An extension study for patients with Spinal Muscular Atrophy who participated to the previous ISIS 396443 studies

• Register: EUCTR
• Last refreshed on: 2 April 2024
• Main ID: EUCTR2015-001870-16-DE
• Date of registration: 28/10/2015
• Prospective Registration: Yes
• Primary sponsor: Biogen Idec Research Limited
• Public title: An extension study for patients with Spinal Muscular Atrophy who participated to the previous ISIS 396443 studies
• Scientific title: An Open-label Extension Study for Patients with Spinal Muscular Atrophy who Previously Participated in Investigational Studies of ISIS 396443
• Date of first enrolment: 08/03/2016
• Target sample size: 292
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001870-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: The study is an open label extension If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Canada, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Spain, Sweden, Turkey, United Kingdom, United States

Contacts

• Name: Medical Director
• Affiliation: Biogen

• Name: Medical Director
• Affiliation: Biogen

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet all of the following criteria at Screening to be
eligible:
1. Signed informed consent of parent or guardian and signed informed assent of subject, if indicated per subject's age and institutional guidelines.
2. Completion of the index study in accordance with the study protocol or as a result of Sponsor decision (e.g., early termination of the index study) within the preceding 16 weeks.
Are the trial subjects under 18? yes
Number of subjects for this age range: 278
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 14
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
Subjects meeting any of the following criteria are not eligible for the study:
- Have any condition or worsening of existing condition which in the opinion
of the Investigator would make the participant unsuitable for enrollment, or could
interfere with the participant participating in or completing the study
- Clinically significant abnormalities in hematology or clinical chemistry parameters or electrocardiogramm (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 or able to meet standard of care guidelines (including vaccinations and respiratory syncytial virus prophylaxis if available), nor provide nutritional and respiratory support throughout the study
- Treatment with another investigational agent, biological agent, or device within
one month of Screening, or 5 half-lives of study agent, whichever is longer
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Spinal Muscular Atrophy (SMA)
MedDRA version: 20.1 Level: PT Classification code 10041582 Term: Spinal muscular atrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Trade Name: Spinraza
Product Name: Survival of Motor Neuron 2 (SMN2) Splicing Modulator Antisense Oligonucleotide
Product Code: ISIS 396443
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Nusinersen
CAS Number: 1258984-36-9
Current Sponsor code: ISIS 396443 (BIIB058)
Other descriptive name: ISIS 396443
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2.4-

Primary Outcome(s)

Main Objective: To evaluate the long-term safety and tolerability of nusinersen (ISIS 396443) administered by intrathecal (IT) injection to subjects with SMA who previously participated in investigational studies of nusinersen.

Primary end point(s): - Number of participants experiencing Adverse events (AEs) and/or Serious Adverse Events (SAEs)
- Number of participants with clinically significant vital sign abnormalities
- Number of participants with clinically significant weight abnormalities
- Number of participants with clinically significant neurological examination abnormalities
- Number of participants with clinically significant laboratory assessment abnormalities
- Number of participants with clinically significant coagulation parameter abnormalities
- Number of participants with clinically significant 12-lead electrocardiograms (ECGs) abnormalities
- Change from Baseline in concomitant medications

Secondary Objective: To examine the long-term efficacy of nusinersen (ISIS 396443) administered by intrathecal (IT) injection to subjects with SMA who previously participated in investigational studies of nusinersen.

Timepoint(s) of evaluation of this end point: Up to Day 1814

Secondary Outcome(s)

Secondary end point(s): - Percentage of participants who attained motor milestones as assessed
by World Health Organization (WHO) criteria
- Percentage of participants who attained motor milestones as assessed
by Section 2 of Hammersmith Infant Neurological Examination (HINE)
- Time to death or permanent ventilation
- Percentage of participants not requiring permanent ventilation
- Change from Baseline in the Children's Hospital of Philadelphia Infant
Test of Neuromuscular Disorders (CHOP INTEND) motor function scale
- Change from Baseline in Hammersmith Functional Motor Scale
- Change from Baseline in Revised Upper Limb Module (RULM)
- Change from Baseline in 6-Minute Walk Test (6MWT)
- Change from Baseline in Compound Muscular Action Potential (CMAP)
- Change from Baseline in body length and/or height (for all
participants)
- Change from Baseline in head circumference (for participants up to 36
months of age)
- Change from Baseline in chest circumference (for participants up to 36
months of age)
- Change from Baseline in arm circumference (for participants up to 36
months of age)
- Proportion of CMAP responders
- Number of participants with motor milestones achieved
- Proportion of participants who achieved standing alone
- Proportion of participants who achieved walking with assistance
- Number of participants with serious respiratory events
- Number of participants hospitalized
- Duration of hospitalizations
- Change from Baseline in Cobb-Angle on X-Ray of the thoracolumbar
spine
- Change from Baseline in Quality of Life (QOL) Questionnaires
- Number of Disease-related hospitalizations and AEs
- Overall survival rate

Timepoint(s) of evaluation of this end point: Up to Day 1814

Secondary ID(s)

NCT02386553

110011

ISIS396443-CS11

Source(s) of Monetary Support

Biogen Idec Research Limited

Ethics review

Status: Approved
Approval date: 08/03/2016
Contact:

Results

• Results available: Yes
• Date Posted: 08/03/2024
• Date Completed: 21/08/2023
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-001870-16/results