Muscular Atrophy, Spinal
Conditions
Brief summary
In this PIERRE-PK study, researchers will learn how the body processes nusinersen when it is given through the ThecaFlex DRx™ System, compared to when nusinersen is given by lumbar puncture (LP). The ThecaFlex DRx system is an investigational implantable medical device developed by Alcyone Therapeutics, Inc. It consists of a catheter, which is a flexible tube, connected to a port which is placed under the skin. Alcyone Therapeutics, Inc. has an ongoing study called PIERRE to test the ThecaFlex DRx system. Participants with spinal muscular atrophy (SMA) in the PIERRE study may be enrolled in the PIERRE-PK study. The main goal of the PIERRE-PK study is to learn how the body processes nusinersen when given by the ThecaFlex DRx system compared to a lumbar puncture. The main questions researchers want to answer are: * What is the highest amount of nusinersen found in the blood after dosing? * How much nusinersen is found in the blood over the first 24 hours after dosing? The PIERRE-PK study will be done as follows: * Participants will be screened to check if they can join the study. The screening period will be up to 30 days for this study and may overlap with the PIERRE study. * Participants will join 1 of 2 groups based on their ongoing nusinersen treatment. One group will be receiving 12 mg doses of nusinersen. The other group will be receiving 28 mg doses of nusinersen. * Participants will first receive a dose of nusinersen by lumbar puncture. * The ThecaFlex DRx system will be implanted after the lumbar puncture, as part of the PIERRE study. * Participants will receive a dose of nusinersen by the ThecaFlex DRx system, as part of the PIERRE study. This dose will be a regular maintenance dose that happens about 4 months after their first dose in this study. * Researchers will take blood samples before and after each dose. The last blood sample will be taken 24 hours after the dose. * The total study duration for each participant in the PIERRE-PK study will be approximately 5 months. This period will overlap with the participant's first 5 months in the PIERRE study.
Detailed description
The primary objective of this study is to assess the Pharmacokinetic (PK) profile of nusinersen delivered via standard LP and via the ThecaFlex DRx System in participants with SMA.
Interventions
DRUGNusinersen
Administered as specified in the treatment arm.
DEVICEThecaFlex DRx System
Implanted as specified in the treatment arm.
Sponsors
Biogen
Alcyone Therapeutics, Inc
Study design
Allocation
NA
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: \- Participants must be screened in the PIERRE study to be eligible for enrollment in the PIERRE PK study. Participants in the 12 mg group * Participant must have completed all 4 required 12 mg loading doses as per the approved 12 mg dose regimen. * Participant is on regular LP maintenance dosing of nusinersen 12 mg every 4 months, with 120 days ± 14 days between the LP-delivered study dose and the last nusinersen dose prior to study enrollment. Participants in the 28 mg group * Participant must have completed 1 or 2 of the 50 mg loading doses as per the approved 50/28 mg dose regimen. * Participant is on regular LP maintenance dosing of nusinersen 28 mg every 4 months, with 120 days ± 14 days between the LP-delivered study dose and the last nusinersen dose prior to study enrollment. Key
Exclusion criteria
* Ongoing participation or participation within 6 months or 5 half-lives of the agent (whichever is longer) of enrollment in other interventional clinical trials for the treatment of SMA (except for the PIERRE study or interventional clinical trials of myostatin inhibitors \[e.g., apitegromab and taldefgrobep alfa\]). * Participant is naïve to nusinersen treatment. * Participant is receiving nusinersen at a dose other than 12 mg or 28 mg. * Participant has already undergone implantation of the ThecaFlex DRx system or any other implantable medical device for intrathecal (IT) administration. * Participant is pregnant, currently breastfeeding, or intending to become pregnant during the study. NOTE: Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Observed Concentration (Cmax) of Nusinersen Delivered via Standard LP and via ThecaFlex DRx System | Pre-dose and at multiple time points post-dose over 4 months |
| Area Under the Plasma Concentration-Time Curve From Zero Time to 24 Hours After Intrathecal Administration (AUC0-24h) of Nusinersen Delivered via Standard LP and via ThecaFlex DRx System | Pre-dose and at multiple time points post-dose over 4 months |
Countries
France, Germany, Italy, Poland, Spain, United Kingdom, United States
Contacts
CONTACTUS Biogen Clinical Trial Center
CONTACTGlobal Biogen Clinical Trial Center
STUDY_DIRECTORMedical Director
Biogen
Outcome results
None listed