TOFERSEN for Amyotrophic lateral sclerosis (SOD1-associated)

Inclusion criteria

• {"criterion_text":"- Participants should have a protocol-defined rapidly progressive SOD1 mutation, confirmed by a central reader, or a SOD1 mutation that is approved for inclusion by an external mutation adjudication committee."}
• {"criterion_text":"- Participants with plasma NfL level less than the protocol-defined threshold."}
• {"criterion_text":"- Participants who are clinically presymptomatic for ALS (i.e., must not have clinically manifest ALS)."}
• {"criterion_text":"- Note: Other protocol defined Inclusion criteria will apply."}

Exclusion criteria

• {"criterion_text":"- History or positive test result at screening for human immunodeficiency virus (HIV). The requirement for testing at Screening may be omitted if it is not permitted by local regulations."}
• {"criterion_text":"- Current hepatitis C infection (defined as positive Hepatitis C Virus (HCV) antibody and detectable HCV RNA). Participants with positive HCV antibody and undetectable HCV Ribonucleic Acid (RNA) are eligible to participate in the study (United States Centers for Disease Control and Prevention)."}
• {"criterion_text":"- Current hepatitis B infection (defined as positive for hepatitis B surface antigen (HBsAg) and/or anti-Hepatitis B Core antibody (HBc)). Participants with immunity to hepatitis B from previous natural infection (defined as negative HBsAg, positive anti-HBc, and positive antihepatitis B surface antibody (HBs) or vaccination (defined as negative HBsAg, negative anti-HBc, and positive anti- HBs) are eligible to participate in the study"}
• {"criterion_text":"- History of systemic hypersensitivity reaction to tofersen, the excipients contained in the formulation, and if appropriate, any diagnostic agents to be administered during the study."}
• {"criterion_text":"- History of confounding neuromuscular or neurological disorder that is expected to have a progressive (i.e., worsening) course during the study, and/or is expected to be associated with elevations in NF, in the opinion of the Investigator."}
• {"criterion_text":"- Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that if not managed optimally could place a participant at an increased risk for intraoperative or postoperative bleeding."}
• {"criterion_text":"- Significant cognitive impairment, clinical dementia, or unstable psychiatric illness, including psychosis, suicidal ideation, suicide attempt, or untreated major depression ≤ 90 days of Screening, which in the opinion of the Investigator would interfere with the study procedures."}
• {"criterion_text":"- Treatment with riluzole, edaravone and/or sodium phenylbutyrate/taurursodiol (also known as ursodoxicoltaurine). If the participant has been on riluzole, edaravone and/or sodium phenylbutyrate/taurursodiol, the medication(s) must be discontinued for at least 5 half-lives prior to screening."}
• {"criterion_text":"- Treatment with another investigational drug (including investigational drugs for ALS through compassionate use programs), biological agent, or device within 1 month or 5 half-lives of study agent, whichever is longer. Specifically, no prior treatment with small interfering RNA, stem cell therapy, or gene therapy is allowed."}
• {"criterion_text":"- Anticipated need, in the opinion of the Investigator, for administration of any antiplatelet or anticoagulant medication (e.g., clopidogrel) that cannot be safely continued or held for an LP procedure, if necessary, according to local or institutional guidelines and/or Investigator determination."}
• {"criterion_text":"- Current enrollment or a plan to enroll in any interventional clinical study in which an investigational treatment, biological agent, device, or approved therapy for investigational use. Participation in a non-interventional study focused on ALS natural history may be allowed at the discretion of the Investigator."}
• {"criterion_text":"- Note: Other protocol defined Exclusion criteria will apply."}

Primary endpoints

• {"endpoint_text":"- Parts B and C: Percentage of Participants with Emergence of Clinically Manifest ALS Within 24 Months of Part B Baseline. [Time Frame: Up to 24 months]","definition_or_measurement_approach":"Percentage of participants who meet the study definition of emergence of clinically manifest ALS within 24 months of Part B baseline; time frame up to 24 months."}

Secondary endpoints

• {"endpoint_text":"- Parts B and C: Time to Emergence of Clinically Manifest ALS. [Time Frame: Up to 5.6 years].","definition_or_measurement_approach":"Time-to-event analysis measuring time until emergence of clinically manifest ALS; time frame up to 5.6 years."}
• {"endpoint_text":"- Parts B and C: Change in ALS Functional Rating Scale (ALSFRS-R) Total Score. The ALSFRS-R measures 4 functional domains: respiratory, bulbar function, gross motor skills, and fine motor skills. There are 12 questions, each scored from 0 to 4, for a total possible score of 48, with higher scores representing better function. [Time Frame: Up to 5.6 years].","definition_or_measurement_approach":"Change from baseline in ALSFRS-R total score (12 items, 0–48); measured longitudinally up to 5.6 years."}
• {"endpoint_text":"- Parts B and C: Change from Baseline in Percent Predicted Slow Vital Capacity (SVC). [Time Frame: Up to 5.6 years].","definition_or_measurement_approach":"Change from baseline in percent predicted slow vital capacity (SVC); measured up to 5.6 years."}
• {"endpoint_text":"- Parts B and C: Percentage of Participants with Outcome as Death or Permanent Ventilation Based on time to Death or Permanent Ventilation Analysis. Permanent ventilation is defined as ≥22 hours of invasive or non-invasive mechanical ventilation per day for ≥21 consecutive days. [Time Frame: Up to 5.6 years].","definition_or_measurement_approach":"Proportion of participants experiencing death or permanent ventilation (≥22 hours/day for ≥21 consecutive days); time-to-event analysis up to 5.6 years."}
• {"endpoint_text":"- Parts B and C: Percentage of Participants with Outcome as Deaths Based on Time to Death Analysis. [Time Frame: Up to 5.6 years].","definition_or_measurement_approach":"Proportion of participants who die during follow-up; time-to-death analysis up to 5.6 years."}
• {"endpoint_text":"- Parts B, C and D: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) during the Treatment Period. [Time Frame: Parts B and C: Up to 5.6 years and Part D: Up to 2 years].","definition_or_measurement_approach":"Counts and incidence of AEs and SAEs during treatment periods (Parts B/C up to 5.6 years; Part D up to 2 years)."}
• {"endpoint_text":"- Parts B, C and D: Change from Baseline in Plasma NfL Concentrations. [Time Frame: Parts B and C: Up to 5.6 years and Part D: Up to 2 years].","definition_or_measurement_approach":"Change from baseline in plasma neurofilament light (NfL) concentrations measured longitudinally (Parts B/C up to 5.6 years; Part D up to 2 years)."}
• {"endpoint_text":"- Parts B, C and D: Change in Total Cerebrospinal Fluid (CSF) SOD1 Concentrations. [Time Frame: Parts B and C: Up to 5.6 years and Part D: Up to 2 years].","definition_or_measurement_approach":"Change from baseline in total CSF SOD1 concentrations measured over specified time frames."}

Methods

• Patient Engagement Brochure (K2) and PE Poster — printed/digital engagement materials for potential participants; country-specific versions available (DE, IT, ES, PL, SWE, FR etc.)
• Site recruitment procedures (K1 Recruitment and Informed Consent Procedure) — site-level recruitment and consent workflow documents
• Patient travel and reimbursement (Greenphire) — support for participant travel to sites
• Digital measurements (Clinical Ink) — in-clinic and/or at-home digital outcome capture
• Remote nursing services (Fortrea) — collect outcome measures & samples for patients unable to travel
• Patient engagement materials produced by Praxis Communications and patient engagement brochure to support identification and enrollment

France

Earliest CTIS Part Ii Submission Date

18-07-2024

Latest Decision Or Authorization Date

09-08-2024

Processing Time Days

22

Number Of Sites

1

Number Of Participants

5

Germany

Earliest CTIS Part Ii Submission Date

18-07-2024

Latest Decision Or Authorization Date

09-08-2024

Processing Time Days

22

Number Of Sites

2

Number Of Participants

10

Italy

Earliest CTIS Part Ii Submission Date

18-07-2024

Latest Decision Or Authorization Date

13-08-2024

Processing Time Days

26

Number Of Sites

1

Number Of Participants

3

Spain

Earliest CTIS Part Ii Submission Date

18-07-2024

Latest Decision Or Authorization Date

09-08-2024

Processing Time Days

22

Number Of Sites

1

Number Of Participants

3

Poland

Earliest CTIS Part Ii Submission Date

18-07-2024

Latest Decision Or Authorization Date

29-08-2024

Processing Time Days

42

Number Of Sites

1

Number Of Participants

3

Sweden

Earliest CTIS Part Ii Submission Date

18-07-2024

Latest Decision Or Authorization Date

08-08-2024

Processing Time Days

21

Number Of Sites

1

Number Of Participants

6

Primary sponsor

Full Name

Biogen Idec Research Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

Pharmaceutical Product Development LLC (PPD)

Name

IQVIA Limited

Responsibilities

Vendor management, 24hr Emergency contact

Name

Fortrea Inc.

Responsibilities

Remote nursing services - collect outcome measures & samples for patients unable to travel

Name

WCG Clinical Inc.

Responsibilities

Adjudication committee

Third parties

• {"country":"United States","full_name":"Preventiongenetics LLC","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Medical Equipment Supplies And Management Limited","duties_or_roles":"Equipment supply (as requested by the sites)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"","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 States","full_name":"WCG Clinical Inc.","duties_or_roles":"Adjudication committee","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Vendor management, 24hr Emergency contact","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Clinical Ink Inc.","duties_or_roles":"Digital Measurements - in clinic and/or at home","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Praxis Communications LLC","duties_or_roles":"Patient engagement materials","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"eResearchTechnology GmbH","duties_or_roles":"SVC, ECG","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Remote nursing services - collect outcome measures & samples for patients unable to travel","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Stichting TRICALS Foundation","duties_or_roles":"increase the identification and enrolment of ALS patients carrying a SOD1 mutation","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"Samples long term storage","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}