 as Day 183;Days >242 to <=362 as Day 302;Days >362 to <=482 as Day 422;Days >482 to <= 600 as Day 540;Days >600 to <= 719 as Day 659;Days >719 to <= 838 as Day 778;Days >838 to <= 958 as Day 898;Days >958 to <= 1078 as Day 1018;Days >1078 to <= 1198 as Day 1138. Part 2: Baseline, Day 15, 29, 64, 183, 302, 422, 540, 659, 778, 898, 1018 and 1138
Primary Change From Baseline in Body Length Participants were analyzed for change in growth parameter of body length to evaluate clinical efficacy. WHO Child Growth Standards were used to determine the body length percentile. Study days were windowed for integrated analysis and labelled as follows: Days <=1 as Baseline; Days >1 to <= 22 as Day 15;Days >22 to <=47 as Day 29;Days >47 to <= 123 as Day 64;Days >123 to <=242 as Day 183;Days >242 to <=362 as Day 302;Days >362 to <=482 as Day 422;Days >482 to <= 600 as Day 540;Days >600 to <= 719 as Day 659;Days >719 to <= 838 as Day 778;Days >838 to <= 958 as Day 898;Days >958 to <= 1078 as Day 1018;Days >1078 to <= 1198 as Day 1138. Part 2: Baseline, Day 15, 29, 64, 183, 302, 422, 540, 659, 778, 898, 1018 and 1138
Primary Number of Participants With Change From Baseline in Neurological Examination Outcomes Neurological examinations included assessment of mental status, level of consciousness, sensory function, motor function, cranial nerve function, reflexes, mood, speech/language and hearing. Part 1: Baseline to Day 422; Part 2: Baseline to Day 596
Primary Number of Participants With Change From Baseline in Activated Partial Thromboplastin Time [aPTT] Activated partial thromboplastin time was evaluated to assess safety. "Shift to low" measured change in normal, high and unknown values of aPTT at baseline to low values postbaseline. "Shift to high" measured change in normal, high and unknown values of aPTT at baseline to high values postbaseline. Part 2: Up to 1080 days
Primary Number of Participants With Change From Baseline in Partial Thromboplastin Time [PTT] PTT was evaluated to assess safety. "Shift to low" measured change in normal, high and unknown values of PTT at baseline to low values postbaseline. "Shift to high" measured change in normal, high and unknown values of PTT at baseline to high values postbaseline. Part 2: Up to 1080 days
Primary Number of Participants With Change From Baseline in International Normalized Ratio [INR]) INR was evaluated to assess safety. "Shift to low" measured change in normal, high and unknown values of INR at baseline to low values postbaseline. "Shift to high" measured change in normal, high and unknown values of INR at baseline to high values postbaseline. Part 2: Up to 1080 days
Primary Number of Participants With Presence of Urine Total Protein Post-baseline Urine total protein was evaluated to assess safety. Part 2: Up to 1080 days
Secondary Plasma Concentration of ISIS 396443 in Part 2 of Study in Participants Who Received Sham Procedure in Part 1 of the Study Study days were windowed for integrated analysis and labelled as follows: Days >47 to <= 123 as Day 64;Days >123 to <=242 as Day 183;Days >482 to <= 600 as Day 540;Days >600 to <= 719 as Day 659. Pre-dose on Days 64, 183, 540 and 659
Secondary Plasma Concentration of ISIS 396443 in Part 1 and 2 of Study in Participants Who Received ISIS 396443 in Part 1 of the Study Study days were windowed for integrated analysis and labelled as follows: Days >47 to <= 123 as Day 64;Days >123 to <=242 as Day 183;Days >242 to <=362 as Day 302;Days >362 to <=482 as Day 422;Days >482 to <= 600 as Day 540;Days >600 to <= 719 as Day 659;Days >719 to <= 838 as Day 778;Days >838 to <= 958 as Day 898;Days >958 to <= 1078 as Day 1018;Days >1078 to <= 1198 as Day 1138. Pre-dose on Days 64, 183, 302, 422, 540, 659, 778, 898, 1018 and 1138
Secondary Cerebrospinal Fluid (CSF) Concentration of ISIS 396443 in Part 2 of Study in Participants Who Received Sham Procedure in Part 1 of the Study CSF samples were analyzed for ISIS 396443 concentrations in participants. Study days were windowed for integrated analysis and labelled as follows: Days >1 to <= 22 as Day 15;Days >22 to <=47 as Day 29;Days >47 to <= 123 as Day 64;Days >123 to <=242 as Day 183;Days >242 to <=362 as Day 302;Days >362 to <=482 as Day 422;Days >482 to <= 600 as Day 540. Pre-dose on Days 15, 29, 64, 183, 302, 422 and 540
Secondary CSF Concentration of ISIS 396443 in Part 1 and 2 of Study in Participants Who Received ISIS 396443 in Part 1 of the Study CSF samples were analyzed for ISIS 396443 concentrations in participants. Study days were windowed for integrated analysis and labelled as follows: Days >1 to <= 22 as Day 15;Days >22 to <=47 as Day 29;Days >47 to <= 123 as Day 64;Days >123 to <=242 as Day 183;Days >242 to <=362 as Day 302;Days >362 to <=482 as Day 422;Days >482 to <= 600 as Day 540;Days >600 to <= 719 as Day 659;Days >719 to <= 838 as Day 778;Days >838 to <= 958 as Day 898;Days >958 to <= 1078 as Day 1018. Pre-dose on Days 15, 29, 64, 183, 302, 422, 540, 659, 778, 898 and 1018
Secondary Number of Participants With Plasma Antibodies to ISIS 396443 Part 2: Baseline to Day 596
See also
  Status Clinical Trial Phase
Completed NCT04851873 - Safety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA) Phase 3
Completed NCT03223051 - Development of a Space Exploration Assessment for Children With Spinal Muscular Atrophy N/A
Completed NCT04335942 - Characterization of the Postural Habits of Wheelchair Users Analysis of the Acceptability of International Recommendations in the Prevention of Pressure Sores Risk by Using a Connected Textile Sensor N/A
Recruiting NCT05794139 - Safety and Efficacy of NMD670 in Ambulatory Adult Patients With Type 3 Spinal Muscular Atrophy Phase 2
Not yet recruiting NCT06300996 - Spinal Cord Stimulation for the Treatment of Motor Deficits in People With Spinal Muscular Atrophy - Upper Limb N/A
Not yet recruiting NCT00961103 - Motor Development and Orthoses in Spinal Muscular Atrophy (SMA) N/A
Completed NCT02003937 - Aerobic Training in Patients With Spinal Muscular Atrophy Type III N/A
Completed NCT00227266 - Valproic Acid and Carnitine in Patients With Spinal Muscular Atrophy Phase 2
Completed NCT00374075 - Study of Safety and Dosing Effect on SMN Levels of Valproic Acid (VPA) in Patients With Spinal Muscular Atrophy Phase 1
Enrolling by invitation NCT05539456 - Reliability and Validity of the Turkish Version of the PedsQL 3.0 Neuromuscular Module for 2-to 4- Year-old
Recruiting NCT05779956 - Personalized Medicine for SMA: a Translational Project
Recruiting NCT03300869 - Natural History of Types 2 and 3 SMA in Taiwan
Recruiting NCT03217578 - Neonatal Spinal Muscular Atrophy (SMA) Screening
Completed NCT01703988 - An Open-label Safety, Tolerability and Dose-Range Finding Study of Multiple Doses of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy Phase 1/Phase 2
Withdrawn NCT02235090 - Study of Feasibility to Reliably Measure Functional Abilities' Changes in Nonambulant Neuromuscular Patients Without Trial Site Visiting N/A
Completed NCT02123186 - Newborn Screening for Spinal Muscular Atrophy N/A
Completed NCT00756821 - A Pilot Study of Biomarkers for Spinal Muscular Atrophy N/A
Completed NCT00004771 - Phase II Study of Leuprolide and Testosterone for Men With Kennedy's Disease or Other Motor Neuron Disease Phase 2
Recruiting NCT05366465 - Quality of Life and Participation of the Adult With Spinal Muscular Atrophy in France
Recruiting NCT06310421 - Spinal Muscular Atrophy Neonatal Screening Program