BIIB115 for Spinal muscular atrophy

Inclusion criteria

• {"criterion_text":"- Part A - Male healthy participants aged 18 to 55 years, inclusive."}
• {"criterion_text":"- Part B - Must have received intravenous (IV) onasemnogene abeparvovec per the approved label or per guidelines including the steroid regimen and monitoring specified therein."}
• {"criterion_text":"- Part B - Treatment with onasemnogene abeparvovec ≥180 days prior to first BIIB115 dose."}
• {"criterion_text":"- Part B LTE - Meets age-appropriate institutional criteria for use of anesthesia/sedation, if use is planned for study procedures (as assessed by the Investigator and either anesthesiologist or pulmonologist)."}
• {"criterion_text":"- Part B - Potential for improvement due to suboptimal clinical status secondary to SMA, as determined by the Investigator."}
• {"criterion_text":"- Part B LTE - Completion of the assessments in Part B"}
• {"criterion_text":"- Part A - Have a body mass index of 18 to 30 kilograms per meter square (kg/m^2), inclusive."}
• {"criterion_text":"- Part A - Must be in good health as determined by the investigator, based on medical history and screening evaluations."}
• {"criterion_text":"- Part B - Age 0.5 to 12 years old, inclusive, at the time of informed consent."}
• {"criterion_text":"- Part B - Weight ≥7 kg at the time of informed consent."}
• {"criterion_text":"- Part B - Genetic diagnosis of SMA (5q SMA homozygous survival motor neuron 1 (SMN1) gene deletion or mutation or compound heterozygous mutation)."}
• {"criterion_text":"- Part B - Survival motor neuron 2 (SMN2) copy number ≥1."}

Exclusion criteria

• {"criterion_text":"- Part A - Any reason, anatomical or otherwise (including abnormal hematology/coagulation), that presents increase of risk of complication from multiple lumbar puncture (LP) procedures required for dosing and CSF collection, per the investigator discretion."}
• {"criterion_text":"- Part B - Interval of <180 days between onasemnogene abeparvovec therapy and first BIIB115 dose."}
• {"criterion_text":"- Part B - Ongoing steroid treatment following onasemnogene abeparvovec at time of screening."}
• {"criterion_text":"- Part B - History of drug induced liver injury or liver failure per Hy’s law definition."}
• {"criterion_text":"- Part B - History of thrombotic micrangiopathy."}
• {"criterion_text":"- Clinically significant abnormalities in hematology, blood chemistry parameters, or electrocardiograms (ECGs) prior to first LTE visit that would make the participant unsuitable for inclusion as assessed by the Investigator."}
• {"criterion_text":"- Treatment with an approved SMN2-splicing modifier (nusinersen or risdiplam)"}
• {"criterion_text":"- Other protocol-defined Inclusion/Exclusion criteria may apply."}
• {"criterion_text":"- Part B - Treatment with any SMN2-splicing modifier (nusinersen or risdiplam) after receiving onasemnogene abeparvovec. Treatment with nusinersen <12 months from the first dose of BIIB115."}
• {"criterion_text":"- Part B - Any reason, anatomical or otherwise (including abnormal hematology/coagulation), that presents increase of risk of complication from the LP procedures, CSF circulation, or safety assessments, including a history of hydrocephalus or implanted shunt for CSF drainage."}
• {"criterion_text":"- Part B - Permanent ventilation, defined as tracheostomy or ≥16 hours ventilation /day continuously for >21 days in the absence of an acute reversible event."}
• {"criterion_text":"- Part B LTE - Any new condition or worsening of an existing condition that, according to the Investigator, would make the participant unsuitable for inclusion, could interfere with the assessment of safety, or would compromise the ability of the participant to undergo study procedures."}
• {"criterion_text":"- Part A - History of any clinically significant cardiac, endocrine, gastrointestinal, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, or renal disease, or other major disease, as determined by the Investigator."}
• {"criterion_text":"- Part A - Chronic, recurrent, or serious infection, as determined by the investigator, within 90 days prior to screening or between screening and Day -1."}
• {"criterion_text":"- Part A - Current enrollment or a plan to enroll in any interventional clinical study of a drug, biologic, or device, in which an investigational treatment or approved therapy for investigational use is administered within 3 months (or 5 half-lives of the agent, whichever is longer) prior to randomization."}
• {"criterion_text":"- Part B - Severe or serious AEs related to onasemnogene abeparvovec therapy that are ongoing during Screening."}

Primary endpoints

• {"endpoint_text":"- Parts A, B and Long Term Extension (LTE): Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time Frame: Part A: Up to Day 393, Part B: Up to Day 720; Part B LTE: Up to Day 2520]","definition_or_measurement_approach":"Number of participants experiencing AEs and SAEs assessed during specified time frames per part: Part A up to Day 393; Part B up to Day 720; Part B LTE up to Day 2520."}

Secondary endpoints

• {"endpoint_text":"- Parts A,B and B LTE: Concentration of BIIB115 in Cerebral Spinal Fluid (CSF) [Time Frame: Part A: Day 1 to Day 180, Part B: Days 1 and 720; Part B LTE: Day 720 to Day 2520].","definition_or_measurement_approach":"BIIB115 concentration measurements in CSF at specified days/time windows per part."}
• {"endpoint_text":"- Part A: Terminal Elimination Half-Life (t½) of BIIB115 in CSF. [Time Frame: Day 1 to Day 180].","definition_or_measurement_approach":"Calculation of terminal elimination half-life (t½) of BIIB115 in CSF measured from Day 1 to Day 180."}
• {"endpoint_text":"- Parts A,B and B LTE: Concentration of BIIB115 in Serum [Time Frame: Part A: Day 1 to Day 180, Part B: Day 1 to 720; Part B LTE: Day 720 to Day 2520].","definition_or_measurement_approach":"BIIB115 concentration measurements in serum at specified days/time windows per part."}
• {"endpoint_text":"- Parts A and B: Terminal Elimination Half-Life (t½) of BIIB115 in Serum. [Time Frame: Part A: Day 1 to Day 180, Part B: Day 1 to Day 720].","definition_or_measurement_approach":"Calculation of terminal elimination half-life (t½) of BIIB115 in serum measured in the specified time windows."}
• {"endpoint_text":"- Parts A and B: Area Under the Concentration-Time Curve from Time 0 to Last Measurable Concentration (AUC0-last) of BIIB115 in Serum. [Time Frame: Part A: Day 1 to Day 180, Part B: Day 1 to Day 720].","definition_or_measurement_approach":"AUC0-last in serum for BIIB115 calculated from concentration-time data over the specified timeframes."}
• {"endpoint_text":"- Parts A and B: Area Under the Concentration-Time Curve from Time 0 to Infinity (AUCinf) of BIIB115 in Serum. [Time Frame: Part A: Day 1 to Day 180, Part B: Day 1 to Day 720].","definition_or_measurement_approach":"AUCinf in serum for BIIB115 calculated from concentration-time data over the specified timeframes."}
• {"endpoint_text":"- Parts A and B: Maximum Observed Concentration (Cmax) of BIIB115 in Serum. [Time Frame: Part A: Day 1 to Day 180, Part B: Day 1 to Day 720].","definition_or_measurement_approach":"Cmax measured in serum for BIIB115 within the specified time windows."}
• {"endpoint_text":"- Parts A and B: Time to Reach Maximum Observed Concentration (Tmax) of BIIB115 in Serum. [Time Frame: Part A: Day 1 to Day 180, Part B: Day 1 to Day 720].","definition_or_measurement_approach":"Tmax determined from serum concentration-time profiles for BIIB115 within the specified time windows."}

Methods

• Patient recruitment and retention by Publicis Healthcare Communications Group Limited (functional role listed: patient recruitment and retention).
• Printing of patient engagement materials by Cyberchrome Inc. (role: printing patient engagement materials).
• Patient travel and reimbursement support by Greenphire LLC (role: patient travel and reimbursement).

Netherlands

Earliest CTIS Part Ii Submission Date

18-03-2024

Latest Decision Or Authorization Date

29-04-2024

Processing Time Days

42

Number Of Sites

2

Number Of Participants

35

France

Earliest CTIS Part Ii Submission Date

18-03-2024

Latest Decision Or Authorization Date

07-05-2024

Processing Time Days

50

Number Of Sites

1

Number Of Participants

1

Italy

Earliest CTIS Part Ii Submission Date

18-03-2024

Latest Decision Or Authorization Date

29-04-2024

Processing Time Days

42

Number Of Sites

2

Number Of Participants

4

Belgium

Earliest CTIS Part Ii Submission Date

18-03-2024

Latest Decision Or Authorization Date

03-05-2024

Processing Time Days

46

Number Of Sites

1

Number Of Participants

1

Poland

Earliest CTIS Part Ii Submission Date

18-03-2024

Latest Decision Or Authorization Date

06-05-2024

Processing Time Days

49

Number Of Sites

2

Number Of Participants

7

Germany

Earliest CTIS Part Ii Submission Date

18-03-2024

Latest Decision Or Authorization Date

11-06-2024

Processing Time Days

85

Number Of Sites

3

Number Of Participants

8

Primary sponsor

Full Name

Biogen Idec Research Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

IQVIA Limited

Responsibilities

Site start-up and management, project & vendor management, medical monitoring.

Name

Iqvia Laboratories Limited

Responsibilities

DNA analyses

Name

Altasciences Compagnie Inc.

Responsibilities

Serum and CSF PK

Name

Suvoda LLC

Responsibilities

IVRS – treatment randomisation

Third parties

• {"country":"United States","full_name":"Cyberchrome Inc.","duties_or_roles":"printing patient engagement materials","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Quest Diagnostics Nichols Institute Inc.","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Iqvia Laboratories Limited","duties_or_roles":"DNA analyses","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Canada","full_name":"Altasciences Compagnie Inc.","duties_or_roles":"Serum and CSF PK","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"IVRS – treatment randomisation","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Canada","full_name":"Charles River Laboratories Montreal ULC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Medical Equipment Supplies And Management Limited","duties_or_roles":"Provide equipment to sites","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Site start-up and management, project & vendor management, medical monitoring.","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Patient travel and reimbursement","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Publicis Healthcare Communications Group Limited","duties_or_roles":"Patient recruitment and retention","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"Long Term Storage Facilities","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Biogen Inc.","duties_or_roles":"Urine and plasma MET ID analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"ECG analysis/ review","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"Questionnaire licenses, scales and translations","organisation_type":"Pharmaceutical company"}