This study is in progress, not accepting new patients

Study to Learn If Tofersen (BIIB067) Can Delay ALS Symptoms and About Its Safety in Adults With a SOD1 Gene Mutation Who Have Not Yet Developed ALS Symptoms

a study on Amyotropic Lateral Sclerosis (ALS)

Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at La Jolla, California and other locations
Dates
study started
study ends around

Description

Summary

In this study, researchers will learn more about the effects of a drug called tofersen, also known as BIIB067 and QALSODY®, in adults with amyotrophic lateral sclerosis (ALS) who have a superoxide dismutase 1 (SOD1) gene mutation.

One of the causes of ALS is a change (or mutation) in the SOD1 gene, which causes abnormal SOD1 protein to be made. This abnormal protein can cause the motor neurons in people with ALS to break down and die. When neurons are damaged, they release a protein called neurofilament light chain, also known as NfL. Previous studies have shown that NfL levels are higher in people with SOD1-ALS, even before any ALS symptoms appear.

In this study, researchers will look at the effect of tofersen treatment in the earlier stages of the disease, even before ALS symptoms appear. Researchers believe that giving tofersen to patients as early as possible may slow the onset of ALS symptoms and the progression of the disease.

This study will have 4 parts. In Part A, participants will have their health monitored and NfL levels tested on a monthly basis, but they will not receive any study drug. Tofersen or placebo will be given to participants in Parts B, while all participants will receive tofersen in Parts C and D.

The main question that researchers want to answer is:

• How long does it take for ALS symptoms to appear?

Researchers will also learn more about:

  • How many participants develop ALS symptoms within 24 months of the start of Part B
  • Changes in participants' ability to perform their daily activities
  • Changes in participants' ability to breathe
  • How many participants die or need long-term breathing support
  • Changes in NfL levels in the blood
  • Changes in SOD1 protein levels in the fluid around the brain and spinal cord
  • How many participants have adverse events or serious adverse events. Adverse events are health problems that may or may not be caused by the study drug.

The study will be done as follows:

  • Participants will first be screened to check if they can join the study. The screening period will be up to 6 weeks. Participants will join the study only after reading and signing an informed consent form, also known as an ICF.
  • In Part A, participants with presymptomatic ALS will not get any study drugs. Researchers will check the levels of NfL in their blood. Participants will be closely checked for any signs or symptoms of ALS.
  • Once a participant's NfL levels rise to a certain amount, they will move onto Part
  • In Part B, participants will be randomly assigned to get either tofersen or a placebo. Neither participants nor researchers will know who gets tofersen or the placebo during Part B. A placebo looks like the study drug but contains no medicine.
  • Participants will get the first 3 doses of tofersen once every 14 days. Afterwards, they will continue getting maintenance doses every 28 days.
  • All doses will be given through an intrathecal (IT) injection done through a lumbar puncture procedure. This involves injecting the drug into the fluid surrounding the spinal cord in the lower back.
  • Participants who develop ALS symptoms during Part B will move to Part C to receive tofersen.
  • Participants who develop ALS symptoms during Part A will move to Part D to receive tofersen.
  • In both Parts C and D, participants will know they are receiving tofersen.
  • Throughout the study, doctors will measure any changes to the participants' function and quality of life using different questionnaires. Doctors will also take blood and urine samples. They will also check the participants' overall health and ask how they are feeling.
  • Participants will have a follow-up visit 28 days after their last dose of study drug.
  • Participants will be in this study for up to about 6.5 years.

Official Title

A Phase 3 Randomized, Placebo-Controlled Trial With a Longitudinal Natural History Run-In and Open-Label Extension to Evaluate BIIB067 Initiated in Clinically Presymptomatic Adults With a Confirmed Superoxide Dismutase 1 Mutation

Details

The primary objective of this study is to evaluate the efficacy of tofersen in presymptomatic adult carriers of a superoxide dismutase 1 (SOD1) mutation with elevated neurofilament (NF). The secondary objectives of this study are to evaluate the safety and tolerability of tofersen and to evaluate the effect of tofersen on pharmacodynamics (PD)/treatment response biomarkers when initiated prior to versus at the time of emergence of clinically manifest ALS.

Keywords

Amyotrophic Lateral Sclerosis Associated With a SOD1 Gene Mutation, tofersen, Natural History Run-in, Open-Label Extension

Eligibility

For people ages 18 years and up

Key Part A Inclusion Criteria:

  • 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.
  • Participants with plasma NfL level less than the protocol-defined threshold.
  • Participants who are clinically presymptomatic for ALS (i.e., must not have clinically manifest ALS).

Key Part A Exclusion Criteria:

  • 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.
  • Current hepatitis C infection [defined as positive Hepatitis C Virus (HCV) antibody and detectable HCV ribonucleic acid (RNA)]. Participants with positive HCV antibody and undetectable HCV RNA are eligible to participate in the study (United States Centers for Disease Control and Prevention).
  • 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 anti-hepatitis B surface antibody (HBs) or vaccination (defined as negative HBsAg, negative anti-HBc, and positive anti- HBs) are eligible to participate in the study.
  • 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.
  • 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.
  • 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.

  • 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.

  • 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.
  • Use of off-label treatments for ALS.
  • 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.
  • 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 a Lumbar Puncture (LP) procedure, if necessary, according to local or institutional guidelines and/or Investigator determination.
  • 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 noninterventional study focused on ALS natural history may be allowed at the discretion of the Investigator.

NOTE: Other protocol defined Inclusion/Exclusion criteria will apply.

Locations

  • University of California San Diego Medical Center
    La Jolla California 92093-0949 United States
  • HonorHealth Neurology
    Scottsdale Arizona 85258 United States

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Biogen
Links
Disclaimer: Residents in the United States may click here to find out more about participation in this trial.
ID
NCT04856982
Phase
Phase 3 Amyotropic Lateral Sclerosis (ALS) Research Study
Study Type
Interventional
Participants
About 158 people participating
Last Updated